FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Danning, CL Illei, GG Lee, EG Boumpas, DT McInnes, IB AF Danning, CL Illei, GG Lee, EG Boumpas, DT McInnes, IB TI alpha v beta 3 integrin expression in psoriatic arthritis (PsA) synovial membrane. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1883 BP S346 EP S346 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601882 ER PT J AU Davis, JC Tassiulas, YO McInnes, IB Illei, GG Fleisher, T Boumpas, DT AF Davis, JC Tassiulas, YO McInnes, IB Illei, GG Fleisher, T Boumpas, DT TI Lymphocyte reconstitution after intravenous fludarabine in patients with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 631 BP S138 EP S138 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600632 ER PT J AU Goldbach-Mansky, R Schumacher, HR Klippel, J Wilder, R Aringer, M Arayssi, T Yarboro, C El-Gabalawy, HS AF Goldbach-Mansky, R Schumacher, HR Klippel, J Wilder, R Aringer, M Arayssi, T Yarboro, C El-Gabalawy, HS TI Lack of concordance between criteria based diagnoses and clinical diagnoses in a cohort of patients with synovitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1426 BP S270 EP S270 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601427 ER PT J AU Goldbach-Mansky, R Schumacher, HR Smith, D Aryassi, T Yarboro, C Wilder, R Klippel, J El-Gabalawy, HS AF Goldbach-Mansky, R Schumacher, HR Smith, D Aryassi, T Yarboro, C Wilder, R Klippel, J El-Gabalawy, HS TI Relationship between infectious symptoms, immune serology to arthritogenic pathogens, and 1 year outcome in patients with synovitis of recent onset. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 693 BP S148 EP S148 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600694 ER PT J AU Goldbach-Mansky, R Hudson, A Gerard, H Wang, G Smith, D Arayssi, T Yarboro, C Wilder, R Klippel, J El-Gabalawy, HS Schumacher, HR AF Goldbach-Mansky, R Hudson, A Gerard, H Wang, G Smith, D Arayssi, T Yarboro, C Wilder, R Klippel, J El-Gabalawy, HS Schumacher, HR TI Does the presence of C-trachomatis in synovial tissue correlate with immune serology and outcome in recent onset synovitis? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 692 BP S148 EP S148 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600693 ER PT J AU Goldbach-Mansky, R Schumaker, HR Bale, S Klippel, J Wilder, R Arayssi, T Yarboro, C El-Gabalawy, HS AF Goldbach-Mansky, R Schumaker, HR Bale, S Klippel, J Wilder, R Arayssi, T Yarboro, C El-Gabalawy, HS TI Immunogenetic associations in patients with early synovitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 180 BP S62 EP S62 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600181 ER PT J AU Griffiths, M Remmers, E Cannon, GW Wilder, R AF Griffiths, M Remmers, E Cannon, GW Wilder, R TI Regulation of collagen-induced arthritis in DA and BN rats by MHC and non-MHC genes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 VAMC, Salt Lake City, UT 84132 USA. Univ Utah, Salt Lake City, UT 84132 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1100 BP S216 EP S216 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601101 ER PT J AU Grimbacher, B Dutra, A Holland, S Malech, H Gallin, J Puck, J AF Grimbacher, B Dutra, A Holland, S Malech, H Gallin, J Puck, J TI Hyper-IgE recurrent infection syndrome (HIERIS): New clinical features, family studies and a case with cytogenetic anomaly. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1387 BP S264 EP S264 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601388 ER PT J AU Hama, N Pallagianni, F Mavrothalassitis, G Yamada, H Boumpas, DT AF Hama, N Pallagianni, F Mavrothalassitis, G Yamada, H Boumpas, DT TI Glucocorticoid modulation of cytokine gene transcription: Opposing effects on pro-inflammatory vs anti-inflammatory cytokine promoters. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 St Marianna Univ, Sch Med, Kawasaki, Kanagawa 216, Japan. NCI, Ft Detrick, MD 21702 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 968 BP S194 EP S194 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600969 ER PT J AU Hirakata, M Suwa, A Nagai, S Genth, E Plotz, P Song, YW Mimori, T Akizuki, M Targoff, IN AF Hirakata, M Suwa, A Nagai, S Genth, E Plotz, P Song, YW Mimori, T Akizuki, M Targoff, IN TI Clinical and immunogenetic features associated with anti-asparaginyl tRNA synthetase antibodies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Seoul Natl Univ Hosp, Seoul 110744, South Korea. VAMC, OKC, Oklahoma City, OK 73104 USA. NIH, Bethesda, MD 20892 USA. Kyoto Univ, Kyoto 606, Japan. Keio Univ, Tokyo 160, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1331 BP S254 EP S254 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601332 ER PT J AU Hoffman, GS Drucker, Y Cotch, MF Locker, GA Easley, K Kwoh, K AF Hoffman, GS Drucker, Y Cotch, MF Locker, GA Easley, K Kwoh, K TI Wegener's granulomatosis (WG): Patient-reported effects of disease on health, function and income. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Case Western Reserve Univ, Med Ctr, Cleveland, OH 44106 USA. NEI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 494 BP S115 EP S115 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600495 ER PT J AU Illei, G McCoy, A Gourley, M Crane, M Yarboro, C Vaughan, E Davis, J Pando, J Austin, H Balow, J Klippel, J Boumpas, D AF Illei, G McCoy, A Gourley, M Crane, M Yarboro, C Vaughan, E Davis, J Pando, J Austin, H Balow, J Klippel, J Boumpas, D TI Renal flares in patients with proliferative lupus nephritis (LN) treated with immunosuppressive therapy: Classification, prevalence and outcomes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1257 BP S242 EP S242 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601258 ER PT J AU Illei, G Schumacher, HR Goldbach-Mansky, R Klippel, J Wilder, R Smith, D Gerber, L Arayssi, T Yarboro, C El-Gabalawy, HS AF Illei, G Schumacher, HR Goldbach-Mansky, R Klippel, J Wilder, R Smith, D Gerber, L Arayssi, T Yarboro, C El-Gabalawy, HS TI Predictors of remission in patients with early synovitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1419 BP S269 EP S269 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601420 ER PT J AU Illei, G Schumacher, HR Arayssi, T Yarboro, C Smith, D Klippel, J El-Gabalawy, HS AF Illei, G Schumacher, HR Arayssi, T Yarboro, C Smith, D Klippel, J El-Gabalawy, HS TI Patterns of antirheumatic drug therapy in patients with early arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, NIH, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1418 BP S269 EP S269 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601419 ER PT J AU Jacobsson, LTH Turesson, C Knowler, WC Pillemer, SR Hanson, RL Pettitt, DJ Bennett, PH AF Jacobsson, LTH Turesson, C Knowler, WC Pillemer, SR Hanson, RL Pettitt, DJ Bennett, PH TI Number of swollen joints predicts cardiovascular death in women; Results from a population study of Pima Indians SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Malmo Univ Hosp, Malmo, Sweden. NIAMS, Phoenix, AZ 85014 USA. NIDDK, Phoenix, AZ 85014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 566 BP S127 EP S127 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600567 ER PT J AU Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL TI IFN-gamma and IL-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis, undifferentiated oligoarthritis and normal volunteers. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1270 BP S244 EP S244 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601271 ER PT J AU Kuroiwa, T Lee, EG McCoy, AL Mcinnes, IB Boumpas, DT AF Kuroiwa, T Lee, EG McCoy, AL Mcinnes, IB Boumpas, DT TI A role for cell-contact in amplification of inflammatory responses in lupus nephritis (LN). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 221 BP S69 EP S69 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600222 ER PT J AU Langevitz, P Livneh, A Shinar, Y Sidi, G Kastner, DL Pras, M Pras, E AF Langevitz, P Livneh, A Shinar, Y Sidi, G Kastner, DL Pras, M Pras, E TI Protracted febrile myalgia (PFM) in familial Mediterranean fever (FMF): Mutation analysis in FMF gene (MEFV) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1199 BP S232 EP S232 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601200 ER PT J AU Lethbridge-Ceiku, M Creamer, P Wilson, PD Hochberg, MC Scott, WW Tobin, JD AF Lethbridge-Ceiku, M Creamer, P Wilson, PD Hochberg, MC Scott, WW Tobin, JD TI Risk factors for incident knee osteoarthritis (OA): Data from the Baltimore longitudinal study on aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 896 BP S182 EP S182 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600897 ER PT J AU Nagaraju, K Raben, N Villalba, MI Casciola-Rosen, LA Rosen, A Danning, C Loeffler, L Plotz, P AF Nagaraju, K Raben, N Villalba, MI Casciola-Rosen, LA Rosen, A Danning, C Loeffler, L Plotz, P TI The mechanism of resistance to apoptosis of muscle cells despite the presence of Fas and Fas-L. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1981 BP S363 EP S363 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601980 ER PT J AU Nagaraju, K Villalba, ML Raben, N Danning, C Loeffler, L Tresser, N Abati, A Fetsch, P Plotz, P AF Nagaraju, K Villalba, ML Raben, N Danning, C Loeffler, L Tresser, N Abati, A Fetsch, P Plotz, P TI Unexpected expression of costimulatory markers, CTLA-4 and CD28 on cultured muscle cells and in the biopsies of patients with idiopathic inflammatory myopathies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1477 BP S279 EP S279 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601478 ER PT J AU Rischmueller, M Scott, J Beroukas, D Gannot, G Fletcher, D Gordon, TP Fox, PC AF Rischmueller, M Scott, J Beroukas, D Gannot, G Fletcher, D Gordon, TP Fox, PC TI Salivary gland apoptosis in primary Sjogren's syndrome: A controlled study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIDR, Bethesda, MD 20892 USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. Flinders Med Ctr, Woodville, SA 5011, Australia. Queen Elizabeth Hosp, Woodville, SA 5011, Australia. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1754 BP S325 EP S325 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601753 ER PT J AU Schumacher, HR Gerard, H Arayssi, T Pando, J Klippel, J Saabi, DL Hudson, AP AF Schumacher, HR Gerard, H Arayssi, T Pando, J Klippel, J Saabi, DL Hudson, AP TI Is Chlamydia pneumonia (C-pneum.) infection another cause of reactive arthritis? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. VAMC, Philadelphia, PA USA. Wayne State Univ, Detroit, MI USA. NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 702 BP S149 EP S149 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600703 ER PT J AU Onken, LS Bootzin, RR AF Onken, LS Bootzin, RR TI Behavioral Therapy Development and Psychological Science: If a tree falls in the forest and no one hears it ... SO BEHAVIOR THERAPY LA English DT Editorial Material C1 NIDA, Treatment Res Branch, NIH, Rockville, MD 20857 USA. Univ Arizona, Tucson, AZ 85721 USA. RP Onken, LS (reprint author), NIDA, Treatment Res Branch, NIH, 5600 Fishers Lane,Room 10A-10, Rockville, MD 20857 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD FAL PY 1998 VL 29 IS 4 BP 539 EP 543 DI 10.1016/S0005-7894(98)80049-X PG 5 WC Psychology, Clinical SC Psychology GA 150YN UT WOS:000077693800001 ER PT J AU Lang, PJ Cuthbert, BN Bradley, MM AF Lang, PJ Cuthbert, BN Bradley, MM TI Measuring emotion in therapy: Imagery, activation, and feeling SO BEHAVIOR THERAPY LA English DT Article ID ACOUSTIC STARTLE RESPONSE; CRIMINAL PSYCHOPATH; FEAR; MODULATION; REFLEX; ANXIETY; PROBE; SENSITIZATION; INFORMATION; BEHAVIOR C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Lang, PJ (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. NR 50 TC 44 Z9 44 U1 2 U2 7 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD FAL PY 1998 VL 29 IS 4 BP 655 EP 674 DI 10.1016/S0005-7894(98)80024-5 PG 20 WC Psychology, Clinical SC Psychology GA 150YN UT WOS:000077693800010 ER PT J AU Corsi, MM Maes, HH Wasserman, K Fulgenzi, A Gaja, G Ferrero, ME AF Corsi, MM Maes, HH Wasserman, K Fulgenzi, A Gaja, G Ferrero, ME TI Protection by L-2-oxothiazolidine-4-carboxylic acid of hydrogen peroxide-induced CD3 zeta and CD16 zeta chain down-regulation in human peripheral blood lymphocytes and lymphokine-activated killer cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE zeta chain; hydrogen peroxide; L-2-oxothiazolidine-4-carboxylic acid; peripheral blood lymphocytes; macrophages; lymphokine-activated killer cells ID GLUTATHIONE METABOLISM; T-CELLS; ZETA-CHAIN; MOLECULES; CARCINOMA; TOXICITY; COMPLEX; CANCER; ESTER AB We investigated whether L-2-oxothiazolidine-4-carboxylic acid (OTC) [in the form of Procysteine(R), kindly donated by Transcend Therapeutics] could protect peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells from CD3 zeta and CD16 zeta chain down-regulation induced by H2O2 produced by lipopolysaccharide (LPS)-activated autologous monocytes. OTC is known to enhance glutathione production in cells in which glutathione was depleted by reactive oxygen species. Our data showed that OTC induced a significant increase in CD3 zeta and CD16 zeta chain expression in peripheral blood lymphocytes and LAK cells, respectively, pretreated for 12 hr at 37 degrees. Moreover, OTC significantly protected peripheral blood lymphocytes and LAK against decreased zeta chain expression induced by lipopolysaccharide-activated monocytes or the addition of H2O2 to the culture medium. Our experiments thus suggested that alterations in signal-transducing molecules, such as decreased CD3 zeta and CD16 zeta expression observed in cytotoxic T lymphocytes and LAK cells in response to oxidative stress, could be prevented by the use of OTC. (C) 1998 Elsevier Science Inc. C1 Univ Milan, Inst Gen Pathol, Fac Med, I-20133 Milan, Italy. CNR, Ctr Studio Patol Cellulare, I-20133 Milan, Italy. Catholic Univ Louvain, Cellular Genet Unit, Inst Cellular Pathol, Brussels, Belgium. Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD USA. RP Corsi, MM (reprint author), Univ Milan, Inst Gen Pathol, Fac Med, Via Mangiagalli 31, I-20133 Milan, Italy. OI Corsi Romanelli, Massimiliano Marco/0000-0001-7928-7697 NR 21 TC 18 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 1998 VL 56 IS 5 BP 657 EP 662 DI 10.1016/S0006-2952(98)00085-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 115BZ UT WOS:000075644800013 PM 9783734 ER PT J AU Han, JS Kim, HC Chung, JK Kang, HS Donaldson, J Koh, JK AF Han, JS Kim, HC Chung, JK Kang, HS Donaldson, J Koh, JK TI The potential role for Cdc42 protein from rat brain cytosol in phospholipase D activation SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE ADP-ribosylation factor; Cdc42; phospholipase D; rat brain; RhoA ID GTP-BINDING-PROTEIN; ADP-RIBOSYLATION FACTOR; CHOLERA-TOXIN; ARF; PURIFICATION; PHOSPHORYLATION; IDENTIFICATION; STIMULATION; NEUTROPHIL; MECHANISM AB Phospholipase D (PLD) has been extracted from rat brain membranes and chromatographically enriched 70-fold. From the rat brain cytosol Cdc42 with a Mr of about 24,000 and ADP-ribosylation Factor (Arf) with a Mr of about 18,000 have been purified to near homogeneity. PLD was activated better by purified cytosolic Arf than by the other small G proteins tested. Cdc42 purified from rat brain cytosol showed 70% of PLD activation activity exerted by cytosolic Arf, suggesting that Cdc42 may be one of the major G proteins involved in the activation of membrane-associated PLD. While Cdc42 or RhoA exhibited synergistic activation of PLD when administered in conjunction with Arf, Cdc42 and RhoA showed an additive effect when used together. It is possible that Arf and Rho family proteins may have different interaction sites on PLD. These findings support a role for GTP-binding proteins of the Rho family as well as Arf in the activation of membrane-associated PLD and further suggest that Cdc42 may be a major G protein involved in the PLD activation in rat brain. C1 Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea. Hanyang Univ, Coll Med, Dept Biochem, Seoul 133791, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Han, JS (reprint author), Hanyang Univ, Coll Med, Inst Biomed Sci, Seoul 133791, South Korea. NR 24 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD SEP PY 1998 VL 45 IS 6 BP 1089 EP 1103 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118HA UT WOS:000075831300003 PM 9762407 ER PT J AU Chang, YY Kim, SJ Park, TK Kang, SS Ha, MJ Mushinski, JF Chun, JS AF Chang, YY Kim, SJ Park, TK Kang, SS Ha, MJ Mushinski, JF Chun, JS TI Modulation of map kinase signaling and growth characteristics by the overexpression of protein kinase C in NIH3T3 cells SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE protein kinase C; MAP kinase; PDGF; phorbol ester ID PHORBOL ESTERS; ACTIVATION; ISOFORMS; EPSILON; DELTA; RAF AB This study was performed to examine effects of the overexpression of protein kinase C (PKC) isoforms (i.e., beta I, beta II, gamma, delta, eta, and zeta)on mitogen-activated protein (MAP) kinase (Erk-1 and -2) signaling and growth characteristics of NIH3T3 cells. Phorbol ester (PMA) activated endogenous and ectopically expressed PKC alpha, beta I, beta II, gamma, delta, epsilon, and eta. Overexpression of the examined PKC isoforms enhanced PMA-induced MAP kinase activation. Potentiation of MAP kinase activation was also observed upon stimulation of cells with platelet-derived growth factor (PDGF) although there was no indication for the activation PKC isoforms by PDGF. Inhibition of PKC blocked PMA- but not PDGF-induced MAP kinase activation. Thus, potentiation of PDGF-induced MAP kinase activation appears to be independent to PKC activity, while PMA-induced MAP kinase activation requires PKC activity. The ability of PKC isoforms to potentiate MAP kinase activation is not related to the growth characteristics of cells because individual PKC isoforms differentially regulated maximum density and proliferation of cells. C1 Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Taegu 702701, South Korea. Ajou Univ, Inst Med Sci, Med Genet Lab, Suwon 441749, South Korea. NCI, Genet Lab, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. RP Chun, JS (reprint author), Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Taegu 702701, South Korea. NR 20 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD SEP PY 1998 VL 45 IS 6 BP 1139 EP 1148 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 118HA UT WOS:000075831300008 PM 9762412 ER PT J AU Anderson, DE AF Anderson, DE TI Cardiorenal effects of behavioral inhibition of breathing SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE blood pressure; digitalis-like factors; hypercapnia; hypertension; hypoventilation; sodium ID PERIPHERAL ARTERIAL CHEMORECEPTORS; BLOOD-PRESSURE; NATURAL-ENVIRONMENT; HYPERTENSION; SODIUM; OUABAIN; RAT; HYPOVENTILATION; ELEVATION; EPISODES AB This article reviews evidence that mild, but sustained, inhibition of breathing can affect blood pressure regulation via effects of increased P-CO2 on sodium regulation. Experiments with micropigs are summarized which show that anticipation of the onset of a familiar avoidance task is accompanied by sustained increases in P-CO2, increases in plasma hydrogen and bicarbonate ion concentrations, decreases in hematocrit, and increases in circulating levels of sodium pump inhibitors that are sensitive to plasma volume. Observational studies with humans using an ambulatory respiration monitor characterize episodes of inhibited breathing occurring in the natural environment. Experimental studies with human subjects show that voluntary maintenance of end-tidal CO, near the upper end of the normal range results in decreases in renal sodium excretion, increases in plasma sodium pump inhibitors and inhibition of sodium pump activity. Together, these studies are consistent with the view that behavioral stress can influence blood pressure regulation via sustained inhibition of respiration which acidifies the plasma and increases sodium/hydrogen exchange in kidneys and blood vessels. Published by Elsevier Science B.V. C1 NIA, Behav Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Anderson, DE (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 1998 VL 49 IS 1-2 BP 151 EP 163 DI 10.1016/S0301-0511(98)00033-7 PG 13 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 130XH UT WOS:000076545300011 PM 9792491 ER PT J AU Anderson, DE AF Anderson, DE TI Critique - Trusting computerized data reduction too much: A critique of Anderson's ambulatory respiratory monitor - Response SO BIOLOGICAL PSYCHOLOGY LA English DT Article C1 NIA, Gerontol Res Ctr, Behav Sci Lab, Baltimore, MD 21224 USA. RP Anderson, DE (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 1998 VL 49 IS 1-2 BP 221 EP 222 DI 10.1016/S0301-0511(98)00037-4 PG 2 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 130XH UT WOS:000076545300015 ER PT J AU Samathanam, CA Adesanya, OO Zhou, J Wang, J Bondy, CA AF Samathanam, CA Adesanya, OO Zhou, J Wang, J Bondy, CA TI Fibroblast growth factors 1 and 2 in the primate uterus SO BIOLOGY OF REPRODUCTION LA English DT Article ID MOUSE UTERUS; EXPRESSION; SEQUENCE; TISSUES; RABBIT AB Fibroblast growth factors (FGF) 1 and 2 are paracrine effecters of proliferation and angiogenesis in many tissues. To elucidate potential roles for these growth factors in uterine plasticity, we used in situ hybridization histochemistry to identify the cellular sources of FGF-1 and -2 production, and immunohistochemistry to identify the cellular and extracellular deposition sites of the peptides in the primate uterus. To evaluate the effects of estradiol on uterine FGFs, uteri from ovariectomized rhesus monkeys treated with estradiol- or vehicle-containing pellets were investigated. FGF-1 and -2 mRNAs were both expressed in uterine epithelial and myometrial cells. Quantitative comparison of their mRNA levels using computerized grain counting showed no significant difference between estradiol- and vehicle-treated animals. FGF-1 immunoreactivity was detected in scattered epithelial, vascular, and myometrial cells in the vehicle-treated animals but found to be significantly more intense and widespread in estradiol-treated animals. In both conditions, FGF-1 immunostaining was predominantly nuclear. FGF-2 immunoreactivity was concentrated extracellularly in the basal lamina of both glandular and surface epithelium and was abundant and diffusely distributed within myometrial and vascular cells in both cytoplasm and nucleus. There was no apparent difference in the pattern or intensity of FGF-2 immunostaining related to estradiol treatment. These data demonstrate that major uterine cell types synthesize both FGF-1 and -2, and that the two peptides are differentially localized in uterine cellular and extracellular compartments and differentially sensitive to regulation by estradiol. C1 NICHD, Sect Womens Hlth, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Sect Womens Hlth, Dev Endocrinol Branch, NIH, Bldg 10,10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@cc1.nichd.nih.gov NR 18 TC 16 Z9 17 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 1998 VL 59 IS 3 BP 491 EP 496 DI 10.1095/biolreprod59.3.491 PG 6 WC Reproductive Biology SC Reproductive Biology GA 114DY UT WOS:000075594900006 PM 9716545 ER PT J AU Coon, SL Begay, V Falcon, J Klein, DC AF Coon, SL Begay, V Falcon, J Klein, DC TI Expression of melatonin synthesis genes is controlled by a circadian clock in the pike pineal organ but not in the trout SO BIOLOGY OF THE CELL LA English DT Article DE melatonin; circadian; pineal; serotonin N-acetyltransferase ID SEROTONIN N-ACETYLTRANSFERASE; PHOTORECEPTOR CELLS; MESSENGER-RNA; GLAND; SECRETION; INVITRO; DARKNESS; CULTURE; RETINA; LIGHT AB The photosensitive teleost pineal organ exhibits a daily rhythm in melatonin production. In most teleosts, including the pike, this is driven by an endogenous pineal clock. An exception is the trout, in which the pineal melatonin rhythm. is a direct response to darkness. This fundamental difference in the regulation of melatonin production in two closely related species provides investigators a novel opportunity to study the molecular mechanisms of vertebrate clock function. We have studied the circadian regulation of mRNA encoding two melatonin synthesis enzymes by Northern blot analysis. These hive enzymes are serotonin N-acetyltransferase (AA-NAT), the penultimate enzyme in melatonin synthesis, and tryptophan hydroxylase (TPH), the first enzyme in melatonin synthesis. A clock controls expression of both AA-NAT and TPH mRNAs in the pineal organ of pike, but not that of trout, in which the levels of these mRNAs are tonically elevated. A parsimoneous explanation of this is that a single circadian system regulates the expression of both AA-NAT and TPH genes in most teleosts, and that in trout this system has been disrupted, perhaps by a single mutation. ((C) Elsevier, Paris). C1 NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Fac Sci Poitiers, Lab Neurobiol Cellulaire, Dept Neurosci, CNRS UMR 6558, F-86022 Poitiers, France. RP Klein, DC (reprint author), NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, NIH Bldg 49,Room 5A38, Bethesda, MD 20892 USA. RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 NR 26 TC 20 Z9 20 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD SEP PY 1998 VL 90 IS 5 BP 399 EP 405 DI 10.1016/S0248-4900(98)80089-0 PG 7 WC Cell Biology SC Cell Biology GA 140FK UT WOS:000077076600004 PM 9835014 ER PT J AU Xu, JL Prorok, PC AF Xu, JL Prorok, PC TI Estimating a distribution function of the tumor size at metastasis SO BIOMETRICS LA English DT Article DE biased sampling model; constraint; metastases; missing data; nonparametric estimation; size distribution; tumor ID NONPARAMETRIC-ESTIMATION; CANCER AB In studying the relationship between the size of primary cancers and the occurrence of metastases, two quantities are of prime importance. The first is the distribution of tumor size at the point of metastatic transition, while the second is the probability that detectable metastases are present when cancer comes to medical attention. Kimmel and Flehinger (1991, Biometrics 47, 987-1004) developed a general nonparametric model and studied its two limiting cases, Because of unidentifiablity of their general model, a new identifiable model is introduced by making the hazard function for detecting a metastatic cancer a constant. The new model includes Kimmel and Flehinger's (1991) second limiting model as a special case. An estimator of the tumor size distribution at metastases is proposed. The result is applied to a set of colorectal cancer data. C1 Univ Houston, Dept Math, Houston, TX 77204 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. RP Xu, JL (reprint author), Univ Houston, Dept Math, Houston, TX 77204 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1998 VL 54 IS 3 BP 859 EP 864 DI 10.2307/2533840 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 192TY UT WOS:000080096700006 PM 9750239 ER PT J AU Shih, JH AF Shih, JH TI Modeling multivariate discrete failure time data SO BIOMETRICS LA English DT Article DE marginal models; multivariate discrete failure times; odds ratio; pseudo-likelihood ID ESTIMATING EQUATIONS; LOGISTIC-REGRESSION; ASSOCIATION; PARAMETER AB A bivariate discrete survival distribution that allows flexible modeling of the marginal distributions and yields a constant odds ratio at any grid point is proposed. The distribution can be extended to a multivariate distribution and is readily generalized to accommodate covariates in the marginal distributions and pairwise odds ratios. In addition, a pseudo-likelihood estimation procedure for estimating the regression coefficients in the marginal models and the association parameters in the pairwise odds ratios is presented. We evaluate the performance of the proposed estimation procedure through simulations. For bivariate data, pseudo-likelihood estimation of the association parameter has high efficiency. Loss of efficiency in the marginal regression coefficient estimates is small when the association is not strong. For both the marginal regression coefficients and the association parameter, coverage probabilities are close to the 95% nominal level. For multivariate data, the simulation results show that the parameter estimates are consistent. Coverage probability for the regression coefficient in the marginal model is close to the 95% nominal level but is slightly less than the nominal level for the association parameter. We illustrate the proposed methods using a subset of the Framingham Heart Study data where a significant positive association was found between the failure times of siblings. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Shih, JH (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. NR 16 TC 14 Z9 14 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1998 VL 54 IS 3 BP 1115 EP 1128 DI 10.2307/2533861 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 192TY UT WOS:000080096700027 PM 9750256 ER PT J AU Midthune, DN Korn, EL Graubard, BI AF Midthune, DN Korn, EL Graubard, BI TI Truncated logistic regression and residual intracluster correlation SO BIOMETRICS LA English DT Letter ID ESTIMATORS C1 Management Informat Serv Inc, Silver Spring, MD 20902 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. RP Midthune, DN (reprint author), Management Informat Serv Inc, 12501 Prosper Dr,Suite 200, Silver Spring, MD 20902 USA. NR 8 TC 0 Z9 0 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1998 VL 54 IS 3 BP 1193 EP 1195 PG 3 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 192TY UT WOS:000080096700037 ER PT J AU Kozlov, MM Chernomordik, LV AF Kozlov, MM Chernomordik, LV TI A mechanism of protein-mediated fusion: Coupling between refolding of the influenza hemagglutinin and lipid rearrangements SO BIOPHYSICAL JOURNAL LA English DT Article ID INDUCED MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; COILED-COIL; PH; BILAYERS; PEPTIDE; CELL; CONFORMATION; HEMIFUSION; PORE AB Although membrane fusion mediated by influenza virus hemagglutinin (HA) is the best characterized example of ubiquitous protein-mediated fusion, it is still not known how the low-pH-induced refolding of HA trimers causes fusion. This refolding involves 1) repositioning of the hydrophobic N-terminal sequence of the HA2 subunit of HA ("fusion peptide"), and 2) the recruitment of additional residues to the cu-helical coiled coil of a rigid central rod of the trimer. We propose here a mechanism by which these conformational changes can cause local bending of the viral membrane, priming it for fusion. In this model fusion is triggered by incorporation of fusion peptides into viral membrane. Refolding of a central rod exerts forces that pull the fusion peptides, tending to bend the membrane around HA trimer into a saddle-like shape. Elastic energy drives self-assembly of these HA-containing membrane elements in the plane of the membrane into a ring-like cluster. Bulging of the viral membrane within such cluster yields a dimple growing toward the bound target membrane. Bending stresses in the lipidic top of the dimple facilitate membrane fusion. We analyze the energetics of this proposed sequence of membrane rearrangements, and demonstrate that this simple mechanism may explain some of the known phenomenological features of fusion. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM misha@devil.tav.ac.i1 NR 58 TC 127 Z9 131 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1998 VL 75 IS 3 BP 1384 EP 1396 PG 13 WC Biophysics SC Biophysics GA 114TL UT WOS:000075625100025 PM 9726939 ER PT J AU Schuck, P AF Schuck, P TI Sedimentation analysis of noninteracting and self-associating solutes using numerical solutions to the Lamm equation SO BIOPHYSICAL JOURNAL LA English DT Article ID MACROMOLECULAR SEPARATIONS; INTERACTING PARTICLES; VELOCITY EXPERIMENTS; GENERALIZED SYSTEMS; TIME COURSE; ULTRACENTRIFUGE; SIMULATION AB The potential of using the Lamm equation in the analysis of hydrodynamic shape and gross conformation of proteins and reversibly formed protein complexes from analytical ultracentrifugation data was investigated. An efficient numerical solution of the Lamm equation for noninteracting and rapidly self-associating proteins by using combined finite-element and moving grid techniques is described. It has been implemented for noninteracting solutes and monomerdimer and monomer-trimer equilibria. To predict its utility, the error surface of a nonlinear regression of simulated sedimentation profiles was explored, Error contour maps were calculated for conventional independent and global analyses of experiments with noninteracting solutes and with monomer-dimer systems at different solution column heights, loading concentrations, and centrifugal fields. It was found that the rotor speed is the major determinant for the shape of the error surface, and that global analysis of different experiments can allow substantially improved characterization of the solutes. We suggest that the global analysis of the approach to equilibrium in a short-column sedimentation equilibrium experiment followed by a high-speed short-column sedimentation velocity experiment can result in sedimentation and diffusion coefficients of very high statistical accuracy. In addition, in the case of a protein in rapid monomer-dimer equilibrium, this configuration was found to reveal the most precise estimate of the association constant. C1 NIH, Mol Interact Resource Bioengn & Phys Sci Program, OD, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, Mol Interact Resource Bioengn & Phys Sci Program, OD, Bldg 13,Rm 3N17,13 S Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 40 TC 257 Z9 258 U1 2 U2 15 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1998 VL 75 IS 3 BP 1503 EP 1512 PG 10 WC Biophysics SC Biophysics GA 114TL UT WOS:000075625100038 PM 9726952 ER PT J AU Nossal, R AF Nossal, R TI Cell transit analysis of ligand-induced stiffening of polymorphonuclear leukocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID PASSIVE MECHANICAL-BEHAVIOR; F-ACTIN DISTRIBUTION; G-PROTEIN ACTIVATION; HUMAN-NEUTROPHILS; SIGNAL-TRANSDUCTION; MONTE-CARLO; SHAPE; NETWORKS; PEPTIDE; DEFORMATION AB A mathematical treatment of the mechanical behavior of transiently bonded polymer networks is used to interpret measurements of the pressure-induced passage of pliant cells through microporous membranes. Cell transit times are inferred to be proportional to the instantaneous shear modulus of the cell cortex, a parameter that we then relate to properties of the cortical F-actin matrix. These theoretical results are used to analyze published data on chemoattractant-induced changes of rigidity of polymorphonuclear leukocytes, We thereby rationalize previously noted, peculiar, power-law logarithmic dependences of transit time on ligand concentration. As a consequence, we are able to deduce a linear relationship between the extent of F-actin polymerization and the logarithm of the chemoattractant concentration. The latter is examined with regard to the G-protein activation that is known to occur when chemoattractants bind to receptors on the surfaces of polymorphonuclear cells. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 12A,Rm 2043, Bethesda, MD 20892 USA. NR 46 TC 9 Z9 9 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1998 VL 75 IS 3 BP 1541 EP 1552 PG 12 WC Biophysics SC Biophysics GA 114TL UT WOS:000075625100042 PM 9726956 ER PT J AU Wiener, MC Richmond, BJ AF Wiener, MC Richmond, BJ TI Using response models to study coding strategies in monkey visual cortex SO BIOSYSTEMS LA English DT Article; Proceedings Paper CT International Workshop on NEURONAL CODING 97 CY SEP 29-OCT 03, 1997 CL VERSAILLES, FRANCE DE visual cortex; information; channel capacity; coding ID SINGLE UNITS; 2-DIMENSIONAL PATTERNS; NEURONAL RESPONSES; CORTICAL-NEURONS; TEMPORAL CORTEX; STRIATE CORTEX; INFORMATION; VARIABILITY; FACES AB Usually the conditional probabilities needed to calculate transmitted information are estimated directly from empirically measured distributions. Here we show that an explicit model of the relation between response strength (here, spike count) and its variability allows accurate estimates of transmitted information. This method of estimating information is reliable for data sets with nine or more trials per stimulus. We assume that the model characterizes all response distributions, whether observed in a given experiment or not. All stimuli eliciting the same response are considered equivalent. This allows us to calculate the channel capacity, the maximum information that a neuron can transmit given the variability with which it sends signals. Channel capacity is uniquely defined, thus avoiding the difficulty of knowing whether the 'right' stimulus set has been chosen in a particular experiment. Channel capacity increases with increasing dynamic range and decreases as the variance of the signal (noise) increases. Neurons in V1 send more variable signals in a wide dynamic range of spike counts, while neurons in IT send less variable signals in a narrower dynamic range. Nonetheless, neurons in the two areas have similar channel capacities. This suggests that variance is being traded off against dynamic range in coding. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, 1B-80,Bldg 49, Bethesda, MD 20892 USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PD SEP-DEC PY 1998 VL 48 IS 1-3 BP 279 EP 286 PG 8 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 152CH UT WOS:000077757600034 PM 9886658 ER PT J AU Whitwam, T Haskins, ME Henthorn, PS Kraszewski, JN Kleiman, SE Seidel, NE Bodine, DM Puck, JM AF Whitwam, T Haskins, ME Henthorn, PS Kraszewski, JN Kleiman, SE Seidel, NE Bodine, DM Puck, JM TI Retroviral marking of canine bone marrow: Long-term, high-level expression of human interleukin-2 receptor common gamma chain in canine lymphocytes SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; HUMAN-GENE-THERAPY; PERIPHERAL-BLOOD; IN-VIVO; LYMPHOID DEVELOPMENT; REPOPULATING CELLS; PROGENITOR CELLS; T-CELLS AB Optimization of retroviral gene transfer into hematopoietic cells of the dog will facilitate gene therapy of canine X-linked severe combined immunodeficiency (XSCID) and in turn advance similar efforts to treat human XSCID. Both canine and human XSCID are caused by defects in the common gamma chain, gamma c, of receptors for interleukin-a and other cytokines. In this study, normal dogs were given retrovirally transduced bone marrow cells with and without preharvest mobilization by the canine growth factors granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Harvey sarcoma virus and Moloney murine leukemia virus constructs were used, both containing cDNA encoding human gamma c. The Harvey-based vector transduced into cytokine-primed marrow yielded persistent detectable provirus in bone marrow and blood and expression of human gamma c on peripheral lymphocytes. In three dogs, human gamma c expression disappeared after 19 to 34 weeks but reappeared and was sustained, iri one dog beyond 16 months posttransplantation, upon immunosuppression with cyclosporin A and prednisone, with up to 25% of lymphocytes expressing human gamma c. The long-term expression of human gamma c in a high proportion of normal canine lymphocytes predicts that retrovirus-mediated gene correction of hematopoietic cells may prove to be of clinical benefit ih humans affected with this XSCID. This is a US government work. There are no restrictions on its use. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Dept Genet, Philadelphia, PA 19104 USA. RP Puck, JM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bldg 49,Rm 3A14,49 Convent Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI33177]; NIDDK NIH HHS [DK54481]; NINDS NIH HHS [NS33526] NR 47 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1565 EP 1575 PG 11 WC Hematology SC Hematology GA 113NP UT WOS:000075558400012 PM 9716584 ER PT J AU Secchiero, P Bertolaso, L Casareto, L Gibellini, D Vitale, M Bemis, K Aleotti, A Capitani, S Franchini, G Gallo, RC Zauli, G AF Secchiero, P Bertolaso, L Casareto, L Gibellini, D Vitale, M Bemis, K Aleotti, A Capitani, S Franchini, G Gallo, RC Zauli, G TI Human herpesvirus 7 infection induces profound cell cycle perturbations coupled to disregulation of cdc2 and cyclin B and polyploidization of CD4(+) T cells SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXANTHEM-SUBITUM; PROTEIN-KINASE; VPR ARRESTS; ACTIVATION; APOPTOSIS; MITOSIS; DEATH; PHASE; G(2) AB Human herpesvirus 7 (HHV-7) infection of both primary CD4(+) T lymphocytes and SupT1 lymphoblastoid T-cell line induced a progressive accumulation of cells exibiting a gap 2/mitosis (G(2)/M) and polyploid content coupled to an increased cell size. The expression of both cyclin-dependent kinase cdc2 and cyclin B was increased in HHV-7-infected cells with respect to the uninfected ones. Moreover, the simultaneous flow cytometric analysis of cyclin B and DNA content showed that cyclin B expression was not only increased but also unscheduled with respect to its usual cell cycle pattern. However, the levers of kinase activity associated to cdc2 were decreased in HHV-7-infected cells with respect to uninfected cultures. To elucidate the origin of the enlarged HHV-7-infected cells, extensive electron and confocal microscopy analyses were performed. Membrane fusion events associated to cytoplasmic bridges, which characterize the formation of syncytia, were never observed. On the other hand, analysis of serial sections of the same cells strongly suggested that enlarged HHV-7-infected cells contained a single polylobated nucleus. This was confirmed by flow cytometry analysis performed on nuclei isolated from HHV-7-infected cells, which showed multiple peaks with a DNA content >4n. Taken together, these data indicate that giant cells, which represent the hallmark of in vitro HHV-7 infection, arise from single CD4(+) T cells undergoing a process of polyploidization. (C) 1998 by The American Society of Hematology. C1 Univ Ferrara, Inst Human Anat, I-44100 Ferrara, Italy. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Bologna, Inst Microbiol, Bologna, Italy. Dept Biomed Sci & Biotechnol, Human Anat Sect, Brescia, Italy. RP Zauli, G (reprint author), Univ Ferrara, Inst Human Anat, Via Fossato Mortara 66, I-44100 Ferrara, Italy. RI secchiero, paola/G-9689-2015; Vitale, Marco/O-8751-2015; OI secchiero, paola/0000-0003-4101-7987; Vitale, Marco/0000-0002-3261-6868; CAPITANI, Silvano/0000-0003-2795-6814; Zauli, Giorgio/0000-0002-3750-8698 NR 51 TC 28 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1685 EP 1696 PG 12 WC Hematology SC Hematology GA 113NP UT WOS:000075558400025 PM 9716597 ER PT J AU Rao, PH Cigudosa, JC Ning, Y Calasanz, MJ Iida, S Tagawa, S Michaeli, J Klein, B Dalla-Favera, R Jhanwar, SC Ried, T Chaganti, RSK AF Rao, PH Cigudosa, JC Ning, Y Calasanz, MJ Iida, S Tagawa, S Michaeli, J Klein, B Dalla-Favera, R Jhanwar, SC Ried, T Chaganti, RSK TI Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma SO BLOOD LA English DT Article ID LARGE-CELL LYMPHOMA; CHROMOSOMAL TRANSLOCATION; CYTOGENETIC ANALYSIS; MOLECULAR-CLONING; GENE; ABNORMALITIES; HYBRIDIZATION; DIAGNOSIS AB Karyotypic information on multiple myeloma (MM) is less extensive than that on other myeloid or lymphoid malignancies due to low mitotic activity of plasma cells. An add(14)(q32) marker chromosome has been reported to be the most frequent recurring abnormality in clonally abnormal cases; in approximately one third of the latter cases, this marker has been identified as a der(14)t(11;14)(q13;q32) chromosome. To map chromosomal breakpoints, characterize the add(14)(q32) marker chromosomes, and to identify other recurring translocations in MM, we used spectral karyotyping (SKY) to analyze a panel of nine bone marrow (BM) biopsy samples from eight patients and 10 tumor cell lines derived from MM patients. SKY involves hybridization of 24 fluorescently labeled chromosome painting probes to metaphase spreads in such a manner that simultaneous visualization of each of the chromosomes in a different color is accomplished. By this method, it was possible to define all chromosomal rearrangements and identify all of the clonal marker chromosomes in tumor cells. By detailed mapping of breakpoints of rearrangement, it was also possible to identify several novel recurring sites of breakage that map to the chromosomal bands 3q27, 17q24-25, and 20q11. The partner chromosomes in translocations that generated the add (14)(q32) marker chromosomes were identified in all cases in which they were detected by G-banding(one biopsy and six eel lines); In addition, two new translocations involving band 14q32, ie, t(12;14)(q24;q32) and t(14;20)(q32;q11) have also been identified. These studies demonstrate the power of SKY in resolving the full spectrum of chromosome abnormalities in tumors. (C) 1998 by The American Society of Hematology. C1 Mem Sloan Kettering Canc Ctr, Cell Biol & Genet Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Univ Navarra, Dept Genet, E-31080 Pamplona, Spain. Osaka City Univ, Sch Med, Dept Clin Hematol, Osaka, Japan. Univ Montpellier, Inst Mol Genet, F-34059 Montpellier, France. Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. RP Chaganti, RSK (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. RI Calasanz, MJ/R-5813-2016 OI Calasanz, MJ/0000-0002-0374-3008 FU NCI NIH HHS [CA-34775, CA-66999] NR 29 TC 106 Z9 108 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1998 VL 92 IS 5 BP 1743 EP 1748 PG 6 WC Hematology SC Hematology GA 113NP UT WOS:000075558400032 PM 9716604 ER PT J AU Schwartz, GN Warren, MK Rothwell, SW Zujewski, J Halverson, DC Cowan, KH Tolcher, A O'Shaughnessy, J Gress, RE AF Schwartz, GN Warren, MK Rothwell, SW Zujewski, J Halverson, DC Cowan, KH Tolcher, A O'Shaughnessy, J Gress, RE TI Post-chemotherapy and cytokine pretreated marrow stromal cell layers suppress hematopoiesis from normal donor CD34(+) cells SO BONE MARROW TRANSPLANTATION LA English DT Article DE bone marrow; hematopoiesis; stem cells; stomal cells; TNF-alpha ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; HUMAN BONE-MARROW; ADVANCED BREAST-CANCER; LONG-TERM CULTURES; PROGENITOR CELLS; CYCLOPHOSPHAMIDE CHEMOTHERAPY; MYELOABLATIVE THERAPY; NEGATIVE REGULATORS; POPULATION FOLLOW AB Marrow stromal layers were used to investigate the potential role of negative regulators produced by the marrow microenvironment as one potential cause of hematopoietic suppression after chemotherapy and cytokines. Stromal layers were established from marrow of normal or prechemotherapy donors and breast cancer patients after hematological recovery from one cycle of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide and GM-CSF or PIXY321 (GM-CSF/IL-3 fusion protein). Normal donor CD34(+) cells were placed in contact with stromal layers, and the number of colony-forming units for granulocytes and macrophages (CFU-GM) was determined. There were 25-79% fewer CFU-GM in post-chemotherapy stromal layer cocultures than in no chemotherapy cocultures. With neutralizing antibody to TNF-a the number of CFU-GM in no chemotherapy and post-chemotherapy stromal cocultures was, respectively, 96 +/- 7% (n = 5) and 142 +/- 8% (n = 5) of the number with no antibody treatment. PIXY321 and GM-CSF pretreated stromal layers also suppressed production of CFU-GM. Anti-TNF-alpha promoted an increase in CFU-GM numbers from GM-CSF, but not PIXY321, pretreated stromal cocultures, The results demonstrate that post-chemotherapy marrow stromal layers were deficient in supporting in vitro hematopoiesis and suggest that negative regulators induced by chemotherapy and cytokines may be one cause for this defect. C1 NCI, Dept Expt Transplantat & Immunol, Med Branch, Bethesda, MD 20892 USA. Otsuka Pharmaceut Co Ltd, Rockville, MD USA. Walter Reed Army Inst Res, Dept Hematol, Washington, DC USA. RP Schwartz, GN (reprint author), NCI, Dept Expt Transplantat & Immunol, Med Branch, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 56 TC 24 Z9 26 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 1998 VL 22 IS 5 BP 457 EP 468 DI 10.1038/sj.bmt.1701364 PG 12 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 112MC UT WOS:000075497600007 PM 9733269 ER PT J AU Gerloff, C Corwell, B Chen, R Hallett, M Cohen, LG AF Gerloff, C Corwell, B Chen, R Hallett, M Cohen, LG TI The role of the human motor cortex in the control of complex and simple finger movement sequences SO BRAIN LA English DT Article DE motor cortex; premotor cortex; finger movements; motor sequences; motor control ID TRANSCRANIAL MAGNETIC STIMULATION; NEURONAL-ACTIVITY; PREMOTOR CORTEX; RHESUS-MONKEYS; NEURAL REPRESENTATIONS; SEQUENTIAL MOVEMENTS; VOLUNTARY MOVEMENTS; LOCAL INACTIVATION; PRIMATE PREMOTOR; 2 FINGERS AB We evaluated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) at different stimulus intensities on finger sequences of varying complexity, Eighteen subjects played unimanual finger sequences of different complexity on an electronic piano. For each finger sequence, 16 notes were played to the 2 Hz beat of a metronome, After the first four notes, rTMS was applied to the scalp location overlying the hand motor representation for approximately 2 s. Accuracy and timing errors were analysed. Stimulation over the M1 had a differential effect on sequences of different complexity. Stimulus intensities capable of disrupting the performance of a complex sequence did not affect simple sequences. To disrupt simple sequences, the stimulus strength had to be augmented, This effect was characteristic of the contralateral M1 position (five other scalp locations were also stimulated). It is argued that the differential effect of rTMS on simple and complex sequences is probably due to interference with M1 function. Interference,vith the lateral premotor cortex (PMC) may play an additional role. The particular relevance of the M1 is supported by results in a patient with PMC stroke. The present findings suggest that the human M1 plays a greater role in the performance of complex than of simple finger movement sequences. One possible explanation could be that the human M1 is not only an executive motor area but can also contribute to movement sequence organization. C1 NINDS, Human Cort Physiol Unit, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, Med Neurol Branch, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 64 TC 118 Z9 119 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 1998 VL 121 BP 1695 EP 1709 DI 10.1093/brain/121.9.1695 PN 9 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 125FL UT WOS:000076226700008 PM 9762958 ER PT J AU Roberts-Thomson, SJ Snyderwine, EG AF Roberts-Thomson, SJ Snyderwine, EG TI mRNA differential display of 2-amino-1-methyl-6-phenylinlidazo[4,5-b]pyridine-induced rat mammary gland tumors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE dietary fat; differential display; heterocyclic amine; mammary gland; rat ID TRANSFERRIN-GENE-EXPRESSION; SPRAGUE-DAWLEY RATS; HUMAN BREAST-CANCER; MESSENGER-RNA; DIETARY-FAT; HETEROCYCLIC AMINES; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; FALSE POSITIVES; COOKED FOODS AB The mRNA differential display technique was used to compare mRNAs between normal mammary gland and turner-derived epithelial cells from female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a high-fat diet (23.5% corn oil). Two genes, beta-casein and transferrin, were identified as differentially expressed. The expression of these genes was examined across a bank of rat mammary gland tumors derived from animals on a low-fat diet (5% corn oil) or the high-fat diet. Carcinomas had over a 10- and 50-fold lower expression of beta-casein and transferrin, respectively than normal mammary gland. In addition, carcinomas from animals on the high-fat diet showed on average a 5-fold higher expression of beta-casein, and transferrin than carcinomas from animals on the low-fat diet. The results indicate the process of mammary gland tumorigenesis alters the expression of certain genes in the mammary gland, and that the level of dietary fat further modulates the expression of these genes. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. Univ Queensland, Sch Pharm, Brisbane, Qld, Australia. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov RI Roberts-Thomson, Sarah/B-4282-2011 OI Roberts-Thomson, Sarah/0000-0001-8202-5786 NR 49 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 1998 VL 51 IS 2 BP 99 EP 107 DI 10.1023/A:1006048014965 PG 9 WC Oncology SC Oncology GA 155BH UT WOS:000077925700001 PM 9879772 ER PT J AU Decensi, A Robertson, C Rotmensz, N Severi, G Maisonneuve, P Sacchini, V Boyle, P Costa, A Veronesi, U AF Decensi, A Robertson, C Rotmensz, N Severi, G Maisonneuve, P Sacchini, V Boyle, P Costa, A Veronesi, U CA Italian Chemoprevention Grp TI Effects of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast neoplasm; chemoprevention; tamoxifen; oestrogen replacement therapy; cholesterol ID CORONARY HEART-DISEASE; NEGATIVE BREAST-CANCER; GROWTH FACTOR-I; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; ESTROGEN REPLACEMENT; RANDOMIZED TRIAL; DRUG-THERAPY; CHOLESTEROL; MORTALITY AB The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term), We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity. C1 European Inst Oncol, FIRC Chemoprevent Unit, I-20141 Milan, Italy. European Inst Oncol, Dept Epidemiol & Biostat, I-20141 Milan, Italy. European Inst Oncol, Div Senol, I-20141 Milan, Italy. Natl Canc Inst, Dept Med Oncol AD 2, I-16132 Genoa, Italy. RP Rotmensz, N (reprint author), European Inst Oncol, FIRC Chemoprevent Unit, Via Ripamonti 435, I-20141 Milan, Italy. RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 NR 45 TC 24 Z9 24 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1998 VL 78 IS 5 BP 572 EP 578 DI 10.1038/bjc.1998.542 PG 7 WC Oncology SC Oncology GA 112MK UT WOS:000075498200003 PM 9744493 ER PT J AU Molldrem, JJ Jiang, YZ Stetler-Stevenson, M Mavroudis, D Hensel, N Barrett, AJ AF Molldrem, JJ Jiang, YZ Stetler-Stevenson, M Mavroudis, D Hensel, N Barrett, AJ TI Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor V-beta profiles SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bone marrow T lymphocytes; myelodysplastic syndrome; immunosuppression ID APLASTIC-ANEMIA; ANTILYMPHOCYTE GLOBULIN; APOPTOSIS; INVITRO; DISEASES; LEUKEMIA AB We have demonstrated that 44% of myelodysplastic syndrome (MDS) patients with cytopenia have a haematological response to antithymocyte globulin (ATG). Three ATG responders and two non-responders with refractory anaemia were further studied for lymphocyte-mediated inhibition of bone marrow using a standard CFU-GM assay. In responders, peripheral blood lymphocytes (PBL) added at a 5:1 ratio suppressed CFU-GM by 54 +/- 9% (P = 0.04) and was reversed by ATG treatment. Pre-treatment marrow depleted of CD3 lymphocytes, increased CFU-GM by 32% (P = 0.02) in an ATG responder, but not in a nonresponder. CD3 lymphocytes from 6-month post-treatment marrow did not inhibit pre-treatment CFU-GM, indicating ATG had affected the T cells. Pre-treatment marrow depleted of CD8 lymphocytes, increased CFU-GM by 60% (P = 0.01) and 49% (P = 0.03) in two ATG responders, but not in a non-responder. Inhibition required cell-cell interaction through MHC I. TCRV beta families, analysed by SSCP, changed from clonal to polyclonal in one ATG responder after 6 months, but clones persisted in a non-responder. These results indicate patients with refractory anaemia who respond to ATG have CDS T-cell clones that mediate MHC-I-restricted suppression of CFU-GM which are replaced by polyclonal T cells that do not suppress CFU-GM after ATG treatment. C1 Univ Texas, Md Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Molldrem, JJ (reprint author), Univ Texas, Md Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Box 24,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 128 Z9 138 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1998 VL 102 IS 5 BP 1314 EP 1322 DI 10.1046/j.1365-2141.1998.00920.x PG 9 WC Hematology SC Hematology GA 121YK UT WOS:000076043500030 PM 9753062 ER PT J AU Raptis, A Clave, E Molldrem, J Van Rhee, F Barrett, AJ AF Raptis, A Clave, E Molldrem, J Van Rhee, F Barrett, AJ TI Polymorphism in CD33 and CD34 genes: a source of minor histocompatibility antigens on haemopoietic progenitor cells? SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD33; CD34; polymorphism; minor histocompatibility antigens; adoptive immunotherapy ID HEMATOPOIETIC STEM-CELLS; MYELOID-LEUKEMIA; H-Y; PEPTIDE; RECOGNITION AB Following bone marrow stem cell transplantation allo-responses against haemopoietic progenitor cells (HPC), causing graft rejection and graft-versus-leukaemia effects, can be induced by donor T cells recognizing peptides derived from polymorphic endogenous proteins present in HPC, Since CD33 and CD34 are both expressed on HPC, we looked for genetic polymorphisms that might be the source of minor histocompatibility antigens (mHA) on such cells. Bone marrow from 14 donors and their HLA-identical recipients undergoing BRIT for haematological malignancies were studied. Using non-radioactive single-strand conformation polymorphism analysis (cold SSCP) of complementary DNA encoding CD33 and CD34, three DNA polymorphisms, two in CD33 and one in CD34 were found and sequenced. Two were in non-coding regions, but in CD33, ATA or ATG at codon 183 resulted in an lie or Met in the protein sequence. Nonapeptides derived from both alleles were predicted to bind to HLA A68.1. Thus two alleles of CD33 protein exist that could be mHA. With an alternate allele frequency of < 10%, allo-responses against CD33 would be uncommon after marrow transplantation. However, donors homozygous for this allele could be used to generate cytotoxic T cells against the frequent CD33 allele, for adoptive therapy of leukaemia. C1 NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Bone Marrow Transplantat Unit, Hematol Branch, NIH, Bldg 10,room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1998 VL 102 IS 5 BP 1354 EP 1358 PG 5 WC Hematology SC Hematology GA 121YK UT WOS:000076043500038 PM 9753070 ER PT J AU Bozzi, F Lefranc, G Villa, A Badolato, R Schumacher, RF Khalil, G Loiselet, J Bresciani, S O'Shea, JJ Vezzoni, P Notarangelo, LD Candotti, F AF Bozzi, F Lefranc, G Villa, A Badolato, R Schumacher, RF Khalil, G Loiselet, J Bresciani, S O'Shea, JJ Vezzoni, P Notarangelo, LD Candotti, F TI Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE severe combined immune deficiency; JAK3; cytokine signalling; mutation; bone marrow transplantation ID MUTATION; GENE AB Severe combined immunodeficiency (SCID) comprises a heterogenous group of disorders that are fatal unless treated by bone marrow transplantation (BMT). The most common form of SCID (T-B+ SCID) is due to mutations of either the common gamma chain (gamma c) or of gamma c-coupled JAK3 kinase. We report an unusual JAK3 defect in a female who was successfully treated > 20 years ago with a BMT using her HLA-identical father as the donor. Persistence of genetically and biochemically defective autologous B cells, associated with reconstitution of cellular and humoral immunity, suggests that integrity of the gamma c-JAK3 signalling pathway is not strictly required for immunoglobulin production. C1 Univ Brescia, Dept Paediat, Spedali Civili, I-25123 Brescia, Italy. CNR, Ist Tecnol Biomed Avanzate, Dept Human Gnome & Multifactorial Dis Res, Segrate, MI, Italy. CNRS, Inst Genet Humaine, Immunogenet Mol Lab, UPR 1142, F-75700 Paris, France. St Josephs Univ, Fac Pharm, Beirut, Lebanon. St Josephs Univ, Fac Med Dent, Beirut, Lebanon. St Josephs Univ, Fac Med, Lab Biol Mol & Cytogenet, Beirut, Lebanon. NIAMS, Lymphocyte Cell Biol Sect, ARB, NIH, Bethesda, MD USA. RP Notarangelo, LD (reprint author), Univ Brescia, Dept Paediat, Spedali Civili, I-25123 Brescia, Italy. RI Badolato, Raffaele/A-8081-2010; Notarangelo, Luigi/F-9718-2016; OI Badolato, Raffaele/0000-0001-7375-5410; Notarangelo, Luigi/0000-0002-8335-0262; Villa, Anna/0000-0003-4428-9013 FU Telethon [E.0495] NR 12 TC 8 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1998 VL 102 IS 5 BP 1363 EP 1366 PG 4 WC Hematology SC Hematology GA 121YK UT WOS:000076043500040 PM 9753072 ER PT J AU Rupp, A Gause, EM Regier, DA AF Rupp, A Gause, EM Regier, DA TI Research policy implications of cost-of-illness studies for mental disorders SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID ECONOMIC COSTS; UNITED-STATES; SCHIZOPHRENIA; HEALTH; DEPRESSION; INSURANCE; ABUSE; CARE C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Rupp, A (reprint author), NIMH, NIH, Pklawn Bldg 10C-06 MSC 8030,5600 Fishers Lane, Bethesda, MD 20892 USA. NR 25 TC 9 Z9 9 U1 1 U2 2 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1998 VL 173 SU 36 BP 19 EP 25 PG 7 WC Psychiatry SC Psychiatry GA 121FB UT WOS:000076001700005 PM 9829007 ER PT J AU Eanes, ED Hailer, AW AF Eanes, ED Hailer, AW TI The effect of fluoride on the size and morphology of apatite crystals grown from physiologic solutions SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE apatite; bone mineral; calcification; crystal texture; fluoride ID CALCIUM PHOSPHATES; HYDROXYAPATITE; PH; SOLUBILITY; IONS; CRYSTALLIZATION; MAGNESIUM; PHASES AB In adult human bone, fluoride uptake is accompanied by an increase in apatite crystal size. This increase, however, is not isotropic but is restricted primarily to growth in width and/or thickness, with no measurable change in length. In the present study, seeded growth experiments were conducted in vitro to determine whether this anisotropic effect is physicochemical in origin, i.e., a direct result of F- selectively enhancing lateral crystal growth, or is an indirect consequence of F--induced alterations in cellular function and matrix development. The growth reactions were maintained at 37 degrees C under physiologic-like solution conditions (1.33 mmol/liter Ca2+, 1.0 mmol/liter total phosphate, 0 or 26 mmol/liter carbonate, 270 mmol/kg osmolality, pH 7.4) using constant-composition methods. When new accretions accumulated to three times the initial seed mass, the solids were collected and net crystal growth was assessed by X-ray diffraction Line broadening analysis. The X-ray results revealed that the carbonate constituent in our physiologic-like solutions promoted the proliferation of new crystals at the expense of further growth of the seed apatite. Solution F- concentrations of similar to 2 mu mol/liter partially offset the repressive effect that carbonate had on primary crystal growth. Moreover, F- stimulated seed crystal growth in the same anisotropic manner as had been observed for adult human bone apatite, a finding that suggests that the latter growth in vivo was the consequence, in part, of direct F--mineral interactions. C1 Natl Inst Stand & Technol, NIDR, Craniofacial & Skeletal Dis Branch, Res Associate Program, Gaithersburg, MD 20899 USA. RP Eanes, ED (reprint author), Natl Inst Stand & Technol, NIDR, Craniofacial & Skeletal Dis Branch, Res Associate Program, Bldg 224,Room A143, Gaithersburg, MD 20899 USA. NR 53 TC 16 Z9 16 U1 1 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 1998 VL 63 IS 3 BP 250 EP 257 DI 10.1007/s002239900522 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 111XH UT WOS:000075463500012 PM 9701630 ER PT J AU Carroll, RJ Freedman, LS Kipnis, V Li, L AF Carroll, RJ Freedman, LS Kipnis, V Li, L TI A new class of measurement-error models, with applications to dietary data SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE errors in variables; estimating equations; linear regression; maximum likelihood; measurement error; method of moments; nutrition ID DOUBLY LABELED WATER; BREAST-CANCER; ENERGY-INTAKE; RECORDS; FAT; HEALTH; TRIAL; WOMEN; RISK AB Measurement-error modelling occurs when one cannot observe a covariate, but instead has possibly replicated surrogate versions of this covariate measured with error. The vast majority of the literature in measurement-error modelling assumes (typically with good reason) that given the value of the true but unobserved (latent) covariate, the replicated surrogates are unbiased for latent covariate and conditionally independent. In the area of nutritional epidemiology, there is some evidence from biomarker studies that this simple conditional independence model may break down due to two causes: (a) systematic biases depending on a person's body mass index, and (b) an additional random component of bias, so that the error structure is the same as a one-way random-effects model. We investigate this problem in the context of (1) estimating distribution of usual nutrient intake, (2) estimating the correlation between a nutrient instrument and usual nutrient intake, and (3) estimating the true relative risk from an estimated relative risk using the error-prone covariate. While systematic bias due to body mass index appears to have little effect, the additional random effect in the variance structure is shown to have a potentially important effect on overall results, both on corrections for relative risk estimates and in estimating the distribution of usual nutrient intake. However, the effect of dietary measurement error on both factors is shown via examples to depend strongly on the data set being used. Indeed, one of our data sets suggests that dietary measurement error may be masking a strong risk of fat on breast cancer, while for a second data set this masking is not so clear. Until further understanding of dietary measurement is available, measurement-error corrections must be done on a study-specific basis, sensitivity analyses should be conducted, and even then results of nutritional epidemiology studies relating diet to disease risk should be interpreted cautiously. C1 Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, Bethesda, MD 20892 USA. NR 14 TC 15 Z9 15 U1 0 U2 7 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 1998 VL 26 IS 3 BP 467 EP 477 DI 10.2307/3315770 PG 11 WC Statistics & Probability SC Mathematics GA 125GQ UT WOS:000076229400009 ER PT J AU Sherman, SI Brierley, JD Sperling, M Ain, KB Bigos, ST Cooper, DS Haugen, BR Ho, MN Klein, I Ladenson, PW Robbins, J Ross, DS Specker, B Taylor, T Maxon, HR AF Sherman, SI Brierley, JD Sperling, M Ain, KB Bigos, ST Cooper, DS Haugen, BR Ho, MN Klein, I Ladenson, PW Robbins, J Ross, DS Specker, B Taylor, T Maxon, HR CA Natl Thyr Canc Treatm Coop Stud Reg Grp TI Prospective multicenter study of thyroid carcinoma treatment - Initial analysis of staging and outcome SO CANCER LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Thyroid-Association CY NOV 13-17, 1996 CL SAN DIEGO, CALIFORNIA SP Amer Thyroid Assoc DE thyroid neoplasms; neoplasm staging; prognosis; comparative study; prospective studies; papillary carcinoma; follicular carcinoma; medullary carcinoma; anaplastic carcinoma ID PROGNOSTIC SCORING SYSTEM; PAPILLARY; CANCER; SURVIVAL AB BACKGROUND. A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with Other available staging classifications. METHODS. Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation. RESULTS. Between 1987 and 1995, 1607 patients were! registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were mc,re likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. I:ive-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage TV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1% for Stage II, 77.8% for Stage III, and 24.6% for Stage nr). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type. CONCLUSIONS. The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma. [See editorial counterpoint on pages 844-7 and reply to counterpoint on pages 848-50, this issue.] (C) 1998 American Cancer Society. C1 Univ Texas, MD Anderson Cancer Ctr, Sect Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada. Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA. Univ Kentucky, Med Ctr, Dept Med, Lexington, KY 40536 USA. Maine Med Ctr, Dept Med, Portland, ME 04102 USA. Sinai Hosp, Dept Med, Baltimore, MD 21215 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. N Shore Univ Hosp, Dept Med, Manhasset, NY 11030 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. S Dakota State Univ, Martin Program Human Nutr, Brookings, SD 57007 USA. Bayer Pharmaceut, New Haven, CT 06511 USA. RP Sherman, SI (reprint author), Univ Texas, MD Anderson Cancer Ctr, Sect Endocrine Neoplasia & Hormonal Disorders, 1515 Holcombe Blvd,Box 15, Houston, TX 77030 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 31 TC 258 Z9 262 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1998 VL 83 IS 5 BP 1012 EP 1021 PG 10 WC Oncology SC Oncology GA 115FQ UT WOS:000075653200028 PM 9731906 ER PT J AU Ritter, L Heath, C Kaegi, E Morrison, H Sieber, S AF Ritter, L Heath, C Kaegi, E Morrison, H Sieber, S CA Natl Canc Inst Canada Panel TI Report of a panel on the relationship between public exposure to pesticides and cancer - Author reply SO CANCER LA English DT Letter ID FOOD C1 Univ Guelph, Dept Environm Biol, Canadian Network Toxicol Ctr, Guelph, ON N1G 2W1, Canada. Amer Canc Soc, Atlanta, GA 30329 USA. Natl Canc Inst, Bethesda, MD USA. Hlth Canada, LCDC, Canc Bur, Behav Risk Assessment Div, Ottawa, ON, Canada. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Ritter, L (reprint author), Univ Guelph, Dept Environm Biol, Canadian Network Toxicol Ctr, Guelph, ON N1G 2W1, Canada. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1998 VL 83 IS 5 BP 1058 EP 1060 DI 10.1002/(SICI)1097-0142(19980901)83:5<1058::AID-CNCR46>3.0.CO;2-3 PG 3 WC Oncology SC Oncology GA 115FQ UT WOS:000075653200046 ER PT J AU Stinson, SF Hill, K Siford, TJ Phillips, LR Daw, TW AF Stinson, SF Hill, K Siford, TJ Phillips, LR Daw, TW TI Determination of flavopiridol (L86 8275; NSC 649890) in human plasma by reversed-phase liquid chromatography with electrochemical detection SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE flavopiridol; L86-8275; NSC 649890; HPLC ID BREAST-CARCINOMA CELLS; KINASE-ACTIVITY; INHIBITION; L86-8275; ARREST AB Purpose: Flavopiridol is a flavone which inhibits several cyclin-dependent kinases, and exhibits potent growth inhibitory activity against a number of human cell lines both in vitro, and when grown as xenografts in mice. It is currently being evaluated in a phase I clinical trial at the National Cancer Institute. The objective of this project was to develop and validate an analytical method for the assay of flavopiridol to be studied during clinical trials. Methods: Flavopiridol was isolated from human plasma samples by extraction with t-butylmethyl ether following alkalinization with borate buffer (pH 8.0). The extract was evaporated, the residue was dissolved in mobile phase, and analyzed by reverse-phase high-pressure liquid chromatography. Chromatography was accomplished with a polymer-based C-18 column eluted with a mobile phase consisting of methanol-phosphate buffer, pH 11.0 (53:47 v/v). Electrochemical detection (ECD) was employed. Results: Flavopiridol was recovered from human plasma with an efficiency of 85-87%. Calibration curves were linear over the concentration range 10-500 nM (4.4-219 ng/ml). Plasma standard concentrations were measured with an accuracy and precision ranging from 3.2% to 10%. Regression analysis of flavopiridol concentrations of 15 clinical trial plasma samples ranging in concentration from approximately 50 to 4000 muM quantitated by both ECD and mass spectrometry showed close agreement. The equation of the regression line was y=1.02x+8 with a correlation coefficient of 0.969. Continuous infusion of flavopiridol in four patients for 72 h at a rate of 50 mg/m(2) per day, resulted in mean steady-state plasma concentrations of from 200 to 300 nM. Levels declined in a biexponential manner following termination of the infusion, falling to approximately 10 nM after 48 h. Conclusions: An analytical method for the assay of flavopiridol in human plasma was developed with sensitivity to at least 10 nM. The assay is accurate, precise and specific, and is suitable for determination of plama flavopiridol concentrations for pharmacokinetic studies during clinical trials. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev therapeut Program,Div Canc Treatment Diag & C, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Stinson, SF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev therapeut Program,Div Canc Treatment Diag & C, Frederick, MD 21702 USA. NR 8 TC 18 Z9 19 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1998 VL 42 IS 4 BP 261 EP 265 DI 10.1007/s002800050815 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 118FG UT WOS:000075827300001 PM 9744769 ER PT J AU Schulte, TW Neckers, LM AF Schulte, TW Neckers, LM TI The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 17-allylamino-17-demethoxygeldanamycin HSP90; p185(erbB2); Raf-1; mutant p53 ID ROUS-SARCOMA VIRUS; GENE-PRODUCT P185; GROWTH-FACTOR EGF; RAT-KIDNEY CELLS; HERBIMYCIN-A; IN-VIVO; TYROSINE KINASE; PROTEIN-KINASE; PROGESTERONE-RECEPTOR; ANTITUMOR AGENT AB Purpose: Benzoquinone ansamycins are antibiotics with anticancer potential. First described as tyrosine kinase inhibitors, they are now frequently used to target HSP90 chaperone function. While herbimycin A and geldanamycin (GA) have been widely used in preclinical studies, both drugs are poor candidates for clinical trials owing to their in vivo toxicity and lack of stability. We therefore examined the biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA. Methods: Binding of 17-AG to HSP90 was studied in vitro using a GA-affinity beads competition assay. We analyzed the drug-induced destabilization of p185erbB2, Raf-l and mutant p53 in SKBR3 breast cancer cells by Western blotting. The antiproliferative activities of 17-AG and GA were compared using the MTT assay. Results: We found that, in a similar manner to GA itself, 17-AG bound specifically to HSP90. It also led to degradation of the receptor tyrosine kinase p185(erbB2), th, serine/threonine kinase Raf-1 and mutant p53. Both GA and 17-AG displayed comparable antiproliferative effects in SKBR3 and MCF7 cells. Even though HSP90 binding by 17-AG was weaker than by GA, 17-AG and GA caused biologic effects in tumor cells at similar doses. Conclusion: 17-AG shares the important biologic features of its parent compound GA. Since 17-AG has a better toxicity profile than GA, it is an interesting candidate benzoquinone ansamycin for clinical development. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Schulte, TW (reprint author), NCI, Med Branch, NIH, Bldg 10,13N240,10 Ctr Dr MSC 1928, Bethesda, MD 20892 USA. NR 36 TC 354 Z9 368 U1 1 U2 10 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1998 VL 42 IS 4 BP 273 EP 279 DI 10.1007/s002800050817 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 118FG UT WOS:000075827300002 PM 9744771 ER PT J AU Vaughan, TL Farrow, DC Hansten, PD Chow, WH Gammon, MD Risch, HA Stanford, JL Schoenberg, JB Mayne, ST Rotterdam, H Dubrow, R Ahsan, H West, AB Blot, WJ Fraumeni, JF AF Vaughan, TL Farrow, DC Hansten, PD Chow, WH Gammon, MD Risch, HA Stanford, JL Schoenberg, JB Mayne, ST Rotterdam, H Dubrow, R Ahsan, H West, AB Blot, WJ Fraumeni, JF TI Risk of esophageal and gastric adenocarcinomas in relation to use of calcium channel blockers, asthma drugs, and other medications that promote gastroesophageal reflux SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISING INCIDENCE; NORMAL ADULTS; CARDIA; DISEASE; THEOPHYLLINE; CANCER; ANTAGONISTS; NIFEDIPINE; ACHALASIA; THERAPY AB Incidence of adenocarcinomas of the esophagus and gastric cardia has risen dramatically over the past 2 decades in the U.S., for reasons that are not yet clear. A number of common medications (e.g., calcium channel blockers, tricyclic antidepressants, and certain asthma medications) promote gastroesophageal reflux by relaxing the lower esophageal sphincter (LES), Reflux is thought to increase cancer risk by promoting cellular proliferation, and by exposing the esophageal epithelium to potentially genotoxic gastric and intestinal contents, Recent studies have suggested that calcium channel blockers may also increase cancer risk by inhibiting apoptosis, Using personal interview data from a multicenter, population-based case-control study conducted between 1993 and 1995 in three areas of the U.S., we evaluated whether the use of LES-relaxing drugs was associated with increased risk of adenocarcinomas of the esophagus and gastric cardia, Cases of esophageal adenocarcinoma (n = 293) and gastric cardia adenocarcinoma (II = 261) were compared with general population controls (n = 695). Information on additional case groups of esophageal squamous cell carcinoma (II = 221) and noncardia gastric cancer (n = 368) were also available for comparison. Overall, 27.4% of controls had used one or more of these drugs for at least 6 months, compared with 30.2% of esophageal adenocarcinoma and 23.8% of gastric cardia adenocarcinoma cases. The adjusted odds ratios (ORs) for ever use were 1.0 [95% confidence interval (CI) = 0.7-1.5] and 0.8 (95% CI = 0.5-1.1), respectively. There was little evidence of increasing risk with increasing duration of use of all LES-relaxing drugs together, We found an increased risk of esophageal adenocarcinoma among persons reporting use of asthma drugs containing theophylline (OR = 2.5; 95% CI = 1.1-5.6) or beta agonists (OR = 1.7; 95% CI = 0.8-3.8). Risks were higher among long-term users (>5 Sears) of these drugs (OR = 3.1; 95% CI = 0.9-10.3 and OR = 2.3; 95% CI = 0.8-7.0, respectively), In contrast, there was no evidence that the use of calcium channel blockers or other specific groups of drugs increased the risk of any of the cancers studied, These results provide reassuring evidence that the increases in incidence of adenocarcinomas of the esophagus and gastric cardia are not likely to be related to the use of LES-relaxing drugs as a group, or calcium channel blockers in particular, but they do suggest that persons treated for long-standing asthma may be at increased risk of esophageal adenocarcinoma. C1 Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. New Jersey Dept Hlth & Senior Serv, Appl Canc Epidemiol Program, Trenton, NJ 08625 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Int Epidemiol Inst, Rockville, MD 20852 USA. RP Vaughan, TL (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, MP-474,POB 19024, Seattle, WA 98109 USA. NR 51 TC 75 Z9 76 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1998 VL 7 IS 9 BP 749 EP 756 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 118GJ UT WOS:000075829800002 PM 9752982 ER PT J AU Titus-Ernstoff, L Longnecker, MP Newcomb, PA Dain, B Greenberg, ER Mittendorf, R Stampfer, M Willett, W AF Titus-Ernstoff, L Longnecker, MP Newcomb, PA Dain, B Greenberg, ER Mittendorf, R Stampfer, M Willett, W TI Menstrual factors in relation to breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYCLE PATTERNS; OVULATORY CYCLES; AGE; WOMEN; EPIDEMIOLOGY; MENARCHE; DISEASE AB We evaluated menstrual factors in relation to breast cancer risk in a large, population-based, case-control study. Case women were ascertained through state-wide registries covering Wisconsin, Western Massachusetts, Maine, and New Hampshire; control women were randomly selected from driver's license and Medicare lists in each state. Information regarding menstrual characteristics was obtained through a telephone interview. The study population comprised 6888 breast cancer cases and 9529 control women. Because exogenous hormones influence menstrual cycle patterns, we repeated our analyses in a subgroup of women who had never used oral contraceptives or hormone replacement therapy. Our results indicate decreased breast cancer risk with menarcheal age of 15 years or more, relative to menarche at age 13; the relation was stronger among premenopausal [odds ratio (OR), 0.72; 95% confidence interval (CI), 0.57-0.91] as opposed to postmenopausal women (OR, 0.90; 95% CI, 0.80-1.03). Risk was slightly reduced among premenopausal women whose menstrual cycles did not become regular until at least 5 years after onset of menses, relative to those whose cycles became regular within 1 year (OR, 0.80; 95% CI, 0.63-1.02). There was no clear relation between breast cancer risk and irregular menstrual cycles, episodes of amenorrhea, or menstrual cycle length. Early menopause, whether natural or surgical, was associated with decreased breast cancer risk; surgical menopause before age 40 conferred the strongest protective effect (OR, 0.57; 95% CI, 0.47-0.71). We found no evidence of increased risk with late natural menopause (OR, 0.92; 95% CI, 0.80-1.06). Results in the subgroup of women who never used exogenous hormones were similar to those for the entire group. C1 Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH 03756 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Bayer Corp, W Haven, CT 06516 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03756 USA. Univ Chicago, Pritzker Sch Med, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, 1 Med Ctr Dr, Lebanon, NH 03756 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 27 TC 68 Z9 68 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1998 VL 7 IS 9 BP 783 EP 789 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 118GJ UT WOS:000075829800006 PM 9752986 ER PT J AU Siders, WM Halloran, PJ Fenton, RG AF Siders, WM Halloran, PJ Fenton, RG TI Melanoma-specific cytotoxicity induced by a tyrosinase promoter-enhancer herpes simplex virus thymidine kinase adenovirus SO CANCER GENE THERAPY LA English DT Article DE herpes simplex virus thymidine kinase; suicide gene; tissue-specific promoter; melanoma ID EXPERIMENTAL BRAIN-TUMORS; VIVO GENE-THERAPY; IN-VIVO; HEPATOCELLULAR-CARCINOMA; TRANSCRIPTION FACTOR; MICROPHTHALMIA GENE; MEDIATED TRANSFER; TRANSGENIC MICE; GAP-JUNCTIONS; CANCER-CELLS AB The ability to specifically and efficiently express selected genes in tumor cells is an important goal for cancer gene therapy. Transcriptional targeting of adenovirus to tumor cells, thereby limiting their expression to specific cell types, represents one experimental approach to this problem. We have previously shown that a recombinant adenovirus containing the murine tyrosinase promoter coupled to a dimer of the tyrosinase-enhancer element can target the expression of beta-galactosidase cDNA to melanoma cells. We now report that this same promoter/enhancer cassette can efficiently drive the expression of the herpes simplex virus thymidine kinase gene in melanoma cells. Infection of melanoma cells with the AdmTyr-tk virus along with subsequent ganciclovir treatment induces S phase cell cycle arrest associated with a profound change in cell size and morphology. Treated cells remain viable for prolonged periods, but clonogenic assays demonstrate that the cell cycle arrest is irreversible, in contrast, nonmelanoma cells are unaffected by this treatment regimen, exhibiting normal growth kinetics, metabolic activity, and cell cycle progression. The therapeutic efficacy of the AdmTyr-tk virus was tested in vivo using a xenograft model of human melanoma. The injection of the AdmTyr-tk virus into established subcutaneous tumor nodules in combination with systemic ganciclovir administration led to a decreased tumor growth rate and to complete tumor regressions in some cases. These studies demonstrate the feasibility of selectively targeting growth-inhibitory genes to melanoma cells in vitro and in vivo. C1 NCI, Dept Expt Transplantat & Immunol, Div Clin Sci, Frederick Canc Res & Dev Ctr, Winston Salem, NC 27102 USA. RP Fenton, RG (reprint author), Univ Maryland Med, Greene Canc Ctr, 655 W Baltimore St, Baltimore, MD 21201 USA. RI Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 47 TC 31 Z9 31 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP-OCT PY 1998 VL 5 IS 5 BP 281 EP 291 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 136UG UT WOS:000076877100003 PM 9824047 ER PT J AU Pass, HA Schwarz, SL Wunderlich, JR Rosenberg, SA AF Pass, HA Schwarz, SL Wunderlich, JR Rosenberg, SA TI Immunization of patients with melanoma peptide vaccines: Immunologic assessment using the ELISPOT assay SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE melanoma; immunotherapy; cancer vaccine; ELISPOT assay; T cells ID ANTIGEN GP100; SYNTHETIC PEPTIDES; MULTIPLE EPITOPES; T-LYMPHOCYTES; TUMOR; IDENTIFICATION; RECOGNITION; REGRESSION; CELLS AB PURPOSE Interest in the development of antimelanoma peptide vaccines has been renewed by the identification of specific epitopes recognized by tumor-infiltrating lymphocytes that mediate tumor regression after adoptive transfer. The human leukocyte antigen (HLA)-A2*0201-restricted, nonmutated melanocyte differentiation antigen gp100 has multiple T-cell epitopes, of which three are recognized by most gp100-reactive tumor infiltrating lymphocytes. Synthetic peptides based on two of these epitopes, or modifications to improve HLA binding affinity, were used individually to vaccinate patients with metastatic melanoma The purpose of this study was to evaluate the success of the vaccinations, as determined by the results of enzyme-linked immunospot (ELISPOT) tests of individual immune cells. PATIENTS AND METHODS The ELISPOT assay was used to measure the immunologic reactivity of peripheral blood lymphocytes from patients with metastatic melanoma before and after vaccination with gp100 peptides mixed with incomplete Freund's adjuvant The peptides were g209 (ITDQVPFSV), g280 (YLEPGPVTA), modified g209 (g209-2M: IMDQVPFSV) or modified g280 (g280-9V: YLEPGPVTV) peptide. The patients' lymphocytes were tested by use of an ELISPOT assay for their ability to secrete interferon gamma with and without 12 days of in vitro sensitization with peptide. RESULTS Patients were successfully vaccinated by gp100 peptides, as judged by the ELISPOT assays. Restimulation of the patients' lymphocytes in vitro with peptide for 12 days before the ELISPOT assay significantly amplified the immune activity. Increased immune activity after vaccination was specific for the immunizing peptide or its altered form, was major histocompatibility complex restricted, and was apparent against HLA-A2+, gp100+ melanoma cell lines and against T2 cells pulsed with the appropriate synthetic peptides. In general, the frequency of immune T cells was 10 to 100-fold higher in ELISPOT assays against peptide-pulsed T2 cells than against melanoma cell lines. Judged by the ELISPOT assays, vaccination was successful in six of seven patients injected with g209-2M when tested against g209-2M peptide and in five of these seven patients when tested against the native g209 peptide. Vaccination was also successful in five of six patients injected with g209, one of three patients injected with g280-9V, and four of seven patients injected with g280. Even without peptide restimulation in vitro before the ELISPOT assay, the frequency of immune T cells among fresh peripheral blood mononuclear cells tested 3 weeks after a second vaccination with g209-2M peptide was elevated in four of sbr patients and was about 1/1000 of cells tested against the same peptide pulsed onto T2 cells. DISCUSSION Gp100 peptides were selected for vaccine development because they are epitopes recognized by tumor-infiltrating lymphocytes that are associated with tumor regression after adoptive immunotherapy in patients with metastatic melanoma. In the present study, most of the patients vaccinated with the gp209-2M peptide in incomplete Freund's adjuvant generated circulating antigen-specific immune T cells that could be detected by restimulation in vitro followed by an ELISPOT assay for individual cells secreting interferon gamma. The immune T cells reacted not only with the HLA-A2 restricted modified peptide but also with the native peptide and with melanoma cells that express gp100 and HLA-A2. Analysis of T-cell responses at the single cell level will be a valuable aid in assessing the effectiveness of melanoma vaccines and in determining optimal vaccine formulations and delivery. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 14 TC 108 Z9 108 U1 0 U2 2 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1998 VL 4 IS 5 BP 316 EP 323 PG 8 WC Oncology SC Oncology GA 124RG UT WOS:000076195200008 PM 9815296 ER PT J AU Halloran, PJ Fenton, RG AF Halloran, PJ Fenton, RG TI Irreversible G(2)-M arrest and cytoskeletal reorganization induced by cytotoxic nucleoside analogues SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGE CHECKPOINT; CELL-CYCLE ARREST; TYROSINE PHOSPHORYLATION; ATAXIA-TELANGIECTASIA; CANCER-THERAPY; CDC42 GTPASES; KINASE; P53; RADIATION; GENE AB The mechanisms by which cytotoxic agents perturb the normal cell biology and cell cycle progression of cancer cells were explored using B16F10 cells genetically modified to express the Herpes Simplex Virus-thymidine kinase gene. Culture in the presence of the nucleoside analogue ganciclovir induced a profound morphological change that required entry of treated cells into S phase and was dependent on prenylated proteins such as those of the rho gene family. Cell cycle arrest occurred in late S phase or G2 phase due to the activation of the G(2)-M DNA damage checkpoint. This checkpoint control operated at the level of inhibition of the activity of Cdc2/cyclin B and occurred by two mechanisms: (a) p53-mediated up-regulation of p21(CIP1/WAF1) expression and its association with Cdc2/cyclin B; and (b) prevention of the dephosphorylation of tyrosine 15 of Cdc2. These events occurred in vitro and in vivo, and were shown to mediate bystander killing in this model. The mechanism of cell death seemed to be due to the irreversible cell cycle arrest at the G(2)-M checkpoint, rather than induction of apoptosis, These data link DNA damage checkpoints with cytoskeletal signaling pathways and the core cell cycle machinery and may represent a general mechanism of cytotoxicity of this class of nucleoside analogues. C1 NCI, Frederick Canc Res & Dev Ctr, Dept Expt Immunol & Transplantat, Div Clin Sci, Frederick, MD 21702 USA. RP Fenton, RG (reprint author), Univ Maryland, Sch Med, Greenebaum Canc Ctr, 655 W Baltimore St, Baltimore, MD 21201 USA. NR 40 TC 40 Z9 40 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1998 VL 58 IS 17 BP 3855 EP 3865 PG 11 WC Oncology SC Oncology GA 115FE UT WOS:000075652200018 PM 9731495 ER PT J AU Mulard, LA Glaudemans, CPJ AF Mulard, LA Glaudemans, CPJ TI Synthesis of ligands related to the O-specific antigen of Shigella dysenteriae type 1. Part 10 - Synthesis of tri- and tetrasaccharide fragments of the Shigella dysenteriae type 1 O-antigen deoxygenated and fluorinated at position 3 of the methyl alpha-D-galactopyranoside terminus SO CARBOHYDRATE RESEARCH LA English DT Article DE Shigella dysenteriae type 1; deoxygenated oligosaccharides; deoxyfluorinated oligosaccharides ID POLYSACCHARIDE; GLYCOSYLATION; ANTIBODIES; CHLORIDE; BINDING AB The blockwise synthesis of methyl alpha tri- and tetrasaccharide analogs of the biochemical repeating unit of the Shigella dysenteriae type 1 O-polysaccharide is described. Modifications include deoxygenation and deoxyfluorination at position 3 of the galactopyranoside residue. Methyl 4,6-O-benzylidene-3-deoxy-alpha-D-xylo-hexopyranoside (8) and methyl 4,6-O-benzylidene-3-deoxy-3-fluoro-alpha-D-galactopyranoside (9) were condensed with (2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl)-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl chloride to give, after deprotection, the target trisaccharide methyl alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-3-deoxy-alpha-D-xylo-hexopyranoside and the corresponding fluorinated oligosaccharide. For the tetrasaccharide synthesis, the glycosyl accepters 8 and 9 were condensed with the temporarily protected (2,4-di-O-benzoyl-3-O-chloroacetyl-alpha-L-rhamnopyranosyl)-(1-->3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl chloride. Removal of the chloroacetyl group was followed by condensation of the resulting selectively deblocked trisaccharides with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl chloride. Reduction and deprotection then gave the free methyl 2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1-->3) -alpha-L-rhamnopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-3-deoxy-alpha-D-xylo-hexopyranoside and the fluorinated analog. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Mulard, LA (reprint author), Inst Pasteur, Unite Chim Organ, Dept BGM, 28 Rue Dr Roux, F-75724 Paris 15, France. EM lmulard@pasteur.fr NR 22 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP PY 1998 VL 311 IS 3 BP 121 EP 133 DI 10.1016/S0008-6215(98)00216-X PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 133QT UT WOS:000076697800002 PM 9825517 ER PT J AU Guo, RJ Wang, Y Kaneko, E Wang, DY Arai, H Hanai, H Takenoshita, S Hagiwara, K Harris, CC Sugimura, H AF Guo, RJ Wang, Y Kaneko, E Wang, DY Arai, H Hanai, H Takenoshita, S Hagiwara, K Harris, CC Sugimura, H TI Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer SO CARCINOGENESIS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; TGF-BETA; CARCINOMA-CELLS; FREQUENT LOSS; PANCREATIC-CANCER; GENOMIC STRUCTURE; TUMORS; COLON; STOMACH AB Mutations in the transforming growth factor beta type II receptor (TGF beta RII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGF beta RII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGF beta RII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele, Mutations of the TGF beta RII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2, Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGF beta RII mutation nor replication error was found in these cases. Immunoreactivity of TGF beta RII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)lo deletion or loss of heterozygosity of TGF beta RII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer. C1 Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 43131, Japan. Hamamatsu Univ Sch Med, Dept Internal Med 1, Hamamatsu, Shizuoka 43131, Japan. Gunma Univ, Sch Med, Dept Surg 1, Maebashi, Gumma 371, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Sugimura, H (reprint author), Hamamatsu Univ Sch Med, Dept Pathol 1, 3600 Handa Cho, Hamamatsu, Shizuoka 43131, Japan. EM hsugimur@hama-med.ac.jp NR 41 TC 14 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1998 VL 19 IS 9 BP 1539 EP 1544 DI 10.1093/carcin/19.9.1539 PG 6 WC Oncology SC Oncology GA 120BM UT WOS:000075934700003 PM 9771922 ER PT J AU Yeowell-O'Connell, K Rothman, N Smith, MT Hayes, RB Li, GL Waidyanatha, S Dosemeci, M Zhang, LP Yin, SN Titenko-Holland, N Rappaport, SM AF Yeowell-O'Connell, K Rothman, N Smith, MT Hayes, RB Li, GL Waidyanatha, S Dosemeci, M Zhang, LP Yin, SN Titenko-Holland, N Rappaport, SM TI Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene SO CARCINOGENESIS LA English DT Article ID PROTEIN ADDUCTS; S-PHENYLCYSTEINE; BONE-MARROW; BENZOQUINONE; BLOOD; RATS; EXCRETION; MUTANT; RISK AB Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be specific biomarkers of exposure to benzene, We analyzed BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19 workers and 19 controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers, The adducts were analyzed by gas chromatography-mass spectrometry following reaction of the protein with trifluoroacetic anhydride and methanesulfonic acid, When subjects were divided into controls (n = 42) and workers exposed to less than or equal to 31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure: Spearman r = 0.67, P < 0.0001), To our knowledge, these results represent the first observation in humans that BO-Hb levels are significantly correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting a significant correlation with exposure (Spearman r = 0.90, P < 0.0001), The blood dose of BO predicted from both Hb and Alb adducts was very similar. These results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of exposure to high levels of benzene, As part of our investigation of the background levels of BO-Hb and BO-Alb found in unexposed persons, me analyzed recombinant human Rb and Alb for BO adducts, Significant levels of both BO-Hb (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the observed background adducts reflect an artifact of the assay, while other portions are indicative of either unknown exposures or endogenous production of adducts. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing 100050, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. FU NIEHS NIH HHS [P42ES04705, P42ES05948] NR 33 TC 47 Z9 47 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1998 VL 19 IS 9 BP 1565 EP 1571 DI 10.1093/carcin/19.9.1565 PG 7 WC Oncology SC Oncology GA 120BM UT WOS:000075934700007 PM 9771926 ER PT J AU McCormick, DL Ryan, BM Findlay, JC Gauger, JR Johnson, TR Morrissey, RL Boorman, GA AF McCormick, DL Ryan, BM Findlay, JC Gauger, JR Johnson, TR Morrissey, RL Boorman, GA TI Exposure to 60 Hz magnetic fields and risk of lymphoma in PIM transgenic and TSG-p53 (p53 knockout) mice SO CARCINOGENESIS LA English DT Article ID ELECTRIC UTILITY WORKERS; OCCUPATIONAL EXPOSURE; ELECTROMAGNETIC-FIELDS; BREAST-CANCER; EPIDEMIOLOGIC EVIDENCE; RESIDENTIAL EXPOSURE; BRAIN CANCER; LEUKEMIA; MORTALITY; CARCINOGEN AB The results of a number of epidemiology studies suggest that exposure to power frequency (50 and 60 Hz) magnetic fields may be a risk factor for hematopoietic neoplasia, To generate experimental data to test this hypothesis, the influence of magnetic field exposure on lymphoma induction was determined in two strains of mice that are genetically predisposed to the disease, PIM mice, which carry the pim-1 oncogene, are highly sensitive to lymphoma induction by N-ethyl-N-nitrosourea (ENU); ENU-treated PIM mice were studied as a 'high incidence' lymphoma model, TSG-p53 (p53 knockout) mice, in which the p53 tumor suppressor gene has been deleted from the germ line, develop lymphoma as an age-related change; hemizygous TSG-p53 mice were studied as a 'low incidence' lymphoma model, Beginning 1 day after a single i.p. injection of 25 mg ENU/kg body wt, groups of 30 PIM mice/sex were exposed for 18.5 h/day to pure, linearly polarized, transient-free 60 Hz magnetic fields at field strengths of 0 (sham control), 0.02, 2.0 or 10.0 Gauss (G), An additional group of 30 PIM mice/sex was exposed intermittently (1 h on, 1 h off) to 10.0 G fields, Groups of 30 TSG-p53 mice/sex were exposed continuously to magnetic field strengths of 0 (sham control) or 10.0 G; TSG-p53 mice received no ENU. Studies were terminated after 23 weeks of magnetic field exposure. Lymphoma incidence in male PIM mice exposed continuously to 10.0 G magnetic fields was significantly reduced from that seen in sex-matched sham controls; survival, lymphoma incidence and lymphoma latency in other groups of PIM mice did not differ from sham controls. Survival and lymphoma incidence in all groups of TSG-p53 mice was 7% or less, regardless of magnetic field exposure regimen. These data do not support the hypothesis that exposure to magnetic fields is a significant risk factor for lymphoid neoplasia in mice with a genetic predisposition to the disease. C1 IIT, Dept Life Sci, Res Inst, Chicago, IL 60616 USA. IIT, Elect & Electromagnet Sect, Res Inst, Chicago, IL 60616 USA. Pathol Associates Int, Chicago, IL 60616 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP McCormick, DL (reprint author), IIT, Dept Life Sci, Res Inst, Chicago, IL 60616 USA. EM dmccormick@iitri.com FU NIEHS NIH HHS [N01-ES-25351] NR 32 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1998 VL 19 IS 9 BP 1649 EP 1653 DI 10.1093/carcin/19.9.1649 PG 5 WC Oncology SC Oncology GA 120BM UT WOS:000075934700018 PM 9771937 ER PT J AU Newbold, RR Hanson, RB Jefferson, WN Bullock, BC Haseman, J McLachlan, JA AF Newbold, RR Hanson, RB Jefferson, WN Bullock, BC Haseman, J McLachlan, JA TI Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol SO CARCINOGENESIS LA English DT Article ID PRENATAL EXPOSURE; UTERINE-TUMORS; CARCINOGENESIS; ESTROGENS; ADENOCARCINOMAS; CHEMICALS; LESIONS; OVIDUCT; CELLS AB Prenatal exposure to diethylstilbestrol (DES) has been associated with the subsequent development of reproductive tract abnormalities, including poor reproductive outcome and neoplasia, in experimental animals and humans. Experimental animal studies with chemical carcinogens have raised the possibility that adverse effects of DES may be transmitted to succeeding generations. To evaluate this possibility and to determine if there is a sensitive window of developmental exposure, outbred CD-I mice were treated with DES during three stages of development: group I was treated on days 9-16 of gestation (2.5, 5 or 10 mu g/kg maternal body wt), the time of major organogenesis; group II was treated once on day 18 of gestation (1000 mu g/kg maternal body wt) just prior to birth; group III was treated on days 1-5 of neonatal life (0.002 mu g/pup/day), Female mice (F1) in each group were raised to sexual maturity and bred to control males. As previously reported, fertility of the F1 DES-exposed females was decreased in all groups. Female offspring (DES lineage or F2) from these matings were raised to maturity and housed with control males for 20 weeks. The fertility of these DES lineage female mice was not affected by DES exposure of their 'grandmothers'. DES lineage mice were killed at 17-19 and 22-24 months of age. An increased incidence of malignant reproductive tract tumors, including uterine adenocarcinoma, was seen in DES lineage mice but not in corresponding controls; the range and prevalence of tumors increased with age. Because uterine adenocarcinomas were seen in all three DES groups, all developmental exposure periods were considered susceptible to the adverse effects of DES, These data suggest that the reduced fertility observed in the DES F1 female mice was not transmitted to their descendants; however, increased susceptibility to tumor formation is apparently transmitted to subsequent generations. C1 NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Toxicol Lab,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Comparat Med, Winston Salem, NC 27103 USA. Tulane Univ, Environm Endocrinol Lab, Tulane Xavier Ctr Bioenvironm Res, New Orleans, LA 70112 USA. Tulane Univ, Dept Pharmacol, New Orleans, LA 70112 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Toxicol Lab,Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 41 TC 124 Z9 130 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1998 VL 19 IS 9 BP 1655 EP 1663 DI 10.1093/carcin/19.9.1655 PG 9 WC Oncology SC Oncology GA 120BM UT WOS:000075934700019 PM 9771938 ER PT J AU Moffett, JR Blinder, KL Venkateshan, CN Namboodiri, MAA AF Moffett, JR Blinder, KL Venkateshan, CN Namboodiri, MAA TI Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs SO CELL AND TISSUE RESEARCH LA English DT Article DE quinolinic acid; tryptophan dioxygenase; indoleamine 2,3-dioxygenase; nicotinamide adenine dinucleotide metabolism; liver; spleen; rat (Sprague Dawley) ID INDOLEAMINE 2,3-DIOXYGENASE; RESPIRATORY BURST; IMMUNE ACTIVATION; ACID FORMATION; CELLS; MACROPHAGES; INTERFERON; BRAIN; LIPOPOLYSACCHARIDE; LOCALIZATION AB Quinolinate is a tryptophan metabolite and an intermediary in nicotinamide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under normal physiological conditions, kynurenine is thought to be produced primarily in the liver as an NAD+ precursor. However, during immune stimulation or inflammation, numerous extrahepatic tissues convert systemic tryptophan to kynurenine, and its concentration subsequently rises dramatically in blood. The fate and role of extrahepatic kynurenine are uncertain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate from either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperitoneal injections of tryptophan led to increased quinolinate immunoreactivity primarily in hepatocytes, with moderate increases in tissue macrophages and splenic follicles. In contrast, intraperitoneal injections of kynurenine did not result in any significant increase in hepatocyte quinolinate immunoreactivity, but rather led to dramatic increases in immunoreactivity in tissue macrophages, splenic white pulp, and thymic medulla. These findings suggest that hepatocytes do not make significant use of extracellular kynurenine for quinolinate or NAD+ synthesis, and that, instead, extrahepatic kynurenine is preferentially metabolized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an immune response is discussed. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Moffett, JR (reprint author), Georgetown Univ, Dept Biol, 37th & O Sts NW, Washington, DC 20057 USA. EM jrmoffett@aol.com NR 27 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD SEP PY 1998 VL 293 IS 3 BP 525 EP 534 DI 10.1007/s004410051145 PG 10 WC Cell Biology SC Cell Biology GA 120BE UT WOS:000075934000017 PM 9716743 ER PT J AU Ortmann, O Tomic, M Weiss, JM Diedrich, K Stojilkovic, SS AF Ortmann, O Tomic, M Weiss, JM Diedrich, K Stojilkovic, SS TI Dual action of androgen on calcium signaling and luteinizing hormone secretion in pituitary gonadotrophs SO CELL CALCIUM LA English DT Article AB An increase in serum androgen levels associated with a suppression of cyclic gonadotropin secretion is frequently observed in females with impaired ovarian function. Here, we addressed the hypotheses that androgens (testosterone and dihydrotestosterone) alter gonadotropin secretion by modulating agonist-induced Ca2+ signaling and/or Ca2+-controlled exocytosis, In mixed populations of pituitary cells from female rats, addition of testosterone reduced basal and agonist (GnRH)-induced gonadotropin secretion in a concentration- and time-dependent manner. The suppressive actions of this androgen on gonadotropin secretion were observed over the full GnRH concentration range. Reduction in agonist-induced gonadotropin secretion was also observed after addition of dihydrotestosterone, indicating that the inhibitory action of testosterone is not mediated by its conversion to estradiol. Both the extracellular Ca2+-independent spike phase and extracellular Ca2+-dependent sustained phase of GnRH-induced gonadotropin secretions were affected by testosterone. In part, the inhibitory action of testosterone was mediated by attenuation of GnRH-induced InsP(3) production and InsP(3)-dependent Ca2+ mobilization. In addition, testosterone exhibited a Ca2+-independent action on gonadotropin secretion, as documented by attenuation of high potassium-induced secretion without an affect on depolarization-induced Ca2+ signals. These results suggest that androgen inhibition of gonadotropin secretion occurs at two distinct steps in the secretory pathway, one prior to and one after elevation in cytosolic Ca2+ concentration. C1 Med Univ Lubeck, Dept Obstet & Gynecol, D-23538 Lubeck, Germany. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Ortmann, O (reprint author), Med Univ Lubeck, Dept Obstet & Gynecol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Tomic, Melanija/C-3371-2016 NR 36 TC 10 Z9 10 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD SEP PY 1998 VL 24 IS 3 BP 223 EP 231 DI 10.1016/S0143-4160(98)90131-2 PG 9 WC Cell Biology SC Cell Biology GA V2598 UT WOS:000165532100007 PM 9883276 ER PT J AU Gannot, G Bermudez, D Lillibridge, D Fox, PC AF Gannot, G Bermudez, D Lillibridge, D Fox, PC TI Fas and Fas-mediated effects on a human salivary cell line in vitro: a model for immune-mediated exocrine damage in Sjogren's syndrome SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Fas; salivary gland; apoptosis; exocrinopathy; Sjogrens syndrome ID SYSTEMIC LUPUS-ERYTHEMATOSUS; APOPTOSIS; ANTIGEN; DEATH; EXPRESSION; LIGAND; AUTOIMMUNITY; LYMPHOCYTES; GLAND; PATHOGENESIS AB Sjogren's syndrome (SS) is an autoimmune exocrinopathy characterized by mononuclear cell infiltration and loss of parenchymal tissue in salivary and lacrimal glands. The mechanisms for these histologic alterations are not known. Apoptotic cell death, induced by the ligation of Fas (APO-1/CD95) with Pas ligand (FasL/CD95L) may be an explanation for the tissue damage seen in SS. Fas and Fast were detected in minor salivary glands from SS patients and healthy individuals using immunohistochemical methods. There was increased expression of both Pas and Fast in the patients. The ability of the Fas-FasL pathway to influence epithelial cell growth and survival was demonstrated in vitro using a human submandibular cell line. The presence of Fas receptor was demonstrated on the cells. Anti-Pas antibody triggered cell death. Cells were also grown in the presence of gamma-interferon (IFN-gamma). IFN-gamma induced an upregulation of Pas receptor expression and pre-treatment of cells with IFN-gamma led to enhanced anti-Pas mediated cell death. C1 NIDR, NIH, Clin Invest & Patient Care Branch, Bethesda, MD 20892 USA. RP Gannot, G (reprint author), NIDR, NIH, Clin Invest & Patient Care Branch, Bldg 10,Room 1N-113,10 Ctr Dr MSC 1190, Bethesda, MD 20892 USA. NR 34 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 1998 VL 5 IS 9 BP 743 EP 750 DI 10.1038/sj.cdd.4400414 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 117ND UT WOS:000075787200005 PM 10200533 ER PT J AU Sebastian, J Richards, RG Walker, MP Wiesen, JF Werb, Z Derynck, R Hom, YK Cunha, GR DiAugustine, RP AF Sebastian, J Richards, RG Walker, MP Wiesen, JF Werb, Z Derynck, R Hom, YK Cunha, GR DiAugustine, RP TI Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN-BREAST-CANCER; STIMULATES TYROSINE PHOSPHORYLATION; EGF RECEPTOR; FACTOR-ALPHA; DUCTAL MORPHOGENESIS; CARCINOMA-CELLS; MICE LACKING; MOUSE; EXPRESSION; ESTROGEN AB The hormonal stimulation of mammary gland morphogenesis is believed to occur through growth factor receptor signaling pathways, To determine the importance of the epidermal growth factor receptor (EGFR) pathway, we examined extracts of inguinal mammary glands from prepubertal and pubertal mice for tyrosine-phosphorylated EGFR and other erbB receptors, Tyrosine phosphorylation of both EGFR and erbB-2 was detected in normal female BALB/c mice at 5-6 weeks of age, but not during the prepubertal stage, e.g., 24 days of age, Treatment of mice with estradiol or epidermal growth factor also stimulated the formation of mammary EGFR/erbB-2 phosphotyrosine, Waved-P mice, which have impaired EGFR kinase activity, exhibited less mammary development than did wild-type (wt) mice when both were evaluated at 36 days of age, Because EGFR knockout (KO) mice die shortly after birth, glands from the newborns were implanted under the renal capsules of female nude mice. Under these conditions, extensive ductal growth was observed in mammary glands from wt animals; in contrast, glands from EGFR KO mice failed to grow beyond rudimentary structures. Tissue recombinants revealed that the wt fat pad supported the morphogenesis of EGFR KO epithelium, whereas the EGFR KO fat pad did not. Taken together, these data suggest that EGFR is essential for morphogenesis of the mammary ducts and functions during this period of mammary development as a heterodimer with erbB-2 in the mammary stroma. C1 NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA. RP DiAugustine, RP (reprint author), NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr,MD D4-04,POB 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA 58207, CA 5762] NR 44 TC 88 Z9 90 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1998 VL 9 IS 9 BP 777 EP 785 PG 9 WC Cell Biology SC Cell Biology GA 119GQ UT WOS:000075887900008 PM 9751121 ER PT J AU Liu, XW Gallego, MI Smith, GH Robinson, GW Hennighausen, L AF Liu, XW Gallego, MI Smith, GH Robinson, GW Hennighausen, L TI Functional rescue of Stat5a-null mammary tissue through the activation of compensating signals including Stat5b SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GLAND; EXPRESSION; DIFFERENTIATION; MOUSE AB Prolactin induces mammopoiesis and lactogenesis through the Janus kinase-signal transducers and activators of transcription pathway, with Stat5a being a principal and obligate cytoplasmic and nuclear signaling molecule. Mice from which the Stat5a gene has been deleted fail to develop functional mammary tissue during their first pregnancy. Lobuloalveolar outgrowth is curtailed, and epithelial cells fail to progress to functional differentiation, Here, we investigate whether the effect of Stat5a deficiency is restricted to the epithelium and whether the gland has the capacity to activate alternative signaling pathways that could restore development and function. Mammary gland transplant experiments showed that Stat5a-deficient epithelium does not differentiate in wild-type stroma, thus demonstrating a cell-autonomous role for Stat5a. The capacity of Stat5a-deficient mammary tissue to develop and secrete milk was measured after consecutive pregnancies and with postpartum suckling. Neither of these regimens could independently restore lactation. However, the combination of several pregnancies and suckling stimuli resulted in a partial establishment of lactation and an increase of Stat5b activity. These experiments demonstrate that the mammary gland has inherent plasticity that allows it to use different signals to achieve its ultimate purpose, the production of milk to nurture newborn offspring. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 NR 17 TC 58 Z9 58 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1998 VL 9 IS 9 BP 795 EP 803 PG 9 WC Cell Biology SC Cell Biology GA 119GQ UT WOS:000075887900010 PM 9751123 ER PT J AU Bezrukov, SM Vodyanoy, I AF Bezrukov, SM Vodyanoy, I TI Stochastic resonance in thermally activated reactions: Application to biological ion channels SO CHAOS LA English DT Article ID SIGNAL-TRANSDUCTION; NOISE; MODEL; ALAMETHICIN; ENHANCEMENT; MEMBRANE; NEURONS; MECHANORECEPTORS; BEHAVIOR; CRAYFISH AB At the molecular level many thermally activated reactions can be viewed as Poisson trains of events whose instantaneous rates are defined by the reaction activation barrier height and an effective collision frequency. When the barrier height depends on an external parameter, variation in this parameter induces variation in the event rate.:Extending our previous work, we offer a detailed theoretical analysis of signal transduction properties of these reactions considering the external parameter as an input signal and the train of resulting events as an output signal. The addition of noise to the system input facilitates signal transduction in two ways. First; for a linear relationship between the barrier height and the external parameter the output signal power grows exponentially with the mean square fluctuation of the noise. Second, for noise of a sufficiently high bandwidth, its addition increases output signal quality measured as the signal-to-noise ratio (SNR). The output SNR reaches a maximum at optimal noise intensity defined by the reaction sensitivity to the external parameter, reaction initial rate, and the noise bandwidth. We apply this theory to ion channels of excitable biological membranes. Based on classical results of Hodgkin and Huxley we show that open/closed transitions of voltage-gated ion channels can be treated as thermally activated reactions whose activation barriers change linearly with applied transmembrane voltage. As an experimental example we discuss our recent results obtained with polypeptide alamethicin incorporated into planar lipid bilayers. (C) 1998 American Institute of Physics. C1 NICHD, Phys & Struct Biol Lab, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. Off Naval Res, London NW1 5TH, England. RP Bezrukov, SM (reprint author), NICHD, Phys & Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM bezrukov@helix.nih.gov NR 40 TC 24 Z9 24 U1 1 U2 5 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1054-1500 J9 CHAOS JI Chaos PD SEP PY 1998 VL 8 IS 3 BP 557 EP 566 DI 10.1063/1.166337 PG 10 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 119LT UT WOS:000075898400004 ER PT J AU Okada, Y Tsukatani, M Taguchi, H Yokoi, T Bryant, SD Lazarus, LH AF Okada, Y Tsukatani, M Taguchi, H Yokoi, T Bryant, SD Lazarus, LH TI Amino acids and peptides. LII. Design and synthesis of opioid mimetics containing a pyrazinone ring and examination of their opioid receptor binding activity SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE 2(1H)-pyrazinone; simple synthetic procedure; amino-containing pyrazinone derivative; pyrazinone-containing tyrosine derivative; opioid-receptor binding activity ID FACILE SYNTHESIS; OPIATE RECEPTOR; POTENT; CONFORMATION; DELTORPHIN; ENKEPHALIN; SELECTIVITY; DERIVATIVES; ANTAGONISTS; RECOGNITION AB An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones, Boc-Tyr-OH was coupled with the amino function, followed bq removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a K-i value of 55.8 nM and to the delta-opioid receptor with a K-i value of 2165 nM and with a K(i)mu/K(i)delta value of 0.026. C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. NR 24 TC 14 Z9 14 U1 1 U2 2 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD SEP PY 1998 VL 46 IS 9 BP 1374 EP 1382 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 121BM UT WOS:000075992300006 PM 9775433 ER PT J AU Bal, W Lukszo, J Bialkowski, K Kasprzak, KS AF Bal, W Lukszo, J Bialkowski, K Kasprzak, KS TI Interactions of nickel(II) with histones: Interactions of Nickel(II) with CH3CO-Thr-Glu-Ser-His-His-Lys-NH2, a peptide modeling the potential metal binding site in the "C-Tail" region of histone H2A SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID STABILITY-CONSTANTS; OXIDATIVE DAMAGE; LINKER HISTONES; L-HISTIDINE; COMPLEXES; DNA; NUCLEOSOME; CHROMATIN; SEQUENCE; NI(II) AB A combined ps-metric and spectroscopic (UV/vis, CD, NMR) study of the Ni(II) binding to CH3CO-Thr-Glu-Ser-His-His-Lys-NH2 (AcTESHHKam), a blocked hexapeptide modeling a part of the C-terminal sequence of the major variant of histone H2A (residues 120-125), revealed the formation of a pseudo-octahedral NiHL complex in weakly acidic and neutral solutions. Ni(II) is bound to the peptide through imidazole nitrogens on both of its histidine residues and the carboxylate of the side chain of glutamic acid. At higher pH, a series of square-planar complexes are formed. This process is accompanied by hydrolytic degradation of the peptide. At pH 7.4, the peptide hydrolyzes in a Ni(II)-assisted fashion, yielding the square-planar Ni(II) complex of SHHKam as the sole product detected by CD, MALDI-TOF MS, and HPLC. Quantitative analysis of complex stabilities indicates that the -TESHHK- motif is a very likely binding site for carcinogenic Ni(II) ions in the cell nucleus. The Ni(II)-assisted hydrolysis of the C-terminal chain of histone H2A may provide a novel mechanism of genotoxicity combining the damage to the nucleosome with the generation of further toxic Ni(II) species. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NIAID, Mol Struct Lab, Rockville, MD 20852 USA. Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland. RP Bal, W (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Bldg 53,Rm 205, Frederick, MD 21702 USA. RI Bialkowski, Karol/E-2328-2014 NR 58 TC 85 Z9 86 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 1998 VL 11 IS 9 BP 1014 EP 1023 DI 10.1021/tx980051y PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 123AE UT WOS:000076103000005 PM 9760275 ER PT J AU Folsom, AR Nieto, FJ Sorlie, P Chambless, LE Graham, DY AF Folsom, AR Nieto, FJ Sorlie, P Chambless, LE Graham, DY CA Atherosclerois Risk Communities Study Investiga TI Helicobacter pylori seropositivity and coronary heart disease incidence SO CIRCULATION LA English DT Article DE Helicobacter pylori; coronary disease; epidemiology ID CARDIOVASCULAR RISK-FACTORS; IMPROVED LIPOLYTIC EFFICIENCY; CHLAMYDIA-PNEUMONIAE; CAROTID ATHEROSCLEROSIS; ENZYMATIC DETERMINATION; INFECTION; CYTOMEGALOVIRUS; POPULATION; PLASMA; QUESTIONNAIRE AB Background-Several epidemiological and clinical reports have suggested seropositivity for Helicobacter pylori may be a risk factor for coronary heart disease. However, there has been no prospective study of this association involving an ethnically diverse sample of middle-aged men and women. Methods and Results-Using a prospective, case-cohort design, we determined H pylori seropositivity in relation to coronary heart disease incidence over a median follow-up period of 3.3 years among middle-aged men and women. There were 217 incident coronary heart disease cases and a cohort sample of 498. We determined H pylori antibody status by measuring IgG antibody to the high-molecular-weight cell-associated proteins of H pylori using a sensitive and specific ELISA. The prevalence of H pylori seropositivity was higher in blacks than whites, in those with less than high school education, in those with lower plasma pyridoxal 5'-phosphate and higher homocyst(e)ine concentrations, in those who did not use vitamin supplements, in those with higher fibrinogen levels, and in those seropositive for cytomegalovirus and herpes simplex type I (all P<0.05). The age-, sex-, race-, and field center-adjusted hazard ratio of coronary heart disease for H pylori seropositivity was 1.03 (95% CI=0.68 to 1.57). After adjustment for other risk factors, including fibrinogen, cytomegalovirus seropositivity, and herpes simplex type I seropositivity, the hazard ratio was 0.85 (95% CI=0.43 to 1.69), H pylori seropositivity also was not associated with increased mean intima-media thickness of the carotid artery, a measure of subclinical atherosclerosis, Conclusions-H pylori infection is probably not an important contributor to clinical coronary heart disease events. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Baylor Coll Med, Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. RP Folsom, AR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Suite 300,1300 S 2nd St, Minneapolis, MN 55454 USA. EM folsom@epivax.epi.umn.edu FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 47 TC 110 Z9 117 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 1 PY 1998 VL 98 IS 9 BP 845 EP 850 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 114VH UT WOS:000075629500006 PM 9738638 ER PT J AU Rakowicz-Szulczynska, EM Jackson, B Szulczynska, AM Smith, M AF Rakowicz-Szulczynska, EM Jackson, B Szulczynska, AM Smith, M TI Human immunodeficiency virus type 1-like DNA sequences and immunoreactive viral particles with unique association with breast cancer SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; OVARIAN-CANCER; SUSCEPTIBILITY GENE; KAPOSIS-SARCOMA; ANTIBODIES; CARCINOMA; CELLS; RAK; MORTALITY; FAMILIES AB RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to the proteins encoded by human immunodeficiency virus type 1 (HIV-1) and are expressed by 95% of breast and gynecological cancer cases in women and prostate cancer cases in men. The binding of an epitope-specific anti-HIV-l gp120 monoclonal antibody (MAb) (amino acids 308 to 322) to cancer RAK antigens has been found to be inhibited by a peptide derived from variable loop V3 of HIV-1. Breast cancer DNAs of 40 patients were PCR amplified with HIV-1 gp41-derived primers, and all of the samples were found to be positive. The DNA fragments amplified in seven blindly selected breast cancer samples were sequenced. The breast cancer DNA sequences showed at least 90% homology to the HIV-1 gene for gp41. Antisense oligonucleotides complementary to the HN-l-like sequences inhibited reverse transcriptase activity and inhibited the growth of breast cancer cells in vitro. Viral particles detected in breast cancer cell lines were strongly immunogold labeled with the anti-HIV-1 gp120 MAb. The results obtained strongly suggest that the long-postulated breast cancer virus may, in fact, be related to HIV-1. C1 Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. NCI, Designated Eppley Canc Ctr, Omaha, NE USA. RP Rakowicz-Szulczynska, EM (reprint author), Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, 600 S 42nd St, Omaha, NE 68198 USA. EM EMRAKOWI@UNMC.edu NR 44 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1998 VL 5 IS 5 BP 645 EP 653 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 117NF UT WOS:000075787400010 PM 9729531 ER PT J AU Xie, H Deng, YJ Notkins, AL Lan, MS AF Xie, H Deng, YJ Notkins, AL Lan, MS TI Expression, characterization, processing and immunogenicity of an insulin-dependent diabetes mellitus autoantigen, IA-2, in Sf-9 cells SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE IA-2; protein tyrosine phosphatase; post-translational modification; baculovirus; expression; autoantibodies ID PROTEIN-TYROSINE-PHOSPHATASE; N-GLYCOSIDASE-F; TRANSMEMBRANE PROTEIN; INSECT CELLS; GLUTAMATE-DECARBOXYLASE; TRYPTIC FRAGMENTS; ANTIBODIES; AUTOANTIBODIES; IDDM; IDENTIFICATION AB Autoantibodies to a 64-kD protein and a 40-kD tryptic fragment from pancreatic islets have been detected at high frequency in the sera of patients with insulin-dependent diabetes mellitus (IDDM). IA-2, a newly isolated transmembrane protein tyrosine phosphatase, is a major islet cell autoantigen in IDDM and the precursor of a 40-kD tryptic fragment. To express large quantities of recombinant IA-2 protein and analyse post-translational modifications we expressed full-length human IA-2 in baculovirus-infected Sf-9 cells. IA-2 expression was analysed by Western blot and by immunoprecipitation of S-35-methionine-radiolabelled proteins with rabbit antisera or IDDM sera. A 120-kD IA-2 protein was detected during the early, but not the late, phase of the infection. Pulse-chase experiments showed that the 120-kD protein was processed into fragments of 64 kD and smaller fragments of approximate to 50 kD, 38 kD and 32 kD. The 64-kD fragment appeared as a doublet. Tunicamycin and PNGase F treatment down-shifted the 120-kD protein and the 64-kD doublet into lower molecular weight bands, suggesting that both were glycosylated. Trypsin treatment converted the 120-kD protein and the 64-kD doublet into a 40-kD fragment. Baculovirus-expressed IA-2 was as sensitive or slightly more sensitive than in vitro translated IA-2 in detecting autoantibodies to IA-2: 66% of sera from newly diagnosed IDDM patients reacted with baculovirus-expressed IA-2 compared with 59% of the same sera which reacted with in vitro translated IA-2. It is concluded that baculovirus-expressed IA-2 is a good source of autoantigen and that a number of lower molecular weight fragments with which IDDM autoantibodies react are derived from the 120-kD full-length IA-2 molecule. C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 124,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 33 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 1998 VL 113 IS 3 BP 367 EP 372 PG 6 WC Immunology SC Immunology GA 118VD UT WOS:000075860400009 PM 9737664 ER PT J AU Nagaraju, K Raben, N Merritt, G Loeffler, L Kirk, K Plotz, P AF Nagaraju, K Raben, N Merritt, G Loeffler, L Kirk, K Plotz, P TI A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE human skeletal muscle cells; proinflammatory stimuli; cytokines; chemokines ID TRANSFORMING GROWTH-FACTOR; MEDIATED CYTO-TOXICITY; MHC CLASS-II; INFLAMMATORY MYOPATHIES; ADHESION MOLECULES; ANTIGEN EXPRESSION; MONONUCLEAR-CELLS; HUMAN MYOBLASTS; HLA-DR; MYOSITIS AB Muscle is an attractive target for gene therapy and for immunization with DNA vaccines and is also the target of immunological injury in myositis. It is important therefore to understand the immunologic capabilities of muscle cells themselves. In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-beta), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the upregulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1). Thus, muscle cells have an inherent ability to express and respond to a variety of cytokines and chemokines. The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Nagaraju, K (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Ctr Clin, Bld 10, Bethesda, MD 20892 USA. NR 29 TC 105 Z9 109 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 1998 VL 113 IS 3 BP 407 EP 414 PG 8 WC Immunology SC Immunology GA 118VD UT WOS:000075860400015 PM 9737670 ER PT J AU Danning, CL Boumpas, DT AF Danning, CL Boumpas, DT TI Commonly used disease-modifying antirheumatic drugs in the treatment of inflammatory arthritis: An update on mechanisms of action SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE rheumatoid arthritis; DMARDs; mechanisms; cytokine production; cell activation; signal transduction ID GOLD SODIUM THIOMALATE; LOW-DOSE METHOTREXATE; NECROSIS-FACTOR-ALPHA; HUMAN T-CELLS; NF-KAPPA-B; PERIPHERAL-BLOOD LYMPHOCYTES; COLLAGENASE GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; CYCLOSPORINE-A; HUMAN-MONOCYTES AB Although disease-modifying drugs are extensively used in the treatment of inflammatory arthritides such as rheumatoid arthritis (RA), the actual underlying mechanisms of action of these agents remains somewhat unclear. Many investigators have studied the effects of these agents, often with particular attention being paid to alterations in inflammatory cytokine production, cell proliferation and activation, signal transduction pathways, and enzyme inhibition. By gaining a more complete understanding of these mechanisms, further information may be had regarding the pathophysiology of RA as well as other autoimmune diseases. In the following review we will examine some of the more recent studies of drug mechanisms, focusing on the most commonly used anti-rheumatic medications in the treatment of RA. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Danning, CL (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 139 TC 17 Z9 18 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1998 VL 16 IS 5 BP 595 EP 604 PG 10 WC Rheumatology SC Rheumatology GA 119YL UT WOS:000075926400016 PM 9779311 ER PT J AU Kasturi, VK Dearing, MP Piscitelli, SC Russell, EK Sladek, GG O'Neil, K Turner, GA Morton, TL Christian, MC Johnson, BE Kelley, MJ AF Kasturi, VK Dearing, MP Piscitelli, SC Russell, EK Sladek, GG O'Neil, K Turner, GA Morton, TL Christian, MC Johnson, BE Kelley, MJ TI Phase I study of a five-day dose schedule of 4-ipomeanol in patients with non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID POTATOES IPOMOEA-BATATAS; METABOLIC-ACTIVATION; CLINICAL-TRIALS; REACTIVE METABOLITES; COLORIMETRIC ASSAY; DIVERSE PANEL; LINES; DRUG; INVITRO; TOXICITY AB The mammalian pulmonary toxin 4-ipomeanol (LPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has irt vitro and in vivo antitumor activity in non-small cell lung cancer (NSCLC) and thus was proposed as a lung cancer-specific antitumor agent. We have completed a directed Phase I trial in patients with NSCLC, Forty-four patients (34 men and 10 women) with NSCLC were treated with IPO, All but two patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, They received 91 courses of therapy with i.v. IPO; 82 courses were administered daily for five days, and 9 were single bolus doses. The dose-limiting toxicity of elevated serum transaminases was observed in three of seven patients at 922 mg/m(2)/day. The maximum tolerated dose was 693 mg/m(2)/day on 5 consecutive days every 3 weeks. One patient developed grade 4 pulmonary toxicity at 167 mg/m(2)/day. There was no significant hematological or renal toxicity. No objective antitumor responses were observed. Pharmacokinetic analysis of 39 patients from day 1 of IPO administration showed biexponential elimination with mean half-lives of 8.6 (alpha half-life) and 76 min (beta half-life). There was a linear relationship between the area under the plasma drug concentration-time curve and the dose of IPO, There was no significant difference between the pharmacokinetic parameters measured on day 1 and day 5, Using a 4-day in vitro cytotoxicity assay, two tumor cell lines established from patients treated at 693 mg/m(2)/day had IC(50)s of similar to 6 mM, a concentration more than 75-fold higher than the plasma levels measured in these patients, Thus, although the total amount of drug administered per cycle on a daily times five dose schedule is more than 2.5-fold higher than the recommended single daily dose, IPO is unlikely to be a useful drug for patients with lung cancer. C1 Natl Naval Med Ctr, Med Branch, Bethesda, MD 20889 USA. Natl Naval Med Ctr, Ctr Clin, Dept Pharm, Bethesda, MD 20889 USA. Natl Naval Med Ctr, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20889 USA. Natl Naval Med Ctr, Natl Canc Inst, Bethesda, MD 20889 USA. Natl Naval Med Ctr, Dept Med, Bethesda, MD 20889 USA. Midwest Res Inst, Kansas City, MO 64110 USA. RP Kelley, MJ (reprint author), Natl Naval Med Ctr, Med Branch, Bldg 8,Room 5101,8901 Rockville Pike, Bethesda, MD 20889 USA. OI Kelley, Michael/0000-0001-9523-6080 FU NCI NIH HHS [N01-CM-27748] NR 40 TC 18 Z9 18 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1998 VL 4 IS 9 BP 2095 EP 2102 PG 8 WC Oncology SC Oncology GA 116TY UT WOS:000075742000010 PM 9748125 ER PT J AU Steller, MA Gurski, KJ Murakami, M Daniel, RW Shah, KV Celis, E Sette, A Trimble, EL Park, RC Marincola, FM AF Steller, MA Gurski, KJ Murakami, M Daniel, RW Shah, KV Celis, E Sette, A Trimble, EL Park, RC Marincola, FM TI Cell-mediated immunological responses in cervical and vaginal cancer patients immunized with a lipidated epitope of human papillomavirus type 16 E7 SO CLINICAL CANCER RESEARCH LA English DT Article ID T-LYMPHOCYTE RESPONSE; IN-VIVO; INFLUENZA NUCLEOPROTEIN; SYNTHETIC PEPTIDES; MELANOMA PATIENTS; PERIPHERAL-BLOOD; HELPER EPITOPES; HLA-A2 SUBTYPES; ANTIGEN; E6 AB Human papillomavirus (HPV) infection has been causally associated with cervical cancer. Ne tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E7(86-93) lipopeptide inoculations at 3-week intervals. HLA-AZ subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8(+) T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination, CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E7(86-93)-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations, Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities, The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer, Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease. C1 NCI, Canc Therapy Evaluat Program, Surg Branch, Gynecol Oncol Sect, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. Cytel Corp, San Diego, CA 92121 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Steller, MA (reprint author), Brown Univ, Women & Infants Hosp, 1 Blackstone Pl,3rd Floor, Providence, RI 02905 USA. EM msteller@wihri.org NR 40 TC 134 Z9 143 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1998 VL 4 IS 9 BP 2103 EP 2109 PG 7 WC Oncology SC Oncology GA 116TY UT WOS:000075742000011 PM 9748126 ER PT J AU Russoniello, C Somasundaram, C Schlom, J Deo, YM Keler, T AF Russoniello, C Somasundaram, C Schlom, J Deo, YM Keler, T TI Characterization of a novel bispecific antibody that mediates Fc gamma receptor type I-dependent killing of tumor-associated glycoprotein-72-expressing tumor cells SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN MONONUCLEAR PHAGOCYTES; MONOCLONAL-ANTIBODIES; RADIOIMMUNOTHERAPY TRIAL; CELLULAR CYTOTOXICITY; COLORECTAL-CANCER; INTERFERON-GAMMA; ANTIGEN; RI; EXPRESSION; GENERATION AB A bispecific antibody was made by chemical conjugation of Fab' fragments from humanized antibodies specific for tumor-associated glycoprotein-72 (TAG-72) and high-affinity immunoglobulin receptor, Fc gamma receptor type I(Fc gamma RI). The purified anti-TAG-72 x anti-Fc gamma RI (HCC49xH22) bispecific antibody had an approximate M-r of 111,000, consistent with a F(ab')(2), and bound specifically to KLEB and LS174T tumor cell lines, which express the TAG-72 tumor antigen. Furthermore, KCC49xH22 was shown to simultaneously bind to KLEB cells and a soluble Fc gamma RI fusion protein, demonstrating the bifunctional nature of the molecule. Using IFN-gamma-treated monocytes as effector cells, concentrations of the bispecific antibody in the range of 1-10,000 ng/ml mediated specific lysis of TAG-72-positive tumor cells. In contrast, the bispecific antibody did not promote antibody-dependent cellular cytotoxicity of a cell line that was negative for TAG-72 antigen, Importantly, the antibody-dependent cellular cytotoxicity activity of the bispecific antibody was significantly greater than that of the monoclonal antibody HCC49. These in vitro data indicate that the humanized bispecific antibody HCC49xH22 has the appropriate specificity and functional activity for Further evaluation as potential immunotherapy for TAG-72-positive malignancies. C1 Medarex Inc, Annandale, NJ 08801 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Keler, T (reprint author), Medarex Inc, 1545 Route 22 E, Annandale, NJ 08801 USA. NR 34 TC 10 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1998 VL 4 IS 9 BP 2237 EP 2243 PG 7 WC Oncology SC Oncology GA 116TY UT WOS:000075742000029 PM 9748144 ER PT J AU Peterson, KP Pavlovich, JG Goldstein, D Little, R England, J Peterson, CM AF Peterson, KP Pavlovich, JG Goldstein, D Little, R England, J Peterson, CM TI What is hemoglobin Alc? An analysis of glycated hemoglobins by electrospray ionization mass spectrometry SO CLINICAL CHEMISTRY LA English DT Article ID NON-ENZYMATIC GLYCOSYLATION; IDENTIFICATION; ACETALDEHYDE; EXCHANGE; GLYCOHEMOGLOBIN; CHROMATOGRAPHY; PEPTIDES; PROTEINS; ADDUCTS; SITES AB Hemoglobin A(1c) (HbA(1c)) is a stable minor Hb variant formed in vivo by posttranslational modification by glucose, originally identified by using cation exchange chromatography, and containing primarily glycated N-terminal beta-chains. However, the structure(s) of the quantified species has not been elucidated, and the available methods lack a reference standard. We used electrospray ionization mass spectrometry to determine the extent of glycation of samples separated by boronate affinity and/or cation exchange chromatography. Analyses of clinical samples were consistent with the curvilinear relationship of patient glucose and HbA(1c). As glycation increased, the ratio of beta-chain to alpha-chain glycation increased, and the number of glycation sites on the beta-chain increased, although these were relatively minor components. We found several glycated species that cochromatographed with HbA(1c) on cation exchange, including species with both glycated alpha- and beta-chains, nonglycated alpha- and glycated beta-chains, and multiply glycated beta-chains. The combined use of affinity and cation exchange chromatography with structural confirmation by electrospray ionization mass spectrometry was found to be useful in producing samples of sufficient purity for the standardization of glycohemoglobin clinical assays. C1 Samsum Med Res Fdn, Santa Barbara, CA 93111 USA. Univ Calif Santa Barbara, Dept Chem, Santa Barbara, CA 93106 USA. Univ Missouri, Sch Med, Columbia, MO 65212 USA. National Heart Lung & Blood Institute, Div Blood Dis & Resources, NIH, Bethesda, MD 20817 USA. RP Peterson, KP (reprint author), 11920 Glen Mill Rd, Potomac, MD 20854 USA. RI Peterson, Karen/E-8084-2015; OI Peterson, Karen/0000-0001-6737-8698; Little, Randie/0000-0001-6450-8012 NR 30 TC 86 Z9 94 U1 3 U2 11 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 1998 VL 44 IS 9 BP 1951 EP 1958 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 115NL UT WOS:000075671500013 PM 9732983 ER PT J AU Uriarte, MM Klein, KO Barnes, KM Pescovitz, OH Loriaux, DL Cutler, GB AF Uriarte, MM Klein, KO Barnes, KM Pescovitz, OH Loriaux, DL Cutler, GB TI Gonadotrophin and prolactin secretory dynamics in girls with normal puberty, idiopathic precocious puberty and precocious puberty due to hypothalamic hamartoma SO CLINICAL ENDOCRINOLOGY LA English DT Article ID TUBER CINEREUM; HORMONE; BOYS AB OBJECTIVE This study was designed to test the hypothesis that hypothalamic hamartoma causes precocious puberty through a different neuroendocrine mechanism than that of normal puberty or of idiopathic precocious puberty. DESIGN AND PATIENTS We compared the pattern of gonadotrophin secretion among 4 girls with precocious puberty due to hypothalamic hamartoma, 27 girls with idiopathic precocious puberty, and 14 girls with normal puberty, All subjects were breast stage 3 or 4, Blood samples were obtained every 20 min for 4 h during the day (1.000 hours to 1400 h) and night (22.00 hours to 0200 h), MEASUREMENTS LH, FSH, and prolactin were measured in each blood sample, Girls also underwent LHRH-stimulation with measurement of LH and FSH before and after stimulation, RESULTS There were no significant differences in mean LH level, LH peak amplitude, or LH or FSH peak frequency during either the day or the night among the three diagnostic groups, However, the mean +/- SD LHRH-stimulated peak LH levels were greater in girls with hypothalamic hamartoma than in girls with normal puberty or with idiopathic precocious puberty (194 +/- 142 vs 85 +/- 60 or 66 +/- 54 IU/l, respectively, P< 0.05). The LHRH-stimulated peak FSH level in girls with hypothalamic hamartoma exceeded the level for the normal pubertal girls (31 +/- 19 vs 17 +/- 7 lull, P< 0.05), but not the level for the girls with idiopathic precocious puberty (25 + 12 lull), The peak LH to peak FSH ratio in the girls with hypothalamic hamartoma exceeded the ratio for the girls with idiopathic precocious puberty (7 3 +/- 3.9 vs 2.6 +/- 3.0 lull, P< 0.05), but not the ratio for the normal pubertal girls (5.0+2.9). There were no significant differences in mean prolactin level, peak amplitude or frequency, or in the ratio of mean night to mean day prolactin, among the 3 diagnostic groups, CONCLUSIONS We conclude that spontaneous gonadotrophin and prolactin secretion are similar among girls with hypothalamic hamartoma, idiopathic precocious puberty, or normal puberty, However, the increased LHRH-stimulated peak LH in the girls with hypothalamic hamartoma suggests subtle differences in neuroendocrine regulation that may underlie their more rapid pubertal maturation. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Klein, KO (reprint author), Dupont Hosp Children, POB 269,1600 Rockland Rd, Wilmington, DE 19899 USA. NR 38 TC 9 Z9 11 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 1998 VL 49 IS 3 BP 363 EP 368 DI 10.1046/j.1365-2265.1998.00518.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 126BA UT WOS:000076271800016 PM 9861328 ER PT J AU Petreska, L Koceva, S Plaseska, D Chernick, M Gordova-Muratovska, A Fustic, S Nestorov, R Efremov, GD AF Petreska, L Koceva, S Plaseska, D Chernick, M Gordova-Muratovska, A Fustic, S Nestorov, R Efremov, GD TI Molecular basis of cystic fibrosis in the Republic of Macedonia SO CLINICAL GENETICS LA English DT Article DE CFTR; cystic fibrosis; haplotypes; mutations ID REGULATOR CFTR GENE; MUTATIONS; DNA; IDENTIFICATION; POLYMORPHISM; DELTA-F508; REGIONS; ORIGIN; AMPLIFICATION; POPULATION AB Eighty-three cystic fibrosis (CF) patients and their families, belonging to various ethnic groups living in the Republic of Macedonia were studied for molecular defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and for the associated extragenic marker loci XV-2c and KM19. The DNA methodology used included characterization of CFTR mutations in 19 exons land flanking sequences) of the gene and analysis of distribution of the XV-2c/KM19 haplotypes among normal (N) and CF chromosomes by polymerase chain reaction (PCR) amplification followed by dot blot hybridization, restriction digestion, single-strand conformational polymorphism; constant denaturing gel electrophoresis, denaturing gradient gel electrophoresis, and sequencing. We identified 58.4% (97/166) of the CF chromosomes. Nine different CFTR gene mutations, including three novel ones, were found. Eight known and one new CFTR intragene polymorphisms were also characterized. The haplotype analysis of the XV-2c/TaqI and KM19/PstI polymorphic loci have shown that haplotype C is the most frequently found haplotype among the non-Delta F508 CF chromosomes from Macedonia (36.5%). The results demonstrate the bread heterogeneity of CF origin in this part of the Balkan Peninsula. C1 Macedonian Acad Sci & Arts, Res Ctr Genet Engn & Biotechnol, Skopje 91000, Macedonia. Fac Med, Dept Pediat, Skopje, Macedonia. Fac Med, Inst Resp Dis Children, Skopje, Macedonia. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Efremov, GD (reprint author), Macedonian Acad Sci & Arts, Res Ctr Genet Engn & Biotechnol, Bul Krste Misirkov 2,POB 428, Skopje 91000, Macedonia. EM gde@manu.edu.mk NR 40 TC 11 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD SEP PY 1998 VL 54 IS 3 BP 203 EP 209 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 122MJ UT WOS:000076075800006 PM 9788722 ER PT J AU Groll, AH Jaeger, G Allendorf, A Herrmann, G Schloesser, R von Loewenich, V AF Groll, AH Jaeger, G Allendorf, A Herrmann, G Schloesser, R von Loewenich, V TI Invasive pulmonary aspergillosis in a critically ill neonate: Case report and review of invasive aspergillosis during the first 3 months of life SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; LOW-BIRTH-WEIGHT; PRIMARY CUTANEOUS ASPERGILLOSIS; LIPOSOMAL AMPHOTERICIN-B; DISSEMINATED FUNGAL-INFECTIONS; BONE-MARROW TRANSPLANTATION; ORAL ITRACONAZOLE THERAPY; COLONY-STIMULATING FACTOR; SYSTEMIC CANDIDIASIS; GAMMA-INTERFERON AB We report a fatal case of invasive pulmonary aspergillosis in a severely ill neonate and review 43 additional cases of invasive aspergillosis reported from 1955 through 1996 that occurred during the first 3 months of life. Eleven of the 44 patients had primary cutaneous aspergillosis, 10 had invasive pulmonary aspergillosis, and 14 had disseminated disease. Most infections were nosocomial in origin. Prematurity (43%); proven chronic granulomatous disease (14%); and a complex of diarrhea, dehydration, malnutrition, and invasive bacterial infections (23%) accounted for the majority of underlying conditions. At least 41% of the patients had received corticosteroid therapy before diagnosis, but only one patient had been neutropenic. Among patients who received medical and/or surgical treatment, outcome was relatively favorable, with an overall survival rate of 73%. Invasive aspergillosis may occur in neonates and young infants and warrants consideration under certain circumstances. Current therapeutic approaches consist of high-dose amphotericin B and appropriate surgical interventions. C1 Univ Frankfurt Hosp, Dept Pediat, Frankfurt, Germany. Univ Frankfurt Hosp, Dept Pathol, Frankfurt, Germany. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 106 TC 63 Z9 68 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1998 VL 27 IS 3 BP 437 EP 452 DI 10.1086/514717 PG 16 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 119VD UT WOS:000075917900006 PM 9770138 ER PT J AU Walsh, TJ AF Walsh, TJ TI Primary cutaneous aspergillosis - An emerging infection among immunocompromised patients SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; FUMIGATUS CONIDIA; FUNGAL-INFECTIONS; RHIZOPUS-ORYZAE; CHILDREN; HYPHAE; MONONUCLEAR; FIBRINOGEN C1 NCI, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Bldg 10,Room 13N-240, Bethesda, MD 20892 USA. NR 40 TC 49 Z9 51 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1998 VL 27 IS 3 BP 453 EP 457 DI 10.1086/514718 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 119VD UT WOS:000075917900007 PM 9770139 ER PT J AU Abati, A Fetsch, P Filie, A AF Abati, A Fetsch, P Filie, A TI If cells could talk - The application of new techniques to cytopathology SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID IN-SITU HYBRIDIZATION; POLYMERASE CHAIN-REACTION; FINE-NEEDLE ASPIRATION; PARAFFIN-EMBEDDED TISSUE; NUMERICAL CHROMOSOMAL-ABNORMALITIES; HUMAN PAPILLOMAVIRUS DNA; TUMOR-SUPPRESSOR GENE; INSITU HYBRIDIZATION; ANTIGEN RETRIEVAL; IMMUNOPEROXIDASE TECHNIQUES AB Cytopathology is no longer simply a screening modality limited to the "Pap mills" of yore. The news in cervicovaginal cytology is automation. The news in FNA cytology is the application of molecular techniques. Whether it is the detection of specific proteins/antigens for definitive diagnoses/treatment guidance in immunotherapy, or it is "reading nucleic acids," the cytopathologist of the future will be called upon to gather and report more detailed and precise information. As we develop methods for extrapolating the secrets previously locked within the individual cells, it becomes evident that the cells were talking all along, we just did not know how to listen. C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, NIH, Bldg 10,Room 2A19,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 66 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 1998 VL 18 IS 3 BP 561 EP + PG 24 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 119LA UT WOS:000075896500010 PM 9742383 ER PT J AU Mazor, M Chaim, W Maymon, E Hershkowitz, R Romero, R AF Mazor, M Chaim, W Maymon, E Hershkowitz, R Romero, R TI The role of antibiotic therapy in the prevention of prematurity SO CLINICS IN PERINATOLOGY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; IDIOPATHIC PRETERM LABOR; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; AMNIOTIC-FLUID INTERLEUKIN-6; RANDOMIZED CONTROLLED TRIAL; BLOOD-CELL COUNT; LOW-BIRTH-WEIGHT; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; BACTERIAL VAGINOSIS AB Prematurity is the leading cause of perinatal morbidity and mortality in the industrial world, occurring in 4% to 9% of all deliveries, a rate that has remained unchanged during the past decades. Despite the relative minority of obstetric patients affected by this problem, prematurity is responsible for approximately 70% to 80% of perinatal morbidity and mortality corrected for congenital anomalies. To date, treatment modalities (tocolysis) that have been applied to patients who have preterm labor (PTL) and preterm premature rupture of membranes have been found to be of limited value in reducing both the rate of prematurity and of perinatal mortality and morbidity. A possible explanation for this failure in prevention of prematurity can be attributed to the poor understanding of the mechanisms of parturition in general and the pathoyhysiology of PTL in particular. C1 Soroka Med Ctr, Dept Obstet & Gynecol, IL-84101 Beer Sheva, Israel. Ben Gurion Univ Negev, Beer Sheva, Israel. NICHHD, Perinatol Res Branch, NIH, Detroit, MI USA. RP Mazor, M (reprint author), Soroka Med Ctr, Dept Obstet & Gynecol, POB 151, IL-84101 Beer Sheva, Israel. NR 146 TC 5 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD SEP PY 1998 VL 25 IS 3 BP 659 EP + PG 28 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 121LV UT WOS:000076016000011 PM 9779340 ER PT J AU Butler, AA Yakar, S Gewolb, IH Karas, M Okubo, Y LeRoith, D AF Butler, AA Yakar, S Gewolb, IH Karas, M Okubo, Y LeRoith, D TI Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Conference of the European-Society-for-Comparative-Physioloyg-and-Biochemistry CY AUG 24-28, 1997 CL BARCELONA, SPAIN SP European Soc Comparat Physiol & Biochem DE insulin-like growth factor-I receptor; signal transduction; physiology; cell biology ID YEAST 2-HYBRID SYSTEM; SH2 DOMAIN PROTEINS; PHOSPHATIDYLINOSITOL 3'-KINASE; TYROSINE PHOSPHORYLATION; CHROMOSOMAL LOCALIZATION; PHOSPHOTYROSINE PROTEIN; SUBSTRATE-1 IRS-1; NEURONAL SURVIVAL; BINDING-PROTEIN; KINASE AKT AB The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism. (C) 1998 Published by Elsevier Science inc. All rights reserved. C1 NIDDKD, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDKD, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Room 8S 235A,Bldg 10,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. NR 59 TC 199 Z9 201 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD SEP PY 1998 VL 121 IS 1 BP 19 EP 26 DI 10.1016/S0305-0491(98)10106-2 PG 8 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 150HA UT WOS:000077657400004 PM 9972281 ER PT J AU Zalla, T Sirigu, A Pillon, B Dubois, B Grafman, J Agid, Y AF Zalla, T Sirigu, A Pillon, B Dubois, B Grafman, J Agid, Y TI Deficit in evaluating pre-determinated sequences of script events in patients with Parkinson's disease SO CORTEX LA English DT Article DE script event sequence; shifting ability; Parkinson's disease ID BASAL GANGLIA; MEMORY; ATTENTION; LESIONS; CORTEX; DAMAGE AB The purpose of the present study was to assess how the striato-frontal system contributes to the manipulation of goal-directed actions. We studied a group off ten patients with Parkinson's disease (PD) in order to investigate which aspects of action knowledge processing are impaired and to define the conditions under which the deficits may occur. PD patients committed errors of sequence and inserted distracters in tasks that required them to order pre-determined events belonging to a given script in a typical sequence. Rather than attributing errors of event sequencing to a deficit of script "syntax" knowledge, we suggest that the difficulties manifested by PD patients were due to an impairment of a switching mechanism that is necessary for processing information in parallel. C1 Hop La Pitie Salpetriere, Inserm U289, Paris, France. Ecole Polytech, Crea, F-75230 Paris, France. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Zalla, T (reprint author), Inst Cognit Sci, 67 Blvd Pinel, F-69675 Bron, France. EM zalla@ext.jussieu.fr OI Grafman, Jordan H./0000-0001-8645-4457 NR 26 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD SEP PY 1998 VL 34 IS 4 BP 621 EP 627 DI 10.1016/S0010-9452(08)70519-7 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 129BT UT WOS:000076443900011 PM 9800095 ER PT J AU Danis, M Grady, C AF Danis, M Grady, C TI Institutional Review Board review and consent for research: What's behind the statistics? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE Institutional Review Board; informed consent; ethics ID INFORMED CONSENT C1 NIH, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1998 VL 26 IS 9 BP 1488 EP 1489 DI 10.1097/00003246-199809000-00013 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 123WX UT WOS:000076149500013 PM 9751583 ER PT J AU Frederikse, PH Zigler, JS AF Frederikse, PH Zigler, JS TI Presenilin expression in the ocular lens SO CURRENT EYE RESEARCH LA English DT Article DE presenilin; cataract; Alzheimer's disease; proteolysis ID BETA-PROTEIN TOXICITY; ALZHEIMERS-DISEASE; TRANSGENIC MICE; CUBOMEDUSAN JELLYFISH; GENES; CELLS; MECHANISM; SCRAPIE; EYE AB Purpose. Mutations in the presenilin (PS) proteins account for the majority of early onset Alzheimer's disease (AD) cases, apparently by influencing the cleavage of the Alzheimer's disease protein (beta APP) to form beta-amyloid (A beta), the major component of plaques in the brains of AD patients. We reported previously that AD proteins are expressed in mammalian lenses, and that beta APP and A beta increased in the epithelium and outer cortex of lenses subjected to oxidative stress. This increase paralleled the increase in AP1 DNA binding activity, which has been shown to accompany proliferative oxidative stress responses. Both cataract and AD have been closely linked with oxidative stress; further, both AD and cataract occur in a majority of Down Syndrome individuals. Here we investigate the expression and post-translational processing of PS proteins in the ocular lens. Methods. In situ hybridization, immuohistochemical detection and immunoblot assays were used to localize mRNA and proteins expression products and determine the approximate molecular weights of the resulting proteins in ocular tissue samples. Results. We report here that PS protein and mRNA are expressed in lenses, and additionally in the cornea, and are proteolytically processed in a manner similar to that demonstrated in brain tissue. PS proteins and mRNAs were localized to the lens epithelium and outer fibers. This pattern agrees with the localization demonstrated by others for mammalian Notch-like receptor proteins. PS and Notch proteins occur together in developmentally regulated cascades of gene expression found in diverse biological systems. Conclusions. PS expression, together with beta APP and A beta proteins, all associated with age-related degenerative disease, are expressed in lens and might contribute to cataractogenesis. C1 National Eye Institute, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Frederikse, PH (reprint author), National Eye Institute, Lab Mechanisms Ocular Dis, NIH, Bldg 6,Room 237, Bethesda, MD 20892 USA. NR 26 TC 26 Z9 26 U1 0 U2 2 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1998 VL 17 IS 9 BP 947 EP 952 DI 10.1076/ceyr.17.9.947.5135 PG 6 WC Ophthalmology SC Ophthalmology GA 114HZ UT WOS:000075604200012 PM 9746443 ER PT J AU Nielsen, S Fror, J Knepper, MA AF Nielsen, S Fror, J Knepper, MA TI Renal aquaporins: key roles in water balance and water balance disorders SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID INDUCED DOWN-REGULATION; KIDNEY COLLECTING DUCT; RAT-KIDNEY; CHANNEL EXPRESSION; FUNCTIONAL EXPRESSION; PLASMA-MEMBRANE; HEART-FAILURE; VASOPRESSIN; CLONING; PROTEIN AB The discovery of a family of molecular water channels, aquaporins, by Agre and co-workers has shed light on the long-standing biophysical question of how water traverses biological membranes, and has provided detailed molecular insight into the fundamental physiology of water balance and the pathophysiology of water balance disorders, in this review, we focus mainly on the vasopressin-regulated water channel, aquaporin 2, and its critical role in acute and chronic regulation of body water balance, as well as in multiple water balance disorders. Curr Opin Nephrol Hypertens 7:509-516. (C) 1998 Lippincott Williams & Wilkins. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. Aarhus Univ, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. EM sn@ana.aau.dk NR 53 TC 28 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 1998 VL 7 IS 5 BP 509 EP 516 DI 10.1097/00041552-199809000-00005 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 130AV UT WOS:000076497800005 PM 9818197 ER PT J AU Maron, BJ AF Maron, BJ TI Heart disease and other causes of sudden death in young athletes SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID LEFT-VENTRICULAR HYPERTROPHY; DESCENDING CORONARY-ARTERY; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; MITRAL-VALVE PROLAPSE; LONG-QT SYNDROME; ANOMALOUS ORIGIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; CARDIAC DEATH; TRANSESOPHAGEAL ECHOCARDIOGRAPHY C1 NHLBI, Bethesda, MD 20892 USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Minneapolis, MN USA. NR 148 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD SEP PY 1998 VL 23 IS 9 BP 482 EP 529 PG 50 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 123NY UT WOS:000076132300002 ER PT J AU Weinstein, M Xu, XL Ohyama, K Deng, CX AF Weinstein, M Xu, XL Ohyama, K Deng, CX TI FGFR-3 and FGFR-4 function cooperatively to direct alveogenesis in the murine lung SO DEVELOPMENT LA English DT Article DE FGFR-3; FGFR-4; receptor cooperativity; lung development; secondary septation; alveogenesis ID FIBROBLAST-GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL INTERACTION; EMBRYONIC MOUSE LUNG; MICE LACKING; LIMB DEVELOPMENT; BRANCHING MORPHOGENESIS; FACTOR RECEPTOR-4; TRACHEAL SYSTEM; VERTEBRATE LIMB; CELL-MIGRATION AB Mammalian lungs begin as an outpocket of the foregut, and depend on multiple stages of branching morphogenesis and alveogenesis to reach their final form. An examination of fgf receptor gene expression indicated that all four receptors (fgfr-1 to fgfr-4) are expressed in postnatal lungs at varying levels. We show that mice homozygous for a targeted mutation of fgfr-4 exhibited no overt abnormalities in the lungs or any other organ. However, mice doubly homozygous for disruptions of the fgfr-3 and fgfr-4 genes display novel phenotypes not present in either single mutant, which include pronounced dwarfism and lung abnormalities. Lungs of fgfr-3(-/-)fgfr-4(-/-) animals, which are normal at birth, are completely blocked in alveogenesis and do not form secondary septae to delimit alveoli. Consequently, air spaces in the lung are expanded and no alveoli can be seen. The mutant lungs failed to downregulate postnatal elastin deposition despite their normal levels of surfactant expression and cell proliferation. These data revealed a cooperative function of FGFR-3 and FGFR-4 to promote the formation of alveoli during postnatal lung development. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Anat, Tokyo 160, Japan. RP Deng, CX (reprint author), NIDDKD, Biochem & Metab Lab, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM ChuxiaD@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 62 TC 305 Z9 312 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1998 VL 125 IS 18 BP 3615 EP 3623 PG 9 WC Developmental Biology SC Developmental Biology GA 129YV UT WOS:000076492400009 PM 9716527 ER PT J AU Mu, XQ Lee, B Louis, JM Kimmel, AR AF Mu, XQ Lee, B Louis, JM Kimmel, AR TI Sequence-specific protein interaction with a transcriptional enhancer involved in the autoregulated expression of cAMP receptor 1 in Dictyostelium SO DEVELOPMENT LA English DT Article DE DNA-binding protein; cAMP regulation; promoter; receptor; Dictyostelium; transcriptional enhancer ID CYCLIC-AMP RECEPTOR; GENE-EXPRESSION; CELL-SURFACE; PRESTALK CELLS; STALK CELL; DISCOIDEUM; DIFFERENTIATION; DNA; BINDING; INDUCTION AB Major stages of Dictyostelium development are regulated by secreted, extracellular cAMP through activation of a serpentine receptor family. During early development, oscillations of extracellular cAMP mobilize cells for aggregation; later, continuous exposure to higher extracellular cAMP concentrations downregulates early gene expression and promotes cytodifferentiation and cell-specific gene expression. The cAMP receptor 1 gene CAR1 has two promoters that are differentially responsive to these extracellular cAMP stimuli. The early CAR1 promoter is induced by nM pulses of cAMP, which in turn are generated by CAR1-dependent activation of adenylyl cyclase (AC). Higher, non-fluctuating concentrations of cAMP will adapt this AC stimulus-response, repress the activated early promoter and induce the dormant late promoter, We now identify a critical element of the pulse-induced CAR1 promoter and a nuclear factor with sequence-specific interaction. Mutation of four nucleotides within the element prevents both in vitro protein binding and in vivo expression of an otherwise fully active early CAR1 promoter and multimerization of the wild-type, but not mutant, sequence will confer cAMP regulation to a quiescent heterologous promoter. These cis and trans elements, thus, constitute a part of the molecular response to the cAMP transmembrane signal cascade that regulates early development of Dictyostelium. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 6-B1-22, Bethesda, MD 20892 USA. RI Mu, Xiuqian/I-9146-2014 OI Mu, Xiuqian/0000-0002-8003-7529 NR 59 TC 6 Z9 7 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1998 VL 125 IS 18 BP 3689 EP 3698 PG 10 WC Developmental Biology SC Developmental Biology GA 129YV UT WOS:000076492400016 PM 9716534 ER PT J AU Post, RM Weiss, SRB Li, H Smith, MA Zhang, LX Xing, G Osuch, EA McCann, UD AF Post, RM Weiss, SRB Li, H Smith, MA Zhang, LX Xing, G Osuch, EA McCann, UD TI Neural plasticity and emotional memory SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; GLUCOCORTICOID RECEPTOR FUNCTION; THYROTROPIN-RELEASING-HORMONE; RECURRENT AFFECTIVE-DISORDER; LONG-TERM POTENTIATION; LOCUS-COERULEUS; MESSENGER-RNAS; HIPPOCAMPAL-NEURONS; HOLOCAUST SURVIVORS AB Posttraumatic stress disorder is the pathological replay of emotional memory formed in response to painful, life-threatening, or horrifying events. In contrast, depression is often precipitated by more social context-related stressors. New data suggest that different types of life experiences can differentially impact biochemistry, physiology, anatomy, and behavior at the level of changes in gene expression. Repeated separation of neonatal rat pups from their mother results in many long-lasting alterations in biology and behavior paralleling that in depression, including hypercortisolism. The role of the amygdala in modulating emotional memory is highlighted, as well as some of its unique properties such as metaplasticity (i.e., the differential direction of long-term adaptation, either potentiation or depression) in response to the same input as a function of the prior history of stimulation. The implications of these emerging data on the physiological and molecular mechanisms underlying emotional memory emphasize the particular importance of prevention and early intervention. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 112 TC 49 Z9 51 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1998 VL 10 IS 4 BP 829 EP 855 DI 10.1017/S0954579498001898 PG 27 WC Psychology, Developmental SC Psychology GA 152BL UT WOS:000077755500013 PM 9886229 ER PT J AU Gajewski, K Kim, Y Choi, CY Schulz, RA AF Gajewski, K Kim, Y Choi, CY Schulz, RA TI Combinatorial control of Drosophila mef2 gene expression in cardiac and somatic muscle cell lineages SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE combinatorial enhancer; D-mef2; founder cells; heart; somatic muscle ID D-MEF2 TRANSCRIPTION FACTOR; HEART TUBE FORMATION; VENTRAL MORPHOGENESIS; SIGNALING PATHWAY; FAMILY MEMBER; FGF-RECEPTOR; EGF RECEPTOR; MESODERM; EMBRYOGENESIS; SPECIFICATION AB The Drosophila mef2 gene encodes a MADS domain transcription factor required for the differentiation of cardiac, somatic, and visceral muscles during embryogenesis and the patterning of adult indirect flight muscles assembled during metamorphosis, A prerequisite for D-MEF2 function in myogenesis is its precise expression in multiple cell types during development. Novel enhancers for D-mef2 transcription in cardiac and adult muscle precursor cells have been identified and their regulation by the Tinman and Twist myogenic factors have been demonstrated. However, these results suggested the existence of additional regulators and provided limited information on the specification of progenitor cells for different muscle lineages. We have further characterized the heart enhancer and show it is part of a complex regulatory region controlling the activation and repression of D-mef2 transcription in several cell types. The mutation of a GATA sequence in the enhancer changes its specificity from cardial to pericardial cells, Also, the addition of flanking sequences to the heart enhancer results in expression in a new cell type, that being the founder cells of a subset of body wall muscles, As tinman function is required for D-mef2 expression in both the cardial and founder cells, these results define a shared regulatory DNA that functions in distinct lineages due to the combinatorial activity of Tinman and other factors that work through adjacent sequences, The analysis of D-mef2-lacZ fusion genes in mutant embryos revealed that the specification of the muscle precursor cells involved the wingless gene and the activation of a receptor tyrosine kinase signaling pathway. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Schulz, RA (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672] NR 63 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD SEP PY 1998 VL 208 IS 7 BP 382 EP 392 DI 10.1007/s004270050194 PG 11 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 124NN UT WOS:000076188800003 PM 9732552 ER PT J AU Yamane, A Bringas, P Mayo, ML Amano, O Takahashi, K Vo, H Shum, L Slavkin, HC AF Yamane, A Bringas, P Mayo, ML Amano, O Takahashi, K Vo, H Shum, L Slavkin, HC TI Transforming growth factor alpha up-regulates desmin expression during embryonic mouse tongue myogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mouse tongue myogenesis; mandibular organ culture; desmin; TGF alpha; EGF receptor; antisense oligonucleotides; tyrphostin ID SKELETAL-MUSCLE; FACTOR-BETA; MYOBLAST DIFFERENTIATION; FACTOR RECEPTORS; GENE-EXPRESSION; TGF-ALPHA; TARGETED INACTIVATION; CELL-ADHESION; EGF RECEPTOR; DNA-BINDING AB Myogenesis is determined by a set of myogenic differentiation factors that are, in turn, regulated by a number of peptide growth factors. During embryonic mouse tongue formation, transforming growth factor alpha (TGF alpha), epidermal growth factor (EGF), and their cog nate receptor (EGFR) are co-expressed spatially and temporally with desmin, a muscle-specific structural protein, This investigation tested the hypothesis that TGF alpha directly regulates the myogenic program in developing tongue myoblasts. Mandibular processes from the first branchial arch of embryonic day 10.5 (E10,5) mouse embryos were microdissected and explanted into an organ culture system using serumless chemically defined medium. Exogenous TGF alpha at 10 and 20 ng/ml specifically increased the amount of desmin expression and the number of desmin-positive cells without affecting the general growth and development of the mandibles. This inductive response was detected as early as 2 days after treatment and sustained up to 9 days in culture. EGFR antisense oligonucleotides (30 mu M) as well as tyrphostin (80 mu M) were able to negate TGF alpha-induced up-regulation of desmin expression. These data indicate that autocrine and/or paracrine action of TGF alpha promotes tongue myogenesis, and that this action is mediated through functional kinase activity of the EGFR, We speculate that the myogenic program in the developing mouse tongue is dependent upon growth factor mediated cell-cell communication of mesenchymal cells originating from the occipital somites and ectomesenchymal cells originating from the cranial neural crest. Dev, Dyn 1998;213:71-81. (C) 1998 Wiley-Liss, Inc. C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA. RP Slavkin, HC (reprint author), NIAMSD, Craniofacial Dev Sect, NIH, 6 Ctr Dr,MSC 2745,Bldg 6,Room 324, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE-02848] NR 76 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 1998 VL 213 IS 1 BP 71 EP 81 DI 10.1002/(SICI)1097-0177(199809)213:1<71::AID-AJA7>3.3.CO;2-1 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 113AB UT WOS:000075526200007 PM 9733102 ER PT J AU Robb, L Mifsud, L Hartley, L Biben, C Copeland, NG Gilbert, DJ Jenkins, NA Harvey, RP AF Robb, L Mifsud, L Hartley, L Biben, C Copeland, NG Gilbert, DJ Jenkins, NA Harvey, RP TI epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads SO DEVELOPMENTAL DYNAMICS LA English DT Article DE basic helix-loop-helix gene; epicardium; kidney; lung; gonad ID DEVELOPING NERVOUS-SYSTEM; CARDIAC MORPHOGENESIS; PARAXIAL MESODERM; MOUSE EMBRYO; NEURAL CREST; MUSCLE CELLS; LINKAGE MAP; HEART; MICE; DIFFERENTIATION AB We report the cloning, chromosomal localization, and analysis of the expression pattern of epicardin, a member of the basic helix-loop-helix (bHLH) family of transcription factors. Within its bHLH domain, the human and murine epicardin genes were most similar to paraxis, a bHLH gene important for segmentation of embryonic paraxial mesoderm. In situ hybridization studies revealed strong epicardin. expression in murine embryos at 9.5 days postcoitum (dpc) in a region of the septum transversum at the base of the heart known as the proepicardial organ. This mesenchymal structure extends villous projections from which epicardial precursor cells emerge and migrate out over the surface of the myocardium. Strong expression was seen in individual migratory cells and clusters at 9.5 dpc and in a continuous epicardial cell layer in more mature hearts. Also from 9.5 dpc, epicardin transcripts were seen in endocardial cushions of the atrioventricular canal and outflow tract, in skeletal myoblasts within branchial arches and in condensing mesenchyme of gut, kidney, urinary tract, gonads, spleen, and lung. Northern analysis showed that expression persisted in mature visceral organs and heart, but was transient in skeletal muscle. The central role played by bHLH factors in pathways for tissue determination in the embryo suggests a function for epicardin in specification of select mesodermal cell populations associated with heart, cranial skeletal muscle, gut, and urogenital system. Dev. Dyn. 1998;213:105-113, (C) 1998 Wiley-Liss, Inc. C1 PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD USA. RP Robb, L (reprint author), PO Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. NR 48 TC 68 Z9 71 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 1998 VL 213 IS 1 BP 105 EP 113 DI 10.1002/(SICI)1097-0177(199809)213:1<105::AID-AJA10>3.0.CO;2-1 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 113AB UT WOS:000075526200010 PM 9733105 ER PT J AU Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Burchinal, P Caldwell, B Campbell, S Clarke-Stewart, A Cox, M Friedman, S Hirsh-Pasek, K Huston, A Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, C Burchinal, P Caldwell, B Campbell, S Clarke-Stewart, A Cox, M Friedman, S Hirsh-Pasek, K Huston, A Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M TI Relations between family predictors and child outcomes: Are they weaker for children in child care? SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INFANT DAY-CARE; NATIONAL LONGITUDINAL SURVEY; SOCIOEMOTIONAL DEVELOPMENT; MATERNAL EMPLOYMENT; ATTACHMENT; KINDERGARTEN; 2-YEAR-OLD; ADJUSTMENT; COMPETENCE; BEHAVIOR AB Studies suggesting that family factors predict developmental outcomes more strongly for children reared principally by their parents than those with extensive early child-care experience stimulated the examination of the differential prediction of child outcomes using a subsample of families participating in the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. A variety of factors were used to predict development of children who averaged 30 hr of nonparental care per week for each month of their lives and for those who never experienced more than 10 hr of care per week by someone other than their mothers. Multivariate analyses provided no evidence that family factors predicted outcomes differentially for these 2 groups, though exploratory analyses revealed several instances of differential prediction. C1 Vanderbilt Univ, Nashville, TN 37240 USA. Penn State Univ, University Pk, PA 16802 USA. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Calif Irvine, Irvine, CA 92717 USA. NICHHD, Bethesda, MD 20892 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Kansas, Lawrence, KS 66045 USA. Wellesley Coll, Wellesley, MA 02181 USA. Univ New Hampshire, Durham, NH 03824 USA. Univ Texas, Dallas, TX 75230 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Wisconsin, Madison, WI USA. RP Appelbaum, M (reprint author), Vanderbilt Univ, Nashville, TN 37240 USA. RI Marshall, Nancy/C-3428-2012 NR 51 TC 42 Z9 42 U1 1 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD SEP PY 1998 VL 34 IS 5 BP 1119 EP 1128 PG 10 WC Psychology, Developmental SC Psychology GA 122FF UT WOS:000076060700030 ER PT J AU Nelson, RG Morgenstern, H Bennett, PH AF Nelson, RG Morgenstern, H Bennett, PH TI Intrauterine diabetes exposure and the risk of renal disease in diabetic Pima Indians SO DIABETES LA English DT Article ID CONVERTING-ENZYME GENE; URINE SAMPLES; NEPHROPATHY; MELLITUS; PROTEINURIA; PREDISPOSITION; HYPERTENSION; PRESSURE; SUSCEPTIBILITY; PREGNANCY AB The association between the diabetic intrauterine environment and renal disease was examined cross-sectionally in 503 Pima Indians with type 2 diabetes. Subjects were selected from participants in an ongoing study of diabetes and its complications in the Gila River Indian Community of Arizona. Subjects' exposure to diabetes in utero was established from periodic examinations conducted as part of the study. The prevalence of elevated urinary albumin excretion (UAE) (albumin-to-creatinine ratio greater than or equal to 30 mg/g) was 40% (83 of 207) in the offspring of nondiabetic mothers, 43% (105 of 246) in the offspring of prediabetic mothers (i.e., women who were not diabetic at the time of the pregnancy but who developed diabetes after the pregnancy), and 58% (29 of 50) in the offspring of mothers who had diabetes during pregnancy. After controlling for age, sex, duration of diabetes, HbA(1c), and mean arterial pressure in the offspring in a logistic regression analysis using generalized estimating equations, maternal diabetes during pregnancy was strongly associated with elevated UAE. The odds of elevated UAE in the offspring of mothers who had diabetes during pregnancy was 3.8 times (95% CI 1.7-8.4) that of the offspring of prediabetic mothers; the odds of elevated UAE in the offspring of nondiabetic and prediabetic mothers were similar (odds ratio of 0.94; 95% CI 0.59-1.5). We concluded that exposure to a diabetic intrauterine environment increases the risk of elevated UAE in diabetic Pima Indians. The effect of this exposure appears to be independent of other susceptibility factors that lead to nephropathy in diabetes. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Nelson, RG (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012 NR 38 TC 51 Z9 51 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1998 VL 47 IS 9 BP 1489 EP 1493 DI 10.2337/diabetes.47.9.1489 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113FD UT WOS:000075539000016 PM 9726239 ER PT J AU Xia, J Scherer, SW Cohen, PTW Majer, M Xi, T Norman, RA Knowler, WC Bogardus, C Prochazka, M AF Xia, J Scherer, SW Cohen, PTW Majer, M Xi, T Norman, RA Knowler, WC Bogardus, C Prochazka, M TI A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes SO DIABETES LA English DT Article ID SYNTHASE PHOSPHATASE-ACTIVITY; PIMA-INDIANS; MESSENGER-RNA; REGULATORY SUBUNIT; PROTEIN PHOSPHATASE-1; SKELETAL-MUSCLE; NIDDM; GENE; DEGRADATION; MELLITUS AB Selected candidate genes have been analyzed in the Pima Indians of Arizona based on evidence that insulin resistance and type 2 diabetes have significant genetic determinants, An amino acid substitution at codon 905 of the glycogen-targeting subunit of type 1 protein phosphatase that regulates skeletal muscle glycogenesis was recently reported to be associated with changes in insulin action in Danish subjects. In addition to the variant at 905, we report here a novel substitution at codon 883 and common variant of an "ATTTA" element in the 3'-untranslated region (UTR) of the corresponding gene (PPP1R3), The 3'-UTR variant resembled the mRNA-destabilizing AT(AU)-rich elements (AREs) and resulted in a 10-fold difference in reporter mRNA half-life, was correlated with PPP1R3 transcript and protein concentrations in vivo, and was associated with insulin resistance and type 2 diabetes in the Pimas. The variant is more common in Pimas (0.56) than in Caucasians (0.40). Because of its apparent effect on expression of PPP1R3, it may, in part, contribute to the higher prevalence of type 2 diabetes in this Native American population. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Univ Toronto, Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Univ Dundee, Dept Biochem, MRC, Prot Phosphorylat Unit, Dundee DD1 4HN, Scotland. RP Prochazka, M (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 NR 33 TC 73 Z9 79 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1998 VL 47 IS 9 BP 1519 EP 1524 DI 10.2337/diabetes.47.9.1519 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113FD UT WOS:000075539000021 PM 9726244 ER PT J AU Perfetti, R Barnett, PS Mathur, R Egan, JM AF Perfetti, R Barnett, PS Mathur, R Egan, JM TI Novel therapeutic strategies for the treatment of type 2 diabetes SO DIABETES-METABOLISM REVIEWS LA English DT Review DE insulin resistance; Type 2 diabetes; novel therapies ID ALPHA-GLUCOSIDASE INHIBITOR; ACTIVATED RECEPTOR-GAMMA; FATTY-ACID OXIDATION; PEPTIDE-1 7-36 AMIDE; RAT ADIPOCYTES; HYPOGLYCEMIC AGENT; FASTING HYPERGLYCEMIA; INSULIN-RESISTANCE; IN-VITRO; ISOLATED HEPATOCYTES AB Diabetes mellitus is the most common endocrine disease, accounting for over 200 million people affected worldwide. It is characterized by a lack of insulin secretion and/or increased cellular resistance to insulin, resulting in hyperglycemia and other metabolic disturbances. People with diabetes suffer from increased morbidity and premature mortality related to cardiovascular, microvascular and neuropathic complications. The Diabetes Control and Complication Trial (DCCT) has convincingly demonstrated the relationship of hyperglycemia to the development and progression of complications and showed that improved glycemic control reduced these complications. Although the DCCT exclusively studied patients with Type 1 diabetes, there is ample evidence to support the belief that the same relationship between metabolic control and clinical outcome exists in patients with Type 2 diabetes. Therefore, a major effort should be made to develop and implement more effective treatment regimes. This article reviews those novel drugs that have been recently introduced for the management of Type 2 diabetes, or that have reached an advanced level of study and will soon be proposed for preliminary clinical trials. They include: (i) compounds that promote the synthesis/secretion of insulin by the P-cell; (ii) inhibitors of the a-glucosidase activity of the small intestine; (iii) substances that enhance the action of insulin at the level of the target tissues; and (iv) inhibitors of free fatty acid oxidation. (C) 1998 John Wiley & Sons, Ltd. C1 Cedars Sinai Med Ctr, Dept Med, Div Endocrinol & Metab, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NIA, Diabet Sect, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Perfetti, R (reprint author), Cedars Sinai Med Ctr, Dept Med, Div Endocrinol & Metab, Rm B-131,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 125 TC 25 Z9 27 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD SEP PY 1998 VL 14 IS 3 BP 207 EP 225 DI 10.1002/(SICI)1099-0895(1998090)14:3<207::AID-DMR214>3.0.CO;2-J PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 135UE UT WOS:000076820300002 PM 9816470 ER PT J AU Fagot-Campagna, A Nelson, RG Knowler, WC Pettitt, DJ Robbins, DC Go, O Welty, TK Lee, ET Howard, BV AF Fagot-Campagna, A Nelson, RG Knowler, WC Pettitt, DJ Robbins, DC Go, O Welty, TK Lee, ET Howard, BV TI Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: The Strong Heart Study SO DIABETOLOGIA LA English DT Article DE lipoproteins; albuminuria; nephropathies; Type II diabetes; Strong Heart Study ID RISK-FACTORS; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; RENAL-FUNCTION; PIMA-INDIANS; SIMVASTATIN TREATMENT; SEX-HORMONES; INSULIN; NEPHROPATHY; PROGRESSION AB Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (greater than or equal to 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA(1c), study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin. C1 NIDDKD, Phoenix, AZ 85016 USA. Medlant Res Inst, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Epidemiol Res, Oklahoma City, OK USA. Aberdeen Area Indian Hlth Serv, Program Epidemiol, Rapid City, SD USA. RP Fagot-Campagna, A (reprint author), CDC, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy,NE MS-K10, Atlanta, GA 30341 USA. RI Nelson, Robert/B-1470-2012 NR 51 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 1998 VL 41 IS 9 BP 1002 EP 1009 DI 10.1007/s001250051023 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118HX UT WOS:000075833400003 PM 9754817 ER PT J AU Hahm, KB Lee, KJ Kim, JH Cho, SW Chung, MH AF Hahm, KB Lee, KJ Kim, JH Cho, SW Chung, MH TI Helicobacter pylori infection, oxidative DNA damage, gastric carcinogenesis, and reversibility by rebamipide SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT 2nd Mucosta International Symposium on Inflammation and Mucosal Injury CY JUN 19-20, 1997 CL MAUI, HAWAII SP Otsuka Pharmaceutical Co DE Helicobacter pylori; 8-hydroxydeoxyguanosine; apoptosis; inducible nitric oxide synthase; gastric carcinogenesis ID NITRIC-OXIDE SYNTHASE; 8-HYDROXYDEOXYGUANOSINE FORMATION; APOPTOSIS; ERADICATION; DISEASE; NITROTYROSINE; EXPRESSION; CARCINOMA; INDUCTION; PROMOTION AB Several epidemiological studies have demonstrated a close association between Helicobacter pylori infection and carcinoma of the mid- or distal stomach. If this can be shown to be a causal association, eradication of the organism may prevent later development of cancer. Several mechanisms have been proposed by which H. pylori infection might lead to predisposition for gastric cancer. Although many potential pathogenic mechanisms, such as increased proliferative gastric epithelial response to H. pylori, lowered gastric ascorbic acid levels, and high occurrences of atrophic gastritis, have been proposed, there is little evidence as to which might be of direct importance to such H. pylori-related disease in vivo. H. pylori-associated inflammation may interact with other causal factors related to gastric carcinogenesis and can result in the intestinal type of gastric cancer and then DNA damage due to oxygen radicals induced by persistent inflammatory cell infiltrations in the gastric mucosa may lead to alterations of the gene and result in the development of diffuse-type carcinoma. In order to know the influence of H. pylori on changes of inflammation-related DNA damage, we measured the sequential changes of 8-hydroxydeoxyguanosine (8-OHdG) contents of DNA and the changes of two biomarkers inducible nitric oxide synthase (iNOS) and apoptosis from human gastric mucosa according to the status of H. pylori. The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS seem to provide the mechanistic links between H. pylori infection and gastric carcinogenesis and rebamipide can abrogate the levels of these hazard factors. C1 Ajou Univ, Sch Med, Dept Gastroenterol, Suwon 441749, South Korea. Seoul Natl Univ, Sch Med, Dept Pharmacol, Seoul, South Korea. RP Hahm, KB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Rm B1111,Lib Dr, Bethesda, MD 20892 USA. NR 31 TC 36 Z9 39 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1998 VL 43 IS 9 SU S BP 72S EP 77S PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 121VF UT WOS:000076034800013 PM 9753230 ER PT J AU Hahm, KB Lee, KJ Kim, YS Kim, JH Cho, SW Yim, H Joo, HJ AF Hahm, KB Lee, KJ Kim, YS Kim, JH Cho, SW Yim, H Joo, HJ TI Quantitative and qualitative usefulness of rebamipide in eradication regimen of Helicobacter pylori SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT 2nd Mucosta International Symposium on Inflammation and Mucosal Injury CY JUN 19-20, 1997 CL MAUI, HAWAII SP Otsuka Pharmaceutical Co DE Helicobacter pylori; rebamipide; oxidative stress; cytokine; eradication ID OXIDATIVE DNA-DAMAGE; SUPEROXIDE-DISMUTASE; CELL-DAMAGE; APOPTOSIS; GASTRITIS; ASSAY AB The aim of the present study was to determine the efficacy of a new combination regimen including antioxidant, proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastritis. From each of 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection, five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for experimental measures. The patients were then treated either with lansoprozole 30 mg + amoxicillin 1.5 g (LB group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, ii situ terminal deoxyribonucleotide transferase (TdT) -mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially in the LAM-treated group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of the antioxidative drug rebamipide to the eradication regimen against H. pylori has quantitative and qualitative advantages such as either augmenting the eradication rates of H. pylori or decreasing oxidative stress and cytokines levels generated by PI. pylori infection. C1 Ajou Univ, Sch Med, Dept Gastroenterol & Anat Pathol, Suwon, South Korea. RP Hahm, KB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Rm B1111, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 14 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1998 VL 43 IS 9 SU S BP 192S EP 197S PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 121VF UT WOS:000076034800032 PM 9753249 ER PT J AU Merrill, RM Henson, DE Ries, LAG AF Merrill, RM Henson, DE Ries, LAG TI Conditional survival estimates in 34,963 patients with invasive carcinoma of the colon SO DISEASES OF THE COLON & RECTUM LA English DT Article DE blacks; whites; colon cancer; conditional survival; relative survival; observed survival; outcome ID CANCER DEATH CERTIFICATES; COLORECTAL-CANCER; MORTALITY; ACCURACY AB PURPOSE: We report colon cancer survival rates that are conditioned on patients having already survived one or more years after diagnosis. These rates have more meaning clinically, because they consider those patients who have already survived a given period of time after treatment. METHODS: The life table method was used to compute conditional survival rates, using population-based data obtained from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Patients were diagnosed between 1983 and 1987 and followed up through 1994. Relative and observed survival rates are considered. RESULTS: Survival rates up to ten years after diagnosis are reported by stage of disease, gender, and race for colon cancer patients who survived from one to five pears after diagnosis. Survival rates are also reported by lymph node involvement. CONCLUSIONS: Five-year and ten-year survival in colon cancer patients having already survived between one and five years after diagnosis continues to be influenced significantly by stage and race. C1 NCI, ARB, CCRP, DCCPS, Bethesda, MD 20892 USA. NCI, Early Detect Branch, Bethesda, MD 20892 USA. NCI, Canc Stat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Merrill, RM (reprint author), NCI, ARB, CCRP, DCCPS, Execut Plaza N,Room 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 27 TC 54 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD SEP PY 1998 VL 41 IS 9 BP 1097 EP 1106 DI 10.1007/BF02239430 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 120MG UT WOS:000075959700003 PM 9749492 ER PT J AU Barrera-Hernandez, G Zhan, QM Wong, R Cheng, SY AF Barrera-Hernandez, G Zhan, QM Wong, R Cheng, SY TI Thyroid hormone receptor is a negative regulator in p53-mediated signaling pathways SO DNA AND CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; CULTURED GC CELLS; DNA-BINDING DOMAIN; WILD-TYPE; TRANSCRIPTIONAL ACTIVITY; STIMULATES GROWTH; NUCLEAR RECEPTOR; G1 PERIOD; P53; GENE AB Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors which regulate growth, differentiation, and development. The molecular mechanism by which TRs mediated these effects remains unclear. A prevailing hypothesis is that TRs exert their biological effects by cooperating with other transcription factors. We have recently shown that the human TR subtype beta 1 (hTR beta 1) interacts with the tumor suppressor p53, which plays a critical role in cell-cycle regulation and tumorigenesis. This interaction of hTR beta 1 with p53 leads to an impairment of TR function. The present study examined whether hTR beta 1 could modulate the function of p53, Mapping of the domains of p53 responsible for the interaction with hTR beta 1 indicated that the regions involved resided in the DNA-binding domain and carboxy terminus of p53, In agreement with this finding, hTR beta 1 increased the binding of p53 to p53 DNA-binding elements. This increase in DNA binding, however, resulted in repression of p53-dependent transcription activation in transfected cells. Furthermore, hTR beta 1 led to an inhibition of the p53-mediated induction of bax and gadd45 expression. In contrast, the p53-induced expression of p21 was not affected by hTR beta 1, suggesting that the expression of p53-regulated genes is differentially modulated by hTR beta 1. Because the expressions of bax, gadd45, and p21 are directly regulated by p53, these results indicate that hTR beta 1 can modulate p53-regulated gene expression and support the hypothesis that there is cross-talk between these two regulatory pathways. The cross-talk between these two transcription factors could play an important role in the biology of normal and cancer cells. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NHLBI, Mol Hematol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Bldg 37,Rm 2D-24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 45 TC 22 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1998 VL 17 IS 9 BP 743 EP 750 DI 10.1089/dna.1998.17.743 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 126ZG UT WOS:000076324800002 PM 9778033 ER PT J AU Siqueland, L Crits-Christoph, P Frank, A Daley, D Weiss, R Chittams, J Blaine, J Luborsky, L AF Siqueland, L Crits-Christoph, P Frank, A Daley, D Weiss, R Chittams, J Blaine, J Luborsky, L TI Predictors of dropout from psychosocial treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; predictors of dropout; treatment for substance dependence ID SUBSTANCE-ABUSE TREATMENT; PSYCHIATRIC COMORBIDITY; EARLY ATTRITION; PSYCHOTHERAPY; RETENTION; ABSTINENCE; SEVERITY; SERVICES; TRIALS AB The current study assessed demographic, drug and psychiatric predictors of dropout in the pilot/training phase of a large, multi-site psychotherapy outcome study for patients with cocaine dependence. The different predictors of dropout were assessed throughout the phases of the study: screening, intake, stabilization and assessment phase, and following randomization to treatment. Results showed that (1) younger patients were less likely to keep their intake appointment. (2) Of the patients who had an intake visit, those who did not complete high school and with more days of cocaine use in the previous month were less likely to complete an initial stabilization and assessment phase requiring 1 week of abstinence from all drugs. A survival analysis was used to examine time to dropout for the 286 patients randomized to individual treatment. (3) Again, younger age was associated with dropout after randomization. (4) Drug use variables did not predict time to dropout. (5) Presence of any current Axis I disorder was associated with later dropout from treatment. Minority treatment information seekers and treatment initiators were less likely to go on to complete the full treatment program. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Harvard Univ, Brookside Hosp, Sch Med, Nashua, NH USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. NIDA, Treatment Res Branch, Lexington, KY USA. RP Siqueland, L (reprint author), Univ Pittsburgh, Sch Med, 3501 Terrace St, Pittsburgh, PA 15261 USA. FU NIDA NIH HHS [R01 DA012249, U18 DA007090, U18-DA07090, U18-DA07663, U18-DA07673] NR 47 TC 48 Z9 48 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 1998 VL 52 IS 1 BP 1 EP 13 DI 10.1016/S0376-8716(98)00039-8 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 121RU UT WOS:000076028400001 PM 9788001 ER PT J AU Wassermann, EM AF Wassermann, EM TI Safety of transcranial magnetic stimulation in patients with implanted electronic equipment - Reply SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Letter RP Wassermann, EM (reprint author), NIH Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD SEP PY 1998 VL 107 IS 3 BP 225 EP 225 PG 1 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA 128RM UT WOS:000076420200007 ER PT J AU Stott, FJ Bates, S James, MC McConnell, BB Starborg, M Brookes, S Palmero, I Ryan, K Hara, E Vousden, KH Peters, G AF Stott, FJ Bates, S James, MC McConnell, BB Starborg, M Brookes, S Palmero, I Ryan, K Hara, E Vousden, KH Peters, G TI The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2 SO EMBO JOURNAL LA English DT Article DE cell cycle; MDM2; p53 response; replicative senescence; tumour suppression ID CELL-CYCLE ARREST; HUMAN-DIPLOID FIBROBLASTS; FUNCTIONAL RETINOBLASTOMA PROTEIN; KINASE INHIBITOR P16; TUMOR-SUPPRESSOR; DEPENDENT KINASES; REPLICATIVE SENESCENCE; INK4A LOCUS; IN-VITRO; SPONTANEOUS IMMORTALIZATION AB The two distinct proteins encoded by the CDKN2A locus are specified by translating the common second exon in alternative reading frames. The product of the a transcript, p16(INK4a), is a recognized tumour suppressor that induces a G(1) cell cycle arrest by inhibiting the phosphorylation of the retinoblastoma protein by the cyclin-dependent kinases, CDK4 and CDK6. In contrast, the product of the human CDKN2A beta transcript, p14(ARF), activates a p53 response manifest in elevated levels of MDM2 and p21(CIP1) and cell cycle arrest in both G(1) and G(2)/M. As a consequence, p14(ARF) induced cell cycle arrest is p53 dependent and can be abrogated by the co-expression of human papilloma virus E6 protein. p14(ARF) acts by binding directly to MDM2, resulting in the stabilization of both p53 and MDM2. Conversely, p53 negatively regulates p14(ARF) expression and there is an inverse correlation between p14(ARF) expression and p53 function in human tumour cell lines. However, p14(ARF) expression is not involved in the response to DNA damage. These results place p14(ARF) in an independent pathway upstream of p53 and imply that CDKN2A encodes two proteins that are involved in tumour suppression. C1 Imperial Canc Res Fund Labs, London WC2A 3PX, England. NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Univ Autonoma Madrid, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. Kyoto Prefectural Univ Med, Dept Surg 22, Dept Prevent Med, Kamigyo Ku, Kyoto 602, Japan. RP Peters, G (reprint author), Imperial Canc Res Fund Labs, POB 123,44 Lincolns Inn Fields, London WC2A 3PX, England. EM pelers@icrf.icnet.uk RI Palmero, Ignacio/B-4346-2013 NR 98 TC 845 Z9 861 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 1998 VL 17 IS 17 BP 5001 EP 5014 DI 10.1093/emboj/17.17.5001 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119PG UT WOS:000075904700010 PM 9724636 ER PT J AU Philpott, CC Rashford, J Yamaguchi-Iwai, Y Rouault, TA Dancis, A Klausner, RD AF Philpott, CC Rashford, J Yamaguchi-Iwai, Y Rouault, TA Dancis, A Klausner, RD TI Cell-cycle arrest and inhibition of G(1) cyclin translation by iron in AFT1-1(up) yeast SO EMBO JOURNAL LA English DT Article DE cell-cycle regulation; G(1) cyclins; iron; translational regulation; yeast ID UBIQUITIN PROTEOLYSIS MACHINERY; SACCHAROMYCES-CEREVISIAE; PARKINSONS-DISEASE; DNA-DAMAGE; G1 CYCLINS; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; TRANSCRIPTIONAL CONTROL; GLUCOSE REPRESSION; TRANSPORT PROTEIN AB Although iron is an essential nutrient, it is also a potent cellular toxin, and the acquisition of iron is a highly regulated process in eukaryotes, In yeast, iron uptake is homeostatically regulated by the transcription factor encoded by AFT1, Expression of AFT1-1(up), a dominant mutant allele, results in inappropriately high rates of iron uptake, and AFT1-1(up) mutants grow slowly in the presence of high concentrations of iron. We present evidence that when Aft1-1(up) mutants are exposed to iron, they arrest the cell division cycle at the G(1) regulatory point Start. This arrest is dependent on high-affinity iron uptake and does not require the activation of the DNA damage checkpoint governed by RAD9. The iron-induced arrest is bypassed by overexpression of a mutant G(1) cyclin, cln3-2, and expression of the G(1)-specific cyclins Cln1 and Cln2 is reduced when yeast are exposed to increasing amounts of iron, which may account for the arrest. This reduction is not due to changes in transcription of CLN1 or CLN2, nor is it due to accelerated degradation of the protein. Instead, this reduction occurs at the level of Cln2 translation, a recently recognized locus of cel-lcycle control in yeast. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), NIDDKD, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr,MSC1800, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov NR 90 TC 50 Z9 50 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 1998 VL 17 IS 17 BP 5026 EP 5036 DI 10.1093/emboj/17.17.5026 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119PG UT WOS:000075904700012 PM 9724638 ER PT J AU Jin, T Soede, RDM Liu, JC Kimmel, AR Devreotes, PN Schaap, P AF Jin, T Soede, RDM Liu, JC Kimmel, AR Devreotes, PN Schaap, P TI Temperature-sensitive G beta mutants discriminate between G protein-dependent and -independent signaling mediated by serpentine receptors SO EMBO JOURNAL LA English DT Article DE adenylyl cyclase; cell fate specification; heterotrimeric G protein; serpentine receptors; temperature-sensitive alleles ID ADENYLYL-CYCLASE; DICTYOSTELIUM-DISCOIDEUM; GENE-EXPRESSION; CYCLIC-AMP; MULTICELLULAR DEVELOPMENT; CHEMOATTRACTANT RECEPTOR; CELL-DIFFERENTIATION; TRANSDUCTION MUTANTS; EXTRACELLULAR CAMP; PHOSPHOLIPASE-C AB Deletion of the single gene for the Dictyostelium G protein beta-subunit blocks development at an early stage. We have now isolated temperature-sensitive alleles of G beta to investigate its role in later development. We show that G beta is directly required for adenylyl cyclase A activation and for morphogenetic signaling during the entire developmental program. G beta was also essential for induction of aggregative gene expression by cAMP pulses, a process that is mediated by serpentine cAMP receptors (cARs), However, G beta was not required for cAR-mediated induction of prespore genes and repression of stalk genes, and neither was G beta needed for induction of prestalk genes by the differentiation inducing factor (DIF), cAMP induction of prespore genes and repression of stalk genes is mediated by the protein kinase GSK-3, GSK-3 also determines cell-type specification in insects and vertebrates and is regulated by the wingless/wnt morphogens that are detected by serpentine fi receptors, The G protein-dependent and -independent modes of cAR-mediated signaling reported here may also exist for the wingless/wnt signaling pathways in higher organisms. C1 Leiden Univ, Inst Mol Plant Sci, Cell Biol Sect, NL-2333 AL Leiden, Netherlands. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. NIH, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. RP Schaap, P (reprint author), Leiden Univ, Inst Mol Plant Sci, Cell Biol Sect, Wassenaarseweg 64, NL-2333 AL Leiden, Netherlands. EM schaap@rulbim.leidenuniv.nl RI Schaap, Pauline/A-3682-2009 OI Schaap, Pauline/0000-0003-4500-2555 FU NIGMS NIH HHS [GM28007] NR 40 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 1998 VL 17 IS 17 BP 5076 EP 5084 DI 10.1093/emboj/17.17.5076 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119PG UT WOS:000075904700017 PM 9724643 ER PT J AU Asano, K Mizobuchi, K AF Asano, K Mizobuchi, K TI Copy number control of Incl alpha plasmid Collb-P9 by competition between pseudoknot formation and antisense RNA binding at a specific RNA SO EMBO JOURNAL LA English DT Article DE antisense RNA; plasmid replication; RNA loop structure; RNA pseudoknot; translational coupling ID REPZ GENE-EXPRESSION; REPLICATION CONTROL; ESCHERICHIA-COLI; LEADER PEPTIDE; DNA; CLONING; INHIBITION; SIGNALS; INVITRO; ORIGINS AB Replication of a low-copy-number IncI alpha plasmid ColIb-P9 depends on expression of the repZ gene encoding the replication initiator protein. repZ expression is negatively controlled by the small antisense Inc RNA, and requires formation of a pseudoknot in the RepZ mRNA consisting of stem-loop I, the Inc RNA target, and a downstream sequence complementary to the loop I. The loop I sequence comprises 5'-rUUGGCG-3', conserved in many prokaryotic antisense systems, and was proposed to be the important site of copy number control. Here we show that the level of repZ expression is rate-limiting for replication and thus copy number, by comparing the levels of repZ expression and copy number from different mutant ColIb-P9 derivatives defective in Inc RNA and pseudoknot formation. Kinetic analyses using in vitro transcribed RNAs indicate that Inc RNA binding and the pseudoknot formation are competitive at the level of initial base paring to loop I. This initial interaction is stimulated by the presence of the loop U residue in the 5'-rUUGGCG-3' motif, These results indicate that the competition between the two RNA-RNA interactions at the specific site is a novel regulatory mechanism for establishing the constant level of repZ expression and thus copy number. C1 Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Tokyo 113, Japan. Univ Electrocommun, Dept Appl Phys & Chem, Chofu, Tokyo 182, Japan. RP Asano, K (reprint author), NICHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM kasano@aghmac1.nichd.nih.gov NR 43 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 1998 VL 17 IS 17 BP 5201 EP 5213 DI 10.1093/emboj/17.17.5201 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 119PG UT WOS:000075904700030 PM 9724656 ER PT J AU Montuenga, LM Mariano, JM Prentice, MA Cuttitta, F Jakowlew, SB AF Montuenga, LM Mariano, JM Prentice, MA Cuttitta, F Jakowlew, SB TI Coordinate expression of transforming growth factor-beta 1 and adrenomedullin in rodent embryogenesis SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; MOUSE DEVELOPMENT; TGF-BETA; EMBRYO CHONDROCYTES; HYPOTENSIVE PEPTIDE; PATTERNS SUGGEST; CDNA CLONING; GENE AB Transforming growth factor-beta (TGF beta) and adrenomedullin (AM) are multifunctional regulatory peptides that are secreted by a variety of normal and malignant cells. The TGF beta s are expressed in developing organs and adults, and their tissue distribution pattern has possible significance for signaling roles in many epithelial-mesenchymal interactions. AM is also expressed in a variety of embryonic and adult tissues. The present study reports a comparison of the patterns of expression of the proteins and messenger RNAs (mRNAs) for TGF beta 1 and AM in the developing mouse embryo. Immunohistochemical and in situ hybridization analyses were performed on formalin-fixed paraffin-embedded sections of developing embryonic mouse tissues using specific antibodies and complementary RNA probes for TGF beta 1 and AM. The early placenta, including the giant trophoblastic cells, showed high levels of staining and hybridization for TGF beta 1 and AM proteins and mRNAs. The heart was the first organ that showed expression of TGF beta 1 and AM during embryogenesis. The spatio-temporal patterns of expression of TGF beta 1 and AM in cardiovascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs showed striking similarities. The lung, kidney, and intestine, in which epithelial-mesenchymal interactions occur, showed similar patterns of TGF beta 1 and AM expression. These data show colocalization of TGF beta 1 and AM in specific cell types associated with several tissues in the developing mouse embryo. Additionally, RT-PCR amplification and Northern blot hybridization showed expression of TGF beta 1 and AM mRNAs in all embryonic and adult mouse and rat tissues examined. Our data show that the expression of TGF beta 1 and AM is regulated in a spatial and temporal manner such that overlapping patterns of expression of TGF beta 1 and AM occur in several tissues at the same stage of development and in the same cellular location in rodent embryogenesis. C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. RP Jakowlew, SB (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowlews@bprb.nci.nih.gov NR 50 TC 27 Z9 28 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1998 VL 139 IS 9 BP 3946 EP 3957 DI 10.1210/en.139.9.3946 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 112NK UT WOS:000075500500035 PM 9724050 ER PT J AU Brewer, HB AF Brewer, HB TI Jeffrey M. Hoeg, MD - In memoriam SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Biographical-Item C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, 10 Ctr Dr MSC 1666,Bldg 10,Room 7N115, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP III EP IV PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000001 ER PT J AU Hoeg, JM AF Hoeg, JM TI Lipid disorders - Preface SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Hoeg, JM (reprint author), NIH, Bldg 10,Room 7N115,10 Ctr Dr,MSC 1666, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP XIII EP XIV PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000002 ER PT J AU Santamarina-Fojo, S AF Santamarina-Fojo, S TI The familial chylomicronemia syndrome SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID LIPOPROTEIN-LIPASE GENE; APOLIPOPROTEIN-C-II; LOW-DENSITY-LIPOPROTEIN; SPLICE-SITE MUTATION; FRENCH-CANADIAN POPULATION; NUCLEIC-ACID SEQUENCE; MISSENSE MUTATION; LPL DEFICIENCY; NONSENSE MUTATION; APOC-II AB The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and fasting chylomicronemia. Genetic causes of the syndrome are rare and include deficiency of lipoprotein lipase (LPL), apolipoprotein C-II, and familial inhibitor of LPL. Patients with familial forms of hypertriglyceridemia in combination with secondary acquired disorders account for most individuals presenting with chylomicronemia. The clinical manifestations-lipid and other biochemical abnormalities-as well as treatment options for chylomicronemic patients are discussed. C1 NHLBI, Mol Biol Sect, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Santamarina-Fojo, S (reprint author), NHLBI, Mol Biol Sect, Mol Dis Branch, NIH, 10 Ctr Dr MSC 1666,Bldg 10,Room 7N115, Bethesda, MD 20892 USA. NR 146 TC 78 Z9 79 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP 551 EP + DI 10.1016/S0889-8529(05)70025-6 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000005 PM 9785052 ER PT J AU Hoeg, JM AF Hoeg, JM TI Lipoproteins and atherogenesis SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID HIGH-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; APOLIPOPROTEIN-A-I; DIET-INDUCED HYPERCHOLESTEROLEMIA; CORONARY HEART-DISEASE; E-DEFICIENT MICE; EXPRESSING HUMAN APOLIPOPROTEIN(A); PRIMARY-PREVENTION TRIAL; LEIDEN TRANSGENIC MICE; B MESSENGER-RNA AB Like many complex disease processes, atherogenesis represents the interaction of an array of genetic and environmental factors. From nonhuman animal models to the investigation of epidemiologic factors in man, no single, overriding cause for the development of this indolent vascular disease has been identified. However, the cholesterol-enriched lipoprotein particles are closely tied to the development of the disease. The genetic and environmental influences on the concentrations of specific Lipoprotein subspecies provide a context for identifying patients at risk as well as for developing effective therapeutic strategies to influence and prevent the sequelae of atherogenesis. C1 NHLBI, Sect Cell Biol, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hoeg, JM (reprint author), NHLBI, Sect Cell Biol, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr Dr MSC 1666, Bethesda, MD 20892 USA. NR 113 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP 569 EP + DI 10.1016/S0889-8529(05)70026-8 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000006 PM 9785053 ER PT J AU Rifkind, BM AF Rifkind, BM TI Clinical trials of reducing low-density lipoprotein concentrations SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; SERUM-CHOLESTEROL; ATHEROSCLEROSIS; PRAVASTATIN; PREVENTION; PROGRESSION; POPULATION; MORTALITY AB Much diverse evidence suggests that the plasma levels of low-density lipoprotein (LDL) cholesterol play a causal role in the pathogenesis of atherosclerotic coronary heart disease. Until recently, clinical trials of LDL lowering, while showing significant reductions in coronary heart disease (CHD) rates, were not entirely convincing and left some questions of long-term toxicity unresolved. The results of a series of new trials using members of the powerful statin class of drugs are now being reported. Whether they are primary or secondary prevention studies, they have been uniformly successful in reducing mortality and morbidity from CHD and even total mortality, and have decreased the need for revascularization procedures. Their effectiveness is apparent in many different subgroups such as women, diabetics, hypertensives, and in stroke prevention. Statin drugs also have proven to be remarkably safe over the duration of the studies. Angiographic studies show an impact on coronary or carotid lesions. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Rifkind, BM (reprint author), Div Heart & Vasc Dis, Vasc Res Program, 6701 Rockledge Dr,MSC 7956,Suite 10193, Bethesda, MD 20892 USA. NR 33 TC 7 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP 585 EP + DI 10.1016/S0889-8529(05)70027-X PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000007 PM 9785054 ER PT J AU Cleeman, JI AF Cleeman, JI TI Detection and evaluation of dyslipoproteinemia SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORONARY HEART-DISEASE; DENSITY LIPOPROTEIN CHOLESTEROL; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; SERUM-CHOLESTEROL; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; MORTALITY; RISK; MEN AB The National Cholesterol Education Program Adult Treatment Panel II guidelines recommend that all adults 20 years of age and older undergo testing to detect dyslipoproteinemia. Clinical trials have proven conclusively that lowering levels of low-density lipoprotein (LDL) cholesterol reduces coronary heart disease (CHD) incidence and mortality and total mortality in patients with and without CHD. There is persuasive scientific evidence to include young adults, women, and the elderly in the recommendation for cholesterol management. In adults without CHD, testing can begin with measurement of total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol in the nonfasting state, and the results can then be used to determine which individuals require a fasting lipoprotein analysis (total cholesterol, HDL, triglycerides, and estimation of LDL); patients with known CHD should begin with lipoprotein analysis. The level of LDL cholesterol and the presence or absence of other CHD risk factors determine the need for cholesterol-lowering therapy. Patients with known CHD are at highest risk for a CHD event and have the lowest LDL cholesterol goal (100 mg/dL); patients without CHD but with elevated LDL-C (130 mg/dL) and two or more other CHD risk factors are at high risk for developing CHD and have an LDL cholesterol goal of less than 130 mg/dL; patients free of CHD with high LDL cholesterol (160 mg/dL) but fewer than two Other risk factors have a lower CHD risk and an LDL cholesterol goal of less than 160 mg/dL. Elevated triglyceride may be a marker for other factors that increase CHD risk. Raising HDL cholesterol, while not proven to be of benefit, is reasonable in patients at high CHD risk. C1 NHLBI, Natl Cholesterol Educ Program, NIH, Bethesda, MD 20892 USA. RP Cleeman, JI (reprint author), NHLBI, Natl Cholesterol Educ Program, NIH, Bldg 31,Room 4A16, Bethesda, MD 20892 USA. NR 40 TC 7 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP 597 EP + DI 10.1016/S0889-8529(05)70028-1 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000008 PM 9785055 ER PT J AU Gordon, DJ AF Gordon, DJ TI Factors affecting high-density lipoproteins SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; EPIDEMIOLOGIC EVIDENCE; INTERVENTION TRIAL; CHOLESTEROL LEVELS; ARTERY DISEASE; RISK FACTOR; MEN; TRIGLYCERIDE; ESTROGEN AB Although it is well established that a low-circulating level of high-density lipoprotein (HDL) cholesterol is strongly associated with the likelihood of developing atherosclerotic coronary heart disease (CHD), the causal nature of this association has not been shown. Low levels of HDL cholesterol frequently are associated with other CHD risk factors, whose correction, often by hygienic means, may reduce CHD risk with minimal risk of adverse side-effects. However, other recommended hygienic interventions may lower HDL cholesterol levels. Specific safe and effective drugs for correcting a low HDL cholesterol level are not available and the potential value of specific pharmacologic treatment of this condition in the treatment or prevention of CHD remains unproven. Thus, while HDL measurement should be incorporated routinely in risk-assessment, intervention efforts should focus primarily on lowering low-density lipoprotein cholesterol. C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Gordon, DJ (reprint author), Rockledge 2 Bldg,Room 9044,6701 Rockledge Dr, Bethesda, MD 20815 USA. NR 40 TC 12 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1998 VL 27 IS 3 BP 699 EP + DI 10.1016/S0889-8529(05)70034-7 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123BB UT WOS:000076105000014 PM 9785061 ER PT J AU Blair, A Ward, MH AF Blair, A Ward, MH TI The value of assessing occupational factors in epidemiologic investigations of general environmental exposures SO ENVIRONMETRICS LA English DT Article DE occupation; environment; epidemiology; cancer; exposures; biomarkers ID NON-HODGKINS-LYMPHOMA; LUNG-CANCER; NASAL CAVITY; FORMALDEHYDE; BIOMARKERS; PHARYNX; SINUS; RISK AB Studies of the role of environmental exposures in the etiology of disease are an important and growing component of public health assessment. Assessment of general environmental exposures, however, is difficult. Simultaneous consideration of occupational exposures may be helpful. There are several reasons why this approach should be considered. First, many chemical exposures occur in both the occupational and environmental setting. Consideration of only one component could lead to an underestimate of exposure and of potential impact of the substance on public health. Second, occupational exposures are typically greater than environmental exposures and information on the shape of the exposure-response curve about the environmental levels may be quite informative. Third, consideration of occupational factors offers the opportunity to create a cumulative index of exposure from all routes and to adjust one route of exposure for the other. Finally, occupational exposures can be used to validate biologic markers for environmental exposures and generally provide useful information in interpretation of environmental results. (C) 1998 John Wiley & Sons, Ltd. C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Occupat Epidemiol Branch, Execut Plaza N,Room 418, Bethesda, MD 20892 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD SEP-OCT PY 1998 VL 9 IS 5 BP 519 EP 524 PG 6 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 125CR UT WOS:000076220300004 ER PT J AU Siegmund, KD Province, MA Higgins, M Williams, RR Keller, J Todorov, AA AF Siegmund, KD Province, MA Higgins, M Williams, RR Keller, J Todorov, AA TI Modeling disease incidence rates in families SO EPIDEMIOLOGY LA English DT Article DE age of onset; coronary heart disease; genetics; multivariate Cox model; risk factors; cohort studies AB We apply an extended Cox model to study latent genes and measured environmental exposures simultaneously as risk factors for disease. Using this method, we assume Mendelian transmission of the genes and either dominant or recessive gene action. We compared the results from this model with those obtained under a model that includes the environmental variables and a family risk score. We demonstrate the method in samples of 1,433 Caucasian families (N = 6,791) and 206 African-American families (N = 771) from the National Heart, Lung, and Blood Institute Family Heart Study, In Caucasians, we found evidence suggesting that having ever smoked increased the risk of coronary heart disease only in individuals who carry a genetic susceptibility. We also noted that in both Caucasian and African-American families, the relative risk of coronary heart disease for ever-treated us never-treated for high serum total cholesterol increased after including an unobserved susceptibility genotype in the model. This finding implied that there may be genes influencing coronary heart disease independent of those that influence total cholesterol. Such findings were not evident when genetic risk was summarized by the family history score. We also discuss the extension of the model to address the etiology of complex diseases. C1 Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NHLBI, Bethesda, MD 20892 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Utah, Salt Lake City, UT USA. RP Siegmund, KD (reprint author), Univ So Calif, Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP-220, Los Angeles, CA 90033 USA. FU NHLBI NIH HHS [N01-HC-25106, N01-HC-25105, N01-HC-25104] NR 8 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1998 VL 9 IS 5 BP 557 EP 562 DI 10.1097/00001648-199809000-00015 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 113EG UT WOS:000075537000015 PM 9730037 ER PT J AU Vinters, HV Kerfoot, C Catania, M Emelin, JK Roper, SN DeClue, JE AF Vinters, HV Kerfoot, C Catania, M Emelin, JK Roper, SN DeClue, JE TI Tuberous sclerosis-related gene expression in normal and dysplastic brain SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT 4th Workshop on the Neurobiology of Epilepsy CY JUN 26-28, 1997 CL ADARE, IRELAND SP Amer Epilepsy Soc, Hoechst Marion Roussel, Japan Fdn Neurosci & Mental Health, Novartis Pharmaceutical Corp, Parke-Davis/Div Warner-Lambert Co DE cortical dysplasia; neuronal migration disorder; epilepsy pediatric; brain development; tuberin ID FOCAL CORTICAL DYSPLASIA; RESECTED CEREBRAL TISSUE; MILLER-DIEKER SYNDROME; TSC2 PRODUCT TUBERIN; ALLELIC LOSS; NEUROPATHOLOGIC FINDINGS; MIGRATION DISORDERS; SURGICAL PATHOLOGY; LISSENCEPHALY GENE; GROWTH SUPPRESSOR AB Cortical dysplasia (CD) broadly defines a complex cerebral malformative lesion associated clinically with intractable, pharmacoresistant epilepsy (including infantile spasms), especially in infants and children. In CD, the spectrum of structural brain abnormalities includes (at a minimum) neuronal dyslamination and (in severe cases) neuronal cytomegaly with cytoskeletal alterations and the presence of gemistocyte-like 'balloon cells'. In some CD variants, the neuropathological features are essentially indistinguishable from those of a tuber of tuberous sclerosis (TSC). Two genes associated with the autosomal dominant, multi-system disorder TSC have recently been cloned: TSC2 (on chromosome 16p13.3) encodes the protein tuberin and TSC1 (on 9q34) encodes hamartin. Tuberin has been immunolocalized to neurons and possibly astrocytes in normal brain and CD/TSC tubers, and is widely expressed in normal viscera; loss of heterozygosity and tissue culture studies suggest it functions as a growth suppressor The TSC1 gene has been cloned within the last year and hamartin as yet has no well-defined cellular function, though its protein product may also function as a growth suppressor. This article focuses on the cellular pathogenesis of CD and TSC brain lesions and how the two may be biologically related. Studies of how TSC1 and TSC2 function in normal and dysplastic cerebral neocortex may provide a paradigm for understanding the neurobiology of other genes that determine epilepsy-associated cerebral malformations (e.g, lissencephaly, double cortex). (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA. Univ Florida, Coll Med, Dept Neurol Surg, Gainesville, FL 32610 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Vinters, HV (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90095 USA. EM hvinters@pathology.medsch.ucla.edu FU NINDS NIH HHS [P01 NS 28383] NR 51 TC 25 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 1998 VL 32 IS 1-2 SI SI BP 12 EP 23 DI 10.1016/S0920-1211(98)00036-9 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 121UX UT WOS:000076034000003 PM 9761305 ER PT J AU Sher, A Sousa, CR AF Sher, A Sousa, CR TI Ignition of the type I response to intracellular infection by dendritic cell-derived interleukin-12 SO EUROPEAN CYTOKINE NETWORK LA English DT Article; Proceedings Paper CT Vth International Workshop on Cytokines at the Joint Meeting of the Ares-Sereno Foundation / European-Cytokine-Society CY MAR 16-18, 1998 CL FLORENCE, ITALY SP Ares-Sereno Fdn, European Cytokine Soc DE IL-12; dendritic cells; Toxoplasma gondii; macrophages; IFN-gamma; intracellular infection ID ENDOGENOUS IFN-GAMMA; TOXOPLASMA-GONDII; LIPOPOLYSACCHARIDE; INDUCTION; MICE AB Host resistance to many intracellular pathogens is dependent on the induction of host IFN-gamma. This response in turn is triggered by the critical initiation cytokine, IL-12. Activated macrophages provide a major source of IL-12 during infection yet are unlikely to be the initial cell to produce the cytokine because of their need for IFN-gamma priming and/or other co-stimulatory signals. We have utilized an at vivo approach to identify the primary IL-12 producing cells which respond to the intracellular protozoan Toxoplasma gondii, Oar results indicate that in spleen interdigitating dendritic cells (IDC) but not macrophages rapidly synthesize IL-12 after injection of parasite products or live tachyzoites, This response is both IFN-gamma and T lymphocyte independent. The same microbial stimulus results in the migration of IDC precursors into T cell areas and the upregulation of co-stimulatory cell-surface molecules. We postulate that these early dendritic cell activation events represent the "ignition switch" for the subsequent Type 1 cytokine response which leads to control of infection. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 18 TC 27 Z9 27 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 SU 3 BP 65 EP 68 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136YD UT WOS:000076885900010 PM 9831188 ER PT J AU Roberts, AB Lechleider, RJ de Caestecker, MP Ashcroft, G Yang, X Deng, CX Letterio, J AF Roberts, AB Lechleider, RJ de Caestecker, MP Ashcroft, G Yang, X Deng, CX Letterio, J TI Novel signal transduction pathways from the TGF-beta family receptor serine-threonine kinases SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIDDK, Biochem & Metab Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 548 BP 298 EP 298 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700015 ER PT J AU Gonsky, R Deem, R Young, H Targan, S AF Gonsky, R Deem, R Young, H Targan, S TI Identification of multiple CD2 response elements within the interferon-gamma promoter: Differential transactivation in PBL and LPL SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 433 BP 312 EP 312 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700044 ER PT J AU Nelms, K Paul, WE AF Nelms, K Paul, WE TI FEIP - A cytokine-activated ras-GAP-binding protein that inhibits growth responses SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 513 BP 321 EP 321 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700059 ER PT J AU Ohtal, Y Qil, CF McCarty, TC Morse, HC AF Ohtal, Y Qil, CF McCarty, TC Morse, HC TI A 55 KDA protein related to the double-stranded RNA-dependent protein kinase, PKR, is expressed in spleen cells from mice with retrovirus-induced immunodeficiency SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD USA. Takeda Chem Ind Ltd, Pharmaceut Res Labs, Osaka 532, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 303 BP 325 EP 325 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700065 ER PT J AU Ozato, K AF Ozato, K TI The IRF family: its diverse roles in regulating gene expression by interferon/cytokine, in host defense, and cancer/apoptosis. SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 268 BP 340 EP 340 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700103 ER PT J AU Leonard, WJ AF Leonard, WJ TI IL-2 signaling from the membrane to the nucleus SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 531 BP 354 EP 354 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700127 ER PT J AU Kovanen, PE Junttila, I Takaluoma, K Valmu, L Saharinen, P Li, WQ Silvennoinen, O AF Kovanen, PE Junttila, I Takaluoma, K Valmu, L Saharinen, P Li, WQ Silvennoinen, O TI Inhibition of JAK2 kinase by PKC is required for macrophage differentiation in IL-3 dependent myeloid progenitor cells SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Tampere Univ, Inst Med Technol, FIN-33101 Tampere, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 10 BP 356 EP 356 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700136 ER PT J AU Shakhov, A Lyakhov, I Nedospasov, SA AF Shakhov, A Lyakhov, I Nedospasov, SA TI Identification of genes downregulated in mice with lymphotoxin deficiency SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 SAIC, IRSP, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Frederick, MD USA. Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia. Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 414 BP 375 EP 375 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700173 ER PT J AU Oppenheim, JJ Chertov, O Kenji, T Murphy, W Grimm, M Howard, Z Ueda, H Wang, JM AF Oppenheim, JJ Chertov, O Kenji, T Murphy, W Grimm, M Howard, Z Ueda, H Wang, JM TI Role of human chemokines in inflammation and host defense SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Clin Res Branch, Div Clin Serv, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 267 BP 390 EP 390 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700206 ER PT J AU Mandler, R Levitzki, A Roettinger, AJ Gazit, A Rakhlin, YY Waldmann, TA AF Mandler, R Levitzki, A Roettinger, AJ Gazit, A Rakhlin, YY Waldmann, TA TI The tyrphostin AG494 reduces IL2-induced activation of Jak3 and inhibits proliferation of human leukemia cells SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Dept Biol Chem, IL-91905 Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 505 BP 401 EP 401 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700232 ER PT J AU Lee, CK Kim, K Han, SS Durum, SK AF Lee, CK Kim, K Han, SS Durum, SK TI Diversion of thymic progenitors from T cell development to macrophages by cytokines produced from a thymic stromal cell line SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 Chungbuk Natl Univ, Coll Pharm, Cheongju 361763, South Korea. Sahm Yook Coll, Dept Food Technol Sci, Seoul 139742, South Korea. NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 225 BP 423 EP 423 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700273 ER PT J AU Vestal, DJ Buss, JE McKercher, SR Copeland, NG Jenkins, NA Kelner, GS Maki, RA AF Vestal, DJ Buss, JE McKercher, SR Copeland, NG Jenkins, NA Kelner, GS Maki, RA TI Murine GBP-2: A new IFN-induced GTPase SO EUROPEAN CYTOKINE NETWORK LA English DT Meeting Abstract C1 Iowa State Univ, Dept Biochem & Biophys, Ames, IA 50011 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Burnham Inst, La Jolla, CA 92037 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. Neurocrine Biosci Inc, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD SEP PY 1998 VL 9 IS 3 MA 184 BP 470 EP 470 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 136CD UT WOS:000076839700394 ER PT J AU Hohman, TC El-Kabbani, O Malamas, MS Lai, KD Putilina, T McGowan, MH Wane, YQ Carper, DA AF Hohman, TC El-Kabbani, O Malamas, MS Lai, KD Putilina, T McGowan, MH Wane, YQ Carper, DA TI Probing the inhibitor-binding site of aldose reductase with site-directed mutagenesis SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE site-directed mutagenesis; human aldose reductase; enzyme inhibition; polyol pathway; diabetes ID DIABETIC COMPLICATIONS; CRYSTAL-STRUCTURE; ACTIVE-SITE; MECHANISM; SUBSTRATE; ENZYME; INVOLVEMENT; EXPRESSION; CATALYSIS; COMPLEXES AB Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes, and enzyme inhibitors have been proposed as therapeutic agents. While effectively preventing the development of diabetic complications in animals, results from clinical studies of AR inhibitors have been disappointing, possibly due to poor potency in man. To assist in the design of more potent and specific inhibitors. crystallographic studies have attempted to identify enzyme-inhibitor interactions. Resolution of crystal complexes has suggested that the inhibitors bind to the enzyme active site and are held in place through hydrogen bonding and van der Waals interactions formed within two hydrophobic pockets. To confirm and extend these findings we quantified inhibitor activity with single, site-directed, mutant, human AB enzymes in which the apolar active-site residues tryptophan 20, -79, -111 and phenylalanine 115 were replaced with alanine or tyrosine, decreasing the potential for van der Waals interactions, Consistent with molecular models, the inhibitory activity of Tolrestat, Sorbinil and Zopolrestat decreased 800-2000-fold when tested with the mutant enzyme in which Trp20 was replaced with alanine. Further, alanine substitution for Trp111 decreased Zopolrestat's activity 400-fold, while mutations to Trp79 and Phe 115 had little effect on the activity of any of the inhibitors. The alanine mutation at Trp111 had no effect on Tolrestat's activity but decreased the activity of Sorbinil by about 1000-fold. These latter effects were unanticipated based on the number of non-bonded interactions between the inhibitors, Tolrestat and Sorbinil, and Trp20 and Trp111 that have been identified in the crystal structures. In spite of these unexpected findings, our results are consistent with the hypothesis that AR inhibitors occupy the enzyme active site and that hydrophobic interactions between the enzyme and inhibitor contribute to inhibitor binding stability. C1 Wyeth Ayerst Res, Princeton, NJ 08543 USA. Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic, Australia. NEI, NIH, Bethesda, MD 20892 USA. RP Hohman, TC (reprint author), Wyeth Ayerst Res, CN 8000, Princeton, NJ 08543 USA. NR 32 TC 21 Z9 21 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP 1 PY 1998 VL 256 IS 2 BP 310 EP 316 DI 10.1046/j.1432-1327.1998.2560310.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117NW UT WOS:000075789300008 PM 9760169 ER PT J AU Cos, T Ford, RA Trilla, JA Duran, A Cabib, E Roncero, C AF Cos, T Ford, RA Trilla, JA Duran, A Cabib, E Roncero, C TI Molecular analysis of Chs3p participation in chitin synthase III activity SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE chitin synthase III; calcofluor resistance; morphogenesis; Saccharomyces cerevisiae ID SACCHAROMYCES-CEREVISIAE; ASPERGILLUS-NIDULANS; CALCOFLUOR WHITE; YEAST; GENE; PROTEINS; BIOSYNTHESIS; MUTAGENESIS; DOMAINS; PATHWAY AB Chitin is a minor but essential component of the cell wall of Saccharomyces cerevisiae, with functions in septum formation in the vegetative life cycle and also in conjugation and spore cell-wall synthesis in the sexual cycle. Of the three chitin synthases present in yeast, chitin synthase III (CSIII) is responsible for the synthesis of most of the chitin found in the cell, including a chitin ring at early budding, chitin interspersed in the cell wall, and chitin laid down during the sexual cycle. We have tagged Chs3p, the putative catalytic subunit of CSIII, with the immunoreactive epitope of influenza virus hemagglutinin to follow expression of the protein. Little correlation was found between the levels of transcription and translation of Chs3p and in vivo function, supporting our previous conclusion that regulation of CSIII occurs at the posttranslational level. To identify possible regions of the protein involved in catalysis or regulation, mutations were generated in the QRRRW 'signature sequence' of chitin synthases. Arginine residue mutations in Chs3p, and in Chs1p and Chs2p, resulted in a loss of both function in vivo and enzymatic activity. Mutations in a serine residue adjacent to glutamine in Chs3p caused loss of function in vivo with a moderate decrease in CSIII activity, suggesting a regulatory role for the serine residue in chitin biosynthesis. Several truncations in the unique hydrophilic carboxy-terminal region of Chs3p identified a sequence of about 25 amino acids that is required for both function and in vitro activity. Since this region is not present in Chs1 or Chs2,, it may be involved in the specific regulation of CSIII. C1 Univ Salamanca, CSIC, Inst Microbiol Bioquim, Edificio Dept, E-37007 Salamanca, Spain. Univ Salamanca, Dept Genet & Microbiol, E-37007 Salamanca, Spain. NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Roncero, C (reprint author), Univ Salamanca, CSIC, Inst Microbiol Bioquim, Edificio Dept, Room 219,Avda Campo Charro S-N, E-37007 Salamanca, Spain. EM crm@gugu.usal.es RI Roncero, Cesar/B-5200-2017 OI Roncero, Cesar/0000-0001-5964-3252 NR 37 TC 50 Z9 54 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP 1 PY 1998 VL 256 IS 2 BP 419 EP 426 DI 10.1046/j.1432-1327.1998.2560419.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117NW UT WOS:000075789300022 PM 9760183 ER PT J AU Miller, JM Martinez, A Moody, T Jahnke, G Smith, L Brown, P O'Connell, P Cuttitta, FC AF Miller, JM Martinez, A Moody, T Jahnke, G Smith, L Brown, P O'Connell, P Cuttitta, FC TI Adrenomedullin: A potential autocrine growth factor for human breast epithelial cells during development and carcinogenesis SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, NIH, DCS, MD,DCCB,Intervent Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1998 VL 34 SU 5 MA 387 BP S83 EP S83 DI 10.1016/S0959-8049(98)80349-3 PG 1 WC Oncology SC Oncology GA 136YM UT WOS:000076886700349 ER PT J AU Litvan, I Jankovic, J Goetz, CG Wenning, GK Sastry, N Jellinger, K McKee, A Lai, EC Brandel, JP Verny, M Ray-Chaudhuri, K Pearce, RKB Bartko, JJ Agid, Y AF Litvan, I Jankovic, J Goetz, CG Wenning, GK Sastry, N Jellinger, K McKee, A Lai, EC Brandel, JP Verny, M Ray-Chaudhuri, K Pearce, RKB Bartko, JJ Agid, Y TI Accuracy of the clinical diagnosis of postencephalitic parkinsonism: a clinicopathologic study SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE accuracy; diagnosis; postencephalitic parkinsonism; pathology ID PROGRESSIVE SUPRANUCLEAR PALSY; POST-ENCEPHALITIC PARKINSONISM; RICHARDSON-OLSZEWSKI SYNDROME; ALZHEIMERS-DISEASE; LETHARGICA; INFLUENZA; CRITERIA; OVERLAP AB The accuracy of the clinical diagnosis of postencephalitic parkinsonism (PEP) is unknown. We determined the validity of the clinical diagnosis of PEP by presenting 105 records with neuropathologic diagnoses of PEP (n = 7), progressive supranuclear palsy (n = 24), Parkinson's disease (n = 15), dementia with Lewy bodies (n = 14), multiple system atrophy (n = 16), corticobasal degeneration (n = 10), Creutzfeldt-Jakob disease (n = 4), and other dementia disorders (n = 15), as clinical vignettes to six neurologists unaware of the autopsy findings. The neurologists' own clinical diagnoses were compared with neuropathologic diagnoses for measures of diagnostic accuracy, including reliability (kappa statistics), sensitivity and positive predictive values for the first and last visits. The group reliability for the diagnosis of PEP was almost perfect (kappa = 0.91, 0.9). The mean sensitivity at the first visit was 86% (range, 71-100%) with minimal change at the last visit (83%; range, 71-100%). Positive predictive values remained unchanged (100%). The high reliability, sensitivity and positive predictive values of the clinical diagnosis of PEP indicate that neurologists identify this disorder even when they report that they have never evaluated a case. In our data set, the best predictors for the diagnosis of PEP included onset below middle age; symptom duration lasting more than 10 years, and the presence of oculogyric crisis. History of encephalitis lethargica, present in most PEP cases, was an important individual diagnostic predictor. (C) 1998 Lippincott Williams & Wilkins. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Rush Med Coll, Dept Neurol, Chicago, IL 60612 USA. Inst Neurol, London WC1N 3BG, England. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Hop La Pitie Salpetriere, INSERM, Raymond Escourolle Neuropathol Lab, U360, Paris, France. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Inst Neurol, Parkinsons Dis Soc Brain Tissue Bank, London WC1N 3BG, England. NIMH, Div Epidemiol & Res Studies, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Federat Neurol, Paris, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. RP Litvan, I (reprint author), NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 37 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 1998 VL 5 IS 5 BP 451 EP 457 DI 10.1046/j.1468-1331.1998.550451.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 128DL UT WOS:000076389900004 ER PT J AU Wink, DA Mitchell, JB AF Wink, DA Mitchell, JB TI Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE nitric oxide; reactive nitrogen oxide species; superoxide; mitochondrial respiration; metal homeostasis; lipid metabolism ID LOW-DENSITY-LIPOPROTEIN; MITOCHONDRIAL RESPIRATORY-CHAIN; OXIDIZED LIPID DERIVATIVES; WOODCHUCK HEPATITIS-VIRUS; PEROXYNITRITE IN-VITRO; PROGRAMMED CELL-DEATH; CYTOCHROME-C-OXIDASE; SMOOTH-MUSCLE CELLS; OXIDATIVE-STRESS; RIBONUCLEOTIDE REDUCTASE AB There has been confusion as to what role(s) nitric oxide (NO) has in different physiological and pathophysiological mechanisms. Some studies imply that NO has cytotoxic properties and is the genesis of numerous diseases and degenerative states, whereas other reports suggest that NO prevents injurious conditions from developing and promotes events which return tissue to homeostasis. The primary determinant(s) of how NO affects biological systems centers on its chemistry. The chemistry of NO in biological systems is extensive and complex. To simplify this discussion, we have formulated the "chemical biology of NO" to describe the pertinent chemical reactions under specific biological conditions. The chemical biology of NO is divided into two major categories, direct and indirect. Direct effects are defined as those reactions fast enough to occur between NO and specific biological molecules. Indirect effects do not involve NO, but rather are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. RNOS formed from NO can mediate either nitrosative or oxidative stress. This report discusses various aspects of the chemical biology of NO relating to biological molecules such as guanylate cyclase, cytochrome P450, nitric oxide synthase, catalase, and DNA and explores the potential roles of NO in different biological events. Also, the implications of different chemical reactions of NO with cellular processes such as mitochondrial respiration, metal homeostasis, and lipid metabolism are discussed. Finally, a discussion of the chemical biology of NO in different cytotoxic mechanisms is presented. Published by Elsevier Science Inc. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 187 TC 922 Z9 979 U1 11 U2 71 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1998 VL 25 IS 4-5 BP 434 EP 456 DI 10.1016/S0891-5849(98)00092-6 PG 23 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 113ET UT WOS:000075538000006 PM 9741580 ER PT J AU Kondo, T Misik, V Riesz, P AF Kondo, T Misik, V Riesz, P TI Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ultrasound; contrast agents; free radicals; spin trapping; EPR spectroscopy ID DIAGNOSTIC ULTRASOUND; AQUEOUS-SOLUTIONS; ALBUMIN; SONOLYSIS AB Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of H-. atoms and (OH)-O-. radicals, thus lowering H2O2 formation (by recombination of (OH)-O-. radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with H-. and (OH)-O-. which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions. Published by Elsevier Science. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Fac Med, Dept Radiol Sci, Sugitani, Toyama 93001, Japan. RP Riesz, P (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 26 TC 23 Z9 25 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1998 VL 25 IS 4-5 BP 605 EP 612 DI 10.1016/S0891-5849(98)00106-3 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 113ET UT WOS:000075538000024 PM 9741598 ER PT J AU Schoen, RE Corle, D Cranston, L Weissfeld, JL Lance, P Burt, R Iber, F Shike, M Kikendall, JW Hasson, M Lewin, KJ Appelman, HD Paskett, E Selby, JV Lanza, E Schatzkin, A AF Schoen, RE Corle, D Cranston, L Weissfeld, JL Lance, P Burt, R Iber, F Shike, M Kikendall, JW Hasson, M Lewin, KJ Appelman, HD Paskett, E Selby, JV Lanza, E Schatzkin, A CA Polyp Prevent Trial TI Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? SO GASTROENTEROLOGY LA English DT Article ID OCCULT BLOOD-TESTS; RISK ASYMPTOMATIC PATIENTS; DIMINUTIVE COLONIC POLYPS; COLORECTAL-CANCER; FLEXIBLE SIGMOIDOSCOPY; SCREENING COLONOSCOPY; HYPERPLASTIC POLYPS; RECTOSIGMOID POLYPS; LARGE BOWEL; FIBEROPTIC SIGMOIDOSCOPY AB Background & Aims: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas, Methods: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. Results: Four hundred sixty patients (46.9%) had greater than or equal to 1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or greater than or equal to 1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas, Conclusions: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma, Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. WESTAT Corp, Comp Syst & Applicat, Rockville, MD 20850 USA. SUNY Buffalo, Div Gastroenterol, Buffalo, NY 14260 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Gastroenterol Sect, Hines, IL 60141 USA. Mem Sloan Kettering Canc Ctr, Div Gastroenterol, New York, NY 10021 USA. Walter Reed Army Med Ctr, Gastroenterol Sect, Bethesda, MD USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Kaiser Fdn, Res Inst, Div Res, Oakland, CA USA. RP Schoen, RE (reprint author), Pittsburgh Univ Hosp, Div Gastroenterol & Hepatol, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 NR 71 TC 69 Z9 70 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1998 VL 115 IS 3 BP 533 EP 541 DI 10.1016/S0016-5085(98)70132-5 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 113PQ UT WOS:000075560800007 PM 9721149 ER PT J AU Yu, J Soma, T Hanazono, Y Dunbar, CE AF Yu, J Soma, T Hanazono, Y Dunbar, CE TI Abrogation of TGF-beta activity during retroviral transduction improves murine hematopoietic progenitor and repopulating cell gene transfer efficiency SO GENE THERAPY LA English DT Article DE retroviral; in vivo; murine; stem cell; inhibitory cytokine; transforming growth factor-beta ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; HUMAN MARROW CULTURES; STEM-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; PERIPHERAL-BLOOD; BONE-MARROW; HUMAN GLUCOCEREBROSIDASE; CYCLE REGULATION; ENGRAFTMENT AB Transforming growth factor-beta has complex activities on hematopoietic cells. We have previously shown that murine long-term repopulating activity is compromised by ex vivo culture in TGF-beta 1 and conversely is increased by abrogating endogenous TGF-beta activity with a neutralizing antibody. In the current study, we investigated the effect of abrogation of autocrine or paracrine TGF-beta present during retroviral transduction on gene transfer efficiency to primitive hematopoietic cells. Murine marrow cells were cultured and retrovirally transduced for 4 days in the presence of interleukin-3 interleukin-6 and stem cell factor, and either a neutralizing anti-TGF-beta antibody or an isotype control. Committed progenitor cells were analyzed for gene transfer efficiency, and cells were also injected into W/W-v recipient mice for analysis of transduction of long-term repopulating cells. The progenitor (CFU-C) transduction efficiency in the presence of anti-TGF-beta was significantly greater Semiquantitative PCR analysis and Southern blot analysis for the retroviral marker gene in the blood and bone marrow of recipient mice revealed a significant increase in the transduction efficiency of long-term repopulating cells after culture and transduction in the presence of the anti-TGF-beta. Thus neutralization of TGF-beta activity during retroviral transduction allows more efficient gene transfer into primitive murine hematopoietic cells and may prove beneficial in future clinical gene transfer or therapy trials. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103, Bethesda, MD 20892 USA. NR 43 TC 15 Z9 15 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 1998 VL 5 IS 9 BP 1265 EP 1271 DI 10.1038/sj.gt.3300732 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 118MG UT WOS:000075841800016 PM 9930329 ER PT J AU Knutsen, T Mickley, LA Ried, T Green, ED du Manoir, S Schrock, E Macville, M Ning, Y Robey, R Polymeropoulos, M Torres, R Fojo, T AF Knutsen, T Mickley, LA Ried, T Green, ED du Manoir, S Schrock, E Macville, M Ning, Y Robey, R Polymeropoulos, M Torres, R Fojo, T TI Cytogenetic and molecular characterization of random chromosomal rearrangements activating the drug resistance gene, MDR1/P-glycoprotein, in drug-selected cell lines and patients with drug refractory ALL SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; MULTIDRUG RESISTANCE; INSITU HYBRIDIZATION; CROSS-RESISTANCE; BURKITT-LYMPHOMA; DNA-SEQUENCES; LOCALIZATION; TRANSLOCATION; EXPRESSION; PHENOTYPE AB resistance, both primary and acquired, is a major obstacle to advances in cancer chemotherapy. In vitro, multidrug resistance can be mediated by P-glycoprotein (PGY 1), a cell surface phosphoglycoprotein that acts to efflux natural products from cells. PGY 1 is encoded by the MDR1 gene located at 7q21.1. Overexpression of MDR1 has been demonstrated in many cancers, both in patient tumors and in cell lines selected with a variety of chemotherapeutic agents. Recent studies in drug-selected cell lines and patients samples have identified hybrid mRNAs comprised of an active, but apparently random, gene fused 5' to MDR1. This observation indicates that random chromosomal rearrangements, such as translocations and inversions, leading to "capture" of MDR1 by constitutively expressed genes may be a mechanism for activation of this gene following drug exposure. In this study, fluorescence in situ hybridization (FISH) using whole chromosome paints (WCP) and bacterial artificial chromosome (BAG)-derived probes showed structural rearrangements involving 7q in metaphase and interphase cells, and comparative genomic hybridization (CGH) revealed high levels of amplification at chromosomal breakpoints. In an adriamycin-selected resistant colon cancer line (S48-3s/Adr), WCP4/WCP7 revealed t(4;7)(q31;q21) and BAG-derived probes demonstrated that the breakpoint lay between MDR1 and sequences 500-1000 KB telomeric to it. Similarly, in a subline isolated following exposure to actinomycin D (S48-3s/ActD), a hybrid MDR1 gene composed of heme oxygenase-2 sequences (at 16p13) fused to MDR1 was identified and a rearrangement confirmed with WCP7 and a subtelomeric 16p probe. Likewise, in a paclitaxel-selected MCF-7 subline where GASP sequences (at 7q22) were shown to be fused to MDR1, WCP7 showed an elongated chromosome 7 with a homogeneously staining regions (hsr); BAG-derived probes demonstrated that the hsr was composed of highly amplified MDR1 and GASP sequences. In all three selected cell lines, CGH demonstrated amplification at breakpoints involving MDR1 (at 7q21) and genes fused to MDR1 at 4q31, 7q22, and 16p13.3. Finally, in samples obtained from two patients with drug refractory ALL, BAG-derived probes applied to archived marrow cells demonstrated that a breakpoint occurred between MDR1 and sequences 500-1000 KB telomeric to MDR1, consistent with a random chromosomal rearrangement. These results support the proposal that random chromosomal rearrangement leading to capture and activation of MDR1 is a mechanism of acquired drug resistance. (C) 1998 Wiley-Liss, Inc. C1 NCI, Med Branch, NIH, Div Clin Sci, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. NHGRI, Lab Genet Dis Res, Bethesda, MD USA. RP Knutsen, T (reprint author), NCI, Med Branch, NIH, Div Clin Sci, Bldg 10,Rm 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM turidk@Box-t.nih.gov NR 31 TC 62 Z9 65 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1998 VL 23 IS 1 BP 44 EP 54 DI 10.1002/(SICI)1098-2264(199809)23:1<44::AID-GCC7>3.0.CO;2-6 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 107ZB UT WOS:000075240200007 PM 9713996 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Joint Genome Institute web site SO GENOME RESEARCH LA English DT Article C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1998 VL 8 IS 9 BP 864 EP 869 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 125AK UT WOS:000076215100002 PM 9750187 ER PT J AU Lavedan, C AF Lavedan, C TI The synuclein family SO GENOME RESEARCH LA English DT Review ID A-BETA COMPONENT; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; PRECURSOR PROTEIN; 14-KDA PROTEIN; PRESYNAPTIC PROTEIN; AMPHIPATHIC HELIX; LEWY BODIES AB The synuclein gene family recently came into the spotlight, when one of its members, alpha-synuclein, was found to be mutated in several Families with autosomal dominant Parkinson's disease (PD). A peptide of the alpha-synuclein protein had been characterized previously as a major component of amyloid plaques in brains of patients with Alzheimer's disease [AD]. The mechanism by which this presynaptic protein is involved in the two most common neurodegenerative disorders, AD and PD, remains unclear. Remarkably, another member of this,gene family, gamma-synuclein, has been shown to be overexpressed in breast carcinomas and may also be overexpressed in ovarian cancer. The possible involvement of the synuclein proteins in the etiology of common human diseases has raised exciting questions and is the subject of intense investigation. Details of the properties of any member of the synuclein family may provide useful information For understanding the characteristics and function of other family members. The present review offers a synopsis of the current state of knowledge of all synuclein family members in different species. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Lavedan, C (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM lavedan@nhgri.nih.gov NR 59 TC 213 Z9 219 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1998 VL 8 IS 9 BP 871 EP 880 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 125AK UT WOS:000076215100003 PM 9750188 ER PT J AU Patel, BKR Keck, CL O'Leary, RS Popescu, NC LaRochelle, WJ AF Patel, BKR Keck, CL O'Leary, RS Popescu, NC LaRochelle, WJ TI Localization of the human Stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors SO GENOMICS LA English DT Article ID GROWTH-FACTOR RECEPTORS; INTERLEUKIN-4; CLONING; IL-4; OVEREXPRESSION; ACTIVATION; EXPRESSION; RESPONSES; PATHWAYS; PROTEINS AB Stat6 signaling pathways have been correlated with functional responses induced by IL-4 and PDGF that may play a role in human malignancy. Utilizing fluorescence in situ hybridization, we mapped the human State gene to chromosome 12q bands 13.3-14.1, a breakpoint region implicated in a wide variety of solid tumors. To understand the genesis of three human State variant cDNAs, including a naturally occurring dominant negative species, we further characterized the genomic structure and flanking regions of the human Stat6 gene. The human State gene encompassed over 19 kb and contained 23 exons. For promoter studies, we introduced flanking sequence 5' of Stat6 exon 1 into a promoterless luciferase reporter vector and characterized basal promoter activity by deletion analysis. DNA sequence analysis revealed potential transcriptional regulation of the putative promoter through numerous consensus binding elements. Finally, we conclude that selective exon deletion and utilization of alternative donor/ acceptor sites appear to explain best human Stat6 variant mRNAs. (C) 1998 Academic Press. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP LaRochelle, WJ (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 1E24, Bethesda, MD 20892 USA. EM billr@helix.nih.gov NR 39 TC 30 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1998 VL 52 IS 2 BP 192 EP 200 DI 10.1006/geno.1998.5436 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 128TD UT WOS:000076421700010 PM 9782085 ER PT J AU Chandross, KJ AF Chandross, KJ TI Nerve injury and inflammatory cytokines modulate gap junctions in the peripheral nervous system SO GLIA LA English DT Review DE connexin32; connexin43; connexin46; degeneration; fibroblast; glial growth factor; junctional coupling; macrophage; mitogens; peripheral nerve injury; regeneration; Schwann cell; transforming growth factor; tumor necrosis factor ID TRANSFORMING GROWTH-FACTOR; SCHWANN-CELL PROLIFERATION; RAT SCIATIC-NERVE; TUMOR-NECROSIS-FACTOR; MARIE-TOOTH DISEASE; MESSENGER-RNA EXPRESSION; STABLY TRANSFECTED CELLS; WALLERIAN DEGENERATION; MYELIN PROTEIN; CYCLIC-AMP AB In the peripheral nervous system (PNS), myelinating Schwann cells express the gap junction protein connexin32 (Cx32) and lower levels of connexin43 (Cx43). Although the function of Cx43 in Schwann cells is not yet known, in adult mammals Cx32 is thought to form reflexive contacts within individual myelinating glial cells and provide direct pathways for intracellular ionic and metabolic exchange from the cell body to the innermost periaxonal cytoplasmic regions. In response to nerve injury, Schwann cells in the degenerating region down-regulate expression of Cx32 and there is increased expression of connexin46 (Cx46) mRNA and protein. The cascade of Schwann cell responses seen after the injury-induced decrease in Cx32, and the observation that dividing Schwann cells express Cx46, and possibly other connexins, and are coupled through gap junction channels, raise the intriguing possibility that there are coordinated changes in Schwann cell proliferation and connexin expression. Moreover, intercellular junctional coupling among cells in general may be important during injury responses. Consistent with this hypothesis, dividing Schwann cells are preferentially coupled through junctional channels as compared to non-dividing cells, which are generally uncoupled. Moreover, the strength of junctional coupling among cultured Schwann cells is modulated by a number of cytokines to which Schwann cells are exposed to in vivo after nerve injury, and Cx46 mRNA and protein levels correlate with the degree of coupling. Other injury-induced cellular changes in connexin expression that may be functionally important during injury responses include a transient increase in Cx43 in endoneurial fibroblasts. This paper reviews what is known about connexin expression and function in the adult mammalian PNS, and focuses on some of the changes that occur following nerve injury. Moreover, evidence that inflammatory cytokines released after injury modulate connexin expression and junctional coupling strength is presented. GLIA 24:21-31, 1998. (C) 1998 Wiley-Liss, Inc.(dagger) C1 NINDS, NIH, Lab Dev Neurogenet, Bethesda, MD 20892 USA. RP Chandross, KJ (reprint author), NINDS, NIH, Lab Dev Neurogenet, Bldg 36,Room 5D21,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chandros@codon.nih.gov NR 163 TC 43 Z9 43 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 1998 VL 24 IS 1 BP 21 EP 31 DI 10.1002/(SICI)1098-1136(199809)24:1<21::AID-GLIA3>3.0.CO;2-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 106UK UT WOS:000075168700003 PM 9700486 ER PT J AU Wiesner, RH Demetris, AJ Belle, SH Seaberg, EC Lake, JR Zetterman, RK Everhart, J Detre, KM AF Wiesner, RH Demetris, AJ Belle, SH Seaberg, EC Lake, JR Zetterman, RK Everhart, J Detre, KM TI Acute hepatic allograft rejection: Incidence, risk factors, and impact on outcome SO HEPATOLOGY LA English DT Article ID LIVER-TRANSPLANTATION; DONOR AGE; SURVIVAL; IMPAIRMENT; RECIPIENTS; DISEASE; SYSTEM; HLA AB Hepatic allograft rejection remains an important problem following liver transplantation, and, indeed, complications related to the administration of immunosuppressive therapy remain a predominant cause of posttransplantation morbidity and mortality. The Liver Transplantation Database (LTD) was used to study a cohort of 762 consecutive adult liver transplantation recipients and determined the incidence, timing, and risk factors for acute rejection. We also evaluated the impact of histological severity of rejection on the need for additional immunosuppressive therapy and on patient and graft survival. Four hundred ninety (64%) of the 762 adult liver transplantation recipients developed at least one episode of rejection during a median follow-up period of 1,042 days (range, 336-1,896 days), most of which occurred during the first 6 weeks after transplantation. Multivariate analysis revealed that recipient age, serum creatinine, aspartate transaminase (AST) level, presence of edema, donor/recipient HLA-DR mismatch, cold ischemic time, and donor age were independently associated with the time to acute rejection. An interesting observation was that the histological severity of rejection was an important prognosticator: the use of antilymphocyte preparations was higher, and the time to death or retransplantation was shorter, for patients with severe rejection. Findings from this study will assist in decision-making for the use of immunosuppressive regimens and call into question whether complete elimination of all rejection or alloreactivity is a desirable goal in liver transplantation. C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Wiesner, RH (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. FU NIDDK NIH HHS [N01-DK-0-2253, N01-DK-0-2252, N01-DK-0-2251] NR 41 TC 260 Z9 272 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1998 VL 28 IS 3 BP 638 EP 645 DI 10.1002/hep.510280306 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JT UT WOS:000075606000006 PM 9731552 ER PT J AU Charlton, M Seaberg, E Wiesner, R Everhart, J Zetterman, R Lake, J Detre, K Hoofnagle, J AF Charlton, M Seaberg, E Wiesner, R Everhart, J Zetterman, R Lake, J Detre, K Hoofnagle, J TI Predictors of patient and graft survival following liver transplantation for hepatitis C SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; RECIPIENTS; RECURRENT; DISEASE; GENOTYPES; REJECTION; SEVERITY; VIREMIA; RNA AB End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1944, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P =.02 and P =.003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P =.001), Recipients who had a pretransplantation HCV-RNA titer of greater than or equal to 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of <1 x 106 vEq/mL (P =.0001), Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While longterm patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients. C1 NIDDK, Liver Transplantat Database, Bethesda, MD 20892 USA. RP Charlton, M (reprint author), Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. FU NCRR NIH HHS [GCRC RR00585] NR 31 TC 400 Z9 406 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1998 VL 28 IS 3 BP 823 EP 830 DI 10.1002/hep.510280333 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JT UT WOS:000075606000033 PM 9731579 ER PT J AU Rouault, TA AF Rouault, TA TI Hereditary hemochromatosis - Sometimes having a real complex can be a good thing SO HEPATOLOGY LA English DT Editorial Material ID IRON C1 Natl Inst Child Hlth & Dev, Sect Human Iron Metab, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), Natl Inst Child Hlth & Dev, Sect Human Iron Metab, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1998 VL 28 IS 3 BP 890 EP 891 DI 10.1002/hep.510280342 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 114JT UT WOS:000075606000040 PM 9731588 ER PT J AU Middleton, LP Merino, MJ Popok, SM Ordonez, NG Ayala, AG Ro, JY AF Middleton, LP Merino, MJ Popok, SM Ordonez, NG Ayala, AG Ro, JY TI Male adnexal tumour of probable Wolffian origin occurring in a seminal vesicle SO HISTOPATHOLOGY LA English DT Article DE female adnexal tumour; seminal vesicle; Wolffian ID ADENOID CYSTIC CARCINOMA; PROSTATE-GLAND; ADENOCARCINOMA; CYSTADENOMA; MALIGNANCY AB Aims: Adnexal tumours of probable Wolffian origin are rare low-grade malignant neoplasms that have been previously described in the broad ligament, ovaries and retroperitoneum of females. All are characterized by small, bland epithelial cells growing in a diffuse, trabecular, or tubular pattern. The majority of the cases reported have pursued a benign clinical course. However, recurrences and distant metastases have been described, We present a case of a male adnexal tumour of probable Wolffian origin occurring in the left seminal vesicle of a 29-year-old man with 23 years of follow-up, Results: The diagnosis is supported by immunohistochemical and electron microscopic findings: The tumour cells were immunoreactive for cytokeratin and vimentin while smooth muscle antigen and S100 protein were uniformly negative. By electron microscopy cells were arranged in an acinar pattern and surrounded flocculent, electron-dense material, Individual cells contained numerous dense bodies and free ribrosomes, The patient had recurrences at 14 and 23 years after initial diagnosis, Conclusion: This is the first report of this entity in a male. The literature on this unusual tumour is reviewed and the clinicopathological, immunohistochemical and ultrastructural features are described. The differential diagnosis of this seemingly indolent tumour is discussed with genitourinary tumours having a more aggressive clinical course. C1 NCI, Natl Inst Hlth, Pathol Lab, Dept Pathol, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Pathol, Houston, TX 77030 USA. Halifax Med Ctr, Dept Pathol, Daytona Beach, FL USA. RP Middleton, LP (reprint author), NCI, Natl Inst Hlth, Pathol Lab, Dept Pathol, Bldg 10,Room 2N212 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD SEP PY 1998 VL 33 IS 3 BP 269 EP 274 DI 10.1046/j.1365-2559.1998.00473.x PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 124KB UT WOS:000076180500011 PM 9777394 ER PT J AU Walker, PS Scharton-Kersten, T Rowton, ED Hengge, U Bouloc, A Udey, MC Vogel, JC AF Walker, PS Scharton-Kersten, T Rowton, ED Hengge, U Bouloc, A Udey, MC Vogel, JC TI Genetic immunization with glycoprotein 63 cDNA results in a helper T cell type 1 immune response and protection in a murine model of leishmaniasis SO HUMAN GENE THERAPY LA English DT Article ID SURFACE-ANTIGEN; DENDRITIC CELLS; MAJOR INFECTION; BACTERIAL-DNA; CPG MOTIFS; CUTANEOUS LEISHMANIASIS; LANGERHANS CELLS; NAKED DNA; IN-VIVO; EXPRESSION AB Genetic immunization is a promising gene therapy approach for the prevention and treatment of infectious disease, Plasmid DNA expressing genes of pathogens is directly introduced into host cells and specific cell-mediated and/or humoral immune responses are elicited against the encoded protein. Leishmaniasis is a significant world-wide health problem for which no vaccine exists, In susceptible animals, such as BALB/c mice, protection from leishmaniasis requires induction of a Th1 immune response, In this study, cell-mediated immunity to Leishmania major (L, major) was induced by injecting BALB/c mice intradermally with plasmid DNA expressing the conserved L, major cell surface glycoprotein gp63 (gp63-pcDNA-3), CD4 T lymphocytes from gp63-pcDNA-3-immunized mice proliferated and produced IFN-gamma (but not IL-4) when stimulated in vitro with freeze-thawed parasites, consistent with a Th1 immune response. In contrast, lymphocyte proliferation in animals immunized with freeze-thawed parasites was associated with IL-4 (but not IFN-gamma) production, suggesting a nonprotective Th2 response. Challenge studies revealed that gp63-pcDNA-3 vaccination protected 30% of susceptible mice (21 of 70) from Leishmania infection while neither gp63 protein (0 of 20) nor freeze-thawed parasite vaccines (0 of 50) were efficacious, Dendritic cells derived from skin of gp63-pcDNA-3-injected mice also immunized naive recipients and protected them from leishmaniasis, We conclude that gp63-pcDNA-3 genetic vaccination results in a CD4-dependent Th1 immune response that correlates with protection from disease, and suggest that skin-derived dendritic cells are involved in priming this response. C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Vogel, JC (reprint author), NIH, Dermatol Branch, Bldg 10 Room 12N260,9600 Rockville Pike, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012 OI Rowton, Edgar/0000-0002-1979-1485; NR 47 TC 66 Z9 66 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 1 PY 1998 VL 9 IS 13 BP 1899 EP 1907 DI 10.1089/hum.1998.9.13-1899 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 114XE UT WOS:000075633800006 PM 9741428 ER PT J AU Sabol, SZ Hu, S Hamer, D AF Sabol, SZ Hu, S Hamer, D TI A functional polymorphism in the monoamine oxidase A gene promoter SO HUMAN GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; SEROTONIN TRANSPORTER GENE; TRANSCRIPTION FACTOR SP1; B-GENES; A GENE; SEXUAL ORIENTATION; X-CHROMOSOME; SUSCEPTIBILITY LOCUS; NORRIE DISEASE; INSULIN GENE AB We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2-10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hamer, D (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Rm 4A13, Bethesda, MD 20892 USA. EM DeanH@helix.nih.gov NR 48 TC 653 Z9 693 U1 7 U2 44 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1998 VL 103 IS 3 BP 273 EP 279 DI 10.1007/s004390050816 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 128JD UT WOS:000076401900002 PM 9799080 ER PT J AU Wei, MH Karavanova, I Ivanov, SV Popescu, NC Keck, CL Pack, S Eisen, JA Lerman, MI AF Wei, MH Karavanova, I Ivanov, SV Popescu, NC Keck, CL Pack, S Eisen, JA Lerman, MI TI In silico-initiated cloning and molecular characterization of a novel human member of the L1 gene family of neural cell adhesion molecules SO HUMAN GENETICS LA English DT Article ID NERVOUS-SYSTEM; RECOGNITION MOLECULES; CHROMOSOME-3; HYBRIDIZATION; MUTATIONS; GROWTH; SITES; MOUSE; BRAIN AB To discover genes contributing to mental retardation in 3p(-) syndrome patients we have used in silico searches for neural genes in NCBI databases (dbEST and Uni-Gene). An EST with strong homology to the rat CAM L1 gene subsequently mapped to 3p26 was used to isolate a full-length cDNA. Molecular analysis of this cDNA, referred to as CALL (cell adhesion L1-like), showed that it is encoded by a chromosome 3p26 locus and is a novel member of the L1 gene family of neural cell adhesion molecules. Multiple lines of evidence suggest CALL is likely the human ortholog of the murine gene CHL1: it is 84% identical on the protein level, has the same domain structure, same membrane topology, and a similar expression pattern. The orthology of CALL and CHL1 was confirmed by phylogenetic analysis. By in situ hybridization, CALL is shown to be expressed regionally in a timely fashion in the central nervous system, spinal cord, and peripheral nervous system during rat development. Northern analysis and EST representation reveal that it is expressed in the brain and also outside the nervous system in some adult human tissues and tumor cell lines. The cytoplasmic domain of CALL is conserved among other members of the L1 subfamily and features sequence motifs that may involve CALL in signal transduction pathways. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Carcinogenesis Lab, Mol Cytogenet Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. RP Lerman, MI (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [N01-CO-56000, R01 CA090915] NR 37 TC 34 Z9 43 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1998 VL 103 IS 3 BP 355 EP 364 DI 10.1007/s004390050829 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 128JD UT WOS:000076401900015 PM 9799093 ER PT J AU Walder, K Norman, RA Hanson, RL Schrauwen, P Neverova, M Jenkinson, CP Easlick, J Warden, CH Pecqueur, C Raimbault, S Ricquier, D Harper, M Silver, K Shuldiner, AR Solanes, G Lowell, BB Chung, WK Leibel, RL Pratley, R Ravussin, E AF Walder, K Norman, RA Hanson, RL Schrauwen, P Neverova, M Jenkinson, CP Easlick, J Warden, CH Pecqueur, C Raimbault, S Ricquier, D Harper, M Silver, K Shuldiner, AR Solanes, G Lowell, BB Chung, WK Leibel, RL Pratley, R Ravussin, E TI Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism obesity in Pima Indians SO HUMAN MOLECULAR GENETICS LA English DT Article ID THYROID-HORMONE; SKELETAL-MUSCLE; ADIPOSE-TISSUE; GENE; EXPENDITURE; EXPRESSION; MEMBER; FAMILY; UCP3 AB The UCP2-UCP3 gene cluster maps to chromosome 11q13 in humans, and polymorphisms in these genes may contribute to obesity through effects on energy metabolism. DNA sequencing of UCP2 and UCP3 revealed three polymorphisms informative for association studies: an Ala-->Val substitution in exon 4 of UCP2, a 45 bp insertion/deletion in the 3'-untranslated region of exon 8 of UCP2 and a C-->T silent polymorphism in exon 3 of UCP3. Initially, 82 young (mean age = 30 +/- 7 years), unrelated, full-blooded, non-diabetic Pima Indians were typed for these polymorphisms by direct sequencing. The three sites were in linkage disequilibrium (P < 0.00001). The UCP2 variants were associated with metabolic rate during sleep (exon 4, P = 0.007; exon 8, P = 0.016) and over 24 h (exon 8, P = 0.038). Heterozygotes for UCP2 variants had higher metabolic rates than homozygotes. The UCP3 variant was not significantly associated with metabolic rate or obesity. In a further 790 full-blooded Pima Indians, there was no significant association between the insertion/deletion polymorphism and body mass index (BMI). However, when only individuals >45 years of age were considered, heterozygotes (subjects with the highest sleeping metabolic rate) had the lowest BMI (P = 0.04). The location of the insertion/deletion polymorphism suggested a role in mRNA stability; however, it appeared to have no effect on skeletal muscle UCP2 mRNA levels in a subset of 23 randomly chosen Pima Indians. In conclusion, these results suggest a contribution from UCP2 (or UCP3) to variation in metabolic rate in young Pima Indians which may contribute to overall body fat content later in life. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. Maastricht Univ, Dept Human Biol, Maastricht, Netherlands. Univ Calif Davis, Rowe Program Genet, Livermore, CA 95616 USA. Univ Calif Davis, Dept Pediat Biol Chem & Med, Livermore, CA 95616 USA. CNRS, CEREMOD, F-92190 Meudon, France. Univ Maryland, Div Diabet Obesity & Nutr, Baltimore, MD 21201 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Columbia Univ Coll Phys & Surg, Div Mol Genet, New York, NY 10032 USA. RP Walder, K (reprint author), NIDDKD, Clin Diabet & Nutr Sect, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. RI Pecqueur, Claire/L-3073-2015; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [R37 DK053477, R01 DK079195] NR 19 TC 228 Z9 241 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1998 VL 7 IS 9 BP 1431 EP 1435 DI 10.1093/hmg/7.9.1431 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 116FG UT WOS:000075713000014 PM 9700198 ER PT J AU Fogt, F Vortmeyer, AO Stolte, M Mueller, E Mueller, J Noffsinger, A Poremba, C Zhuang, ZP AF Fogt, F Vortmeyer, AO Stolte, M Mueller, E Mueller, J Noffsinger, A Poremba, C Zhuang, ZP TI Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas SO HUMAN PATHOLOGY LA English DT Article DE ulcerative colitis; loss of heterozygosity; von Hippel Lindau gene; chromosome 3 ID NEOPLASTIC PROGRESSION; COLORECTAL-CANCER; P53; MUTATIONS; COLONOSCOPY; LESIONS; DISEASE; MUCOSA AB Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12 ro off the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in Oro and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases. Copyright (C) 1998 by W.B. Saunders Company. C1 Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. Staedt Krankenanstalten, Dept Pathol, Bayreuth, Germany. Tech Univ Munich, Dept Pathol, D-8000 Munich, Germany. Univ Cincinnati, Med Ctr, Dept Pathol, Cincinnati, OH 45221 USA. Univ Munster, Dept Pathol, D-4400 Munster, Germany. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Market St, Philadelphia, PA 19104 USA. NR 25 TC 31 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1998 VL 29 IS 9 BP 961 EP 964 DI 10.1016/S0046-8177(98)90201-5 PG 4 WC Pathology SC Pathology GA 119DN UT WOS:000075880700011 PM 9744312 ER PT J AU Hunt, SC Cook, NR Oberman, A Cutler, JA Hennekens, CH Allender, PS Walker, WG Whelton, PK Williams, RR AF Hunt, SC Cook, NR Oberman, A Cutler, JA Hennekens, CH Allender, PS Walker, WG Whelton, PK Williams, RR TI Angiotensinogen genotype, sodium reduction, weight loss, and prevention of hypertension - Trials of hypertension prevention, phase II SO HYPERTENSION LA English DT Article DE blood pressure; clinical trials; genetics; interaction; prospective study; renin ID BLOOD-PRESSURE; GENE; WHITE; RESTRICTION; MECHANISMS; CHILDREN; OBESITY; VARIANT; LOCUS AB The angiotensinogen gene has been linked to essential hypertension and increased blood pressure. A functional variant believed to be responsible for hypertension susceptibility occurs at position -6 in the promoter region of the gene in which an A for G base pair substitution is associated with higher angiotensinogen levels. To test whether an allele within the angiotensinogen gene is related to subsequent incidence of hypertension and blood pressure response to sustained sodium reduction, 1509 white male and female subjects participating in phase II of the Trials of Hypertension Prevention were genotyped at the angiotensinogen locus. Participants had diastolic blood pressures between 83 and 89 mm Hg and were randomized in a 2X2 factorial design to sodium reduction, weight loss, combined intervention, or usual care groups. Persons in the usual care group with the AA genotype at nucleotide position -6 had a higher 3-year incidence rate of hypertension (44.6%) compared with those with the GG genotype (31.5%), with a relative risk of 1.4 (95% confidence interval [0.87, 2.34], test for trend across all 3 genotypes, P=0.10), In contrast, the incidence of hypertension was significantly lower after sodium reduction for persons with the AA genotype (relative risk=0.57 [0.34, 0.98] versus usual care) but not for persons with the CG genotype (relative risk=1.2 [0.79, 1.81], test for trend P=0.02). Decreases of diastolic blood pressure at 36 months in the sodium reduction group versus usual care showed a significant trend across all 3 genotypes (P=0.01), with greater net blood pressure reduction in those with the AA genotype (-2.2 mm Hg) than those with the GG genotype (+1.1 mm Hg). A similar trend across the 3 genotypes for net systolic blood pressure reduction (-2.7 for AA versus -0.2 mm Hg for GG) was not significant (P=0.17), Trends across genotypes for the effects of weight loss on hypertension incidence and decreases in blood pressure were similar to those for sodium reduction. We conclude that the angiotensinogen genotype may affect blood pressure response to sodium or weight reduction and the development of hypertension. C1 Univ Utah, Sch Med, Salt Lake City, UT USA. Brigham & Womens Hosp, Trials Hypertens Prevent Coordinating Ctr, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. RP Hunt, SC (reprint author), Brigham & Womens Hosp, Trials Hypertens Prevent Coordinating Ctr, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM steve@ucvg.med.utah.edu FU NHLBI NIH HHS [HL-37907, HL-37852, HL-37924] NR 33 TC 112 Z9 115 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1998 VL 32 IS 3 BP 393 EP 401 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 119MJ UT WOS:000075900000004 PM 9740601 ER PT J AU Kailasam, MT Diggle, K Wilson, AF O'Connor, DT Parmer, RJ AF Kailasam, MT Diggle, K Wilson, AF O'Connor, DT Parmer, RJ TI Linkage of alpha-adrenergic pressor responsiveness to chromosome 5q in hypertensive families SO HYPERTENSION LA English DT Meeting Abstract C1 Univ Calif San Diego, San Diego, CA 92103 USA. VAMC, San Diego, CA USA. NHGRI, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1998 VL 32 IS 3 MA 23 BP 593 EP 593 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 119MJ UT WOS:000075900000058 ER PT J AU Muller, F Brigger, P Illgner, K Unser, M AF Muller, F Brigger, P Illgner, K Unser, M TI Multiresolution approximation using shifted splines SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article ID FILTERS; CONVERGENCE; L(2) AB We consider the construction of least squares pyramids using shifted polynomial spline basis functions. We derive the pre and postfilters as a function of the degree n and the shift parameter Delta. We show that the underlying projection operator is entirely specified by two transfer functions acting on the even and odd signal samples, respectively. We introduce a measure of shift invariance and show that the most favorable configuration is obtained when the knots of the splines are centered with respect to the grid points (i.e., Delta = 1/2 when n is odd and Delta = 0 when n is even). The worst case corresponds to the standard multiresolution setting where the spline spaces are nested. C1 Rhein Westfal TH Aachen, Inst Elekt Nachrichtentech, D-5100 Aachen, Germany. NIH, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. Ecole Polytech Fed Lausanne, DMT, IOA, Biomed Imaging Grp, CH-1015 Lausanne, Switzerland. RP Muller, F (reprint author), Rhein Westfal TH Aachen, Inst Elekt Nachrichtentech, D-5100 Aachen, Germany. RI Unser, Michael/A-1550-2008 NR 13 TC 8 Z9 8 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD SEP PY 1998 VL 46 IS 9 BP 2555 EP 2558 DI 10.1109/78.709545 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA 113HG UT WOS:000075544300027 ER PT J AU Combadiere, B Sousa, CR Trageser, C Zheng, LX Kim, CR Lenardo, MJ AF Combadiere, B Sousa, CR Trageser, C Zheng, LX Kim, CR Lenardo, MJ TI Differential TCR signaling regulates apoptosis and immunopathology during antigen responses in vivo SO IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL TISSUE FACTOR; PROGRAMMED CELL-DEATH; MATURE T-CELLS; LYMPHOPROLIFERATIVE SYNDROME; PARTIAL AGONISTS; FACTOR-ALPHA; FAS-LIGAND; ACTIVATION; INDUCTION AB Clonal selection theories postulate that lymphocyte fate is regulated by antigen receptor specificity. However, lymphocyte apoptosis is induced through non-antigen-specific receptors such as Fas (CD95/APO-1) or TNFR. We define a selective TCR that controls apoptosis by Fas or TNFR stimulation. Variant ligands can deliver this "competence to die" signal without the full TCR signals necessary for cytokine synthesis. These partial agonists regulate T cell deletion in vivo even when Fas or TNF is provided by T cells of unrelated specificity, but they do not cause the liver necrosis that is associated with T cell elimination by the full agonist. Thus, selective signaling ligands regulate T cell deletion and immune damage in vivo and may be important for peripheral T cell tolerance. C1 NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Combadiere, Behazine/G-3881-2013 NR 35 TC 46 Z9 46 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1998 VL 9 IS 3 BP 305 EP 313 DI 10.1016/S1074-7613(00)80613-5 PG 9 WC Immunology SC Immunology GA 124VA UT WOS:000076202300003 PM 9768750 ER PT J AU Baldwin, WS Curtis, SW Cauthen, CA Risinger, JI Korach, KS Barrett, JC AF Baldwin, WS Curtis, SW Cauthen, CA Risinger, JI Korach, KS Barrett, JC TI BG-1 ovarian cell line: An alternative model for examining estrogen-dependent growth in vitro SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE estrogen; growth factors; estrogen receptor; IGF-1; EGF ID HUMAN-BREAST-CARCINOMA; CANCER-CELLS; REPLACEMENT THERAPY; PROTEIN-KINASE; CROSS-TALK; RECEPTOR; PROLIFERATION; PROGESTERONE; EXPRESSION; SECRETION AB Examination of estrogen-responsive processes in cell culture is used to investigate hormonal influence on cancer cell growth and gene expression. Most experimental studies have used breast cancer cell lines, in particular MCF7 cells, to investigate estrogen responsiveness. In this study we examined an ovarian cancer cell line, BG-1, which is highly estrogen-responsive in vitro. This observation, plus the fact that the cells are of ovarian rather than mammary gland origin, makes it an attractive alternative model. 17 beta-Estradiol, epidermal growth factor, and insulin-like growth factor induced proliferation of BG-1 and MCF7 cells. Viability was dependent on these growth factors in BG-1 cells, but not in MCF7 cells. Therefore, we examined the differences between these two cell lines with respect to estrogen and growth factor receptors. BG-1 cells have twice as many estrogen receptors as MCF7 cells, and BG-1 cells have higher insulin-like growth factor-1 and epidermal growth factor receptor levels than MCF7 cells. This may also explain why BG-1 cells proliferate 56% more robustly in serum and show more serum dependence in culture. In both BG-1 and MCF7 cells, epidermal growth factor receptor number is low (<20 000/cell), while insulin-like growth factor-1 receptor level was highest in estrogen receptor positive cell lines. For example, insulin-like growth factor-1 receptor was higher in BG-1 and MCF? cells than in estrogen receptor negative cells (HeLa > MDA-MB-435 > HBL100). In conclusion, BG-I. cells are an excellent model for understanding hormone responsiveness in ovarian tissue and an alternative for examining estrogen receptor-mediated and insulin-like growth factor-1/epidermal growth factor/estrogen cross-talk processes because of their sensitivity to these factors. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 27 TC 34 Z9 35 U1 0 U2 4 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 1998 VL 34 IS 8 BP 649 EP 654 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 119XG UT WOS:000075923200015 PM 9769151 ER PT J AU Mei, Q Turner, RE Sorial, V Klivington, D Angus, CW Kovacs, JA AF Mei, Q Turner, RE Sorial, V Klivington, D Angus, CW Kovacs, JA TI Characterization of major surface glycoprotein genes of human Pneumocystis carinii and high-level expression of a conserved region SO INFECTION AND IMMUNITY LA English DT Article ID ANTIGENIC VARIATION; INFECTED PATIENTS; MULTIPLE GENES; ANTIBODIES; RESPONSES; RAT; IDENTIFICATION; PNEUMONIA; SITE; IMMUNIZATION AB To facilitate studies of Pneumocystis carinii infection in humans, me undertook to better characterize and to express the major surface glycoprotein (MSG) of human P. carinii, are important protein in host-pathogen interactions. Seven MSG genes mere cloned from a single isolate by PCR or genomic library screening and were sequenced. The predicted proteins, like rat MSGs, were closely related but unique variants, with a high level of conservation among cysteine residues. A conserved immunodominant region (of approximately 100 amino acids) near the carboxy terminus was expressed at high levels in Escherichia coli and used in Western blot studies. All 49 of the serum samples, which were taken from healthy controls as well as from patients with and without P, carinii pneumonia, mere reactive with this peptide by Western blotting, supporting the hypothesis that most adult humans have been infected with P. carinii at some point, This recombinant MSG fragment, which is the first human P. carinii antigen available in large quantities, may be a useful reagent for investigating the epidemiology of P. carinii infection in humans. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 46 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4268 EP 4273 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500038 PM 9712777 ER PT J AU Merkel, TJ Stibitz, S Keith, JM Leef, M Shahin, R AF Merkel, TJ Stibitz, S Keith, JM Leef, M Shahin, R TI Contribution of regulation by the bvg locus to respiratory infection of mice by Bordetella pertussis SO INFECTION AND IMMUNITY LA English DT Article ID SIGNAL-TRANSDUCTION; VIRULENCE FACTORS; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; REPRESSED GENES; RNA-POLYMERASE; BRONCHISEPTICA; VIR; EXPRESSION; MUTATIONS AB Whooping cough is an acute respiratory disease caused by the small, gram-negative bacterium Bordetella pertussis. B. pertussis expresses several factors that contribute to its ability to cause disease. These factors include surface-associated molecules, which are involved in the adherence of the organism to respiratory epithelial cells, as well as several extracellular toxins that inhibit host defenses and induce damage to host tissues, The expression of virulence factors in B, pertussis is dependent upon the bvg locus, which consists of three genes: bvgA, bvgS, and bvgR, The bvgAS genes encode a two-component regulatory system consisting of a sensor protein, BvgS, and a transcriptional activator, BvgA. Upon modification by BvgS, BvgA binds to the promoter regions of the bvg-activated genes and activates transcription. One of the bvg-activated genes, bvgR, is responsible for the regulation of the bvg-repressed genes, the functions of which are unknown, The fact that these genes are regulated by the bvg locus suggests that they play a role in the pathogenesis of the bacterium. In order to evaluate the contribution of bvg-mediated regulation to the virulence of B. pertussis and determine if expression of the bvg-repressed genes is required for the virulence of B. pertussis, we examined the ability of B. pertussis mutants, defective in their ability to regulate the expression of the bvg-activated and/or the bvg-repressed genes, to cause disease in the mouse aerosol challenge model. Our results indicate that the bvgR-mediated regulation of gene expression contributes to respiratory infection of mice. C1 NIDR, OIIB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), NIDR, OIIB, NIH, Bldg 30,Rm 303,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 48 TC 52 Z9 53 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4367 EP 4373 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500050 PM 9712789 ER PT J AU Yap, GS Scharton-Kersten, T Ferguson, DJP Howe, D Suzuki, Y Sher, A AF Yap, GS Scharton-Kersten, T Ferguson, DJP Howe, D Suzuki, Y Sher, A TI Partially protective vaccination permits the development of latency in a normally virulent strain of Toxoplasma gondii SO INFECTION AND IMMUNITY LA English DT Article ID ACUTE INFECTION; IFN-GAMMA; CLONAL LINEAGES; CYST FORMATION; LYMPHOCYTES-T; RH STRAIN; IN-VITRO; MICE; PARASITE; ANTIGEN AB The virulent RH strain of Toxoplasma gondii is acutely lethal in mice and fails to establish chronic infection, Vaccination of BALB/c mice with a soluble tachyzoite antigen preparation, STAg, in combination with the immunostimulatory cytokine interleukin-12 results in partial protection against RH lethal challenge. Nevertheless, brain tissue obtained bean surviving, vaccinated mice as late as 1 year after RH infection contained latent parasite forms as demonstrated by subinoculation into naive recipients. The tachyzoites arising in the subinoculated animals were genetically indistinguishable from the original RH inoculum. Microscopic examination revealed that the persistent parasite forms present in the brains of vaccinated and challenged mice have a tissue cyst-like morphology and express the bradyzoite antigen BAG-1 but not the tachyzoite-specific antigen SAG-2 but are different from the cysts formed by avirulent T. gondii strains in that the internal parasite stages display ultrastructural features intermediate between tachyzoites and bradyzoites, Moreover, the zoites within the RH tissue cysts are clearly distinct from conventional bradyzoites in their sensitivity to pepsin-HCl digestion. In contrast to the observations made with partially resistant STAg/interleukin-12-vaccinated animals, no latent forms could be detected in brain tissue after RH challenge of mice immunized with a live attenuated tachyzoite vaccine which confers fetal protection against this parasite isolate. The above Endings demonstrate the potential of a virulent T. gondii strain to generate latent parasite stages, a process which may be promoted under conditions of incomplete vaccination. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Electron Microscopy Unit, Nuffield Dept Pathol, Oxford OX3 9DU, England. Washington Univ, Dept Mol Microbiol, St Louis, MO 63110 USA. Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. Stanford Univ, Sch Med, Dept Med, Div Infect Dis & Geog Med, Stanford, CA USA. RP Yap, GS (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. OI Ferguson, David/0000-0001-5045-819X FU Wellcome Trust NR 27 TC 20 Z9 22 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4382 EP 4388 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500052 PM 9712791 ER PT J AU Doherty, TM Sher, A Vogel, SN AF Doherty, TM Sher, A Vogel, SN TI Paclitaxel (Taxol)-induced killing of Leishmania major in murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; A-ASSOCIATED PROTEINS; NITRIC-OXIDE; TYROSINE PHOSPHORYLATION; 2ND SIGNAL; TAXOL; LIPOPOLYSACCHARIDE; ENDOTOXIN; MICE; RECEPTORS AB The antitumor drug paclitaxel (Taxol) has been demonstrated to be a lipopolysaccharide mimetic in murine macrophages. In this study, the capacity of paclitaxel to activate macrophages to become microbicidal for Leishmania major was examined. Paclitaxel and gamma interferon synergized to kill intracellular L. major in Lps(n), but not Lps(d), macrophages by a nitric oxide (NO.)-dependent mechanism. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [R37 AI018797, R56 AI018797, R01 AI018797, AI-18797] NR 29 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1998 VL 66 IS 9 BP 4553 EP 4556 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500080 PM 9712819 ER PT J AU Gladwin, MT Pierson, DJ AF Gladwin, MT Pierson, DJ TI Mechanical ventilation of the patient with severe chronic obstructive pulmonary disease SO INTENSIVE CARE MEDICINE LA English DT Review ID ACUTE RESPIRATORY-FAILURE; END-EXPIRATORY PRESSURE; METERED-DOSE INHALER; AIR-FLOW OBSTRUCTION; CRITICALLY ILL PATIENTS; AUTO-PEEP; DYNAMIC HYPERINFLATION; ELECTROMECHANICAL DISSOCIATION; SUPPORT VENTILATION; ACUTE EXACERBATIONS C1 Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Pierson, DJ (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, 325 9Th Ave,Box 359762, Seattle, WA 98104 USA. EM djp@u.washington.edu NR 105 TC 18 Z9 20 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 1998 VL 24 IS 9 BP 898 EP 910 DI 10.1007/s001340050688 PG 13 WC Critical Care Medicine SC General & Internal Medicine GA 124UX UT WOS:000076201900002 PM 9803325 ER PT J AU Guerin, T Walsh, GA Donlon, J Kaufman, S AF Guerin, T Walsh, GA Donlon, J Kaufman, S TI Correlation of rat hepatic phenylalanine hydroxylase, with tetrahydrobiopterin and GTP concentrations SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE rat; liver; phenylalanine hydroxylase; tetrahydrobiopterin; cofactor; GTP; glycerol; fructose; experimental diabetes ID PROTEIN IMPORT; PURIFICATION; METABOLISM; LIVER; CELLS; CHROMATOGRAPHY; BIOSYNTHESIS; DEHYDRATASE; STIMULATION; GLUCAGON AB Hepatic phenylalanine hydroxylase is reported to be more abundant in experimentally-diabetic rats; whereas livers of animals fed a high protein diet, where gluconeogenesis also prevails, have normal amounts of this enzyme. In this study; in addition to seeking an explanation for this effect of experimental diabetes, we also examined the effects of providing alternative dietary gluconeogenic substrates. In rats fed a diet composed of 40% (w/w) glycerol, the specific activities of hepatic phenylalanine hydroxylase are decreased to about 60% of control values. There is no effect on the apparent state of phosphorylation of the enzyme. However, studies on the incorporation of radiolabelled leucine into liver phenylalanine hydroxylase suggested that there was a decreased rate of synthesis. Similarly, animals fed a diet containing 85% (w/w) fructose also have diminished phenylalanine hydroxylase activities. Under all of the above circumstances and also in streptozotocin-induced diabetic animals, alterations in the concentrations of the hydroxylase cofactor, tetrahydrobiopterin and of GTP closely correlate with the effects on the enzyme activities. They are elevated in livers of diabetic animals and significantly diminished in livers of rats fed diets rich in glycerol or fructose. These observations suggest that in adult rat both liver tetrahydrobiopterin concentrations and the expression of hepatic phenylalanine hydroxylase are regulated by GTP [210]. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Natl Univ Ireland Univ Coll Galway, Dept Biochem, Galway, Ireland. NIMH, Neurochem Lab, Bethesda, MD 20892 USA. RP Donlon, J (reprint author), Natl Univ Ireland Univ Coll Galway, Dept Biochem, Galway, Ireland. NR 39 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD SEP PY 1998 VL 30 IS 9 BP 1047 EP 1054 DI 10.1016/S1357-2725(98)00065-X PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 122XX UT WOS:000076097700012 PM 9785468 ER PT J AU Strickler, H Manns, A Escoffery, C Rattray, C Brown, C Vellucci, V Reiss, M AF Strickler, H Manns, A Escoffery, C Rattray, C Brown, C Vellucci, V Reiss, M TI P53 polymorphisms at position 72 and development of cervical cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Letter C1 NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ W Indies, Kingston, Jamaica. Yale Univ, Sch Med, New Haven, CT USA. RP Strickler, H (reprint author), NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RI Reiss, Michael/A-8314-2009 NR 3 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 1998 VL 8 IS 5 BP 439 EP 439 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 141UN UT WOS:000077162800015 ER PT J AU Shi, YB Li, Q Damjanovski, S Amano, T Ishizuya-Oka, A AF Shi, YB Li, Q Damjanovski, S Amano, T Ishizuya-Oka, A TI Regulation of apoptosis during development: Input from the extracellular matrix (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE thyroid hormone; apoptosis; metalloproteinase; extracellular matrix (ECM); transcriptional regulation; Xenopus laevis ID PROGRAMMED CELL-DEATH; MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION; C-ELEGANS; THYROID-HORMONE; XENOPUS-LAEVIS; CYTOCHROME-C; STROMELYSIN-3 GENE; CONNECTIVE-TISSUE; SMALL-INTESTINE AB Programmed eel death or apoptosis is an important aspect in organogenesis and tissue remodeling during development. Extensive investigations have led to the identification of many genes that participate in the regulation of cell death execution. These include the caspases and nucleases, which are involved in the degradation of cellular proteins and nuclear DNA to initiate the irreversible death process. In addition, several families of proteins like Bcl-2 superfamily can either prevent or promote cell death. The function of these proteins are getting to be understood. On the other hand, how these proteins are regulated remains to be investigated. This is in part due to the presence of diverse upstream signals that can influence cell fate. One such signal is the remodeling of the extracellular matrix (ECM), which is largely due to the action of matrix metalloproteinases (MMPs). The regulation of MMPs and ECM remodeling has been shown to affect apoptosis in different systems, including the apoptotic remodeling of the intestine during Xenopus laevis metamorphosis and post-lactation involution of the mouse mammary gland. Current evidence suggests that ECM regulates cell fate at least in part through its membrane receptors, the integrins, which in turn send the signal through yet poorly understood pathways to the nucleus to regulate gene expression. C1 NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Dokkyo Univ, Sch Med, Dept Anat, Mibu, Tochigi 32102, Japan. RP Shi, YB (reprint author), NICHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 121 TC 74 Z9 75 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD SEP PY 1998 VL 2 IS 3 BP 273 EP 282 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118BW UT WOS:000075818700003 PM 9855698 ER PT J AU Park, WS Moon, YW Yang, YM Kim, YS Kim, YD Fuller, BG Vortmeyer, AO Fogt, F Lubensky, IA Zhuang, ZP AF Park, WS Moon, YW Yang, YM Kim, YS Kim, YD Fuller, BG Vortmeyer, AO Fogt, F Lubensky, IA Zhuang, ZP TI Mutations of the STK11 gene in sporadic gastric carcinoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE gastric carcinoma; Peutz-Jeghers syndrome; STK11 gene ID PEUTZ-JEGHERS SYNDROME; P53 MUTATIONS; GERM-LINE; CANCER; SARCOMA AB Gastric carcinoma may occur sporadically or in association with hereditary diseases, such as Peutz-Jehgers syndrome (PJS). The PJS gene (named STK11 or LKB1) was mapped to 19p13.3 and recently cloned. Germ-line mutations of the gene have been detected in familial PJS patients and are predicted to predispose STK11 carriers to the development of a wide range of gastrointestinal and other neoplasms. To elucidate the etiological role of the STK11 gene in sporadic gastric carcinoma tumorigenesis, we analyzed 28 gastric carcinomas (22 of intestinal type and 6 of diffuse type) for STK11 gene mutations. STK11 gene mutations were detected in 3 of 28 gastric carcinomas but were not seen in the corresponding germ-line DNA sequence. In one tumor, a missense mutation, C-to-T transition, was detected at codon 324 resulting in proline to leucine substitution; in the other two, silent mutations were detected at codons 106 and 350, respectively. While these results suggest that somatic STK11 mutations are not common in sporadic gastric carcinomas, they may occur in a subset of these tumors. C1 Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19035 USA. Seoul Clin Lab, Seoul, South Korea. Catholic Univ, Coll Med, Dept Pathol, Seoul, South Korea. NCI, Labs Pathol, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Konkuk Univ, Coll Med, Genet Lab, Premed Course, Chungju, South Korea. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Market St, Philadelphia, PA 19035 USA. NR 32 TC 35 Z9 38 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1998 VL 13 IS 3 BP 601 EP 604 PG 4 WC Oncology SC Oncology GA 110GL UT WOS:000075371900028 PM 9683800 ER PT J AU Pietrini, P Guazzelli, M AF Pietrini, P Guazzelli, M TI Regional brain metabolism in relation to cognitive decline SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. Univ Pisa, Dept Psychiat, Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 1998 VL 30 IS 1-2 SI SI MA 79 BP 32 EP 32 DI 10.1016/S0167-8760(98)90079-4 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 130XY UT WOS:000076546700079 ER PT J AU Pietrini, P Guazzelli, M Grafman, J AF Pietrini, P Guazzelli, M Grafman, J TI Gender differences in brain activation during aggressive imageries: A PET study SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. Univ Pisa, Dept Psychiat, Pisa, Italy. NR 0 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 1998 VL 30 IS 1-2 SI SI MA 81 BP 33 EP 33 DI 10.1016/S0167-8760(98)90081-2 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 130XY UT WOS:000076546700081 ER PT J AU Knox, SS Hausdorff, J Markovitz, J Lewis, B Jacobs, D AF Knox, SS Hausdorff, J Markovitz, J Lewis, B Jacobs, D TI Blood pressure reactivity to psychological stress as a predictor of ambulatory blood pressure in cardia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 1998 VL 30 IS 1-2 SI SI MA 287 BP 112 EP 113 DI 10.1016/S0167-8760(98)90286-0 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 130XY UT WOS:000076546700280 ER PT J AU Knox, SS Siegmund, KD Weidner, G Ellison, RC Adelman, A Paton, C AF Knox, SS Siegmund, KD Weidner, G Ellison, RC Adelman, A Paton, C TI Hostility, social support and CHD in the NHLBI family heart study SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 1998 VL 30 IS 1-2 SI SI MA 288 BP 113 EP 113 DI 10.1016/S0167-8760(98)90287-2 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 130XY UT WOS:000076546700281 ER PT J AU Andres, F Dichgans, J Hallett, M Gerloff, C AF Andres, F Dichgans, J Hallett, M Gerloff, C TI Complex unimanual finger movements are associated with a similar amount of interhemispheric functional coupling as bimanual movements SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Tubingen, Dept Neurol, Cortical Physiol Res Grp, Tubingen, Germany. NINDS, Human Mototr Control Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 1998 VL 30 IS 1-2 SI SI MA 489 BP 188 EP 188 DI 10.1016/S0167-8760(98)90488-3 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 130XY UT WOS:000076546700481 ER PT J AU Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC AF Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC TI Diabetic-like retinopathy: Early and late intervention therapies in galactose-fed rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ALDOSE REDUCTASE INHIBITOR; RETINAL CAPILLARIES; FED DOGS; PREVENTION; TOLRESTAT; SORBINIL; MELLITUS AB PURPOSE. To determine whether the diabetic-like thickening of retinal capillary basement membrane (RCBM) that develops in the galactose-fed rat model of diabetic ocular complications could be halted or ameliorated after 4 or 8 months of galactosemia by treatment with ARI-509, a potent new aldose reductase inhibitor (ARI), or by withdrawal of the galactose diet. METHODS. Weanling female Sprague-Dawley rats were randomized into eight groups and fed laboratory chow plus 50% starch, control group (CON); 50% D-galactose, galactose-fed group (GAL); 50% D-galactose with ARI-509 at 25 mg/kg or 10 mg/kg body wt per day, high-dose prevention group (HDP) and low-dose prevention group (LDP), respectively; 50% D-galactose for 4 or 8 months and then intervention by addition of ARI-509 (25 mg/kg body wt per day), 4-month intervention group (4IN) and 8-month intervention group (8IN), respectively; or 50% D-galactose for 4 or 8 months and then intervention by withdrawing galactose and replacing it with the 50% starch diet, 4-month galactose withdrawal group (4GW) and 8-month galactose withdrawal group (8GW), respectively. After 4, 8, 16, and 24 months of the experimental diets, the levels of carbohydrates in tissues and the extent of RCBM thickening in capillaries of the outer plexiform layer were determined in all groups. RESULTS. Retinal polyol was reduced by 95% in all ARI-treated groups and by 100% in the 4GW and 8GW groups after withdrawal of the galactose. The mean RCBM thickness increased rapidly in GAL rats, becoming almost two times greater (189 +/- 9.4 nm) than in CON rats (103 +/- 3.4 nm) by 24 months. Treatment with ARI-509 in high and low doses (HDP, LDP) initiated with the introduction of the galactose diet significantly prevented RCBM thickening at all time points (P < 0.05). In contrast, intervention by withdrawing galactose from the diet or by adding the high dose of ARI-509 had no significant effect (P < 0.05) on RCBM thickening until the 24-month time point (4IN, 166 +/- 10.3 nm; 8IN, 161 +/- 8.2 nm; 4GW, 136 +/- 5.1 nm; 8GW, 163 +/- 9.6 nm). CONCLUSIONS. Both early and late interventions decreased RCBM thickening compared with that in untreated GAL rats. The decreased thickening, however, was not evident until 16 to 20 months after the intervention Because RCBM thickening is one of the earliest changes in diabetic and galactosemic retinopathy, the findings suggest that RCBM thickening and possibly subsequent retinal lesions are caused by early biochemical alterations induced by the galactose diet that are not readily reversed. The delayed response to therapy is consistent with that observed in the Diabetes Control and Complications Trial. The cumulative evidence indicates that intervention should begin as early after onset of diabetes as possible, and long follow-up periods should be used to evaluate efficacy. C1 National Eye Institute, NIH, Bethesda, MD 20892 USA. Wyeth Ayerst Labs Res, Princeton, NJ USA. RP Robison, WG (reprint author), National Eye Institute, NIH, Bldg 6,Room 316, Bethesda, MD 20892 USA. NR 24 TC 24 Z9 24 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1998 VL 39 IS 10 BP 1933 EP 1941 PG 9 WC Ophthalmology SC Ophthalmology GA 113RD UT WOS:000075564300019 PM 9727416 ER PT J AU Ho, VB Foo, TKF AF Ho, VB Foo, TKF TI Optimization of gadolinium-enhanced magnetic resonance angiography using an automated bolus-detection algorithm (MR SmartPrep) - Original investigation SO INVESTIGATIVE RADIOLOGY LA English DT Article DE magnetic resonance : vascular studies; contrast enhancement; technology; gadolinium ID AORTA; TIME; AORTOGRAPHY; ACQUISITION; ARTERIES; ARRIVAL; DISEASE; ORDER AB Gadolinium (Gd)-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) is a quick method for performing noninvasive diagnostic angiography, A major technical obstacle to the successful implementation of this technique, however, is the proper coordination of the data acquisition with the contrast bolus, In this article, the use of an automated bolus-detection algorithm (MR SmartPrep), which triggers the initiation of data acquisition for Gd-enhanced 3D MRA is reviewed. Potential applications of this evolving technique are illustrated. C1 Uniformed Serv Univ Hlth Sci, Dept Radiol, MR Res Div, Bethesda, MD 20814 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. GE, Med Syst, Appl Sci Lab, Bethesda, MD USA. RP Ho, VB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Radiol, MR Res Div, Bethesda, MD 20814 USA. NR 25 TC 43 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 1998 VL 33 IS 9 BP 515 EP 523 DI 10.1097/00004424-199809000-00006 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118MT UT WOS:000075842800006 PM 9766035 ER PT J AU Fee, E AF Fee, E TI Sir Arthur Newsholme and state medicine, 1885-1935. SO ISIS LA English DT Book Review C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0021-1753 J9 ISIS JI Isis PD SEP PY 1998 VL 89 IS 3 BP 560 EP 561 DI 10.1086/384125 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA 128YN UT WOS:000076436100059 ER PT J AU Judd, LL Akiskal, HS Maser, JD Zeller, PJ Endicott, J Coryell, W Paulus, MP Kunovac, JL Leon, AC Mueller, TI Rice, JA Keller, MB AF Judd, LL Akiskal, HS Maser, JD Zeller, PJ Endicott, J Coryell, W Paulus, MP Kunovac, JL Leon, AC Mueller, TI Rice, JA Keller, MB TI Major depressive disorder: A prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE MDE recovery; residual symptoms; rapid episode relapse ID BRANCH COLLABORATIVE PROGRAM; CONTINUATION THERAPY; FOLLOW-UP; RECOVERY; PSYCHOBIOLOGY; RECURRENCE; REMISSION; ILLNESS AB Background: The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. Methods: MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N = 82) and asymptomatic (N = 155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. Results: Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median = 68 vs. 23 weeks) and to any depressive episode > 5 times faster (median = 33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR = 3.65) and was stronger than history of recurrent MDEs (OR = 1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. Limitations: Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. Conclusions: NIDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Natl Inst Mental Hlth Collaborat Program Psychobi, San Diego, CA USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. San Diego VAMC, Psychiat Serv, San Diego, CA USA. RP Judd, LL (reprint author), Natl Inst Mental Hlth Collaborat Program Psychobi, San Diego, CA USA. FU NIMH NIH HHS [R01 MH025478]; PHPPO CDC HHS [PHSMH30914, PHSMH49671] NR 37 TC 376 Z9 384 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 1998 VL 50 IS 2-3 BP 97 EP 108 DI 10.1016/S0165-0327(98)00138-4 PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 146HC UT WOS:000077422400006 PM 9858069 ER PT J AU Hizawa, N Freidhoff, LR Chiu, YF Ehrlich, E Luehr, CA Anderson, JL Duffy, DL Duston, GM Weber, JL Huang, SK Barnes, KC Marsh, DG Beaty, TH AF Hizawa, N Freidhoff, LR Chiu, YF Ehrlich, E Luehr, CA Anderson, JL Duffy, DL Duston, GM Weber, JL Huang, SK Barnes, KC Marsh, DG Beaty, TH CA Collaborative Study Genetics Asthma TI Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: A genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID HOUSE-DUST-MITE; HUMAN IMMUNE-RESPONSE; IMMUNOGLOBULIN-E RESPONSES; SHORT RAGWEED ALLERGEN; DER-P-I; UNDERLYING ASTHMA; BIOZZI MICE; POLLEN; SENSITIVITY; MARKERS AB Background: Dermatophagoides pteronyssinus (Der p) is one of the most frequently implicated allergens in atopic diseases. Although HLA could play an important role in the development of the IgE response to the Der p allergens, genetic regulation by non-HLA genes influences certain HLA-associated IgE responses to complex allergens. Objective: To clarify genetic control for the expression of Der p-specific IgE, responsiveness, we conducted a genome-wide search for genes influencing Der p-specific IgE antibody levels by using 45 Caucasian and 53 African American families ascertained as part of the Collaborative Study on tho Genetics of Asthma (CSGA). Methods: Specific IgE antibody levels to the Der p crude allergen and to the purified allergens Der p 1 and Der p 2 were measured. Multipoint, nonparametric linkage analysis of 370 polymorphic markers was performed with the GENE-HUNTER program. Results: The best evidence of genes controlling specific IgE response to Der p was obtained in 2 novel regions: chromosomes 2q21-q23 (P =.0033 for Caucasian subjects) and 8p23-p21 (P =.0011 for African American subjects). Three regions previously proposed as candidate regions for atopy, total IgE, or asthma also showed evidence for linkage to Der p-specific IgE responsiveness: 6p21 (P =.0064) and 13q32-q34 (P = 0.0064) in Caucasian subjects and 5q23-q33 (P = 0.0071) in African American subjects. Conclusions: No single locus generated overwhelming evidence for linkage in terms of established criteria and guidelines for a genome-wide screening, which supports previous assertions of a heterogeneous etiology for Der p-specific IgE responsiveness. Two novel regions, 2q21-q23 and 8p23-p21, that were identified in this study merit additional study. C1 Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA. Johns Hopkins Sch Hyg, Dept Biostat, Baltimore, MD USA. Beckman Instruments Inc, Chaska, MN USA. Johns Hopkins Sch Hyg, Dept Epidemiol, Baltimore, MD USA. Queensland Inst Med Res, Epidemiol & Populat Hlth Unit, Brisbane, Qld 4006, Australia. Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. NHLBI, Bethesda, MD 20892 USA. RP Huang, SK (reprint author), Johns Hopkins Asthma & Allergy Ctr, Sch Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. RI Chiu, Yen-Feng /E-3847-2010; Huang, Shau-Ku/F-5509-2010; Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X FU NHLBI NIH HHS [HL/AI 49612]; NIAID NIH HHS [AI20059] NR 47 TC 70 Z9 71 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1998 VL 102 IS 3 BP 436 EP 442 DI 10.1016/S0091-6749(98)70132-0 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 124ZN UT WOS:000076212800017 PM 9768585 ER PT J AU Hizawa, N Collins, G Rafnar, T Huang, SK Duffy, DL Weber, JL Freidhoff, LR Ehrlich, E Marsh, DG Beaty, TH Barnes, KC AF Hizawa, N Collins, G Rafnar, T Huang, SK Duffy, DL Weber, JL Freidhoff, LR Ehrlich, E Marsh, DG Beaty, TH Barnes, KC CA Collaborative Study Genetics Asthma TI Linkage analysis of Dermatophagoides pteronyssinus-specific IgE responsiveness with polymorphic markers on chromosome 6p21 (HLA-D region) in Caucasian families by the transmission/disequilibrium test SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-E RESPONSES; HUMAN IMMUNE-RESPONSE; P-I; ASTHMA; ALLERGEN; ANTIGEN; ASSOCIATION; ACTIVATION; GENOTYPES; GENETICS AB Background: Recently, we have obtained evidence for linkage between Der p 1-specific IgE antibodies and markers on chromosome 6p21 (HLA-D region) in a genome-wide screening in Caucasian families recruited as a part of the Collaborative Study on the Genetics of Asthma (CSGA). Objective: Specific IgE antibodies toward different Dermatophagoides pteronyssinus (Der p) polypeptides were detected by immunoblotting analysis, and the transmission/disequilibrium test (TDT) was performed between specific IgE responsiveness toward each different Der p polypeptide and markers on chromosome 6p21 to better clarify the genetic contribution of HLA-D genes. Methods: We studied 299 individuals in 45 Caucasian families participating in the CSGA. Serum samples from 137 individuals that showed elevated specific IgE antibodies toward the Der p crude allergen (> -0.5 log IU/mL) by ACCESS immunoassay were subjected to immunoblotting analysis. TDT was conducted between the presence of specific IgE antibodies toward each of It different Der p polypeptides and 4 polymorphic markers on chromosome 6p21. Results: The 196-bp allele of D6S1281 and the 104-bp allele of DQCAR showed significant excess transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 55 kd, 45 kd, or 37 kd), In contrast, the 200-bp allele of D6S1281 and the 204-bp allele of D6S291 showed significantly decreased transmission to specific IgE responders toward a particular Der p polypeptide (120 kd, 90 kd, 52 kd, or 45 kd). Deviation from the expected 50% transmission in heterozygous parents was statistically significant after correcting for multiple comparisons. Conclusion: This study supported our previous findings that genes on chromosome 6p21 (HLA-D region) may influence the expression of Der p-specific IgE responsiveness in this Caucasian population. Our results, however, reveal the complexity of genetic regulations of Der p-specific IgE responsiveness by HLA-D genes, suggesting the strong influence of non-HLA loci and perhaps environmental factors for the development of Der p-specific IgE responsiveness. C1 Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol, Baltimore, MD 21224 USA. NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Iceland Canc Soc, Reykjavik, Iceland. Johns Hopkins Sch Hyg, Dept Epidemiol, Baltimore, MD USA. Queensland Inst Med Res, Epidemiol & Pollut Hlth Unit, Brisbane, Qld 4006, Australia. NHLBI, Bethesda, MD 20892 USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. RP Huang, SK (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. RI Huang, Shau-Ku/F-5509-2010; Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X FU NHLBI NIH HHS [HL/AI49612]; NIAID NIH HHS [AI20059] NR 28 TC 29 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1998 VL 102 IS 3 BP 443 EP 448 DI 10.1016/S0091-6749(98)70133-2 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 124ZN UT WOS:000076212800018 PM 9768586 ER PT J AU Hizawa, N Freidhoff, LR Ehrlich, E Chiu, YF Duffy, DL Schou, C Dunston, GM Beaty, TH Marsh, DG Barnes, KC Huang, SK AF Hizawa, N Freidhoff, LR Ehrlich, E Chiu, YF Duffy, DL Schou, C Dunston, GM Beaty, TH Marsh, DG Barnes, KC Huang, SK CA Collaborative Study Genetics Asthma CSGA TI Genetic influences of chromosomes 5q31-q33 and 11q13 on specific IgE responsiveness to common inhaled allergens among African American families SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE atopy; skin prick test; chromosome 5q31-q33; chromosome 11q13; multipoint linkage analysis ID LINKAGE ANALYSIS; SERUM IGE; UNDERLYING ASTHMA; ATOPY; LOCALIZATION; SENSITIVITY; RESPONSES; MARKERS; DENSITY AB Background: We have recently conducted a genome-wide screening for genes influencing Dermatophagoides pteronyssinus-specific IgE responsiveness as a part of the Collaborative Study on the Genetics of Asthma (CSGA), which showed evidence for linkage in some regions, including chromosomes 5q31-q33 and 11q13 in African American families. Objectives: To clarify relative contributions of these regions to atopy in the same African American population, we have conducted further genetic linkage studies of specific IgE responses toward common inhaled allergens. Methods: We studied 328 individuals in 58 African American families participating in the CSGA, Specific IgE responses toward Dermatophagoides farinae, cat, dog, American cockroach, rye grass, and Bermuda grass, as measured by skin tests, were used for multipoint linkage analysis with polymorphic markers on chromosomes 5q31-q33 and 11q13. Results: Specific IgE response toward American cockroach showed evidence for linkage to chromosomes 5q31-q33 (P =.0050) and 11q13 (P =.017). Specific IgE response toward dog showed evidence for linkage with chromosome 5q31-q33 (P =.0043). Evidence for linkage with chromosome 11q13 was obtained for specific IgE responses toward Dermatophagoides farinae (P =.012), cat (P =.035), and Bermuda grass (P =.017). The presence of a positive ST response for at least 1 of 30 common allergens showed evidence for linkage to chromosomes 5q31-q33 (P =.017) and 11q13 (P =.00058). Conclusions: These data support that genes on both chromosomes 5q31-q33 and 11q13 confer susceptibility to upregulated IgE-mediated immune responses in this African American population. The putative genes on chromosomes 5q31-q33 and 11q13, however, showed contrasting effects on atopy, which may result from strong gene-environmental interactions. C1 Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol, Baltimore, MD 21224 USA. Johns Hopkins Sch Hyg, Dept Biostat, Baltimore, MD USA. Johns Hopkins Sch Hyg, Dept Epidemiol, Baltimore, MD USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. ALK Labs, Horsholm, Denmark. Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. RP Huang, SK (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. RI Chiu, Yen-Feng /E-3847-2010; Huang, Shau-Ku/F-5509-2010; Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X FU NHLBI NIH HHS [HL/AI 49612]; NIAID NIH HHS [AI20059] NR 24 TC 62 Z9 63 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1998 VL 102 IS 3 BP 449 EP 453 DI 10.1016/S0091-6749(98)70134-4 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 124ZN UT WOS:000076212800020 PM 9768587 ER PT J AU Worobec, AS Akin, C Scott, LM Metcalfe, DD AF Worobec, AS Akin, C Scott, LM Metcalfe, DD TI Cytogenetic abnormalities and their lack of relationship to the Asp816Val c-kit mutation in the pathogenesis of mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID PROTOONCOGENE C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Worobec, AS (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C-205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 5 TC 13 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1998 VL 102 IS 3 BP 523 EP 524 DI 10.1016/S0091-6749(98)70144-7 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 124ZN UT WOS:000076212800031 PM 9768597 ER PT J AU McLenigan, M Peat, TS Frank, EG McDonald, JP Gonzalez, M Levine, AS Hendrickson, WA Woodgate, R AF McLenigan, M Peat, TS Frank, EG McDonald, JP Gonzalez, M Levine, AS Hendrickson, WA Woodgate, R TI Novel Escherichia coli umuD' mutants: Structure-function insights into SOS mutagenesis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; RECA PROTEIN; ULTRAVIOLET-LIGHT; MUTATOR ACTIVITY; UV MUTAGENESIS; INTACT UMUD; DNA-REPAIR; CLEAVAGE; TRANSFORMATION; MUTATIONS AB Although it has been 10 years since the discovery that the Escherichia coli UmuD protein undergoes a RecA-mediated cleavage reaction to generate mutagenically active UmuD', the function of UmuD' has yet to be determined. In an attempt to elucidate the role of UmuD' in SOS mutagenesis, we have utilized a colorimetric papillation assay to screen for mutants of a hydroxylamine-treated, low-copy-number umuD' plasmid that are unable to promote SOS-dependent spontaneous mutagenesis, Using such an approach, we have identified 14 independent umuD' mutants. Analysis of these mutants revealed that two resulted from promoter changes which reduced the expression of wild-type UmuD', three were nonsense mutations that resulted in a truncated UmuD' protein, and the remaining nine were missense alterations. In addition to the hydroxylamine-generated mutants, we have subcloned the mutations found in three chromosomal umuD1, umuD44, and umuD77 alleles into umuD'. All 17 umuD' mutants resulted in lower levels of SOS dependent spontaneous mutagenesis but varied in the extent to which they promoted methyl methanesulfonate-induced mutagenesis, We have attempted to correlate these phenotypes with the potential effect of each mutation on the recently described structure of UmuD'. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RP Woodgate, R (reprint author), NICHD, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov RI Peat, Thomas/F-9817-2010 OI Peat, Thomas/0000-0002-6488-0831 NR 41 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1998 VL 180 IS 17 BP 4658 EP 4666 PG 9 WC Microbiology SC Microbiology GA 114PZ UT WOS:000075619100045 PM 9721309 ER PT J AU Stevenson, B Bono, JL Elias, A Tilly, K Rosa, P AF Stevenson, B Bono, JL Elias, A Tilly, K Rosa, P TI Transformation of the Lyme disease spirochete Borrelia burgdorferi with heterologous DNA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GENETIC-TRANSFORMATION; NUCLEOTIDE-SEQUENCE; CIRCULAR PLASMID; SERODIAGNOSIS; INACTIVATION; EXPRESSION; VECTORS; CLONING; GYRB AB Studies of the spirochete Borrelia burgdorferi have been hindered by the scarcity of genetic tools that can be used in these bacteria. For the first time, a method has been developed by which heterologous DNA (DNA without a naturally occurring B. burgdorferi homolog) can be introduced into and persistently maintained by B. burgdorferi. This technique uses integration of circular DNA into the bacterial genome via a single-crossover event. The ability to transform B. burgdorferi with heterologous DNA will now permit a wide range of experiments on the biology of these bacteria and their involvement in the many facets of Lyme disease. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. RP Stevenson, B (reprint author), Univ Kentucky, Coll Med, Dept Microbiol & Immunol, Med Ctr MS415, Lexington, KY 40536 USA. NR 36 TC 17 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1998 VL 180 IS 18 BP 4850 EP 4855 PG 6 WC Microbiology SC Microbiology GA 120WG UT WOS:000075979900012 PM 9733687 ER PT J AU Posch, PE Borrego, F Brooks, AG Coligan, JE AF Posch, PE Borrego, F Brooks, AG Coligan, JE TI HLA-E is the ligand for the natural killer cell CD94/NKG2 receptors SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE natural killer cells; HLA-E; CD94; NKG2; major histocompatibility complex, class I ID CLASS-I MOLECULES; MHC CLASS-I; MAJOR HISTOCOMPATIBILITY COMPLEX; ANTI-KP43 MONOCLONAL-ANTIBODY; C-TYPE LECTINS; INHIBITORY RECEPTOR; NK CELL; PEPTIDE BINDING; LYMPHOCYTES-T; ANTIGEN RECOGNITION AB CD94/NKG2 is a recently described receptor present on natural killer (NK) cells and certain T cells that is composed of the CD94 chain covalently associated with a member of the NKG2 family of molecules. Both chains are glycosylated members of the C-type lectin superfamily. The CD94/NKG2 receptors are functionally heterogenous depending on which NKG2 family member is associated with CD94. Initially, it was thought that CD94/NKG2 receptors recognized a broad array of HLA-A, -B and -C (classical), as well as the nonclassical HLA-G, MHC class I molecules. Instead, recent data have suggested that this receptor is specific for HLA-E complexed with a peptide derived from the signal sequence (residues 3-11) of certain classical MHC class I molecules. Position 2 (residue 4) in the signal sequence derived peptides appears pivotal in determining whether the HLA-E/peptide complex confers resistance to NK-mediated lysis. The potential roles that the CD94/NKG2-HLA-E receptor ligand interaction might play in infection and tumor development are discussed. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIAID, Struct Biol Sec, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2, Rockville, MD 20852 USA. NR 102 TC 21 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1998 VL 5 IS 5 BP 321 EP 331 DI 10.1159/000025346 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 127WP UT WOS:000076373800002 PM 9758906 ER PT J AU Shi, YF Chang, AC Jiang, H Wu, TC AF Shi, YF Chang, AC Jiang, H Wu, TC TI Advances in biomedical research - The Fifth Annual Joint Scientific Symposium of NIH/FDA CAA and Washington DC Chapter of SCBA, Bethesda, Md., August 29, 1998 SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article C1 Amer Red Cross, Holland Lab, Washington, DC 20006 USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Shi, YF (reprint author), Amer Red Cross, Holland Lab, Washington, DC 20006 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1998 VL 5 IS 5 BP 395 EP 399 DI 10.1007/BF02253449 PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 127WP UT WOS:000076373800009 ER PT J AU Stanton, H Gavrilovic, J Atkinson, SJ d'Ortho, MP Yamada, KM Zardi, L Murphy, G AF Stanton, H Gavrilovic, J Atkinson, SJ d'Ortho, MP Yamada, KM Zardi, L Murphy, G TI The activation of ProMMP-2 (gelatinase A) by HT1080 fibrosarcoma cells is promoted by culture on a fibronectin substrate and is concomitant with an increase in processing of MT1-MMP (MMP-14) to a 45 kDa form SO JOURNAL OF CELL SCIENCE LA English DT Article DE fibronectin; MMP-2 activation; MT1-MMP; alpha(5)beta(1) integrin ID C-TERMINAL DOMAIN; COLLAGENASE GENE-EXPRESSION; PROGELATINASE-A; MATRIX METALLOPROTEINASE-1; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; TISSUE INHIBITOR; IV COLLAGENASE; GROWTH-FACTORS; INTEGRIN AB We have assessed the effect of fibronectin and laminin-1 on the expression of molecules involved in the activation pathway of MMP-2, a key proteinase in tissue remodelling HT1080 fibrosarcoma cells cultured on fibronectin were shown to activate endogenous MMP-2, to a level comparable with that elicited by treatment with phorbol ester, In contrast, the MMP-2 expressed by HT1080 cells cultured on laminin-1 was mainly in the pro- (inactive form). Culture of the cells on peptide fragments of fibronectin derived from the central cell binding domain also promoted MMP-2 activation, indicating that signals via fibronectin binding to integrin receptors may be involved. HT1080 cells cultured on immobilised antibodies to the alpha 5 and beta 1 integrin subunits secreted levels of active MMP-2 similar to those observed for full length fibronectin, whereas cells cultured an an antibody to the alpha 6 integrin subunit secreted mainly proMMP-2. The data demonstrate that the activation of MMP-2 by HT1080 cells is regulated by the nature of the extracellular matrix, and that signals via the alpha 5 beta 1 integrin receptor may be involved in the fibronectin induced up-regulation of MMP-2 activation, We then assessed the effect of fibronectin on the components of the putative MT1-MMP/TIMP-2 'receptor' complex implicated in MMP-2 activation. Levels of TIMP-2 protein expressed by HT1080 cells did not vary detectably between cells cultured on fibronectin or laminin-1. However, the expression of MT1-MMP protein was upregulated when the cells were cultured on fibronectin, which could be attributed to an increase in levels of a truncated 45 kDa form, Parallel studies using gelatin zymography demonstrated that the up-regulation of the production of the 45 kDa band was concomitant with MMP-2 activation. Inhibitor studies revealed that the truncation of MT1-MMP to a 45 kDa form is MMP mediated, although not inhibited by TIMP-1. In vitro, the 45 kDa form could be generated by cleavage of membrane-bound native MT1-MMP with several recombinant MMPs, including both active MT1-MMP and MMP-2, The implication that either MMP-2 or MT1-MMP can process MT1-MMP to 45 kDa, raises the possibilitS that truncation of MT1-MMP represents a self-regulatory end-point in the activation pathway of MMP-2. C1 Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. Fac Med Creteil, INSERM U492, F-94010 Creteil, France. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Ist Nazl Ric Canc, Cell Biol Lab, I-16132 Genoa, Italy. RP Stanton, H (reprint author), Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England. EM g.murphy@uea.ac.uk OI Yamada, Kenneth/0000-0003-1512-6805 NR 63 TC 192 Z9 192 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1998 VL 111 BP 2789 EP 2798 PN 18 PG 10 WC Cell Biology SC Cell Biology GA 130UL UT WOS:000076538700009 PM 9718371 ER PT J AU Sung, V Stubbs, JT Fisher, L Aaron, AD Thompson, EW AF Sung, V Stubbs, JT Fisher, L Aaron, AD Thompson, EW TI Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha v beta 3 and alpha v beta 5 integrins SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CARCINOMA CELLS; IN-VITRO; ATTACHMENT DOMAIN; RAT OSTEOCLASTS; EXPRESSION; OSTEOPONTIN; MATRIX; ALPHA(V)BETA(3); RECEPTOR; METASTASES AB Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RCD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSP-RGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Cly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the alpha v beta 3 vitronectin receptor, whereas adhesion acid proliferation responses were alpha v beta 5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for alpha v beta 3 or alpha v beta 5 respectively. Although some expression of the alternate alpha v integrin was still retained, the alpha v beta 5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the alpha v beta 3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses io BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs alpha v beta 3 and alpha v beta 5 integrin receptors. J. Cell. Physiol. 176:482-494, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Melbourne, St Vincents Inst Med Res, VBCRC Breast Canc Res Unit, Fitzroy, Vic 3065, Australia. Univ Melbourne, St Vincents Inst Med Res, Dept Surg, Fitzroy, Vic 3065, Australia. Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Dept Orthoped Surg, Washington, DC 20007 USA. NIDR, Bone Res Branch, NIH, Bethesda, MD 20892 USA. RP Thompson, EW (reprint author), Univ Melbourne, St Vincents Inst Med Res, VBCRC Breast Canc Res Unit, 9 Princes St, Fitzroy, Vic 3065, Australia. RI Thompson, Erik/A-1425-2009 OI Thompson, Erik/0000-0002-9723-4924 FU NCI NIH HHS [2P50-CA58185-04] NR 67 TC 95 Z9 105 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1998 VL 176 IS 3 BP 482 EP 494 DI 10.1002/(SICI)1097-4652(199809)176:3<482::AID-JCP5>3.0.CO;2-K PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 105DB UT WOS:000075056400005 PM 9699501 ER PT J AU Ohtsuki, T Jaffe, H Brenner, M Azzam, N Azzam, R Frerichs, KU Hallenbeck, JM AF Ohtsuki, T Jaffe, H Brenner, M Azzam, N Azzam, R Frerichs, KU Hallenbeck, JM TI Stimulation of tyrosine phosphorylation of a brain protein by hibernation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ground squirrel; ischemic tolerance; tyrosine kinase; membrane phosphotyrosine protein ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; CEREBRAL-ISCHEMIA; MAMMALIAN HIBERNATION; KINASE; ACTIVATION; RECEPTOR; HYPOXIA; STROKE AB Mammalian hibernation is a state of natural tolerance to severely decreased brain blood flow. As protein tyrosine phosphorylation is believed to be involved in the development of resistance to potentially cell-damaging insults, we used immunoblotting for the phosphotyrosine moiety to analyze extracts from various tissues of hibernating and nonhibernating ground squirrels. A single, hibernation-specific phosphoprotein was detected in the brain, but not in any other tissue tested. This protein: designated pp98 to reflect its apparent molecular weight, is distributed throughout the brain, and is associated with the cellular membrane fraction. The presence of the protein is tightly linked to the hibernation state; it is not present in contemporaneously assayed animals that are exposed to the same cold temperature as the hibernators, is present for the duration of a hibernation bout (tested from 1 to 14 days), and disappears within 1 hour of arousal from hibernation. The close association of pp98 with the hibernation state, its presence in cellular membranes, and the known properties of membrane phosphotyrosine proteins suggest that it may transduce a signal for adaptation to the limited availability of oxygen and glucose and low cellular temperature that characterizes hibernation in the ground squirrel. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Stroke Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP NINDS, Stroke Branch, NIH, Bldg 36,Rm 4A03,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 28 TC 13 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1998 VL 18 IS 9 BP 1040 EP 1045 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 118LK UT WOS:000075839500015 PM 9740108 ER PT J AU Nicklaus, MC Williams, RW Bienfait, B Billings, ES Hodoscek, M AF Nicklaus, MC Williams, RW Bienfait, B Billings, ES Hodoscek, M TI Computational chemistry on commodity-type computers SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID EXCHANGE AB A number of inexpensive computers were benchmarked with the ab initio program Gaussian 94, using both small standard test jobs and larger density functional (DFT) calculations. Several varieties of Pentium (x86) and Alpha CPU based systems were tested. Most of them were running under the open source code operating system Linux. They were compared with several workstations and supercomputers. The most powerful of:today's commodity-type processors surpassed current supercomputers-in speed. The choice of compilers and compilation options was often found to have a larger influence on job CPU times than details of the hardware. Especially on the x86 type machines, the-jobs always ran faster the less memory (RAM) they. were given. The fastest machine on a per-CPU basis was an Alpha/Linux system. For the DFT calculation, it was close to twice as fast as a Cray J90 supercomputer. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Chem, Ljubljana, Slovenia. RP Nicklaus, MC (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Nicklaus, Marc/N-4183-2014 NR 12 TC 8 Z9 8 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 1998 VL 38 IS 5 BP 893 EP 905 DI 10.1021/ci9800920 PG 13 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 123BU UT WOS:000076106600020 PM 9770303 ER PT J AU Garvey, MA Giedd, J Swedo, SE AF Garvey, MA Giedd, J Swedo, SE TI PANDAS: The search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever SO JOURNAL OF CHILD NEUROLOGY LA English DT Review ID OBSESSIVE-COMPULSIVE-DISORDER; LA-TOURETTES-SYNDROME; A STREPTOCOCCAL INFECTIONS; SINGLE SCHOOL-DISTRICT; 7-YEAR FOLLOW-UP; SYDENHAMS CHOREA; PHARYNGEAL CELLS; ANTINEURONAL ANTIBODIES; CLINICAL PHENOMENOLOGY; HUNTINGTONS-DISEASE AB Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections. The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or ties. This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements. When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever. In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders. We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study. C1 NINDS, Pediat & Dev Neuropsychiat Branch, NIMH, Human Motor Control Sect,MNB, Bethesda, MD 20892 USA. RP Garvey, MA (reprint author), NINDS, Pediat & Dev Neuropsychiat Branch, NIMH, Human Motor Control Sect,MNB, 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 124 TC 77 Z9 79 U1 7 U2 8 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 1998 VL 13 IS 9 BP 413 EP 423 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 112UN UT WOS:000075512900001 PM 9733286 ER PT J AU Merke, DP Cutler, GB AF Merke, DP Cutler, GB TI The role of laparoscopic surgery in adrenal disease: A pediatric perspective SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; HYPERPLASIA; STANDARD; CHILDREN; TUMORS; GIRL; CARE C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Merke, DP (reprint author), NICHHD, Dev Endocrinol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3046 EP 3048 DI 10.1210/jc.83.9.3046 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700006 ER PT J AU Ross, JL Roeltgen, D Feuillan, P Kushner, H Cutler, GB AF Ross, JL Roeltgen, D Feuillan, P Kushner, H Cutler, GB TI Effects of estrogen on nonverbal processing speed and motor function in girls with Turner's syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NORMAL CHILDREN; SEX STEROIDS; BEHAVIOR; COGNITION; GROWTH; RATS AB The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and/or visual-perceptual abilities, and difficulty with motor function. In the current study, we investigated motor function and nonverbal processing speed in estrogen- and placebo-treated girls (aged 10-12 years) with TS and in age-matched female controls. The goal of this study was to examine whether estrogen replacement therapy would reverse deficits in motor function and in nonverbal processing speed, a measure of the time required to perform certain disparate nonverbal tasks, in adolescent girls with TS. Children received either estrogen (ethinyl estradiol, 12.5-50 ng/kg.day), or placebo for durations of 1-7 yr (mean, 4.0 +/- 2.1 yr)in this randomized, double blind study. Cognitive and motor tasks administered included the Wechsler Intelligence Scale for Children-Revised; nonspatial, repetitive motor tasks (tapping and three tasks from the Paness); and spatially mediated motor tasks [nongrooved pegboard (Lafayette), pursuit rotor, visual-motor integration, and money street map]. Questionnaires administered included the Self-Perception Profile, the Child Behavior Checklist, and the Piers-Harris Self-Concept Scale. The major result of this study was the positive estrogen treatment effect on nonverbal processing speed and speeded motor performance in 12-yr-old TS girls. That motor performance would be slower in estrogen-deficient TS females is consistent with previous studies of the influence of estrogen on motor function. Estrogen replacement is thus the most likely explanation for the improved motor speed and nonverbal processing time in the estrogen-treated TS girls compared to that in the placebo-treated TS girls. Whether these findings will influence the psychoeducational outcome or quality of life of females with TS is not yet known. C1 Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA 19107 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Susquehanna Hlth Syst, Williamsport, PA 17701 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Dept Pediat, 1025 Walnut St, Philadelphia, PA 19107 USA. FU NINDS NIH HHS [NS-29857] NR 42 TC 79 Z9 81 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3198 EP 3204 DI 10.1210/jc.83.9.3198 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700032 PM 9745426 ER PT J AU Torpy, DJ Gordon, RD Lin, JP Huggard, PR Taymans, SE Stowasser, M Chrousos, GP Stratakis, CA AF Torpy, DJ Gordon, RD Lin, JP Huggard, PR Taymans, SE Stowasser, M Chrousos, GP Stratakis, CA TI Familial hyperaldosteronism type II: Description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA-RENIN ACTIVITY; LINKAGE ANALYSIS; LONG ARM; HYPERTENSION; DIAGNOSIS; ADENOMA; MAP; HUMAN-CHROMOSOME-8; DEXAMETHASONE; DISORDERS AB Familial hyperaldosteronism type II (FH-II) is characterized by autosomal dominant inheritance and hypersecretion of aldosterone due to adrenocortical hyperplasia or an aldosterone-producing adenoma; unlike FH type I (FH-I), hyperaldosteronism in FH-II is not suppressible by dexamethasone. Of a total of 17 FH-II families with 44 affected members, we studied a large kindred with 7 affected members that was informative for linkage analysis. Family members were screened with the aldosterone/PRA ratio test; patients with aldosterone/PRA ratio greater than 25 underwent fludrocortisone/salt suppression testing for confirmation of autonomous aldosterone secretion. Postural testing, adrenal gland imaging, and adrenal venous sampling were also performed. Individuals affected by FH-II demonstrated lack of suppression of plasma A levels after 4 days of dexamethasone treatment (0.5 mg every 6 h). All patients had neg ative genetic testing for the defect associated with FH-I, the CYP11B1/CYP11B2 hybrid gene. Genetic linkage was then examined between FH-II and aldosterone synthase (the CYP11B2 gene) on chromosome 8q. A polyadenylase repeat within the 5'-region of the CYP11B2 gene and 9 other markers covering an approximately 80-centimorgan area on chromosome 8q21-8qtel were genotyped and analyzed for linkage. Two-point logarithm of odds scores were negative and ranged from -12.6 for the CYP11B2 polymorphic marker to -0.98 for the D8S527 marker at a recombination distance (theta) of 0. Multipoint logarithm of odds score analysis confirmed the exclusion of the chromosome 8q21-8qtel area as a region harboring the candidate gene for FH-II in this family. We conclude that FH-II shares autosomal dominant inheritance and hyperaldosteronism with FH-I, but, as demonstrated by the large kindred investigated in this report, it is clinically and genetically distinct. Linkage analysis demonstrated that the CYP11B2 gene is not responsible for FH-II in this family; furthermore, chromosome 8q21-8qtel most likely does not harbor the genetic defect in this kindred. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Sect Genet Studies, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Greenslopes Hosp, Hypertens Unit, Brisbane, Qld 4120, Australia. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10 N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov RI Stowasser, Michael/F-4121-2010; Gordon, Richard/K-2555-2012 NR 47 TC 51 Z9 52 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3214 EP 3218 DI 10.1210/jc.83.9.3214 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700036 PM 9745430 ER PT J AU Deuster, PA Petrides, JS Singh, A Lucci, EB Chrousos, GP Gold, PW AF Deuster, PA Petrides, JS Singh, A Lucci, EB Chrousos, GP Gold, PW TI High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: Sexually dimorphic responses SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL-AXIS; ARGININE-VASOPRESSIN; TREADMILL EXERCISE; MARKED DIFFERENCES; MEDIAN-EMINENCE; STRESS; DEPRESSION; SECRETION; DISORDERS AB Exercise promotes escape of ACTH and cortisol from suppression by dexamethasone (DEX) in some healthy men and women. To determine whether stimulus strength, diurnal rhythmicity, or gender influences neuroendocrine escape during DEX suppression, we studied men (n = 5) and women (n = 5) during high intensity exercise tests after taking 4 mg DEX: two tests (one at 90% and one at 100% of maximal aerobic capacity) were conducted in the morning and two were performed in the afternoon on nonconsecutive days. Plasma ACTH and cortisol showed significantly greater increases with the 100% compared to the 90% intensity exercise (ACTH: 90%, 2 +/- 0.4; 100%, 3 +/- 0.5 pmol/L; cortisol: 90%, 53 +/- 5.3; 100%, 93 +/- 23.6 nmol/L). Plasma cortisol responses were significantly higher in women than in men (P < 0.01). Plasma arginine vasopressin (AVP) exhibited significant intensity-dependent increases, with higher responses in women than men (P < 0.01). In conclusion, despite high dose glucocorticoid pretreatment, intense exercise can override the glucocorticoid negative feedback of hypothalamic-pituitary-adrenal activation in most normal men and women. This ability to override cortisol negative feedback inhibition may relate to the magnitude of the AVP response, the potency/specificity of the stressor to elicit a CRH/AVP response, and/or the sensitivity of the glucocorticoid negative feedback system at the time of the stress. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Dev Endocrinol Branch, Bethesda, MD 20814 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20814 USA. NICHHD, Bethesda, MD 20814 USA. RP Deuster, PA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Dev Endocrinol Branch, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM pdeuster@usuhs.mil RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 37 TC 40 Z9 41 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3332 EP 3338 DI 10.1210/jc.83.9.3332 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700056 PM 9745450 ER PT J AU Friedman, TC Papanicolaou, DA AF Friedman, TC Papanicolaou, DA TI Comment on high urinary free cortisol excretion in a patient with psychogenic polydipsia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID CUSHINGS-SYNDROME; STATES C1 Cedars Sinai Med Ctr, Div Endocrinol, Los Angeles, CA 90048 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Friedman, TC (reprint author), Cedars Sinai Med Ctr, Div Endocrinol, D-2019,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3378 EP 3378 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700067 PM 9745460 ER PT J AU Mericq, MV AF Mericq, MV TI High fluid intake increases urine free cortisol excretion in normal subjects - Authors' response SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Mericq, MV (reprint author), Univ Chile, IDMI, Casilla 226-3, Santiago, Chile. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3378 EP 3379 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700068 ER PT J AU Tsigos, C Kyrou, I Chrousos, GP Papanicolaou, DA AF Tsigos, C Kyrou, I Chrousos, GP Papanicolaou, DA TI Prolonged suppression of corticosteroid-binding globulin by recombinant human interleukin-6 in man SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID CYTOKINES C1 Hellen Natl Diabet Ctr, Athens 10675, Greece. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Tsigos, C (reprint author), Hellen Natl Diabet Ctr, 3 Ploutarchou St, Athens 10675, Greece. NR 8 TC 32 Z9 32 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1998 VL 83 IS 9 BP 3379 EP 3379 DI 10.1210/jc.83.9.3379 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700069 PM 9745461 ER PT J AU Cohen, CJ Iwane, MK Palensky, JB Levin, DL Meagher, KJ Frost, KR Mayer, KH AF Cohen, CJ Iwane, MK Palensky, JB Levin, DL Meagher, KJ Frost, KR Mayer, KH CA Am Fdn AIDS Res Comm Clin Trial Netw TI A national HIV community cohort: Design, baseline, and follow-up of the AmFAR observational database SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HIV; AIDS; cohort; AmFAR; ODB; observational database AB This article describes the design, methodology, baseline distributions, and general follow-up characteristics of the American Foundation for. AIDS Research (AmFAR) National Observational Database (ODB) Project including the benefits and limitations of collecting information on a large simple cohort in the HIV community setting. The study prospectively followed 15,611 HIV-positive men and women and collected longitudinal and cross sectional data on demographics, medical conditions, drug therapies, laboratory parameters, and survival. Participants were followed between October 1990 and December 1993 by 252 community-based sites coordinated by 22 centers in the Community-Based Clinical Trials Network (CBCT Network) throughout the United States (including Puerto Rico) and Toronto, Canada. The ODB provided quantitative information on a national level needed to track the HIV epidemic and plan clinical trials conducted through the Network, and to provide sites with local databases to monitor patients and facilitate access to therapies in clinical trials. Overall, the ODB contains information on 1,925 women (12%) and 13,686 men (88%), 60% white, 20% African American, 17% Latino/Hispanic, with 56,254 baseline and follow-up farms, a median follow-up of about 12 months, a 16% loss-to-follow-up, and an 11% mortality rate. AmFAR plans to place the ODB in the public domain. J CLIN EPIDEMIOL 51;9:779-793, 1998. (C) 1998 Elsevier Science Inc. C1 Amer Fdn AIDS Res, New York, NY 10005 USA. Community Res Initiat New England, Brookline, MA USA. Stat Collaborat, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. Brown Univ, AIDS Program, Providence, RI 02912 USA. RP Frost, KR (reprint author), Amer Fdn AIDS Res, 120 Wall St,13th Floor, New York, NY 10005 USA. NR 11 TC 14 Z9 14 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 1998 VL 51 IS 9 BP 779 EP 793 DI 10.1016/S0895-4356(98)00043-2 PG 15 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 115DG UT WOS:000075647800010 PM 9731927 ER PT J AU Pracyk, JB Tanaka, K Hegland, DD Kim, KS Sethi, R Rovira, II Blazina, DR Lee, L Bruder, JT Kovesdi, I Goldshmidt-Clermont, PJ Irani, K Finkel, T AF Pracyk, JB Tanaka, K Hegland, DD Kim, KS Sethi, R Rovira, II Blazina, DR Lee, L Bruder, JT Kovesdi, I Goldshmidt-Clermont, PJ Irani, K Finkel, T TI A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GTPase; rac1; myocyte; hypertrophy; signal transduction ID ACTIVATED PROTEIN-KINASE; MUSCLE CELL HYPERTROPHY; ACTIN STRESS FIBERS; GENE-EXPRESSION; C-JUN; ALPHA(1)-ADRENERGIC RECEPTOR; PHOSPHOINOSITIDE 3-KINASE; VENTRICULAR MYOCYTES; CDC42 GTPASES; IN-VITRO AB We have used adenoviral-mediated gene transfer of a constitutively active (V12rac1) and dominant negative (N17rac1) isoform of rad to assess the role of this small GTPase in cardiac myocyte hypertrophy. Expression of V12rac1 in neonatal cardiac myocytes results in sarcomeric reorganization and an increase in cell size that is indistinguishable from ligand-stimulated hypertrophy. In addition, V12rac1 expression leads to an increase in atrial natriuretic peptide secretion. In contrast, expression of N17rac1, but not a truncated form of Raf-1, attenuated the morphological hypertrophy associated with phenylephrine stimulation. Consistent with the observed effects on morphology, expression of V12rac1 resulted in an increase in new protein synthesis, while N17rac1 expression inhibited phenylephrine-induced leucine incorporation. These results suggest rad is an essential element of the signaling pathway leading to cardiac myocyte hypertrophy. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Genvec Inc, Rockville, MD 20852 USA. Ohio State Univ, Heart & Lung Inst, Columbus, OH 43210 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, 10 Ctr Dr,MSC 1650,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 49 TC 110 Z9 111 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1998 VL 102 IS 5 BP 929 EP 937 DI 10.1172/JCI2552 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117JM UT WOS:000075778200009 PM 9727061 ER PT J AU Patel, SB Salen, G Hidaka, H Kwiterovich, PO Stalenhoef, AFH Miettinen, TA Grundy, SM Lee, MH Rubenstein, JS Polymeropoulos, MH Brownstein, MJ AF Patel, SB Salen, G Hidaka, H Kwiterovich, PO Stalenhoef, AFH Miettinen, TA Grundy, SM Lee, MH Rubenstein, JS Polymeropoulos, MH Brownstein, MJ TI Mapping a gene involved in regulating dietary cholesterol absorption - The sitosterolemia locus is found at chromosome 2p21 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE genetics; sitosterolemia; linkage analyses; chromosomal localization ID A REDUCTASE-ACTIVITY; BETA-SITOSTEROLEMIA; LINKAGE ANALYSIS; XANTHOMATOSIS; BIOSYNTHESIS; PHYTOSTEROLEMIA; HETEROZYGOTES; ELIMINATION; METABOLISM; FAMILIES AB The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the body's ability to selectively exclude other dietary sterols are poorly understood. Studies of the rare autosomal recessively inherited disease sitosterolemia (OMIM 210250) may shed some light on these processes. Patients suffering from this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the liver's ability to preferentially and rapidly excrete these non-cholesterol sterols into bile. Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to an advancement in the management of this important cardiovascular risk factor. By studying 10 well-characterized families with this disorder, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0). C1 Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. New Jersey Vet Hlth Care Syst, Gastroenterol Res Lab, E Orange, NJ 07018 USA. Shiga Univ Med Sci, Dept Med 3, Otsu, Shiga 52021, Japan. Johns Hopkins Hosp, Childrens Med & Surg Ctr, Dept Pediat, Baltimore, MD 21287 USA. Univ Nijmegen Hosp, Dept Med, Div Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Helsinki, Cent Hosp, Dept Internal Med, FIN-00290 Helsinki, Finland. NIMH, Gene Mapping Unit, Lab Genet Dis Res, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIMH, Sect Genet People Invest Genes, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Patel, SB (reprint author), Univ Texas, SW Med Ctr, Ctr Human Nutr, Y3-208,5323 Harry Hines Blvd, Dallas, TX 75235 USA. RI Brownstein, Michael/B-8609-2009; Stalenhoef, A.F.H./H-8094-2014; OI Patel, Shailendra/0000-0003-0046-5513 FU NHLBI NIH HHS [HL-17818] NR 25 TC 126 Z9 129 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 1 PY 1998 VL 102 IS 5 BP 1041 EP 1044 DI 10.1172/JCI3963 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117JM UT WOS:000075778200021 PM 9727073 ER PT J AU Lang, PJ Bradley, MM Cuthbert, BN AF Lang, PJ Bradley, MM Cuthbert, BN TI Emotion and motivation: Measuring affective perception SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review ID STARTLE REFLEX MODULATION; ATTENTION; PICTURES; MEMORY; PROBE; FEAR; PARADIGM; PLEASANT; AROUSAL; HUMANS C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Lang, PJ (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, POB 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [MH37757, MH43975, P50-MH52384] NR 77 TC 101 Z9 103 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD SEP PY 1998 VL 15 IS 5 BP 397 EP 408 DI 10.1097/00004691-199809000-00004 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TT UT WOS:000079168400004 PM 9821067 ER PT J AU Senderowicz, AM Headlee, D Stinson, SF Lush, RM Kalil, N Villalba, L Hill, K Steinberg, SM Figg, WD Tompkins, A Arbuck, SG Sausville, EA AF Senderowicz, AM Headlee, D Stinson, SF Lush, RM Kalil, N Villalba, L Hill, K Steinberg, SM Figg, WD Tompkins, A Arbuck, SG Sausville, EA TI Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FLAVONE ACETIC-ACID; BREAST-CARCINOMA CELLS; SECRETORY DIARRHEA; CANCER; L86-8275; PHARMACOKINETICS; ARREST AB Purpose: We conducted a phase I trial of the cyclin-dependent kinase inhibitor, flavopiridol (National Service Center [NSC] 649890), to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacology of flavopiridol given as a 72-hour infusion every 2 weeks. Patients and Methods: Seventy-six patients with refractory malignancies with prior disease progression were treated with flavopiridol, with first-cycle pharmacokinetic sampling. Results: Forty-nine patients defined our first MTD, 50 mg/m(2)/d x 3 with dose-limiting toxicity (DLT) of secretory diarrhea at 62.5 mg/kg/d x 3. Subsequent patients received antidiarrheal prophylaxis (ADP) to define a second MTD, 78 mg/m(2)/d x 3 with DLT of hypotension at 98 mg/m(2)/d x 3. Other toxicities included a proinflammatory syndrome with alterations in acute-phase reactants, particularly at doses >50 mg/m(2)/d x 3, which in some patients prevented chronic therapy every 2 weeks. In some patients, ADP wets not successful, requiring dose-deescalation. Although approximately 70% of patients displayed predictable flavopiridol pharmacology, we observed unexpected interpatient variability and postinfusion peaks in approximately 30% of Eases. At the two MTDs, we achieved a mean plasma flavopiridol concentration of 271 nM(50 mg/m(2)/d x 3) and 344 nM (78 mg/m(2)/d x 3), respectively. One partial response in a patient with renal cancer and minor responses (n = 3) in patients with non Hodgkin's lymphoma, colon, and renal cancer occurred. Conclusion: The MTD of infusional flavopiridol is 50 mg/m(2)/d x 3 with dose-limiting secretory diarrhea at 62.5 mg/m(2)/d x 3. With ADP, 78 mg/m(2)/d x 3 was the MTD, with dose-limiting hypotension at 98 mg/m(2)/d x 3. Based on chronic tolerability, 50 mg/m(2)/d x 3 is the recommended phase II dose without ADP. Antitumor effect was observed in certain patients with renal, prostate, and colon cancer, and non-Hodgkin's lymphoma. Concentrations of flavopiridol (200 to 400 nM) needed for cyclin-dependent kinase inhibition in preclinical models were achieved safely. C1 NCI, Dev Therapeut Program, Clin Trials Unit,Med Branch, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Div Clin Sci & Invest Drug Branch, Canc Treatment Evaluat Program, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery & Dev Res, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), NCI, Dev Therapeut Program, Clin Trials Unit,Med Branch, Biostat & Data Management Sect, 10 Ctr Dr,Bldg 10,Room 6N113, Bethesda, MD 20892 USA. EM sendero@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 42 TC 326 Z9 333 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 2986 EP 2999 PG 14 WC Oncology SC Oncology GA 116PY UT WOS:000075734800013 PM 9738567 ER PT J AU Sandor, V Stark-Vancs, V Pearson, D Nussenblat, R Whitcup, SM Brouwers, P Patronas, N Heiss, J Jaffe, E deSmet, M Kohler, D Simon, R Wittes, R AF Sandor, V Stark-Vancs, V Pearson, D Nussenblat, R Whitcup, SM Brouwers, P Patronas, N Heiss, J Jaffe, E deSmet, M Kohler, D Simon, R Wittes, R TI Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; PRIMARY BRAIN LYMPHOMA; HIGH-DOSE METHOTREXATE; SURVIVAL; THERAPY; PHARMACOLOGY AB Purpose: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. Patients and Methods: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high dose methotrexate total dose of 8.4 g/m(2) with leucovorin rescue; thiotepa 35 mg/m(2); vincristine 1.4 mg/m(2); dexa methasone; and intrathecal cytarabine (Ara-C) and methotrexate (MN) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. Results: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting, Conclusion: The MN regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival. J Clin Oncol 16:3000-3006. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Dept Neurosurg, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NIH, Dept Neuroradiol, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Pathol, Bethesda, MD 20892 USA. NIH, Div Biostat, Bethesda, MD 20892 USA. RP Wittes, R (reprint author), NCI, Dept Neurosurg, Div Canc Treatment & Diagnosis, NIH, Bld 31,Rm 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM wittesb@box-w.nih.gov RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 21 TC 143 Z9 149 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3000 EP 3006 PG 7 WC Oncology SC Oncology GA 116PY UT WOS:000075734800014 PM 9738568 ER PT J AU Cheson, BD Sorensen, JM Vena, DA Montello, MJ Barret, JA Damasio, E Tallman, M Annino, L Conners, J Coiffier, B Lauria, F AF Cheson, BD Sorensen, JM Vena, DA Montello, MJ Barret, JA Damasio, E Tallman, M Annino, L Conners, J Coiffier, B Lauria, F TI Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: A report of 979 patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; BONE-MARROW BIOPSIES; TERM FOLLOW-UP; DURABLE REMISSIONS; PENTOSTATIN; CLADRIBINE; THERAPY; 2'-DEOXYCOFORMYCIN; RELAPSE AB Purpose: To provide cladribine (CdA) to physicians for the treatment of patients with previously treated or untreated hairy cell leukemia (HCL), and to determine the response rate, response duration, survival, and toxicity with this agent. Patients and Methods: This Group C phase II study was open to all eligible patients whose primary physician obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 979 patients registered, 861 were assessable for response and 895 for toxicity, Results: The complete remission (CR) rate was 50% and the partial remission (PR) rate was 37%. At a median follow-vp of 52 months, 12% of patients were reported to have progressed and 62 (7%) have died of disease. Conclusion: This large experience confirms the excellent response rates and remission duration of CdA in patients with HCL. Nevertheless, the response rates in this setting, which approximates general clinical practice, were lower than in other series. In general, CdA was well tolerated, but the potential increased risk for secondary malignancies requires additional bellow-up evaluation. CdA can now be considered as one of the best agents for the treatment of HCL. C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment Diagnosis & Ctr, NIH, Bethesda, MD 20892 USA. EMMES Corp, Potomac, MD USA. RP Cheson, BD (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment Diagnosis & Ctr, NIH, Execut Plaza N,Room 741, Bethesda, MD 20892 USA. NR 36 TC 111 Z9 113 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3007 EP 3015 PG 9 WC Oncology SC Oncology GA 116PY UT WOS:000075734800015 PM 9738569 ER PT J AU Gail, M Rimer, B AF Gail, M Rimer, B TI Risk-based recommendations for mammographic screening for women in their forties SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER RISK; AGE AB Purpose: To develop risk-based recommendations for mammographic screening for women in their 40s that take into account the woman's age, race, and specific risk factors. Methods: We assumed that regular mammographic screening is justified for a 50-year-old woman, even one with no risk factors, and that a younger woman with an expected 1-year breast cancer incidence rate as great or greater than that of a 50-year-old woman with no risk factors would benefit sufficiently to justify regular screening. Recommendations under this criterion were based on age- and race-specific breast cancer incidence rates from the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End Results (SEER) Program; assessments of risk factors from the Breast Cancer Detection and Demonstration Project (BCDDP); and reports in the literature. Results: Two methods, the exact-age procedure (EAP) and the grouped-age procedure (GAP), were developed. The less precise GAP only requires following a flow diagram. The proportion of white women recommended for screening by the EAP ranges from 10% for 40-year-old women to 95% for 49-year-old women, and the corresponding percentages for black women are 16% and 95%. The assumptions that underlie the guidelines are discussed critically. Conclusion: For women or physicians who prefer an individualized approach in deciding whether to initiate regular mammographic screening in the age range of 40 to 49 years, the present report offers recommendations based on individualized risk-factor data and clearly stated assumptions that have an empiric basis. These recommendations can be used to facilitate the counseling process. J Clin Oncol 16:3105-3114. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Div Canc Control & Populat Sci, Rockville, MD USA. RP Gail, M (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN-431, Bethesda, MD 20892 USA. FU NCI NIH HHS [1P01CA72099, 1R01CA63782] NR 32 TC 35 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3105 EP 3114 PG 10 WC Oncology SC Oncology GA 116PY UT WOS:000075734800028 PM 9738582 ER PT J AU Lee, JK Dancik, V Waterman, MS AF Lee, JK Dancik, V Waterman, MS TI Estimation for restriction sites observed by optical mapping using reversible-jump Markov chain Monte Carlo SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE restriction map; optical mapping; hierarchical Bayes model; reversible-jump Markov chain Monte Carlo ID BAYESIAN COMPUTATION; MAPS; DNA AB A fundamentally new molecular-biology approach in constructing restriction maps, Optical Mapping, has been developed by Schwartz et al. (1993), Using this method restriction maps are constructed by measuring the relevant fluorescence intensity and length measurements. However, it is difficult to directly estimate the restriction site locations of single DNA molecules based on these optical mapping data because of the precision of length measurements and the unknown number of true restriction sites in the data. We propose the use of a hierarchical Bayes model based on a mixture model with normals and random noise. In this model we explicitly consider the missing observation structure of the data, such as the orientations of molecules, the allocations of cutting sites to restriction sites, and the indicator variables of whether observed cut sites are true or false. Because of the complexity of the model, the large number of missing data, and the unknown number of restriction sites, we use Reversible-Jump Markov Chain Monte Carlo (MCMC) to estimate the number and the locations of the restriction sites. Since there exists a high multimodality due to unknown orientations of molecules, we also use a combination of our MCMC approach and the flipping algorithm suggested by Dancik and Waterman (1997). The study is highly computer-intensive and the development of an efficient algorithm is required. C1 NCI, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Math Inst, Kosice 04001, Slovakia. Univ So Calif, Dept Math, Los Angeles, CA 90089 USA. RP Lee, JK (reprint author), NCI, NIH, Bldg 37-5D02, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM36230] NR 11 TC 4 Z9 4 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD FAL PY 1998 VL 5 IS 3 BP 505 EP 515 DI 10.1089/cmb.1998.5.505 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 119WL UT WOS:000075921100010 PM 9773346 ER PT J AU Goldszal, AF Davatzikos, C Pham, DL Yan, MXH Bryan, RN Resnick, SM AF Goldszal, AF Davatzikos, C Pham, DL Yan, MXH Bryan, RN Resnick, SM TI An image-processing system for qualitative and quantitative volumetric analysis of brain images SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE phantom and phantoms; image processing; brain, volume; brain, anatomy; magnetic resonance imaging ID MR-IMAGES; SPATIAL NORMALIZATION; SEGMENTATION; ATLAS; MORPHOMETRY; SCHIZOPHRENIA; ABNORMALITIES; NEUROANATOMY; CORTEX; MODEL AB In this work, we developed, implemented, and validated an image-processing system for qualitative and quantitative volumetric analysis of brain images. This system allows the visualization and quantitation of global and regional brain volumes. Global volumes were obtained via an automated adaptive Bayesian segmentation technique that labels the brain into white matter, gray matter, and cerebrospinal fluid. Absolute volumetric errors for these compartments ranged between 1 and 3% as indicated by phantom studies. Quantitation of regional brain volumes was performed through normalization and tessellation of segmented brain images into the Talairach space with a 3D elastic warping model. Retest reliability of regional volumes measured in Talairach space indicated errors of <1.5% for the frontal, parietal, temporal, and occipital brain regions. Additional regional analysis was performed with an automated hybrid method combining a region-of-interest approach and voxel-based analysis, named Regional Analysis of Volumes Examined in Normalized Space (RAVENS). RAVENS analysis for several subcortical structures showed good agreement with operator-defined volumes. This system has sufficient accuracy for longitudinal imaging data and is currently being used in the analysis of neuroimaging data of the Baltimore Longitudinal Study of Aging. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Goldszal, AF (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr,Rm 2C20, Baltimore, MD 21224 USA. RI Bryan, R. Nick/P-1661-2014 FU NIA NIH HHS [AG-93-07] NR 39 TC 193 Z9 194 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1998 VL 22 IS 5 BP 827 EP 837 DI 10.1097/00004728-199809000-00030 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 120JU UT WOS:000075953900031 PM 9754125 ER PT J AU Morris, RD Stuebing, KK Fletcher, JM Shaywitz, SE Lyon, GR Shankweiler, DP Katz, L Francis, DJ Shaywitz, BA AF Morris, RD Stuebing, KK Fletcher, JM Shaywitz, SE Lyon, GR Shankweiler, DP Katz, L Francis, DJ Shaywitz, BA TI Subtypes of reading disability: Variability around a phonological core SO JOURNAL OF EDUCATIONAL PSYCHOLOGY LA English DT Article ID VARIABLE-DIFFERENCE MODEL; SHORT-TERM-MEMORY; DEVELOPMENTAL DYSLEXIA; CLASSIFICATION; RETARDATION; DISCREPANCY; AWARENESS; DEFICITS; READERS; ABILITY AB Eight measures of cognitive and language functions in 232 children were subjected to multiple methods of cluster analysis in an effort to identify subtypes of reading disability. Clustering yielded 9 reliable subtypes representing 90% of the sample, including 2 nondisabled subtypes, and 7 reading-disabled subtypes. Of the reading-disabled subtypes, 2 were globally deficient in language skills, whereas 4 of the 5 specific reading-disabled subtypes displayed a relative weakness in phonological awareness and variations in rapid serial naming and verbal short-term memory. The remaining disabled subtype was impaired on verbal and nonverbal measures associated with rate of processing, including rate and accuracy of oral reading. Studies showed evidence for discriminative validity among the 7 reading-disabled subtypes. Results support the view that children with reading disability usually display impairments on phonological awareness measures, with discriminative variability on other measures involving phonological processing, language, and cognitive skills. C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. NICHHD, Child Dev & Behav Branch, NIH, Bethesda, MD 20892 USA. Haskins Labs Inc, Storrs, CT USA. Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Morris, RD (reprint author), Georgia State Univ, Dept Psychol, Univ Plaza, Atlanta, GA 30303 USA. EM psyrem@panther.gsu.edu OI Francis, David/0000-0003-3944-3274 NR 77 TC 247 Z9 253 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0663 J9 J EDUC PSYCHOL JI J. Educ. Psychol. PD SEP PY 1998 VL 90 IS 3 BP 347 EP 373 DI 10.1037/0022-0663.90.3.347 PG 27 WC Psychology, Educational SC Psychology GA 121KG UT WOS:000076012400001 ER PT J AU Zieler, H Garon, CF Fischer, ER Shahabuddin, M AF Zieler, H Garon, CF Fischer, ER Shahabuddin, M TI Adhesion of Plasmodium gallinaceum ookinetes to the Aedes aegypti midgut: Sites of parasite attachment and morphological changes in the ookinete SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE microvilli-associated network; peritrophic membrane; scanning electron microscopy; transmission electron microscopy ID MOSQUITO MIDGUT; MALARIA; PENETRATION; EPITHELIUM AB Plasmodium gallinaceum ookinetes adhered to Aedes aegypti midgut epithelia when purified ookinetes and isolated midguts were combined in vitro. Ookinetes preferentially bound to the microvillated luminal surface of the midgut, and they seemed to interact with three types of structures on the midgut surface. First, they adhered to and migrated through a network-like matrix, which we have termed microvilli-associated network, that covers the surface of the microvilli. This network forms on the luminal midgut surface in response to blood or protein meals. Second, the ookinetes bound directly to the microvilli on the surface of the midgut and were occasionally found immersed in the thick microvillar layer. Third, the ookinetes associated with accumulations of vesicular structures found interspersed between the microvillated cells of the midgut. The origin of these vesicular structures is unknown, but they correlated with the surface of midgut cells invaded by ookinetes as observed by TEM. After binding to the midgut, ookinetes underwent extensive morphological changes: they frequently developed one or more annular constrictions, and their surface roughened considerably, suggesting that midgut components remain bound to the parasite surface. Our observations suggest that, in a natural infection, the ookinete interacts in a sequential manner with specific components of the midgut surface. Initial binding to the midgut surface may activate the ookinete and cause morphological changes in preparation for invasion of the midgut cells. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Shahabuddin, M (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM shahabuddin@nih.gov NR 22 TC 21 Z9 21 U1 1 U2 2 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1998 VL 45 IS 5 BP 512 EP 520 DI 10.1111/j.1550-7408.1998.tb05110.x PG 9 WC Microbiology SC Microbiology GA 128BF UT WOS:000076384800008 PM 9783452 ER PT J AU Valenzuela, JG Ribeiro, JMC AF Valenzuela, JG Ribeiro, JMC TI Purification and cloning of the salivary nitrophorin from the hemipteran Cimex lectularius SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE Cimex lectularius; bedbug; haemostasis; haematophagy; nitric oxide; nitrophorin; polymerase chain reaction; cDNA synthesis; saliva; salivary protein purification; vasodilator ID ORIGINAL FEEDING-HABITS; NITRIC-OXIDE; BLOODSUCKING INSECT; RHODNIUS-PROLIXUS; HEME PROTEIN; ARTHROPODS; BINDING AB Cimex lectularius and Rhodnius prolixus contain salivary nitric oxide (NO) that may help them to feed on their vertebrate hosts by promoting vasodilation and inhibiting platelet aggregation. Salivary NO is associated with heme proteins (nitrophorins) that store and transport NO from the insect salivary glands to the skin of the host. Ln this study, the salivary nitrophorin of Cimex lectularius was purified by DEAE chromatography and reverse-phase high-performance liquid chromatography, The purified nitrophorin had a molecular mass of 32.9 kDa. The DEAE-purified hemoprotein was able to bind NO, and this binding shifted the absorption maximum from 388 nm to 438 nm, The ratio of heme to apoprotein was estimated to be of 1:1. A cDNA clone of 1079 base pairs was sequenced and was found to code for a protein with a molecular mass of 31.7 kDa. The clone sequence was in agreement with the internal peptide sequences obtained from the purified protein. Sequencing of the isolated clone indicates high similarity to several inositol phosphatases; however, no significant similarities emerged when the sequence of C. lectularius nitrophorin was compared with that of R. prolixus nitrophorin, the only other nitrophorin known in insect saliva. Because C. lectularius and R. prolixus belong to two different families of Hemiptera that evolved independently to blood feeding, a case is made for the convergent evolution of these two insect nitrophorins. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Valenzuela, JG (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 15 TC 49 Z9 49 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD SEP PY 1998 VL 201 IS 18 BP 2659 EP 2664 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 129YZ UT WOS:000076492800009 PM 9716517 ER PT J AU Perez, LA Peynircioglu, ZF Blaxton, TA AF Perez, LA Peynircioglu, ZF Blaxton, TA TI Developmental differences in implicit and explicit memory performance SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article ID PICTURES; AGE; RECOGNITION; CHILDREN; DISSOCIATIONS; UNITIZATION; COMPLETION; ADULTS; NORMS; TASKS AB Performance of preschool, elementary school, and college students was compared on a series of perceptual and conceptual implicit and explicit memory tasks that followed perceptual or conceptual processing during study. As expected, performance on the conceptual explicit memory task improved across age groups. In contrast, performance on the perceptual explicit memory task as well as that on both types of implicit memory tasks showed no developmental change. Also, perceptual processing during study led to better memory performance than conceptual processing for both the perceptual implicit and perceptual explicit tasks and conceptual processing during study led to better memory performance on the conceptual explicit memory task. Performance on the conceptual implicit memory task, in contrast, was affected equally by both types of study processing. The results are discussed in terms of transfer-appropriate processing (Roediger & Blaxton, 1987b) and unitization and grouping processes (Graf & Schacter, 1989). (C) 1998 Academic Press. C1 NCI, Med Illness Counseling Ctr, NIH, Bethesda, MD 20892 USA. American Univ, Washington, DC 20016 USA. RP Perez, LA (reprint author), NCI, Med Illness Counseling Ctr, NIH, Bldg 10,Room 13N-240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 45 TC 31 Z9 32 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD SEP PY 1998 VL 70 IS 3 BP 167 EP 185 DI 10.1006/jecp.1998.2449 PG 19 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 122YV UT WOS:000076099800002 PM 9742178 ER PT J AU Thurman, RG Bradford, BU Iimuro, Y Knecht, KT Arteel, GE Yin, M Connor, HD Wall, C Raleigh, JA Frankenberg, MV Adachi, Y Forman, DT Brenner, D Kadiiska, M Mason, RP AF Thurman, RG Bradford, BU Iimuro, Y Knecht, KT Arteel, GE Yin, M Connor, HD Wall, C Raleigh, JA Frankenberg, MV Adachi, Y Forman, DT Brenner, D Kadiiska, M Mason, RP TI The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Meeting of the Japanese-Hepatic-Cells-Research-Society CY JUN 06-07, 1997 CL JUNTENDO UNIV, TOKYO, JAPAN SP Japanese Hepat Cells Res Soc HO JUNTENDO UNIV DE endotoxin; ethanol; free radicals; hypoxia; Kupffer cells; liver injury ID TUMOR NECROSIS FACTOR; INTRAGASTRIC ETHANOL EXPOSURE; RAT KUPFFER CELLS; HEPATIC MACROPHAGES; PERICENTRAL REGIONS; PLASMA ENDOTOXIN; SWIFT INCREASE; OXYGEN-UPTAKE; DISEASE; PATHOGENESIS AB Previous research from this laboratory using a continuous enteral ethanol (EtOH) administration model demonstrated that Kupffer cells are pivotal in the development of EtOH-induced liver injury. When Kupffer cells were destroyed using gadolinium chloride (GdCl3) or the gut was sterilized with polymyxin B and neomycin, early inflammation due to EtOH was blocked. Anti-tumour necrosis factor (TNF)-alpha antibody markedly decreased EtOH-induced liver injury and increased TNF-mRNA. These findings led to the hypothesis that EtOH-induced liver injury involves increases in circulating endotoxin leading to activation of Kupffer cells. Pimonidazole, a nitro-imidazole marker, was used to detect hypoxia in downstream pericentral regions of the lobule. Following one large dose of EtOH or chronic enteral EtOH for 1 month, pimonidazole binding was increased significantly in pericentral regions of the liver lobule, which was diminished with GdCl3. Enteral EtOH increased free radical generation detected with electron spin resonance (ESR). These radical species had coupling constants matching alpha-hydroxyethyl radical and were shown conclusively to arise from EtOH based on a doubling of the ESR lines when C-13-EtOH was given. alpha-Hydroxyethyl radical production was also blocked by the destruction of Kupffer cells with GdCl3. It is known that females develop more severe EtOH-induced liver injury more rapidly and with less EtOH than males. Female rats on the enteral protocol exhibited more rapid injury and more widespread fatty changes over a larger portion of the liver lobule than males. Plasma endotoxin, ICAM-1, free radical adducts, infiltrating neutrophils and transcription factor NF kappa B were approximately two-fold greater in livers from females than males after 4 weeks of enteral EtOH treatment. Furthermore, oestrogen treatment increased the sensitivity of Kupffer cells to endotoxin. These data are consistent with the hypothesis that Kupffer cells participate in important gender differences in liver injury caused by ethanol. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. NIEHS, Mol Biophys Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Thurman, RG (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. EM thurman@med.unc.edu FU NIAAA NIH HHS [AA-03626, AA-09156] NR 88 TC 64 Z9 65 U1 1 U2 5 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD SEP PY 1998 VL 13 SU S BP S39 EP S50 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 128VR UT WOS:000076429500007 PM 9792033 ER PT J AU Stern, MD AF Stern, MD TI Exploring local calcium feedback: Trying to fool mother nature SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Editorial Material ID SKELETAL-MUSCLE; MODEL C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Stern, MD (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD SEP PY 1998 VL 112 IS 3 BP 259 EP 262 DI 10.1085/jgp.112.3.259 PG 4 WC Physiology SC Physiology GA 118HZ UT WOS:000075833600001 PM 9725888 ER PT J AU Muramatsu, SI Handa, A Kajigaya, S Brown, KE AF Muramatsu, SI Handa, A Kajigaya, S Brown, KE TI Transcription-positive cofactor 4 enhances rescue of adeno-associated virus genome from an infectious clone SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID REP PROTEIN; TERMINAL REPEATS; BINDING-SITE; TYPE-2; REPLICATION; PROMOTER; DNA; COACTIVATOR; ACTIVATION; PC4 AB While Rep proteins are required for adenoassociated virus (AAV) replication, little is known about cellular proteins that interact with Rep. We demonstrate here that transcription-positive cofactor 4 (PC4, p15) fused to Gal4-activating domain interacted with both AAV-2 and AAV-3 Rep proteins fused to Gal4 DNA-binding domain, leading to reporter activation in the:yeast two-hybrid system. In addition to its coactivating function, PC4 recently has been shown to be involved in replication of simian virus 40. To study a functional role for the PC4-Rep protein interaction, 293-31 cells were cotransfected with a PC4 expression plasmid and an infectious clone of AAV-3, followed by superinfection with helper adenovirus. A significantly increased number of AAV-3 genomes were rescued in PC4 transfected cells. Our results support a possible involvement of PC4 in AAV replication and may be used in efficient production of AAV vectors for gene therapy. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Muramatsu, SI (reprint author), NHLBI, Hematol Branch, Bldg 10,Rm 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Muramatsu, Shinichi/0000-0002-3185-7790 NR 33 TC 4 Z9 4 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1998 VL 79 BP 2157 EP 2161 PN 9 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 114CY UT WOS:000075592600010 PM 9747724 ER PT J AU Yunus, AS Collins, PL Samal, SK AF Yunus, AS Collins, PL Samal, SK TI Sequence analysis of a functional polymerase (L) gene of bovine respiratory syncytial virus: determination of minimal trans-acting requirements for RNA replication SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; AVIAN PNEUMOVIRUS; VIRAL POLYMERASE; PROTEIN; TRANSCRIPTION; EXPRESSION; MINIREPLICONS; INFECTION; RESCUE AB The complete nucleotide sequence of a functional clone of the large polymerase (L) gene of bovine respiratory syncytial virus (BRSV) strain A51908 was determined by analysis of cloned cDNAs obtained from genomic and mRNAs, The BRSV L gene is 6573 nt in length and the derived polypeptide has 2162 aa, Alignment of the sequences of the BRSV L gene, and its encoded protein, with sequences of the L gene and protein of human respiratory syncytial virus strain A2 showed 77% identity at the nucleotide level and 84% identity at the amino acid level, By comparison, the L gene and protein of avian pneumovirus showed only 50% identity at the nucleotide level and 64% identity at the amino acid level, A minigenome was constructed to encode a BRSV vRNA analogue containing the gene for chloramphenicol acetyltransferase (CAT) under the control of putative BRSV transcription motifs and Ranked by the BRSV genomic termini, Transfection of plasmids encoding the BRSV minigenome, nucleocapsid protein (N), phosphoprotein (P) and L protein, each under the control of T7 promoter, into cells infected with a vaccinia virus recombinant expressing the T7 RNA polymerase gave rise to CAT activity and progeny with the minigenome, This result indicates that the N, P and L proteins are necessary and sufficient for transcription and replication of the BRSV minigenome and are functional, Further, inclusion of small amounts of the M2 protein along with the N, P and L proteins greatly augmented minigenome transcription. C1 Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. EM ss5@umail.umd.edu NR 36 TC 12 Z9 14 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1998 VL 79 BP 2231 EP 2238 PN 9 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 114CY UT WOS:000075592600019 PM 9747733 ER PT J AU Baumann, CT Lim, CS Hager, GL AF Baumann, CT Lim, CS Hager, GL TI Simultaneous visualization of the yellow and green forms of the green fluorescent protein in living cells SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE green fluorescent protein; confocal microscopy; protein localization ID TRANSCRIPTION AB In this study we sought to develop a method for the co-localization of proteins in living cells utilizing the enhanced green fluorescent protein (EGFP) and a redshifted EGFP variant, EYFP (enhanced yellow fluorescent protein). EYFP was expressed as an unsubstituted molecule while EGFP was fused to NF1 (EGFP-NF1), a transcription factor found exclusively in the nucleus. The Leica TCS SP laser scanning confocal microscope was used. This microscope allows the user to monitor the emitted light at defined wavelengths owing to the presence of a monochrometer in the emission light path. pEGFP-NF1 and pEYFP were co-expressed in the same cell and excited with the 476-nm and 488-nm argon laser lines. To separate the EYFP and EGFP fluorescence, EGFP-NF1 emission was recorded between 496 and 505 nm. These wavelengths are on the left shoulder of the EGFP emission peak and exclude most of the EYFP fluorescence. The EYFP emission was followed between 670 and 754 nm, utilizing the tail of EYFP emission that extends well beyond that for EGFP. Under these conditions we obtained excellent discrimination between EYFP fluorescence and EGFP-NF1 emission. These observations demonstrate that EYFP- and EGFP-substituted chimeras can be used for simultaneous detection in living cells. C1 NCI, Lab Receptor & Gene Express, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor & Gene Express, Bldg 41,Room B602, Bethesda, MD 20892 USA. NR 7 TC 20 Z9 20 U1 1 U2 6 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1998 VL 46 IS 9 BP 1073 EP 1076 PG 4 WC Cell Biology SC Cell Biology GA 114MP UT WOS:000075613500011 PM 9705973 ER PT J AU Elenkov, IJ Webster, E Papanicolaou, DA Fleisher, TA Chrousos, GP Wilder, RL AF Elenkov, IJ Webster, E Papanicolaou, DA Fleisher, TA Chrousos, GP Wilder, RL TI Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INTERLEUKIN-10 PRODUCTION; COLORECTAL-CANCER; INTERFERON-GAMMA; CELLS; RELEASE; DISEASE; LYMPHOCYTES; EXPRESSION; CIMETIDINE AB IL-12 and IL-10, respectively, stimulate Th1 and Th2 immune responses. The development of some allergic reactions, infections, and tumors are associated with excessive histamine production and a shift toward Th2 responses. Here we address the possibility that this association is causally linked, at least in part, to modulation of IL-12 and IL-10 production by histamine. We report that histamine dose-dependently inhibited the secretion of human IL-12 (p70) and increased the production of IL-10 in LPS-stimulated whole blood cultures. These effects of histamine were antagonized by cimetidine, an H2 receptor antagonist, but not by selective H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist, The effects of histamine on IL-12 and IL-10 secretion were independent of endogenous secretion of IL-10 or exogenous addition of IL-12, while Ro 20-1724, a phosphodiesterase inhibitor, potentiated the effects of histamine on IL-12 and IL-10 production, implicating cAMP in its actions. Similar modulatory effects of histamine on IL-12 and IL-10 production, which were reversed by the H2 antagonist cimetidine, were observed in PBMC and isolated monocytes stimulated by Staphylococcus aureus Cowan strain 1 and LPS, respectively. Thus, histamine, via stimulation of H2 receptors on peripheral monocytes and subsequent elevation of cAMP, suppresses IL-12 and stimulates IL-10 secretion, changes that may result in a shift of Th1/Th2 balance toward Th2-dominance, This may represent a novel mechanism by which excessive secretion of histamine potentiates Th2-mediated allergic reactions and contributes to the development of certain infections and tumors normally eliminated by Th1-dependent immune mechanisms. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Serv Immunol, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N240,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 31 TC 258 Z9 263 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1998 VL 161 IS 5 BP 2586 EP 2593 PG 8 WC Immunology SC Immunology GA 112UB UT WOS:000075511600065 PM 9725260 ER PT J AU Tewari, D Goldstein, SL Notkins, AL Zhou, P AF Tewari, D Goldstein, SL Notkins, AL Zhou, P TI cDNA encoding a single-chain antibody to HIV p17 with cytoplasmic or nuclear retention signals inhibits HIV-1 replication SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MATRIX PROTEIN; INTRACELLULAR EXPRESSION; ENVELOPE GLYCOPROTEIN; MATURE VIRIONS; T-LYMPHOCYTES; LIFE-CYCLE; INFECTION; MYRISTOYLATION; FRAGMENTS AB HIV-1 gag p17 protein is an attractive target for molecular intervention, because it is involved in the viral replication cycle at both the pre- and postintegration levels. In the present experiments, we targeted p17 by intracellularly expressing a cDNA encoding an Ab to p17, cDNA from a hybridoma-secreting Ab to p17 was cloned, sequenced, reconstructed as a single-chain Ab fragment (scFv), and expressed in the cytoplasm or nucleus with appropriate retention signals, The expressed scFvs had no effect on T cell growth or CD4 expression and bound specifically to HIV-1 p17, Human CD4(+) Jurkat T cells that expressed scFvs and were infected with HIV-1 showed a marked reduction in virus replication compared with cells expressing vector alone. The inhibition of virus replication was more pronounced when scFvs were expressed in the cytoplasm rather than the nucleus, From these studies, we conclude that the intracellular expression of a single-chain Ab to p17 inhibits HIV replication; in addition, the degree of inhibition is related to the intracellular targeting site. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Rockville, MD 20852 USA. RP Zhou, P (reprint author), NIDR, Oral Infect & Immun Branch, NIH, 30 Convent Dr MSC 4322,Bldg 30,Room 114, Bethesda, MD 20892 USA. EM zhou@yoda.nidr.nih.gov NR 32 TC 26 Z9 27 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1998 VL 161 IS 5 BP 2642 EP 2647 PG 6 WC Immunology SC Immunology GA 112UB UT WOS:000075511600072 PM 9725267 ER PT J AU Nishimura, MI Custer, MC Schwarz, SL Parker, LL Mixon, A Clay, TM Yannelli, JR Rosenberg, SA AF Nishimura, MI Custer, MC Schwarz, SL Parker, LL Mixon, A Clay, TM Yannelli, JR Rosenberg, SA TI T cell-receptor V gene use by CD4(+) melanoma-reactive clonal and oligoclonal T-cell lines SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE T-cell receptor; melanoma antigen; CD4(+) T cells ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; VARIABLE REGION GENES; NECROSIS-FACTOR-ALPHA; HUMAN BREAST-CANCER; AUTOLOGOUS TUMOR; ADOPTIVE IMMUNOTHERAPY; CYTOKINE SECRETION; ANTIGEN RECEPTOR; TCR USAGE AB rumor-reactive CD4(+) T cells can be isolated and expanded from the peripheral blood and tumor lesions of patients with melanoma. In contrast to CD8(+) T cells, little is known about the antigens recognized by these CD4(+) T cells. As a consequence, little is known about the diversity of the T-cell receptor (TcR) use by melanoma-reactive CD4(+) T cells. To address these questions, a panel of clonal or highly oligoclonal CDC T-cell lines was established from a patient with metastatic melanoma. A CD4+ tumor-infiltrating lymphocyte (TIL) line was established that was highly oligoclonal and recognized only autologous melanoma cells but not allogeneic melanomas, suggesting the expression of a mutated or uniquely expressed antigen by this melanoma. The antigen recognized by the CD4(+) TILs could be presented by intact melanoma cells or by autologous Epstein-Barr virus (EBV) B cells pulsed with melanoma cell lysates. A panel of CD4+ clonal and highly oligoclonal T-cell lines was isolated from peripheral blood mononuclear cells (PBMC) from this patient; these were also reactive with autologous melanoma cells or tumor extracts pulsed on autologous EBV B cells. Despite their reactivity with the autologous melanoma, we found no evidence of restricted TcR V gene use, because all six T-cell lines recognized antigen via different TcR alpha/beta rearrangements. Furthermore, there were no conserved amino acids in the CDR3 regions of these TcRs, indicating that multiple TcR clonotypes could mediate recognition of a single unique major histocompatibility (MHC) complex class II restricted melanoma antigen or that multiple MHC class II restricted melanoma antigens are expressed by the melanoma. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Nishimura, MI (reprint author), NCI, Surg Branch, NIH, Bldg 10-2B06,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1998 VL 21 IS 5 BP 352 EP 362 DI 10.1097/00002371-199809000-00003 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 123BH UT WOS:000076105600003 PM 9789197 ER PT J AU Pikis, A Donkersloot, JA Rodriguez, WJ Keith, JM AF Pikis, A Donkersloot, JA Rodriguez, WJ Keith, JM TI A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meetings American-Pediatric-Society / Society-for-Pediatric-Research CY MAY 09, 1996 CL WASHINGTON, D.C. SP Amer Pediat Soc, Soc Pediat Res ID CONSTITUTIVELY ACTIVATING MUTATIONS; BACTERIOPHAGE-T7 DNA-POLYMERASE; LUTEINIZING-HORMONE RECEPTOR; LIMITED PRECOCIOUS PUBERTY; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; SEQUENCE-ANALYSIS; UNITED-STATES; HETEROGENEITY; MUTAGENESIS AB Multidrug-resistant Streptococcus pneumoniae strains have emerged over the past decade at an alarming rate, The molecular mechanism of trimethoprim resistance was investigated in 5 pneumococcal strains isolated in the Washington, DC, area from patients with invasive infections. Cloning and sequencing of the trimethoprim resistance determinant from these pneumococci indicated that an altered chromosome-encoded dihydrofolate reductase (DHFR) was responsible for the observed resistance. Comparison of DHFR sequences from pneumococcal strains with various susceptibilities to trimethoprim, together with site-directed mutagenesis, revealed that substitution of isoleucine-100 with a leucine residue resulted in trimethoprim resistance. Hydrogen bonding between the carbonyl oxygen of isoleucine-100 and the 4-amino group of trimethoprim is proposed to play a critical role in the inhibition of DHFR by trimethoprim, This enzyme-substrate model should facilitate: the design of new antibacterial agents with improved activity against S, pneumoniae. C1 NIDR, Oral Infect & Immunity Branch, Vaccine & Therapuet Dev Sect, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20010 USA. RP Pikis, A (reprint author), NIDR, Oral Infect & Immunity Branch, Vaccine & Therapuet Dev Sect, NIH, Bldg 30,Room 316,30 Convent Dr,MSC4350, Bethesda, MD 20892 USA. EM apikis@yoda.nidr.nih.gov NR 48 TC 35 Z9 38 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 700 EP 706 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700013 PM 9728538 ER PT J AU Swanson, DS Pan, X Kline, MW McKinney, RE Yogev, R Lewis, LL Brady, MT McSherry, GD Dankner, WM Musser, JM AF Swanson, DS Pan, X Kline, MW McKinney, RE Yogev, R Lewis, LL Brady, MT McSherry, GD Dankner, WM Musser, JM TI Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 16-23, 1995 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID HEAT-SHOCK-PROTEIN; MULTILOCUS ENZYME ELECTROPHORESIS; FRAGMENT-LENGTH-POLYMORPHISM; INTRACELLULARE COMPLEX; AIDS PATIENTS; NONTUBERCULOUS MYCOBACTERIA; SUBSPECIFIC DIFFERENTIATION; SEQUENCE DETERMINATION; INSERTION ELEMENT; MOLECULAR-LEVEL AB The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M, avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M, avium (chi(2) test, P <.0131), M, avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M, avium strain causing infection was detected. C1 Baylor Coll Med, Dept Pathol, Inst Study Human Bacterial Pathogenesis, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Sect Allergy & Immunol, Dept Pediat, Houston, TX 77030 USA. Duke Univ, Med Ctr, Dept Pediat, Div Infect Dis, Durham, NC 27710 USA. Northwestern Univ, Sch Med, Dept Pediat, Div Infect Dis, Chicago, IL 60611 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Ohio State Univ, Dept Pediat, Infect Dis Sect, Columbus, OH 43210 USA. UMD New Jersey Med Sch, Dept Pediat, Newark, NJ USA. Univ Calif San Diego, Dept Med, Div Infect Dis, San Diego, CA 92103 USA. RP Musser, JM (reprint author), Baylor Coll Med, Dept Pathol, Inst Study Human Bacterial Pathogenesis, 1 Baylor Plaza000, Houston, TX 77030 USA. EM jmusser@path.bcm.tmc.edu FU NIAID NIH HHS [AI-37004]; NIDA NIH HHS [DA-09238] NR 51 TC 17 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 776 EP 782 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700022 PM 9728547 ER PT J AU Bornstein, SR Preas, HL Chrousos, GP Suffredini, AF AF Bornstein, SR Preas, HL Chrousos, GP Suffredini, AF TI Circulating leptin levels during acute experimental endotoxemia and antiinflammatory therapy in humans SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CYTOKINES; RECEPTOR; ANOREXIA; GENE AB Leptin, a newly discovered adipose tissue-derived weight-reducing hormone, is increased in acute inflammation and may be involved in the anorexia and wasting syndrome associated with infection. To determine whether this hormone responds to an acute inflammatory stimulus, plasma leptin concentrations were measured in 12 healthy subjects after intravenous administration of endotoxin, These subjects were randomized to receive concurrently ibuprofen or placebo normal saline (6 in each group). Endotoxin administration resulted in fever, leukocytosis, and an increase in plasma levels of the stress hormones adrenocorticotropic hormone (3.2 +/- 0.3 to 132.6 +/- 75.5 pmol/L, P =.001) and cortisol (431.6 +/- 44 to 796.9 +/- 99 mmol/L, P =.001), Plasma leptin levels, however, did not change significantly from baseline values after administration of endotoxin (0 h: 6.9 +/- 3.1 ng/mL,; 6 h: 6.0 +/- 2.2; 24 h: 6.5 +/- 2.8). While ibuprofen suppressed fever and symptoms associated with endotoxemia, it had no effect on the plasma levels of leptin, In conclusion, acute experimental human endotoxinemia is not associated with acute changes in circulating leptin levels. C1 NICHHD, NIH, Ctr Clin, Pediat Endocrinol Sect,Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Bornstein, SR (reprint author), NICHHD, NIH, Ctr Clin, Pediat Endocrinol Sect,Dev Endocrinol Branch, Bldg 10,Room 10N242,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bornstes@ccl.nichd.nih.gov NR 15 TC 55 Z9 56 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 887 EP 890 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700041 PM 9728566 ER PT J AU Vymazal, J Brooks, RA Bulte, JWM Gordon, D Aisen, P AF Vymazal, J Brooks, RA Bulte, JWM Gordon, D Aisen, P TI Iron uptake by ferritin: NMR relaxometry studies at low iron loads SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE ferritin; relaxometry; iron ID RELAXATION-TIMES; CORE FORMATION; BRAIN IRON; IONS; APOFERRITIN; T2 AB Twenty ferritin samples were prepared at pH 6.5 with average loadings of 0-89 Fe atoms per molecule. Nuclear magnetic relaxation times T-1 and T-2 were measured at 3 degrees C, 23 degrees C, and 37 degrees C and at field strength from 0.025 to 1.5 T. The field dependence, temperature dependence, and approximate equality of T-1 and T-2 at low fields all suggest that nuclear magnetic relaxation in this range is caused primarily by solitary Fe3+ ions. The relaxivity (relaxation rate per mM ferritin) increases quickly with initial iron loading, reaches a peak at 13-14 Fe atoms per molecule, and then declines. This provides supportive evidence for the formation of antiferromagnetically-coupled clusters during early stages in iran loading; the failure to see a similar peak in an earlier study may be related to the nonphysiological pH that was used. Above 50 atoms per molecule, the relaxivity remains approximately constant, except that 1/T-2 at high fields increases slightly, consistent with early core growth. The residual ionic relaxivity in this region is consistent with about three solitary Fe3+ ions remaining on the protein shell, indicating that spin cancellation is not complete. A similar value is obtained by extrapolating relaxation data at high loadings (up to 3000 Fe atoms per molecule), suggesting that these uncoupled spins persist on the protein shell even after an appreciable core has been built. (C) 1998 Published by Elsevier Science Inc. C1 NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, CC, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Biophys, Bronx, NY 10461 USA. RP Brooks, RA (reprint author), NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. EM karbro@msn.com RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 FU NIDDK NIH HHS [DK 15056] NR 20 TC 21 Z9 23 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD SEP PY 1998 VL 71 IS 3-4 BP 153 EP 157 DI 10.1016/S0162-0134(98)10047-8 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 139PU UT WOS:000077038800006 PM 9833320 ER PT J AU Trempus, CS Mahler, JF Ananthaswamy, HN Loughlin, SM French, JE Tennant, RW AF Trempus, CS Mahler, JF Ananthaswamy, HN Loughlin, SM French, JE Tennant, RW TI Photocarcinogenesis and susceptibility to UV radiation in the v-Ha-ras transgenic Tg.AC mouse SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE papilloma; p53; skin cancer ID P53 GENE; SKIN TUMORS; MULTISTAGE CARCINOGENESIS; PAPILLOMA DEVELOPMENT; MICE; MUTATIONS; NONCARCINOGENS; TUMORIGENESIS; EXPRESSION; INITIATION AB The v-Ha-ras transgenic Tg.AC mouse line has proven to be a useful model for the study of chemical carcinogenic potential. We undertook experiments designed to study the effect of the physical carcinogen, UV radiation, on tumorigenesis in this mouse strain. Following a total of three exposures on alternating days to a radiation source covering a cumulative UVR exposure range of 2.6-42.6 kJ per m(2), squamous papillomas developed by 4 wk after initial exposure in a dose-dependent manner, Malignancies developed within 18-30 wk following the initial UVR exposure and were all diagnosed as squamous cell carcinoma or spindle cell tumors. In contrast to other mouse stains used in photocarcinogenesis studies, few p53 mutations were found in Tg.AC malignancies upon polymerase chain reaction-single stranded conformational polymorphism analysis of exons 4-8 followed by sequencing of suspicious bands; however, all tumors analyzed by in sib hybridization expressed the v-Ha-ras transgene. Immunohistochemical analysis of UVR-exposed skin taken 24 h after the last of three exposures (13.1 kJ per m(2) total UVR) showed expression of p53 in hair follicles and in interfollicular epidermis, which indicates that the gene was functional, Thus, although there are some differences between the Tg.AC and other mouse models, these results suggest that the Tg.AC mouse may be a useful model for the study of acute exposure photocarcinogenesis. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Univ Texas, Md Anderson Canc Ctr, Houston, TX USA. RP Trempus, CS (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA-46523] NR 35 TC 30 Z9 30 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1998 VL 111 IS 3 BP 445 EP 451 DI 10.1046/j.1523-1747.1998.00237.x PG 7 WC Dermatology SC Dermatology GA 114CU UT WOS:000075592200018 PM 9740239 ER PT J AU Boni, R Vortmeyer, AO Pack, S Park, WS Burg, G Hofbauer, G Darling, T Liotta, L Zhuang, ZP AF Boni, R Vortmeyer, AO Pack, S Park, WS Burg, G Hofbauer, G Darling, T Liotta, L Zhuang, ZP TI Somatic mutations of the MEN1 tumor suppressor gene detected in sporadic angiofibromas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID ENDOCRINE NEOPLASIA TYPE-1 C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. NCI, NIH, Pathol Lab, Bethesda, MD USA. NCI, NIH, Dept Dermatol, Bethesda, MD USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. RI Hofbauer, Gunther/B-2671-2010; Pack, Svetlana/C-2020-2014 OI Hofbauer, Gunther/0000-0003-0542-7989; NR 6 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1998 VL 111 IS 3 BP 539 EP 540 PG 2 WC Dermatology SC Dermatology GA 114CU UT WOS:000075592200034 PM 9740255 ER PT J AU Arseven, A McDermott, MM O'Brien, E Guralnik, JM AF Arseven, A McDermott, MM O'Brien, E Guralnik, JM TI Increased prevalence of depressive symptoms among men and women with peripheral arterial disease. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Chicago, IL USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1998 VL 46 IS 7 SU S BP 281A EP 281A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 113YX UT WOS:000075582600195 ER PT J AU Kanegane, C Sgadari, C Kanegane, H Teruya-Feldstein, J Yao, L Gupta, G Farber, JM Liao, F Liu, L Tosato, G AF Kanegane, C Sgadari, C Kanegane, H Teruya-Feldstein, J Yao, L Gupta, G Farber, JM Liao, F Liu, L Tosato, G TI Contribution of the CXC chemokines IF-10 and Mig to the antitumor effects of IL-12 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Burkitt lymphoma; athymic mice, angiogenesis; cancer treatment ID CELL STIMULATORY FACTOR; NATURAL-KILLER-CELLS; INTERFERON-INDUCIBLE PROTEIN-10; LYMPHOCYTE MATURATION FACTOR; ANGIOGENESIS IN-VIVO; X-C CHEMOKINE; IFN-GAMMA; HETERODIMERIC CYTOKINE; FACTOR INTERLEUKIN-12; RECOMBINANT IL-12 AB The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferon-gamma-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IF-10 or Mg injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-gamma (IFN-gamma), IP-10, and Mig genes and proteins in the tumor. Levels of IF-10 and Mig expression in the tumor; the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IF-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IF-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. PharMingen, San Diego, CA USA. RP Tosato, G (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Bldg 29A,Rm 2D16,1401 Rockville Pike HFM-538, Rockville, MD 20852 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 42 TC 131 Z9 136 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1998 VL 64 IS 3 BP 384 EP 392 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 116VE UT WOS:000075745100014 PM 9738666 ER PT J AU Clore, GM Murphy, EC Gronenborn, AM Bax, A AF Clore, GM Murphy, EC Gronenborn, AM Bax, A TI Determination of three-bond (1)H3 '-P-31 couplings in nucleic acids and protein nucleic acid complexes by quantitative J correlation spectroscopy SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE H-1-P-31 couplings; quantitative J correlation; nucleic acids; protein-nucleic acid complexes ID TWO-DIMENSIONAL NMR; C-13 NMR; CONFORMATIONAL-ANALYSIS; CORRELATION SPECTRA; KARPLUS EQUATION; TORSION ANGLE; CONSTANTS; FRAGMENTS; REPARAMETRIZATION; OLIGONUCLEOTIDES AB A new sensitive two-dimensional quantitative J correlation experiment is described for measuring 3J(H3'-P) couplings in nucleic acids and protein-nucleic acid complexes. The method is based on measuring the change in intensity of the H-1-H-1 cross peaks in a constant-time H-1-H-1 COSY experiment which occurs in the presence and absence of 3J(H3'-P) dephasing during the constant-time evolution period. For protein-nucleic acid complexes where the protein is C-13-labeled but the nucleic acid is not,C-12-filtering is readily achieved by the application of a series of C-13 purge pulses during the constant time evolution period without any loss of signal-to-noise of the nucleic acid cross peaks. The method is demonstrated for the Dickerson DNA dodecamer and a 19 kDa complex of the transcription factor SRY with a 14mer DNA duplex. The same approach should be equally applicable to numerous other problems, including the measurement of J(H-Cd) couplings in cadmium-ligated proteins, or (3)J(CH) couplings in other selectively enriched compounds. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 17 TC 31 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 1998 VL 134 IS 1 BP 164 EP 167 DI 10.1006/jmre.1998.1513 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 126CP UT WOS:000076275600021 PM 9740744 ER PT J AU Luo, YQ Kokkonen, GC Wang, XT Neve, KA Roth, GS AF Luo, YQ Kokkonen, GC Wang, XT Neve, KA Roth, GS TI D2 dopamine receptors stimulate mitogenesis through pertussis toxin-sensitive G proteins and ras-involved ERK and SAP/JNK pathways in rat C6-D2L glioma cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE D2 receptors; mitogen-activated protein kinase; c-Jun NH2-terminal kinase; G proteins; signal transduction; mitogenesis; astrocytes; C6 glioma cells ID SIGNAL-REGULATED KINASE; BETA-GAMMA-SUBUNITS; CILIARY NEUROTROPHIC FACTOR; DOMINANT-NEGATIVE MUTANT; ANTERIOR-PITUITARY-CELLS; ARACHIDONIC-ACID RELEASE; LONG-TERM POTENTIATION; HAMSTER OVARY CELLS; MAP KINASE; C-JUN AB Dopamine D2 receptors are members of the G protein-coupled receptor superfamily and are expressed on both neurons and astrocytes, Using rat C6 glioma cells stably expressing the rat D2L receptor, we show here that dopamine (DA) can activate both the extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) pathways through a mechanism involving D2 receptor-G protein complexes and the Ras GTP-binding protein. Agonist binding to D2 receptors rapidly activated both kinases within 5 min, reached a maximum between 10 and 15 min, and then gradually decreased by 60 min. Maximal activation of both kinases occurred with 100 nM DA, which produced a ninefold enhancement of ERK activity and a threefold enhancement of JNK activity. DA-induced kinase activation was prevented by either (+)-butaclamol, a selective D2 receptor antagonist, or pertussis toxin, an uncoupler of G proteins from receptors, but not by (-)-butaclamol, the inactive isomer of (+)-butaclamol. Cotransfection of RasN17, a dominant negative Ras mutant, prevented DA-induced activation of both ERK and JNK. PD098059, a specific MEK1 inhibitor, also blocked ERK activation by DA. Transfection of SEK1 (K --> R) vector, a dominant negative SEK1 mutant, specifically prevented DA-induced JNK activation and subsequent c-Jun phosphorylation without effect on ERK activation. Furthermore, stimulation of D2 receptors promoted [H-3]thymidine incorporation with a pattern similar to that far kinase activation. DA mitogenesis was tightly linked (MAPK) and JNK pathways. Transfection with RasN17 and application of PD098059 blocked DA-induced DNA synthesis. Transfection with Flag Delta 169, a dominant negative c-Jun mutant, also prevented stimulation of to Ras-dependent mitogen-activated protein kinase [H-3]thymidine incorporation by DA. The demonstration of D2 receptor-stimulated MAPK pathways may help to understand dopaminergic physiological functions in the CNS. C1 NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, Baltimore, MD 21224 USA. NIA, Gene Express & Aging Sect, Ctr Gerontol Res, Baltimore, MD 21224 USA. VA Med Ctr, Portland, OR USA. RP Luo, YQ (reprint author), NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, 940 Eastern Ave,4E02,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 74 TC 78 Z9 79 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1998 VL 71 IS 3 BP 980 EP 990 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 112DG UT WOS:000075478400010 PM 9721723 ER PT J AU Edelman, JA Keller, EL AF Edelman, JA Keller, EL TI Dependence on target configuration of express saccade-related activity in the primate superior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENTS; BURST NEURONS; MONKEY; STIMULI; METRICS; CORTEX; FIELDS; CELLS AB To help understand how complex visual stimuli are processed into short-latency saccade motor programs, the activity of visuomotor neurons in the deeper layers of the superior colliculus was recorded while two monkeys made express saccades to one target and to two targets. It has been shown previously that the visual response and perimotor discharge characteristic of visuomotor neurons temporally coalesce into a single burst of discharge for express saccades. Here we seek to determine whether the distributed visual response to two targets spatially coalesces into a command appropriate for the resulting saccade. Two targets were presented at identical radial eccentricities separated in direction by 45 degrees. A gap paradigm was used to elicit express saccades. Express saccades were more likely to land in between the two targets than were saccades of longer latency. The speeds of express saccades to two targets were similar to those of one target of similar vector, as were the trajectories of saccades to one and two targets. The movement fields for express saccades to two targets were more broad than those for saccades to one target for all neurons studied. For most neurons, the spatial pattern of discharge for saccades to two targets was better explained as a scaled version of the visual response to two spatially separate targets than as a scaled version of the perimotor response accompanying a saccade to a single target. Only the discharge of neurons with large movement fields could be equally well explained as a visual response to two targets or as a perimotor response for a one-target saccade. For most neurons, the spatial properties of discharge depended on the number of targets throughout the entire saccade-related burst. These results suggest that for express saccades to two targets the computation of saccade vector is not complete at the level of the superior colliculus for most neurons and an explicit process of target selection is not necessary at this level for the programming of an express saccade. C1 Univ Calif Berkeley, Grad Grp Bioengn, Berkeley, CA 94720 USA. Smith Kettlewell Eye Res Inst, San Francisco, CA 94115 USA. RP Edelman, JA (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. NR 34 TC 75 Z9 75 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1998 VL 80 IS 3 BP 1407 EP 1426 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 125JB UT WOS:000076233500032 PM 9744949 ER PT J AU Gottschalk, W Pozzo-Miller, LD Figurov, A Lu, B AF Gottschalk, W Pozzo-Miller, LD Figurov, A Lu, B TI Presynaptic modulation of synaptic transmission and plasticity by drain-derived neurotrophic factor in the developing hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; presynaptic; hippocampus; LTP; synaptic fatigue; plasticity ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; DEVELOPING NEUROMUSCULAR SYNAPSES; RAT HIPPOCAMPUS; TRANSMITTER RELEASE; CORTICAL-NEURONS; DENDRITIC GROWTH; VISUAL-CORTEX; PAIRED-PULSE; TIME-COURSE AB In addition to the regulation of neuronal survival and differentiation, neurotrophins may play a role in synapse development and plasticity. Application of brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) in CA1 synapses of neonatal hippocampus, which otherwise exhibit only shortterm potentiation. This is attributable, at least in part, to an attenuation of the synaptic fatigue induced by high-frequency stimulation (HFS). However, the prevention of synaptic fatigue by BDNF could be mediated by an attenuation of synaptic vesicle depletion from presynaptic terminals and/or a reduction of the desensitization of postsynaptic receptors. Here we provide evidence supporting a presynaptic effect of BDNF. The effect of BDNF on synaptic fatigue depended on the stimulation frequency, not on the stimulus duration nor on the number of stimulation pulses. BDNF was only effective when the synapses were stimulated at frequencies >50 Hz. Treatment with BDNF also potentiated paired-pulse facilitation (PPF), a parameter reflecting changes in the properties of presynaptic terminals. This effect of BDNF was restricted only to PPF elicited with interpulse intervals less than or equal to 20 msec. Changes in the extracellular calcium concentration altered the magnitude of the BDNF effect on PPF and synaptic responses to HFS, suggesting that BDNF regulates neurotransmitter release. When the desensitization of glutamate receptors was blocked by cyclothiazide or aniracetam, the BDNF potentiation of the synaptic responses to HFS was unaltered. Taken together, these results suggest that BDNF acts presynaptically. When two pathways in the same slice were monitored simultaneously, BDNF treatment potentiated the tetanized pathway without affecting the synaptic efficacy of the untetanized pathway. The selective potentiation of high-frequency transmission by BDNF appears to contribute directly to the effect of BDNF on LTP rather than indirectly by inducing the release of additional diffusible factors. The preferential potentiation of highly active synapses by BDNF may have implications in the Hebbian mechanism of synaptic plasticity. C1 NICHHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38,49 Convent Dr, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; yu, yan/C-2322-2012 NR 53 TC 214 Z9 219 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 1998 VL 18 IS 17 BP 6830 EP 6839 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 112NT UT WOS:000075501200022 PM 9712654 ER PT J AU Ziemann, U Hallet, M Cohen, LG AF Ziemann, U Hallet, M Cohen, LG TI Mechanisms of deafferentation-induced plasticity in human motor cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mechanisms of cortical plasticity; transient ischemic forearm deafferentation; pharmacological blockade of plasticity; GABA; glutamate; paired-pulse inhibition; human motor cortex ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; ACTIVITY-DEPENDENT REGULATION; PRIMARY SOMATOSENSORY CORTEX; POST-TETANIC POTENTIATION; METHYL-D-ASPARTATE; RAT VISUAL-CORTEX; ADULT FLYING-FOX; NMDA RECEPTORS; CORTICAL REORGANIZATION AB Deafferentation induces rapid plastic changes in the cerebral cortex, probably via unmasking of pre-existent connections. Several mechanisms may contribute, such as changes in neuronal membrane excitability, removal of local inhibition, or various forms of short- or long-term synaptic plasticity. To understand further the mechanisms involved in cortical plasticity we tested the effects of CNS-active drugs in a plasticity model, in which forearm ischemic nerve block (INB) was combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) of the deafferented human motor cortex, rTMS was used to upregulate the plastic changes caused by INB. We studied six healthy subjects. In two control sessions without drug application, INB plus rTMS increased the motor-evoked potential (MEP) size and decreased intracortical inhibition (ICI) measured with single- and paired-pulse TMS in the biceps brachii muscle proximal to INB. A single oral dose of the benzodiazepine lorazepam (2 mg) or the voltage-gated Na+ and Ca2+ channel blocker lamotrigine (300 mg) abolished these changes. The NMDA receptor blocker dextromethorphan (150 mg) suppressed the reduction in ICI but not the increase in MEP size. With sleep deprivation, used to eliminate sedation as a major factor of these drug effects, INB plus rTMS induced changes similar to that seen in the control sessions. The findings suggest that (1) the INB plus rTMS-induced increase in MEP size involves rapid removal of GABA-related cortical inhibition and short-term changes in synaptic efficacy dependent on Na+ or Ca2+ channels and that (2) the long-lasting (>60 min) reduction in ICI is related to long-term potentiation-like mechanisms given its duration and the involvement of NMDA receptor activation. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 85 TC 252 Z9 255 U1 1 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 1998 VL 18 IS 17 BP 7000 EP 7007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 112NT UT WOS:000075501200036 PM 9712668 ER PT J AU Forsberg-Nilsson, K Behar, TN Afrakhte, M Barker, JL McKay, RDG AF Forsberg-Nilsson, K Behar, TN Afrakhte, M Barker, JL McKay, RDG TI Platelet-derived growth factor induces chemotaxis of neuroepithelial stem cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE nestin; migration; development; rat ID CENTRAL-NERVOUS-SYSTEM; FACTOR ALPHA-RECEPTOR; CEREBRAL-CORTEX; PROGENITOR CELLS; BETA-RECEPTOR; FACTOR PDGF; B-CHAIN; DEVELOPMENTAL EXPRESSION; POSTMITOTIC NEURONS; VENTRICULAR ZONE AB The ability of differentiating cells to migrate within the developing central nervous system (CNS) depends on extrinsic guidance signals, some of which are growth factors. In this study we have investigated the chemotactic response of cultured stem cells from the embryonic rat cortex to platelet-derived growth factor (PDGF). Nestin-positive stem cells from the developing CNS can be maintained and expanded in vitro under serum-free conditions in the presence of basic fibroblast growth factor (bFGF). Northern blot analysis of PDGF receptor expression revealed both alpha- and P-receptors on bFGF-treated neural stem cells. Both PDGF-AA and PDGF-BB readily induced directed migration of cultured neuroepithelial cells as measured in a microchemotaxis assay. Blocking of the migratory response was achieved by incubation with PDGF isoform-specific antibodies. More than 90% of the migrating cells were nestin-positive and incorporation of BrdU was also seen suggesting the cells to be immature and not yet committed to a specific cell lineage. These findings suggest a role for PDGF in cell migration in the developing cortex. J. Neurosci. Res. 53:521-530, 1998, (C) 1998 Wiley-Liss, Inc. C1 Uppsala Univ, Dept Pathol, S-75185 Uppsala, Sweden. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Forsberg-Nilsson, K (reprint author), Uppsala Univ, Dept Pathol, S-75185 Uppsala, Sweden. NR 55 TC 61 Z9 65 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1998 VL 53 IS 5 BP 521 EP 530 DI 10.1002/(SICI)1097-4547(19980901)53:5<521::AID-JNR2>3.0.CO;2-B PG 10 WC Neurosciences SC Neurosciences & Neurology GA 112EV UT WOS:000075481900002 PM 9726423 ER PT J AU Luepker, RV Perry, CL Osganian, V Nader, PR Parcel, GS Stone, EJ Webber, LS AF Luepker, RV Perry, CL Osganian, V Nader, PR Parcel, GS Stone, EJ Webber, LS TI The child and adolescent trial for cardiovascular health (CATCH) SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on the Determination, Treatment, and Prevention of Obesity CY OCT 23-25, 1997 CL SUNSET BEACH, NORTH CAROLINA SP Univ N Carolina Chapel Hill, Inst Nutr, Univ N Carolina Chapel Hill, Sch Public Hlth, Univ N Carolina Chapel Hill, Dept Nutr, Univ N Carolina, Sch Med, E Carolina Univ DE cardiovascular disease; nutrition; physical activity; smoking; youth; school health ID ELEMENTARY-SCHOOL-CHILDREN; LONG-TERM OUTCOMES; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; 3RD-GRADE CHILDREN; EDUCATION-PROGRAM; INTERVENTION; PREVENTION; PROMOTION; TRACKING AB The Child and Adolescent Trial for Cardiovascular Health (CATCH) is a field study conducted in elementary schools that was designed to assess the outcomes of health behavior interventions for the primary prevention of cardiovascular disease. Beginning in 1991, third grade students (N = 5106) from ethnically diverse backgrounds in 96 public schools in California, Louisiana, Minnesota, and Texas were randomized to intervention or control status. Twenty-eight schools participated in a third through fifth gr-ade intervention that included food service modifications, enhanced physical education, and classroom health curricula. An additional 28 schools received these components plus family education. Outcomes were assessed using pre-randomization measures in early third grade and follow-up at the end of fifth grade. At the school level, the two primary endpoints were changes in the fat content of food service lunch offerings and the amount of moderate to vigorous physical activity in the physical education programs. At the individual student level, endpoints included psychosocial factors, measures of eating and physical activity patterns, and physiologic measures. In the intervention school lunches, the percentage of energy intake from fat fell significantly more (from 38.7% to 31.9%) than in control lunches (from 38.9% to 36.2%) (P < 0.001). The intensity of physical activity in CATCH intervention schools was increased significantly compared with the control schools (P < 0.02). Self-reported energy intake from fat among students in the intervention schools was significantly reduced (from 32.7% to 30.3%) compared with the controls (from 32.6% to 32.2%) (P < 0.001). Intervention students reported significantly more daily vigorous physical activity than controls (58.6 vs. 46.5 minutes) (P < 0.003). Blood pressure, body size, and cholesterol measures did not differ significantly between treatment groups. No evidence of deleterious effects of the intervention on growth or development was observed. The CATCH intervention was able to modify the fat content of school lunches, increase daily school physical activity, and improve individual eating patterns and physical activity in children during three school years. Follow-lip of this cohort continues. (J. Nutr. Biochem. 9:525-534, 1998) (C) Elsevier Science Inc. 1998. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. Univ Texas, Ctr Hlth Promot Res & Dev, Houston, TX USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Tulane, LA USA. RP Luepker, RV (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. NR 64 TC 10 Z9 10 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 1998 VL 9 IS 9 BP 525 EP 534 DI 10.1016/S0955-2863(98)00042-4 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 119UN UT WOS:000075916400009 ER PT J AU Caballero, B Davis, S Davis, CE Ethelbah, B Evans, M Lohman, T Stephenson, L Story, M White, J AF Caballero, B Davis, S Davis, CE Ethelbah, B Evans, M Lohman, T Stephenson, L Story, M White, J TI Pathways: A school-based program for the primary prevention of obesity in American Indian children SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on the Determination, Treatment, and Prevention of Obesity CY OCT 23-25, 1997 CL SUNSET BEACH, NORTH CAROLINA SP Univ N Carolina Chapel Hill, Inst Nutr, Univ N Carolina Chapel Hill, Sch Public Hlth, Univ N Carolina Chapel Hill, Dept Nutr, Univ N Carolina, Sch Med, E Carolina Univ DE obesity; prevention; schoolchildren; American Indians ID NUTRITION EXAMINATION SURVEYS; CARDIOVASCULAR HEALTH CATCH; DAILY ENERGY-EXPENDITURE; DOUBLY LABELED WATER; PHYSICAL-ACTIVITY; HEART-RATE; PRESCHOOL-CHILDREN; ADOLESCENT TRIAL; NATIONAL-HEALTH; DIETARY-INTAKE AB This report describes the proposed intervention and outcome measurement procedures for the Pathways study. Pathways is a multicenter school-based study aimed at reducing the alarming increase in the prevalence of obesity in American Indian children. It is designed as a randomized clinical trial, involving approximately 2,000 third grade children in 40 schools in seven different American Indian communities. During a 3-year feasibility phase, which was just completed, the major components of the intervention (school food service, classroom curriculum, physical education program, and family involvement) were developed and pilot-tested. The measurement instruments for body composition; physical activity; dietary intake; and knowledge, attitudes, and behavior were also developed and validated. Comprehensive process evaluation procedures also were defined. As of this writing, the full-scale intervention program is being initiated and is scheduled to be completed in the spring of 2000. The primary aim of the Pathways intervention is to reduce average percent body fat in intervention-school children by at least 3% compared with control-school children by the end of the 3-year intervention. This goal is to be achieved primarily by an increase in physical activity and a reduction in the percent of dietary fat intake. The program does not seek to seduce dietary energy intake. Rather, it is based on the assumption that a healthier, lower-fat diet, combined with an increase in energy expenditure by increased physical activity, will result in fewer excess calories deposited as body fat. (J. Nutr. Biochem. 9:535-543, 1998) (C) Elsevier Science Inc. 1998. C1 Johns Hopkins Univ, Ctr Human Nutr, Baltimore, MD 21205 USA. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Arizona, Tucson, AZ USA. RP Caballero, B (reprint author), Johns Hopkins Univ, Ctr Human Nutr, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Biguzzi, Felipe/E-4724-2015 FU NHLBI NIH HHS [U01 HL050885, U01 HL050867, U01 HL050869, U01 HL050905, U01 HL050907] NR 51 TC 45 Z9 45 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 1998 VL 9 IS 9 BP 535 EP 543 DI 10.1016/S0955-2863(98)00049-7 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 119UN UT WOS:000075916400010 PM 27340341 ER PT J AU Medlicott, NJ Foster, KA Audus, KL Gupta, S Stella, VJ AF Medlicott, NJ Foster, KA Audus, KL Gupta, S Stella, VJ TI Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC) SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID CORNEAL EPITHELIAL-CELLS; MUSCLE DAMAGE; PHARMACEUTICAL APPLICATIONS; INTRAMUSCULAR INJECTIONS; BETA-CYCLODEXTRIN; SAFETY EVALUATION; INVITRO MODEL; CYTOTOXICITY; DERIVATIVES; TOXICITY AB The effect of dilution of parenteral vehicles (organic cosolvent and 0.1 M cyclodextrin solutions) on cultured endothelial cells (HUV-EC) were compared in vitro. Cell morphology was observed by phase contrast light microscopy and cell viability by measuring 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction or intracellular lactate dehydrogenase (LDH) activity and total protein. Disruption of the HUV-EC monolayer was observed at dilutions of 1 in 20 for the melphalan and PEP cosolvents, 1 in 100 for an investigational drug cosolvent, and 1 in 10 for 0.1 M dimethyl-beta-cyclodextrin. In comparison, 0.1 M SBE7M- and HP-beta-cyclodextrin caused only minor disruption at a 1 in 5 dilution. MTT reduction, intracellular LDH, and total protein were decreased following exposure to 1 in 10 dilution of the melphalan cosolvent. For other test solutions, intracellular LDH activity and total protein were measured, and reductions were observed following exposure to 1 in 10, 20, and 50 dilutions of the investigational drug cosolvent and 1 in 5 dilution of DM-beta-cyclodextrin (0.1 M). At a dilution of 1 in 10, no delayed toxicity was observed for cosolvents or cyclodextrin solutions. Hence, 0.1 M SBE7M- or HP-beta-cyclodextrin formulations may be less damaging to the venous endothelium at the site of injection than organic cosolvent formulations. C1 Univ Kansas, Sch Pharm, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. NCI, Bethesda, MD 20892 USA. RP Medlicott, NJ (reprint author), Univ Otago, Sch Pharm, POB 913, Dunedin, New Zealand. FU NCI NIH HHS [N01-CM-27755] NR 24 TC 24 Z9 26 U1 5 U2 7 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD SEP PY 1998 VL 87 IS 9 BP 1138 EP 1143 DI 10.1021/js9704442 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 117MQ UT WOS:000075785600017 PM 9724567 ER PT J AU Ekins, S Vandenbranden, M Ring, BJ Gillespie, JS Yang, TJ Gelboin, HV Wrighton, SA AF Ekins, S Vandenbranden, M Ring, BJ Gillespie, JS Yang, TJ Gelboin, HV Wrighton, SA TI Further characterization of the expression in liver and catalytic activity of CYP2B6 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HUMAN CYTOCHROME-P450; MICROSOMAL CYTOCHROME-P-450; N-DEMETHYLATION; DRUG-METABOLISM; MESSENGER-RNAS; BINDING; MIDAZOLAM; P4502B6; RAT; INHIBITORS AB Previous studies in this laboratory have determined the lack of specificity of several antibody and substrate probes of CYP2B6. The goals of the current study were to examine the expression of CYP2B6 in a bank of human liver microsome (HLM) samples using a new specific monoclonal antibody (MAb 49-10-20) and to further characterize the substrate specificity of CYP2B6. A 100-fold variability in expression of immunodetactable CYP2B6 was demonstrated in a bank of 19 HLM samples (0.7 pmol/mg protein to 71.1 pmol/mg protein) using MAb 49-10-20. CYP2B6 levels were found to significantly (P < .0001) correlate with S-mephenytoin N-demethylation to nirvanol (r(2) = -0.89), 7-hydroxy-4-trifluoromethylcoumarin formation (r(2) = 0.81) and several markers of CYP3A levels and activity. The relationships between nirvanol formation and CYP3A levels or activity were found to depend on two HLM samples. K-m(apparent) values were generated for benzyloxyresorufin O-deethylation (1.3 mu M), benzphetamine N-demethylation (93.4 mu M), 3-cyano 7-ethoxycoumarin O-deethylation (71.3 mu M), midazolam 1'-hydroxylation (46.1 mu M) and 4-chloromethyl-7-ethoxycoumarin O-deethylation (33.7 mu M) using expressed CYP2B6. Testosterone 16 beta-hydroxylation by expressed CYP2B6 resulted in atypical kinetics characteristic of substrate activation. The data best fit the Hill equation with a K-m (apparent) of 50.5 mu M and an n of 1.3 (n = number of sites bound by activator). In conclusion, the highly specific MAb 49-10-20 was used to provide further confirmation that S-mephenytoin N-demethylation to nirvanol is a CYP2B6 selective probe. Finally, some, but not all substrates of CYP2B6 demonstrate autoactivation. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Dept Drug Disposit, Indianapolis, IN 46285 USA. NCI, Bethesda, MD 20892 USA. RP Wrighton, SA (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Dept Drug Disposit, Drop Code 0825, Indianapolis, IN 46285 USA. OI Ekins, Sean/0000-0002-5691-5790 NR 40 TC 141 Z9 146 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1998 VL 286 IS 3 BP 1253 EP 1259 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120KB UT WOS:000075954600020 PM 9732386 ER PT J AU Ibeanu, GC Goldstein, JA Meyer, U Benhamou, S Bouchardy, C Dayer, P Ghanayem, BI Blaisdell, J AF Ibeanu, GC Goldstein, JA Meyer, U Benhamou, S Bouchardy, C Dayer, P Ghanayem, BI Blaisdell, J TI Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID S-MEPHENYTOIN; OXIDATION POLYMORPHISM; ESCHERICHIA-COLI; CHINESE SUBJECTS; HYDROXYLATION; EXPRESSION; PHENOTYPE; DEBRISOQUIN; POPULATIONS; SUBFAMILY AB A genetic polymorphism in the metabolism of the anticonvulsant drug S-mephenytoin has been attributed to defective CYP2C19 alleles. This genetic polymorphism displays large interracial differences with the poor metabolizer (PM) phenotype representing 2-5% of Caucasian and 13-23% of Oriental populations. In the present study, we identified two new mutations in CYP2C19 in a single Swiss Caucasian PM outlier (JOB I)whose apparent genotype (CYP2C19*1/CYP2C19*2) did not agree with his PM phenotype. These mutations consisted of a single base pair mutation (G(395)A) in exon 3 resulting in an Arg(132)-->Gln coding change and a (G(276)C) mutation in exon 2 resulting in a coding change Glu(92)-->Asp. However, the G(276)C mutation and the G(395)A mutation resided on separate alleles. Genotyping tests of a family study of JOB1 showed that the exon 2 change occurred on the CYP2C19*2 allele, which also contained the known splice mutation in exon 5 (this variant is termed CYP2C19*2B to distinguish it from the original splice variant now termed CYP2C19*2A). The exon 3 mutation resided on a separate allele (termed CYP2C19*6). In all other respects this allele was identical to one of two wild-type alleles, CYP2C19*1B. The incidence of CYP2C19*6 in a European Caucasian population phenotyped for mephenytoin metabolism was 0/344 (99% confidence limits of 0 to 0.9%). Seven of 46 Caucasian CYP2C19*2 alleles were CYP2C19*2B(15%) and 85% were CYP2C19*2A. The Arg,,,Gln mutation was produced by site-directed mutatgenesis and the recombinant protein expressed in a bacterial cDNA expression system. Recombinant CYP2C19 6 had negligible catalytic activity toward S-mephenytoin compared with CYP2C19 1B, which is consistent with the conclusion that CYP2C19*6 represents a PM allele. Thus, the new CYP2C19*6 allele contributes to the PM phenotype in Caucasians. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Basel, Biozentrum, Dept Pharmacol, CH-4056 Basel, Switzerland. INSERM U351, Vilnius, Lithuania. Geneva Canc Registry, Geneva, Switzerland. Univ Hosp Geneva, Geneva, Switzerland. RP Blaisdell, J (reprint author), NIEHS, POB 12233,Room C324,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Blaisdel@NIEHS.NIH.GOV RI Benhamou, Simone/K-6554-2015 NR 41 TC 92 Z9 98 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1998 VL 286 IS 3 BP 1490 EP 1495 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120KB UT WOS:000075954600049 PM 9732415 ER PT J AU Mayer, ML Bahring, R Bowie, D AF Mayer, ML Bahring, R Bowie, D TI Glutamate receptor channel block by polyamines SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract ID RECOMBINANT C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RI Bahring, Robert/F-7146-2010; Mayer, Mark/H-5500-2013 NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP PY 1998 VL 511P SI SI BP 16S EP 16S PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 130RX UT WOS:000076535100252 ER PT J AU Nedvidkova, J Haluzik, M Pacak, K Nedvidek, J Schreiber, V AF Nedvidkova, J Haluzik, M Pacak, K Nedvidek, J Schreiber, V TI Methylene Blue inhibits oestrogen-induced anterior pituitary growth: role of NO synthase and the dopaminergic systems SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract ID RATS C1 Charles Univ, Fac Med 1, Inst Endocrinol, Prague, Czech Republic. Charles Univ, Fac Med 1, Dept Med 3, Prague, Czech Republic. AS CR, Inst Physiol, Prague, Czech Republic. NICHD, Dev Endocrinol Branch, Bethesda, MD USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP PY 1998 VL 511P SI SI BP 50P EP 50P PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 130RX UT WOS:000076535100066 ER PT J AU McBain, CJ AF McBain, CJ TI A short-term mechanism of plasticity for interneurones? SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID AMPA; RECTIFICATION; RECEPTORS; BLOCK C1 NICHD, CMN, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, CMN, Room 5A72,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. EM chrismcb@codon.nih.gov NR 6 TC 12 Z9 12 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 1998 VL 511 IS 2 BP 331 EP 331 DI 10.1111/j.1469-7793.1998.331bh.x PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 125JD UT WOS:000076233700001 ER PT J AU Horowitz, AM Moon, HS Goodman, HS Yellowitz, JA AF Horowitz, AM Moon, HS Goodman, HS Yellowitz, JA TI Maryland adults' knowledge of oral cancer and having oral cancer examinations SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE Maryland adults' knowledge about oral cancer; oral cancer examinations; prevention; early detection ID PREVENTION AB Objectives: This study sought to determine (1) knowledge of risk factors for oral cancer, (2) knowledge of signs and symptoms of oral cancers, and (3) factors associated with having had an oral cancer examination among 916 Maryland adults 18 years of age and older. Methods: A statewide, random-digit dial, computer-assisted telephone survey was conducted. The pretested instrument consisted of 32 questions that required 12 minutes to complete. Results: Overall, level of knowledge about risk factors for and signs and symptoms of oral cancers was low; misinformation was high. Although 85 percent reported hearing about oral or mouth cancer, only 28 percent of the respondents reported having had an oral cancer examination. Of these, 20 percent had the exam during the past year-the recommended frequency for persons 40 years of age or older. In logistic regression analysis, adults more likely to have had an oral cancer examination included those who thought personal behavior causes more cancer than environmental factors; had more knowledge about risk factors for oral cancer; and were 40-64 years of age, white, and better educated than their counterparts (P<.05). The primary reasons for not having an exam were "no reason/didn't know I should" and "doctor/dentist didn't recommend." Conclusions: These results demonstrate a need for interventions designed to increase knowledge levels of risk factors for, signs, and symptoms of oral cancers and the need for oral cancer examinations; and to increase oral cancer examinations. C1 NIDR, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Sch Dent, Seoul, South Korea. Maryland Dept Hlth & Mental Hyg, Off Oral Hlth, Baltimore, MD USA. Univ Maryland, Dept Oral Hlth Care Delivery, College Pk, MD 20742 USA. RP Horowitz, AM (reprint author), NIDR, NIH, Bethesda, MD 20892 USA. NR 15 TC 50 Z9 51 U1 0 U2 2 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1998 VL 58 IS 4 BP 281 EP 287 DI 10.1111/j.1752-7325.1998.tb03010.