FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DEVITO, LD MASON, B SCHNECK, J MARGULIES, DH SOLLINGER, HW BURLINGHAM, WJ AF DEVITO, LD MASON, B SCHNECK, J MARGULIES, DH SOLLINGER, HW BURLINGHAM, WJ TI IMMUNOCHEMICAL ANALYSIS OF A RECOMBINANT, GENETICALLY ENGINEERED, SECRETED HLA-A2/Q10B FUSION PROTEIN SO HUMAN IMMUNOLOGY LA English DT Article ID I HISTOCOMPATIBILITY ANTIGENS; HUMAN ALLOANTIBODY PROBES; MONOCLONAL-ANTIBODY; ANTIIDIOTYPIC ANTIBODIES; RENAL-TRANSPLANTATION; IDIOTYPE DIVERSITY; FINE SPECIFICITY; HLA ANTIBODIES; LYMPHOCYTES-T; MOLECULES AB We engineered a fusion gene which encodes the alpha-1 and alpha-2 domains of HLA-A2 with the alpha-3 and truncated transmembrane domains of the murine class I-like protein Q10b, and transferred it into mouse L cells along with the gene for human beta-2-microglobulin (beta-2-m). The secreted rA2/Q10b gene product consisted of a single heavy chain of molecular weight 42 kd that was non-covalently associated with the human beta-2-m light chain. Native detergent-solubilized HLA-A2 and secreted rA2/Q10b proteins were found to be similar by: (a) the binding to mouse monoclonal anti-HLA antibodies in an ELISA; (b) the blocking of lysis of HLA-A2+ cells by human anti-HLA-A2,-B17, anti-HLA-A2,9,28, and anti-HLA-A2,28 cross-reactive group (CREG) antisera in a complement-dependent cytotoxicity assay; and (c) the ability when coupled to Sepharose to selectively purify HLA-A2,9,28 and HLA-A2,28 CREG-specific antibodies. Mouse L cells expressing rA2/Q10b produced as much as 2.5-mu-g protein per 10(6) cells/day, or 50- to 100-fold more antigen on a per cell basis than the level of HLA-A2 expressed by B-lymphoblastoid cell line or spleen cells. Thus rA2/Q10b represents a viable alternative to detergent-solubilized HLA-A2 for purification of anti-HLA-A2 antibodies and analysis of anti-HLA-A2 immune responses. C1 JOHNS HOPKINS UNIV,CTR ASTHMA ALLERGY,BALTIMORE,MD 21218. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP DEVITO, LD (reprint author), UNIV WISCONSIN,DEPT SURG,H4-747 CSC 600 HIGHLAND AVE,MADISON,WI 53705, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 47 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD OCT PY 1991 VL 32 IS 2 BP 125 EP 133 DI 10.1016/0198-8859(91)90109-M PG 9 WC Immunology SC Immunology GA GK074 UT WOS:A1991GK07400007 PM 1744002 ER PT J AU CHARNY, CK LEVIN, RL AF CHARNY, CK LEVIN, RL TI A 3-DIMENSIONAL THERMAL AND ELECTROMAGNETIC MODEL OF WHOLE LIMB HEATING WITH A MAPA SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID BLOOD-FLOW; TEMPERATURE; HYPERTHERMIA; MUSCLE; TISSUE; BODY AB Previous studies by the authors have shown that if properly implemented, the Pennes assumptions can be applied to quantify bioheat transfer during extremity heating. Given its relative numerical simplicity and its ability to predict temperatures in thermoregulated tissue, the Pennes model of bioheat transfer was utilized in a three-dimensional thermal model of limb heating. While the arterial blood temperature was assumed to be radially uniform within a cross section of the limb, axial gradients in the arterial and venous blood temperatures were computed with this three-dimensional model. A realistically shaped, three-dimensional finite element model of a tumor-bearing human lower leg was constructed and was "attached" mathematically to the whole body thermal model of man described in previous studies by the authors. The central as well as local thermoregulatory feedback control mechanisms which determine blood perfusion to the various tissues and rate of evaporation by sweating were input into the limb model. In addition, the temperature of the arterial blood which feeds into the most proximal section of the lower leg was computed by the whole body thermal model. The variations in the shape of the tissues which comprise the limb were obtained from computerized tomography scans. Axial variations in the energy deposition patterns along the length of the limb exposed to a miniannular phased array (MAPA) applicator were also input into this model of limb heating. Results indicate that proper positioning of the limb relative to the MAPA is a significant factor in determining the effectiveness of the treatment. A patient-specific hyperthermia protocol can be designed using this coupled electromagnetic and thermal model. C1 NIH,DIV RES SERV,BIOMED ENGN & INSTRUMENTAT BRANCH,MECH ENGN SECT,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,MECH ENGN SECT,BETHESDA,MD 20892. NR 27 TC 10 Z9 12 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 1991 VL 38 IS 10 BP 1030 EP 1039 DI 10.1109/10.88448 PG 10 WC Engineering, Biomedical SC Engineering GA GG471 UT WOS:A1991GG47100010 PM 1761290 ER PT J AU BENDELAC, A SCHWARTZ, RH AF BENDELAC, A SCHWARTZ, RH TI TH0 CELLS IN THE THYMUS - THE QUESTION OF T-HELPER LINEAGES SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SPLENIC NON-B; T-HELPER-2 CELLS; FUNCTIONAL HETEROGENEITY; INTRATHYMIC MATURATION; SECRETE INTERLEUKIN-4; LYMPHOKINE SECRETION; MURINE LEISHMANIASIS; MOUSE THYMOCYTES; INTERFERON-GAMMA; MEDIATING GRAFT RP BENDELAC, A (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BLDG 4,ROOM 111,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 58 TC 42 Z9 42 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1991 VL 123 BP 169 EP 188 DI 10.1111/j.1600-065X.1991.tb00610.x PG 20 WC Immunology SC Immunology GA GP273 UT WOS:A1991GP27300008 PM 1684778 ER PT J AU MOSMANN, TR SCHUMACHER, JH STREET, NF BUDD, R OGARRA, A FONG, TAT BOND, MW MOORE, KWM SHER, A FIORENTINO, DF AF MOSMANN, TR SCHUMACHER, JH STREET, NF BUDD, R OGARRA, A FONG, TAT BOND, MW MOORE, KWM SHER, A FIORENTINO, DF TI DIVERSITY OF CYTOKINE SYNTHESIS AND FUNCTION OF MOUSE CD4+ T-CELLS SO IMMUNOLOGICAL REVIEWS LA English DT Review ID DELAYED-TYPE HYPERSENSITIVITY; STIMULATORY FACTOR-I; INTERFERON-GAMMA; IFN-GAMMA; LYMPHOCYTES-T; TH1 CLONES; IMMUNE REGULATION; AUTOCRINE GROWTH; MESSENGER-RNA; HELPER CELLS C1 DNAX INC,RES INST,DEPT IMMUNOL,PALO ALTO,CA 94304. NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. SYNTEX INC,PALO ALTO,CA 94304. UNIV TEXAS,SW MED CTR,DEPT CANC IMMUNOBIOL,DALLAS,TX 75235. UNIV VERMONT,SCH MED,RHEUMATOL & CLIN IMMUNOL UNIT,BURLINGTON,VT 05405. RP MOSMANN, TR (reprint author), UNIV ALBERTA,DEPT IMMUNOL,ROOM 865 MED SCI BLDG,EDMONTON T6G 2H7,ALBERTA,CANADA. NR 52 TC 373 Z9 377 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1991 VL 123 BP 209 EP 229 DI 10.1111/j.1600-065X.1991.tb00612.x PG 21 WC Immunology SC Immunology GA GP273 UT WOS:A1991GP27300010 PM 1684780 ER PT J AU LAL, RB DHAWAN, RR TARRAND, JJ AYOUB, EM OTTESEN, EA AF LAL, RB DHAWAN, RR TARRAND, JJ AYOUB, EM OTTESEN, EA TI LACK OF IGG4 ANTIBODY-RESPONSE TO CARBOHYDRATE ANTIGENS IN PATIENTS WITH LYMPHATIC FILARIASIS SO IMMUNOLOGY LA English DT Article ID BRUGIA-MALAYI; SUBCLASS RESTRICTION; V-REGIONS; PHOSPHOCHOLINE; INFECTION; IMMUNOGLOBULIN; POLYSACCHARIDE; PARASITES; SERA AB It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens. To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein [streptolysin-O (SO), deoxyribonuclease B (DB)] and carbohydrate [group A carbohydrate (GAC)] antigens. Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P < 0.01), and the subclass composition of these antibodies proved heterogenous. Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P < 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group. These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. MD ANDERSON CANC CTR,HOUSTON,TX. UNIV FLORIDA,DEPT PEDIAT,GAINESVILLE,FL 32611. UNIFORMED SERV UNIV HLTH SCI,DIV TROP PUBL HLTH,BETHESDA,MD 20814. NR 29 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD OCT PY 1991 VL 74 IS 2 BP 333 EP 337 PG 5 WC Immunology SC Immunology GA GN517 UT WOS:A1991GN51700025 PM 1748481 ER PT J AU CHOPRA, DP TAYLOR, GW MATHIEU, PA HUKKU, B RHIM, JS AF CHOPRA, DP TAYLOR, GW MATHIEU, PA HUKKU, B RHIM, JS TI IMMORTALIZATION OF HUMAN TRACHEAL GLAND EPITHELIAL-CELLS BY ADENOVIRUS12-SV40 HYBRID VIRUS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Letter C1 WAYNE STATE UNIV,DEPT PEDIAT,DETROIT,MI 48201. CHILDRENS HOSP MICHIGAN,DEPT PEDIAT,DETROIT,MI 48201. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP CHOPRA, DP (reprint author), WAYNE STATE UNIV,INST CHEM TOXICOL,2727 2ND AVE 4000,DETROIT,MI 48201, USA. FU NHLBI NIH HHS [R01-HL33142, R01-HL41979] NR 9 TC 12 Z9 12 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD OCT PY 1991 VL 27 IS 10 BP 763 EP 765 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GP874 UT WOS:A1991GP87400003 PM 1660049 ER PT J AU PATTON, LL POLLACK, S WELLNER, RB AF PATTON, LL POLLACK, S WELLNER, RB TI RESPONSIVENESS OF A HUMAN PAROTID EPITHELIAL-CELL LINE (HSY) TO AUTONOMIC STIMULATION - MUSCARINIC CONTROL OF K+ TRANSPORT SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Article DE SALIVARY; CELL LINE; MUSCARINIC; CA2+ SIGNAL; K+ TRANSPORT; PROTEIN KINASE-C ID ACTIVATED POTASSIUM CHANNELS; CALCIUM; SECRETION; MOBILIZATION AB Salivary electrolyte secretion is under the control of the autonomic nervous system. In this paper we report that HSY, an epithelial cell line derived from the acinar-intercalated duct region of the human parotid gland, responds to muscarinic-cholinergic (generation of Ca2+ signal) and beta-adrenergic (generation of cAMP signal), but not to alpha-adrenergic (lack of Ca2+ signal), receptor stimulation. The muscarinic response was studied in detail. Carbachol (10(-4) M, muscarinic agonist) or A23187 (5-mu-M, calcium ionophore) stimulation of HSY cells increases both Rb-86 (K+) influx and efflux, resulting in no change in net equilibrium Rb-86 content. Atropine (10(-5) M, muscarinic antagonist) blocks both the carbachol-generated Ca2+ signal and carbachol-stimulated Rb-86 fluxes, but has no effect on either the A23187-generated Ca2+ signal or A23187-stimulated Rb-86 fluxes. Carbachol- and A23187-stimulated Rb-86 fluxes are substantially inhibited by two K+ channel blockers, quinine (0.3 mM) and scorpion venom containing charybdotoxin (33-mu-g/ml). The inhibition of these stimulated fluxes by another K+ channel blocker, tetraethylammonium chloride (5 mM), is less pronounced. Protein kinase C (PKC) seems to be involved in the regulation of the Rb-86 fluxes as 10(-7) M PMA (phorbol ester, phorbol-12-myristate-13-acetate) substantially