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 206MD UT WOS:000080882100005 PM 10390710 ER PT J AU O'Connell, PG Siegel, KL Kepple, TM Stanhope, SJ Gerber, LH AF O'Connell, PG Siegel, KL Kepple, TM Stanhope, SJ Gerber, LH TI Forefoot deformity, pain, and mobility in rheumatoid and nonarthritic subjects SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; foot; biomechanics; gait ID FOOT; GAIT; ARTHRITIS; ANKLE AB Objective. To evaluate how painful metatarsal arthritis affects foot and ankle mechanics and mobility. Methods. We studied 16 symptomatic forefeet in 10 patients with rheumatoid arthritis (RA) and compared them with 14 asymptomatic forefeet in 7 nonarthritic subjects. RA limbs with significant disease at other locations were excluded. We measured pain and deformity of the foot using a visual analog scale and a modified articular index. A video based 3 dimensional gait analysis system and farce platform were used to collect data on subjects walking barefoot at a self-selected pace according to an established protocol. Mobility level was quantified using the Sickness Impact Profile (SIP) ambulation subscale. Results. We observed considerable pain and deformity of the forefeet of RA subjects. During gait, motion and force measures revealed that RA subjects significantly (p < 0.005) delayed and reduced forefoot loading, which minimized use of the foot as a rigid level for push off. As a result, stride lengths were shorter and gait was slower compared to nonarthritic subjects. SIP scores revealed that these changes in gait resulted in moderate disability in RA subjects (p = 0.05). Conclusion. Impairments of the forefoot due to RA include pain and deformity, which produce characteristic stance phase abnormalities in foot function, a slow walking speed, and moderate disability. C1 NIH, Dept Rehabil Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gerber, LH (reprint author), NIH, Dept Rehabil Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 6S 235,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 23 TC 44 Z9 44 U1 2 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1998 VL 25 IS 9 BP 1681 EP 1686 PG 6 WC Rheumatology SC Rheumatology GA 118LM UT WOS:000075839800005 PM 9733446 ER PT J AU Davis, JC Fessler, BJ Tassiulas, IO McInnes, IB Yarboro, CH Pillemer, S Wilder, R Fleisher, TA Klippel, JH Boumpas, DT AF Davis, JC Fessler, BJ Tassiulas, IO McInnes, IB Yarboro, CH Pillemer, S Wilder, R Fleisher, TA Klippel, JH Boumpas, DT TI High dose versus low dose fludarabine in the treatment of patients with severe refractory rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; fludarabine; nucleoside analog; treatment ID CONTROLLED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; GOLD SODIUM THIOMALATE; FACTOR-ALPHA CA2; MONOCLONAL-ANTIBODY; DOUBLE-BLIND; FUSION PROTEIN; METHOTREXATE; THERAPY; COMBINATION AB Objective. Fludarabine, a nucleoside analog that targets both resting and proliferating lymphocytes, is a promising drug for the treatment of autoimmune diseases. We conducted a 2 dose, open label clinical trial to evaluate the toxicity/safety of the fludarabine treatment and its clinical and immunological effects. Methods. Twenty-six patients with severe rheumatoid arthritis (RA) refractory to treatment with at least one slow acting antirheumatic drug were treated with intravenous fludarabine [20 mg/m(2) body surface area (n = 12) or 30 mg/m(2) body surface area (n = 14) per day for 3 consecutive days] given monthly for 6 months. Second line agents with the exception of glucocorticoids were discontinued at least 4 weeks before study entry. Measurements included toxicity and tolerability monitored at monthly intervals; efficacy, by both a 50% reduction in tender or swollen joint count and American College of Rheumatology (ACR) criteria for 20% response; and phenotypic analysis of peripheral blood mononuclear cells and T cell functional assays. Results. Using intention-to-treat analysis, 2 of 12 (17%) patients in the low dose and 7 of 14 (50%) in the high dose groups had 50% or greater reduction in tender and/or swollen joint count after 6 months of therapy compared to baseline (p = 0.09). Two of 12 (17%) in the low dose group and 5 of 14 (36%) in the high dose group met ACR criteria for 20% improvement (p = 0.28). No immediate toxicity was observed. Several infections occurred, including 3 episodes of limited Herpes zoster, which responded to standard therapy. Significant lymphopenia involving T and B cells was observed in all patients. Both naive (CD4+CD45RA+) and memory CD4+ T cells (CD4+CD45RO+) were reduced (naive > memory), No significant regeneration of naive T cells was observed, which may suggest limited thymic regenerative capacity, Fludarabine decreased the proliferative response of peripheral blood lymphocytes to mitogens, as well as the production of T cell (interleukin 2 and interferon-gamma) and monocyte derived (tumor necrosis factor-alpha and IL-10) cytokines. Conclusion, Fludarabine treatment of patients with severe, refractory RA resulted in significant lymphopenia, suppression of lymphocyte function, and clinical improvement in the high dose group. There was no immediate toxicity; however, several infections occurred. Controlled trials are needed to substantiate the clinical improvement observed in this open label trial. C1 NIAMSD, Clin Invest Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Serv Immunol, Bethesda, MD 20892 USA. RP Davis, JC (reprint author), Univ Calif San Francisco, Div Rheumatol, 533 Parnassus Ave,Room U-383,Box 0633, San Francisco, CA 94143 USA. NR 71 TC 18 Z9 20 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1998 VL 25 IS 9 BP 1694 EP 1704 PG 11 WC Rheumatology SC Rheumatology GA 118LM UT WOS:000075839800007 PM 9733448 ER PT J AU Fraenkel, L Roubenoff, R LaValley, M McAlindon, T Chaisson, C Evans, S Harris, T Dinarello, CA Felson, DT AF Fraenkel, L Roubenoff, R LaValley, M McAlindon, T Chaisson, C Evans, S Harris, T Dinarello, CA Felson, DT TI The association of peripheral monocyte derived interleukin 1 beta (IL-1 beta), IL-1 receptor antagonist, and tumor necrosis factor-alpha with osteoarthritis in the elderly SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE blood; cytokines; osteoarthritis; cohort study ID CARTILAGE PANNUS JUNCTION; HUMAN ARTICULAR-CARTILAGE; BLOOD MONONUCLEAR-CELLS; C-REACTIVE PROTEIN; RHEUMATOID-ARTHRITIS; SYNOVIAL-MEMBRANE; KNEE OSTEOARTHRITIS; CYTOKINE PRODUCTION; MESSENGER-RNA; FACTOR-BETA AB Objective. To examine the association of peripheral blood mononuclear cell (PBMC) derived interleukin 1 beta (IL-1 beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor alpha (TNF-alpha), and radiographic osteoarthritis (OA) in the elderly. Methods. A total of 703 subjects (436 women, 267 men, mean age 78.5 +/- 3.5 yrs) had both knee and hand radiographs, and cytokines were measured during the 22nd biennial examination of the Framingham Cohort. PBMC derived IL-1 beta, IL-1Ra, and TNF-a production was assessed using a non-cross reacting polyclonal radioimmunoassay, Knee OA was defined as a score of greater than or equal to 2 using a modified Kellgren and Lawrence scale. The presence of osteophytes and joint space narrowing were scored separately db a 0-3 scale, in which disease was defined a priori as a score >0 for each feature. Sex-specific odds ratios were calculated for knee OA after adjusting for weight, history of knee injury, and use of estrogen and nonsteroidal antiinflammatory drugs. Results, No uniform associations were found for IL-1 beta or IL-1Ra in men, or for TNF-alpha production and radiographic OA in either sex. We found possible associations for the highest levels of IL-1 beta production and the presence of knee osteophytes [OR = 2.0 (1.2-3.5)] and joint space narrowing [OR = 1.7 (1.1-2.8)] in women. Our data suggested a possible protective effect for IL-1Ra production and hand OA in women [OR = 0.6 (0.4-1.0)]. Conclusion. We found no consistent association of PBMC cytokine production and radiographic OA. However. women with the highest production of IL-1 beta and IL-1Ra had respectively higher rates of knee OA and lower rates of hand OA than expected. C1 Boston Univ, Med Ctr, Arthrit Ctr, Boston, MA 02118 USA. Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Fraenkel, L (reprint author), Boston Univ, Med Ctr, Arthrit Ctr, 715 Albany St,A203, Boston, MA 02118 USA. FU NIA NIH HHS [AG09300]; NIAID NIH HHS [AI15614]; NIAMS NIH HHS [AR20613] NR 48 TC 7 Z9 7 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1998 VL 25 IS 9 BP 1820 EP 1826 PG 7 WC Rheumatology SC Rheumatology GA 118LM UT WOS:000075839800025 PM 9733466 ER PT J AU Dries, DL Exner, DV Gersh, BJ Domanski, MJ Waclawiw, MA Stevenson, LW AF Dries, DL Exner, DV Gersh, BJ Domanski, MJ Waclawiw, MA Stevenson, LW TI Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: A retrospective analysis of the SOLVD trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; AMIODARONE; ABLATION; SURVIVAL; RHYTHM AB Objective. This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death. Background Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias. The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure. Methods. A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was con ducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality, progressive pump-failure death and arrhythmic death. Results. The patients with atrial fibrillation at baseline, compared to those in sinus rhythm, had greater all cause mortality (34% vs. 23%, p < 0.001), death attributed to pump-failure (16.7% vs. 9.4%, p < 0.001) and were more likely to reach the composite end point of death or hospitalization for heart failure (45% vs. 33%, p < 0.001), but there was no significant difference between the groups in arrhythmic deaths. After multivariate analysis, atrial fibrillation remained significantly associated with all-cause mortality (relative risk [RR] 1.34, 95% confidence interval [CI] 1.12 to 1.62, p = 0.002), progressive pump-failure death (RR 1.42, 95% CI 1.09 to 1.85, p = 0.01), the composite end point of death or hospitalization for heart failure (RR 1.26, 95% CI 1.03 to 1.42, p = 0.02), but not arrhythmic death (RR 1.13; 95% CI 0.75 to 1.71; p = 0.55). Conclusions. The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality, largely explained by an increased risk for pump-failure death. These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction. (J Am Cell Cardiol 1998;32:695-703) (C) 1998 by the American College of Cardiology. C1 NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, Rockledge Ctr 2, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Dries, DL (reprint author), NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, Rockledge Ctr 2, Room 8149,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM Ddries@aol.com NR 29 TC 522 Z9 542 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1998 VL 32 IS 3 BP 695 EP 703 DI 10.1016/S0735-1097(98)00297-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 118LE UT WOS:000075839000022 PM 9741514 ER PT J AU Slavkin, HC AF Slavkin, HC TI Building a dynamic picture of the dental and craniofacial complex: Progress in imaging SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 1998 VL 129 IS 9 BP 1301 EP 1306 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 118RK UT WOS:000075853600029 PM 9766113 ER PT J AU Maggi, S Minicuci, N Martini, A Langlois, J Siviero, P Pavan, M Enzi, G AF Maggi, S Minicuci, N Martini, A Langlois, J Siviero, P Pavan, M Enzi, G TI Prevalence rates of hearing impairment and comorbid conditions in older people: The Veneto study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MENTAL STATE; ADULTS; QUALITY; NOISE; LIFE AB OBJECTIVES: To investigate the prevalence rate of hearing impairment, assessed by both the Sanders' questionnaire and the speech audiometry test, and its association with health-related factors in the older population of the Veneto region of Italy. DESIGN: A cross-sectional survey. SETTING: A community-based population. PARTICIPANTS: 2398 noninstitutionalized individuals aged 65 years and older residing in the Veneto region of Italy. MEASUREMENTS: Prevalence rates of hearing impairment and odds ratios for its association with potential risk factors. MAIN RESULTS: The prevalence of self-reported hearing impairment at home was 8.1% in men and 7.4% in women, and in a social environment it was 11.1% and 9.3%, respectively. Women were less likely to report hearing difficulties in both environments, and increased risks were found for depression, age, and poor self-rated health. Participants with diabetes or cognitive impairment had increased odds only at home, in contrast to people with a low education level, who had increased odds only in a social environment. The prevalence assessed by speech audiometry was 19% in both sexes. Increased age, diabetes, and poor self-rated health were associated with impaired speech intelligibility, cognitive impairment was associated with 4-fold increased odds among past users of alcohol, and men with a low education level were about three times as likely as others to have hearing impairment. CONCLUSIONS: Speech audiometry testing detected a higher prevalence of hearing impairment than use of a self-reported questionnaire and was associated with poor self-rated health, history of diabetes, and cognitive impairment among past users of alcohol and among men with low levels of education. The association between hearing deficit and depressive symptomatology was confirmed only with self-reported hearing impairment. C1 Natl Res Council, Ctr Aging Study, Padova, Italy. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD USA. Univ Padua, Inst Internal Med, Padua, Italy. Univ Ferrara, Dept Otorhinolaryngol, Ferrara, Italy. RP Maggi, S (reprint author), Ist Igiene, Via Loredan 18, I-35131 Padua, Italy. RI MINICUCI, NADIA/D-5237-2016 OI MINICUCI, NADIA/0000-0002-0970-6531 NR 36 TC 31 Z9 31 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 BP 1069 EP 1074 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400001 PM 9736097 ER PT J AU Christmas, C Harman, SM St Clair, S Roy, T Tobin, JD O'Connor, KG Jayme, J Bellantoni, MF Blackman, MR AF Christmas, C Harman, SM St Clair, S Roy, T Tobin, JD O'Connor, KG Jayme, J Bellantoni, MF Blackman, MR TI Relationships of GH, IGF-I, testosterone (T), and body composition with bone in healthy elderly men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA A35 BP S16 EP S16 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400065 ER PT J AU Ebersold, C Vaitkevicius, P May, K Bryant, K Narrett, NGM Katz, R Andrus, B Bingham, R Parrish, S Fleg, J AF Ebersold, C Vaitkevicius, P May, K Bryant, K Narrett, NGM Katz, R Andrus, B Bingham, R Parrish, S Fleg, J TI Improvements in peak VO2 with aerobic training in subjects over 80 years. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Div Geriatr, Baltimore, MD 21205 USA. NIA, Div Geriatr, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P121 BP S47 EP S47 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400187 ER PT J AU Kiel, DP Langlois, JA Visser, M Rosen, CJ Hannan, MT Harris, T AF Kiel, DP Langlois, JA Visser, M Rosen, CJ Hannan, MT Harris, T TI Insulin-like growth factor (IGF-I) and bone mineral density (BMD) in older women and men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Hebrew Rehabil Ctr Aged, Div Aging,NIA,Maine Ctr Osteo Res & Educ, Boston, MA 02131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P151 BP S54 EP S54 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400217 ER PT J AU Pahor, M Guralnik, JM Wan, JY Ferrucci, L Penninx, B Lyles, A Ling, S AF Pahor, M Guralnik, JM Wan, JY Ferrucci, L Penninx, B Lyles, A Ling, S TI Osteoarticular pain and dose of analgesic medications: The women's health and aging study (WHAS) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P378 BP S111 EP S111 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400444 ER PT J AU Resnick, HE Halter, JB Harris, TB AF Resnick, HE Halter, JB Harris, TB TI Was the health status of older diabetic patients better in the 1980's than in the 1970's? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. VA Med Ctr, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P8 BP S18 EP S18 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400074 ER PT J AU Studenski, S Wallace, D Guralnik, J Chandler, J Duncan, P AF Studenski, S Wallace, D Guralnik, J Chandler, J Duncan, P TI Gait speed as a clinical vital sign SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NIA, KCVA, Bethesda, MD 20892 USA. Merck Res Labs, Blue Bell, PA USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P170 BP S59 EP S59 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400236 ER PT J AU Studenski, S Wallace, D Guralnik, J Chandler, J Duncan, P AF Studenski, S Wallace, D Guralnik, J Chandler, J Duncan, P TI Clinically meaningful differences in gait speed SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, KCVA, Kansas City, KS 66103 USA. NIA, Bethesda, MD 20892 USA. Merck Res Labs, Blue Bell, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P302 BP S92 EP S92 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400368 ER PT J AU Vaitkevicius, P Ebersold, C May, K Bryant, K Gill, N Narrett, M Katz, R Andrus, B Bingham, R Parrish, S Fleg, J AF Vaitkevicius, P Ebersold, C May, K Bryant, K Gill, N Narrett, M Katz, R Andrus, B Bingham, R Parrish, S Fleg, J TI Clinical factors limiting exercise compliance in the elderly. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Div Geriatr, Baltimore, MD USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P122 BP S47 EP S47 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400188 ER PT J AU Schoolman, HM AF Schoolman, HM TI Then and now and when SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material AB Since the 1970s, it has been clear that the health community needs to develop a health care system that matches a person's needs with We expertise and technology to address those needs. The logical solution is a multi-tiered system. In such a system, physicians would provide second- and third-tier services and other health professionals would provide first- and second-tier services. Medical informatics should take on the challenge of supporting the decision to triage patients from one tier of service to another. Triage decisions are different from other decisions in health sciences because they take place early in the life of a problem, when little information is available, and can be made safely if adjusted to tolerate erring on the side of referral. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Schoolman, HM (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 1998 VL 5 IS 5 BP 401 EP 403 PG 3 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 120AQ UT WOS:000075932200002 PM 9760386 ER PT J AU Baker, SG AF Baker, SG TI Analysis of survival data from a randomized trial with all-or-none compliance: Estimating the cost-effectiveness of a cancer screening program SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE all-or-none compliance; cancer screening; composite linear models; cost-effectiveness; Kaplan-Meier; missing data; noncompliance; survival analysis ID FAILURE TIME MODEL; CLINICAL-TRIALS; CONFOUNDING FACTORS; CAUSAL INFERENCE; BREAST-CANCER; DESIGN; IDENTIFICATION; NONCOMPLIANCE; EFFICACY; SMOKING AB Many randomized cancer screening trials involve all-or-none compliance. Some subjects randomized to an offer of screening refuse screening, and some subjects randomized to no offer of screening obtain Screening outside the trial. The primary analysis to test whether or not cancer screening reduces cancer mortality is by intent-to-treat. To estimate the cost-effectiveness of screening, it is necessary to adjust for all-or-none compliance. Heretofore, adjustments for all-or-none compliance have been limited to a fixed-time endpoint. Estimating cost-effectiveness as dollars per life year saved requires an extension to the analysis of yearly survival data. In general, this involves modeling both the hazard for death from cancer and death from competing risk. Unconstrained estimates and variances can be written in closed-form notation. For the four yearly breast cancer screens with physical examination and mammography in the Health Insurance Plan of Greater New York study, the estimated cost-effectiveness for a $100 mammogram and $900 biopsy is $16,000 per life year saved with 95% confidence interval ($10,000, $45,000): In contrast, under an inappropriate intent-to-treat analysis, the estimated cost-effectiveness is $23,000 with 95% confidence interval ($14,000, $66,000). C1 NCI, Biometry Branch, Div Canc Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Branch, Div Canc Prevent, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 46 TC 45 Z9 45 U1 1 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 1998 VL 93 IS 443 BP 929 EP 934 DI 10.2307/2669831 PG 6 WC Statistics & Probability SC Mathematics GA 123BG UT WOS:000076105500013 ER PT J AU Rodriguez, GC Walmer, DK Cline, M Krigman, H Lessey, BA Whitaker, RS Dodge, R Hughes, CL AF Rodriguez, GC Walmer, DK Cline, M Krigman, H Lessey, BA Whitaker, RS Dodge, R Hughes, CL TI Effect of progestin on the ovarian epithelium of macaques: Cancer prevention through apoptosis? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE progestins; apoptosis; ovarian cancer; oral contraceptives ID ORAL-CONTRACEPTIVE USE; RETINOIC ACID; CELL-LINES; CHEMOPREVENTION; N-(4-HYDROXYPHENYL)RETINAMIDE; CARCINOGENESIS; RISK; LOCALIZATION; INDUCTION; THERAPY AB OBJECTIVE: The apoptosis pathway is a vital mechanism in vivo that functions to eradicate genetically damaged cells prone to malignancy. The purpose of this study was to determine whether oral contraceptives, which confer significant protection against subsequent epithelial ovarian cancer, induce apoptosis in the ovarian epithelium. METHODS: Female cynomolgus macaques (N = 75) were randomized to receive a diet for 35 months containing either no hormones, the oral contraceptive Triphasil (Wyeth-Ayerst Laboratories, Philadelphia, PA), the estrogenic component of Triphasil (ethinyl estradiol) alone, or the progestin component of Triphasil (levonorgestrel) alone, each administered in a cyclic fashion. At study termination, the animals underwent ovariectomy and the ovarian epithelium was examined morphologically and immunohistochemically for apoptosis. The percentage of ovarian epithelial cells undergoing apoptosis was measured in each animal and compared between the treatment groups. RESULTS: The median percentage of ovarian epithelial cells undergoing apoptosis by treatment was control (3.8%), ethinyl estradiol (1.8%), Triphasil (14.5%), and levonorgestrel (24.9%). Compared with control and ethinyl estradiol-treated monkeys, a statistically significant increase in the proportion of apoptotic cells was noted in the ovarian epithelium of monkeys treated with the oral contraceptive Triphasil (P less than or equal to .01) or levonorgestrel (P < .001), with a maximal effect (six-fold) seen in the group treated with levonorgestrel alone. CONCLUSION: Oral contraceptive progestin induces apoptosis in the ovarian epithelium. Given the importance of the apoptosis pathway for cancer prevention, an effective chemopreventive strategy may be possible using progestins or other agents that selectively induce apoptosis in the ovarian epithelium to prevent the development of ovarian cancer. Copyright (C) 1998 by the Society for Gynecologic Investigation. C1 Duke Univ, Med Ctr, Div Gynecol Oncol, Dept Gynecol & Obstet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Reprod Endocrinol, Dept Obstet & Gynecol, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Comparat Med, Winston Salem, NC 27103 USA. Duke Univ, Ctr Med, Dept Pathol, Durham, NC 27710 USA. Univ N Carolina, Ctr Med, Div Reprod Endocrinol, Chapel Hill, NC USA. Duke Univ, Ctr Med, Duke Comprehens Canc Ctr, Dept Biostat, Durham, NC USA. RP Rodriguez, GC (reprint author), Duke Univ, Med Ctr, Div Gynecol Oncol, Dept Gynecol & Obstet, DUMC 3079, Durham, NC 27710 USA. FU NHLBI NIH HHS [R01HL46409] NR 43 TC 150 Z9 156 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD SEP-OCT PY 1998 VL 5 IS 5 BP 271 EP 276 DI 10.1016/S1071-5576(98)00017-3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 118RQ UT WOS:000075854100008 PM 9773403 ER PT J AU Tao, Q Robertson, KD Manns, A Hildesheim, A Ambinder, RF AF Tao, Q Robertson, KD Manns, A Hildesheim, A Ambinder, RF TI The Epstein-Barr virus major latent promoter Qp is constitutively active, hypomethylated, and methylation sensitive SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL LYMPHOMAS; CPG BINDING-PROTEIN; BAMHI-F-PROMOTER; DNA METHYLATION; BURKITT-LYMPHOMA; NASOPHARYNGEAL CARCINOMA; NUCLEAR ANTIGEN-1; GENE-TRANSCRIPTION; HODGKINS-DISEASE; EBNA-1 GENE AB Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is indispensable for viral DNA replication and episome maintenance in latency. Four promoters, Cp, Wp, Qp, and Fp, are known to drive EBNA1 expression. Here we show that the TATA-less Qp is constitutively active in a variety of EBV-positive [EBV(+)] tumors and cell lines, irrespective of the activities of other EBNA1 promoters, the type of viral latency, and the cell type. The transcription of highly regulated promoters such as the EBV Cp is known to be directly regulated by CpG methylation. To characterize the role of CpG methylation in the regulation of the constitutively active Qp, we performed bisulfite genomic sequencing and functional analyses using a methylation cassette transcriptional reporter assay. Twenty consecutive CpG sites (16 proximal to the Qp initiation site and 4 upstream of the adjacent Fp initiation site) were studied by bisulfite sequencing of DNA extracted from EBV(+) tumors and cell lines. Eighteen EBV(+) tumors of lymphoid (B, T, and NK cell) or epithelial origin and five Burkitt's lymphoma cell lines were studied. The 16 CPG sites proximal to Qp were virtually all unmethylated, but the 4 CpG sites upstream of the Fp initiation site were variably methylated. The methylation cassette assay showed that in vitro methylation of the Qp cassette (-172 to +32) resulted in strong repression of Qp activity in transient transfection. Thus, Qp is susceptible to repression by methylation but was found to be consistently hypomethylated and expressed in all tumors and tumor-derived cell lines studied. C1 Johns Hopkins Univ, Ctr Oncol, Sch Med, Baltimore, MD 21231 USA. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Ambinder, RF (reprint author), Johns Hopkins Univ, Ctr Oncol, Sch Med, 418 N Bond St, Baltimore, MD 21231 USA. FU NCI NIH HHS [R01 CA63532] NR 68 TC 53 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7075 EP 7083 PG 9 WC Virology SC Virology GA 109NK UT WOS:000075328600013 PM 9696800 ER PT J AU Park, EJ Vujcic, LK Anand, R Theodore, TS Quinnan, GV AF Park, EJ Vujcic, LK Anand, R Theodore, TS Quinnan, GV TI Mutations in both gp120 and gp41 are responsible for the broad neutralization resistance of variant human immunodeficiency virus type 1 MN to antibodies directed at V3 and non-V3 epitopes SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN; ANTIGENIC VARIATION; POINT MUTATION; IN-VIVO; HIV-1; INFECTION; GENERATION; REGION AB The escape of human immunodeficiency virus type 1 from effects of neutralizing antibodies was studied by using neutralization-resistant (NR) variants generated by growing the neutralization-sensitive (NS) wild-type MN virus in the presence of human serum with neutralizing antibodies, more than 99% of which were directed at the V3 region of gp120. The variants obtained had broad neutralization resistance to human sera, without limitation with respect to the V3 specificity of the sera. The molecular basis for the resistance was evaluated with molecularly cloned viruses, as well as with pseudoviruses expressing envelope glycoproteins of the NS and NR phenotypes. Nucleotide sequence analyses comparing NS and NR clones revealed a number of polymorphisms, including six in the V1/V2 region, two in C4/V5 of gp120, three in the leucine zipper (LZ) domain of gp41, and two id the second external putative alpha-helix region of gp41. A series of chimeras from NS and NR env genes was constructed, and each was presented on pseudoviruses to locate the domain(s) which conferred the phenotypic changes. The neutralization phenotypes of the chimeric clones were found to be dependent on mutations in both the C4/V5 region of gp120 and the LZ region of gp41. Additionally, interaction between mutations in gp120 and gp41 was demonstrated in that a chimeric env gene consisting of a gp120 coding sequence from an NS clone and a gp41 sequence from an NR clone yielded a pseudovirus with minimal infectivity. The possible significance of predicted amino acid changes in these domains is discussed. The results indicate that polyvalent antibodies predominantly directed against V3 can induce NR through selection for mutations that alter interactions of other domains in the envelope complex. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. US Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20850 USA. NIAID, Mol Biol Lab, Bethesda, MD 20892 USA. RP Quinnan, GV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM Quinnan@USUHSB.USUHS.mil FU NIAID NIH HHS [R21 AI037438, AI37438, R01 AI037438] NR 79 TC 49 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7099 EP 7107 PG 9 WC Virology SC Virology GA 109NK UT WOS:000075328600016 PM 9696803 ER PT J AU Chen, D Patton, JT AF Chen, D Patton, JT TI Rotavirus RNA replication requires a single-stranded 3 ' end for efficient minus-strand synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; SECONDARY STRUCTURE; SEQUENCE; PROTEIN; BINDING; PANHANDLE; GENOME; IDENTIFICATION; VISUALIZATION; POLYMERASE AB The segmented double-stranded (ds) RNA genome of the rotaviruses is replicated asymmetrically, with viral mRNA serving as the template for the synthesis of minus-strand RNA. Previous studies with cell-free replication systems have shown that the highly conserved termini of rotavirus gene 8 and 9 mRNAs contain cis-acting signals that promote the synthesis of dsRNA. Based on the location of the cis-acting signals and computer modeling of their secondary structure, the ends of the gene 8 or 9 mRNAs are proposed to interact in cis to form a modified panhandle structure that promotes the synthesis of dsRNA. In this structure, the last 11 to 12 nucleotides of the RNA, including the cis-acting signal that is essential for RNA replication, extend as a single-stranded tail from the panhandled region, and the 5' untranslated region folds to form a stem-loop motif. To understand the importance of the predicted secondary structure in minus-strand synthesis, mutations were introduced into viral RNAs which affected the 3' tail and the 5' stem-loop. Analysis of the RNAs with a cell-free replication system showed that, in contrast to mutations which altered the structure of the 5' stem-loop, mutations which caused complete or near-complete complementarity between the 5' end and the 3' tail significantly inhibited (greater than or equal to 10-fold) minus-strand synthesis. Likewise, incubation of wild-type RNAs,vith oligonucleotides which were complementary to the 3' tail inhibited replication. Despite their replication-defective phenotype, mutant RNAs with complementary 5' and 3' termini were shown to competitively interfere with the replication of wild-type mRNA and to bind the viral RNA polymerase VP1 as efficiently as wild-type RNA. These results indicate that the single strand nature of the 3' end of rotavirus mRNA is essential for efficient dsRNA synthesis and that the specific binding of the RNA polymerase to the mRNA template is required but not sufficient for the synthesis of minus-strand RNA. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. EM jpatton@atlas.niaid.nih.gov RI Patton, John/P-1390-2014 NR 49 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7387 EP 7396 PG 10 WC Virology SC Virology GA 109NK UT WOS:000075328600048 PM 9696835 ER PT J AU Lee, B Doranz, BJ Rana, S Yi, YJ Mellado, M Frade, JMR Martinez, C O'Brien, SJ Dean, M Collman, RG Doms, RW AF Lee, B Doranz, BJ Rana, S Yi, YJ Mellado, M Frade, JMR Martinez, C O'Brien, SJ Dean, M Collman, RG Doms, RW TI Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; VACCINIA VIRUS; FUSION; ENTRY; EXPRESSION; 7-TRANSMEMBRANE; DESENSITIZATION; REPLICATION; PROGRESSION; COFACTOR AB The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I is associated with a 2- to ii-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor activities, and their effects on the expression and receptor activities of the major HIV-1 coreceptors. CCR2b and CCR2b-V64I were expressed at similar levels, and neither molecule affected the expression or coreceptor activity of CCR3, CCR5, or CXCR4 in cotransfected cell lines. Peripheral blood mononuclear cells (PBMCs) from CCR2-V64I heterozygotes had normal levels of CCR2b and CCR5 but slightly reduced levels of CXCR4. CCR2b and CCR2b-V64I functioned equally well as HIV-1 coreceptors, and CCR2-V64I PBMCs were permissive for HIV-1 infection regardless of viral tropism. The MCP-l-induced calcium mobilization mediated by CCR2b signaling was unaffected by the polymorphism, but MCP-1 signaling mediated by either CCR2b- or CCR2-V64I-encoded receptors resulted in heterologous desensitization (i.e., limiting the signal response of other receptors) of both CCR5 and CXCR4. The heterologous desensitization of CCR5 and CXCR4 signaling by both CCR2 allele receptor types provides a mechanistic link that might help explain the in vivo effects of CCR2 gene variants on progression to AIDS as well as the reported antiviral activity of natural CCR2 ligands. C1 Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Div Pulm & Crit Care, Philadelphia, PA 19104 USA. Univ Autonoma Madrid, Dept Immunol & Oncol, E-28049 Madrid, Spain. Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. RP Doms, RW (reprint author), Univ Penn, Dept Pathol & Lab Med, 806 Abramson,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM doms@mail.med.upenn.edu RI Dean, Michael/G-8172-2012; Mellado, Mario/M-9893-2014; Rodriguez Frade, Jose Miguel/K-4266-2014; Lee, Benhur/A-8554-2016 OI Dean, Michael/0000-0003-2234-0631; Mellado, Mario/0000-0001-6325-1630; Rodriguez Frade, Jose Miguel/0000-0002-7753-1462; Lee, Benhur/0000-0003-0760-1709 FU NIAID NIH HHS [R01 AI035502, R01 AI040880, R01-AI-35502]; PHS HHS [R01-40880] NR 60 TC 125 Z9 131 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7450 EP 7458 PG 9 WC Virology SC Virology GA 109NK UT WOS:000075328600054 PM 9696841 ER PT J AU Raychaudhuri, G Govindarajan, S Shapiro, M Purcell, RH Emerson, SU AF Raychaudhuri, G Govindarajan, S Shapiro, M Purcell, RH Emerson, SU TI Utilization of chimeras between human (HM-175) and simian (AGM-27) strains of hepatitis a virus to study the molecular basis of virulence SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; NTP-BINDING MOTIF; A VIRUS; CELL-CULTURE; ATTENUATED HEPATITIS; EXPERIMENTAL-INFECTION; GENETIC-ANALYSIS; VACCINE; ADAPTATION; GROWTH AB Chimeras between human (HM-175) and simian (AGM-27) strains of hepatitis A virus (HAV) were constructed to evaluate the effect of the 2C gene of AGM-27 on HAV replication in cell culture and virulence in tamarins (Saguinus mystax) and chimpanzees (Pan troglodytes). Kinetic studies and radioimmunofocus assays demonstrated that replacement of the 2C gene of HAV/7, a cell culture-adapted strain of HM-175, with that of AGM-27 drastically reduced the ability of the virus to replicate in cultured cells. Intragenic chimeras containing AGM-27 sequences in either the 5' or 3' half of the 2C gene replicated in cell culture at an intermediate level. Whereas HAV/7 is attenuated for tamarins, a chimera containing the simian virus 2C gene in the HAV/7 background was virulent in tamarins, demonstrating that the simian virus 2C gene alone can confer the phenotype of virulence to an otherwise attenuated virus. Clusters of AGM-27-specific residues near both ends of the 2C protein were required for virulence since a chimera containing AGM-27 sequences in the carboxyterminal half of 2C was partially attenuated for tamarins while one containing AGM-27 sequences only in the amino-terminal half of 2C was even more attenuated. Chimeras containing either the entire or only the 3' half of the simian virus 2C gene in the HAV/7 background were attenuated for chimpanzees. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. Univ So Calif, Rancho Los Amigos Hosp, Downey, CA 90242 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Raychaudhuri, G (reprint author), NIAID, Infect Dis Lab, Bldg 7,Room 203,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. EM graychaudh@atlas.niaid.nih.gov FU PHS HHS [N01-A0-05069, N01-A0-45180] NR 47 TC 19 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7467 EP 7475 PG 9 WC Virology SC Virology GA 109NK UT WOS:000075328600056 PM 9696843 ER PT J AU Wang, JH Roderiquez, G Oravecz, T Norcross, MA AF Wang, JH Roderiquez, G Oravecz, T Norcross, MA TI Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macrophages through modulation of CCR5 expression SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; GM-CSF PRODUCTION; MONONUCLEAR PHAGOCYTES; MOLECULAR-CLONING; HIV-1 INFECTION; T-LYMPHOCYTES; CDNA CLONING; CELL-LINES; IN-VITRO; RECEPTOR AB Human macrophages express chemokine receptors that act as coreceptors for human immunodeficiency virus type 1 (HIV-1) and are major targets for HIV-1 infection in vivo. The effects of cytokines on HIV-1 infection of macrophages and on the expression of CCR5, the principal coreceptor for macrophage-tropic viruses, have now been investigated. Expression of CCR5 on the surface of freshly isolated human monocytes was virtually undetectable by flow cytometry with the monoclonal antibody 5C7. However, after culture of monocytes for 48 h in serum-free medium, approximately 30% of the resulting macrophages expressed CCR5 and the cells were susceptible to infection by macrophage-tropic HIV-1. Addition of either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) to the cultures markedly increased both the extent of HIV-1 entry and replication as well as surface expression of CCR5. In contrast, addition of the T-helper 2 (Th2) cell-derived cytokine interleukin-il (IL-4) or IL-13 prevented the expression of CCR5 induced by culture in medium alone, and IL-il inhibited virus entry, replication, and cytopathicity under these conditions. IL-4 or IL-13 also prevented the stimulatory effects of M-CSF or GM-CSF on CCR5 expression as well as HIV-1 entry and replication. In addition, IL-10 reversed the increase in CCR5 expression induced by pretreatment of cells with M-CSF. Although IL-10 also inhibits HIV-1 replication in macrophages, it did not suppress surface CCR5 expression induced by colony-stimulating factors. These results indicate that the cytokine environment determines the susceptibility of macrophages to HIV-1 infection by various mechanisms, one of which is the regulation of HIV-1 coreceptor expression. C1 NIH, US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Norcross, MA (reprint author), NIH, US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29B,Room 4E12, Bethesda, MD 20892 USA. NR 65 TC 112 Z9 114 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7642 EP 7647 PG 6 WC Virology SC Virology GA 109NK UT WOS:000075328600081 PM 9696868 ER PT J AU Pyper, JM Clements, JE Zink, MC AF Pyper, JM Clements, JE Zink, MC TI The nucleolus is the site of borna disease virus RNA transcription and replication SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; INFECTED-CELLS; NEUROBLASTOMA-CELLS; TARGETING SIGNAL; NUCLEAR EXPORT; MINUTE VIRUS; I REX; PROTEIN; LOCALIZATION; IDENTIFICATION AB Borna disease virus (BDV) is a neurotropic nonsegmented negative-strand RNA virus with limited homology to rhabdoviruses and paramyxoviruses. A distinguishing feature of BDV is that it replicates in the nucleus of infected cells. Strand-specific probes used for in situ hybridization of infected rat brain showed that there was differential localization of positive- and negative-strand RNAs within the nucleus of neurons. Within nuclei, sense-strand RNAs were preferentially localized within nucleolar regions while genomic-sense RNAs were found in both nucleolar and nonnucleolar regions. These results suggested a role for the nucleolus in BDV replication. Nucleoli isolated from persistently infected neuroblastoma cells contained both genomic and antigenomic BDV RNA species as well as an enrichment of the 39/38-kDa and gp18 BDV proteins. Since the nucleolus is the site of rRNA transcription, we examined BDV transcription in the presence of inhibitors of RNA polymerase I. Inhibition of RNA polymerase I did not affect levels of BDV transcription. C1 Johns Hopkins Univ, Sch Med, Div Comparat Med, Baltimore, MD 21205 USA. RP Pyper, JM (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 9,Rm 1E127,MSC 0930, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS31908] NR 38 TC 35 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7697 EP 7702 PG 6 WC Virology SC Virology GA 109NK UT WOS:000075328600092 PM 9696879 ER PT J AU Picchio, GR Gulizia, RJ Wehrly, K Chesebro, B Mosier, DE AF Picchio, GR Gulizia, RJ Wehrly, K Chesebro, B Mosier, DE TI The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes (vol 72, pg 2002, 1998) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Picchio, GR (reprint author), Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1998 VL 72 IS 9 BP 7707 EP 7707 PG 1 WC Virology SC Virology GA 109NK UT WOS:000075328600094 ER PT J AU Rantanen, T Guralnik, JM Leveille, S Izmirlian, G Hirsch, R Simonsick, E Ling, S Fried, LP AF Rantanen, T Guralnik, JM Leveille, S Izmirlian, G Hirsch, R Simonsick, E Ling, S Fried, LP TI Racial differences in muscle strength in disabled older women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MAXIMAL ISOMETRIC STRENGTH; AGED 65-89 YEARS; BODY-COMPOSITION; 75-YEAR-OLD MEN; FUNCTIONAL ABILITY; PHYSICAL-ACTIVITY; BLACK-WOMEN; WHITE WOMEN; MASS; WALKING AB This study examines racial differences in muscle strength, and associations of muscle strength to level of physical activity and severity of disability, among a community sample of 254 black and 665 white, moderately to severely disabled women aged 65 and older: Potential confounders that were adjusted for in the models included age, body weight and height, joint pain, number of chronic conditions, and socioeconomic status. Hand grip, hip flexion, and knee extension forces were measured using portable hand-held dynamometers in the participants' homes. Hand grip strength was measured as the maximal isometric force. Hip flexion and knee extension forces were measured as the greatest force the tester had to apply to break the isometric contraction. A declining strength gradient was observed with increasing severity of disability and for decreasing level of physical activity ill both races. At equal levels of disability or physical activity, blacks had better hand grip and hip flexion strength, but knee extension strength did not differ by race. The greater hand grip and hip flexion strength found in black women may be related to their greater muscle mass and known racial differences in body dimensions. No consistent racial differences were observed in the relationship between physical activity and muscle strength, or muscle strength and disability, suggesting that the role of muscle strength in the disablement process does not differ between races. Physical activity and exercise programs may be feasible ways to prevent worsening of disability disability in blacks and whites. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Rantanen, T (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. EM rantanet@gw.nia.nih.gov RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 42 TC 29 Z9 29 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1998 VL 53 IS 5 BP B355 EP B361 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120JK UT WOS:000075953100007 PM 9754133 ER PT J AU Landerman, LR Fillenbaum, GG Pieper, CF Maddox, GL Gold, DT Guralnik, JM AF Landerman, LR Fillenbaum, GG Pieper, CF Maddox, GL Gold, DT Guralnik, JM TI Private health insurance coverage and disability among older Americans SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID BODY-MASS INDEX; MAINTAINING MOBILITY; SOCIOECONOMIC-STATUS; LATE-LIFE; ADULTS; EXPLANATIONS; POPULATION; PREDICTORS; SERVICES; PATTERNS AB Objectives. This study examines the relationship between the lack of private supplemental health insurance coverage and the development of disability among adults aged 65 and older. Methods. Data are from the baseline and six follow-up waves of the Duke Established Populations for Epidemiologic Studies of the Elderly survey (N = 4,000). Discrete-time hazard models were used to estimate the impact of insurance coverage and other risk factors on the incidence of disability among those unimpaired at baseline. Results. Controlling for education, income, and other potential confounders, the odds of developing disability were 35-49% higher among those without private coverage. Insurance coverage also statistically explained part of the increased risk of disability among low-income persons. Discussion. The results indicate that changes in health insurance coverage as well as in individual behaviors may be needed to reduce disability generally and disability among the socioeconomically disadvantaged, in particular. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Dept Sociol, Durham, NC 27710 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Landerman, LR (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3003, Durham, NC 27710 USA. EM 1rl@geri.duke.edu FU NIA NIH HHS [N01-AG-1-2102] NR 54 TC 17 Z9 17 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD SEP PY 1998 VL 53 IS 5 BP S258 EP S266 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 120MZ UT WOS:000075961300011 PM 9750574 ER PT J AU McLaughlin, JK Lipworth, L Chow, WH Blot, WJ AF McLaughlin, JK Lipworth, L Chow, WH Blot, WJ TI Analgesic use and chronic renal failure: A critical review of the epidemiologic literature SO KIDNEY INTERNATIONAL LA English DT Article DE analgesics; chronic renal failure; epidemiology; acetaminophen; phenacetin; non-steroidal anti-inflammatory drugs; NSAIDs ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DISEASE; NEPHROPATHY; ACETAMINOPHEN; RISK; PARACETAMOL; PHENACETIN; NECROSIS; DAMAGE; ABUSE AB Heavy use of analgesics, particularly over-the-counter (OTC) products, has long been associated with chronic renal failure. Most of;he earlier reports implicated phenacetin-containing analgesics as the risk factor. Since the early 1980s, several case-control studies have reported associations between chronic renal failure and use of other forms of analgesics, including acetaminophen, aspirin, and other non-steroidal antiinflammatory drugs (NSAIDs). Findings from these studies, how ever, should be interpreted with caution because of a number of inherent limitations and potential biases in the study design and data collection procedures. These limitations include: failure to identify patients early enough in the natural history of their disease to collect reliable information on analgesic use at an etiologically relevant time period; selection bias due to incomplete identification of subjects or low response rates; selection of cases and controls from different population bases; failure to employ survey techniques to improve reliability of recall of analgesic use; failure to collect detailed information on analgesic use such as year started and ended and reasons for switching analgesics; lack of standardization in the definition of regular analgesic use; and failure to adjust for phenacetin use and other confounding factors when assessing associations with analgesics other than those containing phenacetin. It is our hope that this review of study design limitations will lead to improvements in future studies of chronic renal failure risk. Since use of analgesics is widespread and new OTC products are introduced frequently, the potential impact of these drugs on the development of chronic renal failure may be significant, thus warranting continued evaluation of these products for any renal toxicity. C1 Int Epidemiol Inst, Rockville, MD 20850 USA. Mt Sinai Sch Med, Dept Community Med, New York, NY USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP McLaughlin, JK (reprint author), Int Epidemiol Inst, 1550 Res Blvd, Rockville, MD 20850 USA. EM jmclaug@ieiltd.com NR 48 TC 37 Z9 39 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1998 VL 54 IS 3 BP 679 EP 686 DI 10.1046/j.1523-1755.1998.00043.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 113MC UT WOS:000075553900001 PM 9734593 ER PT J AU Schnermann, J Traynor, T Yang, TX Arend, L Huang, YNG Smart, A Briggs, JP AF Schnermann, J Traynor, T Yang, TX Arend, L Huang, YNG Smart, A Briggs, JP TI Tubuloglomerular feedback: New concepts and developments SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on Renal Hemodynamics - Cellular and Molecular Determinants CY SEP 18-21, 1997 CL SEEON, GERMANY DE juxtaglomerular apparatus; micropuncture; nitric oxide synthase; renin-angiotensin system; transgenic mice ID NITRIC-OXIDE SYNTHASE; GLOMERULAR CAPILLARY-PRESSURE; EMBRYONIC STEM-CELLS; TRANSGENIC MICE; BLOOD-PRESSURE; MACULA DENSA; RECEPTOR GENE; MOUSE; ANGIOTENSIN; DISRUPTION AB Luminal [NaCl] at the macula densa (MD) has two established effects: regulation of glomerular arteriolar resistance through tubuloglomerular feedback (TGF) and control of renin secretion. TGF acts as a minute-to-minute stabilizer of distal salt delivery, thereby minimizing the impact of random perturbations in filtration and absorption forces an NaCl excretion. During long-lasting perturbations of MD [NaCl], control of renin secretion becomes the dominant function of the MD. The potentially maladaptive effect of TGF under chronic conditions is prevented by TGF adaptations permitting adjustments in glomerular filtration rate to occur. TGF adaptation is mechanistically coupled to the endpoint targeted by chronic deviations in MD [NaCl], the rate of local and systemic angiotensin II generation. Studies of TGF in transgenic mice are expected to provide further insights into the mechanisms mediating between luminal [NaCl] and afferent arterioles. TGF responses are virtually abolished in mice in which either the AT(1A) gene or the angiotensin converting enzyme gene is rendered nonfunctional by homologous recombination. In contrast, TGF responses are unaltered in nitric oxide synthase 1 knockout mice. Thus, an intact renin-angiotensin system appears to be critical for the TGF signaling pathway. C1 Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), Univ Michigan, Dept Physiol, Med Sci Bldg 2,7712, Ann Arbor, MI 48109 USA. NR 31 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1998 VL 54 SU 67 BP S40 EP S45 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 115KA UT WOS:000075662400009 ER PT J AU Garnett, NL DeHaven, WR AF Garnett, NL DeHaven, WR TI OPRR and USDA commentary SO LAB ANIMAL LA English DT Editorial Material C1 NIH, Div Anim Welf, OPRR, Bethesda, MD 20892 USA. USDA, APHIS, Washington, DC USA. RP Garnett, NL (reprint author), NIH, Div Anim Welf, OPRR, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 1998 VL 27 IS 8 BP 18 EP 18 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 116FM UT WOS:000075713700007 ER PT J AU Boissy, RE Zhao, Y Gahl, WA AF Boissy, RE Zhao, Y Gahl, WA TI Altered protein localization in melanocytes from Hermansky-Pudlak syndrome: Support for the role of the HPS gene product in intracellular trafficking SO LABORATORY INVESTIGATION LA English DT Article ID PALE EAR EP; PLATELET; MOUSE; VESICLES; PATHWAYS; DISORDER; MELANIN; DEFECTS; FAMILY; CELLS AB Patients with Hermansky-Pudlak syndrome (HPS) exhibit moderate to mild hypopigmentation of the skin, hair. and eyes. To understand the inherent basis for this reduced pigmentation, pure cultures of melanocytes were derived using skin biopsies obtained from four patients with HPS. A nucleotide lesion in the HPS gene was identified in these individuals. Expression of HPS mRNA, parameters of melanin synthesis, characteristics in ultrastructural morphology, and expression of melanocyte-specific proteins were assessed in HPS melanocytes. The patients' cells appeared microscopically hypopigmented, and melanin content ranged from 0% to 50% of that for normal melanocytes. In cell lysates of HPS melanocytes, tyrosine hydroxylase activity was within the normal range, but in intact HPS melanocytes, it was almost half that of normal melanocytes. I-IFS melanocytes also appeared refractory to stimulators of melanization, eg, a combination of isobutyl methylxanthine and cholera toxin (IBMX/CT). HPS melanocytes contained many morphologically normal melanosomes, mostly Stage II with a few Stage I or Ill. After dihydroxyphenylalanine (DOPA) incubation, there appeared to be an equal number of Stage II and III melanosomes with the addition of a moderate number of Stage IV melanosomes. A characteristic ultrastructural feature of most HPS melanocytes was a variety of unusual cellular structures. These aberrancies include the following: (a) large membrane-bound complexes containing membranous chambers, unpigmented, and pigmented melanosomes, irregular deposits of DOPA reaction products, and granular/amorphous material sometimes resembling the cytoplasm; and (b) DOPA-positive rings delineated on either side by limiting membranes. The expression of tyrosinase-related protein-1 and granulophysin, a 40-kd membrane protein originally identified as a component of platelet-dense bodies that are undetectable in HPS, was assessed by light microscopy immunofluorescence. For both proteins, HPS melanocytes exhibited a large granular pattern of expression throughout the cell, which seems to correlate with the large membrane complexes observed ultrastructurally. These observations support the hypothesis that the HPS gene product is involved in organellogenesis. We propose that in the melanocyte, the HPS gene product regulates in part the trafficking of melanocyte-specific proteins from the trans-Golgi network to preformed premelanosomes. C1 Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH 45267 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Boissy, RE (reprint author), Univ Cincinnati, Coll Med, Dept Dermatol, POB 670592, Cincinnati, OH 45267 USA. FU NIAMS NIH HHS [AR 43368] NR 48 TC 46 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 1998 VL 78 IS 9 BP 1037 EP 1048 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 122FY UT WOS:000076062300001 PM 9759648 ER PT J AU McDonald, MP Wong, R Goldstein, G Weintraub, B Cheng, SY Crawley, JN AF McDonald, MP Wong, R Goldstein, G Weintraub, B Cheng, SY Crawley, JN TI Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta 1 receptor gene SO LEARNING & MEMORY LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE RATS; BEHAVIORAL VIGILANCE; GENERALIZED RESISTANCE; SUSTAINED ATTENTION; BASAL FOREBRAIN; DISORDER; CHILDREN; ADHD; DELETION; GIRLS AB Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor beta (TR beta) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TR beta gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TR beta gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TR beta gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD. C1 NIMH, Expt Therapeut Branch, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. NIDDKD, Mol & Cellular Endocrinol Branch, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP McDonald, MP (reprint author), NIMH, Expt Therapeut Branch, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. NR 62 TC 46 Z9 47 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP-OCT PY 1998 VL 5 IS 4-5 BP 289 EP 301 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 135PX UT WOS:000076812700004 PM 10454355 ER PT J AU Paylor, R Nguyen, M Crawley, JN Patrick, J Beaudet, A Orr-Urtreger, A AF Paylor, R Nguyen, M Crawley, JN Patrick, J Beaudet, A Orr-Urtreger, A TI alpha 7 nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: A behavioral characterization of Acra7-deficient mice SO LEARNING & MEMORY LA English DT Article ID ACOUSTIC STARTLE REFLEX; INBRED MOUSE STRAINS; AUDITORY-EVOKED RESPONSE; IN-VIVO CHARACTERIZATION; TRAIT LOCI ANALYSES; ACETYLCHOLINE-RECEPTOR; PREPULSE INHIBITION; SPATIAL MEMORY; ANIMAL-MODELS; SINGLE-GENE AB The alpha 7 nicotinic acetylcholine receptor (nAChR) subunit is abundantly expressed In. the hippocampus and contributes to hippocampal cholinergic synaptic transmission suggesting that it may contribute to learning and memory. There is also evidence for an association between levels of alpha 7 nAChR and in sensorimotor gating impairments. To examine the role of alpha 7 nAChRs in learning and memory and sensorimotor gating, Acra7 homozygous mutant mice and their wild-type littermates were tested in a Pavlovian conditioned fear test, for spatial learning in the Morris water task, and in the prepulse inhibition paradigm. Exploratory activity, motor coordination, and startle habituation were also evaluated. Acra7 mutant mice displayed the same levels of contextual and auditory-cue condition fear as wild-type mice. Similarly, there were no differences in spatial learning performance between mutant and wild-type mice. Finally, Acra7 mutant and wild-type mice displayed similar levels of prepulse inhibition. Other behavioral responses in Acra7 mutant mice were also normal, except for an anxiety-related behavior in the open-field test. The results of this study show that the absence of alpha 7 nAChRs has little impact on normal, base-line behavioral responses. Future studies will examine the contribution of alpha 7 nAChR to the enhancement of learning and sensorimotor gating following nicotine treatments. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NIMH, Expt Therapeut Branch, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. Howard Hughes Med Inst, Houston, TX 77030 USA. Tel Aviv Sourasky Med Ctr, Inst Genet, IL-64239 Tel Aviv, Israel. RP Paylor, R (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NR 56 TC 227 Z9 229 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP-OCT PY 1998 VL 5 IS 4-5 BP 302 EP 316 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 135PX UT WOS:000076812700005 PM 10454356 ER PT J AU Valentinuzzi, VS Kolker, DE Vitaterna, MH Shimomura, K Whiteley, A Low-Zeddies, S Turek, FW Ferrari, EAM Paylor, R Takahashi, JS AF Valentinuzzi, VS Kolker, DE Vitaterna, MH Shimomura, K Whiteley, A Low-Zeddies, S Turek, FW Ferrari, EAM Paylor, R Takahashi, JS TI Automated measurement of mouse freezing behavior and its use for quantitative trait locus analysis of contextual fear conditioning in (BALB/cJ x C57BL/6J)F-2 mice SO LEARNING & MEMORY LA English DT Article ID INBRED STRAINS; LENGTH POLYMORPHISMS; MENDELIAN FACTORS; MUTANT MICE; LINKAGE MAP; GENETIC-MAP; MEMORY; EMOTION AB The most commonly measured mouse behavior in fear conditioning tests is freezing. A technical Limitation, particularly for genetic studies, is the method of direct observation used for quantifying this response, with the potential for bias or inconsistencies. We report the use of a computerized method based on latency between photobeam interruption measures as a reliable scoring criterion in mice. The different computer measures obtained during contextual fear conditioning tests showed high correlations with hand-scored freezing; r values ranged from 0.87 to 0.94. Previously reported strain differences between C57BL/6J and DBA/2J in context-dependent fear conditioning were also detected by the computer-based system. In addition, the use of computer-scored freezing of 199 (BALB/cJ x C57BL/6J)F-2 mice enabled us to detect a suggestive gender-dependent chromosomal locus for contextual fear conditioning on distal chromosome 8 by QTL analysis. Automation of freeze scoring would significantly increase efficiency and reliability of this learning and memory test. C1 Northwestern Univ, Dept Neurobiol & Physiol, Ctr Circadian Biol & Med, Evanston, IL 60208 USA. Univ Estadual Campinas, Inst Biol, Dept Fisiol & Biofis, Lab Sistemas Neurais & Comportamento, BR-13083970 Campinas, SP, Brazil. NIMH, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA. RP Takahashi, JS (reprint author), Northwestern Univ, Dept Neurobiol & Physiol, Ctr Circadian Biol & Med, 2153 Sheridan Rd, Evanston, IL 60208 USA. RI Ferrari, Elenice/C-4856-2012; Takahashi, Joseph/E-8482-2012 OI Takahashi, Joseph/0000-0003-0384-8878 FU NIA NIH HHS [R01 AG10870, P01 AG011412, P01 AG11412, R01 AG09297]; NIAAA NIH HHS [R01 AA010870] NR 33 TC 60 Z9 60 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP-OCT PY 1998 VL 5 IS 4-5 BP 391 EP 403 PG 13 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 135PX UT WOS:000076812700012 PM 10454363 ER PT J AU Knutsen, T AF Knutsen, T TI Cytogenetic changes in the progression of lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Review DE non-Hodgkin's lymphoma; progression; chromosome translocations; chromosome deletions; secondary chromosomal abnormalities; gene rearrangements; oncogenes; tumor suppressor genes ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; IN-SITU HYBRIDIZATION; CONSECUTIVELY ASCERTAINED SPECIMENS; NONRANDOM CHROMOSOME-ABNORMALITIES; INTERMEDIATE LYMPHOCYTIC LYMPHOMA; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; FOLLICULAR LYMPHOMA; MALIGNANT-LYMPHOMA; LOW-GRADE AB The study of chromosomal changes related to tumor progression in NHL is complicated by the various histologic classification systems and the lack of large serial studies comparing abnormalities at different disease stages. The T-cell lymphomas frequently involve rearrangements of the T-cell receptors and tumor progression is marked by a change from single cell aberrations and polyclonality in low grade disease to monoclonal formation, complex clones, polyploidy, and abnormalities of 1p, 6q, 7, and 13 in high grade T-NHL. In B-cell NHL, specific translocations and oncogene rearrangements are associated with specific NHL subtypes de novo; many of these translocations involve immunoglobulin genes, such as t(14;18) in follicular lymphoma, t(11;14) in MCL, t(3;14) in DLLC, and t(8;14) in Burkitt's lymphoma. Tumor progression is associated with secondary abnormalities which are generally not confined to a particular NHL subtype. Some abnormalities, such as those involving chromosomes 1, 6, and 17, >4-6 clonal markers/cell, and rearrangements of c-MYC and TP53, have prognostic significance while others, such as trisomies 7, 12, 18, and X, are associated with tumor progression but their influence on overall survival is uncertain. C1 NCI, Cytogenet Lab, Expt Therapeut Sect Med Branch, NIH, Bethesda, MD 20892 USA. RP Knutsen, T (reprint author), NCI, Cytogenet Lab, Expt Therapeut Sect Med Branch, NIH, Bethesda, MD 20892 USA. EM turidk@Box-t.nih.gov NR 126 TC 24 Z9 24 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 1998 VL 31 IS 1-2 BP 1 EP + DI 10.3109/10428199809057581 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 110BC UT WOS:000075358500001 PM 9720711 ER PT J AU Davis, RE Greenberg, PL AF Davis, RE Greenberg, PL TI Bcl-2 expression by myeloid precursors in myelodysplastic syndromes: relation to disease progression SO LEUKEMIA RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Hematology CY DEC 02-06, 1994 CL NASHVILLE, TENNESSEE SP Amer Soc Hematol DE myelodysplastic syndromes; bcl-2; marrow; immunostaining; apoptosis ID PROGRAMMED CELL-DEATH; BONE-MARROW HISTOLOGY; LEUKEMIC-CELLS; PROTOONCOGENE EXPRESSION; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; APOPTOSIS; SURVIVAL; GENE; PROTEIN AB Rationale and methods: the bcl-2 oncogene blocks apoptosis in various cell types and is expressed by normal myeloid precursors, declining with maturation. To investigate whether bcl-2 plays a role in the increase of myeloblasts in myelodysplastic syndromes (MDS) and their progression to acute myeloid leukemia (AML), we studied bcl-2 expression in initial (pre-therapy) bone marrow biopsies from MDS at early (refractory anemia, RA, with or without ring sideroblasts) and advanced stages (RA with excess blasts, and in transformation). Sequential biopsies were also studied to evaluate the effect of time or disease progression, including evolution to AML, or therapy with granulocyte colony stimulating factor (G-CSF). Early myeloid precursors (EMPs), predominantly myeloblasts, were identified in paraffin sections after immunostaining; bcl-2-positive EMPs were enumerated as a percentage of all EMPs (Bcl-2%), and by their absolute frequency per x 900 microscopic field (Bcl-2 index). Findings: in initial biopsies, the Bcl-2% and Bcl-2 index in early MDS (9.9 +/- 2.6 and 1.4 +/- 0.6, respectively; mean +/- S.E.) were significantly lower than in advanced MDS (26.4 +/- 3.6, 4.6 +/- 1.4), but similar to controls (8.1 +/- 0.3 and 0.8 +/- 01). The Bcl-2% and Bcl-2 index in three patients with AML evolved from MDS (57.4 +/- 17.9 and 85.1 +/- 62.4) were similar to values for seven patients with de novo AML (63.0 +/- 10.0, 98.4 +/- 29.8) and significantly higher than values for other groups. Bcl-2% showed relative increments with time or disease progression (range, 21-273%; 11 of 18 sequential biopsies from six of ten MDS patients), which was not clearly altered by G-CSF therapy (four of six patients with, two of four patients without treatment). Conclusions: bcl-2 expression by EMPs (*in both proportion and absolute number) correlated with initial MDS stage, progressed over time independent of G-CSF therapy, and was associated with evolution to AML. These data provide support for the hypothesis that MDS progression is related to accumulation of immature myeloid cells with increased bcl-2 expression and decreased apoptosis. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Stanford Univ, Med Ctr, Dept Pathol, Palo Alto, CA 94304 USA. Stanford Univ, Med Ctr, Dept Med, Div Hematol, Palo Alto, CA 94304 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP Davis, RE (reprint author), NCI, Metab Branch, 10 Ctr Dr,MSC 1374, Bethesda, MD 20892 USA. NR 61 TC 45 Z9 50 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 1998 VL 22 IS 9 BP 767 EP 777 DI 10.1016/S0145-2126(98)00051-4 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 108XW UT WOS:000075292300001 PM 9716007 ER PT J AU Lu, LD Gowda, GAN Suryaprakash, N Khetrapal, CL Weiss, RG AF Lu, LD Gowda, GAN Suryaprakash, N Khetrapal, CL Weiss, RG TI Solute induced liquid crystalline behaviour of a quaternary ammonium salt and its application to structure determination SO LIQUID CRYSTALS LA English DT Article ID INDUCED SMECTIC PHASES; MIXTURES AB A new liquid crystalline phase, induced by the addition of small amounts of a non-mesogenic solute (such as dimethyl sulphoxide or methyl iodide) to a quaternary ammonium salt, N-methyl-N,N,N-trioctadecylammonium iodide (MTAI), has been detected by NMR and optical microscopic studies. In some cases, there is a coexistence of nematic and smectic phases. Information on the ordering of the phases in the magnetic field of the spectrometer has been derived from NMR spectra of a dissolved molecule, C-13-enriched methyl iodide. The low order parameter of the pure thermotropic nematic phase of the salt provides first-order spectra of the dissolved oriented molecules. Analyses of spectra of cis,cis-mucononitrile exemplifies the utility of the MTAI nematic phase in the determination of structural parameters of the solute. C1 Indian Inst Sci, Sophisticated Instruments Facil, Bangalore 560012, Karnataka, India. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. RP Weiss, RG (reprint author), Indian Inst Sci, Sophisticated Instruments Facil, Bangalore 560012, Karnataka, India. NR 13 TC 9 Z9 9 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0267-8292 J9 LIQ CRYST JI Liq. Cryst. PD SEP PY 1998 VL 25 IS 3 BP 295 EP 300 PG 6 WC Chemistry, Multidisciplinary; Crystallography; Materials Science, Multidisciplinary SC Chemistry; Crystallography; Materials Science GA 109YL UT WOS:000075351900002 ER PT J AU Yang, HK Scott, FM Trepel, JB Battey, JF Johnson, BE Kelley, MJ AF Yang, HK Scott, FM Trepel, JB Battey, JF Johnson, BE Kelley, MJ TI Correlation of expression of bombesin-like peptides and receptors with growth inhibition by an anti-bombesin antibody in small-cell lung cancer cell lines SO LUNG CANCER LA English DT Article DE lung neoplasm; monoclonal antibody; gastrin releasing peptide; neuromedin B ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; NEUROMEDIN-B; CARCINOMA-CELLS; MOLECULAR-CLONING; STIMULATION AB The murine anti-bombesin monoclonal antibody, 2A11, has been demonstrated to inhibit growth of some small-cell lung cancer (SCLC) cells in nude mice xenografts and in a clinical trial. To determine if the expression of bombesin-like peptides (BLP) and their receptors (GRP-R and NMB-R) correlate with an in vitro response to 2A11, we measured these parameters in seven SCLC cell lines. Gastrin releasing peptide (GRP) mRNA was detected in three of seven cell lines (NCI-H69, NCI-H345, NCI-H510) and neuromedin B (NMB) mRNA was detected in all seven lines using an RNase protection assay (RPA). Immunoreactive BLP was detected in the cell pellets of all lines (range 0.11-59.90 pmol/mg protein) by a solid phase GRP radioimmunoassay (RIA) using I-125-labeled 2A11. RPA detected GRP-receptor mRNA in two cell lines (NCI-H69 and NCI-H345) and NMB-receptor in three lines (NCI-H345, NCI-H510, and NCI-H660). Reverse transcriptase-PCR confirmed the presence of receptor mRNA in these lines and detected NMB-receptor in an additional three lines (NCI-H69, NCI-H82, and NCI-H187). Calcium mobilization in response to BLP stimulation was detected in the six cell lines expressing either GRP-R or NMB-R mRNA but not in NCI-N417, which had no detectable BLP-receptor. 2A11 (5 mu g/ml) inhibited colony formation by 26-61% after 2 weeks in all cell lines except NCI-N417. Thus, growth inhibition by 2A11 requires the presence of at least one BLP-receptor. These findings may be useful in selecting patients with SCLC for treatment with 2A11. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Canc Inst, Med Branch, Bethesda, MD 20889 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Kelley, MJ (reprint author), Natl Canc Inst, Med Branch, Bldg 8,Room 5101,8901 Rockville Pike, Bethesda, MD 20889 USA. RI Yang, Han-Kwang/J-2767-2012; OI Kelley, Michael/0000-0001-9523-6080 NR 27 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 1998 VL 21 IS 3 BP 165 EP 175 DI 10.1016/S0169-5002(98)00054-3 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 142NF UT WOS:000077206000002 PM 9857994 ER PT J AU Sampson, SB Higgins, DC Elliot, RW Taylor, BA Lueders, KK Koza, RA Paigen, B AF Sampson, SB Higgins, DC Elliot, RW Taylor, BA Lueders, KK Koza, RA Paigen, B TI An edited linkage map for the AXB and BXA recombinant inbred mouse SO MAMMALIAN GENOME LA English DT Article ID DNA RAPD PCR; STRAINS; POLYMORPHISMS; MARKERS; SEQUENCE AB We have updated the history of the AXB and BXA recombinant inbred (RI) strains, typed additional loci, and edited the AXB, BXA RI database. Thirteen of the original 51 AXB and BXA RI strains are either extinct or genetically contaminated, leaving 33 living strains available from The Jackson Laboratory. However, we found a high degree of similarity among three sets of strains, indicating that these strains are not independent, which leaves 27 independent RI strains in the set. Accordingly, we modified the database by combining the AXB and BXA RI sets and eliminating strains that were genetically contaminated or extinct with no available DNA. We added 92 newly typed loci, retyped some questionable genotypings, and removed loci with excessive double crossovers or an insufficient number of typed strains. The edited strain distribution pattern (SDP) is available on the World Wide Web (WWW) (http://www.informatics.jax.org/riset.html) and now includes over 700 loci. Each locus is linked to adjacent loci with a LOD score of at least 3.0 with a few described exceptions. We also carried out a second editing designed for the analysis of quantitative trait loci by deleting extinct strains and loci with identical SDPs; this edited database is also available on the WWW. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Paigen, B (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NCI NIH HHS [CA34196]; NCRR NIH HHS [RR12305]; NIGMS NIH HHS [GM33160] NR 21 TC 28 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1998 VL 9 IS 9 BP 688 EP 694 DI 10.1007/s003359900849 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 115FY UT WOS:000075653900002 PM 9716653 ER PT J AU Teichmann, U Ray, ME Ellison, J Graham, C Wistow, G Meltzer, PS Trent, JM Pavan, WJ AF Teichmann, U Ray, ME Ellison, J Graham, C Wistow, G Meltzer, PS Trent, JM Pavan, WJ TI Cloning and tissue expression of the mouse ortholog of AIM1, a beta gamma-crystallin superfamily member SO MAMMALIAN GENOME LA English DT Article ID HUMAN-MALIGNANT MELANOMA; TUMOR SUPPRESSION; LENS CRYSTALLINS; NONLENS MEMBER; GENE FAMILY; C-KIT; CHROMOSOME-6; GROWTH; MICE; MELANOCYTES AB We report the isolation of the murine ortholog of AIM1, a human gene whose expression is associated with the reversal of tumorigenicity in an experimental model of melanoma. Mouse and human AIM1 are more than 90% identical in amino acid sequence in the py-crystallin repeats and the C-terminal domain, and more than 75% identical in the extended N-terminal domain. Consistent with the isolated cDNA representing the authentic AIM1 ortholog, linkage analysis localized mouse Aim1 to proximal mouse Chromosome (Chr) 10 in a conserved linkage group with genes localized to human Chr band 6q21. Searches of EST databases identified a second AIM1-like gene in both mouse and human, suggesting the existence of a gene family. Northern analysis demonstrates Aim1 is expressed most abundantly in adult skin, lung, heart, liver, and kidney and is temporally regulated during embryogenesis. Aim1 is expressed highly in the shaft region of the hair follicles and the presumptive ectoderm, but not at detectable levels in melanocytes or melanocyte precursor cells. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, 49 Covent Dr,MSC4472, Bethesda, MD 20892 USA. NR 46 TC 13 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 EI 1432-1777 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1998 VL 9 IS 9 BP 715 EP 720 DI 10.1007/s003359900852 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 115FY UT WOS:000075653900005 PM 9716656 ER PT J AU Esumi, N Budarf, M Ciccarelli, L Sellinger, B Kozak, CA Wistow, G AF Esumi, N Budarf, M Ciccarelli, L Sellinger, B Kozak, CA Wistow, G TI Conserved gene structure and genomic linkage for D-dopachrome tautomerase (DDT) and MIF SO MAMMALIAN GENOME LA English DT Article ID MIGRATION INHIBITORY FACTOR; CRYSTAL-STRUCTURE; PROTEIN-STRUCTURE; MACROPHAGE; CLONING; CELLS; LOCALIZATION; PSEUDOGENES; RESOLUTION AB Macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (DDT) are small proteins, which are related both by sequence and by in vitro enzyme activity. Here we show that the gene for DDT in human and mouse is identical in exon structure to MIF. Both genes have two introns that are located at equivalent positions, relative to a twofold repeat in protein structure. Although in similar positions, the introns are in different phases relative to the open reading frame. Other members of this superfamily exist in nematodes and a plant, and a related gene in C, elegans shares an intron position with MIF and DDT. Ln addition to similarities in structure, the genes for DDT and MIF are closely linked on human Chromosome (Chr) 22 and mouse Chr 10. C1 NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 6,Room 331, Bethesda, MD 20892 USA. NR 33 TC 32 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1998 VL 9 IS 9 BP 753 EP 757 DI 10.1007/s003359900858 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 115FY UT WOS:000075653900011 PM 9716662 ER PT J AU Norquist, GS Magruder, KM AF Norquist, GS Magruder, KM TI National Institute of Mental Health SO MEDICAL CARE LA English DT Editorial Material C1 NIMH, Div Serv & Intervent REs, Rockville, MD 20857 USA. NIMH, Serv Res & Clin Epidemiol Branch, Rockville, MD 20857 USA. RP Norquist, GS (reprint author), NIMH, Div Serv & Intervent REs, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1998 VL 36 IS 9 BP 1306 EP 1308 DI 10.1097/00005650-199809000-00002 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 120AV UT WOS:000075932600002 PM 9749653 ER PT J AU Klabunde, CN Potosky, AL Harlan, LC Kramer, BS AF Klabunde, CN Potosky, AL Harlan, LC Kramer, BS TI Trends and black/white differences in treatment for nonmetastatic prostate cancer SO MEDICAL CARE LA English DT Article DE prostate cancer; treatment; practice variation; race; socioeconomic status; comorbidity ID LONG-TERM SURVIVAL; MEDICARE BENEFICIARIES; RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; COLORECTAL-CANCER; CARE DELIVERY; PATIENT-CARE; POPULATION; OUTCOMES; MEN AB OBJECTIVES. Controversy and uncertainty surround use of radical prostatectomy, radiation therapy, and conservative symptomatic management in treating elderly men with nonmetastatic prostate cancer. Prior studies have demonstrated variations in use of these therapies by patient age, race, and geographic region. This study examined trends in treatment for nonmetastatic prostate cancer in black and white men aged 65 and older during the period 1986 to 1993. The study also explored factors related to use of initial therapies in these men. METHODS. A cohort of 52,915 men (48,410 white; 4,505 black) obtained from the linked SEER-Medicare dataset was used in an observational design. Various sociodemographic and clinical measures were incorporated in the analysis. RESULTS. For both races, use of aggressive therapy had increased with time, although this trend appears to be slowing. Black men were less likely to undergo radical prostatectomy than were white men, but use of radiation therapy did not differ markedly by race. High socioeconomic status and a lack of comorbid conditions were among the factors predictive of aggressive therapy receipt. The relation between race and receipt of aggressive therapy was dependent on whether prostate cancer was detected by transurethral resection of the prostate. Sociodemographic and clinical characteristics explained approximately half the difference between black men and white men in radical prostatectomy use. CONCLUSIONS. This study documents racial differences and changing practice patterns in the treatment of nonmetastatic prostate cancer in elderly men. Further research is required to more fully understand reasons for racial differences, as well as to promote rational use of health care resources. C1 NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Klabunde, CN (reprint author), NCI, Appl Res Branch, Div Canc Control & Populat Sci, Execut Plaza N room 313,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. NR 56 TC 118 Z9 121 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1998 VL 36 IS 9 BP 1337 EP 1348 DI 10.1097/00005650-199809000-00006 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 120AV UT WOS:000075932600006 PM 9749657 ER PT J AU Cragg, GM AF Cragg, GM TI Paclitaxel (Taxol (R)): A success story with valuable lessons for natural product drug discovery and development SO MEDICINAL RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT 1st Monroe Wall Symposium on Harnessing Biodiversity for Therapeutic Drugs and Food - Developing Products for the 21st Century CY JUN 02-05, 1996 CL NEW BRUNSWICK, NEW JERSEY SP Rutgers State Univ, New Jersey, Xechem, New Brunswick, New Jersey DE novel screens; mechanisms of action; supply; multidisciplinary collaboration ID NATIONAL-CANCER-INSTITUTE; PHASE-II; AGENT; ANTICANCER AB The discovery and development of paclitaxel, which covered a time span of some 30 years, has provided some important lessons for those involved in natural product drug discovery and development. These include the adoption of novel screens as they become available, the elucidation of mechanisms of action, and addressing the supply issue at an early stage of development. These issues, as applied to paclitaxel, are illustrated. The development of the NCI human cancer cell line screen, and its application to mechanistic studies through use of COMPARE analyses, are discussed, as is the production of the marine-derived anticancer agent, bryostatin 1, which provides another illustration of a successful approach to solving a supply issue. The history of the development of paclitaxel also illustrates the importance of multidisciplinary collaboration, and the various mechanisms used by the NCI Developmental Therapeutics Program for promoting such collaboration are presented. (C) 1998 John Wiley & Sons, Inc. C1 NCI, Dev Therapeut Program, Div Canc Treatment, Bethesda, MD 20892 USA. RP Cragg, GM (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment, Bethesda, MD 20892 USA. NR 35 TC 75 Z9 79 U1 1 U2 19 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1998 VL 18 IS 5 BP 315 EP 331 DI 10.1002/(SICI)1098-1128(199809)18:5<315::AID-MED3>3.0.CO;2-W PG 17 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 114UQ UT WOS:000075627900003 PM 9735872 ER PT J AU Segal, BH DeCarlo, ES Kwon-Chung, KJ Malech, HL Gallin, JI Holland, SM AF Segal, BH DeCarlo, ES Kwon-Chung, KJ Malech, HL Gallin, JI Holland, SM TI Aspergillus nidulans infection in chronic granulomatous disease SO MEDICINE LA English DT Article ID PULMONARY ASPERGILLOSIS; INTERFERON-GAMMA; GENE-TRANSFER; HOST-DEFENSE; NEUTROPHILS; CHILDHOOD; THERAPY; ITRACONAZOLE; FUMIGATUS; HYPHAE C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,MSC 1896, Bethesda, MD 20892 USA. EM smh@nih.gov NR 46 TC 144 Z9 152 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 1998 VL 77 IS 5 BP 345 EP 354 DI 10.1097/00005792-199809000-00004 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 124EH UT WOS:000076168100004 PM 9772923 ER PT J AU Klaiman, MD Shrader, JA Danoff, JV Hicks, JE Pesce, WJ Ferland, J AF Klaiman, MD Shrader, JA Danoff, JV Hicks, JE Pesce, WJ Ferland, J TI Phonophoresis versus ultrasound in the treatment of common musculoskeletal conditions SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE musculoskeletal injuries; tendinitis; pressure algometry; corticosteroids ID TRANSDERMAL DRUG DELIVERY; HYDROCORTISONE PHONOPHORESIS; PRESSURE THRESHOLD; SONOPHORESIS; RELIABILITY; THERAPY; MEDIA AB Purpose: The purpose of this study was to determine whether the pain response after phonophoresis (PH) differs from the pain response after ultrasound (US) alone. Methods: Forty-nine subjects with soft tissue injuries including epicondylitis, tendinitis, and tenosynovitis were randomly assigned (double blinded technique) to PH or US treatment groups. Both groups received 8 min of continuous US at 1.5 w.cm(-2), three times per week for 3 wk. For the PH group a gel containing 0.05% fluocinonide was used as a coupling agent. An identical gel absent the steroid was used for the US group. Subjects indicated their pain level by marking on a visual analog scale (VAS) at the start of treatment and at the end of weeks 1, 2, and 3. Pressure algometry was used to note tolerance to direct pressure over the target tissue. ANOVA for repeated measures was used to analyze data. Results: At the end of 3 wk of treatment, both groups combined showed a significant decrease in pain level and an increase in pressure tolerance (P < 0.05), but there were no differences between groups from the onset of treatment to the end of week 3 (VAS: US 5.5-1.9, PH 5.0-2.0; algometry (involved limb): US 4.7 lb-7.1 Ib, PH 5.1 lb-6.6 Ib). Conclusions: We conclude that US results in decreased pain and increased pressure tolerance in these selected soft tissue injuries. The addition of PH with fluocinonide does not augment the benefits of US used alone. C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. Hosp Special Care, Dept Phys Med, New Britain, CT USA. RP Klaiman, MD (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. EM mark_klaiman@nih.gov NR 53 TC 30 Z9 31 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 1998 VL 30 IS 9 BP 1349 EP 1355 DI 10.1097/00005768-199809000-00002 PG 7 WC Sport Sciences SC Sport Sciences GA 116ZE UT WOS:000075754600002 ER PT J AU Chima, SC Ryschkewitsch, CF Stoner, GL AF Chima, SC Ryschkewitsch, CF Stoner, GL TI Molecular epidemiology of human polyomavirus JC in the Biaka Pygmies and Bantu of Central Africa SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article; Proceedings Paper CT 3rd International Meeting on Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases CY JUN 07-10, 1998 CL RIO JANEIRO, BRAZIL SP ORSTOM, CNRS, Ctr Dis Control & Prevent, Oswaldo Cruz Fdn, Oswaldo Cruz Inst, CNPq, Brazil, FAPERJ, Brazil, CAPES, Brazil, FNS, Brazil, INTERACTIVA Biotechnol Gmbh, Sigma Chem Co, Brazil DE polyomavirus; JC virus; genotypes; Pygmies; Bantu; Africa ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRUS; INDIVIDUALS; PATHOLOGY; SEQUENCE; BRAIN; HIV AB Polyomavirus JC (JCV) is ubiquitous in humans and causes a chronic demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy which is common in AIDS. JCV is excreted in urine of 30-70% of adults worldwide. Based on sequence analysis of JCV complete genomes or fragments thereof, JCV can be classified into geographically derived genotypes. Types 1 and 2 are of European and Asian origin respectively while Types 3 and 6 are African in origin. Type 4, a possible recombinant of European and African genotypes ( 1 and 3) is common in the USA. To delineate the JCV genotypes in an aboriginal African population, random urine samples were collected from the Biaka Pygmies and Bantu from the Central African Republic. There were 43 males and 25 females aged 4-55 years, with an average age of 26 years. After PCR amplification of JCV in urine, products were directly cycle sequenced. Five of 23 Pygmy adults (22%) and four of 20 Bantu adults (20%) were positive for JC viruria. DNA sequence analysis revealed JCV Type 6. Type 3 and 6 strains of JCV are the predominant strains in central Africa. The presence of multiple subtypes of JCV in Biaka Pygmies may be a result of extensive interactions of Pygmies with their African tribal neighbors during their itinerant movements in the equatorial forest. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Chima, SC (reprint author), NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. EM chimasc@helix.nih.gov RI Chima, Sylvester Chidi/N-5564-2013 NR 30 TC 25 Z9 25 U1 0 U2 3 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD SEP-OCT PY 1998 VL 93 IS 5 BP 615 EP 623 DI 10.1590/S0074-02761998000500010 PG 9 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 119UJ UT WOS:000075915900010 PM 9830527 ER PT J AU Brinton, LA Brogan, DR Coates, RJ Swanson, CA Potischman, N Stanford, JL AF Brinton, LA Brogan, DR Coates, RJ Swanson, CA Potischman, N Stanford, JL TI Breast cancer risk among women under 55 years of age by joint effects of usage of oral contraceptives and hormone replacement therapy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE breast cancer; oral contraceptives; hormone replacement therapy; risk ID EXPANDED CASE-CONTROL; POSTMENOPAUSAL WOMEN; MENOPAUSAL ESTROGENS; COHORT AB Objective: To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure. Design: A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted. Results: Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0), When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation. Conclusions: Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy. (Menopause 1998;5:145-151. (C) 1998, The North American Menopause Society.). C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Execut Plaza N,Room 443,6130 Execut Blvd,MSC 7374, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 32 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD FAL PY 1998 VL 5 IS 3 BP 145 EP 151 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 120QF UT WOS:000075966600003 PM 9774759 ER PT J AU Mills, JL Jovanovic, L Knopp, R Aarons, J Conley, M Park, E Lee, YJ Holmes, L Simpson, JL Metzger, B AF Mills, JL Jovanovic, L Knopp, R Aarons, J Conley, M Park, E Lee, YJ Holmes, L Simpson, JL Metzger, B TI Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: The diabetes in early pregnancy study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID TOLERANCE; WOMEN; METABOLISM AB Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters. All subjects were instructed to fast overnight for 10 to 12 hours. Three hundred sixty-one women were studied between 6 and 12 weeks of gestation. A median decrease in plasma glucose of 2 mg/dL was observed between weeks 6 and 10 (P = .007). In a smaller group of subjects evaluated through the third trimester, little further glucose reduction was observed. A reduction in glycosylated hemoglobin levels between 10 and 20 weeks (P = .002) followed the earlier reduction in first trimester glucose levels. Analysis by body mass index (BMI) showed a smaller first trimester reduction with increasing BMI, and none among severely obese women (BMI > 29.9 kg/m(2)). The decline in fasting plasma glucose in pregnancy begins early in the first trimester, well before fetal glucose requirements can contribute to the decline in the glucose level. Thereafter, plasma glucose levels decrease little. These results suggest that in the setting in which this study was performed (an overnight fast) maternal physiologic adjustments account for a reduction in plasma glucose early in the first trimester of pregnancy, and possibly even later in gestation as well. This is a US government work. There are no restrictions on its use. C1 NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. NICHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. Sansum Med Res Fdn, Santa Barbara, CA 93105 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Med, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Genet & Teratol Unit, Boston, MA USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. NR 28 TC 68 Z9 70 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1998 VL 47 IS 9 BP 1140 EP 1144 DI 10.1016/S0026-0495(98)90290-6 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 119MA UT WOS:000075899200018 PM 9751245 ER PT J AU Schmidt, HHJ Gregg, RE Tietge, UJF Beisiegel, U Zech, LA Brewer, HB Manns, MP Bojanovski, D AF Schmidt, HHJ Gregg, RE Tietge, UJF Beisiegel, U Zech, LA Brewer, HB Manns, MP Bojanovski, D TI Upregulated synthesis of both apolipoprotein A-I and apolipoprotein B in familial hyperalphalipoproteinemia and hyperbetalipoproteinemia SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; DEFECTIVE APOLIPOPROTEIN-B-100; HEPATIC LIPASE; ARTERY DISEASE; CHOLESTEROL; PLASMA; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; MUTATION AB A family was identified with vertical transmission through three generations with simultaneous increases of apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol, which we have designated familial hyperalphalipoproteinemia and hyperbetalipoproteinemia (HA/HBL). Affected patients develop xanthomas and coronary artery disease (CAD). HA/HBL apoA-I and LDL-apoB were isolated and characterized. The in vivo kinetics of radiolabeled apoA-I and LDL-apoB were evaluated in two HA/HBL probands and three controls. Structural and metabolic characterization showed normal apoA-I and LDL-apoB. The kinetics of metabolism of HA/HBL apoA-I in the HA/HBL subjects showed that elevated apoA-I levels were solely due to an increased synthesis rate (15.2 to 17.6 mg/kg/d v 11.1 to 11.4 mg/kg/d) with a normal apoA-I residence time in plasma (4.2 to 5.4 days v 5.1 to 5.3 days). The elevation of LDL-apoB levels resulted from both an increased synthetic rate (16.6 to 22.9 mg/kg/d v 12.3 to 13.8 mg/kg/d) and a prolonged residence time (3.3 to 3.8 days v 1.4 to 1.9 days). In addition, we evaluated another HA/HBL proband of an unrelated family with HA/HBL to confirm the kinetic data. LDL-receptor binding studies of HA/HBL fibroblasts showed normal binding, uptake, and degradation of LDL isolated from a normolipemic control. The serum concentration of the cholesterol ester transfer protein (CETP) was normal in the studied probands. An apoB 3500 and apoB 3531 mutant, respectively, was ruled out by polymerase chain reaction (PCR), In conclusion, the site of the molecular defect in HA/HBL subjects may be involved in the coordinate regulation of metabolism for both LDL and HDL. Copyright (C) 1998 by W.B. Saunders Company. C1 Med Hsch Hannover, Gastroenterol & Hepatol Abt, D-30623 Hannover, Germany. Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA. Univ Klin Eppendorf, Hamburg, Germany. NHLBI, Mol Dis Branch, Bethesda, MD 20892 USA. RP Schmidt, HHJ (reprint author), Med Hsch Hannover, Gastroenterol & Hepatol Abt, OE 6852, D-30623 Hannover, Germany. NR 50 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1998 VL 47 IS 9 BP 1160 EP 1166 DI 10.1016/S0026-0495(98)90294-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 119MA UT WOS:000075899200022 PM 9751249 ER PT J AU Mishima, K Yamada, E Masui, K Shimokawara, T Takayama, K Sugimura, M Ichijima, K AF Mishima, K Yamada, E Masui, K Shimokawara, T Takayama, K Sugimura, M Ichijima, K TI Overexpression of the ERK/MAP kinases in oral squamous cell carcinoma SO MODERN PATHOLOGY LA English DT Article DE in situ hybridization; Ki-67; MAPK; oral squamous cell carcinoma; overexpression ID C-MYC GENES; MAP KINASE; PROTEIN-KINASE; EGF RECEPTOR; EXPRESSION; AMPLIFICATION; ADENOCARCINOMA; FIBROBLASTS; ACTIVATION; MUTATIONS AB Mitogen-activated protein kinase (MAPK) is a serine-threonine kinase that is activated by various extracellular stimuli, Extracellular signal-regulated kinases (ERK1 and ERK2), an MAPK subfamily, are activated by many oncogenes, such as ras and raf and they induce cell proliferation. myc is also an oncogene and one of the targets of ERKs, Mutations of ras and overexpression of myc were found in various human cancers, and ERKs were also reported to play a role in carcinogenesis. In this study, we examined 39 biopsy specimens of oral squamous cell carcinoma (OSCC) and 5 of normal gingival mucosa for the expression of ERK protein and the proliferation marker, MIB-1 (Ki-67 antibody). Thirteen OSCC specimens and five normal gingival biopsies were also examined for the expression of ERKs mRNA by in situ hybridization. Double staining for ERKs and MIB-1 was also performed. Histologically, 18 patients (46%) were diagnosed with well-differentiated SCC, 17 (44%) with moderately differentiated SCC, and 4 (10%) with poorly differentiated SCC. The histologic grade correlated with the MIB-1 index The localization of ERK1 was similar to that of ERK2. Positive signals for ERK proteins were localized in superficial keratinocytes in normal gingival mucosa, whereas these mRNAs were weakly positive in the basal and spinous layer. Basal and suprabasal cells were positive for MIB-1. In well-differentiated and moderately differentiated OSCC, positive signals for ERK mRNA and proteins were found at higher levels than in normal gingival mucosa in keratotic cells around cancer pearls. Some cells showed positive signals for ERKs and MIB-1. Furthermore, most cancer cells in poorly differentiated SCC were positive for both ERK and MIB-1. The histologic grade was statistically related to the percentage of cells positive for both ERK and MIB-1. This suggested that ERKs might be related to proliferation in OSCC. C1 NIDR, Gene Therapy Therapeut Branch, NIH, Bethesda, MD 20892 USA. Nara Med Univ, Dept Pathol, Kashihara, Nara 634, Japan. Nara Med Univ, Dept Oral & Maxillofacial Surg, Kashihara, Nara 634, Japan. RP Mishima, K (reprint author), NIDR, Gene Therapy Therapeut Branch, NIH, Bldg 10-1N114, Bethesda, MD 20892 USA. NR 28 TC 43 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1998 VL 11 IS 9 BP 886 EP 891 PG 6 WC Pathology SC Pathology GA 120QC UT WOS:000075966200011 PM 9758369 ER PT J AU Harrod, R Tang, Y Nicot, C Lu, HS Vassilev, A Nakatani, Y Giam, CZ AF Harrod, R Tang, Y Nicot, C Lu, HS Vassilev, A Nakatani, Y Giam, CZ TI An exposed KID-like domain in human T-cell lymphotropic virus type 1 Tax is responsible for the recruitment of coactivators CBP/p300 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID I TRANSCRIPTIONAL ACTIVATOR; NUCLEAR-PROTEIN CBP; DNA-BINDING; 21-BASE-PAIR REPEATS; TRANSACTIVATOR TAX; CREB BINDING; BZIP PROTEINS; LEUKEMIA; FAMILY; ONCOPROTEIN AB Human T-cell lymphotropic virus type 1 (HTLV-1) transcriptional activation is mediated by the viral transactivator, Tax, and three 21-bp repeats (Tax response element [TxRE]) located in the U3 region of the viral long terminal repeat (LTR). Each TxRE contains a core cyclic AMP response element (CRE) flanked by 5' G-rich and 3' C-rich sequences. The TxRE binds CREB (CRE-binding protein) and Tax to form a ternary complex and confers Tax-dependent transactivation. Recent data indicate that Tax functions as a specific link to connect CREB-binding protein (CBP)/p300 in a phosphorylation-independent manner to CREB/ATF-1 assembled on the viral 21-bp repeats. Glutathione S-transferase pull-down performed with Tax deletion mutants and peptide competition have localized the site in Tax critical for binding CBP/p300 to a highly protease-sensitive region around amino acid residues 81 to 95 ((81)QRTSKTLKTVLTPPIT(95)) which lies between the domains previously proposed to be important for CREB binding and Tax subunit dimerization, Amino acid residues around the trypsin- and chymotrypsin-sensitive sites (88KVL90) of Tax bear resemblance to those in the kinase-inducible domain of CREB (129SRRPSYRKILNE140) surrounding Ser-133, which undergoes signal-induced phosphorylation to recruit CBP/p300. Site-directed mutagenesis of residues in this domain (R82A, K85A, K88A, and V89A) resulted in proteins which failed to transactivate from the HTLV-1 LTR in vivo. These mutants (K85A, K88A, and V89A) bind CREB with similar affinities as wild-type Tax, vet interaction with CBP/p300 is abrogated in various biochemical assays, indicating that the recruitment of CBP/p300 is crucial for Tax transactivation. A Tax mutant, M47, defective in the COOH-terminal transactivation domain, continued to interact with CBP/p300, suggesting that interactions with additional cellular factors are required for proper Tax function. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Amgen Inc, Dept Prot Struct, Thousand Oaks, CA 91320 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Giam, CZ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NCI NIH HHS [R01 CA048709, R01 CA48709] NR 58 TC 144 Z9 146 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5052 EP 5061 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300012 PM 9710589 ER PT J AU Mikovits, JA Young, HA Vertino, P Issa, JPJ Pitha, PM Turcoski-Corrales, S Taub, DD Petrow, CL Baylin, SB Ruscetti, FW AF Mikovits, JA Young, HA Vertino, P Issa, JPJ Pitha, PM Turcoski-Corrales, S Taub, DD Petrow, CL Baylin, SB Ruscetti, FW TI Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; T-CELLS; HIV-INFECTION; COLON-CANCER; HUMAN FIBROBLASTS; CPG METHYLATION; HUMAN NEOPLASIA; LYMPH-NODES; EXPRESSION; PROGRESSION AB The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12 tumor necrosis factor alpha, and gamma interferon (IFN-gamma), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-gamma, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-gamma gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV 1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-gamma gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-gamma gene, and increased IFN-gamma production, demonstrating a direct link between methyltransferase and IFN-gamma gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-gamma gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. Johns Hopkins Med Inst, Ctr Oncol, Baltimore, MD 21231 USA. CBER, Rockville, MD 20892 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. RP Mikovits, JA (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, POB B,Bldg 567,Rm 253, Frederick, MD 21702 USA. FU NCI NIH HHS [CA43318, N0I-CO-56000, R01 CA043318] NR 87 TC 109 Z9 112 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5166 EP 5177 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300024 PM 9710601 ER PT J AU Chen, W Martindale, JL Holbrook, NJ Liu, YS AF Chen, W Martindale, JL Holbrook, NJ Liu, YS TI Tumor promoter arsenite activates extracellular signal-regulated kinase through a signaling pathway mediated by epidermal growth factor receptor and Shc SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE; TYROSINE KINASE; HUMAN-BREAST; TRANSDUCTION PATHWAY; HUMAN FIBROBLASTS; BLADDER-CANCER; RAS ACTIVATION; AP-1 ACTIVITY; EGF RECEPTOR; CELLS AB Although arsenite is an established carcinogen, the mechanisms underlying its tumor-promoting properties are poorly understood. Previously, we reported that arsenite treatment leads to the activation of the extracellular signal-regulated kinase (ERK) in rat PC12 cells through a Ras-dependent pathway. To identify potential mediators of the upstream signaling cascade,,ve examined the tyrosine phosphorylation profile in cells exposed to arsenite. Arsenite treatment rapidly stimulated tyrosine phosphorylation of several proteins in a Ras-independent manner, with a pattern similar to that seen in response to epidermal growth factor (EGF) treatment. Among these phosphorylated proteins were three isoforms of the proto-oncoprotein Shc as well as the EGF receptor (EGFR). Tyrosine phosphorylation of Shc allowed for enhanced interactions between Shc and Grb2 as identified by coimmunoprecipitation experiments. The arsenite-induced tyrosine phosphorylation of Shc, enhancement of Shc and Grb2 interactions, and activation of ERI( were all drastically reduced by treatment of cells with either the general growth factor receptor poison suramin or the EGFR-selective inhibitor tyrphostin AG1478. Do cm-regulation of EGFR expression through pretreatment of cells with EGF also attenuated ERK activation and Shc tyrosine phosphorylation in response to arsenite treatment. These results demonstrate that the EGFR and Shc are critical mediators in the activation of the Ras/ERK signaling cascade by arsenite and suggest that arsenite acts as a tumor promoter largely by usurping this growth factor signaling pathway. C1 NIA, Gene Express & Aging Sect, Biol Chem Lab, Intramural Res Program,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Liu, YS (reprint author), NIA, Gene Express & Aging Sect, Biol Chem Lab, Intramural Res Program,Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 66 TC 123 Z9 124 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5178 EP 5188 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300025 PM 9710602 ER PT J AU Cho, H Orphanides, G Sun, XQ Yang, XJ Ogryzko, V Lees, E Nakatani, Y Reinberg, D AF Cho, H Orphanides, G Sun, XQ Yang, XJ Ogryzko, V Lees, E Nakatani, Y Reinberg, D TI A human RNA polymerase II complex containing factors that modify chromatin structure SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-TERMINAL DOMAIN; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; SACCHAROMYCES-CEREVISIAE; REMODELING FACTOR; REPEAT DOMAIN; LARGEST SUBUNIT; N-COR; HOLOENZYME; YEAST AB We have isolated a human RNA polymerase II complex that contains chromatin structure remodeling activity and histone acetyltransferase activity. This complex contains the Srb proteins, the Swi-Snf complex, and the histone acetyltransferases CBP and PCAF in addition to RNA polymerase II. Notably, the general transcription factors are absent from this complex. The complex was purified by two different methods: conventional chromatography and affinity chromatography using antibodies directed against CDK8, the human homolog of the yeast Srb10 protein. Protein interaction studies demonstrate a direct interaction between RNA polymerase II and the histone acetyltransferases p300 and PCAF. Importantly, p300 interacts specifically with the nonphosphorylated, initiation-competent form of RNA polymerase II. In contrast, PCAF interacts with the elongation-competent, phosphorylated form of RNA polymerase II. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Div Nucleic Acid Enzymol,Howard Hughes Med Inst, Piscataway, NJ 08854 USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Reinberg, D (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Div Nucleic Acid Enzymol,Howard Hughes Med Inst, 663 Hoes Ln, Piscataway, NJ 08854 USA. EM reinbedf@umdnj.edu RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 FU NIGMS NIH HHS [GM-37120, R01 GM037120, R37 GM037120] NR 82 TC 228 Z9 240 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5355 EP 5363 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300042 PM 9710619 ER PT J AU Singh, J Goel, V Klar, AJS AF Singh, J Goel, V Klar, AJS TI A novel function of the DNA repair gene rhp6 in mating-type silencing by chromatin remodeling in fission yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ORIGIN RECOGNITION COMPLEX; UBIQUITIN-CONJUGATING ENZYME; ASSEMBLY FACTOR-I; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; MEIOTIC RECOMBINATION; TRANSCRIPTION FACTOR; RAD6 GENE; S-PHASE; REPLICATION AB Recent studies have indicated that the DNA replication machinery is coupled to silencing of mating-type loci in the budding yeast Saccharomyces cerevisiae, and a similar silencing mechanism may operate in the distantly related yeast Schizosaccharomyces pombe. Regarding gene regulation, an important function of DNA replication may be in coupling of faithful chromatin assembly to reestablishment of the parental states of gene expression in daughter cells. We have been interested in isolating mutants that are defective in this hypothesized coupling. An S. pombe mutant fortuitously isolated from a screen for temperature-sensitive growth and silencing phenotype exhibited a novel defect in silencing that was dependent on the switching competence of the mating-type loci, a property that differentiates this mutant from other silencing mutants of S. pombe as well as of S. cerevisiae. This unique mutant phenotype defined a locus which we named sng1 (for silencing not governed). Chromatin analysis revealed a switching-dependent unfolding of the donor loci mat2P and mat3M in the sng1(-) mutant, as indicated by increased accessibility to the in vivo-expressed Escherichia coli dam methylase. Unexpectedly, cloning and sequencing identified the gene as the previously isolated DNA repair gene rhp6. RAD6, an rhp6 homolog in S. cerevisiae, is required for postreplication DNA repair and ubiquitination of histones H2A and H2B. This study implicates the Rad6/rhp6 protein in gene regulation and, more importantly, suggests that a transient window of opportunity exists to ensure the remodeling of chromatin structure during chromosome replication and recombination. We propose that the effects of the sng1(-)/rhp6(-) mutation on silencing are indirect consequences of changes in chromatin structure. C1 Inst Microbial Technol, Chandigarh 160036, Punjab, India. NCI, Dev Genet Sec,Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Singh, J (reprint author), Inst Microbial Technol, Sector 39 A, Chandigarh 160036, Punjab, India. EM klar@ncifcrf.gov NR 72 TC 37 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5511 EP 5522 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300058 PM 9710635 ER PT J AU Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J AF Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J TI Dual roles for Pax-6: a transcriptional repressor of lens fiber cell-specific beta-crystallin genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHICKEN DELTA-1-CRYSTALLIN GENE; ALPHA-A-CRYSTALLIN; PAIRED DOMAIN; TRANSGENIC MICE; SEQUENCE RECOGNITION; REGULATORY PROTEINS; DELTA-CRYSTALLIN; EYE DEVELOPMENT; MESSENGER-RNA; HOMEOBOX GENE AB It has been demonstrated previously that Pax-6, a paired domain (PD)/homeodomain (HD) transcription factor critical for eye development, contributes to the activation of the alpha B-, alpha A-, delta 1-, and zeta-crystallin genes in the lens. Here we have examined the possibility that the inverse relationship between the expression of Pax-6 and beta-crystallin genes within the developing chicken lens reflects a negative regulatory role of Pax-6. Cotransfection of a plasmid containing the beta B1-crystallin promoter fused to the chloramphenicol acetyltransferase reporter gene and a plasmid containing the full length mouse Pax-6 coding sequences into primary embryonic chicken lens epithelial cells or fibroblasts repressed the activity of this promoter by as much as 90%, Pax-6 constructs lacking the C-terminal activation domain repressed beta B1-crystallin promoter activity as effectively as the full-length protein, but the PD alone or Pax-6 (ja), a splice variant with an altered PD affecting its DNA binding specificity, did not. DNase footprinting analysis revealed that truncated Pax-6 (PD+HD) binds to three regions (-183 to -152, -120 to -48, and -30 to +1) of the beta B1-crystallin promoter. Earlier experiments showed that the beta B1-crystallin promoter sequence from -120 to -48 contains a cis element (PL2 at -90 to -76) that stimulates the activity of a heterologous promoter in lens cells but not in fibroblasts. In the present study, we show by electrophoretic mobility shift assay and cotransfection that Pax-6 binds to PL2 and represses its ability to activate promoter activity; moreover, mutation of PL2 eliminated binding by Pax-6, Taken together, our data indicate that Pax-6 (via its PD and HD) represses the beta B1-crystallin promoter by direct interaction with the PL2 element. We thus suggest that the relatively high concentration of Pax-6 contributes to the absence of beta B1-crystallin gene expression in lens epithelial cells and that diminishing amounts of Pax-6 in lens fiber cells during development allow activation of this gene. C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. RP NEI, Mol & Dev Biol Lab, Bldg 6,Room 205,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. EM Joram@helix.nih.gov RI Cvekl, Ales/B-2427-2013 NR 50 TC 101 Z9 102 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5579 EP 5586 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300064 PM 9710641 ER PT J AU Conte, D Barber, E Banerjee, M Garfinkel, DJ Curcio, MJ AF Conte, D Barber, E Banerjee, M Garfinkel, DJ Curcio, MJ TI Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3 (vol 18, pg 2502, 1998) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 SUNY Albany, Mol Genet Program, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA. NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Ft Detrick, MD 21702 USA. RP Conte, D (reprint author), SUNY Albany, Mol Genet Program, Wadsworth Ctr, Albany, NY 12201 USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5620 EP 5620 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300069 ER PT J AU Zhan, QM Chen, IT Antinore, MJ Fornace, AJ AF Zhan, QM Chen, IT Antinore, MJ Fornace, AJ TI Tumor suppressor p53 can participate in transcriptional induction of the GADD45 promoter in the absence of direct DNA binding (vol 18, pg 2768, 1998) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Zhan, QM (reprint author), NCI, Div Basic Sci, Bethesda, MD 20892 USA. NR 1 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5620 EP 5620 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300068 ER PT J AU Deyev, SM Yazynin, SA Kuznetsov, DA Jukovich, M Hartley, RW AF Deyev, SM Yazynin, SA Kuznetsov, DA Jukovich, M Hartley, RW TI Ribonuclease-charged vector for facile direct cloning with positive selection SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE molecular cloning; barnase; polylinker ID GENE; BARNASE; EXPRESSION; PROTEINS; BARSTAR AB Plasmid vectors for positive selection of cloned inserts in Escherichia coli were devised, based on an expression plasmid (pMT416) for the bacterial ribonuclease barnase. In addition to the barnase gene under control of a synthetic tac promoter, these plasmids carry the gene for the barnase inhibitor, barstar, the constitutive expression of which protects the bacterium from the detrimental effects of moderate barnase production. Full expression of the barnase gene overcomes protection by barstar and becomes lethal. Having a unique SmaI/XmaI site in the barnase structural gene, pMT416 itself can be used as a selective vector: uncut or religated pMT416 will preclude growth while plasmids with inserts in the barnase gene will allow the cells to survive. The entire pUC polylinker was inserted into the barnase gene in place of the Val-36 codon. This insert of nineteen largely hydrophilic amino acids does not prevent the lethal effect of full expression of the gene. The resulting plasmid, pMT440, is a generally useful selective cloning vector representing the "kill-the-rest" approach. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 117984, Russia. Natl Inst Diabet Nutr Dis & Kidney, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Deyev, SM (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Vavilova St 32, Moscow 117984, Russia. RI Deyev, Sergey/F-8191-2014 OI Deyev, Sergey/0000-0002-3952-0631 NR 18 TC 12 Z9 14 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD SEP PY 1998 VL 259 IS 4 BP 379 EP 382 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 128CV UT WOS:000076388400005 PM 9790592 ER PT J AU Zhang, ZH Diwan, BA Anderson, LM Logsdon, D Olivero, OA Haines, DC Rice, JM Yuspa, SH Poirier, MC AF Zhang, ZH Diwan, BA Anderson, LM Logsdon, D Olivero, OA Haines, DC Rice, JM Yuspa, SH Poirier, MC TI Skin tumorigenesis and Ki-ras and Ha-ras mutations in tumors from adult mice exposed in utero to 3 '-azido-2 ',3 '-dideoxythymidine SO MOLECULAR CARCINOGENESIS LA English DT Article DE transplacental exposure; liver tumor; lung tumor; initiation/promotion ID INDUCED LUNG-TUMORS; IMMUNODEFICIENCY-VIRUS TYPE-1; CD-1 MICE; TRANSPLACENTAL EXPOSURE; ACTIVATING MUTATIONS; ZIDOVUDINE TREATMENT; LIVER-TUMORS; MOUSE SKIN; DNA-DAMAGE; GENE AB This study was designed to evaluate the potential initiating effects of transplacental 3'-azido-2',3'-dideoxythymine (AZT) and the role of ras mutational activation in skin tumors induced in a two-stage mouse skin model. In addition, mouse liver and lung tumors from a transplacental AZT tumorigenicity study reported elsewhere (Olivero et al., J Natl Cancer Inst 89:1602-1608, 1997) were examined for evidence of ras activation. For both tumor studies, pregnant CD-1 mice were given either vehicle or 25 mg of AZT daily on days 12-18 of gestation. In the 1997 study, the offspring were given no further exposure and were killed at 1 yr of age. For the skin tumor study, all mice received twice-weekly topical 1 2-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment from weeks 5-35; half of the mice had been exposed to AZT in utero. At weeks 16-18, 30, 31, and 34-41, the skin tumor incidences in mice given AZT and TPA were significantly higher than in mice given TPA alone (P less than or equal to 0.05). At week 41, the average numbers of tumors per mouse were 1.44 +/- 0.36 (mean +/- standard error of the mean) and 0.57 +/- 0.13 for mice given AZT plus TPA and TPA alone, respectively (P = 0.006). Mutagenesis in ras exons I and II was determined by polymerase chain reaction (PCR) and dye-terminator cycling sequencing of PCR products. Ha-ras exon I codons 12 and 13 were mutated in 1 1 of 19 tumors (58%) from mice given AZT and TPA and in one of 15 tumors (7%) from mice given PPA alone (P = 0.004). The only mutation in Ha-ras codon 12 (four in four tumors examined) was a G-->A transition in the second base, and the major mutation in codon 13 (six in seven tumors examined) was a G-->T transversion in the second base. In skin tumors, AZT exposure did not increase the number of Ha-ras codon 61 mutations, and no Ki-ras mutations were observed. Analysis of ras mutations in liver and lung tumors from mice exposed to AZT in utero (Olivero et al., J Natl Cancer Inst 89:1602-1608, 1997) with no TPA promotion showed ro significant AZT-related increases. (C) 1998 Wiley-Liss, Inc.(dagger). C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Int Agcy Res Canc, F-69372 Lyon, France. RP Poirier, MC (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 3B12,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 38 TC 34 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1998 VL 23 IS 1 BP 45 EP 51 DI 10.1002/(SICI)1098-2744(199809)23:1<45::AID-MC6>3.0.CO;2-G PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 123WU UT WOS:000076149200006 PM 9766437 ER PT J AU Grigoriev, M Hsieh, P AF Grigoriev, M Hsieh, P TI Migration of a holliday junction through a nucleosome directed by the E-coli RuvAB motor protein SO MOLECULAR CELL LA English DT Article ID BRANCH MIGRATION; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; ESCHERICHIA-COLI; STRAND-EXCHANGE; HOMOLOGOUS RECOMBINATION; HISTONE OCTAMER; DNA HELICASE; RECA PROTEIN; DUPLEX DNA AB Chromatin plays a critical role in regulating access to DNA by proteins that direct recombination and repair. The E. coli RuvAB protein complex promotes branch migration of the Holliday junction recombination intermediate. The ability of RuvAB to negotiate passage of the junction through nucleosomal DNA is examined. The model system involves the formation of a Holliday junction positioned upstream of a nucleosome. Unassisted, the junction is blocked by a histone octamer. In the presence of RuvAB and ATF, rapid branch migration through the nucleosome is observed. It results in disruption of the histone-DNA interactions leading to the removal of the octamer from the junction intermediate. These results suggest that eukaryotic DNA motor proteins analogous to RuvAB could function during recombination to promote branch migration through chromatin. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Hsieh, P (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM hsieh@ncifcrf.gov NR 43 TC 17 Z9 17 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD SEP PY 1998 VL 2 IS 3 BP 373 EP 381 DI 10.1016/S1097-2765(00)80281-6 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NY UT WOS:000076189700009 PM 9774975 ER PT J AU Liu, JL Grinberg, A Westphal, H Sauer, B Accili, D Karas, M LeRoith, D AF Liu, JL Grinberg, A Westphal, H Sauer, B Accili, D Karas, M LeRoith, D TI Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: Manipulation using the Cre/loxP system in transgenic mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID IGF-I; CRE RECOMBINASE; MILK-BORNE; EXPRESSION; RECEPTOR; RETARDATION; CELLS; DIFFERENTIATION; DISRUPTION; MUTATIONS AB Insulin-like growth factor-I (IGF-I) is essential for cell growth, differentiation and postnatal development. A null mutation in igf-1 causes intrauterine growth retardation and perinatal lethality, The present study was designed to test the lower limit of igf-l gene dosage that ensures survival and postnatal growth by using the Cre/loxP system. Mice with variable reductions in IGF-I levels were generated by crossing EIIa-cre transgenic mice and mice with loxP-flanked igf-1 locus (igf-1/flox), EIIa-cre mice express bacteriophage P1 Cre (causes recombination) recombinase under the adenovirus promoter EIIa, during early embryonic development before implantation, and cause genomic recombination of the igf-1/flox locus. Mice with the most extensive recombination die immediately after birth, while the survivors have significant growth retardation in proportion to the reduction in their igf-1 gene, Interestingly, this gene dosage effect on body weight was not very significant before weaning, However, when the young animals were weaned at 3 weeks, the igf-1 gene dosage was the only independent predictor of the weight gain between 3 and 6 weeks among the parameters tested. Although growth retarded, mice with Ore-induced partial igf-1 deficiency were fertile and gave birth to null mice. Thus Cre-induced genomic recombination using the EIIa promoter occurs during development and creates distinct phenotypes compared with the conventional null mutation. This variability allows for postnatal survival and will enable one to begin to explore the role of the endocrine vs, paracrine effects of IGF-I. C1 NIDDKD, Diabet Branch, Sect Cellular & Mol Physiol, NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDKD, Diabet Branch, Sect Cellular & Mol Physiol, NIH, Room 8S235A,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 32 TC 125 Z9 130 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1998 VL 12 IS 9 BP 1452 EP 1462 DI 10.1210/me.12.9.1452 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 114GR UT WOS:000075601200016 PM 9731712 ER PT J AU Thibodeau, J Lavoie, PM Samaan, A Corre, JP Sekaly, RP Cazenave, PA AF Thibodeau, J Lavoie, PM Samaan, A Corre, JP Sekaly, RP Cazenave, PA TI Conserved structural features between HLA-DO beta and -DR beta SO MOLECULAR IMMUNOLOGY LA English DT Article DE HLA-DO; antigen presentation; MHC class II; superantigens; CD4 ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MHC; STAPHYLOCOCCAL ENTEROTOXIN-A; ALPHA-CHAIN GENE; INVARIANT CHAIN; MONOCLONAL-ANTIBODIES; BINDING-SITE; INTRACELLULAR-TRANSPORT; TARGETING SIGNAL; DM AB HLA-DO is a non-classical MHC class II molecule presumed to play a specialized role in the antigen processing pathway. We have modeled the HLA-DO beta-chain and found its overall structure compatible with the one of DR beta. Functional studies further highlighted the similarity between these beta-chains of the class II family of proteins. Indeed, a mixed heterodimer composed of the DR alpha and a chimeric DO beta-chains presented bacterial superantigens to T cells and was shown to interact with CD4. The implications of such structural conservation for the in vivo functions of HLA-DO are discussed. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Inst Pasteur, Paris, France. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. McGill Sch Med, Div Expt Med, Montreal, PQ, Canada. NIH, NIAID, Immunogenet Lab, Rockville, MD USA. Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. RP Thibodeau, J (reprint author), Inst Pasteur, Paris, France. EM thiobodj@magellan.umontreal.ca OI Lavoie, Pascal/0000-0002-2205-0362 FU NCPDCID CDC HHS [NCIC-007273] NR 59 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 1998 VL 35 IS 13 BP 885 EP 893 DI 10.1016/S0161-5890(98)00061-3 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 140DT UT WOS:000077072100008 PM 9839557 ER PT J AU Barker, LP Brooks, DM Small, PLC AF Barker, LP Brooks, DM Small, PLC TI The identification of Mycobacterium marinum genes differentially expressed in macrophage phagosomes using promoter fusions to green fluorescent protein SO MOLECULAR MICROBIOLOGY LA English DT Article ID SHUTTLE VECTORS; HOST-CELLS; INFECTION; TUBERCULOSIS; GFP; IMMUNODEFICIENCY; MARKER; TOOL AB Mycobacterium marinum, like Mycobacterium tuberculosis, is a slow-growing pathogenic mycobacteria that is able to survive and replicate in macrophages. Using the promoter-capture Vector pFPV27, we have constructed a library of 200-1000 bp fragments of M. marinum genomic DNA inserted upstream of a promoterless green fluorescent protein (GFP) gene. Only those plasmids that contain an active promoter will express GFP. Macrophages were infected with this fusion library, and phagosomes containing fluorescent bacteria were isolated. Promoter constructs that were more active intracellularly were isolated with a fluorescence-activated cell sorter, and inserts were partially sequenced. The promoter fusions expressed intracellularly exhibited homology to mycobacterial genes encoding, among others, membrane proteins and biosynthetic enzymes. Intracellular expression of GFP was 2-20 times that of the same clones grown in media. Several promoter constructs were transformed into Mycobacterium smegmatis, Mycobacterium bovis BCG and Mycobacterium tuberculosis. These constructs were positive for GFP expression in all mycobacterial strains tested. Sorting fluorescent bacteria in phagosomes circumvents the problem of isolating a single clone from macrophages, which may contain a mixed bacterial population. This method has enabled us to isolate 12 M. marinum clones that contain promoter constructs differentially expressed in the macrophage. C1 NIAID, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. RP Barker, LP (reprint author), NIAID, Rocky Mt Labs, Microscopy Branch, 903 S 4th St, Hamilton, MT 59840 USA. EM LBARKER@NIH.GOV NR 43 TC 72 Z9 72 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1998 VL 29 IS 5 BP 1167 EP 1177 DI 10.1046/j.1365-2958.1998.00996.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 117KW UT WOS:000075781300005 PM 9767585 ER PT J AU Yuan, Y Zhu, YQ Crane, DD Barry, CE AF Yuan, Y Zhu, YQ Crane, DD Barry, CE TI The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis SO MOLECULAR MICROBIOLOGY LA English DT Article ID BIOSYNTHESIS; IDENTIFICATION; PERMEABILITY; POINT AB There are three major structural classes of mycolic acids in the cell envelope of Mycobacterium tuberculosis (MTB): alpha-, methoxy- and ketomycolate. The two oxygen-containing classes are biosynthetically related through a common cu-methyl hydroxymycolate intermediate. BCG strains that fail to produce methoxymycolate and instead produce only keto- and alpha-mycolic acids show apparent defects in the O-methyltransferase MMAS-3. Overproduction of MMAS-3 from MTB resulted in a complete replacement of ketomycolate by methoxymycolate in both BCG and MTB. In vitro growth of these recombinant strains lacking ketomycolate was impaired at reduced temperatures but appeared to be normal at 37 degrees C. Glucose uptake was significantly decreased in such strains, but uptake of chenodeoxycholate and glycine was unaffected. Although sensitivity to INH remained unchanged, these cells were found to be hypersensitive to ampicillin and rifampicin. Infectivity of BCG and H37Rv wild type or MMAS-3 overproducers in THP-1 cells was somewhat affected, but the ability of the strains lacking ketomycolate to grow within this macrophage-like cell line was severely compromised. In vivo labelling of mycolic acids during growth of H37Rv within THP-1 cells revealed a substantial increase in ketomycolate and alphamycolate synthesized by intracellularly grown mycobacteria. These results establish a critical role for mycolate composition in proper cell wall function during the growth of MTB in vivo. C1 NIAID, TB Res Stn, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Barry, CE (reprint author), NIAID, TB Res Stn, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 25 TC 113 Z9 119 U1 1 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1998 VL 29 IS 6 BP 1449 EP 1458 DI 10.1046/j.1365-2958.1998.01026.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 123FX UT WOS:000076116100011 PM 9781881 ER PT J AU Qu, W Rippe, RA Ma, JX Scarborough, P Biagini, C Fiedorek, FT Travlos, GS Parker, C Zeldin, DC AF Qu, W Rippe, RA Ma, JX Scarborough, P Biagini, C Fiedorek, FT Travlos, GS Parker, C Zeldin, DC TI Nutritional status modulates rat liver cytochrome P450 arachidonic acid metabolism SO MOLECULAR PHARMACOLOGY LA English DT Article ID EPOXYEICOSATRIENOIC ACIDS; DIABETIC RAT; ENANTIOFACIAL SELECTIVITY; EXPRESSION; EPOXYGENASE; HORMONE; MICROSOMES; STARVATION; OXYGENATION; RELEASE AB Alterations in nutritional status affect hepatic cytochrome P450 levels. Since cytochromes P450 participate in the metabolism of arachidonic acid, we hypothesized that changes in liver P450 arachidonic acid metabolism occur during fasting and refeeding. Male Fisher 344 rats were either fed, fasted 48 hr (F48), fasted 48 hr and then refed 6 hr (F48/R6), or fasted 48 hr and then refed 24 hr (F48/R24). F48 rats had reduced body weight, increased plasma beta-hydroxybutyrate, and reduced plasma insulin compared with the other groups. Although there was no significant change in total liver P450 content, there was a significant 20%, 48%, and 24% reduction in total hepatic microsomal arachidonic acid metabolism in F48, F48/R6, and F48/R24 rats, respectively, compared with fed rats. Epoxygenase activity decreased by 28%, 51%, and 26% in F48, F48/ R6, and F48/R24 rats, respectively. In contrast, omega-1 hydroxylase activity increased by 126% in F48 rats compared with fed rats. Immunoblotting revealed that levels of CYP2C11 protein were markedly reduced, whereas levels of CYP2E1 protein were markedly increased in the F48 and F48/R6 groups. In contrast, levels of CYP1A1, CYP1A2, CYP2B1, CYP2J3, CYP4A1, and CYP4A3 were unchanged with fasting/refeeding. Northern blots revealed that levels of CYP2C11 mRNAs were decreased, whereas CYP2E1 mRNAs were increased in F48 and F48/R6 rats. Recombinant CYP2C11 metabolized arachidonic acid primarily to epoxides with preference for the 14(S),15(R)-, 11(R),12(S)-, and 8(S),9(R)- epoxyeicosatrienoic acid enantiomers. We conclude that (1) nutritional status affects hepatic microsomal arachidonic acid metabolism, (2) reduced epoxygenase activity in F48 and F48/R6 rats is accompanied by decreased levels of CYP2C11, (3) increased omega-1 hydroxylase activity is accompanied by augmented levels of CYP2E1, and (4) the effects of fasting on CYP2C11 and CYP2E1 expression occur at the pretranslational level. C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Expt Pathol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Signal Transduct Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIAAA NIH HHS [R29-AA10459]; NIDDK NIH HHS [P30-DK34987] NR 37 TC 27 Z9 31 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1998 VL 54 IS 3 BP 504 EP 513 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120BH UT WOS:000075934300007 PM 9730909 ER PT J AU Lazarovici, P Jiang, H Fink, D AF Lazarovici, P Jiang, H Fink, D TI The 38-amino-acid form of pituitary adenylate cyclase-activating polypeptide induces neurite outgrowth in PC12 cells that is dependent on protein kinase C and extracellular signal-regulated kinase but not on protein kinase A, nerve growth factor receptor tyrosine kinase, p21(ras) G protein, and pp60(c-src) cytoplasmic tyrosine kinase SO MOLECULAR PHARMACOLOGY LA English DT Article ID MAP KINASE; NEURONAL DIFFERENTIATION; PHEOCHROMOCYTOMA CELLS; NEUROTROPHIN RECEPTORS; SELECTIVE INHIBITOR; DOWN-REGULATION; PC-12 CELLS; CYCLIC-AMP; ACID FORM; CAMP AB The 38-amino-acid isoform of pituitary adenylate cyclase-activating polypeptide (PACAP38) elicits a robust outgrowth of neurites in cultured PC12 cells. Initiation of neurite outgrowth occurs within 4-8 hr after the addition of PACAP38. Treatment with PACAP38 does not elicit collateral activation of p140(trk) nerve growth factor receptor tyrosine kinase activity, nor is it associated with tyrosine phosphorylation of suc1-associated neurotrophic factor target, a selective target of neurotrophin tyrosine kinase receptors. Coadministration of epidermal growth factor with PACAP38 elicits an enhanced response. Induction of neurites is also observed on the addition of PACAP38 to dominant negative Src and Ras PC12 cell variants. PACAP38 stimulates extracellular signal-regulated kinase (Erk) activity >10-fold within 5 min, and the effect is augmented by cotreatment with epidermal growth factor. Pretreatment with the cAMP-dependent protein kinase-selective inhibitor, H-89, is ineffective as an antagonist of PACAP38-induced neurite outgrowth, whereas down-regulation of protein kinase C (PKC) by phorbol ester or incubation with PKC-selective inhibitors GF109203X and calphostin C effectively blocks PACAP38-stimulated neurite formation. Stimulation of Erk activity is inhibited by incubation with PD90859, a pharmacological antagonist of the threonine/tyrosine dual-specificity Erk. inhibition of ligand-stimulated Erk activation prevents PACAP38-induced neurite outgrowth. Collectively, these findings indicate that PACAP38-stimulated neuritogenesis requires PKC and Erk activation but is independent of cAMP-dependent protein kinase, nerve growth factor receptor tyrosine kinase, p21(ras) G protein, and pp60(c-src) cytoplasmic tyrosine kinase. C1 Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Dept Pharmacol, IL-91010 Jerusalem, Israel. NICHHD, Growth Factors Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Fink, D (reprint author), US FDA, CBER, Div Cytokine Biol, 1401 Rockville Pike,Suite 200 N-HFM-505, Rockville, MD 20852 USA. NR 38 TC 75 Z9 75 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1998 VL 54 IS 3 BP 547 EP 558 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120BH UT WOS:000075934300012 PM 9730914 ER PT J AU Pasternak, KI Timo-Iaria, C Rodrigues, CJ Maria, DA Duarte, AJS Paiva, L Pozzi, DH de Mendonca, BB Wong, ML Licinio, J AF Pasternak, KI Timo-Iaria, C Rodrigues, CJ Maria, DA Duarte, AJS Paiva, L Pozzi, DH de Mendonca, BB Wong, ML Licinio, J TI Circumscribed lesion of the medial forebrain bundle area causes structural impairment of lymphoid organs and severe depression of immune function in rats SO MOLECULAR PSYCHIATRY LA English DT Article DE lymphoid organs; cytotoxicity; medial forebrain bundle; hypothalamus; thymus; spleen ID NORADRENERGIC SYMPATHETIC INNERVATION; SPLENIC WHITE PULP; INFLAMMATORY DISEASE; MULTIPLE-SCLEROSIS; EXPRESSION; SPLEEN; BRAIN; LYMPHOCYTES; MODULATION; SYSTEM AB Interactions between the immune system and the brain are a key element in the pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and Alzheimer's, which affect large numbers of individuals and are associated with a high social cost. However, the neuroanatomical basis of brain-immune interactions has not been elucidated. We report that in Wistar rats of either sex bilateral electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7 days after lesioning, and causes widespread infections, aphagia, adypsia, structural damage to the lymphoid organs and heavy depression of T lymphocytes cytotoxicity. The following alterations occur in the immune system after those lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%, 49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is reduced and lymphoid cells from periarteriolar zones and at the chords are almost absent. In lymph nodes cortical small lymphocytes are depleted and primary and secondary nodules and germinal centers ail but disappear. Cytotoxicity of lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in lymph nodes. The critical area of lesion is at the medialmost portion of the medial forebrain bundle, at the preoptic area and rostral part of the anterior hypothalamus. We suggest that this area contains neural circuits that are crucial for keeping the structure of lymphoid organs and the functional integrity of the immune system. C1 NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Fac Med, BR-01246903 Sao Paulo, Brazil. RP Pasternak, KI (reprint author), Rua Austria 141, BR-01447 Sao Paulo, Brazil. RI Wong, Ma-Li/D-7903-2011; Mendonca, Berenice/C-2827-2012; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 45 TC 5 Z9 5 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1998 VL 3 IS 5 BP 397 EP 404 DI 10.1038/sj.mp.4000426 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 118PZ UT WOS:000075848700006 PM 9774772 ER PT J AU Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, W Marsh, WL Walter, JM Hamburger, SD Ginns, E Rapoport, JL Sidransky, E AF Castellanos, FX Lau, E Tayebi, N Lee, P Long, RE Giedd, JN Sharp, W Marsh, WL Walter, JM Hamburger, SD Ginns, E Rapoport, JL Sidransky, E TI Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses SO MOLECULAR PSYCHIATRY LA English DT Article DE dopamine 4 receptor; VNTR; magnetic resonance imaging; replication studies; case-control studies ID DEFICIT HYPERACTIVITY DISORDER; D4 RECEPTOR; TOURETTE SYNDROME; NOVELTY SEEKING; LINKAGE DISEQUILIBRIUM; LOCUS; CHILDREN; ALLELE; PARENT AB Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family,(1) adoption,(2) and twin studies(3) suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding,4 and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD.(5,6) We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls,(7) did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,Room 3B19,Room 3N202, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 27 TC 98 Z9 102 U1 2 U2 9 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1998 VL 3 IS 5 BP 431 EP 434 DI 10.1038/sj.mp.4000430 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 118PZ UT WOS:000075848700011 PM 9774777 ER PT J AU Blanchet, PJ Konitsiotis, S Chase, TN AF Blanchet, PJ Konitsiotis, S Chase, TN TI Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys SO MOVEMENT DISORDERS LA English DT Article DE levodopa; dyskinesia; Parkinson's disease; MPTP ID RECEPTOR AGONISTS; DISEASE; MEMANTINE; BLOCKADE; DRUGS; BRAIN AB The antidyskinetic potential of the glutamate NMDA receptor channel blocker amantadine was evaluated in four levodopa-primed parkinsonian monkeys using two differ ent regimens (1.25 or 2.5 mg/kg administered subcutaneously twice daily for 3-6 days). When administered with a relatively low dose of levodopa, amantadine produced a near-total suppression of choreiform dyskinesias and a substantial reduction in dystonic dyskinesias at the expense of a significant reduction in antiparkinsonian response. With a high dose of levodopa, amantadine had a smaller but still significant effect on dyskinesias without altering the antiparkinsonian response. These results lend support to the view that glutamate receptor-mediated mechanisms contribute to levodopa-induced dyskinesias. They also suggest that amantadine could alleviate such complications in parkinsonian patients, especially with careful dose optimization. C1 NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, Bldg 10,Room 5C103,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 19 TC 124 Z9 127 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 1998 VL 13 IS 5 BP 798 EP 802 DI 10.1002/mds.870130507 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 119LX UT WOS:000075898900005 PM 9756148 ER PT J AU Clark, LS Hart, DW Vojta, PJ Harrington-Brock, K Barrett, JC Moore, MM Tindall, KR AF Clark, LS Hart, DW Vojta, PJ Harrington-Brock, K Barrett, JC Moore, MM Tindall, KR TI Identification and chromosomal assignment of two heterozygous mutations in the Trp53 gene in L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cells SO MUTAGENESIS LA English DT Article ID P53 PROTEIN; LOCUS; CARCINOGENICITY; APOPTOSIS; COMPLEX; LESIONS; CANCER AB The thymidine kinase locus (Tk1) in Tk(+/-)-3.7.2C mouse lymphoma cells is widely used to identify mutagenic agents. Because Trp53 (the mouse homolog of human TP53) is located with Tk1 on chromosome 11 and is critical in regulating cellular responses following exposure to DNA damaging agents, we wanted to determine if these mouse lymphoma cells harbor mutations in Trp53, Single-stranded conformation polymorphism (SSCP) analysis of PCR-amplified exons 4-9 of Trp53 indicated mutations in both exons 4 and 5, We sequenced exons 4-9 from isolated clones of Tk(+\-)-3.7.2C cells and a Tk(-\-) mutant (G4). Mutant G4 has two copies of the chromosome carrying the Tk1(+) allele and no copy of the chromosome carrying the Tk1(+) allele and thus could establish linkage of the individual Trp53 and Tk1 alleles, DNA sequence analysis revealed no mutations in exons 6-9 in any Tk(+\-)-3.7.2C or G4 clones. As suggested by SSCP, there was a nonsense mutation in exon 4 at bp 301 (codon 101) in one Trp53 allele, Tk(+\-)-3.7.2C clones have both mutant and wild-type sequences at bp 301; G4 clones have wild-type exon 4 sequence, These data allow assignment of the Trp53 exon 4 mutated allele to chromosome 11 carrying the Tk1(+) allele, The exon 4 mutation leads to a stop codon early in translation, thus functionally deleting the Trp53 allele on the Tk1(+)-bearing chromosome. As previously reported, we find a missense mutation in exon 5 at bp 517 (codon 173) in one Trp53 allele, Using the G4 clones we determined that the exon 5 mutation is linked to the Tk1(-) allele, Thus the Tk(+/-)-3.7.2C mouse lymphoma cells have two mutant Trp53 alleles, likely accounting for their rapid cell growth and contributing to their ability to detect the major types of mutational damage associated with the etiology of tumor development. This ability to integrate across the mutational events seen in the multiple stages of tumor development further supports the use of the assay in chemical and drug safety studies and its recommendation as part of the required screening battery for regulatory agency submissions. C1 US EPA, Genet & Cellular Toxicol Branch, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27515 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Clark, LS (reprint author), US EPA, Genet & Cellular Toxicol Branch, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, MD-68, Res Triangle Pk, NC 27711 USA. EM clark.scott@epamail.epa.gov NR 37 TC 35 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1998 VL 13 IS 5 BP 427 EP 434 DI 10.1093/mutage/13.5.427 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 124PB UT WOS:000076189900002 PM 9800187 ER PT J AU Liechty, MC Scalzi, JM Sims, KR Crosby, HC Spencer, DL Davis, LM Caspary, WJ Hozier, JC AF Liechty, MC Scalzi, JM Sims, KR Crosby, HC Spencer, DL Davis, LM Caspary, WJ Hozier, JC TI Analysis of large and small colony L5178Y tk(-/-) mouse lymphoma mutants by loss of heterozygosity (LOH) and by whole chromosome 11 painting: detection of recombination SO MUTAGENESIS LA English DT Article ID THYMIDINE KINASE LOCUS; TK-/-MUTANTS; TRIFLUOROTHYMIDINE-RESISTANT; MITOTIC RECOMBINATION; CYTOGENETIC ANALYSIS; ASSAY SYSTEM; CELL-LINE; SACCHAROMYCES-CEREVISIAE; SIZE DISTRIBUTION; MAMMALIAN-CELLS AB Analysis of 122 spontaneous large and small colony mutants derived from L5178Y tk(+/-) mouse lymphoma cells at 28 heteromorphic microsatellite loci on chromosome 11 showed that extensive loss of heterozygosity (LOH) is common in both large colony and small colony mutants, eliminating most chromosome 11 loci as candidates for a putative growth control locus. These results, in conjunction with historical cytogenetic data, suggest that a putative growth control locus lies distal to the thymidine kinase (Tk1) gene, near the telomere. Thirty seven mutants were hybridized with a chromosome Ii-specific whole chromosome painting probe for analysis of rearrangements. Generally, painting confirmed earlier observations that large colony mutants are karyotypically normal, whereas small colony mutants frequently have detectable rearrangements. A point probe distal to Tk1 revealed no evidence of chromosome breakage in small colony mutants that appeared normal on whole 11 painting and had no LOH. Therefore, the molecular difference between large and small colony mutants remains unknown. Models to explain large and small colony mutants consistent with our findings are presented, including loss of a putative growth control gene, differential mechanisms of chromosome breakage/repair and second site mutations as explanations for small colony mutants. Painting revealed translocations and aneuploidy and showed that non-disjunction was not a common explanation for complete LOH. The most common finding was that large regions of LOH do not result from deletions, demonstrating that these cells can detect recombination events as well as previously observed chromosomal rearrangements, deletions and point mutations. C1 Appl Genet Labs Inc, Melbourne, FL 32901 USA. NIH, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Liechty, MC (reprint author), Appl Genet Labs Inc, 1335 Gateway Dr,Suite 2001, Melbourne, FL 32901 USA. FU NIEHS NIH HHS [N44-ES-32002, N44-ES-92003] NR 74 TC 22 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1998 VL 13 IS 5 BP 461 EP 474 DI 10.1093/mutage/13.5.461 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 124PB UT WOS:000076189900006 PM 9800191 ER PT J AU Watson, DE Cunningham, ML Tindall, KR AF Watson, DE Cunningham, ML Tindall, KR TI Spontaneous and ENU-induced mutation spectra at the cII locus in Big Blue (R) Rat2 embryonic fibroblasts SO MUTAGENESIS LA English DT Article ID LACI TRANSGENIC MICE; ETHYLNITROSOUREA-INDUCED MUTATION; IN-VIVO MUTATIONS; BACTERIOPHAGE-LAMBDA; PHAGE-LAMBDA; DNA; GENE; HPRT; FREQUENCY; SOFTWARE AB Big Blue(R) Rat2 embryonic fibroblasts carry the lambda-Liz shuttle vector which is also present in the Big Blue(R) mouse and rat. Mutations in the Big Blue(R) systems have most often been measured at the lad locus. However, a method for positive selection of mutations at the lambda cll locus was recently described. This assay appears to have many advantages over the use of lad as a mutational target, but it has yet to be well characterized in mammalian mutagenesis studies. The objective of these studies was to determine the spontaneous and ethylnitrosourea (ENU)-induced mutant frequencies (MFs) and mutational spectra at cII using Big Blue(R) Rat2 embryonic fibroblasts. The average spontaneous MF was 13 +/- 1.4 x 10(-5), The average induced MF was 60 +/- 10 x 10(-5) 10 days following a 30 min treatment with 0.1 mg/ml ENU, Eighty four independent spontaneous mutants were sequenced: 23 (27.4%) were frameshift mutations and 61 (72.6%) were base substitutions. Two spontaneous frameshift hotspots were detected, both in mononucleotide runs. G:C-->A:T transitions were the most common type of base substitution in cll; of these 71% occurred at CpG sites, The ENU-induced mutational spectrum at cll (44 mutants) consisted of 42 base substitutions (95.5%) and two -1 frameshift mutations (4.5%). Compared with the spontaneous spectrum, the ENU-induced spectrum had significantly fewer frameshift mutations (4.5 versus 27%) and base substitutions occurred predominantly at A:T base pairs (71 versus 34%). Overall, the spontaneous cll mutational spectrum reported here differs slightly from spontaneous spectra reported at the Big Blue(R) lad locus, but the mutational spectra and base substitution MFs following treatment with ENU were comparable at both loci. These data support the continued use of cm as a selectable marker in mutagenesis studies involving cells or tissues that carry a lambda transgene. C1 NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Tindall, KR (reprint author), NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. EM tindall@niehs.nih.gov NR 33 TC 37 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1998 VL 13 IS 5 BP 487 EP 497 DI 10.1093/mutage/13.5.487 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 124PB UT WOS:000076189900009 PM 9800194 ER PT J AU Adler, ID Bootman, J Favor, J Hook, G Schriever-Schwemmer, G Welzl, G Whorton, E Yoshimura, I Hayashi, M AF Adler, ID Bootman, J Favor, J Hook, G Schriever-Schwemmer, G Welzl, G Whorton, E Yoshimura, I Hayashi, M TI Recommendations for statistical designs of in vivo mutagenicity tests with regard to subsequent statistical analysis SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE experimental design; statistical analysis; micronucleus test in mouse bone marrow peripheral blood; chromosomal aberration tests in mouse bone marrow differentiating spermatogonia; mouse dominant lethal test ID MARROW MICRONUCLEUS ASSAY; DOMINANT LETHAL ASSAY; CURRENT ISSUES; DOSE-RESPONSE; CARCINOGENESIS; MUTAGENESIS; MICE; NEED AB A workshop was held on September 13 and 14, 1993, at the GSF, Neuherberg, Germany, to start a discussion of experimental design and statistical analysis issues for three in vivo mutagenicity test systems, the micronucleus test in mouse bone marrow/peripheral blood, the chromosomal aberration tests in mouse bone marrow/differentiating spermatogonia, and the mouse dominant lethal test. The discussion has now come to conclusions which we would like to make generally known. Rather than dwell upon specific statistical tests which could be used for data analysis, serious consideration was given to test design. However, the test design, its power of detecting a given increase of adverse effects and the test statistics are interrelated. Detailed analyses of historical negative control data led to important recommendations for each test system. Concerning the statistical sensitivity parameters, a type I error of 0.05 tone tailed), a type II error of 0.20 and a dose related increase of twice the background (negative control) frequencies were generally adopted. It was recommended that sufficient observations (cells, implants) be planned for each analysis unit (animal) so that at least one adverse outcome (micronucleus, aberrant cell, dead implant) would likely be observed. The treated animal was the smallest unit of analysis allowed. On the basis of these general consideration the sample size was determined for each of the three assays. A minimum of 2000 immature erythrocytes/animal should be scored for micronuclei from each of at least 4 animals in each comparison group in the micronucleus assays. A minimum of 200 cells should be scored for chromosomal aberrations from each of at least 5 animals in each comparison group in the aberration assays. In the dominant lethal test, a minimum of 400 implants (40-50 pregnant females) are required per dose group for each mating period. The analysis unit for the dominant lethal test would be the treated male unless the background frequency of dead implants (DI) is so low that multiple males would need to be integrated to meet the minimum observation of one adverse outcome (DI) per analysis unit. A three-step strategy of data analysis was proposed for the cytogenetic assays. Use of negative historical controls was allowed in certain circumstances for interpretation of results from micronucleus tests and chromosomal aberration tests. (C) 1998 Elsevier Science B.V. All rights reserved. C1 GSF, Inst Saugetiergenet, D-85758 Neuherberg, Germany. Pharmaco LSR, Eye IP23 7PX, Suffolk, England. NIEHS, Res Triangle Pk, NC 27709 USA. GSF, Inst Med Informat & Sytemforsch, D-85758 Neuherberg, Germany. Univ Texas, Med Branch, Div Epidemiol & Biostat, Galveston, TX 77555 USA. Sci Univ Tokyo, Fac Engn, Shinjuku Ku, Tokyo 162, Japan. Natl Inst Hyg Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 158, Japan. RP Adler, ID (reprint author), GSF, Inst Saugetiergenet, D-85758 Neuherberg, Germany. EM adler@gsf.de NR 37 TC 17 Z9 18 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD SEP 1 PY 1998 VL 417 IS 1 BP 19 EP 30 DI 10.1016/S1383-5718(98)00091-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 118MV UT WOS:000075843000003 PM 9729247 ER PT J AU Koonin, EV AF Koonin, EV TI Genomic microbiology: Right on target? SO NATURE BIOTECHNOLOGY LA English DT News Item ID SEQUENCE; FAMILIES C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 13 TC 3 Z9 3 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 1998 VL 16 IS 9 BP 821 EP 822 DI 10.1038/nbt0998-821 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 115NN UT WOS:000075671700023 PM 9743110 ER PT J AU Redston, M Nathanson, KL Yuan, ZQ Neuhausen, SL Satagopan, J Wong, N Yang, D Nafa, D Abrahamson, J Ozcelik, H Antin-Ozerkis, D Andrulis, I Daly, M Pinsky, L Schrag, D Gallinger, S Kaback, M King, MC Woodage, T Brody, LC Godwin, A Warner, E Weber, B Foulkes, W Offit, K AF Redston, M Nathanson, KL Yuan, ZQ Neuhausen, SL Satagopan, J Wong, N Yang, D Nafa, D Abrahamson, J Ozcelik, H Antin-Ozerkis, D Andrulis, I Daly, M Pinsky, L Schrag, D Gallinger, S Kaback, M King, MC Woodage, T Brody, LC Godwin, A Warner, E Weber, B Foulkes, W Offit, K TI The APC I1307K allele and breast cancer risk SO NATURE GENETICS LA English DT Letter ID CARCINOMAS; MUTATIONS C1 McGill Univ, Dept Med, SMBD JGH, Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Surg, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal Gen Hosp, Inst Res, Montreal, PQ H3G 1A4, Canada. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. Univ Calif San Diego, Childrens Hosp, La Jolla, CA 92093 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Utah, Sch Med, Dept Med Informat, Genet Epidemiol Grp, Salt Lake City, UT USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ Penn, Stellar Chance Labs, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Stellar Chance Labs, Dept Genet, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON, Canada. Univ Toronto, Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Toronto, Ontario Canc Inst Network, Toronto, ON, Canada. Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. RP Foulkes, W (reprint author), McGill Univ, Dept Med, SMBD JGH, Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada. RI Andrulis, Irene/E-7267-2013; Gallinger, Steven/E-4575-2013 FU NCI NIH HHS [R01 CA5760, R01-CA74415]; NIGMS NIH HHS [1TG32GM08638] NR 11 TC 47 Z9 48 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 13 EP 14 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400010 PM 9731522 ER PT J AU Ermolaeva, O Rastogi, M Pruitt, KD Schuler, GD Bittner, ML Chen, YD Simon, R Meltzer, P Trent, JM Boguski, MS AF Ermolaeva, O Rastogi, M Pruitt, KD Schuler, GD Bittner, ML Chen, YD Simon, R Meltzer, P Trent, JM Boguski, MS TI Data management and analysis for gene expression arrays SO NATURE GENETICS LA English DT Article ID SERIAL ANALYSIS; HYBRIDIZATION; GENOME; MICROARRAY; PATTERNS; MAP AB Microarray technology makes it possible to simultaneously study the expression of thousands of genes during a single experiment. We have developed an information system, ArrayDB, to manage and analyse large-scale expression data. The underlying relational database was designed to allow flexibility in the nature and structure of data input and also in the generation of standard or customized reports through a web-browser interface. ArrayDB provides varied options for data retrieval and analysis tools that should facilitate the interpretation of complex hybridization results. A sampling of ArrayDB storage, retrieval and analysis capabilities is available (www.nhgri.nih.gov/DIR/LCG/15K/HTML/), along with information on a set of approximately 15,000 genes used to fabricate several widely used microarrays. Information stored in ArrayDB is used to provide integrated gene expression reports by linking array target sequences with NCBl's Entrez retrieval system, UniGene and KEGG pathway views. The integration of externa I information resources is essential in interpreting intrinsic patterns and relationships in large-scale gene expression data. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Boguski, MS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 232 Z9 245 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 19 EP 23 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400012 PM 9731524 ER PT J AU Litingtung, Y Lei, L Westphal, H Chiang, C AF Litingtung, Y Lei, L Westphal, H Chiang, C TI Sonic hedgehog is essential to foregut development SO NATURE GENETICS LA English DT Article ID MAMMALIAN LUNG DEVELOPMENT; MORPHOGENESIS; MESENCHYME; DIFFERENTIATION; MALFORMATIONS; EPITHELIUM; INDUCTION; GENES AB Congenital malformation of the foregut is common in humans, with an estimated incidence of 1 in 3000 live births(1), although its aetiology remains largely unknown. Mice with a targeted deletion of Sonic hedgehog (Shh) have foregut defects that are apparent as early as embryonic day 9.5, when the tracheal diverticulum begins to outgrow. Homozygous Shh-null mutant mice show oesophageal atresia/stenosis, tracheo-oesophageal fistula and tracheal and lung anomalies, features similar to those observed in humans with foregut defects. The lung mesenchyme shows enhanced cell death, decreased cell proliferation and downregulation of Shh target genes. These results indicate that Shh, is required for the growth and differentiation of the oesophagus, trachea and lung, and suggest: that mutations in SHH and its signalling components may be involved in foregut defects in humans. C1 Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. RP Chiang, C (reprint author), Vanderbilt Univ, Med Ctr, Dept Cell Biol, 1161 21st Ave S, Nashville, TN 37232 USA. EM chin.chiang@ccmail.vanderbilt.edu NR 21 TC 442 Z9 454 U1 1 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 58 EP 61 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400020 PM 9731532 ER PT J AU Woodage, T King, SM Wacholder, S Hartge, P Struewing, JP McAdams, M Laken, SJ Tucker, MA Brody, LC AF Woodage, T King, SM Wacholder, S Hartge, P Struewing, JP McAdams, M Laken, SJ Tucker, MA Brody, LC TI The APC 11307K allele and cancer risk in a community-based study of Ashkenazi Jews SO NATURE GENETICS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; BREAST-CANCER; BETA-CATENIN; GENE; CARCINOMAS; MUTATIONS AB Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer(1) (CRC). APC is a tumour-suppressor gene, and somatic Loss occurs in tumours. The germline T-to-A transversion responsible for the APC I1307K allele converts the wild-type sequence to a homopolymer tract (A,) that is genetically unstable and prone to somatic mutation. The I1307K allele was found in 6.1% of unselected Ashkenazi Jews and higher proportions of Ashkenazim with family or personal histories of CRC (ref. 2). To evaluate the role of I1307K in cancer, we genotyped 5,081 Ashkenazi volunteers in a community survey. Risk of developing colorectal, breast and other cancers were compared between genotyped I1307K carriers and non-carriers and their first-degree relatives. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. RP Brody, LC (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 20 TC 123 Z9 125 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 62 EP 65 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400021 PM 9731533 ER PT J AU Zhuang, ZP Park, WS Pack, S Schmidt, L Vortmeyer, AO Pak, E Pham, T Weil, RJ Candidus, S Lubensky, IA Linehan, WM Zbar, B Weirich, G AF Zhuang, ZP Park, WS Pack, S Schmidt, L Vortmeyer, AO Pak, E Pham, T Weil, RJ Candidus, S Lubensky, IA Linehan, WM Zbar, B Weirich, G TI Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas SO NATURE GENETICS LA English DT Article ID HUMAN CANCER; MUTATIONS; LYMPHOMA; TUMORS AB The gene defect for hereditary papillary renal carcinoma(1) (HPRC) has recently been mapped to chromosome 7q, and germline mutations of MET (also known as c-met) at 7q31 have been detected in patients with HPRC (ref, 2). Tumours from these patients commonly show trisomy of chromosome 7 when analysed by cytogenetic studies and comparative genomic hybridization(3) (CGH), However, the relationship between trisomy 7 and MET germline mutations is not clear. We studied 16 renal tumours from two patients with documented germline mutations in exon 16 of MET. Flourescent in situ hybridization (FISH) analysis showed trisomy 7 in all tumours, To determine whether the chromosome bearing the mutant or wild-type MET gene was duplicated, we performed duplex PCR and phosphoimage densitometry using polymorphic microsatellite markers D7S1801 and D7S1822, which were linked to the disease gene locus, and D1S1646 as an internal control. We determined the parental origin of chromosome alleles by genotyping parental DNA, In ail 16 tumours there was an increased signal intensity (2:1 ratio) of the microsatellite allele from the chromosome bearing the mutant MET compared with the allele from the chromosome bearing the wild-type MET. Our study demonstrates a non-random duplication of the chromosome bearing the mutated MET in HPRC and implicates this event in tumorigenesis. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 11 TC 198 Z9 202 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 66 EP 69 DI 10.1038/1727 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400022 PM 9731534 ER PT J AU Xu, TS Bianco, P Fisher, LW Longenecker, G Smith, E Goldstein, S Bonadio, J Boskey, A Heegaard, AM Sommer, B Satomura, K Dominguez, P Zhao, CY Kulkarni, AB Robey, PG Young, MF AF Xu, TS Bianco, P Fisher, LW Longenecker, G Smith, E Goldstein, S Bonadio, J Boskey, A Heegaard, AM Sommer, B Satomura, K Dominguez, P Zhao, CY Kulkarni, AB Robey, PG Young, MF TI Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice SO NATURE GENETICS LA English DT Article ID GROWTH-FACTOR-BETA; PROTEOGLYCANS BIGLYCAN; HUMAN SKELETAL; BONE; DECORIN; EXPRESSION; HISTOMORPHOMETRY; FRAGILITY; LETHALITY; COLLAGEN AB The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone(1-3) and other non-skeletal connective tissues. in vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils(4) and TGF-beta (refs 5,6), and may promote neuronal survival(7). To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Univ Rome, I-00161 Rome, Italy. NIDR, Gene Targeting & Res Core Facil, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Orthopaed, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Hosp Special Surg, Mineralized Tissue Res Sect, New York, NY 10021 USA. RP Young, MF (reprint author), Bldg 30,Room 106,30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM young@yoda.nidr.nih.gov RI Dominguez, Pedro/A-8266-2012; Robey, Pamela/H-1429-2011; OI Dominguez, Pedro/0000-0003-4788-1071; Robey, Pamela/0000-0002-5316-5576; Boskey, Adele/0000-0002-6181-2219 NR 33 TC 380 Z9 391 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1998 VL 20 IS 1 BP 78 EP 82 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 115NK UT WOS:000075671400025 PM 9731537 ER PT J AU Yang, F Gustafson, KR Boyd, MR Wlodawer, A AF Yang, F Gustafson, KR Boyd, MR Wlodawer, A TI Crystal structure of Escherichia coli HdeA SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN C1 NCI, Frederick Canc Res & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, DTP, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol Struct Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NR 15 TC 52 Z9 54 U1 6 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1998 VL 5 IS 9 BP 763 EP 764 DI 10.1038/1796 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 114NB UT WOS:000075614600009 PM 9731767 ER PT J AU Long, JM Kalehua, AN Muth, NJ Calhoun, ME Jucker, M Hengemihle, JM Ingram, DK Mouton, PR AF Long, JM Kalehua, AN Muth, NJ Calhoun, ME Jucker, M Hengemihle, JM Ingram, DK Mouton, PR TI Stereological analysis of astrocyte and microglia in aging mouse hippocampus SO NEUROBIOLOGY OF AGING LA English DT Article DE stereology; CAI; dentate gyrus; hilus; glia; mouse ID FIBRILLARY ACIDIC PROTEIN; GFAP MESSENGER-RNA; ALZHEIMERS-DISEASE; RAT-BRAIN; NEURODEGENERATIVE DISEASES; TOTAL NUMBER; AGE; NEURONS; INCREASES; CELLS AB Recent evidence suggests neuroglia-mediated inflammatory mechanisms may stimulate neurodegenerative processes in mammalian brain during aging. To test the hypothesis that the number of microglia and astrocytes increase in the hippocampus during normal aging, unbiased stereological techniques were used to estimate total cell number in hippocampal subregions (CAI, dentate gyrus and hilus) of male C57BL/6J mice of different ages: 4-5 months, 13-14 months and 27-28 months. Immunocytochemical visualization for microglia and astrocytes were via Mac-1 and GFAP antibody, respectively. Estimates of total microglia and astrocyte number were assessed using the optical fractionator. No statistically significant age differences were found in the numbers of microglia or astrocytes in the hippocampal regions sampled. These findings suggest that age-related increases in the total numbers of hippocampal microglia and astrocytes is not causal for observed age-related increases in cytokine response. (C) 1998 Elsevier Science Inc. C1 NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, Baltimore, MD 21224 USA. Essex Community Coll, Dept Psychol, Baltimore, MD 21237 USA. Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Neuropathol Lab, Baltimore, MD 21205 USA. RP Long, JM (reprint author), NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LongJ@vax.grc.nia.nih.gov NR 45 TC 102 Z9 108 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP-OCT PY 1998 VL 19 IS 5 BP 497 EP 503 DI 10.1016/S0197-4580(98)00088-8 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 151NA UT WOS:000077725500015 PM 9880052 ER PT J AU Engel, WK AF Engel, WK TI The essentiality of histo- and cytochemical studies of skeletal muscle in the investigation of neuromuscular disease (Reprinted from Neurology, vol 12, 1962) SO NEUROLOGY LA English DT Reprint C1 Natl Inst Neurol Dis & Blindness, Med Neurol Branch, NIH, US PHS,Dept Hlth Educ & Welfare, Bethesda, MD 20892 USA. RP Engel, WK (reprint author), Natl Inst Neurol Dis & Blindness, Med Neurol Branch, NIH, US PHS,Dept Hlth Educ & Welfare, Bethesda, MD 20892 USA. NR 65 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP PY 1998 VL 51 IS 3 BP A778 EP A794 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 119LR UT WOS:000075898300002 ER PT J AU DeGraba, TJ AF DeGraba, TJ TI The role of inflammation after acute stroke - Utility of pursuing anti-adhesion molecule therapy SO NEUROLOGY LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; CEREBRAL-ARTERY OCCLUSION; TUMOR-NECROSIS-FACTOR; ISCHEMIC CELL-DAMAGE; CENTRAL-NERVOUS-SYSTEM; BRAIN INJURY; MONOCLONAL-ANTIBODY; REPERFUSION INJURY; ENDOTHELIAL-CELLS; FACTOR-ALPHA AB A growing body of evidence, primarily from animal models of cerebral ischemia and preliminary human studies, indicates that inflammatory mechanisms contribute to secondary neuronal injury after acute cerebral ischemia. Ischemia followed by reperfusion rapidly leads to the expression of inflammatory cytokines, particularly tumor necrosis factor-alpha and interleukin-1 beta, which stimulate a complex cascade of events involving local endothelial cells, neurons, astrocytes, and perivascular cells. A secondary response includes the release of other cytokines, an increase in components of the coagulation system, an upregulation of cell adhesion molecule expression, and changes in the expression of components of the immune response. The net effect of these events is transformation of the local endothelium to a prothrombotic/proinflammatory state and induction of leukocyte migration to the site of injury. A number of studies have shown that leukocyte migration occurs within hours of reperfusion. Leukocytes accumulate in the injured region, where they cause tissue injury by several mechanisms, including occlusion of microvasculature, generation of oxygen free radicals, release of cytotoxic enzymes, alteration of vasomotor reactivity, and increase in cytokine and chemoattractant release. Monoclonal antibodies against leukocyte adhesion molecules have been shown to reduce infarct volume in animal models of ischemia-reperfusion. However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial. A number of factors may complicate the use of antibody directed adhesion molecule blockade in acute stroke and will be discussed in this article. Overall, an increased understanding of inflammatory and immunologic mechanisms still offers great potential for reducing acute stroke injury. C1 NINDS, NIH, Stroke Branch, Clin Invest Sect, Bethesda, MD 20892 USA. RP DeGraba, TJ (reprint author), NINDS, NIH, Stroke Branch, Clin Invest Sect, 36 Convent Dr,MS 4128,Bldg 36-4A-03, Bethesda, MD 20892 USA. NR 63 TC 98 Z9 105 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1998 VL 51 IS 3 SU 3 BP S62 EP S68 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 120EL UT WOS:000075941900018 PM 9744839 ER PT J AU Marks, AR Cermak, LS AF Marks, AR Cermak, LS TI Intact temporal memory in amnesic patients SO NEUROPSYCHOLOGIA LA English DT Article DE amnesia; recency ID SHORT-TERM-MEMORY; FREE RECALL; SELECTIVE IMPAIRMENT; REHEARSAL PROCESSES; RECENCY; DISTINCTIVENESS; RETRIEVAL; HYPOTHESIS; STORES; LEARN AB Current theories propose that amnesia is caused by an inability to encode the temporal properties of recent events and/or to associate information across time. The present investigation tested this postulation by manipulating the recency effect which is theorized to be caused by the encoding of temporal information. The continual-distractor paradigm was used to vary the temporal properties of recently presented lists. Amnesics' recall responded normally to the temporal manipulations in lists ranging from 18-54 s. In contrast, overall recall was impaired compared to normals in all conditions and across all positions, including the final position. These findings dissociate memory for temporal information from overall levels of recall. They suggest that the amnesic patient's memory deficit is not caused by an inability to encode temporally associated information. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. RP Marks, AR (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C-205, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [DC00017-12]; PHS HHS [26985] NR 46 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 1998 VL 36 IS 9 BP 935 EP 943 DI 10.1016/S0028-3932(98)00013-X PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 112NR UT WOS:000075501100011 PM 9740366 ER PT J AU Post, RM Frye, MA Denicoff, KD Leverich, GS Kimbrell, TA Dunn, RT AF Post, RM Frye, MA Denicoff, KD Leverich, GS Kimbrell, TA Dunn, RT TI Beyond lithium in the treatment of bipolar illness SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE carbamazepine; valproate; calcium channel blockers; lamotrigine; gabapentin; rTMS ID MANIC-DEPRESSIVE ILLNESS; TRANSCRANIAL MAGNETIC STIMULATION; REFRACTORY AFFECTIVE-DISORDERS; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND TRIAL; MAINTENANCE TREATMENT; CALCIUM-ANTAGONISTS; CARBAMAZEPINE PROPHYLAXIS; CONTINGENT TOLERANCE; ADJUNCTIVE TREATMENT AB Dramatic changes have recently occurred in the availability of treatment options for bipolar illness. Second generation mood stabilizing anticonvulsants carbamazepine and valproate are no zu widely used as alternatives or adjuncts to lithium. High potency benzodiazepines are also used as alternatives to typical neuroleptics, and now atypical neuroleptics are demonstrating efficacy and better side-effects profiles than the typicals. Thyroid augmentation strategies and dihydropyridine L-type calcium channel blockers require further clinical trials to define their role. Putative third generation moon stabilizing anticonvulsants lamotrigine, gabapentin, and topiramate have unique mechanisms of action and deserve further systematic study, Its noes the potential role for nonconvulsive brain stimulation with repeated transcranial magnetic stimulation (rTMS). These and a host of other potential treatment options note require a new generation of clinical trials to help identify clinical and biological markers of response and optimal use alone and in complex combination therapeutic regimens. Published by Elsevier Science Inc. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 144 TC 62 Z9 65 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1998 VL 19 IS 3 BP 206 EP 219 DI 10.1016/S0893-133X(98)00020-7 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZW576 UT WOS:000074425300007 PM 9653709 ER PT J AU Fields, RD AF Fields, RD TI Clostridial neurotoxins in synaptic research SO NEUROSCIENTIST LA English DT Article DE tetanus toxin; botulinum toxin; synaptic transmission; VAMP; syntaxin; synaptotagmin ID NEUROTRANSMITTER RELEASE; FUSION COMPLEX; VESICLE FUSION; CA2+ CHANNELS; CORE COMPLEX; T-SNARE; V-SNARE; SYNAPTOTAGMIN; PROTEIN; SYNTAXIN AB Research on clostridial neurotoxins provides a recent illustration of how medical research can spark fundamental breakthroughs in basic science. Clostridia are anaerobic bacilli that live in dust, soil, vegetation, and the gastrointestinal tract of animals and humans. Most are benign, but the pathogenic species produce potent neural toxins. In addition to their involvement in disease and germ warfare, interest in these toxins has increased within the basic research community with the appreciation that these agents can be used as precise experimental tools for dissecting the molecular basis of synaptic transmission, which is without question the most essential process in the nervous system. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD SEP PY 1998 VL 4 IS 5 BP 324 EP 328 DI 10.1177/107385849800400512 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 119CE UT WOS:000075877100012 ER PT J AU Zhang, Z Schaffer, AA Miller, W Madden, TL Lipman, DJ Koonin, EV Altschul, SF AF Zhang, Z Schaffer, AA Miller, W Madden, TL Lipman, DJ Koonin, EV Altschul, SF TI Protein sequence similarity searches using patterns as seeds SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLETE GENOME SEQUENCE; STATISTICAL DISTRIBUTION; ACID-SEQUENCES; ELEGANS CED-4; CYTOCHROME-C; IDENTIFICATION; GENERATION; ACTIVATION; ALIGNMENTS; DATABASES AB Protein families often are characterized by conserved sequence patterns or motifs, A researcher frequently wishes to evaluate the significance of a specific pattern within a protein, or to exploit knowledge of known motifs to aid the recognition of greatly diverged but homologous family members, To assist in these efforts, the pattern-hit initiated BLAST (PHI-BLAST) program described here takes as input both a protein sequence and a pattern of interest that it contains. PHI-BLAST searches a protein database for other instances of the input pattern, and uses those found as seeds for the construction of local alignments to the query sequence. The random distribution of PHI-BLAST alignment scores is studied analytically and empirically. In many instances, the program is able to detect statistically significant similarity between homologous proteins that are not recognizably related using traditional single-pass database search methods, PHI-BLAST is applied to the analysis of CED4-like cell death regulators, HS90-type ATPase domains, archaeal tRNA nucleotidyltransferases and archaeal homologs of DnaG-type DNA primases. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. Natl Human Genome Res Inst, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. RP NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.nih.gov RI Schaffer, Alejandro/F-2902-2012 NR 51 TC 185 Z9 187 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1998 VL 26 IS 17 BP 3986 EP 3990 DI 10.1093/nar/26.17.3986 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117FF UT WOS:000075769700018 PM 9705509 ER PT J AU Taft-Benz, SA Schaaper, RM AF Taft-Benz, SA Schaaper, RM TI Mutational analysis of the 3 '-> 5 ' proofreading exonuclease of Escherichia coli DNA polymerase III SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MISMATCH REPAIR; 3'-5' EXONUCLEASE; ACTIVE-SITE; ALPHA-SUBUNIT; MUTATOR GENE; AMINO-ACID; CODING PROPERTIES; EPSILON-SUBUNIT; THETA-SUBUNIT; REPLICATION AB The epsilon subunit of Escherichia coli DNA polymerase III holoenzyme, the enzyme primarily responsible for the duplication of the bacterial chromosome, is a 3'-->5' exonuclease that functions as a proofreader for polymerase errors. In addition, it plays an important structural role within the pol III core, To gain further insight into how epsilon performs these joint structural and catalytic functions, we have investigated a set of 20 newly isolated dnaQ mutator mutants, The mutator effects ranged from strong (700-8000-fold enhancement) to moderate (6-20-fold enhancement), reflecting the range of proofreading deficiencies. Complementation assays revealed most mutators to be partially or fully dominant, suggesting that they carried an exonucleolytic defect but retained binding to the pol III core subunits, One allele, containing a stop codon 3 amino acids from the C-terminal end of the protein, was fully recessive. Sequence analysis of the mutants revealed mutations in the fro I, fro II and recently proposed fro III epsilon. motifs, as well as in the intervening regions. Together, the data support the functional significance of the proposed motifs, presumably in catalysis, and suggest that the C-terminus of epsilon may be specifically involved in binding to the alpha (polymerase) subunit. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov NR 57 TC 42 Z9 42 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1998 VL 26 IS 17 BP 4005 EP 4011 DI 10.1093/nar/26.17.4005 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117FF UT WOS:000075769700021 PM 9705512 ER PT J AU Usdin, K AF Usdin, K TI NGG-triplet repeats form similar intrastrand structures: implications for the triplet expansion diseases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; FRAGILE-X; IN-VITRO; HAIRPIN; SEQUENCES; OLIGONUCLEOTIDES; NUCLEOTIDE; MUTATIONS; TRACTS; MOTIF AB Tandem repeats of certain trinucleotides show extensive intergenerational instability in humans that is associated with a class of genetic disorders known as the Triplet Expansion Diseases. This instability is thought to be a consequence of the formation of intrastrand structures, including hairpins, triplexes and tetraplexes, by the tandem repeats. I show here that COO-repeats which are associated with this group of diseases, and AGG-and TOO-repeats which are not currently known to be, form several intrastrand structures including tetraplexes. In all cases the tetraplexes have the same overall conformation in which all the G residues are involved in G(4)-tetrads. COO-repeats also form stable hairpins, but AGG- and TOO-repeats do not form hairpins of comparable stability. However, since tetraplexes can be thought of as folded hairpins, many of the properties ascribed to disease-associated triplets that form hairpins, may apply to these sequences as well. The fact that AGG- and TOO-repeats are not currently associated with any triplet expansion disease suggests either that the ability to adopt an intrastrand folded structure is not sufficient for expansion, or that other diseases associated with such triplets might remain to be identified. C1 NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 202,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. NR 32 TC 72 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1998 VL 26 IS 17 BP 4078 EP 4085 DI 10.1093/nar/26.17.4078 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117FF UT WOS:000075769700031 PM 9705522 ER PT J AU Cocco, P Figgs, L Dosemeci, M Hayes, R Linet, MS Hsing, AW AF Cocco, P Figgs, L Dosemeci, M Hayes, R Linet, MS Hsing, AW TI Case-control study of occupational exposures and male breast cancer SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE male breast cancer; socioeconomic status; occupation ID RISK-FACTORS; ELECTROMAGNETIC-FIELDS; UNITED-STATES; MEN; MORTALITY AB Objective-To investigate whether risk of male breast cancer is associated with workplace exposures. Methods-A case-control study of 178 cases of male breast cancer and 1041 controls was carried out with data from the United States national mortality follow-back survey, which collected questionnaire information from proxy respondents of a 1% sample of all 1986 United States deaths among subjects aged 25-74 years. Occupational exposure to electromagnetic fields, high temperatures, polycyclic aromatic hydrocarbons (PAHs), herbicides, other pesticides, and organic solvents was assessed by applying job-exposure matrices, based on the 1980 United States census occupation and industry codes, to the longest job held by study subjects as reported by the informants. A socioeconomic status index was created by combining information on annual family income, education, assets, and occupation to assess the association of socioeconomic status with male breast cancer. Relative risks were derived from logistic regression modelling, which included age, socioeconomic status, marital status, and body mass index, as well as occupational exposures. Results-Risk of male breast cancer increased significantly with increasing socioeconomic status index (test for trend: p< 0.01), but the risks associated with individual socioeconomic status variables were smaller and the trends were not significant. A significant increase in risk of male breast cancer was associated with employment in blast furnaces, steel works, and rolling mills (odds ratio (OR) 3.4; 95% confidence interval (95% CI) 1.1 to 10.1, based on six cases), and motor vehicle manufacturing (OR 3.1; 95% CI 1.2 to 8.2, based on seven cases). However, exposures to electromagnetic fields, high temperature, PAHs, herbicides, other pesticides, and organic solvents were not associated with risk of male breast cancer. Conclusions-The role of workplace exposures in increasing risk of breast cancer among men employed in motor vehicle manufacturing and in blast furnaces, steel works, and rolling mills deserves further investigation. The finding on socioeconomic status suggests that, as well as reproductive factors, other lifestyle factors such as diet that may be related to high socioeconomic status in men should be investigated further. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Cagliari, Inst Occupat Med, I-09124 Cagliari, Italy. St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN Room 443, Bethesda, MD 20892 USA. NR 32 TC 37 Z9 38 U1 1 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 1998 VL 55 IS 9 BP 599 EP 604 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 114FH UT WOS:000075598100004 PM 9861181 ER PT J AU Kogevinas, M Sala, M Boffetta, P Hoar-Zahm, S Kazerouni, N Kromhout, H AF Kogevinas, M Sala, M Boffetta, P Hoar-Zahm, S Kazerouni, N Kromhout, H TI Cancer risk in the rubber industry: a review of recent epidemiological evidence SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Letter C1 Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, E-08003 Barcelona, Spain. Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69372 Lyon, France. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Wageningen Univ Agr, Dept Environm & Occupat Hlth, Wageningen, Netherlands. RP Kogevinas, M (reprint author), Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, 80 Doctor Aiguader Rd, E-08003 Barcelona, Spain. RI Kromhout, Hans/A-9159-2008; sala, maria/A-2593-2011; Zahm, Shelia/B-5025-2015; Fernandez , Irene/E-5705-2016; Martinez, Esther/H-2562-2013; Kogevinas, Manolis/C-3918-2017 NR 0 TC 2 Z9 2 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 1998 VL 55 IS 9 BP 646 EP 647 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 114FH UT WOS:000075598100015 ER PT J AU Savion, S Silver, PB Chan, CC Caspi, RR AF Savion, S Silver, PB Chan, CC Caspi, RR TI Acute immunosuppression and syngeneic bone marrow transplantation in ocular autoimmunity abort disease, but do not result in induction of long-term protection SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE experimental autoimmune uveoretinitis; acute immunosuppression; total body irradiation; cyclophosphamide; syngeneic bone marrow transplantation ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RETINOID-BINDING PROTEIN; T-CELL LINES; S-ANTIGEN; UVEORETINITIS EAU; TOTAL-BODY; MICE; MODEL; IRRADIATION; MECHANISMS AB Acute immunosuppression induced by total body irradiation (TBI) or cyclophosphamide (Cy) treatment, followed by syngeneic bone marrow transplantation (SBMT), was reported to be effective in inducing long-term tolerance in some autoimmune disease models. We examined the efficacy of this approach in the mouse model of experimental autoimmune uveoretinitis (EAU). Development of EAU induced by the interphotoreceptor retinoid binding protein (IRBP) was abolished almost completely by either TBI or Cy treatment, followed by SBMT, instituted one week after priming. In parallel, IRBP-specific delayed-type hypersensitivity (DTH) responses and lymph node cell proliferation were strongly suppressed or abolished. However, when these IRBP-immunized, lymphoablated and BM reconstituted mice were rechallenged with the immunizing antigen seven weeks after the primary immunization, they were not protected from developing disease, despite the fact that DTH and lymph node cell proliferation to the antigen were suppressed relative to controls. TBI treatment appeared somewhat more effective than Cy treatment as judged by its more profound effect on immunological responses. These results demonstrate the ability of acute immunosuppression followed by reconstitution of the immune system to inhibit the development of EAU, although long-term protection from disease was not achieved. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Savion, S (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Embryol & Teratol, IL-69978 Tel Aviv, Israel. NR 32 TC 0 Z9 0 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD SEP PY 1998 VL 6 IS 3 BP 163 EP 172 DI 10.1076/ocii.6.3.163.4037 PG 10 WC Ophthalmology SC Ophthalmology GA 130PK UT WOS:000076528400004 PM 9785606 ER PT J AU de Smet, MD Dayan, M Nussenblatt, RB AF de Smet, MD Dayan, M Nussenblatt, RB TI A novel method for the determination of T-cell proliferative responses in patients with uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE S-antigen; lymphocyte proliferation; uveitis; autoimmunity ID RETINAL S-ANTIGEN; LIMITING DILUTION ANALYSIS; MYELIN BASIC-PROTEIN; IMMUNE RESPONSIVENESS; SYMPATHETIC OPHTHALMIA; HELPER LYMPHOCYTES; RECOGNITION; ENUMERATION AB Standard proliferation assays using autoantigens such as S-Ag have given erratic responses when studied with human peripheral blood mononuclear cells. This erratic response is a reflection of the low number of circulating cells in the peripheral blood capable of generating a response as well as the presence of competing cells for the available cytokines in culture. The present study compares the standard proliferation assay with a novel technique in which multiple short-term cell lines are established to S-Ag in medium enriched in helper cytokines. After 12-14 days of culture, these lines were tested for their response to S-Ag. A significant difference was found between patients and controls in the ability to generate responsive cell lines. This translated to a frequency of responsive cells of 0-4 per 10(7) peripheral blood mononuclear cells (PBMC) in normal individuals and 0-200 per 10(7) PBMC in patients. This novel technique may provide a means of determining the number of responsive cells to specific autoantigens in the peripheral blood of patients and the ability to follow the response over time. C1 Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands. NEI, Clin Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. RP de Smet, MD (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, Meibergdreef 9,Rm G2-217, NL-1105 AZ Amsterdam, Netherlands. EM m.d.desmet@amc.uva.nl OI de Smet, Marc/0000-0002-9217-5603 NR 20 TC 8 Z9 8 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD SEP PY 1998 VL 6 IS 3 BP 173 EP 178 DI 10.1076/ocii.6.3.173.4044 PG 6 WC Ophthalmology SC Ophthalmology GA 130PK UT WOS:000076528400005 PM 9785607 ER PT J AU Shen, DF Zhuang, ZP LeHoang, P Boni, R Zheng, S Nussenblatt, RB Chan, CC AF Shen, DF Zhuang, ZP LeHoang, P Boni, R Zheng, S Nussenblatt, RB Chan, CC TI Utility of microdissection and polymerase chain reaction for the detection of immunoglobulin gene rearrangement and translocation in primary intraocular lymphoma SO OPHTHALMOLOGY LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; PROGNOSTIC-SIGNIFICANCE; MALIGNANT-LYMPHOMA; MOLECULAR ANALYSIS; CLINICAL-FEATURES; DIAGNOSIS; BCL-2; CLONALITY; DNA AB Objective: Primary intraocular lymphoma, a non-Hodgkin's lymphoma, is a primary central nervous system lymphoma (PCNSL). Diagnosis is usually made by identifying malignant, large B lymphocytes in the vitreous, eye, brain, and cerebral spinal fluid; however, these cells ave few, friable, and difficult to recognize. Recently, clonal heavy chain immunoglobulin (IgH) gene rearrangement and bcl-2 gene translocation have been reported in systemic B-cell lymphoma and are used for the detection of malignant cells and in making a diagnosis. The authors investigated the molecular changes in three eyes and a chorioretinal biopsy specimen of four patients with PCNSL. Design: Human tissue study. Materials: Five ocular specimens of PCNSL were collected. Intervention: The first patient had a diagnostic enucleation of the left eye. The second patient underwent diagnostic chorioretinal biopsy. In the third case, a pair of autopsied eyes with reactive lymphoplasmacytic infiltrates of a patient with acquired immune deficiency syndrome (AIDS) were studied. In the fourth case, an enucleated eye of a patient with AIDS-associated lymphoma was sampled. Main Outcome Measures: The bcl-2 and IgH genes of the lymphoma cells from routine, paraffin-embedded, formaldehyde-fixed, or frozen histologic tissue sections were analyzed using microdissection and polymerase chain reaction (PCR) technique. Results: Lymphoma cells obtained from the above four cases showed IgH rearrangement gene in the third framework of the V-H region. Bcl-2-associated translocation also was detected in three cases (cases 1, 2, and 4). Conclusion: Rearrangement of the IgH gene can serve as a molecular marker for PCNSL. Microdissection allows for procurement and analysis of specific, selected, minute cell populations that are obtained from histologic sections of the complex, heterogeneous tissue. Translocation of IgH and bcl-2, the apoptotic "survival" signal and proto-oncogene, could contribute to the pathogenesis of PCNSL. The combination of microdissection and PCR is a powerful tool for studies of small lesions and cell populations and for understanding disease mechanisms. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Dept Ophthalmol, Paris, France. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr,MSC 1858, Bethesda, MD 20892 USA. NR 47 TC 84 Z9 91 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1998 VL 105 IS 9 BP 1664 EP 1669 DI 10.1016/S0161-6420(98)99036-4 PG 6 WC Ophthalmology SC Ophthalmology GA 121NE UT WOS:000076019400037 PM 9754175 ER PT J AU Alkon, DL Favit, A Nelson, T AF Alkon, DL Favit, A Nelson, T TI Evolution of adaptive neural networks: The role of voltage-dependent K+ channels SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Conference on Vestibular Adaptation CY MAY 23-25, 1996 CL SANTA MONICA, CALIFORNIA SP NIH, NIDOCD ID ASSOCIATIVE MEMORY; CURRENTS; FIBROBLASTS; REDUCTION; RETENTION; NEURONS; PROTEIN; RAT AB The vestibular pathway of the mollusk Hermissenda crassicornis mediates a reflexive, unconditioned response to disorientation, clinging, that has been conserved during evolution even to the emergence of our own species. This response becomes associated with a visual stimulus (mediated by a precisely ordered visual-vestibular synaptic network) according to principles of Pavlovian conditioning that are also followed in human learning. It is not entirely surprising therefore that molecular and biophysical cascades responsible for this associative learning appear to function in both mollusks and mammals. In brief, combinational elevation of (Ca2+)(i), diacylglycerol, and arachidonic acid activates protein kinase C to phosphorylate the Ca2+ and guanosine triphosphate-binding protein, cp20 (now called calexcitin (Nelson T, et al. Proc Natl Acad Sci USA 1996;93:13808-13)), which potently inactivates postsynaptic voltage-dependent K+ currents and thereby increases synaptic weight. Longer term changes included rearrangement of synaptic terminals and modified protein synthesis. This cascade has also been implicated in other associative-learning paradigms (e.g., spatial maze, olfactory discrimination) and as a pathophysiologic target in early Alzheimer's disease. Recent molecular biologic experiments also demonstrate the dependence of associative memory (but not longterm potentiation) on voltage-dependent K+ currents. Theoretic learning models based on these findings focus on dendritic spine clusters and yield computer implementations with powerful pattern-recognition capabilities. C1 NIH, Lab Adapt Syst, Bethesda, MD 20892 USA. RP Alkon, DL (reprint author), NIH, Lab Adapt Syst, 36 Convent Dr,MSC 4124,Bldg 36,Room 4A21, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 1998 VL 119 IS 3 BP 204 EP 211 DI 10.1016/S0194-5998(98)70055-5 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 117VG UT WOS:000075802900009 PM 9743076 ER PT J AU Hirunpetcharat, C Stanisic, D Liu, XQ Vadolas, J Strugnell, RA Lee, R Miller, LH Kaslow, DC Good, MF AF Hirunpetcharat, C Stanisic, D Liu, XQ Vadolas, J Strugnell, RA Lee, R Miller, LH Kaslow, DC Good, MF TI Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP1(19)) induces protective immunity to blood stage malaria infection in mice SO PARASITE IMMUNOLOGY LA English DT Article DE vaccine; MSP1; mucosal immunity; CTB; antibody ID CHOLERA-TOXIN; MUCOSAL ADJUVANT; TH2 CELLS; T-CELLS; ANTIBODIES; RESPONSES; ANTIGENS; SUBUNIT; VACCINE AB Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1(19)) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP119 plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP1(19)-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia <1%) in mice with the highest MSP1(19)-specific titre (greater than or equal to 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%-1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4(+) T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP1(19) to protect against malaria. C1 Royal Brisbane Hosp, Queensland Inst Med Res, Malaria & Arbovirus Unit, Brisbane, Qld 4029, Australia. Univ Queensland, Dept Parasitol, St Lucia, Qld 4067, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Good, MF (reprint author), Royal Brisbane Hosp, Queensland Inst Med Res, Malaria & Arbovirus Unit, Brisbane, Qld 4029, Australia. OI Strugnell, Richard/0000-0003-0614-5641 NR 21 TC 36 Z9 36 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD SEP PY 1998 VL 20 IS 9 BP 413 EP 420 DI 10.1046/j.1365-3024.1998.00161.x PG 8 WC Immunology; Parasitology SC Immunology; Parasitology GA 223EB UT WOS:000081826500003 PM 9767608 ER PT J AU Rosensweig, JN Omori, M Page, K Potter, CJ Perlman, EJ Thorgeirsson, SS Schwarz, KB AF Rosensweig, JN Omori, M Page, K Potter, CJ Perlman, EJ Thorgeirsson, SS Schwarz, KB TI Transforming growth factor-beta 1 in plasma and liver of children with liver disease SO PEDIATRIC RESEARCH LA English DT Article ID GENE-EXPRESSION; FACTOR-BETA; FIBROSIS; GROWTH-FACTOR-BETA-1; RAT AB Although several liver diseases of childhood, particularly biliary atresia (BA) and cystic fibrosis (CF) liver disease (CFLD) are characterized by hepatic fibrosis, the pathogenesis of this process is incompletely understood. The cytokine transforming growth factor-beta 1 (TGF-beta 1) has been implicated in hepatic fibrosis in experimental animals, in which both the hepatic expression and plasma concentration of this cytokine are increased. The objective of our study was to determine whether there are similar alterations of TGF-beta 1 in patients with hepatic fibrosis secondary to either BA and/or CFLD. The study design was as follows. In study 1, plasma TGF-beta 1 was assessed by ELISA in 9 children with BA undergoing Liver transplantation, 11 patients with CFLD, and appropriate control subjects. In study 2, hepatic expression of TGF-beta 1 protein (assessed immunohistochemically) and hepatic fibrosis were scored semiquantitatively, on a 1-3 scale, by blinded investigators, in archival liver biopsy specimens from 10 children with BA, 10 with CFLD, and from 10 older children with normal hepatic histology, as well as in 4 patients with Liver diseases of various etiologies. Simultaneous plasma and liver TGF-beta 1 studies were performed in 8 patients with Liver disease. Results were as follows. Plasma TGF-PL values were inversely correlated with age in healthy subjects (r = -0.54, p < 0.0001). The plasma TGF-beta 1 protein of children with BA was decreased (13 +/- 2 ng/mL) compared with values for healthy children (42 +/- 6 ng/mL, n = 10, p < 0.005). Similarly, the plasma TGF-beta 1 concentration in patients with CFLD was also decreased compared with values for children with CF and normal serum liver profiles (n = 14) (2 +/- 1 ng/mL versus 12 +/- 1, p < 0.05). However, the plasma TGF-beta 1 concentration was increased in two patients with other types of liver disease. The hepatic expression of TGF-beta 1 was increased in the presence of hepatic fibrosis in all types of liver diseases studied. Forty-six percent of patients had both marked hepatic fibrosis and marked TGF-beta 1 labeling; 86% of samples without fibrosis showed no TGF-beta 1 labeling, p = 0.007. In conclusion, these studies have established the association of hepatic TGF-beta 1 protein and hepatic fibrosis in several common liver diseases of childhood. Our data also suggest that, in children, plasma TGF-beta 1 does not appear to be a useful marker of hepatic expression of this cytokine. C1 Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21210 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21210 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Childrens Hosp, Dept Pediat, Columbus, OH 43210 USA. RP Schwarz, KB (reprint author), Johns Hopkins Hosp, Dept Pediat, 600 N Wolfe St,320 Brady, Baltimore, MD 21287 USA. NR 18 TC 22 Z9 26 U1 1 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 1998 VL 44 IS 3 BP 402 EP 409 DI 10.1203/00006450-199809000-00023 PG 8 WC Pediatrics SC Pediatrics GA 112NF UT WOS:000075500100023 PM 9727721 ER PT J AU Abbott, RD White, LR Ross, GW Petrovitch, H Masaki, KH Snowdon, DA Curb, JD AF Abbott, RD White, LR Ross, GW Petrovitch, H Masaki, KH Snowdon, DA Curb, JD TI Height as a marker of childhood development and late-life cognitive function: The Honolulu-Asia Aging Study SO PEDIATRICS LA English DT Article DE dementia; cognitive function; childhood development ID ADULT BRAIN-WEIGHT; MINI-MENTAL STATE; LOW-BIRTH-WEIGHT; ALZHEIMERS-DISEASE; HEAD SIZE; PREVALENCE; AGE; DEMENTIA; ABILITY; HAWAII AB Objective. Growing evidence suggests that structural and functional brain reserves, thought to develop in childhood and adolescence, may be crucial in determining when cognitive impairment begins. The purpose of this report is to examine the relationship of height, as a marker of childhood development, to late-life cognitive function in a sample of elderly Japanese-American men. Method. Cognitive performance was assessed from 1991 to 1993 in the Honolulu-Asia Aging Study in 3733 men aged 71 to 93 years and related to height that was measured 25 years earlier. Results. Among the study sample, shorter men were older, leaner, and less educated than taller men. Shorter men also spent more years of their childhood living in Japan and were more likely to have had fathers in unskilled professions. After adjustment for age, the prevalence of poor cognitive performance declined consistently with increasing height from 25% in men shorter than 154 cm (61 in) to 9% in those taller than 174 cm (69 in). Excluding men with stroke or dementia did not alter the association between height and cognitive performance. Apolipoprotein E4 was unrelated to height and did not effect the association between height and cognitive function. The prevalence of Alzheimer's disease was higher in men who were 154 cm (61 in) or shorter as compared with men who were taller (4.7% vs 2.9%, respectively). There was no association between height and vascular dementia. Conclusion. Efforts to improve prenatal and early life conditions to maximize growth in childhood and adolescence could diminish or delay the expression of cognitive impairments that occur later in life. prevention of some late-life cognitive impairments may have pediatric origins. C1 Univ Virginia, Sch Med, Div Biostat & Epidemiol, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. NIA, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Kentucky, Coll Med, Dept Prevent Med, Lexington, KY 40506 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Abbott, RD (reprint author), Univ Virginia, Sch Med, Div Biostat & Epidemiol, Dept Hlth Evaluat Sci, Box 600, Charlottesville, VA 22908 USA. FU NCRR NIH HHS [P20 RR/AI 11091]; NIA NIH HHS [N01-AG-4-2149] NR 36 TC 81 Z9 83 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1998 VL 102 IS 3 BP 602 EP 609 DI 10.1542/peds.102.3.602 PG 8 WC Pediatrics SC Pediatrics GA 117EB UT WOS:000075766800023 PM 9738183 ER PT J AU Marcin, J Slonim, A Pollack, MM AF Marcin, J Slonim, A Pollack, MM TI Characteristics of long-stay patients and their effect on institutional efficiency. SO PEDIATRICS LA English DT Meeting Abstract C1 George Washington Univ, Sch Med, Childrens Natl Med Ctr, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1998 VL 102 IS 3 SU 1 BP 707 EP 707 PG 1 WC Pediatrics SC Pediatrics GA 117YM UT WOS:000075810500083 ER PT J AU Gershon, ES AF Gershon, ES TI Making progress: Does clinical research lead to breakthroughs in basic biomedical sciences? SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article ID FRAGILE-X-SYNDROME; CGG REPEAT; INSTABILITY; DNA; REGION C1 NIMH, Clin Neurogenet Branch, Bethesda, MD 20892 USA. RP Gershon, ES (reprint author), Univ Chicago, Dept Psychiat, Div Biol Sci, Chicago, IL 60637 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD FAL PY 1998 VL 42 IS 1 BP 95 EP 102 PG 8 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 153ZK UT WOS:000077863400008 PM 9894357 ER PT J AU Cassola, AC Jaffe, H Fales, HM Afeche, SC Magnoli, F Cipolla-Neto, J AF Cassola, AC Jaffe, H Fales, HM Afeche, SC Magnoli, F Cipolla-Neto, J TI omega-Phonetoxin-IIA: a calcium channel blocker from the spider Phoneutria nigriventer SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE calcium channel; high-voltage-activated calcium channel; omega-phonetoxin-IIA; spider toxins; L-type calcium channel; N-type calcium channel ID PANCREATIC BETA-CELLS; PATCH-CLAMP; CA CHANNELS; SENSORY NEURONS; AGA-IIIA; N-TYPE; RAT; CONOTOXIN; AGATOXINS; CURRENTS AB A peptide with neurotoxic effect on mammals, purified from the venom of the spider Phoneutria nigriventer, was studied regarding its primary structure and its effects on voltage-gated calcium channels. The peptide, named omega-phonetoxin-IIA, has 76 amino acids residues, with 14 Cys forming 7 disulphide bonds, and a molecular weight of 8362.7 Da. The neurotoxicity is a consequence of the peptide's blocking effects on high-voltage-activated (HVA) calcium channels. N-type HVA calcium channels of rat dorsal root ganglion neurons are blocked with affinity in the sub-nanomolar concentration range. The toxin also blocks L-type channels of rat beta pancreatic cells, with an affinity 40 times lower. Although not studied in detail, evidence indicates that the toxin also blocks other types of HVA calcium channels, such as P and Q. No effect was observed on low-voltage-activated, T-type calcium channels. The significant homologies between omega-phonetoxin-IIA and the peptides of the omega-agatoxin-III family, and the overlapping inhibitory effects on calcium channels are discussed in terms of the structure-activity relationship. C1 Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, SP, Brazil. NINDS, LNC, Protein Peptide Sequencing Facil, Bas Neurosci Program,NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Butantan Inst, Pharmacol Lab, Sao Paulo, Brazil. Butantan Inst, Lab Imunochem, Sao Paulo, Brazil. RP Cassola, AC (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Lineu Prestes 1524, BR-05508900 Sao Paulo, SP, Brazil. RI Cipolla-Neto, Jose/B-1619-2009; castro afeche, solange/D-4287-2014 OI Cipolla-Neto, Jose/0000-0003-3748-3731; castro afeche, solange/0000-0001-6195-7859 NR 28 TC 40 Z9 42 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD SEP PY 1998 VL 436 IS 4 BP 545 EP 552 DI 10.1007/s004240050670 PG 8 WC Physiology SC Physiology GA 108UC UT WOS:000075283000007 PM 9683727 ER PT J AU Patterson, RE Kristal, AR Biener, L Varnes, J Feng, ZD Glanz, K Stables, G Chamberlain, RM Probart, C AF Patterson, RE Kristal, AR Biener, L Varnes, J Feng, ZD Glanz, K Stables, G Chamberlain, RM Probart, C CA Working Well Res Grp TI Durability and diffusion of the nutrition intervention in the Working Well Trial SO PREVENTIVE MEDICINE LA English DT Article DE worksite health promotion; cancer control; nutrition AB Background. The Working Well Trial (WWT) emphasized employee participation in the planning and implementation of the health promotion intervention. These participatory strategies were intended to promote institutionalization of the health promotion program and thereby encourage maintenance of the intervention activities. We used data from 107 worksites in the WWT to test whether the nutrition intervention activities were maintained after the research program (i.e., durability) or were adopted by control sites (i.e., diffusion). Methods. At baseline, upon the completion of the 2-year intervention, and 2 years later, we conducted organization surveys regarding worksite health promotion activities. A nutrition activity score from 0 to 3 was calculated based on availability of nutrition-related programs, self-help manuals or guides, and videos, tapes, brochures, or posters. Results. From baseline to the end of the intervention, there was a significant increase in the nutrition activity score in intervention worksites compared with the controls (P < 0.001), However, 2 years later, there was no difference between intervention and control worksites. In addition, there was no significant increase in the nutrition activity score in control site 2 years after they received the intervention protocols and materials. Conclusions. Research is needed to develop and test worksite-based interventions to promote institutionalization, durability, and diffusion. (C) 1998 American Health Foundation and Academic Press. C1 Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Univ Florida, Gainesville, FL 32611 USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NCI, Rockville, MD 20852 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. RP Patterson, RE (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. EM rpatters@fhcrc.org RI Kristal, Alan/A-8779-2008; OI Biener, Lois/0000-0002-4130-8138; Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [U01 CA51678, U01 CA51671]; PHS HHS [U01 51686] NR 20 TC 21 Z9 22 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP 668 EP 673 DI 10.1006/pmed.1998.0342 PN 1 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 127UM UT WOS:000076369000004 PM 9808797 ER PT J AU Crane, LA Leakey, TA Rimer, BK Wolfe, P Woodworth, MA Warnecke, RB AF Crane, LA Leakey, TA Rimer, BK Wolfe, P Woodworth, MA Warnecke, RB TI Effectiveness of a telephone outcall intervention to promote screening mammography among low-income women SO PREVENTIVE MEDICINE LA English DT Article DE screening mammography; telephone outcalls; Transtheoretical Model; behavioral intervention ID HEALTH BELIEF MODEL; BREAST-CANCER; BLACK-WOMEN; WHITE WOMEN; OLDER WOMEN; ADHERENCE; COMMUNITY; PREVENTION; USAGE; CARE AB Background. This study evaluated the impact of a telephone outcall intervention (based on the Transtheoretical Model) on Screening mammography behavior among lower income, older women. Methods. A geodemographic database, INFORUM, was used to identify low-income and minority neighborhoods throughout the state of Colorado. Residences were assigned randomly to three study groups: (1) control, (2) outcall only, and (3) advance "invitation" + outcall. Information Specialists of the Cancer Information Service implemented the protocol. Mammography adherence was assessed in telephone interviews conducted 6 months and 2 years after the initial call. Results. Neither intervention had a significant effect on the main outcome, receipt of mammography in the 6-month follow-up period. At 6 months, intentions to have a mammogram were significantly stronger in the intervention groups compared with the control group, particularly among those who were precontemplators at baseline. The a-year follow-up indicated a small increase in mammography adherence attributable to the advance invitation + outcall, but this effect was restricted to those adherent at baseline. Mammography behavior during the 6-month follow-up period was predicted strongly by decisional balance, intentions, receipt of a physical and clinical breast exam, and previous mammography behavior. Conclusions. The intervention promoted minimal movement in the stages of change for mammography. Outcall interventions may have promise for encouraging repeat mammography behavior, but more intensive interventions are likely to be necessary to promote behavior change among nonadherent women. (C) 1998 American Health Foundation and Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. AMC Canc Res Ctr, Ctr Behav Studies, Denver, CO 80214 USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO 80214 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Penrose St Francis Hlth Syst, Reg Canc Informat Serv 16, Colorado Springs, CO 80933 USA. Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. RP Crane, LA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, 4200 E 9th Ave,Box C-245, Denver, CO 80262 USA. EM lori.crane@uchsc.edu FU NCI NIH HHS [P01-CA57586] NR 47 TC 33 Z9 33 U1 7 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP S39 EP S49 DI 10.1006/pmed.1998.0395 PN 2 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 134WH UT WOS:000076766400005 PM 9808823 ER PT J AU Crane, LA Leakey, TA Woodworth, MA Rimer, BK Warnecke, RB Heller, D George, VS AF Crane, LA Leakey, TA Woodworth, MA Rimer, BK Warnecke, RB Heller, D George, VS TI Cancer information service-initiated outcalls to promote screening mammography among low-income and minority women: Design and feasibility testing SO PREVENTIVE MEDICINE LA English DT Article DE Cancer Information Service; telephone outcalls; INFORUM; targeted health interventions; outreach to underserved populations; screening mammography promotion; geodemographic targeting ID HEALTH BELIEF MODEL; BREAST-CANCER; SOCIOECONOMIC-STATUS; OLDER WOMEN; COMMUNITY; ADHERENCE; SURVIVAL; RACE AB Background The telephone information service of the Cancer Information Service (CIS) historically is most effective in eliciting calls from higher income, white women. This article describes the design and feasibility of a project that tested the use of telephone outcalls to extend the reach of the telephone information service to underserved women. Methods. Neighborhoods throughout Colorado were identified using a geodemographic database (INFORUM) that allowed selection of census block groups according to demographic characteristics. Households were assigned randomly to: (1) a control group; (2) an outcall-only group, which received "cold" telephone outcalls promoting screening mammography; and (3) an advance card plus outcall group, which received a card introducing the program prior to the outcall. Results. The use of INFORUM to target low-income, less educated, and black women was largely successful. While quality of intervention delivery was high, the protocol was labor intensive, requiring an average of 40 min to identify and counsel each eligible woman. The advance card did not increase acceptance of the outcalls. Conclusions. This approach successfully extended the CIS's audience; however, its labor intensity may limit its applicability. Strategies for increasing the efficiency of outcall efforts are suggested. (C) 1998 American Health Foundation and Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. AMC Canc Res Ctr, Ctr Behav Res, Denver, CO 80214 USA. Penrose St Francis Hlth Syst, Reg Canc Informat Serv 16, Colorado Springs, CO 80933 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO 80214 USA. RP Crane, LA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, 4200 E 9th Ave,Box C-245, Denver, CO 80262 USA. FU NCI NIH HHS [P01-CA57586] NR 50 TC 7 Z9 7 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP S29 EP S38 DI 10.1006/pmed.1998.0247 PN 2 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 134WH UT WOS:000076766400004 PM 9808822 ER PT J AU Marcus, AC Heimendinger, J Wolfe, P Rimer, BK Morra, M Cox, D Lang, PJ Stengle, W Van Herle, MP Wagner, D Fairclough, D Hamilton, L AF Marcus, AC Heimendinger, J Wolfe, P Rimer, BK Morra, M Cox, D Lang, PJ Stengle, W Van Herle, MP Wagner, D Fairclough, D Hamilton, L TI Increasing fruit and vegetable consumption among callers to the CIS: Results from a randomized trial SO PREVENTIVE MEDICINE LA English DT Article DE cancer, prevention and control; diet; telephone; information services; health education ID CANCER PREVENTION; PLASMA CAROTENOIDS; UNITED-STATES; WORKING WELL; HEALTH; NUTRITION; PROGRAM; MODEL; WOMEN; QUESTIONNAIRE AB Background. Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the Cancer Information Service (CIS). Methods. CIS callers assigned to the intervention group received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention subjects. Subjects were interviewed by telephone at both 4-week (n = 1,672) and 4-month (n = 1,286) follow-up. Results. A single-item measure of fruit and vegetable consumption revealed a significant intervention effect of approximately 0.65 servings per day at 4-week follow-up (P < 0.001) and 0.41 servings per day at 4-month follow-up (P < 0.001). Using a seven-item food frequency measure that was also included in the 4-month interviews, a similar intervention effect of 0.34 servings per day was obtained (P = 0.006). The vast majority of CIS callers (88%) endorsed the strategy of providing 5 A Day information proactively. Conclusions. A brief educational intervention delivered to CIS callers at the end of usual service was associated with an increase in self-reported fruit and vegetable intake. (C) 1998 American Health Foundation and Academic Press. C1 AMC Canc Res Ctr, Denver, CO 80214 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27705 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Morra Commun Inc, Milford, CT 06460 USA. Johns Hopkins Univ, Canc Informat Serv, Baltimore, MD 21205 USA. Univ Kansas, Med Ctr, Canc Informat Serv, Kansas City, KS 66160 USA. Karmanos Canc Inst, Canc Informat Serv, Detroit, MI 48201 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Canc Informat Serv, Los Angeles, CA 90025 USA. Kentucky Canc Informat Serv, Lexington, KY 40536 USA. Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. RP Marcus, AC (reprint author), AMC Canc Res Ctr, 1600 Pierce St, Denver, CO 80214 USA. FU NCI NIH HHS [P01-CA57586] NR 57 TC 32 Z9 32 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP S16 EP S28 DI 10.1006/pmed.1998.0405 PN 2 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 134WH UT WOS:000076766400003 PM 9808821 ER PT J AU Marcus, AC Morra, ME Bettinghaus, E Crane, LA Cutter, G Davis, S Rimer, BK Thomsen, C Warnecke, RB AF Marcus, AC Morra, ME Bettinghaus, E Crane, LA Cutter, G Davis, S Rimer, BK Thomsen, C Warnecke, RB TI The cancer information service research consortium: An emerging laboratory for cancer control research SO PREVENTIVE MEDICINE LA English DT Article DE neoplasms, prevention and control; information services; research ID SMOKING AB The Cancer Information Service (CIS) was established in 1975 by the National Cancer Institute (NCI) to provide accurate, up-to-date information about cancer to the nation. Although the CIS has in the past served as a venue for cancer communications research, up until very recently the research capacity of the CIS was underutilized. In 1993, this situation changed dramatically with funding from the NCI to form the Cancer Information Service Research Consortium (CISRC), In this article the CISRC is described for the first time, including its research agenda and administrative structure. Early indications from the CISRC suggest that the CIS can serve as one of the premiere laboratories in the country for cancer communications and cancer control research. Several factors are suggested for the early success of the CISRC in sustaining this collaborative effort with the CIS, The progress that has been made by the CISRC could provide a useful model far other large health information programs to maximize their contributions to behavioral science and health promotion research, as well as to establish their own program of policy-relevant research. (C) 1998 American Health Foundation and Academic Press. C1 AMC Canc Res Ctr, Denver, CO 80214 USA. Yale Univ, Ctr Comprehens Canc, New Haven, CT 06520 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. No Calif Canc Ctr, Ctr Informat Serv, Union City, CA 94587 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. NCI, Canc Informat Serv, Bethesda, MD 20892 USA. Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. RP Marcus, AC (reprint author), AMC Canc Res Ctr, 1600 Pierce St, Denver, CO 80214 USA. NR 26 TC 21 Z9 21 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1998 VL 27 IS 5 BP S3 EP S15 DI 10.1006/pmed.1998.0245 PN 2 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 134WH UT WOS:000076766400002 PM 9808820 ER PT J AU Aldroubi, A Feichtinger, H AF Aldroubi, A Feichtinger, H TI Exact iterative reconstruction algorithm for multivariate irregularly sampled functions in spline-like spaces: The L-p-theory SO PROCEEDINGS OF THE AMERICAN MATHEMATICAL SOCIETY LA English DT Article DE non-uniform sampling; shift-invariant spaces; Riesz basis ID WAVELET AB We prove that the exact reconstruction of a function s from its samples s(x(i)) on any "sufficiently dense" sampling set {x(i)}(i epsilon Lambda) can be obtained, as long as s is known to belong to a large class of spline-like spaces in L-p(R-n). Moreover, the reconstruction can be implemented using fast algorithms. Since a limiting case is the space of bandlimited functions, our result generalizes the classical Shannon-Whittaker sampling theorem on regular sampling and the Paley-Wiener theorem on non-uniform sampling. C1 NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. Univ Vienna, Dept Math, A-1090 Vienna, Austria. RP Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. EM aldroubi@math.vanderbilt.edu; fei@tyche.mat.univie.ac.at RI Aldroubi, Akram/J-7186-2012 NR 25 TC 70 Z9 70 U1 0 U2 1 PU AMER MATHEMATICAL SOC PI PROVIDENCE PA 201 CHARLES ST, PROVIDENCE, RI 02940-2213 USA SN 0002-9939 EI 1088-6826 J9 P AM MATH SOC JI Proc. Amer. Math. Soc. PD SEP PY 1998 VL 126 IS 9 BP 2677 EP 2686 DI 10.1090/S0002-9939-98-04319-6 PG 10 WC Mathematics, Applied; Mathematics SC Mathematics GA 111HB UT WOS:000075430300021 ER PT J AU Marples, D Frokiaer, J Knepper, MA Nielsen, S AF Marples, D Frokiaer, J Knepper, MA Nielsen, S TI Disordered water channel expression and distribution in acquired nephrogenic diabetes insipidus SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE water balance disorders; aquaporin-2; water channels; collecting duct; regulated exocytosis ID INDUCED DOWN-REGULATION; RAT-KIDNEY MEDULLA; COLLECTING DUCT; HEART-FAILURE; VASOPRESSIN; AQUAPORIN-2; LITHIUM; PATHOGENESIS; MEMBRANE AB A series of recent studies have demonstrated that expression of aquaporin-2 (AQP2), the vasopressin-regulated water channel of the kidney collecting duct, is greatly reduced in acquired forms of nephrogenic diabetes insipidus (NDI). In some forms of NDI, there is also impaired delivery of these channels to the apical plasma membrane, where they permit water reabsorption from the urine. The combination of these factors is likely to underlie the urinary concentrating defect that defines these conditions. Direct infusion of vasopressin causes an increase in AQP2 expression, probably via a rise in cytosolic adenosine 3:5-cyclic phosphate, which also acts as the second messenger, triggering the delivery of AQP2 to the plasma membrane. However, it is clear from the studies described that there are also vasopressin-independent pathways that regulate the expression of AQP2, some of which appear to reflect intranephric changes, whereas others involve systemic signals. These studies also show that recovery of AQP2 expression, even after correction of the underlying condition, can be slow, consistent with the clinical observation that recovery of urinary-concentrating ability often takes weeks or months. An understanding of the cellular signals and mechanisms responsible for the decrease in AQP2 expression may make it possible to develop treatments for this common clinical problem. C1 Univ Leeds, Dept Physiol, Leeds LS2 9NQ, W Yorkshire, England. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Inst Anat, Dept Cell Biol, Aarhus, Denmark. RP Marples, D (reprint author), Univ Leeds, Dept Physiol, Worsley Med & Dent Bldg, Leeds LS2 9NQ, W Yorkshire, England. NR 28 TC 20 Z9 21 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD SEP-OCT PY 1998 VL 110 IS 5 BP 401 EP 406 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 118HR UT WOS:000075832900005 PM 9756090 ER PT J AU Rhee, S Martin, RG Rosner, JL Davies, DR AF Rhee, S Martin, RG Rosner, JL Davies, DR TI A novel DNA-binding motif in MarA: The first structure for an AraC family transcriptional activator SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; PROTEIN; RECOGNITION; DOMAIN; SUPEROXIDE; COMPLEX; PURIFICATION; PARAMETERS AB A crystal structure for a member of the AraC prokaryotic transcriptional activator family, MarA, in complex with its cognate DNA-binding site is described. MarA consists of two similar subdomains, each containing a helix-turn-helix DNA-binding motif. The two recognition helices of the motifs are inserted into adjacent major groove segments on the same face of the DNA but are separated by only 27 Angstrom thereby bending the DNA by approximate to 35 degrees. Extensive interactions between the recognition helices and the DNA major groove provide the sequence specificity. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 190 Z9 194 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10413 EP 10418 DI 10.1073/pnas.95.18.10413 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500015 PM 9724717 ER PT J AU Wei, SQ Mizuuchi, K Craigie, R AF Wei, SQ Mizuuchi, K Craigie, R TI Footprints on the viral DNA ends in Moloney murine leukemia virus preintegration complexes reflect a specific association with integrase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETROVIRAL DNA; IN-VITRO; INVITRO; AUTOINTEGRATION; TERMINI AB Retroviral DNA integration is mediated by the preintegration complex, a large nucleoprotein complex derived from the core of the infecting virion. We previously have used Mu-mediated PCR to probe the nucleoprotein organization of Moloney murine leukemia virus preintegration complexes. A region of protection spans several hundred base pairs at each end of the viral DNA, and strong enhancement are present near the termini, Here, we show that these footprints reflect a specific association between integrase and the viral DNA ends in functional preintegration complexes. Barrier-to-autointegration factor, a cellular protein that blocks autointegration of Moloney murine leukemia virus DNA, also plays an indirect role in generating the footprints at the ends of the viral DNA. We have exploited Mu-mediated PCR to examine the effect of mutations at the viral DNA termini on complex formation. We find that a replication competent mutant with a deletion at one end of the viral DNA still exhibits a strong enhancement about 20 hp from the terminus of the mutant DNA end. The site of the enhancement therefore appears to be at a fixed distance from the ends of the viral DNA. We also find that a mutation at one end of the viral DNA, which renders the virus incompetent for replication, abolishes the enhancements and protection at both the U3 and U5 ends. A pair of functional viral DNA ends therefore are required to interact before the chemical step of 3' end processing. C1 NIDDKD, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDKD, NIH, Mol Biol Lab, Bldg 5,Room 301,5 Ctr Dr,MSC 0560, Bethesda, MD 20892 USA. NR 18 TC 43 Z9 43 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10535 EP 10540 DI 10.1073/pnas.95.18.10535 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500036 PM 9724738 ER PT J AU Berrueta, L Kraeft, SK Tirnauer, JS Schuyler, SC Chen, LB Hill, DE Pellman, D Bierer, BE AF Berrueta, L Kraeft, SK Tirnauer, JS Schuyler, SC Chen, LB Hill, DE Pellman, D Bierer, BE TI The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DETYROSINATED TUBULIN; MITOTIC SPINDLE; YEAST; MOTORS AB The evolutionarily conserved protein EB1 originally was identified by its physical association with the carboxyl-terminal portion of the adenomatous polyposis coli (APC) tumor suppressor protein, an APC domain commonly mutated in familial and sporadic forms of colorectal neoplasia, The subcellular localization of EB1 in epithelial cells was studied by using immunofluorescence and biochemical techniques. EB1 colocalized both to cytoplasmic microtubules in interphase cells and to spindle microtubules during mitosis, with pronounced centrosome staining. The cytoskeletal array detected by anti-EB1 antibody was abolished by incubation of the cells with nocodazole, an agent that disrupts microtubules; upon drug removal, EB1 localized to the microtubule-organizing center. Immunofluorescence analysis of SW480, a colon cancer cell line that expresses only carboxyl-terminal-deleted APC unable to interact with EB1, demonstrated that EB1 remained localized to the microtubule cytoskeleton, suggesting that this pattern of subcellular distribution is not mediated by its interaction with APC, rn vitro cosedimentation with taxol-stabilized microtubules demonstrated that a significant fraction of EB1 associated with microtubules, Recent studies of the yeast EB1 homologues Mal3 and Bim1p have demonstrated that both proteins localize to microtubules and are important in vivo for microtubule function. Our results demonstrate that EB1 is a novel component of the microtubule cytoskeleton in mammalian cells. Associating with the mitotic apparatus, EB1 may play a physiologic role connecting APC to cellular division, coordinating the control of normal growth and differentiation processes in the colonic epithelium. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Los Andes, Inst Clin Immunol, Merida 5101, Venezuela. Oncogene Res Prod, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP NHLBI, Bldg 10,Room 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM biererb@nih.gov RI Hill, David/B-6617-2011; OI Berrueta, Lisbeth/0000-0002-5674-6448 NR 16 TC 141 Z9 142 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10596 EP 10601 DI 10.1073/pnas.95.18.10596 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500047 PM 9724749 ER PT J AU Love, DC Sweitzer, TD Hanover, JA AF Love, DC Sweitzer, TD Hanover, JA TI Reconstitution of HIV-1 Rev nuclear export: Independent requirements for nuclear import and export SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS TYPE-1 REV; PROTEIN IMPORT; TRANSPORT FACTOR; CELLULAR COFACTOR; MESSENGER-RNA; SIGNAL; IDENTIFICATION; CRM1; LOCALIZATION; RECEPTOR AB The Rev protein of HIV-1 actively shuttles between nucleus and cytoplasm and mediates the export of unspliced retroviral RNAs. The localization of shuttling proteins such as Rev is controlled by the relative rates of nuclear import and export. To study nuclear export in isolation, we generated cell lines expressing a green fluorescent protein-labeled chimeric protein consisting of HIV-1 Rev and a hormone-inducible nuclear localization sequence. Steroid removal switches off import thus allowing direct visualization of the Rev export pathway in living cells. After digitonin permeabilization of these cells, we found that a functional nuclear export sequence (NES), ATP, and fractionated cytosol were sufficient for nuclear export in vitro. Nuclear pore-specific lectins and leptomycin B were potent export inhibitors. Nuclear export was not inhibited by antagonists of calcium metabolism that block nuclear import. These data further suggest that nuclear pores do not functionally close when luminal calcium stores are depleted. The distinct requirements for nuclear import and export argue that these competing processes may be regulated independently. This system should have wide applicability for the analysis of nuclear import and export. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bldg 8,Room 402,8 Ctr Dr, Bethesda, MD 20892 USA. NR 45 TC 70 Z9 71 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10608 EP 10613 DI 10.1073/pnas.95.18.10608 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500049 PM 9724751 ER PT J AU Brinkmann, U Vasmatzis, G Lee, BK Yerushalmi, N Essand, M Pastan, I AF Brinkmann, U Vasmatzis, G Lee, BK Yerushalmi, N Essand, M Pastan, I TI PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; expressed sequence tags; cDNA; libraries ID CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; SEQUENCE; FAMILY; IDENTIFICATION; LOCALIZATION; REGION; CANCER AB We have used a combination of computerized database mining and experimental expression analyses to identify a gene that is preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus, and placenta, as well as in prostate cancer, testicular cancer, and uterine cancer. This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins. GAGE proteins are expressed in a variety of tumors and in testis. We designate the novel gene PAGE-1 because the expression pattern in the Cancer Genome Anatomy Project libraries indicates that it is predominantly expressed in normal and neoplastic prostate. Further database analysis indicates the presence of other genes with high homology to PAGE-1, which were found in cDNA libraries derived from testis, pooled libraries (with testis), and in a germ cell tumor library. The expression of PAGE-1 in normal and malignant prostate, testicular, and uterine tissues makes it a possible target for the diagnosis and possibly for the vaccine-based therapy of neoplasms of prostate, testis, and uterus. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 29 TC 74 Z9 78 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10757 EP 10762 DI 10.1073/pnas.95.18.10757 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500075 PM 9724777 ER PT J AU Wang, JX Hoshino, T Redner, RL Kajigaya, S Liu, JM AF Wang, JX Hoshino, T Redner, RL Kajigaya, S Liu, JM TI ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HISTONE DEACETYLASE; CO-REPRESSOR; N-COR; PROTEIN; GENE; AML1; IDENTIFICATION; TARGET; TRANSLOCATION; HEMATOPOIESIS AB The t(8;21) translocation between two genes known as AMLI and ETO is seen in approximately 12-15% of all acute myeloid leukemia (AML) and is the second-most-frequently observed nonrandom genetic alteration associated with AML, AML1 up-regulates a number of target genes critical to normal hematopoiesis, whereas the AML1/ETO fusion interferes with this trans-activation. We discovered that the fusion partner ETO binds to the human homolog of the murine nuclear receptor corepressor (N-CoR), The interaction is mediated by two unusual zinc finger motifs present at the carboxyl terminus of ETO, Human N-CoR (HuN-CoR), which we cloned and sequenced in its entirety, encodes a 2,440-amino acid polypeptide and has a central domain that binds ETO, N-CoR, mammalian Sin3 (mSin3A and B), and histone deacetylase 1 (HDAC1) form a complex that alters chromatin structure and mediates transcriptional repression by nuclear receptors and by a number of oncoregulatory proteins, We found that ETO, through its interaction with the N-CoR/mSin3/HDAC1 complex, is also a potent repressor of transcription. This observation provides a mechanism for how the AML1/ETO fusion may inhibit expression of AML1-responsive target genes and disturb normal hematopoiesis. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,room 7C103, Bethesda, MD 20892 USA. NR 35 TC 312 Z9 334 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10860 EP 10865 DI 10.1073/pnas.95.18.10860 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500093 PM 9724795 ER PT J AU Sterneck, E Paylor, R Jackson-Lewis, V Libbey, M Przedborski, S Tessarollo, L Crawley, JN Johnson, PF AF Sterneck, E Paylor, R Jackson-Lewis, V Libbey, M Przedborski, S Tessarollo, L Crawley, JN Johnson, PF TI Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein delta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM FACILITATION; INBRED MOUSE STRAINS; DEFICIENT MICE; KNOCKOUT MICE; BEHAVIORAL PHENOTYPES; CORTICAL ASTROCYTES; TARGETED DISRUPTION; ADENYLYL-CYCLASE; MUTANT MICE; C/EBP-BETA AB CCAAT/enhancer binding protein delta (C/EBP delta) is a transcriptional regulator implicated in the hepatic acute phase response and in adipogenic and myeloid cell differentiation. We found that C/EBP delta is widely expressed in the peripheral and central nervous systems, including neurons of the hippocampal formation, indicating a role in neural functions. To examine the role of C/EBP delta in vivo, we generated mice with a targeted deletion of the C/EBP delta gene. This mutation does not interfere with normal embryonic and postnatal development. Performance in a battery of behavioral tests indicates that basic neurological functions are normal. Furthermore, performance in a Morris water maze task suggests that C/EBP delta mutant mice have normal spatial learning. However, in the contextual and auditory-cue-conditioned fear task, C/EBP delta null mice displayed significantly more conditioned freezing to the test context than did wild-type controls, but equivalent conditioning to the auditory cue, These data demonstrate a selectively enhanced contextual fear response in mice carrying a targeted genomic mutation and implicate C/EBP delta in the regulation of a specific type of learning and memory. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Transcript Regulat Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Neural Dev Grp, Frederick, MD 21702 USA. Columbia Univ, Dept Neurol, Neurol Res Movement Disorders Div, New York, NY 10032 USA. NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Johnson, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Transcript Regulat Sect, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NINDS NIH HHS [NS01724, NS37345] NR 50 TC 107 Z9 108 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10908 EP 10913 DI 10.1073/pnas.95.18.10908 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500101 PM 9724803 ER PT J AU Colangelo, AM Johnson, PF Mocchetti, I AF Colangelo, AM Johnson, PF Mocchetti, I TI beta-adrenergic receptor-induced activation of nerve growth factor gene transcription in rat cerebral cortex involves CCAAT/enhancer-binding protein delta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR MESSENGER-RNA; VASOACTIVE-INTESTINAL-PEPTIDE; C6-2B GLIOMA-CELLS; C-FOS; FACTOR BIOSYNTHESIS; ASTROCYTOMA-CELLS; LEUCINE-ZIPPER; C/EBP-BETA; BRAIN; STIMULATION AB Stimulation of beta-adrenergic receptors (BAR) by clenbuterol (CLE) increases nerve growth factor (NGF) biosynthesis in the rat cerebral cortex but not in other regions of the brain. We have explored the transcription mechanisms that may account for the cortex-specific activation of the NGF gene. Although the NGF promoter contains an AP-1 element, AP-1-binding activity in the cerebral cortex was not induced by CLE, suggesting that other transcription factors govern the brain area-specific induction of NGF. Because BAR activation increases cAMP levels, we examined the role of CCAAT/enhancer-binding proteins (C/EBP), some of which are known to be cAMP-inducible, In C6-2B glioma cells, whose NGF expression is induced by BAR agonists, (i) CLE increased C/EBP delta-binding activity, (ii) NGF mRNA levels were increased by overexpressing C/EBP delta, and (iii) C/EBP delta increased the activity of an NGF promoter-reporter construct. Moreover, DNase footprinting and deletion analyses identified a C/EBP delta site in the proximal region of the NGF promoter. C/EBP delta appears to be responsible for the BAR-mediated activation of the NGF gene in vivo, since CLE elicited a time-dependent increase in C/EBP delta-binding activity in the cerebral cortex only. Our data suggest that, while AP-1 may regulate basal levels of NGF expression, C/EBP delta is a critical component determining the area-specific expression of NGF in response to BAR stimulation. C1 Georgetown Univ, Sch Med, Dept Cell Biol, Washington, DC 20007 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Eukaryot Transcript Regulat Grp, Frederick, MD 21702 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Sch Med, Dept Cell Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. RI Johnson, Peter/A-1940-2012; OI Johnson, Peter/0000-0002-4145-4725; COLANGELO, ANNA MARIA/0000-0002-7971-4289 FU NINDS NIH HHS [NS 01675, NS 29664] NR 45 TC 52 Z9 52 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10920 EP 10925 DI 10.1073/pnas.95.18.10920 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500103 PM 9724805 ER PT J AU Inoue, M Kobayashi, M Kozaki, S Zimmer, A Ueda, H AF Inoue, M Kobayashi, M Kozaki, S Zimmer, A Ueda, H TI Nociceptin/orphanin FQ-induced nociceptive responses through substance P release from peripheral nerve endings in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ORPHANIN-FQ; G-PROTEIN; RECEPTOR ANTAGONIST; TISSUE DISTRIBUTION; PHOSPHOLIPASE-C; ALPHA-SUBUNITS; NK1 RECEPTOR; SPINAL-CORD; FORMALIN; MEMBRANE AB We have studied the in vivo signaling mechanisms involved in nociceptin/orphanin FQ (Noci)-induced pain responses by using a flexor-reflex paradigm. Noci was 10,000 times more potent than substance P (SP) in eliciting flexor responses after intraplantar injection into the hind limb of mice, but the action of Noci seems to be mediated by SP. Mice pretreated with an NK1 tachykinin receptor antagonist or capsaicin, or mice with a targeted disruption of the tachykinin 1 gene no longer respond to Noci. The action of Noci appears to be mediated by the Noci receptor, a pertussis toxin-sensitive G protein-coupled receptor that stimulates inositol trisphosphate receptor and Ca2+ influx. These findings suggest that Noci indirectly stimulates nerve endings of nociceptive primary afferent neurons through a local SP release. C1 Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, Nagasaki 8528521, Japan. Osaka Univ, Fac Pharmaceut Sci, Dept Pharmacognosy, Suita, Osaka 565, Japan. Univ Osaka Prefecture, Coll Agr, Dept Vet Sci, Sakai, Osaka 593, Japan. NIMH, Genet Sect, Bethesda, MD 20892 USA. RP Ueda, H (reprint author), Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, Nagasaki 8528521, Japan. RI Zimmer, Andreas/B-8357-2009 NR 38 TC 92 Z9 92 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10949 EP 10953 DI 10.1073/pnas.95.18.10949 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500108 PM 9724810 ER PT J AU Quinones-Hinojosa, A Derrick, BE Barea-Rodriguez, EJ Janak, PH Martinez, JL AF Quinones-Hinojosa, A Derrick, BE Barea-Rodriguez, EJ Janak, PH Martinez, JL TI Long-term potentiation at the lateral perforant path nucleus accumbens synapse in the rat in vivo SO PSYCHOBIOLOGY LA English DT Article ID ENTORHINAL CORTEX; IN-VIVO; STRIATUM; HIPPOCAMPUS; STIMULATION; PROJECTIONS; RESPONSES; IDENTIFICATION; PLASTICITY; MEMORY AB The nucleus accumbens (NAcb), a basal forebrain structure implicated in drug-mediated reward, receives afferents from a variety of limbic and cortical structures, including the prefrontal cortex, the amygdala, the entorhinal cortex, and the subicular complex. In the present study, monosynaptic projections from the lateral entorhinal cortex (lateral perforant path) to the NAcb are shown to display sustained increases in field EPSP magnitudes following high-frequency stimulation of the perforant path in anesthetized rats. By contrast, stimulation of the medial aspect of the perforant path, although capable of evoking responses in the dentate gyrus, produced no observable synaptic responses within the nucleus accumbens. Intra-accumbens administration of (+/-)-CPP(-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), a selective competitive NMDA-receptor antagonist, blocked both short-term potentiation and long-term potentiation (LTP). Thus afferents from the entorhinal cortex to the NAcb display NMDA-receptor-dependent synaptic potentiation that appears similar to NMDA-receptor-dependent LTP observed at other targets of the perforant path, such as the hippocampal formation. C1 Univ Texas, Div Life Sci, San Antonio, TX 78240 USA. NIDA, Baltimore, MD USA. RP Martinez, JL (reprint author), Univ Texas, Div Life Sci, San Antonio, TX 78240 USA. RI Barea-Rodriguez, Edwin/E-3917-2010; Derrick, Brian/P-3005-2014 OI Derrick, Brian/0000-0001-6940-6509 NR 33 TC 1 Z9 1 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0889-6313 J9 PSYCHOBIOLOGY JI Psychobiology PD SEP PY 1998 VL 26 IS 3 BP 169 EP 175 PG 7 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 134LR UT WOS:000076745000001 ER PT J AU Litten, RZ Allen, JP AF Litten, RZ Allen, JP TI Advances in development of medications for alcoholism treatment SO PSYCHOPHARMACOLOGY LA English DT Review DE pharmacotherapy; medications; craving; comorbidity; depression ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RELAPSE PREVENTION; SOCIAL DRINKERS; NALTREXONE PRETREATMENT; CONSUMMATORY BEHAVIORS; WEANED ALCOHOLICS; HEAVY DRINKERS; ETHANOL INTAKE; DEPENDENCE AB Over the past decade, research on medications to treat alcohol problem has flourished. Naltrexone and acamprosate are tangible fruits of such endeavors and each has now earned approval in a large number of countries. Recent studies on naltrexone indicate that patient compliance is important if full benefits are to be achieved. Several laboratory studies with human subjects are beginning to elucidate the mechanisms underlying efficacy of naltrexone, as well as explaining variability of response among subpopulations of drinkers. In addition to these two agents, recent investigations have also demonstrated that: the antidepressants desipramine, imipramine, and fluoxetine reduce mood-related symptoms and, to some extent, drinking itself in alcoholics who are depressed. Research to date suggests that opioid antagonists and selective serotonin reuptake inhibitors are more effective in reducing alcohol intake when used in combination. Clinical issues, methodology, and directions for future research are also reviewed in this article. In particular, issues addressed include alternative dosage regimens, necessary duration of treatment, employment of medications in combination, integration of pharmacologic agents with behavioral interventions, enhancement of patient compliance, and concurrent treatment of psychiatric comorbidity. C1 NIAAA, Treatment Res Branch, Rockville, MD 20852 USA. RP Litten, RZ (reprint author), NIAAA, Treatment Res Branch, Willco Bldg,Suite 505,60000 Execut Blvd, Rockville, MD 20852 USA. NR 68 TC 48 Z9 49 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1998 VL 139 IS 1-2 BP 20 EP 33 DI 10.1007/s002130050686 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 119TC UT WOS:000075912400003 PM 9768539 ER PT J AU Cott, JM AF Cott, JM TI In vitro receptor binding and enzyme inhibition by an extract of Hypericum perforatum SO PSYCHOPHARMAKOTHERAPIE LA German DT Article DE Hypericum; receptor binding; GABA receptors; NMDA receptors; hypericin ID LOCOMOTOR STIMULATION; DEPRESSION; GABA; PSEUDOHYPERICIN; SUPPRESSION; TOXICITY; AGENTS; DRUGS AB To assess pharmacologic mechanisms of Hypericum perforatum (St. John's wort) as an antidepressant a hypericum extract and its specific constituent hypericin were tested in a battery of 39 in vitro receptor assays and 2 enzyme assays. Hypericin had affinity only for NMDA receptors while the whole extract demonstrated significant affinity for adenosine (nonspecific), GABA(A), GABA(B), benzodiazepine, inositol triphosphate receptors and monoamine oxidase (MAO) A and B. With the exception of GABA(A) and GABA(B) receptors, the concentrations of hypericum extract required for these in vitro activities are unlikely to be attained after oral administration in whole animals or humans. These data are consistent with recent pharmacologic evidence suggesting that other constituents of this plant may be of greater importance for the reported antidepressant activity C1 NIMH, Forschungsprogramm Pharmakotherapie, Rockville, MD 20857 USA. RP Cott, JM (reprint author), NIMH, Forschungsprogramm Pharmakotherapie, 5600 Fishers Lane,Raum 18-105, Rockville, MD 20857 USA. NR 39 TC 0 Z9 0 U1 0 U2 3 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0944-6877 J9 PSYCHOPHARMAKOTHERAP JI Psychopharmakotherapie PD SEP PY 1998 VL 5 IS 3 SU 8 BP 51 EP 55 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 129AM UT WOS:000076441100011 ER PT J AU Siqueland, L Chittams, J Frank, A Thase, ME Gastfriend, DR Mercer, D Muenz, L Crits-Christoph, P Blaine, J AF Siqueland, L Chittams, J Frank, A Thase, ME Gastfriend, DR Mercer, D Muenz, L Crits-Christoph, P Blaine, J TI The protocol deviation patient: Characterization and implications for clinical trials research SO PSYCHOTHERAPY RESEARCH LA English DT Article ID ADDICTION SEVERITY INDEX; COGNITIVE THERAPY; COCAINE ABUSERS; DEPRESSION; PHARMACOTHERAPY; PREDICTORS; ALCOHOL AB This paper addresses those patients who neither complete treatment nor drop out from clinical trials but who deviate from the protocol treatment by seeking or receiving additional treatment. Psychotherapy researchers may be missing important information by withdrawing these: patients from analyses or combining them with dropouts from treatment. In a multisite psychotherapy outcome study for patients with cocaine dependence, patients who deviated from protocol could be distinguished from completers and dropouts on pretreatment patient characteristics. Patients who deviated from protocol were more likely to be African American, to have higher psychiatric severity, and to have had more previous drug treatment attempts. Data indicate that there is a value in obtaining follow-up assessment after the protocol deviation and including these patients in data analysis to avoid bias in findings. Differential outcome for protocol deviation patients compared to dropouts and completers is discussed. C1 Univ Penn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brookside Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Natl Inst Drug Abuse, Treatment Res Branch, Rockville, MD 20857 USA. RP Siqueland, L (reprint author), Room 705,3600 Market St, Philadelphia, PA USA. NR 31 TC 1 Z9 1 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD FAL PY 1998 VL 8 IS 3 BP 287 EP 306 PG 20 WC Psychology, Clinical SC Psychology GA 120CM UT WOS:000075937100004 ER PT J AU Astakhova, LN Anspaugh, LR Beebe, GW Bouville, A Drozdovitch, VV Garber, V Gavrilin, YI Khrouch, VT Kuvshinnikov, AV Kuzmenkov, YN Minenko, VP Moschik, KV Nalivko, AS Robbins, J Shemiakina, EV Shinkarev, S Tochitskaya, SI Waclawiw, MA AF Astakhova, LN Anspaugh, LR Beebe, GW Bouville, A Drozdovitch, VV Garber, V Gavrilin, YI Khrouch, VT Kuvshinnikov, AV Kuzmenkov, YN Minenko, VP Moschik, KV Nalivko, AS Robbins, J Shemiakina, EV Shinkarev, S Tochitskaya, SI Waclawiw, MA TI Chernobyl-related thyroid cancer in children of Belarus: A case-control study SO RADIATION RESEARCH LA English DT Article ID RADIATION; I-131 AB The accident at the Chernobyl nuclear power plant on April 26, 1986, released approximately 2 EBq of I-131 and other radioiodine isotopes that heavily contaminated southern Belarus. An increase in thyroid cancer reported in 1992 and attributed to the Chernobyl accident was challenged as possibly the result of intensive screening. We began a case-control study to test the hypothesis that the Chernobyl accident caused the increase in thyroid cancer. Records of childhood thyroid cancer in the national therapy centers in Minsk in 1992 yielded 107 individuals with confirmed pathology diagnoses and available for interview. Pathways to diagnosis were (1) routine endocrinological screening in 63, (2) presentation with enlarged or nodular thyroid in 25 and (3) an incidental finding in 19. Two sets of controls were chosen, one matched on pathway to diagnosis, the other representing the area of heavy fallout, both matched on age, sex and rural/urban residence in 1986. The I-131 dose to the thyroid was estimated from ground deposition of Cs-137, ground deposition of I-131, a data bank of 1986 thyroid radiation measurements, questionnaires and interviews. Highly significant differences were observed between cases and controls (both sets) with respect to dose. The differences persisted within pathway to diagnosis, gender, age and year of diagnosis, and level of iodine in the soil, and were most marked in the southern portion of the Gomel region. The case-control comparisons indicate a strong relationship between thyroid cancer and estimated radiation dose from the Chernobyl accident. (C) 1998 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Minist Hlth, Res Inst Radiat Med, Minsk, Byelarus. Univ Utah, Div Radiobiol, Salt Lake City, UT 84112 USA. NCI, NIH, Bethesda, MD 20892 USA. State Res Ctr Russia, Inst Biophys, Moscow, Russia. NIDDKD, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Beebe, GW (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, EPN 400, Bethesda, MD 20892 USA. RI Shinkarev, Sergey /B-3254-2017 NR 33 TC 102 Z9 110 U1 0 U2 14 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD SEP PY 1998 VL 150 IS 3 BP 349 EP 356 DI 10.2307/3579983 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 115ND UT WOS:000075670600010 PM 9728663 ER PT J AU Dagher, AP Fitzpatrick, M Flanders, AE Eng, J AF Dagher, AP Fitzpatrick, M Flanders, AE Eng, J TI Enhancing Web applications in radiology with Java: Estimating MR imaging relaxation times SO RADIOGRAPHICS LA English DT Article DE computers; Internet; Java; magnetic resonance (MR), image processing AB Java is a relatively new programming language that has been used to develop a World Wide Web-based tool for estimating magnetic resonance (MR) imaging relaxation times, thereby demonstrating how Java may be used for Web-based radiology applications beyond improving the user interface of teaching files, A standard processing algorithm coded with Java is downloaded along with the hypertext markup language (HTML) document. The user (client) selects the desired pulse sequence and inputs data obtained from a region of interest on the MR images. The algorithm is used to modify selected MR imaging parameters in an equation that models the phenomenon being evaluated. MR imaging relaxation times are estimated, and confidence intervals and a P value expressing the accuracy of the final results are calculated. Design features such as simplicity, object-oriented programming, and security restrictions allow Java to expand the capabilities of HTML by offering a more versatile user interface that includes dynamic annotations and graphics. Java also allows the client to perform more sophisticated information processing and computation than is usually associated with Web applications. Java is likely to become a standard programming option, and the development of stand-alone Java applications may become more common as Java is integrated into future versions of computer operating systems. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. Johns Hopkins Hosp, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. Sch Med, Baltimore, MD USA. RP Dagher, AP (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 1998 VL 18 IS 5 BP 1287 EP 1293 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 117BJ UT WOS:000075759800022 PM 9747620 ER PT J AU Budinger, TF Berson, A McVeigh, ER Pettigrew, RI Pohost, GM Watson, JT Wickline, SA AF Budinger, TF Berson, A McVeigh, ER Pettigrew, RI Pohost, GM Watson, JT Wickline, SA TI Cardiac MR imaging: Report of a working group sponsored by the National Heart, Lung, and Blood Institute SO RADIOLOGY LA English DT Article DE heart, MR; magnetic resonance (MR), vascular studies; special reports AB Dramatic progress has been made over the past several years in the research and development of magnetic resonance (MR) techniques for imaging biologic structure and function, and much of this work has been supported by the National Institutes of Health (NIH). MR imaging has capabilities that are unique, as compared with other imaging modalities, for measurement and monitoring of biologic processes in vivo. Despite these capabilities, the use of MR imaging by cardiovascular and cardiopulmonary clinicians remains limited; in many institutions, clinicians rarely refer patients for MR examinations. The principal reasons for this include long imaging times with associated patient discomfort, low postprocessing speeds, inadequate access to patients during imaging, and lack of understanding of MR processes and benefits by clinicians and their associates. On October 28-29, 1996, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a Working Group to explore the potential of MR for imaging the heart, lung, and vasculature. They recommend areas of research and development that could lead to more extensive clinical use of MR methods to improve the diagnosis and management of cardiovascular and cardiopulmonary disorders. Approximately 50 scientists, bioengineers, and clinicians from academia, industry, and government convened at the NIH Natcher Conference Center, Bethesda, Md.Dramatic progress has been made over the past several years in the research and development of magnetic resonance (MR) techniques for imaging biologic structure and function, and much of this work has been supported by the National Institutes of Health (NIH). MR imaging has capabilities that are unique, as compared with other imaging modalities, for measurement and monitoring of biologic processes in vivo. Despite these capabilities, the use of MR imaging by cardiovascular and cardiopulmonary clinicians remains limited; in many institutions, clinicians rarely refer patients for MR examinations. The principal reasons for this include long imaging times with associated patient discomfort, low postprocessing speeds, inadequate access to patients during imaging, and lack of understanding of MR processes and benefits by clinicians and their associates. On October 28-29, 1996, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a Working Group to explore the potential of MR for imaging the heart, lung, and vasculature. They recommend areas of research and development that could lead to more extensive clinical use of MR methods to improve the diagnosis and management of cardiovascular and cardiopulmonary disorders. Approximately 50 scientists, bioengineers, and clinicians from academia, industry, and government convened at the NIH Natcher Conference Center, Bethesda, Md. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Ctr Funct Imaging, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Jewish Hosp, Dept Internal Med, St Louis, MO USA. RP Berson, A (reprint author), NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 13 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1998 VL 208 IS 3 BP 573 EP 576 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112HN UT WOS:000075488200006 PM 9722831 ER PT J AU Polak, JF Shemanski, L O'Leary, DH Lefkowitz, D Price, TR Savage, PJ Brant, WE Reid, C AF Polak, JF Shemanski, L O'Leary, DH Lefkowitz, D Price, TR Savage, PJ Brant, WE Reid, C CA Cardiovascular Hlth Study TI Hypoechoic plaque at US of the carotid artery: An independent risk factor for incident stroke in adults aged 65 years or older SO RADIOLOGY LA English DT Article DE carotid arteries; carotid arteries, diseases; carotid arteries, stenosis or obstruction; carotid arteries, US ID CARDIOVASCULAR HEALTH; MORPHOLOGY; ATHEROSCLEROSIS; STENOSES; DISEASE; ENDARTERECTOMY; HEMORRHAGE; SYMPTOMS AB PURPOSE: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US). MATERIALS AND METHODS: A cohort of 4,886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressures, elevated low-density lipoprotein cholesterol level. RESULTS: incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1.42, 4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (P = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36, 5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28,,7.41)were associated with ipsilateral, nonfatal stroke. CONCLUSION: In asymptomatic adults aged 65 years or older, the risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Washington, CHS Coordinating Ctr, Seattle, WA 98195 USA. Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27103 USA. Univ Maryland Baltimore Cty, Dept Neurol, Baltimore, MD 21228 USA. NHLBI, Div Epidemiol & Clin Applicat, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Univ Calif Davis, Med Ctr, Dept Radiol, Davis, CA USA. Univ Calif Irvine, Div Cardiol, Irvine, CA 92717 USA. RP Polak, JF (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [N01-HC-5079, N01-HC-85086] NR 36 TC 238 Z9 240 U1 0 U2 9 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1998 VL 208 IS 3 BP 649 EP 654 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112HN UT WOS:000075488200016 PM 9722841 ER PT J AU Burstein, GR Waterfield, G Joffe, A Zenilman, JM Quinn, TC Gaydos, CA AF Burstein, GR Waterfield, G Joffe, A Zenilman, JM Quinn, TC Gaydos, CA TI Screening for gonorrhea and Chlamydia by DNA amplification in adolescents attending middle school health centers - Opportunity for early intervention SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; NEISSERIA-GONORRHOEAE; TRACHOMATIS INFECTION; FEMALE ADOLESCENTS; REACTION ASSAY; URINE; DISEASE; WOMEN; PREVALENCE; DIAGNOSIS AB Goal: To determine prevalence and incidence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) infection and assess risk factors predictive for such infections in a middle school-based clinic sample. Study Design: 170 female students and 43 male students making 256 and 47 visits, respectively, greater than or equal to 30 days apart, in urban middle school clinics for primary care screening, reproductive health, or illness/injury were routinely asked to provide urine specimens for GC and CT ligase chain reaction testing if sexually active in the preceding 3-month period. Information regarding prior sexually transmitted diseases, reason for visit, and sexual risk behaviors was obtained, Results: GC: 11.4% of female student and 2.1% of male student tests were positive, Incidence was 34.0 cases/1,000 person months (95% Confidence interval [CI]: 19.5-67.5), Median time to first positive and repeat positive test was 4.6 and 2.6 months, respectively. For CT: 16.4 % of female student and 2.1% of male student tests were positive. Incidence was 57.5 cases/1,000 person months (95% CI: 35,2-93.8), Median time to first positive and repeat positive CT test was 6.0 and 4.8 months, respectively. Assessed risk factors failed to specify a candidate screening population. Conclusion: These data suggest that all sexually active adolescent girls in this high risk setting should be offered testing for GC and CT at least twice per year, regardless of;age or other sexual risk behaviors and that STD control efforts in high risk middle schools should be encouraged. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Div Gen Pediat & Adolescent Med, Baltimore, MD USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Baltimore City Hlth Dept, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Burstein, GR (reprint author), Johns Hopkins Univ, Div Infect Dis, 720 Rutland Ave,Room 1159, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 41 TC 78 Z9 78 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP PY 1998 VL 25 IS 8 BP 395 EP 402 DI 10.1097/00007435-199809000-00001 PG 8 WC Infectious Diseases SC Infectious Diseases GA 119MT UT WOS:000075900800001 PM 9773430 ER PT J AU Howell, MR Gaydos, CA Quinn, TC AF Howell, MR Gaydos, CA Quinn, TC TI Cost-effectiveness of Chlamydial screening SO SEXUALLY TRANSMITTED DISEASES LA English DT Letter ID TRACHOMATIS C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Howell, MR (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, Ross Res Bldg 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP PY 1998 VL 25 IS 8 BP 406 EP 407 DI 10.1097/00007435-199809000-00003 PG 2 WC Infectious Diseases SC Infectious Diseases GA 119MT UT WOS:000075900800003 ER PT J AU Shah, V Braverman, R Prasad, GL AF Shah, V Braverman, R Prasad, GL TI Suppression of neoplastic transformation and regulation of cytoskeleton by tropomyosins SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID RAT CULTURED-CELLS; SIGNAL-TRANSDUCTION; MULTIPLE ISOFORMS; FOCAL ADHESIONS; STRESS FIBERS; NRK CELLS; EXPRESSION; CDNA; FIBROBLASTS; GROWTH AB Down regulation of Tropomyosins (TMs) is a consistent biochemical change observed in many transformed cells. Our previous work has demonstrated that Tropomyosin-1 is an antioncogene and it is a class II tumor suppressor. Using ras-transformed murine fibroblasts (DT cells), we have examined the effects of co-expression of two isoforms of TM on cell morphology: cytoskeleton and tumorigenecity. Enhanced expression of TMI, a suppressor of transformation, along with TM2 which is not a tumor suppressor results in the formation of well-organized microfilaments, a morphology that resembles normal fibroblasts, and suppression of tumorigenecity. Tumor formation in vivo was compatible with the persistence of high-level of TM2, brit not TMI. Homodimers of TM1 and TM2 were observed in these cells, Thus, restoration of expression of TM1 and TM2 protein in ras-transformed cells suppresses the transformed phenotype with dramatic re-organization of microfilaments. These data show thar TM2 cooperates with TMI in the reorganization of microfilaments, while TM1 is a suppressor of the transformed phenotype. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Shah, V (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD SEP PY 1998 VL 24 IS 5 BP 273 EP 280 DI 10.1023/B:SCAM.0000007130.08611.fc PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 269FR UT WOS:000084466500002 PM 10696235 ER PT J AU Kauppila, LI Eustace, S Kiel, DP Felson, DT Wright, AM AF Kauppila, LI Eustace, S Kiel, DP Felson, DT Wright, AM TI Degenerative displacement of lumbar vertebrae - A 25-year follow-up study in Framingham SO SPINE LA English DT Article DE back pain; disability; retrolisthesis; spondylolisthesis ID SPONDYLOLISTHESIS AB Study Design. The authors assessed degenerative lumbar displacement in a population-based cohort of 217 men and 400 women who had lateral lumbar radiographs performed at the mean age of 54 years and again at 79 years, and who had completed interviews on back symptoms and functional performance in connection with the follow-vp examination. Objectives. To assess the prevalence and incidence of degenerative slippage and its association with back pain and physical disability. Summary of Background Data. Degenerative displacement of lumbar vertebrae may cause instability, nerve root compression, and spinal stenosis. Its incidence in the older population and association with back pain and disability are unknown. Methods. The authors assessed the prevalence and incidence of degenerative slippage from lateral lumbar radiographs performed 25 years apart and its association with back pain and physical disability from interviews performed in connection with the follow-up examination. Results. At the follow-up examination, 23 (12%) men and 100 (25%) women had developed degenerative slippage exceeding 3 mm; two of them had this already at the baseline. A forward displacement was found in 8 men and 76 women (P < 0.0001 for difference between the genders) and a backward one in 16 men and 35 women. On average, forward slip was 18% +/- 5.5, and backward slip, 15% +/- 4.0 of the anteroposterior diameter of the vertebra below. At the time of the second lumbar radiograph, 39 (32%) of the subjects with slippage, compared with 90 (19%) of the controls, had pain, aching, or stiffness in their back on most days (P = 0.001). After adjustment for endplate sclerosis, wh ich was also related to pain (P = 0.015), slippage still had association With daily back symptoms (P = 0.009). However, Subjects with slippage had not experienced mor back symptoms during the preceding year or in earlier ages of life, and they did not report more disability than the controls. Conclusions. Degenerative displacement of lumbar vertebrae is common in an older population and is associated with Increased prevalence of daily back symptoms However, two thirds of the subjects with degenerative displacement do not report ongoing back symptoms and the disorder is also unrelated to long-term back pain and physical disability. C1 Natl Heart & Lung Inst, Framingham, MA USA. Blood Inst Framingham Heart Study, Framingham, MA USA. Natl Inst Hlth, Framingham, MA USA. Boston Univ, Med Ctr, Dept Musculoskeletal Radiol, Boston, MA USA. Boston City Hosp, Boston, MA 02118 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Med, Arthrit Sect, Hlth Serv Epidemiol Res Unit, Boston, MA 02118 USA. Tufts Univ, New England Baptist Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02111 USA. RP Kauppila, LI (reprint author), Lansilinnake 6A, Espoo 02160, Finland. RI Abbott, J./B-2976-2008; OI Abbott, J./0000-0001-6468-7284; Kiel, Douglas/0000-0001-8474-0310 FU NIA NIH HHS [AG09300]; NIAMS NIH HHS [AR/AG41398, AR20613] NR 15 TC 38 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0362-2436 J9 SPINE JI SPINE PD SEP 1 PY 1998 VL 23 IS 17 BP 1868 EP 1873 DI 10.1097/00007632-199809010-00014 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 118JV UT WOS:000075835500013 PM 9762744 ER PT J AU Boja, JW Carroll, FI Vaughan, RA Kopajtic, T Kuhar, MJ AF Boja, JW Carroll, FI Vaughan, RA Kopajtic, T Kuhar, MJ TI Multiple binding sites for [I-125]RTI-121 and other cocaine analogs in rat frontal cerebral cortex SO SYNAPSE LA English DT Article DE cocaine; RTI-121; dopamine transporter; serotonin transporter; norepinephrine transporter ID MEDIAL PREFRONTAL CORTEX; H-3 GBR-12935 BINDING; HUMAN DOPAMINE TRANSPORTER; NUCLEUS-ACCUMBENS; REINFORCING PROPERTIES; STRIATAL MEMBRANES; BRAIN SYNAPTOSOMES; SELF-STIMULATION; GLYCOSYLATION; LOCALIZATION AB In an effort to identify novel binding sites for cocaine and its analogs, we carried out binding studies with the high-affinity and selective ligand [I-125]RTI-121 in rat frontal cortical tissue. Very low densities of binding sites were found. Saturation analysis revealed that the binding was to both high- and low-affinity sites. Pharmacological competition studies were carried out with inhibitors of the dopamine, norepinephrine, and serotonin transporters. The various transporter inhibitors inhibited the binding of 15 pM [I-125]RTI-121 in a biphasic fashion following a two-site binding model. The resultant data were complex and did not suggest a simple association with any single transporter. Correlational analysis supported the following hypothesis: [I-125] RTI-121 binds to known transporters and not to novel sites; these include dopamine, norepinephrine, and serotonin transporters. Immunoprecipitation of transporters photoaffinity labeled with [(125)] RTI-82 and subsequent analysis of SDS-page gels revealed the presence of authentic dopamine transporters in these samples; displacement of the photoaffinity label occurred with a typical dopamine transporter pharmacology. These data are compatible with the binding properties of RTI-181 and the presence of several known transporters in the tissue studied. Synapse 30:9-17, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 NE Ohio Univ, Coll Med, Dept Pharmacol, Rootstown, OH 44266 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Intramural Res Program, Neurosci Branch, NIH, Baltimore, MD USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Boja, JW (reprint author), NE Ohio Univ, Coll Med, Dept Pharmacol, 4209 SR 44,POB 95, Rootstown, OH 44266 USA. NR 52 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1998 VL 30 IS 1 BP 9 EP 17 DI 10.1002/(SICI)1098-2396(199809)30:1<9::AID-SYN2>3.0.CO;2-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 104NW UT WOS:000075021500002 PM 9704876 ER PT J AU Huang, KX Bergstrom, DA Ruskin, DN Walters, JR AF Huang, KX Bergstrom, DA Ruskin, DN Walters, JR TI N-methyl-D-aspartate receptor blockade attenuates D1 dopamine receptor modulation of neuronal activity in rat substantia nigra SO SYNAPSE LA English DT Article DE reserpine; MK-801; CPP; HA-966; single unit recording; 6-hydroxydopamine; glutamate; Parkinson's disease ID C-FOS EXPRESSION; SUBTHALAMIC NUCLEUS NEURONS; PARS RETICULATA NEURONS; RESERPINE-TREATED RATS; BASAL GANGLIA; GENE-EXPRESSION; PARKINSONS-DISEASE; 6-HYDROXYDOPAMINE-LESIONED RATS; NMDA RECEPTORS; CELL-ACTIVITY AB It has been proposed that dopamine and glutamate affect basal ganglia output, in part, through interactions between D1 receptors and NMDA receptors. The present study examined whether N-methyl-D-aspartate (NMDA) receptor antagonists affect the neurophysiological responses of substantia nigra pars compacta (SNpc; dopaminergic) and pars reticulate (SNpr; non-dopaminergic) neurons to a systemically administered D1 dopamine agonist in two animals models of Parkinson's disease, reserpine treatment and nigrostriatal lesion. Previous studies using extracellular single unit recording techniques have shown that the D1 dopamine agonist SKF 38393 (10 mg/kg) exerts different effects on the firing rates of SNpr neurons after these two dopamine-depleting treatments, suggesting the involvement of multiple mechanisms. SKF 38393 consistently increased the firing rates of SNpr neurons in rats treated subchronically with reserpine, and markedly decreased SNpr firing rates in rats with nigrostriatal damage, Pretreatment with the non-competitive NMDA antagonist MK-801 (0.15 mg/kg i.v.) blocked, and the competitive NMDA antagonist (+/-)CPP (30 mg/kg i.p.) attenuated, the rate effects of SKF 38393 in both dopamine-depleted preparations. SKF 38393 consistently inhibited the firing rate of SNpc dopamine neurons after acute reserpine treatment (10 mg/kg, 4-7 hours), an effect specifically mediated by D1 receptors. Pretreatment with MK-801 (0.1 mg/kg i.v.) or the competitive NMDA antagonist (+)-HW-966 (30 mg/kg i.v.) also effectively attenuated SKF 38393's inhibitory effect on SNpc dopamine neurons. Therefore, NMDA receptor blockade markedly reduces the ability of D1 receptor stimulation to modulate firing rates of both dapaminergic and non-dopaminergic cells in the substantia nigra. Although multiple mechanisms appear to underlie D1-mediated effects on substantia nigra firing rates in reserpine and 6-OHDA-treated rats, these results demonstrate a common dependence on glutamatergic transmission and a permissive role for NMDA receptor activation in the ability of D1 receptor stimulation to both enhance and reduce neuronal activity in the substantia nigra. Synapse 30:18-29, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 NINDS, Neurophysiol Pharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. EM jwalters@helix.nih.gov NR 90 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1998 VL 30 IS 1 BP 18 EP 29 DI 10.1002/(SICI)1098-2396(199809)30:1<18::AID-SYN3>3.0.CO;2-N PG 12 WC Neurosciences SC Neurosciences & Neurology GA 104NW UT WOS:000075021500003 PM 9704877 ER PT J AU Genova, LM Hyman, SE AF Genova, LM Hyman, SE TI 5-HT3 receptor activation is required for induction of striatal c-Fos and phosphorylation of ATF-1 by amphetamine SO SYNAPSE LA English DT Article DE cyclic AMP response element binding protein; immediate early gene; striatum ID DEPENDENT PROTEIN-KINASE; DOPAMINE RELEASE INVIVO; RAT NUCLEUS-ACCUMBENS; FREELY MOVING RATS; EXTRACELLULAR DOPAMINE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; COCAINE; SEROTONIN; MICRODIALYSIS AB Dopamine (DA) has been shown to be required for the induction of striatal gene expression by psychostimulants. However, direct DA agonists or selective inhibitors of DA reuptake are relatively weak inducers of striatal gene expression compared with cocaine or amphetamine. So although necessary, DA alone is not sufficient to mediate the full gene induction response to psychostimulants. In addition to its actions on the DA transporter, amphetamine also enhances serotonin (5-HT) release in the striatum. In this study, we investigated the mechanism by which 5-HT contributes to the regulation of striatal gene expression by amphetamine. We found that selective lesions of serotonergic terminals in the rat forebrain using 5,7-dihydroxytryptamine prevented the full induction of striatal c-Fos by 4 mg/kg amphetamine. Furthermore, amphetamine-induced striatal c-Fos was completely inhibited by administration of the 5-HT3 receptor antagonist, MDL-72222, but not by the 5-HT2A/2C receptor antagonist, ritanserin. Consistent with this finding, the induction of c-Fos by S-HT in primary cultures of E18 striatal neurons devoid of DA input was blocked by the 5-HT3 receptor antagonists, MDL-72222 and ICS 205-930, but not by 5-HT2A/2C antagonism. Additionally, blockade of 5-HT3 receptors by MDL-72222 inhibited the phosphorylation of activating transcription factor-1 (ATF-1) at Ser(63) by amphetamine, but not the phosphorylation of cAMP response element binding protein (CREB) at Ser(133). These results suggest that 5-HT3 receptor activation may be required for amphetamine-induced expression of ATF-l-regulated target genes in the striatum, which may include c-Fos. Synapse 30:71-78, 1998. (C) 1998 Wiley -Liss, Inc. C1 NINDS, Mol Plast Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Program Neurosci, Boston, MA 02115 USA. RP Genova, LM (reprint author), NINDS, Mol Plast Sect, NIH, Bldg 36,Rm 4C-24,36 Convent Dr, Bethesda, MD 20892 USA. NR 59 TC 19 Z9 19 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1998 VL 30 IS 1 BP 71 EP 78 DI 10.1002/(SICI)1098-2396(199809)30:1<71::AID-SYN9>3.0.CO;2-H PG 8 WC Neurosciences SC Neurosciences & Neurology GA 104NW UT WOS:000075021500009 PM 9704883 ER PT J AU Rea, WP Rothman, RB Shippenberg, TS AF Rea, WP Rothman, RB Shippenberg, TS TI Evaluation of the conditioned reinforcing effects of phentermine and fenfluramine in the rat: Concordance with clinical studies SO SYNAPSE LA English DT Article DE conditioned place preference paradigm; psychostimulants; conditioned reward ID DISCRIMINATIVE STIMULUS; AMPHETAMINE; DOPAMINE; BEHAVIOR; WITHDRAWAL; COCAINE; OPIOIDS; HUMANS AB An unbiased place-preference conditioning procedure was used to characterize the conditioned reinforcing effects of phentermine (PHEN), fenfluramine (FEN), and their combination (PHEN/FEN) in previously drug-naive rats. Animals exhibited marked preferences for an environment previously associated with the administration of phentermine. The minimum dose producing a significant effect was 3.0 mg/kg. In contrast, FEN produced dose-related. place aversions. In animals which received a subthreshold dose of FEN in combination with a dose of PHEN that produced a conditioned place preference, no preference or aversion for the drug-paired place was seen. Similarly, no significant conditioning in response to administration of PHEN (3.0 mg/kg) and FEN (3.0 mg/kg) was seen. The failure of PHEN/FEN to produce conditioned reinforcing effects is in line with recent clinical studies, and suggests that PHEN/FEN and drug combinations sharing the same neurochemical mechanisms of action will have low potential for abuse. Synapse 30:107-111, 1998, (C) 1998 Wiley-Liss, Inc.dagger C1 NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Div Intramural Res,NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov NR 30 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD SEP PY 1998 VL 30 IS 1 BP 107 EP 111 DI 10.1002/(SICI)1098-2396(199809)30:1<107::AID-SYN13>3.0.CO;2-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 104NW UT WOS:000075021500013 PM 9704887 ER PT J AU Cheatham, TE Brooks, BR AF Cheatham, TE Brooks, BR TI Recent advances in molecular dynamics simulation towards the realistic representation of biomolecules in solution SO THEORETICAL CHEMISTRY ACCOUNTS LA English DT Review DE molecular dynamics; biomolecular simulation ID PARTICLE-MESH-EWALD; FAST MULTIPOLE METHOD; CALCULATING ELECTROSTATIC INTERACTIONS; PERIODIC BOUNDARY-CONDITIONS; FINITE-SIZE CORRECTIONS; B-DNA TRANSITION; FORCE-FIELD; COMPUTER-SIMULATION; A-DNA; AQUEOUS-SOLUTION AB Coupled advances in empirical force fields and classical molecular dynamics simulation methodologies, combined with the availability of faster computers, has lead to significant progress towards accurately representing the structure and dynamics of biomolecular systems, such as proteins, nucleic acids, and lipids in their native environments. Thanks to these advances, simulation results are moving beyond merely evaluating force fields, displaying expected structural fluctuations, or demonstrating low root-mean-squared deviations from experimental structures and now provide believable structural insight into a variety of processes such as the stabilization of A-DNA in mixed water and ethanol solution or reversible beta-peptide folding in methanol. The purpose of this overview is to take stock of these recent advances in biomolecular simulation and point out some common deficiencies exposed in longer simulations. The most significant methodological advances relate to the development of fast methods to properly treat long-range electrostatic interactions, and in this regard the fast Ewald methods are becoming the de facto standard. C1 NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Cheatham, TE (reprint author), NHLBI, Biophys Chem Lab, 12A-2041,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 130 TC 64 Z9 65 U1 0 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1432-881X J9 THEOR CHEM ACC JI Theor. Chem. Acc. PD SEP PY 1998 VL 99 IS 5 BP 279 EP 288 DI 10.1007/s002140050337 PG 10 WC Chemistry, Physical SC Chemistry GA 125RC UT WOS:000076250000001 ER PT J AU Cooper, DS Specker, B Ho, M Sperling, M Ladenson, PW Ross, DS Ain, KB Bigos, ST Brierley, JD Haugen, BR Klein, I Robbins, J Sherman, SI Taylor, T Maxon, HR AF Cooper, DS Specker, B Ho, M Sperling, M Ladenson, PW Ross, DS Ain, KB Bigos, ST Brierley, JD Haugen, BR Klein, I Robbins, J Sherman, SI Taylor, T Maxon, HR TI Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: Results from the National Thyroid Cancer Treatment Cooperative Registry SO THYROID LA English DT Article ID MEDICAL THERAPY; LEVOTHYROXINE AB The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for ail patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. S Dakota State Univ, Ethel Austin Program Nutr, Brookings, SD 57007 USA. Univ Cincinnati, Med Ctr, Dept Pediat, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. Johns Hopkins Univ, Sch Med, Div Endocrinol, Baltimore, MD USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Univ Kentucky, Med Ctr, Div Endocrinol, Lexington, KY USA. Maine Med Ctr, Div Endocrinol, Portland, ME 04102 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO USA. N Shore Univ Hosp, Div Endocrinol, Manhasset, NY USA. Cornell Univ, Coll Med, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Div Endocrinol, Houston, TX 77030 USA. Bayer Corp, W Haven, CT USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA. RP Cooper, DS (reprint author), Sinai Hosp, Div Endocrinol, 2401 W Belvedere Ave, Baltimore, MD 21215 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 12 TC 140 Z9 153 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 1998 VL 8 IS 9 BP 737 EP 744 DI 10.1089/thy.1998.8.737 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 124UC UT WOS:000076199600001 PM 9777742 ER PT J AU Delfino, L Morabito, A Longo, A Ferrara, GB AF Delfino, L Morabito, A Longo, A Ferrara, GB TI HLA-C high resolution typing: analysis of exons 2 and 3 by sequence based typing and detection of polymorphisms in exons 1-5 by sequence specific primers SO TISSUE ANTIGENS LA English DT Article DE HLA-C; PCR-SBT; PCR-SSP; serological typing ID BONE-MARROW TRANSPLANTATION; DONOR-RECIPIENT PAIRS; LYMPHOCYTE-T CLONE; ALLELES; IDENTIFICATION; ANTIGENS; CELLS; RECOGNITION; ASSOCIATION; REJECTION AB HLA-C high resolution sequence based typing developed in this study involves a unique DNA amplification encompassing exon 1 to intron 3 and four fluorescent sequencing reactions covering exon 2 and 3. Both dye primer and dye terminator sequencing techniques were performed and results compared. This approach allowed the identification of all of the 50 HLA-C allelic variants so far described, except for two allele pairs that are distinguished by non-coding nucleotide changes (Cw*12021=12022, Cw*15051 = 15052) and three allele pairs (Cw*0701 = 0706, Cw*1701 = 1702 and Cw*1801 = 1802) that share the same nucleotide sequence in exon 2 and 3. For complete subtyping of these allelic variants, an amplification based on sequence specific primers (PCR-SSP) was used. No ambiguous heterozygous combinations of alleles were detected in our panel so far. HLA-C typing data obtained by this method were compared with data from serological and low resolution PCR-SSP typing, which had been performed previously on the samples sequenced. C1 IST, Natl Canc Inst, Adv Biotechnol Ctr, Genoa, Italy. RP Ferrara, GB (reprint author), Adv Biotechnol Ctr, Immunogenet Lab, Lgo R Benzi 10, I-16132 Genoa, Italy. EM ferrara@sirlo.cba.unige.it NR 44 TC 21 Z9 22 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD SEP PY 1998 VL 52 IS 3 BP 251 EP 259 DI 10.1111/j.1399-0039.1998.tb03040.x PG 9 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 124AJ UT WOS:000076157900008 PM 9802605 ER PT J AU Hailey, JR Haseman, JK Bucher, JR Radovsky, AE Malarkey, DE Miller, RT Nyska, A Maronpot, RR AF Hailey, JR Haseman, JK Bucher, JR Radovsky, AE Malarkey, DE Miller, RT Nyska, A Maronpot, RR TI Impact of Helicobacter hepaticus infection in B6C3F(1) mice from twelve national toxicology program two-year carcinogenesis studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver neoplasia; mice; hemangiosarcoma; cell proliferation; H-ras; hepatitis ID CHRONIC ACTIVE HEPATITIS; LIVER-TUMORS; GASTRIC-CARCINOMA; PYLORI INFECTION; RAS MUTATIONS; A/JCR MICE; F344 RATS; SP-NOV; IDENTIFICATION; PCR AB Male and female B6C3F(1) mice from 12 National Toxicology Program (NTP) 2-yr carcinogenesis studies were found to be infected with Helicobacter hepaticus. Many of the male mice from 9 of these studies had an associated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis and hepatocellular neoplasms in the A/JCr male mouse. We attempted to determine if the data from the Helicobacter-affected NTP B6C3F(1) mouse studies were compromised and unsuitable for cancer hazard identification. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F(1) mice were increased in affected studies as compared with control males from unaffected studies. The increased incidence of hepatocellular neoplasms was observed in those males exhibiting H. hepaticus-associated hepatitis. Other observations further differentiated control male mice from affected and unaffected studies. H-ras codon 61 CAA to AAA mutations were less common in liver neoplasms from males from affected studies as compared with historical and study controls. Tn addition, increases in cell proliferation rates and apoptosis were observed in the livers of male mice with H. hepaticus-associated hepatitis. These data support the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in the pathogenesis. Therefore, interpretation of carcinogenic effects in the liver of B6C3F(1) mice may be confounded if there is H. hepaticus-associated hepatitis. C1 NIEHS, Lab Expt Pathol, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Hailey, JR (reprint author), NIEHS, Lab Expt Pathol, Natl Toxicol Program, POB 12233,Mail Drop B3-03, Res Triangle Pk, NC 27709 USA. EM hailey@niehs.nih.gov NR 45 TC 69 Z9 72 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1998 VL 26 IS 5 BP 602 EP 611 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 126LR UT WOS:000076295300003 PM 9789946 ER PT J AU Hong, HHL Devereux, TR Roycroft, JH Boorman, GA Sills, RC AF Hong, HHL Devereux, TR Roycroft, JH Boorman, GA Sills, RC TI Frequency of ras mutations in liver neoplasms from B6C3F(1) mice exposed to tetrafluoroethylene for two years SO TOXICOLOGIC PATHOLOGY LA English DT Article DE proto-oncogene; tetrachloroethylene; inhalation; Teflon; hepatocarcinogenicity; hepatocellular; malignant ID INDUCED LUNG-TUMORS; PROTOONCOGENE ACTIVATION; MOUSE; CARCINOGENESIS; POLYMERASE; ONCOGENE; DNA AB Tetrafluoroethylene (TFE) was evaluated for carcinogenicity in inhalation studies because of its high use in the production of Teflon. There was clear evidence of hepatocarcinogenic activity in B6C3F(1) mice after 2 yr of TFE exposure. The present study was designed to characterize the mutation profiles of H- and K-ras oncogenes in liver neoplasms in mice after exposure to 0, 312, 625, or 1,250 ppm TFE. ras mutations were identified by restriction fragment length polymorphism, single-stranded conformation polymorphism analysis, and direct sequencing of polymerase chain reaction amplified-DNA isolated from frozen or paraffin-embedded liver neoplasms. A low frequency (15%, 9/59) of H-ras codon 61 mutations was detected in hepatocellular neoplasms when compared with the higher frequency (59% of this study and 56% of historical data) in spontaneously occurring liver neoplasms. There was no difference in the mutation frequency or spectrum among exposure groups or between benign and malignant hepatocellular neoplasms. K-ras mutations at codons 12, 13, and 61 and H-ras mutations at codon 117 were not detected in hepatocellular neoplasms. These data suggest that TFE-induced hepatocellular neoplasms are developed by pathways that are mostly independent of ras mutations. The ras mutation frequency and spectrum were similar to those of the structurally related chemical tetrachloroethylene. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Hong, HHL (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 28 TC 11 Z9 11 U1 0 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1998 VL 26 IS 5 BP 646 EP 650 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 126LR UT WOS:000076295300008 PM 9789951 ER PT J AU Peano, S Conz, A Carbonatto, M Goldstein, J Nyska, A AF Peano, S Conz, A Carbonatto, M Goldstein, J Nyska, A TI Atriocaval mesothelioma in a male Sprague-Dawley rat SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neoplasm; heart tumor; histology; immunohistochemistry; electron microscopy ID ATRIOVENTRICULAR NODE AB The histological, immunohistochemical, and electron microscopic characteristics of a spontaneous case of atriocaval mesothelioma are described in a 102-wk-old male Sprague-Dawley rat. The immunohistochemical characteristics of the tumor are compared with those of a pericardial mesothelioma in a female Sprague-Dawley rat. C1 Ist Ric Biomed Antoine Marxer SPA, RBM, I-10015 Ivrea, Italy. RP Nyska, A (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1998 VL 26 IS 5 BP 695 EP 698 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 126LR UT WOS:000076295300016 PM 9789959 ER PT J AU Chan, PC Herbert, RA Roycroft, JH Haseman, JK Grumbein, SL Miller, RA Chou, BJ AF Chan, PC Herbert, RA Roycroft, JH Haseman, JK Grumbein, SL Miller, RA Chou, BJ TI Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice SO TOXICOLOGICAL SCIENCES LA English DT Article AB Inhalation studies of molybdenum trioxide (MoO3) were conducted because of its wide use in industry, human exposure, and lack of data on carcinogenicity. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MoO3 by inhalation at 0, 10, 30, or 100 mg/m(3), 6 h/day, 5 days/week, for 2 years. In both rats and mice, survival and mean body weights of exposed groups of males and females were similar to those of their respective controls. There were significant exposure-dependent increases in blood molybdenum concentration in exposed rats and mice. There were no toxicological differences in bone density or curvature between exposed animals and their respective controls. In rats, dose-dependent increases in incidence of hyaline degeneration in the nasal olfactory epithelium and squamous metaplasia of the epithelium lining the base of the epiglottis were observed. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) was marginally increased in males but not in females compared with controls. In mice, the incidences of squamous metaplasia of the epithelium lining the base of the epiglottis, hyperplasia of the laryngeal epithelium, and metaplasia of the alveolar epithelium were significantly increased in all exposed males and females compared with controls. The incidence of alveolar/bronchiolar adenoma or carcinoma (combined) in exposed groups of males and females was significantly greater than that in the control groups. (C) 1998 Society of Toxicology. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Pacific NW Lab, Richland, WA 99352 USA. RP Chan, PC (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 19 TC 11 Z9 12 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 1998 VL 45 IS 1 BP 58 EP 65 DI 10.1093/toxsci/45.1.58 PG 8 WC Toxicology SC Toxicology GA 138VX UT WOS:000076995000007 PM 9848111 ER PT J AU Rao, GN Lindamood, C Heath, JE Farnell, DR Giles, HD AF Rao, GN Lindamood, C Heath, JE Farnell, DR Giles, HD TI Subchronic toxicity of human immunodeficiency virus and tuberculosis combination therapies in B6C3F1 mice SO TOXICOLOGICAL SCIENCES LA English DT Article ID RIFAMPIN; AGENTS AB Combination therapy with anti-HIV drugs and opportunistic infection drugs is a common practice in treatment of AIDS patients. Although toxic effects of most individual therapies are known, the toxic potential of most combination therapies has not been established. To understand the toxic consequences of combination therapies, the commonly used anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) and tuberculosis infection therapies pyrazinamide, isoniazid, and rifampicin were evaluated by 13-week gavage studies in B6C3F1 mice, either alone or AZT in combination with one of the antituberculosis drugs. The doses include AZT 100, 200, and 400; pyrazinamide 1000 and 1500; isoniazid 50, 100, and 150; and rifampicin 100, 200, and 400 mg/kg/day, AZT alone caused hematopoietic toxicity with dose-related bone marrow suppression, macrocytic anemia, and thrombocytosis. Pyrazinamide or isoniazid alone at the doses tested did not cause significant toxicity. Rifampicin alone caused hematopoietic toxicity and possibly mild hepatic toxicity. Pyrazinamide below 10 times the therapeutic dose when given with AZT did not increase the hematological toxicity of AZT, Isoniazid markedly increased the hematological toxicity of AZT and contributed to mortality at 3 to 4 times the therapeutic dose combinations. Administration of rifampicin with AZT at the calculated therapeutic doses resulted in toxicity of far greater magnitude than that caused by AZT or rifampicin alone. Combination treatment with AZT and rifampicin caused severe anemia with mortality at 2 to 4 times the therapeutic dose combinations. However, AZT did not enhance the hepatotoxicity of rifampicin. Increased hematopoietic toxicity of AZT when given in combination with the above antituberculosis drugs may be due to changes in the metabolism of AZT, Results of these studies indicate that toxicological effects of combination therapies could be considerably more severe than and different from the toxicity of individual therapies, C1 NIEHS, Res Triangle Pk, NC 27709 USA. So Res Inst, Birmingham, AL 35255 USA. RP Rao, GN (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 1998 VL 45 IS 1 BP 113 EP 127 DI 10.1006/toxs.1998.2488 PG 15 WC Toxicology SC Toxicology GA 138VX UT WOS:000076995000014 PM 9848118 ER PT J AU Zaher, H Buters, JTM Ward, JM Bruno, MK Lucas, AM Stern, ST Cohen, SD Gonzalez, FJ AF Zaher, H Buters, JTM Ward, JM Bruno, MK Lucas, AM Stern, ST Cohen, SD Gonzalez, FJ TI Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID SELECTIVE PROTEIN ARYLATION; BINDING LIVER PROTEINS; INDUCED HEPATOTOXICITY; COVALENT BINDING; REACTIVE METABOLITES; HEPATIC NECROSIS; PARACETAMOL; MOUSE; ACTIVATION; RATS AB Acetaminophen (APAP) hepatotoxicity is due to its biotransformation to a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI), that is capable of binding to cellular macromolecules. At least two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated in this reaction in mice. To test the combined roles of CYP1A2 and CYP2E1 in an intact animal model, a double-null mouse line lacking functional expression of CYP1A2 and CYP2E1 was produced by cross-breeding Cypla2-/- mice with Cyp2e1-/- mice. Animals deficient in the expression of both P450s developed normally and exhibited no obvious phenotypic abnormalities. Comparison of the dose-response to APAP (200-1200 mg/kg) indicated that double-null animals were highly resistant to APAP-induced toxicity whereas the wild-type animals were sensitive. Administration of 600 to 800 mg/kg of this drug to male wild-type animals resulted in increased plasma concentrations of liver enzymes (alanine aminotransferase, sorbitol dehydrogenase), lipidosis, hepatic necrosis, and renal tubular necrosis. In contrast, when APAP of equivalent or higher dose was administered to the double-null mice, plasma levels of liver enzymes and liver histopathology were normal. However, administration of 1200 mg of APAP/kg to the double-null mice resulted in infrequent liver lipidosis and mild kidney lesions. Consistent with the protection from hepatotoxicity, the expected depletion of hepatic glutathione (GSH) content was significantly retarded and APAP covalent binding to hepatic cytosolic proteins was not detectable in the double-null mice. Likewise, in vitro activation of APAP by liver microsomes from the double-null mice was approximately one tenth of that in microsomes from wild-type mice. Thus, the protection against APAP toxicity afforded by deletion of both CYP2E1 and CYP1A2 likely reflects greatly diminished production Of the toxic electrophile, NAPQI. (C) 1998 Academic Press. C1 NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Anim Sci Branch, Frederick, MD 21702 USA. Univ Connecticut, Dept Pharmaceut Sci, Toxicol Program, Storrs, CT 06269 USA. RP Zaher, H (reprint author), NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Buters, Jeroen/G-5070-2011 FU NCEH CDC HHS [NIEHS/07163] NR 39 TC 183 Z9 185 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1998 VL 152 IS 1 BP 193 EP 199 DI 10.1006/taap.1998.8501 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 135GH UT WOS:000076792300022 PM 9772215 ER PT J AU Bloch, P Simonsen, PE Weiss, N Nutman, TB AF Bloch, P Simonsen, PE Weiss, N Nutman, TB TI The significance of guinea worm infection in the immunological diagnosis of onchocerciasis and bancroftian filariasis SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE dracunculiasis; guinea worm infection; Dracunculus medinensis; onchocerciasis; Onchocerca volvulus; filariasis; Wuchereria bancrofti; immunodiagnosis ID OG4C3 CIRCULATING ANTIGEN; DRACUNCULUS-MEDINENSIS; VOLVULUS; ELISA; MARKER; ASSAY AB Infections with Dracunculus medinensis frequently occur in the same geographical area as infections with Onchocerca volvulus and Wuchereria bancrofti. This study analysed the significance of D. medinensis infections for the specificity and sensitivity of available tests for antibody-based diagnosis of onchocerciasis (using individual recombinant clones OV-10, OV-11 and OV-16, and the OV-7/OV-10/OV-16 tri-cocktail, in an enzyme-linked immunosorbent assay) and for circulating antigen-based diagnosis of bancroftian filariasis (using the TroBio(TM) and the ICT(TM) card tests). Some immunological cross-reactivity was observed with all tests. When using individual recombinant O. volvulus antigens, the highest assay indices were obtained for clone OV-10, and the lowest: for clone OV-16. Testing the serum responses against the tri-cocktail of recombinant antigens did not notably improve the assay indices. Two of 40 serum samples from individuals with patent dracunculiasis gave a false positive response in the ICT(TM) test and one of these was also positive in the TropBio(TM) test. Possible implications of applying these diagnostic assays in areas endemic for dracunculiasis are discussed. C1 Danish Bilharziasis Lab, DK-2920 Charlottenlund, Denmark. Swiss Trop Inst, CH-4002 Basel, Switzerland. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Bloch, P (reprint author), Danish Bilharziasis Lab, Jaegersborg Alle 1, DK-2920 Charlottenlund, Denmark. NR 22 TC 9 Z9 9 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD SEP-OCT PY 1998 VL 92 IS 5 BP 518 EP 521 DI 10.1016/S0035-9203(98)90899-9 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 133LZ UT WOS:000076689200014 PM 9861367 ER PT J AU Brown, P Rohwer, RG Dunstan, BC MacAuley, C Gajdusek, DC Drohan, WN AF Brown, P Rohwer, RG Dunstan, BC MacAuley, C Gajdusek, DC Drohan, WN TI The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; KURU PLAQUES; CONTAMINATION; TRANSFUSION; SCRAPIE; VIRUS AB BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt-Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been "spiked" with trypsinized cells from a scrapie-infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse-adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals. RESULTS: Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin-K-dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V. CONCLUSION: Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but, minimal risk of acquiring Creutzfeldt-Jakob disease from the administration of human plasma protein concentrates. C1 NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Mol Neurvirol Lab, Med Res Serv, Baltimore, MD USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. RP Brown, P (reprint author), NINDS, CNS Studies Lab, NIH, Bldg 36,Room 5B20, Bethesda, MD 20892 USA. NR 21 TC 251 Z9 253 U1 2 U2 6 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1998 VL 38 IS 9 BP 810 EP 816 DI 10.1046/j.1537-2995.1998.38998408999.x PG 7 WC Hematology SC Hematology GA 117UW UT WOS:000075801700003 PM 9738619 ER PT J AU Dodson, G Wlodawer, A AF Dodson, G Wlodawer, A TI Catalytic triads and their relatives SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID HUMAN CYTOMEGALOVIRUS PROTEASE; REFINED CRYSTAL-STRUCTURE; BETA-LACTAMASE; SERINE-PROTEASE; ACTIVE-SITE; FOLD; RESOLUTION; MECHANISM; LIPASE; ASPARAGINASE AB Interactions among the residues in the serine protease Asp-His-Ser catalytic triad, in the special environment of the enzyme-substrate complex, activate the nucleophilic potential of the seryl Oy. In the subtilisin and trypsin families, the composition and arrangement of the catalytic triad do not vary significantly. However, the mechanisms of action of many other hydrolytic enzymes, which target a wide range of substrates, involve nucleophilic attack by a serine (or threonine) residue. Review of these enzymes shows that the acid-base-ser/thr pattern of catalytic residues is generally conserved, although the individual acids and bases can vary. The variations in sequence and organization illustrate the adaptability shown by proteins in generating catalytic stereochemistry on different main-chain frameworks. C1 Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England. Natl Inst Med Res, London NW7 1AA, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Dodson, G (reprint author), Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England. NR 41 TC 370 Z9 379 U1 6 U2 57 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD SEP PY 1998 VL 23 IS 9 BP 347 EP 352 DI 10.1016/S0968-0004(98)01254-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126AC UT WOS:000076269400008 PM 9787641 ER PT J AU Shisler, JL Gooding, LR AF Shisler, JL Gooding, LR TI Adenoviral inhibitors of the apoptotic cascade SO TRENDS IN MICROBIOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; E3 REGION; PROTEIN; LYSIS; CD95 C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. RP Shisler, JL (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-58736] NR 13 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 1998 VL 6 IS 9 BP 337 EP 339 DI 10.1016/S0966-842X(98)01342-0 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 119PR UT WOS:000075905800001 PM 9778723 ER PT J AU Taylor, WF Chen, S Barshtein, G Hyde, DE Yedgar, S AF Taylor, WF Chen, S Barshtein, G Hyde, DE Yedgar, S TI Enhanced aggregability of human red blood cells by diving SO UNDERSEA & HYPERBARIC MEDICINE LA English DT Article DE hyperbaria; erythrocyte; peripheral circulation ID COMPUTERIZED IMAGE-ANALYSIS; HYDROSTATIC-PRESSURE; AGGREGATION; TRANSPORT; FLOW AB In vitro studies have shown that mild pressure increases red blood cell (RBC) aggregation. Enhanced RBC aggregation in pathologic states can drive the circulation into stasis. This investigation examined the effects of pressure on RBC aggregation in human volunteers. The hypothesis tested is that RBC aggregation is increased during hyperbaric exposure. Eleven subjects participated in dives to 300 feet of seawater (fsw) in a man-rated chamber complex. Blood samples were taken at the surface, at 66 fsw, and at 300 fsw. Data were analyzed with a repeated measures one-way analysis of variance for a complete randomized design. Statistical significance was achieved at P < 0.05. Data are expressed as mean +/- SEM. The median aggregate size (number of RBC/aggregate) of RBCs was significantly increased at depth. At a shear stress of 0.1 dyne/cm(2), median aggregate size was 12.0 +/- 2.1, 33.0 +/- 7.3, and 48.8 +/- 10.8 at the surface, at 66 fsw, and at 300 fsw, respectively. These results show that mild pressure increases RBC aggregation in the human circulation. C1 NIH, Natl Ctr Res Resources, Rockledge Ctr 1, Bethesda, MD 20892 USA. USN, Med Res Inst, Diving & Environm Physiol Dept, Bethesda, MD 20889 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. RP Taylor, WF (reprint author), NIH, Natl Ctr Res Resources, Rockledge Ctr 1, Ste 6030,6705 Rockledge Dr,MSC 7965, Bethesda, MD 20892 USA. NR 16 TC 7 Z9 7 U1 0 U2 1 PU UNDERSEA & HYPERBARIC MEDICAL SOC INC PI KENSINGTON PA 10531 METROPOLITAN AVE, KENSINGTON, MD 20895 USA SN 1066-2936 J9 UNDERSEA HYPERBAR M JI Undersea Hyperb. Med. PD FAL PY 1998 VL 25 IS 3 BP 167 EP 170 PG 4 WC Marine & Freshwater Biology; Medicine, Research & Experimental SC Marine & Freshwater Biology; Research & Experimental Medicine GA 125HJ UT WOS:000076231100004 PM 9789336 ER PT J AU Poulsen, DJ Robertson, SJ Favara, CA Portis, JL Chesebro, BW AF Poulsen, DJ Robertson, SJ Favara, CA Portis, JL Chesebro, BW TI Mapping of a neurovirulence determinant within the envelope protein of a polytropic murine retrovirus: Induction of central nervous system disease by low levels of virus SO VIROLOGY LA English DT Article ID LEUKEMIA-VIRUS; ANTIGEN RETRIEVAL; SECONDARY STRUCTURE; MICROGLIAL CELLS; INFECTION; BRAIN; IMMUNODEFICIENCY; NEURONS; GP120; ASSAY AB Murine leukemia virus (MuLV) clone Fr98 is a recombinant polytropic virus that causes neurological disease characterized by ataxia in susceptible mouse strains. The envelope gene of Fr98 has been previously shown to encode at least two separate neurovirulence determinants. In tie present study, the determinant encoded within the EcoRI/AvrII fragment of the envelope gene was further defined. In these experiments, neurovirulence was associated with a change from a serine to an arginine at position 195 and a glycine to an alanine at position 198 within the envelope protein. Neurovirulent and nonvirulent virus clones, which differed only at these two amino acid residues, showed no difference in the type or location of cells infected. Furthermore, equivalent levels of viral p30 capsid protein were detected in the brains of mice infected with either the neurovirulent or nonvirulent virus clones. These results were consistent with the interpretation that the envelope protein of the neurovirulent virus differed from that of the nonvirulent virus by having a greater toxic effect on central nervous system function. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Chesebro, BW (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 41 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1998 VL 248 IS 2 BP 199 EP 207 DI 10.1006/viro.1998.9258 PG 9 WC Virology SC Virology GA 117CC UT WOS:000075761800004 PM 9721229 ER PT J AU Schaefer-Klein, J Givol, I Barsov, EV Whitcomb, JM VanBrocklin, M Foster, DN Federspiel, MJ Hughes, SH AF Schaefer-Klein, J Givol, I Barsov, EV Whitcomb, JM VanBrocklin, M Foster, DN Federspiel, MJ Hughes, SH TI The EV-O-derived cell line DF-1 supports the efficient replication of avian leukosis-sarcoma viruses and vectors SO VIROLOGY LA English DT Article ID RETROVIRAL VECTORS; EXPRESSION; EMBRYO AB The lack of a well-behaved permanent, adherent, nontransformed chicken cell line has made some experiments with avian leukosis-sarcoma viruses (ASLV) and vectors considerably more difficult. The EV-O-derived line, DF-I, supports the efficient replication of subgroups (A), (B), and (C) ASLV, as well as amphotrophic murine leukemia virus and an ASLV-derived vector that has its env gene derived from the env gene from an amphotrophic murine leukemia virus. The cell line responds appropriately to the expression of a transforming oncogene (v-myc) to a growth suppressor gene [p21(wail)] and can be sorted (using FAGS) ii infected by an ASLV vector that expresses GFP. (C) 1998 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Retroviral Replicat & Vector Design Sect, ABL Basic Res Program, Frederick, MD 21702 USA. Mayo Clin & Mayo Fdn, Program Mol Med, Rochester, MN 55905 USA. ViroLog Inc, S San Francisco, CA 94080 USA. Univ Minnesota, Dept Anim Sci, St Paul, MN 55108 USA. RP Hughes, SH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Retroviral Replicat & Vector Design Sect, ABL Basic Res Program, POB B,Bldg 539, Frederick, MD 21702 USA. EM hughes@bcuforf.giv NR 13 TC 139 Z9 143 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1998 VL 248 IS 2 BP 305 EP 311 DI 10.1006/viro.1998.9291 PG 7 WC Virology SC Virology GA 117CC UT WOS:000075761800014 PM 9721239 ER PT J AU De Weerd, P Desimone, R Ungerleider, LG AF De Weerd, P Desimone, R Ungerleider, LG TI Perceptual filling-in: a parametric study SO VISION RESEARCH LA English DT Article DE psychophysics; filling-in; boundary; adaptation ID PRIMARY VISUAL-CORTEX; RECEPTIVE-FIELD; BRIGHTNESS PERCEPTION; HORIZONTAL CONNECTIONS; 3-DIMENSIONAL FORM; CORTICAL DYNAMICS; MACAQUE MONKEY; HUMAN VISION; NEURONS; AREAS AB We studied perceptual filling-in during maintained peripheral viewing of a uniform gray or red figure presented on a large textured background. Changes in the figure's size, shape, and eccentricity caused variations in the time required for filling-in that could be predicted from the size of its cortical projection within early visual areas. The data suggest that the time which elapsed before the figure was filled-in by its background reflects the time required for figure-ground segregation to fail, rather than a slow spread of the background across the figure. Our findings reveal interactions between surface segregation and filling-in which may be at the basis of normal surface perception. Published by Elsevier Science Ltd. All rights reserved. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP De Weerd, P (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 49,Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA. EM pdw@ln.nimh.nih.gov NR 48 TC 81 Z9 82 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD SEP PY 1998 VL 38 IS 18 BP 2721 EP 2734 DI 10.1016/S0042-6989(97)00432-X PG 14 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 100NH UT WOS:000074821900003 PM 9775321 ER PT J AU Stewart, RL Burgdorfer, W Needham, GR AF Stewart, RL Burgdorfer, W Needham, GR TI Evaluation of three commercial tick removal tools SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Article DE tick removal; Amblyomma americanum; Dermacentor variabilis; Lyme disease ID BORRELIA-BURGDORFERI; TRANSMISSION; DURATION; ATTACHMENT; NYMPHS AB Objective.-To evaluate three commercially available tick removal tools against medium-tipped nontissue tweezers. Methods.-We evaluated three commercially available tick removal tools against medium-tipped tweezers. Three inexperienced users randomly removed attached American dog ticks (Dermacentor variabilis Say) and lone star ticks (Amblyomma americanum L,) from laboratory rabbits in a university animal facility using all tools during one removal session. Results.-Tick damage occurring from removal and quantity of attachment cement were compared. No tool removed nymphs without damage and all tools removed adults of both species successfully. American dog ticks proved easier to remove than lone star ticks, whose mouthparts often remained in the skin. Conclusions.-Nymphal ticks were consistently removed more successfully with commercial tools when compared with tweezers but with more difficulty than adults were removed. The commercial tick removal tools tested are functional for removal of nymphs and adults and should be considered as viable alternatives to medium-tipped tweezers. C1 Ohio State Univ, Dept Entomol, Acarol Lab, Columbus, OH 43210 USA. Natl Inst Hlth, Rocky Mt Lab, Hamilton, MT 59840 USA. RP Stewart, RL (reprint author), Ohio State Univ, Dept Entomol, Acarol Lab, 484 W 12th Ave, Columbus, OH 43210 USA. NR 24 TC 19 Z9 20 U1 1 U2 5 PU WILDERNESS MEDICAL SOC PI COLORADO SPRINGS PA 3595 E FOUNTAIN BLVD, STE A1, COLORADO SPRINGS, CO 80910 USA SN 1080-6032 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD FAL PY 1998 VL 9 IS 3 BP 137 EP 142 DI 10.1580/1080-6032(1998)009[0137:EOTCTR]2.3.CO;2 PG 6 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA 192XK UT WOS:000080104900002 PM 11990185 ER PT J AU Desimone, R AF Desimone, R TI Visual attention mediated by biased competition in extrastriate visual cortex SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article DE attention; vision; primates; inferior temporal cortex; V4 ID INFERIOR TEMPORAL CORTEX; POSTERIOR PARIETAL CORTEX; SHORT-TERM-MEMORY; DORSOLATERAL PREFRONTAL CORTEX; DELAYED-RESPONSE PERFORMANCE; SACCADE TARGET SELECTION; MONKEY PRESTRIATE CORTEX; FRONTAL EYE FIELD; RHESUS-MONKEY; NEURAL MECHANISMS AB According to conventional neurobiological accounts of visual attention, attention serves to enhance extrastriate neuronal responses to a stimulus at one spatial location in the visual field. However, recent results from recordings in extrastriate cortex of monkeys suggest that any enhancing effect of attention is best understood in the context of competitive interactions among neurons representing all of the stimuli present in the visual field. These interactions can be biased in favour of behaviourally relevant stimuli as a result of many different processes, both spatial and non-spatial, and both bottom-up and top-down. The resolution of this competition results in the suppression of the neuronal representations of behaviourally irrelevant stimuli in extrastriate cortex. A main source of top-down influence may derive from neuronal systems underlying working memory. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Desimone, R (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM bobd@ln.nimh.nih.gov NR 100 TC 383 Z9 394 U1 0 U2 14 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD AUG 29 PY 1998 VL 353 IS 1373 BP 1245 EP 1255 DI 10.1098/rstb.1998.0280 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 115KW UT WOS:000075664500002 PM 9770219 ER PT J AU Chen, EY Li, CCH AF Chen, EY Li, CCH TI Association of Cdk2/cyclin E and NF-kappa B complexes at G1/S phase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE NF-kappa B; Cdk2; cyclin E; c-Rel ID CYCLIN-DEPENDENT KINASES; LYMPHOMA CELL-LINES; C-REL; SIGNAL-TRANSDUCTION; DNA-BINDING; V-REL; PROTEINS; TRANSITION; ACTIVATION; FAMILY AB NF-kappa B/Rel family plays a pivotal role in a wide variety of cellular functions including growth, development, apoptosis and stress responses. Recent studies indicated that NF-kappa B is also involved in the cell cycle regulation, and high expression of c-Rel results in a cell cycle arrest at the G1/S-phase transition (Bash, J., Zong, W.-X., and Gelinas, C. (1997) Mel. Cell. Biol. 17, 6526-6536). Here we report the detection of Cdk2, a critical kinase responsible for the G1/S-phase transition, in immune complexes precipitated by the NF-kappa B antisera. Cdk2 and NF-kappa B association was detected by co-precipitation in the nuclear lysates of the G1/S-phase cells, and was found in cultured cell lines and in T cells purified from human peripheral blood. Using an affinity column containing the C-terminal peptide of human c-Rel, we isolated cyclin E, the regulatory subunit of the Cdk2 complex, as a c-Rel-binding protein. These findings support and provide physical basis for the involvement of NF-kappa B in the G1/S-phase cell cycle control, and suggest an important role played by the C-terminal sequence of c-Rel. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Li, CCH (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-56000] NR 35 TC 28 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 28 PY 1998 VL 249 IS 3 BP 728 EP 734 DI 10.1006/bbrc.1998.9224 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116XV UT WOS:000075751100030 PM 9731206 ER PT J AU Szallasi, A Biro, T Modarres, S Garlaschelli, L Petersen, M Klusch, A Vidari, G Jonassohn, M De Rosa, S Sterner, O Blumberg, PM Kraus, JE AF Szallasi, A Biro, T Modarres, S Garlaschelli, L Petersen, M Klusch, A Vidari, G Jonassohn, M De Rosa, S Sterner, O Blumberg, PM Kraus, JE TI Dialdehyde sesquiterpenes and other terpenoids as vanilloids SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE vanilloid receptor; resiniferatoxin; capsaicin; dialdehyde, unsaturated ID ACTIVE NATURAL COMPOUNDS; ROOT GANGLION MEMBRANES; FUNGAL METABOLITES; STEREOSPECIFIC TRANSFORMATION; CAPSAICIN RECEPTOR; SENSORY NEURONS; UVIDIN-A; RAT; RESINIFERATOXIN; BINDING AB Selected naturally occurring unsaturated dialdehyde sesquiterpenes and related bioactive terpenoids were assayed for vanilloid-like activity. Out of the 25 compounds tested, eight inhibited completely the specific binding of [H-3]resiniferatoxin by rat spinal cord membranes: binding affinities ranged from 0.6 mu M for cinnamodial to 19.0 mu M for hebelomic acid F. These values were comparable to the binding affinity of capsaicin (2.7 mu M). With the exception of four ligands, compounds that inhibited resiniferatoxin binding to rat spinal cord membranes were also pungent on the human tongue where they showed cross-tachyphylaxis with capsaicin. As expected from their reactive nature, these compounds possess additional sites of action, as reflected in the complex behavior of the stimulation of calcium influx by cinnamodial and cinnamosmolide at high concentrations. This observation might explain the unexpectedly weak membrane depolarization by cinnamodial compared to capsaicin. We conclude that a range of sesquiterpene dialdehydes and related terpenoids, both pungent and non-pungent, may function as vanilloids. These compounds may represent a new chemical lead for the development of vanilloid drugs, structurally unrelated to either capsaicin or resiniferatoxin. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Mol Mechanisms Tumor Promot Sect, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Univ Pavia, Dipartimento Chim Organ, I-27100 Pavia, Italy. Univ Wurzburg, Dept Physiol, D-97070 Wurzburg, Germany. Univ Lund, Dept Organ Chem 2, S-22100 Lund, Sweden. CNR, Ist Chim Mol Interesse Biol, I-80072 Arco Felice, Naples, Italy. RP Szallasi, A (reprint author), NCI, Mol Mechanisms Tumor Promot Sect, 37-3A13 Convent Dr MSC, Bethesda, MD 20892 USA. OI Vidari, Giovanni/0000-0003-4606-2154 NR 45 TC 44 Z9 44 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 28 PY 1998 VL 356 IS 1 BP 81 EP 89 DI 10.1016/S0014-2999(98)00514-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 118JU UT WOS:000075835400011 PM 9761427 ER PT J AU Alexandrov, I Romanova, L Mushinski, F Nordan, R AF Alexandrov, I Romanova, L Mushinski, F Nordan, R TI Sodium butyrate suppresses apoptosis in human Burkitt lymphomas and murine plasmacytomas bearing c-myc translocations SO FEBS LETTERS LA English DT Article DE plasmacytoma; butyrate; apoptosis; c-myc ID CELL-CYCLE; REGULATORY ELEMENTS; CARCINOMA CELLS; WILD-TYPE; EXPRESSION; GENE; FIBROBLASTS; INTERLEUKIN-3; ACTIVATION; MODULATION AB We report that sodium butyrate, a natural product of fiber degradation by colonic bacteria, markedly suppresses c-Myc-mediated apoptosis induced in murine plasmacytomas and human Burkitt lymphomas by growth factor deprivation, but not in cell lines devoid of c-myc translocations. Attenuation of cell death is associated with downregulation of the rearranged c-myc and activation of pRb via its dephosphorylation, We suggest that in vivo sodium butyrate may play an important role in plasmacytomagenesis by supporting the survival of cells,vith c-myc translocations, which otherwise mould be eliminated by the lack of growth factors. (C) 1998 Federation of European Biochemical Societies. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Alexandrov, I (reprint author), Russian Acad Med Sci, Mental Hlth Res Ctr, Lab Cytogenet, Zagorodne Sh 2, Moscow 113152, Russia. NR 29 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 28 PY 1998 VL 434 IS 1-2 BP 209 EP 214 DI 10.1016/S0014-5793(98)00926-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 117RG UT WOS:000075795100041 PM 9738480 ER PT J AU Mills, EM Takeda, K Yu, ZX Ferrans, V Katagiri, Y Jiang, H Lavigne, MC Leto, TL Guroff, G AF Mills, EM Takeda, K Yu, ZX Ferrans, V Katagiri, Y Jiang, H Lavigne, MC Leto, TL Guroff, G TI Nerve growth factor treatment prevents the increase in superoxide produced by epidermal growth factor in PC12 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; SIGNAL-TRANSDUCTION; FACTOR RECEPTORS; RAS; GENERATION; PATHWAYS; RESPOND; KINASE; LIPIDS; LINE AB Stimulation of pheochromocytoma (PC12) cells with the mitogen epidermal growth factor (EGF) produced a rapid and robust accumulation of intracellular reactive oxygen species (ROS), an accumulation which, in other systems, has been shown to be essential for mitogenesis, Brief pretreatment of the cells with nerve growth factor (NGF) suppressed the EGF-mediated ROS increase. EGF failed to produce elevations in ROS in a PC12 variant stably expressing a dominant-negative p2(ras) construct (PC12-N17) or in cells pretreated with the MEK inhibitor PD098059, NGF failed to suppress the increase in ROS in the PC12 variant nnr5, which lacks p140(trk) receptors, The suppression of the increase in ROS by NGF was restored in nnr5 cells stably expressing p140(trk) (nnr5-trk), but NGF failed to prevent the increase in ROS in nnr cells expressing mutant p140(trk) receptors that lack binding sites for Shc and phospholipase C gamma, Among several inhibitors of superoxide-generating enzymes, only the lipoxygenase inhibitor, nordihydroguaiaretic acid reduced EGF-mediated ROS accumulation. The inhibitory action of NGF on ROS production was mimicked by the nitric oxide donor, sodium nitroprusside, and was blocked by an inhibitor of nitric-oxide synthetase, L-nitroarginine methyl ester, These results suggest a novel mechanism for the rapid interruption of mitogenic signaling by the neurotrophin NGF. C1 NICHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Guroff, G (reprint author), NICHD, Growth Factors Sect, NIH, Bldg 49,Rm 5A64, Bethesda, MD 20892 USA. EM gordong@helix.nih.gov NR 25 TC 50 Z9 53 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22165 EP 22168 DI 10.1074/jbc.273.35.22165 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600002 PM 9712826 ER PT J AU Marks-Konczalik, J Chu, SC Moss, J AF Marks-Konczalik, J Chu, SC Moss, J TI Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor kappa B-binding sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; PROTEOLYTIC DEGRADATION; SIGNAL-TRANSDUCTION; MOUSE MACROPHAGES; INTERFERON-GAMMA; P50 SUBUNIT; JUN-D; PROMOTER; FOS; CELLS AB The involvement of AP-1 and NF-kappa B transcription factors in cytokine-mediated induction of human inducible nitric oxide synthase (hiNOS) promoter activity was examined. Luciferase reporter plasmids, containing mutations in AP-1 and NF-kappa B sites, in a hiNOS promoter extending from -8.3 kilobase pairs (kb) to +168, were transiently expressed in A549 cells, and promoter activity was determined after treatment with a cytokine mixture (CM) containing interleukin 1-beta, interferon-gamma, and tumor necrosis factor-alpha. Mutation of the AP-1 heptad located -5301 base pairs upstream decreased gene activation by 90% in a -8.3-kb promoter and a shorter -5.574-kb promoter. Disruption of AP-1 (at -5115) or NF-kappa B (at -115 and -8283) sites reduced promoter activity by 45, 67, and 52%, respectively. Responsiveness to CM was decreased by 85% in constructs mutated in both NF-kappa B sites. By gel retardation analyses, CM increased AP-1- and NF-kappa B binding. Supershift analysis identified Jun D and Fra-2 as components of AP-1 complexes. Each kappa B Site bound different complements of NF-kappa B/Rel family members (downstream site, Rel A/p50; upstream site, Rel A/Rel A). Rel A was maximally, whereas I kappa B-alpha was minimally, expressed in nuclei after 1 h of CM treatment, corresponding with the peak in NF-kappa B inding activity. Thus, AP-1 and NF-kappa B are important cis-elements for induction of hiNOS gene transcription. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Marks-Konczalik, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. EM markrsj@gwgate.nhlbi.nih.gov NR 65 TC 237 Z9 238 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22201 EP 22208 DI 10.1074/jbc.273.35.22201 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600009 PM 9712833 ER PT J AU Yuasa, T Ohno, S Kehrl, JH Kyriakis, JM AF Yuasa, T Ohno, S Kehrl, JH Kyriakis, JM TI Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38 - Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; C-JUN; CELL-DEATH; TERMINAL KINASE; TNF RECEPTOR-1; TRANSDUCTION PATHWAYS; CYTOPLASMIC DOMAIN; FACTOR-ALPHA; EXPRESSION; APOPTOSIS AB Tumor necrosis factor (TNF) elicits a diverse array of inflammatory responses through engagement of its type-1 receptor (TNFR1). Many of these responses require de novo gene expression mediated by the activator protein-1 (AP-1) transcription factor. We investigated the mechanism by which TNFR1 recruits the stress-activated protein kinases (SAPKs) and the p38s, two mitogen-activated protein kinase (MAPK) families that together regulate AP-1. We show that the human SPS1 homologue germinal center kinase (GCK) can interact in vivo with the TNFR1 signal transducer TNFR-associated factor-2 (TRAF2) and with MAPK/ERK kinase kinase 1 (MEKK1), a MAPK kinase kinase (MAPKKK) upstream of the SAPKs, thereby coupling TRAF2 to the SAPKs. Receptor interacting protein (RIP) is a second TNFR1 signal transducer which can bind TRAF2. We show that RIP activates both p38 and SAPK; and that TRAF2 activation of p38 requires RIP. We also demonstrate that the RIP noncatalytic intermediate domain associates in vivo with an endogenous MAPKKK that can activate the p38 pathway in vitro. Thus, TRAF2 initiates SAPK and p38 activation by binding two proximal protein kinases: GCK and RIP. GCK and RIP, in turn, signal by binding MAPKKKs upstream of the SAPKs and p38s. C1 Massachusetts Gen Hosp E, Diabet Res Lab, Med Res Lab, Charlestown, MA 02129 USA. Yokohama City Univ, Sch Med, Dept Mol Biol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kyriakis, JM (reprint author), Massachusetts Gen Hosp E, Diabet Res Lab, Med Res Lab, 149 13th St, Charlestown, MA 02129 USA. RI Yuasa, Takashi/B-2595-2010 FU NIGMS NIH HHS [GM46577] NR 58 TC 224 Z9 226 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22681 EP 22692 DI 10.1074/jbc.273.35.22681 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600074 PM 9712898 ER PT J AU Ge, NL Elferink, CJ AF Ge, NL Elferink, CJ TI A direct interaction between the aryl hydrocarbon receptor and retinoblastoma protein - Linking dioxin signaling to the cell cycle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AH-RECEPTOR; NUCLEAR TRANSLOCATOR; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; TRANSCRIPTIONAL ACTIVATION; EXPRESSION; DROSOPHILA; CLONING; BINDING; DOMAINS; GENE AB The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor in eukaryotic cells that alters gene expression in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), In 5L hepatoma cells, TCDD induces a G(1), cell cycle arrest through a mechanism that involves the AhR. The retinoblastoma tumor suppressor protein (pRb) controls cell cycle progression through G(1), in addition to promoting differentiation, We examined whether the human AhR or its dimerization partner, the AhR nuclear translocator, interacts with pRb as a basis of the TCDD-induced cell cycle arrest. In vivo and in vitro assays reveal a direct interaction between pRb and the AhR but not the AhR nuclear translocator protein. Binding between the AhR and pRb occurs through two distinct regions in the AhR. A high affinity site lies within the N-terminal 364 amino acids of the AhR, whereas a lower affinity binding region colocalizes with the glutamine-rich transactivation domain of the receptor. AhR ligand binding is not required for the pRb interaction per se, although immunoprecipitation experiments in 5L cells reveal that pRb associates preferentially with the liganded AhR, consistent with a requirement for ligand-induced nuclear translocation. These observations provide a mechanistic insight into AhR-mediated cell cycle arrest and a new perspective on TCDD-induced toxicity. C1 Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA. RP Elferink, CJ (reprint author), NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. EM Cornelis_Elferink@wayne.edu FU NIEHS NIH HHS [ES06639, R29ES07800] NR 47 TC 190 Z9 196 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22708 EP 22713 DI 10.1074/jbc.273.35.22708 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600077 PM 9712901 ER PT J AU Cheong, J Coligan, JE Shuman, JD AF Cheong, J Coligan, JE Shuman, JD TI Activating transcription factor-2 regulates phosphoenolpyruvate carboxykinase transcription through a stress-inducible mitogen-activated protein kinase pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING-PROTEIN; GROWTH-HORMONE GENE; TRANSGENIC MICE; C/EBP-ALPHA; GTP GENE; DIETARY-REGULATION; HEPATOMA-CELLS; RAT-LIVER; EXPRESSION; PHOSPHORYLATION AB Several protein-nucleic acid complexes are observed when nuclear extracts from hepatoma cells are assayed for binding to the cAMP response element found in the phosphoenolpyruvate carboxykinase-cytosolic (PEPCK-C) promoter. Although cAMP response element-binding protein and CCAAT/enhancer binding proteins alpha and beta have been identified as Liver factors that bind this motif, an uncharacterized, slower migrating complex was also observed. We identify activating transcription factor-2 (ATF-2) as the factor in this complex and show that ATF-S stimulates expression from the PEPCK-C promoter. ATF-2 is a basic-leucine zipper transcription factor and a target for stress-activated protein kinases. We demonstrate that p38 beta mitogen-activated protein (MAP) kinase augments ATF-S transactivation activity on the PEPCK-C promoter, which is consistent with the interpretation that PEPCK-C promoter activity is maintained under stress through a p38 MAP kinase dependent pathway. In this regard, we show that treatment with sodium arsenite, a known activator of p38 MAP kinases, also stimulates expression from the PEPCK promoter. These results show that ATF-2 can stimulate transcription of the PEPCK-C promoter and support a role for stress inducible kinases in the maintenance of PEPCK-C expression. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Shuman, JD (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 39 TC 37 Z9 37 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22714 EP 22718 DI 10.1074/jbc.273.35.22714 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600078 PM 9712902 ER PT J AU Kundu, GC Mandal, AK Zhang, ZJ Mantile-Selvaggi, G Mukherjee, AB AF Kundu, GC Mandal, AK Zhang, ZJ Mantile-Selvaggi, G Mukherjee, AB TI Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; RECOMBINANT HUMAN UTEROGLOBIN; TISSUE-SPECIFIC EXPRESSION; RABBIT UTEROGLOBIN; PROGESTERONE-BINDING; GENE-EXPRESSION; 10-KDA PROTEIN; PHOSPHOLIPASE-A2 ACTIVITY; QUATERNARY STRUCTURE; POSSIBLE MECHANISM AB Uteroglobin (UG) is a steroid-inducible, multifunctional, secreted protein with antiinflammatory and antichemotactic properties. Recently, we have reported a high affinity UG-binding protein (putative receptor), on several cell types, with an apparent molecular mass of 190 kDa (Kundu, G. C., Mantile, G., Miele, L., Cordella-Miele, E., and Mukherjee, A. B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 2915-2919). Since UG is a homodimer in which the 70 amino acid subunits are connected by two disulfide bonds, we sought to determine whether UG monomers also interact with the 190-kDa UG-binding protein and if so, whether it has the same biological activity as the dimer. Surprisingly, we discovered that in addition to the 190-kDa species, another protein, with an apparent molecular mass of 49 kDa, binds reduced UG with high affinity and specificity. Both 49- and 190-kDa proteins are readily detectable on nontransformed NIH 3T3 and some murine cancer cells (e.g. mastocytoma, sarcoma, and lymphoma), while lacking on others (e.g. fibrosarcoma). Most interestingly, pretreatment of the cells, which express the binding proteins, with reduced UG dramatically suppresses extracellular matrix (ECM) invasion, when such treatment had no effect on fibrosarcoma cells that lack the UG-binding proteins. Tissue-specific expression studies confirmed that while both 190- and 49-kDa UG-binding proteins are present in bovine heart, spleen, and the liver, only the 190-kDa protein is detectable in the trachea and in the lung. Neither the 190-kDa nor the 49-kDa protein was detectable in the aorta. Purification of these binding proteins from bovine spleen by UG-affinity chromatography and analysis by SDS-polyacrylamide gel electrophoresis followed by silver staining identified two protein bands with apparent molecular masses of 40 and 180 kDa, respectively. Treatment of the NIH 3T3 cells with specific cytokines (i.e. interleukin-6) and other agonists (i.e. lipopolysaccharide) caused a substantially increased level of I-125-UG binding but the same cells, when treated with platelet-derived growth factor, tumor necrosis factor-alpha, interferon-gamma, and phorbol 12-myristate 13-acetate, did not alter the UG binding. Taken together, these findings raise the possibility that UG, through its binding proteins, plays critical roles in the regulation of cellular motility and ECM invasion. C1 NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241, Bethesda, MD 20892 USA. EM mukherja@cc1.nichd.nih.gov NR 69 TC 39 Z9 43 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22819 EP 22824 DI 10.1074/jbc.273.35.22819 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600092 PM 9712916 ER PT J AU Dimon-Gadal, S Gerbaud, P Keryer, G Anderson, W Evain-Brion, D Raynaud, F AF Dimon-Gadal, S Gerbaud, P Keryer, G Anderson, W Evain-Brion, D Raynaud, F TI In vitro effects of oxygen-derived free radicals on type I and type II cAMP-dependent protein kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOSINE 3'-5'-CYCLIC MONOPHOSPHATE; CULTURED HUMAN KERATINOCYTES; REGULATORY SUBUNIT; HYDROGEN-PEROXIDE; HUMAN-FIBROBLASTS; BINDING-SITES; MESSENGER-RNA; AMINO-ACIDS; OXIDATION; EXPRESSION AB Oxygen free radicals may act as second messengers in signal transduction pathways and contribute to inflammatory diseases. We studied the action in vitro of radiolytically generated hydroxyl radicals ((OH)-O-.) and superoxide radicals (O(2)radical anion) on the cAMP-dependent protein kinases, I and II (PKAI and -II, respectively). The effects of the gasses O-2, and N2O used to produce O(2)radical anion or (OH)-O-. radicals by gamma-radiolysis of the water were also studied. PKAI is more sensitive than PKAII to oxygen gas (10 mM sodium formate) and to hydroxyl and superoxide radicals. Hydroxyl radicals decreased the kinase phosphotransferase activities stimulated either by cAMP or its site-specific analogs for both PKAI and PKAII; however, PKAI was more affected. The binding of [H-3]cAMP and of 8-N-3-[P-32]cAMP to RI regulatory subunits was decreased. (OH)-O-. caused a loss of tryptophan 260 fluorescence at site A of PKAI and of bityrosine production. Superoxide radicals affected only PKAI. O(2)radical anion modified both cAMP-binding sites A and B of the regulatory subunit but had a smaller effect on the catalytic subunit, The catalytic subunit was more sensitive to radicals when free than when part of the holoenzymes during exposure to the oxygen free radicals. These results suggest that oxygen free radicals alter the structure of PKA enzymes. Thus, oxidative modifications may alter key enzymes, including cAMP-dependent protein kinases, in certain pathological states. C1 Univ Paris 05, Fac Sci Pharmaceut & Biol Paris, INSERM, U427, F-75270 Paris 06, France. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Raynaud, F (reprint author), Univ Paris 05, Fac Sci Pharmaceut & Biol Paris, INSERM, U427, 4 Ave Observ, F-75270 Paris 06, France. NR 51 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 1998 VL 273 IS 35 BP 22833 EP 22840 DI 10.1074/jbc.273.35.22833 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 114NY UT WOS:000075616600094 PM 9712918 ER PT J AU Martiniuk, F Chen, A Mack, A Arvanitopoulos, E Chen, Y Rom, WN Codd, WJ Hanna, B Alcabes, P Raben, N Plotz, P AF Martiniuk, F Chen, A Mack, A Arvanitopoulos, E Chen, Y Rom, WN Codd, WJ Hanna, B Alcabes, P Raben, N Plotz, P TI Letter to the editor - Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID ACID ALPHA-GLUCOSIDASE; MESSENGER-RNA; GENETIC-HETEROGENEITY; CDNA C1 NYU, Med Ctr, Dept Med, Div Pulm & Crit Care Med, New York, NY 10016 USA. Bellevue Hosp Ctr, Clin Mycobacterial Lab, New York, NY 10016 USA. NYU, Med Ctr, Dept Environm Med, New York, NY 10016 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Martiniuk, F (reprint author), NYU, Med Ctr, Dept Med, Div Pulm & Crit Care Med, 550 1St Ave,New Bellevue 7N24, New York, NY 10016 USA. EM martif02@mcrcr6.med.nyu.edu FU NCRR NIH HHS [MO1 RR00096] NR 13 TC 100 Z9 112 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 27 PY 1998 VL 79 IS 1 BP 69 EP 72 DI 10.1002/(SICI)1096-8628(19980827)79:1<69::AID-AJMG16>3.0.CO;2-K PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 114QL UT WOS:000075620300016 PM 9738873 ER PT J AU Vamecq, J Lambert, D Poupaert, JH Masereel, B Stables, JP AF Vamecq, J Lambert, D Poupaert, JH Masereel, B Stables, JP TI Anticonvulsant activity and interactions with neuronal voltage-dependent sodium channel of analogues of ameltolide SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; POTENT ANTICONVULSANT; DEVELOPMENT PROGRAM; LY201116; MICE; METABOLISM; BINDING; RATS; 4-AMINO-N-(2,6-DIMETHYLPHENYL)BENZAMIDE; PHARMACOKINETICS AB Fifteen compounds related to ameltolide (LY 201116) were studied for (i) anticonvulsant potential in the maximal electroshock-induced seizures (MES) and the subcutaneous pentylenetetrazol (sc Ptz) tests in mice and rats and (ii) interactions with neuronal voltage-dependent sodium channels. Compounds were chosen ranging in anticonvulsant activity in mice from very active to inactive. The active compounds were defined as those protecting 50% of the animals at doses between 10 and 50 mu mol/kg and inactive compounds as those protecting 50% of the animals at doses greater than 1 mmol/kg. The series studied included three N-(2,6-dimethylphenyl)benzamides (compounds 1, 2 (ameltolide), and 3), three N-(2,2,6,6-tetramethyl)piperidinyl-4-benzamides (compounds 4, 5, 6), one phenylthiourea (compound 7), five N-(2,6-dimethylphenyl)phthalimides (compounds 8, 9, 10, 13, and 14), two N-phenylphthalimide derivatives (compounds 11 and 12), and one N-(2,2,6,6-tetramethyl)piperidinyl-4-phtalimide (compound 15). Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. After inital screening in mice, compounds 1, 2, 3, 5, 8, 9, 10, 13, and 14 were selected for further testing in rats. Anticonvulsant ED(50)s (effective doses in at least 50% of animals tested) of compounds in the MES test were determined in rats dosed orally and amounted to 52 (1), 135 (2), 284 (3), 31 (8), 131 (9), 25 (10), 369 (13), 354 (14), and 121 (PHT) mu mol/kg, compound 5 presenting with an ED50 value higher than 650 mu mol/kg. In our hands, the apparent IC(50)s (inhibitory concentrations 50) of compounds toward binding to rat brain synaptosomes of [H-3]batrachotoxinin-A-20 alpha-benzoate were 0.25 (1), 0.97 (2), 0.35 (3), 25.8 (5), 161.3 (8), 183.5 (9), 0.11 (10), 1.86 (13), 47.8 (14), and 0.86 (PHT) mu M. The relationship between the activity in the MES test and the capacity to interact in vitro with neuronal voltage-dependent sodium channels and the fact that the IC50 values obtained in the in vitro test are close to the brain concentrations at which anticonvulsant activities are reported to occur for ameltolide strongly suggest that the anticonvulsant properties of most compounds tested could be a direct result of their interaction with the neuronal voltage-dependent sodium channel. C1 CHRU Lille, INSERM, F-59651 Villeneuve Dascq, France. Univ Catholique Louvain, Ecole Pharm, Unite Chim Therapeut, B-1200 Brussels, Belgium. Univ Liege, Inst Gilkinet, Dept Chim Therapeut, B-4000 Liege, Belgium. NINCDS, Preclin Pharmacol Sect, Epilepsy Branch, DCDND,NIH, Bethesda, MD 20892 USA. RP Vamecq, J (reprint author), CHRU Lille, INSERM, Domaine Certia,369 Rue Jules Guesede,BP 39, F-59651 Villeneuve Dascq, France. NR 40 TC 40 Z9 40 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 27 PY 1998 VL 41 IS 18 BP 3307 EP 3313 DI 10.1021/jm9608772 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 115DF UT WOS:000075647700002 PM 9719582 ER PT J AU Argade, AB Devraj, R Vroman, JA Haugwitz, RD Hollingshead, M Cushman, M AF Argade, AB Devraj, R Vroman, JA Haugwitz, RD Hollingshead, M Cushman, M TI Design and synthesis of brefeldin A sulfide derivatives as prodrug candidates with enhanced aqueous solubilities SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID FLAVIN-CONTAINING MONOOXYGENASE; SECRETORY PROTEINS; CELL-SURFACE; REVERSIBLE BIOTRANSFORMATION; INTRACELLULAR-TRANSPORT; SULFONE METABOLITES; PHARMACOKINETICS; RAT; GOLGI; SULFINPYRAZONE AB The addition of a variety of thiols to the alpha,beta-unsaturated lactone functionality present in brefeldin A has been carried out, and the resulting sulfides have been oxidized to the corresponding sulfoxides. These sulfoxides have the potential to undergo syn elimination to regenerate brefeldin A. The sulfoxides were more active than the sulfides as cytotoxic agents in a variety of human cancer cell cultures with the activities of the sulfoxides approaching that of brefeldin A itself. The cytotoxicities of the sulfoxides may be due to their conversion back to brefeldin A. The kinetics of sulfoxide elimination to form brefeldin A were studied in four cases, and the results indicate that substantial amounts of brefeldin A are likely to be generated during the cytotoxicity assays of the sulfoxide derivatives. Since the oxidation of sulfides to sulfoxides is a common metabolic reaction, the sulfides derived from brefeldin A can be considered as potential brefeldin A prodrugs. Several of the sulfide derivatives were determined to have enhanced aqueous solubilities relative to brefeldin A itself, A number of brefeldin A succinates, glutarates, oxidation products, and sulfone derivatives were also prepared and evaluated for cytotoxicity in dancer cell cultures. Some of the more active brefeldin A derivatives were tested in an in vivo animal model in which hollow fibers containing cancer cell cultures were implanted subcutaneously (SC) and intraperitoneally (IF), and the compounds were administered IP. Greater cytotoxic activity was observed at the SC site than at the IP site for the majority of these compounds, an observation which is consistent with the hypothesis that they are acting as brefeldin A prodrugs in vivo. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Rockville, MD 20852 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH,Fairview Ctr, Frederick, MD 21701 USA. RP Cushman, M (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. FU NCI NIH HHS [N01-CM-67260]; PHS HHS [5T32-09634] NR 43 TC 27 Z9 27 U1 3 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 27 PY 1998 VL 41 IS 18 BP 3337 EP 3346 DI 10.1021/jm970746g PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 115DF UT WOS:000075647700006 PM 9719586 ER PT J AU Krishna, MC DeGraff, W Hankovszky, OH Sar, CP Kalai, T Jeko, J Russo, A Mitchell, JB Hideg, K AF Krishna, MC DeGraff, W Hankovszky, OH Sar, CP Kalai, T Jeko, J Russo, A Mitchell, JB Hideg, K TI Studies of structure-activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CARBON-CENTERED RADICALS; SODIUM CYANOBOROHYDRIDE; DERIVATIVES; SUPEROXIDE; METABOLISM; REDUCTION; TEMPOL; MIMICS AB The protective effects of stable nitroxides, as well as their hydroxylamine and amine precursors, have been tested in Chinese hamster V79 cells subjected to H2O2 exposure at fixed concentration or exposure to ionizing radiation. Cytotoxicity was evaluated by monitoring the viability of the cells assessed by the clonogenic assay. The compounds tested at fixed concentration varied in terms of ring size, oxidation state, and ring substituents. Electrochemical studies were carried out to measure the redox midpoint potentials. The studies show that in the case of protection against H2O2 exposure, the protection was determined by the ring size, oxidation state, and redox midpoint potentials. In general the protection factors followed the order nitroxides > hydroxylamines > amines. Both the six-membered ring nitroxides and substituted five-membered ring nitroxides were efficient protectors. For six-membered ring nitroxides, the compounds exhibiting the lowest midpoint potentials exhibited maximal protection. In the case of X-radiation, nitroxides were the most protective though some hydroxylamines were also efficient. The amines were in some cases found to sensitize the toxicity of aerobic radiation exposure. The protection observed by the nitroxides was not dependent on the ring size. However, the ring substituents had significant influence on the protection. Compounds containing a basic side chain were found to provide enhanced protection. The results in this study suggest that these compounds are novel antioxidants which can provide cytoprotection in mammalian cells against diverse types of oxidative insult and identify structural determinants optimal for protection against individual types of damage. C1 Univ Pecs, Inst Organ & Med Chem, H-7643 Pecs, Hungary. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. ICN Alkaloida Co Ltd, H-4440 Tiszavasvari, Hungary. RP Hideg, K (reprint author), Univ Pecs, Inst Organ & Med Chem, POB 99, H-7643 Pecs, Hungary. NR 51 TC 128 Z9 131 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 27 PY 1998 VL 41 IS 18 BP 3477 EP 3492 DI 10.1021/jm9802160 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 115DF UT WOS:000075647700021 PM 9719601 ER PT J AU McMurry, TJ Pippin, CG Wu, CC Deal, KA Brechbiel, MW Mirzadeh, S Gansow, OA AF McMurry, TJ Pippin, CG Wu, CC Deal, KA Brechbiel, MW Mirzadeh, S Gansow, OA TI Physical parameters and biological stability of yttrium(III) diethylenetriaminepentaacetic acid derivative conjugates SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; RADIOIMMUNOTHERAPY; DTPA; STEREOCHEMISTRY; COMPLEXES; LYMPHOMA; LIGANDS; CHELATE; AGENTS AB The solution equilibria, acid dissociation, and serum stability of a series of Y(III) complexes of DTPA ligands functionalized with p-nitrobenzyl, methyl, and trans-cyclohexyl substituents were studied. The thermodynamic stability of the complexes studied ranged from log K = 21.53 to 24.7. Acid dissociation rates were found to decrease as the substitution on the carbon backbone increased, and significant differences in dissociation rates were observed for the Y(III) complexes of a pair of diasteriomeric cyclohexyl-DTPA ligands. While one diastereomer was found to have the slowest acid dissociation rate of the entire DTPA series, it was remarkably labile in both serum stability and in vivo studies. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, NIH, 9000 Rockville Pike,Bldg 10,Room B3B69, Bethesda, MD 20853 USA. EM martinwb@box-m.nih.gov NR 34 TC 59 Z9 59 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 27 PY 1998 VL 41 IS 18 BP 3546 EP 3549 DI 10.1021/jm980152t PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 115DF UT WOS:000075647700028 PM 9719608 ER PT J AU Zohar, M Teramoto, H Katz, BZ Yamada, KM Gutkind, JS AF Zohar, M Teramoto, H Katz, BZ Yamada, KM Gutkind, JS TI Effector domain mutants of Rho dissociate cytoskeletal changes from nuclear signaling and cellular transformation SO ONCOGENE LA English DT Article DE Rho A GTPase; Ras; small G-proteins; transformation; stress fibers; signal transduction ID ACTIVATED PROTEIN-KINASE; SERUM RESPONSE ELEMENT; SMALL GTPASE RHO; RAS TRANSFORMATION; FAMILY GTPASES; TRANSCRIPTIONAL ACTIVATION; SERINE/THREONINE KINASE; ACTIN POLYMERIZATION; INDEPENDENT PATHWAYS; CYCLE PROGRESSION AB The small GTP-binding Rho proteins control a variety of biological activities, including organization of the actin cytoskeleton, regulation of gene expression and cellular transformation. In contrast, Ras proteins do not induce actin stress fibers, but potently transform cells which exhibit a morphology clearly distinct from that caused by activated forms of Rho. To investigate whether nuclear signaling and oncogenic potential of Rho are a consequence of its profound effect on cytoskeletal organization, we replaced each amino acid in the Rho effector loop with those of Ras, or replaced conserved residues with others known to result in differential signaling capability when introduced into Ras and Rad. These Rho mutants did not gain the ability to induce the MAPK, JNK or p38 pathways but, surprisingly, all Rho effector loop mutants still continued to induce actin stress fiber formation. However, three of these Rho mutants, with substitutions of leucine-39, glutamic acid-39, or cysteine-42, lost the ability to stimulate gene transcription via the serum response factor (SRF) and failed to induce neoplastic transformation. Thus, these results indicate that cytoskeletal changes are not sufficient to induce the transformed phenotype, and that Rho-effector molecules regulating the actin cytostructure are distinct from those signaling to the nucleus and subverting normal growth control. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 41 TC 46 Z9 46 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 27 PY 1998 VL 17 IS 8 BP 991 EP 998 DI 10.1038/sj.onc.1202022 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 113PR UT WOS:000075560900007 PM 9747878 ER PT J AU Kim, JO Nau, MM Allikian, KA Makela, TP Alitalo, K Johnson, BE Kelley, MJ AF Kim, JO Nau, MM Allikian, KA Makela, TP Alitalo, K Johnson, BE Kelley, MJ TI Co-amplification of a novel cyclophilin-like gene (PPIE) with L-myc in small cell lung cancer cell lines SO ONCOGENE LA English DT Article DE gene amplification; L-myc; cyclophilin; small cell lung cancer; tumor cell line; alternative splicing ID NEURONAL CEROID-LIPOFUSCINOSIS; COMPLEX PATTERN; EXPRESSION; IDENTIFICATION; IMMUNOPHILINS; PROTEINS; ONCOGENE; BINDING; RLF AB Specific genetic alterations affecting proto-oncogenes of the myc gene family are frequently detected in human lung cancer. Among 11 SCLC cell lines with L-myc gene amplification, four were found to have alteration of the RLF gene by Southern blot and RT-PCR analyses. One cell line, NCI-H378, contained aberrantly-sized L-myc-hybridizing bands by Southern and Northern blot hybridization but had no alteration of RLF: Some L-myc-hybridizing cDNAs from NCI-H378 contained a novel sequence with close homology to the cyclophilins joined to antisense L-myc exon 2 sequence. Full length cDNAs isolated from human skeletal muscle containing only the novel sequence identify open reading frames of 301 and 296 amino acids and differ in the C-terminal region by 22 and 17 amino acids. This gene, tentatively named PPIE (peptidyl-prolyl cis-trans isomerase E), has 83% amino acid identity with the central conserved region of cyclophilin A, is evolutionarily conserved by Southern blot, and exhibits differential tissue expression with highest levels found in muscle and brain. Coamplification of PPIE was observed in seven of eleven L-myc amplified cell lines. Analysis of radiation hybrids suggests that the gene order is RLF-PPIE-L-myc on chromosome Ip and pulse-field gel electrophoresis localizes all three genes to an 800 megabase Mlu I fragment. The prognostic and functional consequences of PPIE gene amplification in SCLC can now be determined. C1 NCI, Lung Canc Biol Sect, Med Branch, Div Clin Sci, Bethesda, MD 20889 USA. Univ Helsinki, Canc Biol Lab, Dept Virol & Pathol, FIN-00290 Helsinki, Finland. RP Kelley, MJ (reprint author), NCI, Lung Canc Biol Sect, Med Branch, Div Clin Sci, Bethesda, MD 20889 USA. RI makela, tomi/B-3734-2009; Alitalo, Kari/J-5013-2014; OI makela, tomi/0000-0002-4869-8044; Alitalo, Kari/0000-0002-7331-0902; Kelley, Michael/0000-0001-9523-6080 NR 27 TC 18 Z9 19 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 27 PY 1998 VL 17 IS 8 BP 1019 EP 1026 DI 10.1038/sj.onc.1202006 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 113PR UT WOS:000075560900010 PM 9747881 ER PT J AU Zetterman, RK Belle, SH Hoofnagle, JH Lawlor, S Wei, YL Everhart, J Wiesner, RH Lake, JR AF Zetterman, RK Belle, SH Hoofnagle, JH Lawlor, S Wei, YL Everhart, J Wiesner, RH Lake, JR TI Age and liver transplantation - A report of the liver transplantation database SO TRANSPLANTATION LA English DT Article ID OLDER AB Background. The average age of liver transplant recipients has increased steadily during the last decade. The effects of recipient age on outcome of liver transplantation were evaluated in a large prospective database. Methods. A total of 735 adult recipients of single-organ liver transplants for nonfulminant liver disease enrolled in a large prospective database between 1990 and 1994 were analyzed for associations of patient age with outcomes. Patients were categorized into two groups: younger being <60 and older being greater than or equal to 60 years of age. Results. Older liver transplant recipients were more likely to be female, white, and have the diagnoses of primary biliary cirrhosis or cryptogenic cirrhosis than younger recipients, who were more likely to have the diagnosis of alcoholic liver disease. Disease severity was similar between the two groups. After transplantation, the durations of stay in the intensive care unit and hospital were longer for older than for younger transplant recipients, but episodes of acute rejection were less frequent. The quality of life at 1 year was similar among older and younger recipients, Patient survival was lower for older than for younger recipients (81% vs. 90% at 1 year; P=0.004), whereas graft survival was not different (80% vs. 85% at 1 year; P=0.163), The excess mortality among older recipients was largely due to nonhepatic causes, including infectious, cardiac, and neurological diseases occurring within 6 months after transplantation. Conclusions. Although patient survival was significantly lower among liver transplant recipients above the age of 60 years, the excess mortality was due to nonhepatic, largely age-related problems. The overall success of liver transplantation and improvement in quality of life for older recipients is excellent. C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A23, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2252, N01-DK-0-2253] NR 19 TC 96 Z9 104 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1998 VL 66 IS 4 BP 500 EP 506 DI 10.1097/00007890-199808270-00015 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 116HM UT WOS:000075718800015 PM 9734495 ER PT J AU Zhu, PP Herzberg, O Peterkofsky, A AF Zhu, PP Herzberg, O Peterkofsky, A TI Topography of the interaction of HPr(Ser) kinase with HPr SO BIOCHEMISTRY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; CONTAINING PHOSPHOCARRIER PROTEIN; GRAM-POSITIVE BACTERIA; HISTIDINE-CONTAINING PROTEIN; ESCHERICHIA-COLI; MYCOPLASMA-CAPRICOLUM; RESOLUTION STRUCTURE; BACILLUS-SUBTILIS; ENZYME-I; PHOSPHOENOLPYRUVATE AB The phosphocarrier protein, HPr, from Gram-positive organisms and mycoplasmas is a substrate for an ATP-dependent kinase that phosphorylates serine 46, In Gram-negative organisms, the corresponding HPr is not phosphorylated on serine 46 and the ATP-dependent kinase is absent. To determine the specificity requirements for phosphorylation of Mycoplasma capricolum HPr, a chimera in which residues 43-57 were replaced by the Escherichia coli sequence was constructed. The chimeric protein folded properly, but was not phosphorylated on either serine 46 or histidine 15. A dissection of the region required for phosphorylation specificity was carried out by further mutagenesis. The deficiency in phosphorylation at histidine 15 was localized primarily to the region including residues 51-57. Activity studies revealed that residues 48, 49, and 51-53 are important for recognition of M. capricolum HPr by its cognate HPr(Ser) kinase. The characteristics of this region suggest that the Kinase-HPr interaction occurs mainly through a hydrophobic region. Molecular modeling comparisons of M, capricolum HPr and the chimeric construct provided a basis for interpreting the results of the activity assays. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RP Peterkofsky, A (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 36,Room 4C-11, Bethesda, MD 20892 USA. NR 30 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 25 PY 1998 VL 37 IS 34 BP 11762 EP 11770 DI 10.1021/bi980455p PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117QK UT WOS:000075793100006 PM 9718298 ER PT J AU Kuznetsova, N Chi, SL Leikin, S AF Kuznetsova, N Chi, SL Leikin, S TI Sugars and polyols inhibit fibrillogenesis of type I collagen by disrupting hydrogen-bonded water bridges between the helices SO BIOCHEMISTRY LA English DT Article ID INCREASED THERMAL-STABILITY; X-RAY-DIFFRACTION; FIBRIL FORMATION; TRIPLE HELICES; INVITRO; HYDRATION; MECHANISM; FORCES; STABILIZATION; PROTEINS AB To better understand the mechanism of collagen fibrillogenesis, we studied how various sugars and polyols affect the formation and stability of collagen fibers. We combined traditional fiber assembly assays with direct measurement of the interaction between collagen triple helices in fibers by osmotic stress and X-ray diffraction. We found that the effects of sugars and polyols were highly specific with respect to small structural differences between these solutes. For example, 1,2-propane diol only weakly inhibited the fiber assembly and practically did not affect the interaction between collagen helices in fibers. At the same concentration, 1,3-propane diol eliminated the attraction between collagen helices and strongly suppressed fibrillogenesis. The two diols have the same atomic composition and differ only by the position of one of their hydroxyls. Still, their ability to inhibit fiber assembly differs by more than an order of magnitude, as judged by protein solubility. We argue that this is because collagen fibrillogenesis requires formation of hydrogen-bonded water clusters bridging recognition sites on the opposing helices. The ability of various sugars and polyols to inhibit the fiber assembly and to destabilize existing fibers is determined by how efficiently these solutes can compete with water for crucial hydrogen bonds and, thus, disrupt the water bridges. The effect of a sugar or a polyol appears to be strongly dependent on the specific stereochemistry of the solute hydroxyls that defines the preferred hydrogen-bonding pattern of the solute. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Princeton Univ, Princeton, NJ 08544 USA. RP Leikin, S (reprint author), NICHD, LPSD, NIH, Bldg 12A,Rm 2041, Bethesda, MD 20892 USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 28 TC 63 Z9 63 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 25 PY 1998 VL 37 IS 34 BP 11888 EP 11895 DI 10.1021/bi980089+ PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117QK UT WOS:000075793100020 PM 9718312 ER PT J AU Abati, A Jaffurs, W Wilder, AM AF Abati, A Jaffurs, W Wilder, AM TI Squamous atypia in the atrophic cervical vaginal smear - A new look at an old problem SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-29, 1996 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol DE cervical vaginal smears; atrophy; atypia; postmenopausal ID UNDETERMINED SIGNIFICANCE; POSTMENOPAUSAL WOMEN; CYTOLOGY; CELLS AB BACKGROUND. Squamous atypia in postmenopausal (PM) cervical vaginal smears (CVS) only rarely is associated with a biopsy-proven squamous intraepithelial lesion (SIL), and thus most commonly represents an atrophy-associated benign reactive change. METHODS. To distinguish atypical squamous cells of undetermined significance (ASCUS) and SIL from atrophy-associated benign reactive changes, a review of atypical atrophic PM CVS was performed. Ninety CVS exhibiting an atrophic smear pattern were considered appropriate for study. Repeat smears and/or biopsy after local estrogen therapy were requested to distinguish atrophic/reactive from dysplastic changes. RESULTS. Generally, atrophic CVS exhibit uniform nuclear enlargement in the squamous cell population, which, using the criterion of nuclear enlargement alone, would qualify the majority of these cases to be classified as ASCUS. The nuclear enlargement associated with atrophy resolves with the local application of estrogen. Follow-up after local estrogen treatment was available for 84 of 90 patients and revealed 10 cases of SIL (12%) and 9 cases of ASCUS (11%), 6 of which were favored to be of a reactive etiology. Nuclear features most commonly noted in the cases considered to be ASCUS (nonreactive) and SIL were nuclear hyperchromasia and nuclear contour irregularities. CONCLUSIONS. Nuclear enlargement alone is not sufficient for diagnosing ASCUS or SIL in PM CVS. Nuclear enlargement in squamous cells is an expected normal reactive change present in PM CVS that resolves with the application of local estrogen. Nuclear hyperchromasia and irregular nuclear contours remain the most reliable cellular characteristics for diagnosing SIL in atrophic CVS. [See editorial on pages 200-1, this issue.] Cancer (Cancer Cytopathol) 1998;84:218-25. (C) 1998 American Cancer Society. C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. Cytol Serv Maryland, Laurel, MD USA. RP Abati, A (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, Bldg 10,Room 2A19,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 36 Z9 37 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1998 VL 84 IS 4 BP 218 EP 225 DI 10.1002/(SICI)1097-0142(19980825)84:4<218::AID-CNCR6>3.0.CO;2-I PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 113GA UT WOS:000075541000006 PM 9723596 ER PT J AU Naujokas, MF Southwood, S Mathies, SJ Appella, E Sette, A Miller, J AF Naujokas, MF Southwood, S Mathies, SJ Appella, E Sette, A Miller, J TI T cell recognition of flanking residues of murine invariant chain-derived CLIP peptide bound to MHC class II SO CELLULAR IMMUNOLOGY LA English DT Article ID COMPLEX-CLASS-II; HLA-DR MOLECULES; ANTIGEN-PROCESSING MUTANT; MICE LACKING; IN-VIVO; BINDING; RECEPTOR; SPECIFICITY; ASSOCIATION; EPITOPES AB The major site of interaction between MHC class II molecules and invariant chain has been mapped to occupancy of the class II peptide-binding site by the CLIP region of invariant chain. CLIP is also seen as a degradation product of invariant chain and can be found in association with class II as a processing intermediate. Here we analyzed the relative contribution of single amino acids in the murine CLIP (86-102) peptide for binding to I-A(b) and I-A(d) and for recognition by a CLIP-specific T cell hybridoma. Interestingly, the I-A(b)-restricted murine T cell hybridoma that recognizes murine CLIP peptide (86-102) is dependent on Met 102 for activation. This amino acid is outside of the core binding region and in the CLIP/DR3 crystal structure extends outside of the class II peptide-binding site. These data suggest that a T cell epitope presented on CLIP/class II complexes can be located predominantly in flanking residues that extend out of the peptide binding groove of class II. (C) 1998 Academic Press. C1 Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. Cytel Corp, San Diego, CA 92121 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Naujokas, MF (reprint author), Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. FU NCI NIH HHS [CA-14599] NR 56 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG 25 PY 1998 VL 188 IS 1 BP 49 EP 54 DI 10.1006/cimm.1998.1347 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 125NN UT WOS:000076243800006 PM 9743557 ER PT J AU Saitoh, A Hansen, LA Vogel, JC Udey, MC AF Saitoh, A Hansen, LA Vogel, JC Udey, MC TI Characterization of Wnt gene expression in murine skin: Possible involvement of epidermis-derived Wnt-4 in cutaneous epithelial-mesenchymal interactions SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Wnt; skin; keratinocyte; fibroblast ID BASAL-CELL CARCINOMA; MAMMARY-GLAND; HUMAN HOMOLOG; SONIC HEDGEHOG; PATCHED PTCH; SIGNALING PATHWAY; MESSENGER-RNA; GROWTH-FACTOR; FAMILY; TRANSFORMATION AB Wnt glycoproteins mediate short range intracellular communication that facilitates morphogenesis and, in some settings, promotes tumor formation. Although the involvement of the Drosophila homolog wingless in ectodermal patterning is well established, the role that Wnt genes play in mammalian skin biology is not defined. We detected Wnt-4 and Wnt-10b mRNA in adult murine epidermis using degenerate primers and reverse transcriptase PCR, and confirmed expression by RNase protection. Normal murine keratinocytes and a melanocyte cell line (melan-A) propagated in vitro also contained Wnt-4 mRNA, whereas dermal fibroblasts and Langerhans cell-like dendritic cells did not. Because Wnt-4 mRNA was more abundant than Wnt-10b mRNA in epidermis and Wnt-10b trancripts were not detected in cells propagated in vitro, additional studies emphasized Wnt-4 exclusively. Wnt-4 mRNA levels were increased in cultured keratinocytes as they approached confluence and were strikingly downregulated by mitogenic growth factors. Although Wnt-4 mRNA levels were not modulated during calcium induced keratinocyte differentiation in vitro, assessment of Wnt-4 transcripts in keratinocyte cell lines suggested that loss of Wnt-4 gene expression was associated with a less differentiated, more malignant, phenotype. Despite this, epidermal abnormalities were not identified in newborn Wnt-4 null (-/-) skin, or in full-thickness -/- skin that was engrafted to nude or athymic mice and allowed to mature for as long as 3 months. However, histologic examination of newborn Wnt-4 null skin did reveal fibroplasia involving the dermis with increased accumulation of type I collagen fibrils. These results indicate that several Wnt genes are expressed in adult murine epidermis and suggest that Wnt-4 proteins may be involved in epidermal-dermal interactions in mammalian skin. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 59 TC 38 Z9 39 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 25 PY 1998 VL 243 IS 1 BP 150 EP 160 DI 10.1006/excr.1998.4152 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 116YT UT WOS:000075753200017 PM 9716459 ER PT J AU Nephew, KP Sheeler, CQ Dudley, MD Gordon, S Nayfield, SG Khan, SA AF Nephew, KP Sheeler, CQ Dudley, MD Gordon, S Nayfield, SG Khan, SA TI Studies of dehydroepiandrosterone (DHEA) with the human estrogen receptor in yeast SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE dehydroepiandrosterone; estradiol; estrogen receptor; hormone; yeast ID PROTEIN-PROTEIN INTERACTIONS; LONG-TERM TREATMENT; RAT MAMMARY-GLAND; SACCHAROMYCES-CEREVISIAE; NUCLEAR RECEPTORS; HORMONE-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; 2-HYBRID SYSTEM; IN-VIVO; INHIBITION AB Dehydroepiandrosterone (DHEA) is a C-19 adrenal steroid synthesized in the human adrenal cortex and serving as a biosynthetic precursor to testosterone and 17 beta-estradiol. Despite the fact that it is one of the most abundant steroid hormones in circulation, the physiological role of DHEA in humans remains unclear. The action of DHEA itself, such as its interactions with receptors and nuclear transcription factors, is not well understood, and a specific DHEA receptor has yet to be identified. Although the activity of DHEA can be due to its metabolism into androgens and estrogens, DHEA has been shown to interact with the androgen receptor and the estrogen receptor (ER) in vitro. We demonstrate in this study that DHEA (3 beta-Hydroxy-5 alpha-androstan17-one) inhibits 17 beta-estradiol (E-2) binding to its receptor in vivo in yeast. DHEA stimulates human ER dimerization in yeast, as determined by ER fusion protein interactions, GAL4 reconstitution and subsequent measurement of increased beta-galactosidase activity. DHEA causes an increase in estrogen response element-dependent beta-galactosidase activity, demonstrating that the ER dimer induced by DHEA is transcriptionally active, but at a concentration of DHEA about 1000 times greater than E-2. Inclusion of the nuclear receptor co-activator RIP140 in the yeast enhances ER transactivation by DHEA or E-2 in a ligand-dependent manner; moreover, only in the presence of RIP140 is DHEA able to stimulate P-galactosidase activity to levels similar to those achieved by E-2. Ligand-receptor interaction for other C-19-steroids was also examined. While 5-androstene-3 beta, 17 beta-diol (ADIOL) displayed estrogenic activity in this system, 4-androstene-17-dione (androstenedione) and 4-androstene-17 beta-ol,3-one (testosterone) did not. We have investigated whether DHEA can interact with the human ER in vivo. Our findings demonstrate a mechanism by which DHEA interacts directly with estrogen signaling systems; however, because DHEA is several orders of magnitude less potent than E-2 in this system, we conclude that it essentially is not an estrogen agonist. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Indiana Univ, Sch Med, Med Sci Program, Bloomington, IN 47405 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. Hoechst Mar Roussel, Cincinnati, OH USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Nephew, KP (reprint author), Indiana Univ, Sch Med, Med Sci Program, 302 Jordon Hall, Bloomington, IN 47405 USA. EM knephew@indiana.edu FU NCI NIH HHS [CA72309, CA74748] NR 72 TC 43 Z9 44 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD AUG 25 PY 1998 VL 143 IS 1-2 BP 133 EP 142 DI 10.1016/S0303-7207(98)00128-2 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 127JB UT WOS:000076346400014 PM 9806358 ER PT J AU Borlongan, CV Saporta, S Poulos, SG Othberg, A Sanberg, PR AF Borlongan, CV Saporta, S Poulos, SG Othberg, A Sanberg, PR TI Viability and survival of hNT neurons determine degree of functional recovery in grafted ischemic rats SO NEUROREPORT LA English DT Article DE cell viability; cell line; cerebral ischemia; functional recovery; neural transplantation; xenograft ID EMBRYONIC DOPAMINE NEURONS; FETAL MESENCEPHALIC GRAFTS; MIDDLE CEREBRAL-ARTERY; PARKINSONS-DISEASE; NIGRAL GRAFTS; TRANSPLANTATION; TISSUE; CRYOPRESERVATION; STRIATUM; STORAGE AB WE recently reported behavioral improvements following intrastriatal transplantation of cryopreserved cultured human neuroteratocarcinoma-derived cells (hNT neurons) in rats with cerebral ischemia induced by occlusion of the middle cerebral artery. In the present study, the viability and survival of hNT neurons were evaluated immediately prior to the transplantation surgery and at 3 months post-transplantation in ischemic rats. Cryopreserved hNT neurons were routinely thawed, and trypan blue exclusion viability counts revealed 52-95% viable hNT neurons before transplantation. Monthly behavioral tests, starting at 1 month and extending to 3 months post-transplantation, revealed that ischemic animals that were intrastriatally transplanted with hNT neurons (similar to 40 000) and treated with an immunosuppressive drug displayed normalization of asymmetrical motor behavior compared with ischemic animals that received medium alone. Within-subject comparisons of cell viability and subsequent behavioral changes revealed that a high cell viability just prior to transplantation surgery correlated highly with a robust and sustained functional improvement in the transplant recipient. Furthermore, histological analysis of grafted brains revealed a positive correlation between number of surviving hNT neurons and degree of functional recovery. In concert with similar reports on fetal tissue transplantation, we conclude that high cell viability is an important criterion for successful transplantation of cryopreserved neurons derived from cell lines to enhance graft-induced functional effects. (C) 1998 Lippincott Williams & Wilkins. C1 Univ S Florida, Coll Med, Dept Surg, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Psychiat, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Psychol & Pharmacol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Anat, Tampa, FL 33612 USA. RP Borlongan, CV (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 28 TC 46 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 24 PY 1998 VL 9 IS 12 BP 2837 EP 2842 DI 10.1097/00001756-199808240-00028 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 124LP UT WOS:000076184100030 PM 9760130 ER PT J AU Abu-Raya, S Bloch-Shilderman, E Yedgar, S Yiang, H Lazarovici, P AF Abu-Raya, S Bloch-Shilderman, E Yedgar, S Yiang, H Lazarovici, P TI Cellular signaling in PC12 cells affected by pardaxin. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med, Dept Biochem, IL-91120 Jerusalem, Israel. NICHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 140-AGFD BP U66 EP U66 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900140 ER PT J AU Alonso, R Shin, KJ Marquez, VE AF Alonso, R Shin, KJ Marquez, VE TI A concise approach to the antiviral nucleoside (1R,2S,4S,5S)-1-hydroxymethyl-2-hydroxy-4-(6-amino-9-purinyl)bicyclo[3.1 .0]hexane. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 240-MEDI BP U274 EP U274 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000890 ER PT J AU Antonucci, JM Skrtic, D Eanes, ED AF Antonucci, JM Skrtic, D Eanes, ED TI Bioactive polymeric composites based on hybrid amorphous calcium phosphates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, ADAHF, PRC, Gaithersburg, MD 20899 USA. NIDR, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 405-POLY BP U121 EP U121 PN 3 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WZ UT WOS:000075235100402 ER PT J AU Bal, W Lukszo, J Bialkowski, K Kasprzak, KS AF Bal, W Lukszo, J Bialkowski, K Kasprzak, KS TI Ni(II)-assisted hydrolysis of CH3CO-Thr-Glu-Ser-His-His-Lys-NH2, a peptide modeling the metal binding site in histone H2A SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland. NIAAA, Mol Struct Lab, Rockville, MD 20852 USA. Univ Sch Med Sci, Dept Clin Biochem, PL-85092 Bydgoszcz, Poland. RI Bialkowski, Karol/E-2328-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 067-TOXI BP U565 EP U565 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901637 ER PT J AU Barchi, JJ Long, YQ Voigt, JH Milne, GW Lung, FDT King, CR Roller, PP AF Barchi, JJ Long, YQ Voigt, JH Milne, GW Lung, FDT King, CR Roller, PP TI Conformational analysis of a non-phosphorylated cyclic peptide ligand of the Grb2-SH2 domain by NMR and molecular modeling. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 266-MEDI BP U281 EP U282 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000916 ER PT J AU Brock, J Rubin, C Marcus, M Dorgan, J Longnecker, M Hoyer, A Needham, L AF Brock, J Rubin, C Marcus, M Dorgan, J Longnecker, M Hoyer, A Needham, L TI Studies of human health effects of endocrine-active xenobiotic compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Copenhagen Univ Hosp, Copenhagen, Denmark. RI Needham, Larry/E-4930-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 115-ENVR BP U794 EP U794 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902335 ER PT J AU Dai, F Zhang, HP Malinowski, N Kelley, JA Ford, H AF Dai, F Zhang, HP Malinowski, N Kelley, JA Ford, H TI Fluorimetric determination of 2 '-fluoro-2 ',3 '-dideoxyadenosine-5 ' triphosphate, the active metabolite of a new anti-aids drug in human peripheral blood mononuclear cells by paired-ion, reversed phase chromatography. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 087-ANYL BP U165 EP U165 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900429 ER PT J AU Dress, KR Goossen, LJ Jerina, DM Kroth, H Liu, H Ramesha, A Sharpless, KB AF Dress, KR Goossen, LJ Jerina, DM Kroth, H Liu, H Ramesha, A Sharpless, KB TI Catalytic aminohydroxylation with adenine-derivatives as nitrogen sources. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RI Goossen, Lukas/L-9764-2015 OI Goossen, Lukas/0000-0002-2547-3037 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 396-ORGN BP U482 EP U482 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235001522 ER PT J AU Eaton, WA Munoz, V Thompson, PA Henry, ER Jas, G Hofrichter, J AF Eaton, WA Munoz, V Thompson, PA Henry, ER Jas, G Hofrichter, J TI Kinetics and mechanism of protein secondary structure formation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Phys Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 469-PHYS BP U796 EP U796 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235002398 ER PT J AU Fowler, BO Stansbury, JW AF Fowler, BO Stansbury, JW TI Facile syntheses of oligomeric organofluorosilsesquioxanes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIST, Gaithersburg, MD 20899 USA. NIDR, NIH, Bethesda, MD 20982 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 213-POLY BP U63 EP U63 PN 3 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WZ UT WOS:000075235100212 ER PT J AU Gussio, R Pattabiraman, N Zaharevitz, DW Kellogg, GE Wiegand, A Pallansch, LA Buckheit, RW AF Gussio, R Pattabiraman, N Zaharevitz, DW Kellogg, GE Wiegand, A Pallansch, LA Buckheit, RW TI A molecular model of the binding modality of the thiocarboxanilide UC781 to HIV-1 reverse transcriptase. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, TSBDDG, ITB, DTP,Frederick Biomed Supercomp Ctr,SAIC, Frederick, MD 21702 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23284 USA. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 327-MEDI BP U300 EP U300 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000975 ER PT J AU Gussio, R Pattabiraman, N Zaharevitz, DW Weigand, A Pallansch, LA Buckheit, RW AF Gussio, R Pattabiraman, N Zaharevitz, DW Weigand, A Pallansch, LA Buckheit, RW TI A two site binding modality of dihydrocostatolide to HIV-1 reverse transcriptase. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, FBSC, SAIC, SRI, Frederick, MD 21702 USA. NCI, TSBDDG, ITB, DTP,SRI, Frederick, MD 21702 USA. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 326-MEDI BP U300 EP U300 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000974 ER PT J AU Kasianowicz, JJ Akeson, M Henrickson, SE Bezrukov, SM Brandin, E Branton, D Deamer, DW AF Kasianowicz, JJ Akeson, M Henrickson, SE Bezrukov, SM Brandin, E Branton, D Deamer, DW TI Charged and neutral polymer transport in a single ionic channel. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. NIH, Bethesda, MD USA. Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. NIST, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 263-PHYS BP U737 EP U737 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235002203 ER PT J AU Keefer, LK Lyle, RE Lyle, AC AF Keefer, LK Lyle, RE Lyle, AC TI Dr. Gloria Gilbert Lyle, researcher, teacher, role model and mentor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. GRL Consultants, San Antonio, TX 78230 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 048-HIST BP U907 EP U907 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902678 ER PT J AU Keefer, LK AF Keefer, LK TI Is nitric oxide cytotoxic or cytoprotective? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 106-TOXI BP U576 EP U576 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901674 ER PT J AU Khan, QA Vousden, KH Dipple, A AF Khan, QA Vousden, KH Dipple, A TI Carcinogen-DNA damage induces p53 but fails to induce G1 arrest in cell cultures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 115-TOXI BP U578 EP U578 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901683 ER PT J AU Kim, YC Camaioni, E Ziganshin, AU Ji, XD King, BF Wildman, SS Rychkov, A Kim, HO Mohanram, A Harden, TK Boyer, JL Burnstock, G Jacobson, KA AF Kim, YC Camaioni, E Ziganshin, AU Ji, XD King, BF Wildman, SS Rychkov, A Kim, HO Mohanram, A Harden, TK Boyer, JL Burnstock, G Jacobson, KA TI Synthesis and SAR studies of pyridoxal-6-azoaryl-5 '-phosphate and phosphonate derivatives as P2 receptor antagonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Royal Free Sch Med, London NW3 2PF, England. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Kazan Med Inst, Kazan 420012, Russia. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 055-MEDI BP U217 EP U218 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000705 ER PT J AU Kirk, KL Jayachandran, B Herbert, B AF Kirk, KL Jayachandran, B Herbert, B TI Chemical and biochemical approaches to non-racemic fluorinated catecholamines and amino acids SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Muenster, Inst Organ Chem, D-48149 Muenster, Germany. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 012-FLUO BP U823 EP U823 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902422 ER PT J AU Kunkel, TA AF Kunkel, TA TI Studies of eukaryotic DNA mismatch repair. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 091-TOXI BP U571 EP U572 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901659 ER PT J AU Li, AH Moro, S Melman, N Ji, XD Jacobson, KA AF Li, AH Moro, S Melman, N Ji, XD Jacobson, KA TI Sar and molecular modeling studies of pyridine derivatives as selective A(3) adenosine antagonists. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 093-MEDI BP U229 EP U229 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000743 ER PT J AU Long, YQ Lung, FDT Barchi, JJ King, CR Roller, PP AF Long, YQ Lung, FDT Barchi, JJ King, CR Roller, PP TI Structure-activity studies on non-phosphorylated cyclic peptides binding to Grb2-SH2 domain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 265-MEDI BP U281 EP U281 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000915 ER PT J AU Lucier, GW AF Lucier, GW TI The changing face of toxicology - Mechanisms, human studies and risk assessment for endocrine disruptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 113-ENVR BP U794 EP U794 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902333 ER PT J AU McGrath, CF Tawa, GJ Luke, BT Kellogg, GE Zaharevitz, DW Pattabiraman, N Gussio, R AF McGrath, CF Tawa, GJ Luke, BT Kellogg, GE Zaharevitz, DW Pattabiraman, N Gussio, R TI A 3D-QSAR of pyridinone binding at the non-nucleoside binding site of HIV-1 reverse transcriptase: A hydropathic molecular dynamics approach. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 VCU, MCV, Richmond, VA 23284 USA. NCI, AVP, SAIC, FBSC, Frederick, MD 21702 USA. NCI, TSBDDG, ITB, DTP, Frederick, MD 21702 USA. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 085-COMP BP U708 EP U708 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902107 ER PT J AU McGrath, CF Urbaneja, MA Sudhakar, K Michaels, G Casas, J AF McGrath, CF Urbaneja, MA Sudhakar, K Michaels, G Casas, J TI Homology modeling and comparison of retroviral zinc finger structures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 George Mason Univ, Fairfax, VA 22030 USA. NCI, Frederick Canc Res & Dev Ctr, AVP, SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 040-BIOL BP U217 EP U217 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900597 ER PT J AU Moro, S Li, AH Jacobson, KA AF Moro, S Li, AH Jacobson, KA TI Molecular modeling studies of human A(3) adenosine antagonists: Structure similarity and receptor docking. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 094-MEDI BP U229 EP U229 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000744 ER PT J AU Moschel, RC AF Moschel, RC TI Inactivation of DNA repair for chemotherapy. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 083-TOXI BP U569 EP U569 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901651 ER PT J AU Mowery, KA Schoenfisch, MH Meyerhoff, ME Saavedra, JE Keefer, LK AF Mowery, KA Schoenfisch, MH Meyerhoff, ME Saavedra, JE Keefer, LK TI Polymeric diazeniumdiolates for fabricating thromboresistant electrochemical sensors via nitric oxide release. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 034-PMSE BP U821 EP U821 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235002463 ER PT J AU Newlin, DB AF Newlin, DB TI Evolutionary game theory of multiple chemical sensitivity and neural sensitization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 057-AGRO BP U100 EP U100 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900235 ER PT J AU Park, G Lu, FH Ye, N Brechbiel, MW Torti, SV Torti, FM Planalp, RP AF Park, G Lu, FH Ye, N Brechbiel, MW Torti, SV Torti, FM Planalp, RP TI Iron complexes of chelators based on cis,cis-1,3,5-triaminocyclohexane. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27157 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 544-INOR BP U164 EP U164 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000545 ER PT J AU Pattabiraman, N Gussio, R Zaharevitz, DW Kellogg, GE Weigand, A Pallansch, LA Buckheit, RW AF Pattabiraman, N Gussio, R Zaharevitz, DW Kellogg, GE Weigand, A Pallansch, LA Buckheit, RW TI A mechanistic proposal for the non-nucleoside binding site of HIV-1 reverse transcriptase: An explanation of mutations and drug resistance. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, FBSC, SAIC, SRI, Frederick, MD 21702 USA. NCI, TSBDDG, ITB, DTP,SRI, Frederick, MD 21702 USA. Virginia Commonwealth Univ, MCU, Dept Med Chem, Richmond, VA 23284 USA. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 039-BIOL BP U217 EP U217 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900600 ER PT J AU Rick, SW Cachau, RE AF Rick, SW Cachau, RE TI Molecular dynamics simulations of proteins with a polarizable two-state model for the peptide bond. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 067-COMP BP U703 EP U704 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902089 ER PT J AU Rogers, RD Brechbiel, MW Planalp, RP AF Rogers, RD Brechbiel, MW Planalp, RP TI Structural and steric effect study of metal complexes of novel hexadentate ligands derived from cis-1, 3, 5-triaminocyclohexane framework. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. NIH, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 645-INOR BP U195 EP U195 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000644 ER PT J AU Sharma, V Oksman, A Gluzman, IY Wellems, TE Goldberg, DE Piwnica-Worms, D AF Sharma, V Oksman, A Gluzman, IY Wellems, TE Goldberg, DE Piwnica-Worms, D TI Targeting Plasmodium falciparum candidate chloroquine-resistance protein (CG2) with novel antimalarial metal(III) complexes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 226-MEDI BP U269 EP U269 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000876 ER PT J AU Shelby, MD AF Shelby, MD TI Issues of test system validation in endocrine disruptor toxicology. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 111-ENVR BP U793 EP U793 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234902331 ER PT J AU Shin, KJ Marquez, VE AF Shin, KJ Marquez, VE TI Conformationally constrained carbocyclic analogues of S-adenosylmethionine and S-adenosylhomocysteine. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 241-MEDI BP U274 EP U274 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000891 ER PT J AU Stillwell, WG Turesky, RJ Sinha, R Tannenbaum, SR AF Stillwell, WG Turesky, RJ Sinha, R Tannenbaum, SR TI Measurement of the glucuronide metabolite of 2-(hydroxyamino)-MelQx in human urine. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Nestle Res Ctr, CH-1000 Lausanne, Switzerland. MIT, Div Toxicol, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 041-TOXI BP U557 EP U557 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901611 ER PT J AU Tarasov, S Casas-Finet, J Cholody, WM Michejda, CJ AF Tarasov, S Casas-Finet, J Cholody, WM Michejda, CJ TI Photophysical properties of DNA-bisimidazoacridone complexes and related model systems. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 117-TOXI BP U579 EP U579 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901685 ER PT J AU Tawa, GJ Gussio, R Pattabiraman, N Wiegand, A Pallansch, LA Buckheit, RW Zaharevitz, DW AF Tawa, GJ Gussio, R Pattabiraman, N Wiegand, A Pallansch, LA Buckheit, RW Zaharevitz, DW TI Selecting compounds for biological testing by using a computational estimate of solvation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Biomed Supercomp Ctr, SAIC, So Res Inst, Frederick, MD 21702 USA. NCI, Target Struct Based Drug Discovery Grp, ITB, DTP,So Res Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 328-MEDI BP U300 EP U300 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000976 ER PT J AU Tian, X Dersch, CM McCullough, K Horel, R Rothman, RB Rice, KC AF Tian, X Dersch, CM McCullough, K Horel, R Rothman, RB Rice, KC TI Synthesis and biological activities of 14-alkyl opioid ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, IRP, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 23 PY 1998 VL 216 MA 296-MEDI BP U291 EP U291 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000944 ER PT J AU Ioannidis, JPA Lau, J AF Ioannidis, JPA Lau, J TI Can quality of clinical trials and meta-analyses be quantified? SO LANCET LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIALS C1 NIAID, Therapeut Res Program, DAIDS, NIH, Rockville, MD 20852 USA. Tufts Univ, Sch Med, New England Med Ctr Hosp, Div Clin Care Res, Boston, MA 02111 USA. RP Ioannidis, JPA (reprint author), NIAID, Therapeut Res Program, DAIDS, NIH, Rockville, MD 20852 USA. RI Ioannidis, John/G-9836-2011 NR 7 TC 48 Z9 49 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 22 PY 1998 VL 352 IS 9128 BP 590 EP 591 DI 10.1016/S0140-6736(98)22034-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 113TE UT WOS:000075567400002 PM 9746014 ER PT J AU Wolf, E Vassilev, A Makino, Y Sali, A Nakatani, Y Burley, SK AF Wolf, E Vassilev, A Makino, Y Sali, A Nakatani, Y Burley, SK TI Crystal structure of a GCN5-related N-acetyltransferase: Serratia marcescens aminoglycoside 3-N-acetyltransferase SO CELL LA English DT Article ID COENZYME-A BINDING; PROTEIN STRUCTURES; ANOMALOUS DIFFRACTION; HISTONE ACETYLATION; GENE; RECOGNITION; CHROMATIN; ALIGNMENT; PROGRAM; ERRORS AB The X-ray structure of a canonical GCN5-related N-acetyltransferase (GNAT), Serratia marcescens aminoglycoside 3-N-acetyltransferase, bound to coenzyme A (CoA) has been determined at 2.3 Angstrom resolution. The single domain alpha/beta protein resembles a cupped right hand wrapped around a cylinder and consists of a highly curved, six-stranded beta sheet of mixed polarity that is sandwiched between four alpha helices. The structure includes all four conserved GNAT motifs (C, D, A, and B) and represents the catalytic core of this large enzyme superfamily. Acetyl CoA recognition is mediated by a beta alpha structure derived from GNAT motif A, which presents an invariant Arg/Gln-X-X-Gly-X-Gly/Ala segment for hydrogen bonding with the cofactor. Motif B contributes acidic residues to the binding site for the positively charged antibiotic substrate. C1 Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Burley, SK (reprint author), Rockefeller Univ, Lab Mol Biophys, 1230 York Ave, New York, NY 10021 USA. RI Wolf, Eva/G-7340-2014 FU NIGMS NIH HHS [GM54762] NR 49 TC 156 Z9 168 U1 6 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 21 PY 1998 VL 94 IS 4 BP 439 EP 449 DI 10.1016/S0092-8674(00)81585-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 113GB UT WOS:000075541100006 PM 9727487 ER PT J AU Hiom, K Melek, M Gellert, M AF Hiom, K Melek, M Gellert, M TI DNA transposition by the RAG1 and RAG2 proteins: A possible source of oncogenic translocations SO CELL LA English DT Article ID POLYNUCLEOTIDYL TRANSFER-REACTIONS; V(D)J RECOMBINATION; CHROMOSOMAL TRANSLOCATION; STRAND TRANSFER; SIGNAL ENDS; TARGET SITE; MECHANISM; CLEAVAGE; INTEGRATION; GENES AB The RAG1 and RAG2 proteins are known to initiate V(D)J recombination by making a double-strand break between the recombination signal sequence (RSS) and the neighboring coding DNA. We show that these proteins can also drive the coupled insertion of cleaved recombination signals into new DNA sites in a transpositional reaction. This RAG-mediated DNA transfer provides strong evidence for the evolution of the V(D)J recombination system from an ancient mobile DNA element and suggests that repeated transposition may have promoted the expansion of the antigen receptor loci. The inappropriate diversion of V(D)J rearrangement to a transpositional pathway may also help to explain certain types of DNA translocation associated with lymphatic tumors. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Hiom, Kevin/B-4374-2009 NR 40 TC 368 Z9 375 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 21 PY 1998 VL 94 IS 4 BP 463 EP 470 DI 10.1016/S0092-8674(00)81587-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 113GB UT WOS:000075541100008 PM 9727489 ER PT J AU Sueyoshi, T Kakuta, Y Pedersen, LC Wall, FE Pedersen, LG Negishi, M AF Sueyoshi, T Kakuta, Y Pedersen, LC Wall, FE Pedersen, LG Negishi, M TI A role of Lys(614) in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase SO FEBS LETTERS LA English DT Article DE lysine-614; sulfotransferase ID HAMSTER OVARY CELLS; ESTROGEN SULFOTRANSFERASE; MOLECULAR-CLONING; PURIFICATION; EXPRESSION; BINDING AB An active sulfotransferase (ST, residues 558-882) domain of the human heparan sulfate N-deacetylase/N-sulfotransferase (hHSNST) has been identified by aligning the amino acid sequence of hHSNST to that of mouse estrogen sulfotransferase (EST), The bacterially expressed ST domain transfers the 5'-sulfuryl group of 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to only deacetylated heparin with an efficiency similar to that previously reported for the purified rat HSNST. Moreover, the K-m,K-PAPS (2.1 mu M) of the ST domain is also similar to that of the rat enzyme. Lys(48) is a key residue in mEST catalysis, The residue corresponding to Lys(48) is conserved in all known heparan sulfate sulfotransferases (Lys(614) in the ST domain of hHSNST). Mutation of Lys(614) to Ala abolishes N-sulfotransferase activity, indicating an important catalytic role of Lys(614) in the ST domain. Crystals of the ST domain have been grown (orthorhombic space group P2(1)2(1)2) with diffraction to 2.5 A resolution. (C) 1998 Federation of European Biochemical Societies. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27541 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 23 TC 44 Z9 46 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 21 PY 1998 VL 433 IS 3 BP 211 EP 214 DI 10.1016/S0014-5793(98)00913-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 115EB UT WOS:000075649600006 PM 9744796 ER PT J AU Moss, J Vaughan, M AF Moss, J Vaughan, M TI Molecules in the ARF orbit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; NUCLEOTIDE-EXCHANGE PROTEIN; GUANINE-NUCLEOTIDE; FACTOR DOMAIN; BREFELDIN-A; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SACCHAROMYCES-CEREVISIAE; HOMOLOGY DOMAINS; CHOLERA-TOXIN C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10,10 Ctr Dr MSC 1434, Bethesda, MD 20892 USA. NR 57 TC 280 Z9 281 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21431 EP 21434 DI 10.1074/jbc.273.34.21431 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600001 PM 9705267 ER PT J AU McEnery, MW Copeland, TD Vance, CL AF McEnery, MW Copeland, TD Vance, CL TI Altered expression and assembly of N-type calcium channel alpha(1B) and beta subunits in epileptic lethargic (lh/lh) mouse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OMEGA-CONOTOXIN GVIA; MUTANT MICE; ABSENCE SEIZURES; CA2+ CHANNELS; RAT-BRAIN; ATAXIA; HETEROGENEITY; RECEPTOR; CLONING; BINDING AB Voltage-dependent calcium channels (VDCC) are multisubunit complexes whose expression and targeting require the assembly of the pore-forming alpha(1) with auxiliary beta and alpha(2)/delta subunits, The developmentally regulated expression and differential assembly of beta isoforms with the cu,, subunit to form N-type VDCC suggested a unique role for the beta 4 isoform in VDCC maturation (Vance, C. L., Begg, C. M., Lee, W.-L., Haase, H., Copeland, T. D., and McEnery, M. W. (1998) J, Biol. Chem, 273, 14495-14502), The focus of this study is the expression and assembly of alpha(1B) and beta isoforms in the epileptic mouse, lethargic (lh/lh), a mutant anticipated to produce a truncated beta 4 subunit (Burgess, D, L,, Jones, J, M., Meisler, M. H., and Noebels, J, L, (1997) Cell 88, 385-392), In this report, we demonstrate that neither full-length nor truncated beta 4 protein is expressed in lh/lh mice. The absence of beta 4 in lh/lh mice is associated with decreased expression of N-type VDCC in forebrain and cerebellum. The most surprising characteristic of the lh/lh mouse is increased expression of beta 1b protein. This result suggests a previously unidentified cellular mechanism wherein expression of the total pool of available beta subunits is under tight metabolic regulation. As a consequence of increased beta 1b expression, the beta 1b is increased in its incorporation into alpha(1B)/beta complexes relative to wild type. Thus, in striking similarity to the population of N-type VDCC present in immature rat brain, the population of N-type VDCC present in adult lh/lh mice is characterized by the absence of beta 4 with increased beta 1b expression and assembly into N-type VDCC, It is intriguing to speculate that the increased excitability and susceptibility to seizures observed in the lh/lh mouse arises from the inappropriate expression of an immature population of N-type VDCC throughout neuronal development. C1 Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. RP McEnery, MW (reprint author), Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 33 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21435 EP 21438 DI 10.1074/jbc.273.34.21435 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600002 PM 9705268 ER PT J AU Kamitani, H Geller, M Eling, T AF Kamitani, H Geller, M Eling, T TI Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN COLON-CANCER; HAMSTER EMBRYO FIBROBLASTS; SODIUM-BUTYRATE; NORDIHYDROGUAIARETIC ACID; ALVEOLAR MACROPHAGES; MOLECULAR-CLONING; EPITHELIAL-CELLS; ARACHIDONIC-ACID; SYNTHASE-2 GENE; PHORBOL ESTER AB We studied arachidonic acid metabolism and the expression of cyclooxygenase(Cox) and 15-lipoxygenase (15-LO) in the human colorectal carcinoma cell line, Caco-2, which undergo apoptosis and cell differentiation in the presence of sodium butyrate (NaBT), Caco-2 cells expressed very low levels of Cox-1 but highly expressed Cox-a. NaBT treatment shifted the arachidonic acid metabolites by cell lysates from prostaglandins to 15-hydroxyeicosatetraenoic acid, indicating the presence of a 15-LO. Linoleic acid, an excellent substrate for 15-LO, was metabolized poorly by the Caco-2 cells, but NaBT treatment shifted metabolism to 15-LO metabolite, 13(S)-hydroxyoctadecadienoic acid. Caco-2 cells expressed a 15-LO but only after treatment with NaBT, as determined by Northern blotting. Immunoblotting with anti-human 15-LO antibody detected a 72-kDa band in NaBT-treated Caco-2 cells. Expression of 15-LO mRNA was dependent on the duration of NaBT treatment, with the highest expression observed between 10 and 24 h, Results from expression and metabolism studies with arachidonic and linoleic acid cells indicated Cox-a was responsible for the lipid metabolism in control cells, whereas 15-LO was the major enzyme responsible after NaBT induction of apoptosis and cell differentiation. The 15-LO in Caco-2 cells was characterized as human reticulocyte 15-LO by reverse transcription-polymerase chain reaction and restriction enzyme analysis. The expression of 15-LO and 15-hydroxyeicosatetraenoic acid or 13(S)-hydroxyoctadecadienoic acid formation correlates with cell differentiation or apoptosis in Caco-2 cells induced by NaBT, The addition of nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly increased NaBT-induced apoptosis, whereas the addition of indomethacin did not alter NaBT-induced apoptosis in the Caco-2 cells. However, indomethacin treatment decreased the expression of Cox-a in NaBT-treated cells and significantly increased the expression of 15-LO during NaBT treatment, These studies suggest a role for 15-LO, in addition to Cox-a, in modulating NaBT-induced apoptosis and cell differentiation in human colorectal carcinoma cells. C1 NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eling, T (reprint author), NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 53 TC 127 Z9 127 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21569 EP 21577 DI 10.1074/jbc.273.34.21569 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600021 PM 9705287 ER PT J AU Winkler, DG Cutler, RE Drugan, JK Campbell, S Morrison, DK Cooper, JA AF Winkler, DG Cutler, RE Drugan, JK Campbell, S Morrison, DK Cooper, JA TI Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; PLASMA-MEMBRANE; PROTEIN-KINASE; MAP KINASE; TYROSINE PHOSPHORYLATION; HA-RAS; ACTIVATION; 14-3-3-PROTEINS; TRANSFORMATION; COMPLEX AB We have identified mutations in Raf-l that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-l binding (Winkler, D. G., Johnson, J. C., Cooper, J, A., and Vojtek, A. B. (1997) J. Biol, Chem. 272, 24402-24409). One mutation in Raf-l, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-l cysteine-rich domain were isolated multiple times. These Raf-l mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-l, We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-l is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-l and increasing Raf-l activity. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Mol Basis Carcinogenesis Lab, ABL Basic Res, Frederick Canc Res & Dev Ctr, Frederick, MD 20702 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Cooper, JA (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N A2025,POB 9024, Seattle, WA 98109 USA. FU NCI NIH HHS [CA54786, CA70308, CA66281] NR 48 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21578 EP 21584 DI 10.1074/jbc.273.34.21578 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600022 PM 9705288 ER PT J AU Reed, AL Yamazaki, H Kaufman, JD Rubinstein, Y Murphy, B Johnson, AC AF Reed, AL Yamazaki, H Kaufman, JD Rubinstein, Y Murphy, B Johnson, AC TI Molecular cloning and characterization of a transcription regulator with homology to GC-binding factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; FACTOR RECEPTOR GENE; PROTO-ONCOGENE; CELL-LINES; REPRESSES TRANSCRIPTION; MESSENGER-RNA; RETINOIC ACID; HUMAN P53; PROMOTER; IDENTIFICATION AB GC-binding factor (GCF) represses transcription of certain genes and is encoded by a 3.0-kilobase mRNA (Kageyama, R., and Pastan, I. (1989) Cell 59, 815-825). The GCF cDNA hybridizes to two additional mRNA species, 4.2 and 1.2 kilobases. We have used differential hybridization to identify a cDNA clone (termed GCF2) for the 4.2-kilobase mRNA and find that it is highly expressed in HUT-102 cells. The open reading frame consists of 2256 nucleotides and encodes a protein of 752 amino acids with a calculated molecular mass of 83 kilodaltons. GCF2 expressed in vitro using reticulocyte lysates and Escherichia coli migrates as a 160-kilodalton protein in SDS-polyacrylamide gel electrophoresis but has a molecular mass of 83 kilodaltons as determined by mass spectrum analysis. GCF2 binds to epidermal growth factor receptor promoter fragments, and the major binding site is located between nucleotides -249 and -233. Cotransfection assays show that GCF2 acts to repress transcription from the epidermal growth factor receptor promoter in constructs containing the major GCF2 binding site and not when the site had been mutated. Thus, GCF2 is a newly identified transcriptional repressor with aberrant electrophoretic mobility. C1 NCI, Mol Biol Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Johnson, AC (reprint author), NCI, Mol Biol Lab, DBS, NIH, Bldg 37,Rm 2D18,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 45 TC 39 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21594 EP 21602 DI 10.1074/jbc.273.34.21594 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600024 PM 9705290 ER PT J AU Pan, CJ Lei, KJ Chou, JY AF Pan, CJ Lei, KJ Chou, JY TI Asparagine-linked oligosaccharides are localized to a luminal hydrophilic loop in human glucose-6-phosphatase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; ENDOPLASMIC-RETICULUM; ENZYME-DEFICIENT; GENE; MUTATIONS; 1A; GLYCOPROTEINS; MEMBRANE; TYPE-1A AB yDeficiency of glucose-6-phosphatase (G6Pase), an endoplasmic reticulum transmembrane glycoprotein, causes glycogen storage disease type la, We have recently shown that human G6Pase contains an odd number of transmembrane segments, supporting a nine-transmembrane helical model for this enzyme. Sequence analysis predicts the presence of three potential asparagine (N)-linked glycosylation sites, (NTS)-T-96, N(203)AS, and (NSS)-S-276, conserved among mammalian G6Pases. According to this model, Asn(96), located in a 37-residue luminal loop, is a potential acceptor for oligosaccharides, whereas Asn(203) and Asn(276), located in a 12-residue cytoplasmic loop and helix 7, respectively, would not be utilized for this purpose. We therefore characterized mutant G6Pases lacking one, two, or all three potential N-linked glycosylation sites. Western blot and in vitro translation studies showed that G6Pase is glycosylated only at Asn(96), further validating the nine-transmembrane topology model. Substituting Asn96 with an Ala (N96A) moderately reduced enzymatic activity and had no effect on G6Pase synthesis or degradation, suggesting that oligosaccharide chains do not play a major role in protecting the enzyme from proteolytic degradation. Ln contrast, mutation of Asn(276) to an Ala (N276A) destabilized the enzyme and markedly reduced enzymatic activity. We present additional evidence suggesting that the integrity of transmembrane helices is essential for C6Pase stability and catalytic activity. C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHD, Heritable Disorders Branch, NIH, Bldg 10,Rm 98241, Bethesda, MD 20892 USA. NR 24 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 21658 EP 21662 DI 10.1074/jbc.273.34.21658 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600033 PM 9705299 ER PT J AU Radko, SP Chrambach, A Weiss, GH AF Radko, SP Chrambach, A Weiss, GH TI Asymmetry of protein peaks in capillary zone electrophoresis: effect of starting zone length and presence of polymer SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 11th International Symposium on High Performance Capillary Electrophoresis and Related Microscale Techniques (HPCE 98) CY FEB 01-05, 1998 CL ORLANDO, FLORIDA DE band profiles; buffer composition; proteins ID GEL-ELECTROPHORESIS; WALL ADSORPTION; DNA; POLYACRYLAMIDE; SIMULATION; INJECTION; MODEL AB The asymmetry of R-phycoerythrin (M-r=240000) peaks in capillary zone electrophoresis measured as ln[(t(m)-t(1))/(t(2)-t(m))], where t(m), t(1) and t(2) are migration times of the peak mode and at the intersection of the peak width at half-height with the ascending and descending limbs, respectively, was found to undergo a transition from negative to positive values with increasing starting zone length. The transition is compatible with a mathematical model of peak dispersion which assumes that an interaction of protein with the capillary walls governs the evolution of the peak during capillary zone electrophoresis. Models assuming a final peak shape defined solely by longitudinal diffusion, or by a heterogeneity with regard to mobility or by a conductivity difference between analyte zone and background electrolyte, have failed to give rise to a change in the sign of peak asymmetry when the starting zone length is varied. The presence of polyethylene glycol in the buffer within a concentration range up to 4% does not appreciably affect the peak asymmetry regardless of whether the concentration regime is dilute or semi-dilute. Above 4% of polyethylene glycol, the asymmetry becomes nearly independent of starting zone length, and progressively negative with increasing polymer concentration. The concentration range at which the transition from negative to positive asymmetry disappears coincides with that at which the average mesh size of the polymer network falls below the size of the protein. (C) 1998 Published by Elsevier Science B.V. C1 NICHD, Macromol Anal Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHD, Macromol Anal Sect, Mol & Cellular Biol Lab, NIH, Bldg 10,Room 9D50, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 21 PY 1998 VL 817 IS 1-2 BP 253 EP 262 DI 10.1016/S0021-9673(98)00470-1 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 120MP UT WOS:000075960400032 PM 9764498 ER PT J AU Bera, TK Onda, M Brinkmann, U Pastan, I AF Bera, TK Onda, M Brinkmann, U Pastan, I TI A bivalent disulfide-stabilized Fv with improved antigen binding to erbB2 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE antibody engineering; bivalent dsFv; cancer therapy ID SINGLE-CHAIN FV; BISPECIFIC ANTIBODY FRAGMENTS; ESCHERICHIA-COLI; RECOMBINANT IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; IMMUNOGLOBULIN FORMS; ANTITUMOR-ACTIVITY; FUSION PROTEINS; MINIANTIBODIES; EXPRESSION AB We have used protein engineering to generate a stable bivalent Fv molecule of the anti-erbB2 monoclonal antibody e23. The V-H and V-L domains of the Fv are Linked to each other by a disulfide bond and the two Fvs are connected by a flexible 15 amino acid residue (Gly(4)-Ser)(3) linker. The e23 (dsFv)(2) molecule is fused to a truncated form of Pseudomonas exotoxin to generate a bivalent disulfide-stabilized, (dsFv)(2), immunotoxin. The immunotoxin was expressed in Escherichia coli, refolded in vitro and purified to about 95% purity. Binding studies demonstrated that the (dsFv)(2) molecule has a much higher affinity for erbB2 than a monovalent dsFv molecule and a similar binding affinity as the parental antibody e23. The (dsFv)(2) immunotoxin was 5 to 20-fold more cytotoxic to two e23 antigen-positive cell Lines than the monovalent dsFv immunotoxin. The bivalent dsFv molecule is very stable, retaining 94% of its activity after a 24 hours incubation in human serum at 37 degrees C. Two other molecules with shorter linkers five and ten amino acid residues in length were produced and showed similar activities as the molecule containing a 15 amino acid residue linker. The bivalency, stability and the relative ease of purification makes these e23 (dsFv)(2) molecules valuable reagents for cancer immunotherapy and diagnosis. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 51 TC 29 Z9 34 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 21 PY 1998 VL 281 IS 3 BP 475 EP 483 DI 10.1006/jmbi.1998.1948 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112UR UT WOS:000075513200009 PM 9698563 ER PT J AU Pozsgay, V AF Pozsgay, V TI Synthesis of glycoconjugate vaccines against Shigella dysenteriae type I SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID O-SPECIFIC POLYSACCHARIDE; INFLUENZAE TYPE-B; ARTIFICIAL SALMONELLA VACCINES; NUCLEAR-MAGNETIC-RESONANCE; CONJUGATE VACCINES; T-CELL; OLIGOSACCHARIDE-PROTEIN; CAPSULAR POLYSACCHARIDE; PROMOTED REACTIONS; NMR-SPECTROSCOPY AB Syntheses of a hexadecasaccharide and smaller fragments corresponding to one-four repeating units of the O-specific polysaccharide of Shigella dysenteriae type 1 are reported in a reactive aglyconlinked from. Two tetrasaccharide donor/acceptor repeating units were assembled from monosaccharide precursors in a stepwise fashion and used in a linear, iterative manner to construct the higher-membered saccharides using Schmidt's glycosylation technique that proved superior to others tested. Single-point attachment of the saccharides to human serum albumin, using a secondary heterobifunctional spacer, afforded a range of glycoconjugates for a detailed evaluation of their immunological characteristics. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 86 TC 59 Z9 60 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 21 PY 1998 VL 63 IS 17 BP 5983 EP 5999 DI 10.1021/jo980660a PG 17 WC Chemistry, Organic SC Chemistry GA 116XL UT WOS:000075750300044 ER PT J AU Martinez, L Chignell, CF AF Martinez, L Chignell, CF TI Photocleavage of DNA by the fluoroquinolone antibacterials SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE fluoroquinolones; lomefloxacin; fleroxacin; norfloxacin; nalidixic acid; enoxacin; DNA; photocleavage ID STRAND-BREAKING ACTIVITIES; ANTIMICROBIAL AGENTS; COMET ASSAY; PHOTOLYSIS; PHOTOCHEMISTRY; LOMEFLOXACIN; IRRADIATION; ACID AB We have determined the relative efficiencies for the formation of single strand breaks (ssbs) after the UVA irradiation of pBR322 DNA and various fluoroquinolone (fleroxacin, lomefloxacin, norfloxacin) and naphthyridine (nalidixic acid, enoxacin) antibacterials. After correcting for the differences in absorption, the relative order for DNA photocleaving activity under anaerobic conditions is: fleroxacin, lomefloxacin > nalidixic acid >> norfloxacin > enoxacin. In general, fluoroquinolones having fluorine substituents at the C-6 and C-8 positions (lomefloxacin and fleroxacin) are 10-fold more efficient in generating ssbs than those having only a C-6 fluorine atom (norfloxacin). The effect of oxygen on photoinduced DNA damage caused by these antibacterials is complex, but our data imply that active oxygen species are not necessary for DNA scission by these molecules, and indeed, may sometimes inhibit it. Lomefloxacin ethyl ester, which cannot undergo decarboxylation, is as active as lomefloxacin itself. Thus the free radical generated by decarboxylation is unlikely to be the active species involved in photoinduced fluoroquinolone DNA cleavage. For lomefloxacin and fleroxacin, DNA damage probably results from the generation of a carbene at C-8 as a result of photoinduced loss of their F-8 atom as fluoride upon UVA irradiation. Fluoroquinolones lacking a C-8 fluorine atom must operate by a different mechanism. While photocleavage of pBR322 DNA does not necessarily mean that duplex DNA will be cleaved under the same conditions, nevertheless lomefloxacin and fleroxacin, the two most photogenotoxic fluoroquinolones, did cause the most damage to the plasmid DNA. Published by Elsevier Science S.A. C1 NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 73 Z9 74 U1 3 U2 7 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD AUG 21 PY 1998 VL 45 IS 1 BP 51 EP 59 DI 10.1016/S1011-1344(98)00160-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 136VE UT WOS:000076879200009 PM 9819899 ER PT J AU Gold, PW AF Gold, PW TI ADHD and the nature of self control SO SCIENCE LA English DT Book Review C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, 10-3S231,10 Ctr Dr MSC-1284, Bethesda, MD 20892 USA. NR 1 TC 3 Z9 3 U1 1 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 21 PY 1998 VL 281 IS 5380 BP 1149 EP 1150 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 113CE UT WOS:000075531200033 ER PT J AU Huhn, RD Dave, HP AF Huhn, RD Dave, HP TI Staphylococcal psoas abscess SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 NHLBI, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. RP Huhn, RD (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 1998 VL 339 IS 8 BP 519 EP 519 DI 10.1056/NEJM199808203390805 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 111PN UT WOS:000075447000005 PM 9709045 ER PT J AU Breman, JG Henderson, DA AF Breman, JG Henderson, DA TI Poxvirus dilemmas - Monkeypox, smallpox, and biologic terrorism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VIRUS STOCKS; GENOME; SEQUENCE; STRAIN; DNA C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. RP Breman, JG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 112 Z9 116 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 20 PY 1998 VL 339 IS 8 BP 556 EP 559 DI 10.1056/NEJM199808203390811 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 111PN UT WOS:000075447000011 PM 9709051 ER PT J AU Stucki, M Pascucci, B Parlanti, E Fortini, P Wilson, SH Hubscher, U Dogliotti, E AF Stucki, M Pascucci, B Parlanti, E Fortini, P Wilson, SH Hubscher, U Dogliotti, E TI Mammalian base excision repair by DNA polymerases delta and epsilon SO ONCOGENE LA English DT Article DE DNA repair; DNA polymerases; abasic sites ID CELL NUCLEAR ANTIGEN; REPLICATION PROTEIN-A; MISMATCH REPAIR; ESCHERICHIA-COLI; CALF THYMUS; LIGASE-I; FACTOR-C; BETA; REQUIREMENT; BINDING AB Two distinct pathways for completion of base excision repair (BER) have been discovered in eukaryotes: the DNA polymerase beta (Pol beta)-dependent short-patch pathway that involves the replacement of a single nucleotide and the long-patch pathway that entails the resynthesis of 2-6 nucleotides and requires PCNA, We have used cell extracts from Pol beta-deleted mouse fibroblasts to separate subfractions containing either Pol delta or Pol epsilon. These fractions were then tested for their ability to perform both short- and long-patch BER in an in vitro repair assay, using a circular DNA template, containing a single abasic site at a defined position. Remarkably, both Pol delta and Pol epsilon were able to replace a single nucleotide at the lesion site, but the repair reaction is delayed compared to single nucleotide replacement by Pol beta, Furthermore, our observations indicated, that either Pol delta and/or Pol epsilon participate in the long-patch BER. PCNA and RF-C, but not RP-A are required for this process. Our data show for the first time that Pol delta and/or Pol epsilon are directly involved in the long-patch BER of abasic sites and might function as back-up system for Pol beta in one-gap filling reactions. C1 Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, I-00161 Rome, Italy. Univ Zurich, Inst Vet Biochem, CH-8057 Zurich, Switzerland. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Dogliotti, E (reprint author), Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, Vle Regina Elena 299, I-00161 Rome, Italy. NR 38 TC 147 Z9 150 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 20 PY 1998 VL 17 IS 7 BP 835 EP 843 DI 10.1038/sj.onc.1202001 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 111QH UT WOS:000075448800005 PM 9780000 ER PT J AU Burke, TR Yao, ZJ Zhao, H Milne, GWA Wu, L Zhang, ZY Voigt, JH AF Burke, TR Yao, ZJ Zhao, H Milne, GWA Wu, L Zhang, ZY Voigt, JH TI Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides SO TETRAHEDRON LA English DT Article ID SOLID-PHASE SYNTHESIS; ENZYME-CATALYZED-HYDROLYSIS; DERIVATIVES; ANALOGS; PHENYLALANINE; DOMAIN; PTP1 AB Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus-containing phosphotyrosyl (pTyr) mimetics, which utilize carboxylic groups to provide functionality normally afforded by the pTyr phosphate group. To demonstrate the utility of these analogues, the protein-tyrosine phosphatase-directed peptides Ac-D-A-D-E-X-L-amide (28 - 30) were prepared, where X = pTyr mimetic. In the case where X = 3-carboxy-4-(O-carboxymethyl)-L-tyrosine (8) a K-i value of 3.6 mu M was obtained against PTP1, which equals the Km of the parent pTyr containing peptide. Besides tyrosine phosphatases, these analogues may be useful in a number of contexts, including SH2 domain and phosphotyrosine binding domain systems. Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, Bldg 37,Rm 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 30 TC 54 Z9 55 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD AUG 20 PY 1998 VL 54 IS 34 BP 9981 EP 9994 DI 10.1016/S0040-4020(98)00590-0 PG 14 WC Chemistry, Organic SC Chemistry GA 107DB UT WOS:000075190800004 ER PT J AU Ragano-Caracciolo, M Berlin, WK Miller, MW Hanover, JA AF Ragano-Caracciolo, M Berlin, WK Miller, MW Hanover, JA TI Nuclear glycogen and glycogen synthase kinase 3 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE phosphorylation ID PROTEIN PHOSPHATASE-1; MOLECULAR-CLONING; PORE COMPLEX; EGG EXTRACTS; CELL-CYCLE; EXPRESSION; CHROMATIN; ENVELOPE; IDENTIFICATION; NEURONS AB Glycogen is the principal storage form of glucose in animal cells. It accumulates in electron-dense cytoplasmic granules and is synthesized by glycogen synthase (GS), the rate-limiting enzyme of glycogen deposition. Glycogen synthase kinase-3 (GSK-3) is a protein kinase that phosphorylates GS. Two nearly identical forms of GSK-3 exist: GSK-3 alpha and GSK-3 beta. Both are constitutively active in resting cells and their activity can be modulated by hormones and growth factors. GSK-3 is implicated in the regulation of many physiological responses in mammalian cells by phosphorylating substrates including neuronal cell adhesion molecule, neurofilaments, synapsin I, and tau. Recent observations point to functions for glycogen and glycogen metabolism in the nucleus. GSK-3 phosphorylates several transcription factors, and we have recently shown that it modifies the major nuclear pore protein p62. It also regulates PK1, a protein kinase required for maintaining the interphase state and for DNA replication in cycling Xenopus egg extracts. Recently, glycogen was shown to be required for nuclear reformation in vitro using ovulated Xenopus laevis egg lysates. Because neither glycogen nor GSK-3 has been localized to the nuclear envelope or intranuclear sites, glycogen and GSK-3 activities were measured in rat liver nuclei and nuclear reformation extracts. Significant quantities of glycogen-like material co-purified with the rat-liver nuclear envelope. GSK-3 is also highly enriched in the glycogen pellet of egg extracts of Xenopus that is required for nuclear assembly in vitro. Eased on the finding that enzymes of glycogen metabolism copurify with glycogen, we propose that glycogen may serve a structural role as a scaffold for nuclear assembly and sequestration of critical kinases and phosphatases in the nucleus. (C) 1998 Academic Press. C1 NIDKDD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. RP Ragano-Caracciolo, M (reprint author), NIDKDD, Lab Cell Biochem & Biol, NIH, Bldg 8,Rm 402,8 Ctr Dr, Bethesda, MD 20892 USA. NR 35 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 19 PY 1998 VL 249 IS 2 BP 422 EP 427 DI 10.1006/bbrc.1998.9159 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112VT UT WOS:000075515900023 PM 9712712 ER PT J AU Ceha, HM Nasser, I Medema, RH Slebos, RJC AF Ceha, HM Nasser, I Medema, RH Slebos, RJC TI Several noncontiguous domains of CDK4 are involved in binding to the p16 tumor suppressor protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cell cycle; p16; CDK4; charged-to-alanine scanning mutagenesis ID MUTATIONS; CANCER; MELANOMA; PATHWAY; GENE; P16(INK4A); CELLS; MDM2 AB Cyclin-dependent kinase 4 (CDK4) is a key molecule in the regulation of cell cycle progression at the G(1)-S phase restriction point. Its activity is specifically regulated by pie (also known as p16/CDKN2A, p16(INK4a), and MTS1), a tumor suppressor frequently altered in human cancers. A specific mutation in CDK4 codon 24 (Arginine to Cysteine) prevents p16 binding and thus inhibition by p16. This mutated CDK4 acts as a dominant oncogene and has been found in both sporadic and familial melanoma. To study the effects of other mutations in CDK4, we generated a panel of 18 CDK4 mutants using Charged-to-Alanine scanning mutagenesis, and investigated the pie-binding capacity of these mutants to identify novel sites involved in pie binding. The mutant CDK4 proteins were generated by direct coupled transcription-translation in vitro and tested for binding to p16 using a p16-GST fusion protein. Several mutants demonstrated loss of pie binding. In addition to the previously identified codon 24 mutants, alterations in and around codon 22, 25, 97, and 281 all showed loss of pie binding capacity. These results indicate that several noncontiguous amino acid sequences on CDK4 are required for binding to pie, which suggests the existence of multiple sites of interaction with pie. Since pie-binding deficient CDK4 has oncogenic potential, these mutations may be present in melanomas or other human neoplasms. (C) 1998 Academic Press. C1 Univ Amsterdam, Acad Med Ctr, Dept Radiotherapy, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. Univ Utrecht Hosp, Dept Haematol, Jordan Lab, NL-3508 GA Utrecht, Netherlands. RP Slebos, RJC (reprint author), NIEHS, Mol Carcinogenesis Lab, Maildrop C2-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM SLEBOS@NIEHS.NIH.GOV OI Medema, Rene/0000-0002-6754-0381 NR 26 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 19 PY 1998 VL 249 IS 2 BP 550 EP 555 DI 10.1006/bbrc.1998.9183 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112VT UT WOS:000075515900046 PM 9712735 ER PT J AU Naficy, A Rao, MR Clemens, JD Antona, D AF Naficy, A Rao, MR Clemens, JD Antona, D TI Cholera vaccine in refugee settings - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Epictr, Paris, France. NICHHD, Bethesda, MD 20892 USA. Med Sans Frontieres, Paris, France. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Naficy, A (reprint author), Epictr, Paris, France. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 19 PY 1998 VL 280 IS 7 BP 601 EP 602 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 110ME UT WOS:000075384300020 ER PT J AU Hatch, EE Palmer, JR Titus-Ernstoff, L Noller, KL Kaufman, RH Mittendorf, R Robboy, SJ Hyer, M Cowan, CM Adam, E Colton, T Hartge, P Hoover, RN AF Hatch, EE Palmer, JR Titus-Ernstoff, L Noller, KL Kaufman, RH Mittendorf, R Robboy, SJ Hyer, M Cowan, CM Adam, E Colton, T Hartge, P Hoover, RN TI Cancer risk in women exposed to diethylstilbestrol in utero SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BREAST-CANCER; FOLLOW-UP; STILBESTROL THERAPY; YOUNG-WOMEN; PREGNANCY; MOTHERS; ADENOCARCINOMA; ESTROGENS; VAGINA AB Context. - The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers, As many as 3 million women in the United States may have been exposed to DES in utero. Objective. - To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up. Design. - A cohort study with mailed questionnaires and medical record review of reported cancer outcomes. Participants. - A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s. Main Outcome Measures. - Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters. Results. - To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result. Conclusions. - Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Stone Epidemiol Unit, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Univ Massachusetts, Med Ctr, Dept Obstet & Gynecol, Worcester, MA USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Informat Management Serv, Rockville, MD USA. RP Hatch, EE (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,MSC7362, Bethesda, MD 20892 USA. NR 29 TC 121 Z9 124 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 19 PY 1998 VL 280 IS 7 BP 630 EP 634 DI 10.1001/jama.280.7.630 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 110ME UT WOS:000075384300032 PM 9718055 ER PT J AU Enyedy, IJ Kovach, IM Brooks, BR AF Enyedy, IJ Kovach, IM Brooks, BR TI Alternate pathways for acetic acid and acetate ion release from acetylcholinesterase: a molecular dynamics study SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ACTIVE-SITE DYNAMICS; LIGAND-BINDING; SUBSTRATE-SPECIFICITY; GLOBULAR-PROTEINS; RATE CONSTANTS; FREE-ENERGY; SIMULATION; FASCICULIN; MECHANISM; RESIDUES AB Two competing passageways for the exit of acetic acid and acetate ion in Torpedo californica (Tc) acetylcholinesterase (ACHE) were studied by examining free energies of passage through two potential trajectories using the umbrella sampling technique as implemented in CHARMM. The coordinates for migration were defined as the distance from Se200 O gamma, one through the 20-Angstrom long active-site gorge ending with Trp279 and a 14-Angstrom long route ending at Arg244. The free energies were calculated in successive windows 0.5 Angstrom wide for 40-90 ps. The potential of mean force (PMF) was calculated along the coordinate for migration. The PMF for the migration of acetic acid decreases by similar to 8 kcal/mol after 8-Angstrom travel through the main gorge. The PMF profile for acetate ion migration falls to a 6 kcal/mol lower value than for acetic acid migration in the main gorge. The free energy barrier for the migration of acetate ion is 1.5 kcal/mol due to a constriction formed by Tyr121, Phe290, Phe330, and Phe331 in the main gorge. The interaction between acetic acid/acetate ion and the OH group of Tyr121 appears to guide product release through the main gorge. Acetate ion remains hydrogen-bonded to Tyr121 until it approaches Trp279 when it is expelled into bulk water. Acetic acid encounters a 6 kcal/mol barrier through the alternate pathway, while the PMF for acetate ion drops similar to 27 kcal/mol when it approaches Arg244. This is the lowest energy path. Full molecular dynamics simulations, free of restraint for 170 ps, result in the migration of acetate ion through the short channel but not through the main gorge. The results indicate that if the nascent acetic acid should ionize within 3.5 Angstrom from Ser200 O gamma it would be more likely to exit via the alternate channel than through the main gorge. C1 Catholic Univ Amer, Dept Chem, Washington, DC 20064 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kovach, IM (reprint author), Catholic Univ Amer, Dept Chem, Washington, DC 20064 USA. NR 58 TC 28 Z9 28 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 19 PY 1998 VL 120 IS 32 BP 8043 EP 8050 DI 10.1021/ja973131h PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 113LX UT WOS:000075553400005 ER PT J AU Taylor, PR Albanes, D AF Taylor, PR Albanes, D TI Selenium, vitamin E, and prostate cancer - Ready for prime time? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SUBSEQUENT RISK; SERUM SELENIUM; CARCINOMA C1 NCI, Div Clin Sci, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Taylor, PR (reprint author), NIH, 6006 Execut Blvd,Rm 321, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 12 TC 23 Z9 23 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 19 PY 1998 VL 90 IS 16 BP 1184 EP 1185 DI 10.1093/jnci/90.16.1184 PG 2 WC Oncology SC Oncology GA 112CN UT WOS:000075476700002 PM 9719074 ER PT J AU Roller, PP Wu, L Zhang, ZY Burke, TR AF Roller, PP Wu, L Zhang, ZY Burke, TR TI Potent inhibition of protein-tyrosine phosphatase-1B using the phosphotyrosyl mimetic fluoro-O-malonyl tyrosine (FOMT) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PEPTIDES AB To enhance PTP binding interactions, both inside and outside the pTyr binding pocket, a thioether-cyclized peptide has been designed based on the EGF receptor autophosphorylation sequence (EGFR(988-993)) "Asp-Ala-Asp-GlU-pTyr-Leu", in which the pTyr residue has been replaced by the nonphosphorus-containing pTyr mimetic fluoro-O-malonyltyrosine (FOMT, 2). The resulting peptide 4 exhibits a K-i value of 170 nM, making it one of the most potent inhibitors of PTP1B yet reported. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Rm 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 9 TC 26 Z9 26 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 18 PY 1998 VL 8 IS 16 BP 2149 EP 2150 DI 10.1016/S0960-894X(98)00376-X PG 2 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 115XT UT WOS:000075692200018 PM 9873503 ER PT J AU Tang, MJ Bruck, I Eritja, R Turner, J Frank, EG Woodgate, R O'Donnell, M Goodman, MF AF Tang, MJ Bruck, I Eritja, R Turner, J Frank, EG Woodgate, R O'Donnell, M Goodman, MF TI Biochemical basis of SOS-induced mutagenesis in Escherichia coli: Reconstitution of in vitro lesion bypass dependent on the UmuD ' C-2 mutagenic complex and RecA protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-POLYMERASE-III; REVERSE-TRANSCRIPTASE; MUTATOR ACTIVITY; ABASIC LESIONS; UV-MUTAGENESIS; REPAIR; UMUC; PURIFICATION; REPLICATION; INSERTION AB Damage-induced SOS mutagenesis requiring the UmuD'C proteins occurs as part of the cells' global response to DNA damage. In vitro studies on the biochemical basis of SOS mutagenesis have been hampered by difficulties in obtaining biologically active UmuC protein, which, when overproduced, is insoluble in aqueous solution. We have circumvented this problem by purifying the UmuD(2)'C complex in soluble form and have used it to reconstitute an SOS lesion bypass system in vitro. Stimulated bypass of a site-directed model abasic lesion occurs in the presence of UmuD(2)'C, activated RecA protein (RecA*), beta-sliding clamp, gamma-clamp loading complex, single-stranded binding protein (SSB), and either DNA polymerases III or II. Synthesis in the presence of UmuD(2)'C is nonprocessive on damaged and undamaged DNA. No lesion bypass is observed when wild-type RecA is replaced with RecA1730, a mutant that is specifically defective for Umu-dependent mutagenesis. Perhaps the most noteworthy property of UmuD(2)'C resides in its ability to stimulate both nucleotide misincorporation and mismatch extension at aberrant and normal template sites. These observations provide a biochemical basis for the role of the Umu complex in SOS-targeted and SOS-untargeted mutagenesis. C1 Univ So Calif, Dept Biol Sci, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. European Mol Biol Org, D-69012 Heidelberg, Germany. Rockefeller Univ, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Hedco Mol Biol Labs, SHS Room 172,Univ Pk, Los Angeles, CA 90089 USA. EM mgoodman@mizar.usc.edu RI eritja, ramon/B-5613-2008 OI eritja, ramon/0000-0001-5383-9334 FU NIGMS NIH HHS [GM29558, GM42554] NR 41 TC 162 Z9 163 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 9755 EP 9760 DI 10.1073/pnas.95.17.9755 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200011 PM 9707548 ER PT J AU Shioda, T Lechleider, RJ Dunwoodie, SL Li, HC Yahata, T de Caestecker, MP Fenner, MH Roberts, AB Isselbacher, KJ AF Shioda, T Lechleider, RJ Dunwoodie, SL Li, HC Yahata, T de Caestecker, MP Fenner, MH Roberts, AB Isselbacher, KJ TI Transcriptional activating activity of Smad4: Roles of SMAD hetero-oligomerization and enhancement by an associating transactivator SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR; PROTEIN; MAD; DPC4; PHOSPHORYLATION; MUTATIONS; SER(465); COMPLEX; ENCODES AB Smad4 plays a pivotal role in signal transduction of the transforming growth factor beta superfamily cytokines by mediating transcriptional activation of target genes. Hetero-oligomerization of Smad4 with the pathway-restricted SMAD proteins is essential for Smad4-mediated transcription. We provide evidence that SMAD hetero-oligomerization is directly required for the Smad4 C-terminal domain [Smad4(C)] to show its transcriptional transactivating activity; this requirement obtains even when Smad4(C) is recruited to promoters by heterologous DNA binding domains and in the absence of the inhibitory Smad4 N-terminal domain. Defined mutations of GAL4 DNA-binding domain fusion of Smad4(C) that disrupt SMAD hetero-oligomerization suppressed transcriptional activation, Importantly, we found that an orphan transcriptional activator MSG1, a nuclear protein that has strong transactivating activity but apparently lacks DNA-binding activity, functionally interacted with Smad4 and enhanced transcription mediated by GAL4 DNA-binding domain-Smad4(C) and full length Smad4, Transcriptional enhancement by MSG1 depended on transforming growth factor beta signaling and was suppressed by Smad4(C) mutations disrupting SMAD hetero-oligomerization or by the presence of Smad4 N-terminal domain. Furthermore, Smad4(C) did not show any detectable transactivating activity in yeast when fused to heterologous DNA binding domains. These results demonstrate additional roles of SMAD hetero-oligomerization in Smad4-mediated transcriptional activation. They also suggest that the transcriptional-activating activity observed in the presence of Smad4 in mammalian cells may be derived, at least in part, from endogenously expressed separate transcriptional activators, such as MSG1. C1 Massachusetts Gen Hosp E, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Mammalian Dev, London NW7 1AA, England. RP Shioda, T (reprint author), Massachusetts Gen Hosp E, Ctr Canc, Lab Tumor Biol, Bldg 149,7th Floor,13th St, Charlestown, MA 02129 USA. EM shioda@helix.mgh.harvard.edu RI Fenner, Martin/A-7225-2008; OI Fenner, Martin/0000-0003-1419-2405; Dunwoodie, Sally/0000-0002-2069-7349 NR 33 TC 90 Z9 98 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 9785 EP 9790 DI 10.1073/pnas.95.17.9785 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200016 PM 9707553 ER PT J AU Rebagliati, MR Toyama, R Haffter, P Dawid, IB AF Rebagliati, MR Toyama, R Haffter, P Dawid, IB TI cyclops encodes a nodal-related factor involved in midline signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-A; FLOOR PLATE; SONIC HEDGEHOG; SPINAL-CORD; NEURAL-TUBE; FATE MAP; XENOPUS-EMBRYOS; ZEBRAFISH; EXPRESSION AB Ventral structures in the central nervous system are patterned by signals emanating from the underlying mesoderm as well as originating within the neuroectoderm. Mutations in the zebrafish, Danio rerio, are proving instrumental in dissecting these midline signals. The cyclops mutation leads to a loss of medial floor plate and to severe deficits in ventral forebrain development, leading to cyclopia. Here, we report that the cyclops locus encodes the nodal-related protein Ndr2, a member of the transforming growth factor type beta superfamily of factors. The evidence includes identification of a missense mutation in the initiation codon and rescue of the cyclops phenotype by expression of ndr2 RNA, here renamed "cyclops." Thus, in interaction with other molecules implicated in these processes such as sonic hedgehog and one-eyed-pinhead, cyclops is required for ventral midline patterning of the embryonic central nervous system. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 45 TC 300 Z9 306 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 9932 EP 9937 DI 10.1073/pnas.95.17.9932 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200041 PM 9707578 ER PT J AU Becker, KG Simon, RM Bailey-Wilson, JE Freidlin, B Biddison, WE McFarland, HF Trent, JM AF Becker, KG Simon, RM Bailey-Wilson, JE Freidlin, B Biddison, WE McFarland, HF Trent, JM TI Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENOME-WIDE SEARCH; DEPENDENT DIABETES-MELLITUS; OLD ORDER AMISH; MULTIPLE-SCLEROSIS; GENETIC-ANALYSIS; MOUSE CHROMOSOME-6; AFFECTIVE-DISORDER; UNDERLYING ASTHMA; TRAIT; MICE AB Human autoimmune diseases are thought to develop through a complex combination of genetic and environmental factors. Genome-wide linkage searches of autoimmune and inflammatory/immune disorders have identified a large number of non-major histocompatibility complex loci that collectively contribute to disease susceptibility. A comparison was made of the linkage results from 23 published autoimmune or immune-mediated disease genome-wide scans. Human diseases included multiple sclerosis, Crohn's disease, familial psoriasis, asthma, and type-I diabetes (IDDM). Experimental animal disease studies included murine experimental autoimmune encephalomyelitis, rat inflammatory arthritis, rat and murine IDDM, histamine sensitization, immunity to exogenous antigens, and murine lupus (systemic lupus erythematosus; SLE). A majority (approximate to 65%) of the human positive linkages map nonrandomly into 18 distinct clusters. Overlapping of susceptibility loci occurs between different human immune diseases and by comparing conserved regions with experimental autoimmune/immune disease models. This nonrandom clustering supports a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of susceptibility genes. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Sect Stat Genet, Ctr Inherited Dis Res, NIH, Baltimore, MD 21224 USA. Emmes Corp, Potomac, MD 20854 USA. RP Becker, KG (reprint author), Natl Human Genome Res Inst, Canc Genet Branch, NIH, 49 Convent Dr,Room 4B11, Bethesda, MD 20892 USA. EM kbecker@nhgri.nih.gov OI Becker, Kevin/0000-0002-6794-6656; Bailey-Wilson, Joan/0000-0002-9153-2920 NR 65 TC 484 Z9 503 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 9979 EP 9984 DI 10.1073/pnas.95.17.9979 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200049 PM 9707586 ER PT J AU Fijalkowska, IJ Jonczyk, P Tkaczyk, MM Bialoskorska, M Schaaper, RM AF Fijalkowska, IJ Jonczyk, P Tkaczyk, MM Bialoskorska, M Schaaper, RM TI Unequal fidelity of leading strand and lagging strand DNA replication on the Escherichia coli chromosome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MISPAIR EXTENSION KINETICS; POLYMERASE-III HOLOENZYME; MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE; REVERSE-TRANSCRIPTASE; MUTATOR MUTD5; MUTAGENESIS; MUTATIONS; GENE; MECHANISMS AB We have investigated the question whether during chromosomal DNA replication in Escherichia coli the two DNA strands may be replicated with differential accuracy. This possibility of differential replication fidelity arises from the distinct modes of replication in the two strands, one strand (the leading strand) being synthesized continuously, the other (the lagging strand) discontinuously in the form of short Okazaki fragments. We have constructed a series of lacZ strains in which the lac operon is inserted into the bacterial chromosome in the two possible orientations with regard to the chromosomal replication origin oriC. Measurement of lac reversion frequencies for the two orientations, under conditions in which mutations reflect replication errors, revealed distinct differences in mutability between the two orientations. As gene inversion causes a switching of leading and lagging strands, these findings indicate that leading and lagging strand replication have differential fidelity. Analysis of the possible mispairs underlying each specific base pair substitution suggests that the lagging strand replication on the E. coli chromosome may be more accurate than leading strand replication. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RI Fijalkowska, Iwona/I-7796-2016 NR 42 TC 111 Z9 113 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 10020 EP 10025 DI 10.1073/pnas.95.17.10020 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200056 PM 9707593 ER EF