inhibits the muscarinic-stimulated Rb-86 efflux and influx. Because this concentration of PMA totally inhibits the carbachol-generated Ca2+ signal and only 80% of the muscarinic-stimulated Rb-86 influx, it seems that a portion of the carbachol-stimulated Rb-86 flux (i.e. that portion not inhibited by PMA) might occur independently of the Ca2+ signal. PMA fails to inhibit the A23187-stimulated Rb-86 fluxes, however, suggesting that PKC regulates Ca2+-sensitive K+ channel activity by regulating the Ca2+ signal, and not steps distal to this event. 4-alpha-Phorbol-12,13-didecanoate, a phorbol ester which fails to activate PKC, fails to inhibit either the carbachol-stimulated increase in intracellular free Ca2+, or carbachol-stimulated Rb-86 fluxes. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FREDERICK,MD 21701. OI Patton, Lauren/0000-0002-8253-4588 NR 28 TC 11 Z9 11 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD OCT PY 1991 VL 27 IS 10 BP 779 EP 785 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GP874 UT WOS:A1991GP87400007 PM 1960145 ER PT J AU GRAY, T RUNDHAUG, J NETTESHEIM, P AF GRAY, T RUNDHAUG, J NETTESHEIM, P TI CRITICAL VARIABLES CONTROLLING CELL-PROLIFERATION IN PRIMARY CULTURES OF RAT TRACHEAL EPITHELIAL-CELLS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Article DE RAT TRACHEAL EPITHELIAL CELLS; COLONY FORMING UNIT; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR ALPHA; BOVINE SERUM ALBUMIN; CHOLERA TOXIN ID RETINOIC ACID; DNA-REPAIR; SQUAMOUS DIFFERENTIATION; TRANSFORMATION; INVITRO; GROWTH; CARCINOGENS; BENZOPYRENE; RESPONSIVENESS; SUBSTRATUM AB The purpose of our experiments was to examine variables affecting early events in the establishment of rat tracheal epithelial (RTE) cultures as well as factors regulating long-term RTE cell growth. The experiments showed that when RTE cells were seeded into complete serum-free medium between 13 and 30% of the seeded cells attached. Of the seeded cells, only approximately 2% entered into DNA synthesis and underwent repeated cell divisions to form colonies containing > 20 cells. Coating the dishes with extracellular matrix components had little effect on cell attachment or colony forming efficiency (CFE). However, coating the dishes with fetal bovine serum markedly increased CFE. The media components bovine serum albumin and bovine pituitary extract were shown to be important in promoting cell attachment as well as CFE. Cholera toxin on the other hand had no effect on cell attachment but significantly increased CFE. These and other studies showed that cell attachment and cell proliferation are independently regulated. Studies on long-term culture growth indicated that the number of progeny produced per colony forming unit (CFU) is inversely proportional to the number of CFUs seeded. Inasmuch as the cultures did not become confluent under any of the culture conditions tested and media obtained from high density cultures were shown to be growth inhibitory, these findings suggest that a diffusible growth restraining factor is being produced by the cultures limiting clonal expansion. Experiments showing growth inhibitory effects of media conditioned by high cell density cultures support this interpretation. The putative factor reaches critical concentrations earlier in cultures seeded with high numbers of CFU than in cultures seeded with low numbers of CFU. Because the cultures are known to produce transforming growth factor-beta, this growth regulator probably plays a role in controlling RTE cell proliferation. However, it is likely than other events, such as depletion of growth factors from the media, also are significant in regulating the growth of the cultures. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 41 TC 6 Z9 6 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD OCT PY 1991 VL 27 IS 10 BP 805 EP 814 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GP874 UT WOS:A1991GP87400011 PM 1960148 ER PT J AU DEVI, SJN SCHNEERSON, R EGAN, W ULRICH, TJ BRYLA, D ROBBINS, JB BENNETT, JE AF DEVI, SJN SCHNEERSON, R EGAN, W ULRICH, TJ BRYLA, D ROBBINS, JB BENNETT, JE TI CRYPTOCOCCUS-NEOFORMANS SEROTYPE-A GLUCURONOXYLOMANNAN-PROTEIN CONJUGATE VACCINES - SYNTHESIS, CHARACTERIZATION, AND IMMUNOGENICITY SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE; IMMUNOLOGICAL-UNRESPONSIVENESS; SOLUBLE POLYSACCHARIDE; MONOCLONAL-ANTIBODIES; MURINE CRYPTOCOCCOSIS; PASSIVE-IMMUNIZATION; MENINGITIS; MICE; VARIANT AB We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P < 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation. C1 RIBI IMMUNOCHEM RES INC,HAMILTON,MT 59840. US FDA,DIV BIOCHEM & BIOPHYS,CTR DRUGS & BIOL,BETHESDA,MD 20892. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. RP DEVI, SJN (reprint author), NICHHD,DEV & MOLEC IMMUNITY LAB,BETHESDA,MD 20892, USA. NR 59 TC 122 Z9 125 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1991 VL 59 IS 10 BP 3700 EP 3707 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GH076 UT WOS:A1991GH07600052 PM 1716613 ER PT J AU YAN, LZ SEKURA, RD AF YAN, LZ SEKURA, RD TI PURIFICATION AND CHARACTERIZATION OF THE HEAT-LABILE TOXIN OF BORDETELLA-PERTUSSIS SO INFECTION AND IMMUNITY LA English DT Article ID DERMONECROTIC TOXIN; ADENYLATE-CYCLASE; BRONCHISEPTICA; PROTEIN; AGENTS; ASSAY; SKIN AB A procedure is described for purification of pertussis heat-labile toxin (PEHLT) from cells of Bordetella pertussis. The purification procedure, performed in the cold and in the presence of protease inhibitors, gives 1,350-fold purification with yields of about 60%. The toxin was shown to be a single-chain polypeptide of 140 kDa, pI 6.02. It was completely inactivated by heating at 56-degrees-C for 60 min. Rabbit antiserum prepared against PEHLT neutralized the toxin and gave a single precipitin line on immunodiffusion. In immunodiffusion assays, this anti-PEHLT serum did not react with pertussis toxin, filamentous hemagglutinin, or preparations of pertussis adenylate cyclase. Purified PEHLT elicited dermonecrosis and atrophy of the spleen. PEHLT is extraordinarily active; 0.4 x 10(-12) g caused necrotic lesions in newborn mice, and with 18- to 20-g mice the 50% lethal dose was about 11 x 10(-9) g. C1 NICHHD,MOLEC & DEV IMMUNITY LAB,BETHESDA,MD 20892. NR 34 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1991 VL 59 IS 10 BP 3754 EP 3759 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GH076 UT WOS:A1991GH07600058 ER PT J AU SU, H SPANGRUDE, GJ CALDWELL, HD AF SU, H SPANGRUDE, GJ CALDWELL, HD TI EXPRESSION OF FC-GAMMA-RIII ON HELA 229 CELLS - POSSIBLE EFFECT ON INVITRO NEUTRALIZATION OF CHLAMYDIA-TRACHOMATIS SO INFECTION AND IMMUNITY LA English DT Note ID OUTER-MEMBRANE PROTEIN; PROTECTIVE MONOCLONAL-ANTIBODIES; RECEPTORS; IGG AB The neutralizing activities of a murine immunoglobulin G3 (IgG3) monoclonal antibody specific for the major outer membrane protein of Chlamydia trachomatis and its monovalent Fab fragments were studied by using Syrian hamster kidney (HaK) cells and human epithelial (HeLa 229) cells. The intact IgG3 antibody was neutralizing for HaK cells but was nonneutralizing for HeLa cells. In contrast, monovalent Fab antibody fragments neutralized chlamydial infectivity for both HaK and HeLa cells. Immunofluorescence analysis of HeLa 229 cells with a panel of monoclonal antibodies specific to human Fc-gamma receptors revealed the expression of cell surface Fc-gamma-RIII. We propose that Fc-gamma-RIII may obscure the chlamydia-neutralizing activity of certain IgG isotypes by facilitating the Fc-gamma-R-mediated entry of chlamydiae into HeLa 229 cells. These findings may help explain the inconsistencies that are commonly observed in results when HeLa 229 cells are used in chlamydia neutralization assays. C1 NIH,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NIH,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 18 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1991 VL 59 IS 10 BP 3811 EP 3814 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GH076 UT WOS:A1991GH07600066 PM 1832664 ER PT J AU COOPER, JK MUNGAS, D VERMA, M WEILER, PG AF COOPER, JK MUNGAS, D VERMA, M WEILER, PG TI PSYCHOTIC SYMPTOMS IN ALZHEIMERS-DISEASE SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE ALZHEIMERS DISEASE; HALLUCINATIONS; DELUSIONS; PSYCHOTIC SYMPTOMS ID SENILE DEMENTIA; DISORDERS; DIAGNOSIS C1 ALZHEIMERS DIS DISORDERS PROGRAM,RES,SACRAMENTO,CA. RP COOPER, JK (reprint author), NIA,GERIATR PROGRAM,BLDG 31,ROOM 3B58,BETHESDA,MD 20892, USA. RI Mungas, Dan/E-6810-2011 NR 23 TC 36 Z9 36 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD OCT PY 1991 VL 6 IS 10 BP 721 EP 726 DI 10.1002/gps.930061006 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA GM125 UT WOS:A1991GM12500005 ER PT J AU SOLOMON, D AF SOLOMON, D TI THE BETHESDA SYSTEM FOR REPORTING CERVICAL VAGINAL CYTOLOGIC DIAGNOSES - AN OVERVIEW SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article ID UTERINE CERVIX RP SOLOMON, D (reprint author), NCI,PATHOL LAB,CYTOPATHOL SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 11 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1991 VL 10 IS 4 BP 323 EP 325 DI 10.1097/00004347-199110000-00003 PG 3 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA GH079 UT WOS:A1991GH07900002 PM 1774102 ER PT J AU FITZGERALD, TJ SANTUCCI, MA DAS, I KASE, K PIERCE, JH GREENBERGER, JS AF FITZGERALD, TJ SANTUCCI, MA DAS, I KASE, K PIERCE, JH GREENBERGER, JS TI THE V-ABL, C-FMS, OR V-MYC ONCOGENE INDUCES GAMMA-RADIATION RESISTANCE OF HEMATOPOIETIC PROGENITOR-CELL LINE 32D CL 3 AT CLINICAL LOW-DOSE RATE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 32ND ANNUAL MEETING OF THE AMERICAN SOC FOR THERAPEUTIC RADIOLOGY AND ONCOLOGY CY OCT 15-19, 1990 CL MIAMI BEACH, FL SP AMER SOC THERAPEUT RADIOL & ONCOL DE RADIORESISTANCE; V-ABL ONCOGENE; HEMATOPOIETIC STEM CELL; STROMAL CELL ID MURINE LEUKEMIA-VIRUS; CHRONIC MYELOGENOUS LEUKEMIA; TRANSFORMING GENE-PRODUCT; SARCOMA-VIRUS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; LYMPHOID-CELLS; MESSENGER-RNA; FOS GENE; EXPRESSION AB A variety of viral and cellular oncogenes have been described with differing mechanisms of action but with the common property of inducing morphologic alteration of cells in culture. Subclonal lines of oncogene expressing cells have been shown to produce tumors in vivo. Expression of the N-ras oncogene in embryofibroblast NIH/3T3 cells has been demonstrated to increase radioresistance in vitro, and these results have been confirmed and extended to human cell lines expressing the c-raf oncogene. In the present report, we have examined the effects of expression of the c-fms, v-abl, or v-myc oncogene in a clonal hematopoietic progenitor cell line 32D cl 3. The 32D cell line is nonmalignant in vivo and is dependent upon a source of Interleukin-3 (IL-3) for growth in vitro. The radiation survival of 32D cl 3 cells transfected and expressed in the c-fms oncogene showed significant increase in the radioresistance at both 5 cGy/min and 116 cGy/min. A clone of 32D cl 3 transfected and expressing the v-myc oncogene demonstrated increased radioresistance at both dose rates. Results of split dose experiments suggested significant repair of sublethal irradiation damage of 32D-v-abl cells. Results were compared with expression of the same v-abl oncogene in the NIH/3T3 embryofibroblast cell line. The data demonstrate that gamma irradiation resistance is significantly increased by each oncogene expressed in 32D cl 3 cells. The data on cell line 32D cl 3 may correlate with the radioresistance of v-abl expressing human hematopoietic cell malignancies treated by irradiation therapy. C1 NCI,DEPT MOLEC & CELLULAR BIOL,BETHESDA,MD 20892. RP FITZGERALD, TJ (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT RADIAT ONCOL,55 LAKE AVE W,WORCESTER,MA 01655, USA. FU NCI NIH HHS [CA39851]; NIDCR NIH HHS [DE08798] NR 47 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT PY 1991 VL 21 IS 5 BP 1203 EP 1210 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA GL715 UT WOS:A1991GL71500013 PM 1938518 ER PT J AU WAYNE, LG GOOD, RC KRICHEVSKY, MI BLACKLOCK, Z DAVID, HL DAWSON, D GROSS, W HAWKINS, J LEVYFREBAULT, VV MCMANUS, C PORTAELS, F RUSCHGERDES, S SCHRODER, KH SILCOX, VA TSUKAMURA, M VANDENBREEN, L YAKRUS, MA AF WAYNE, LG GOOD, RC KRICHEVSKY, MI BLACKLOCK, Z DAVID, HL DAWSON, D GROSS, W HAWKINS, J LEVYFREBAULT, VV MCMANUS, C PORTAELS, F RUSCHGERDES, S SCHRODER, KH SILCOX, VA TSUKAMURA, M VANDENBREEN, L YAKRUS, MA TI 4TH REPORT OF THE COOPERATIVE, OPEN-ENDED STUDY OF SLOWLY GROWING MYCOBACTERIA BY THE INTERNATIONAL-WORKING-GROUP-ON-MYCOBACTERIAL-TAXONOMY SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID BINARY PHENETIC DATA; NUMERICAL-ANALYSIS; DEPENDENT MYCOBACTERIA; COMPUTER METHODS; AVIUM COMPLEX; INTRACELLULARE; DNA; DIFFERENTIATION; IDENTIFICATION; HYBRIDIZATION AB The open-ended study of the International Working Group on Mycobacterial Taxonomy is an ongoing project to characterize slowly growing strains of mycobacteria that do not belong to well-established or thoroughly characterized species. In this fourth report we describe two numerical taxonomic clusters that represent subspecies or biovars of Mycobacterium simiae, one cluster that encompasses the erstwhile type strain of the presently invalid species "Mycobacterium paraffinicum," one cluster that is phenotypically very similar to Mycobacterium avium and Mycobacterium intracellulare but may be a separate genospecies, one cluster that appears to be phenotypically distinct from M. avium but reacts with a nucleic acid probe specific for M. avium, and three tentatively defined clusters in proximity to a cluster that encompasses the type strain of Mycobacterium malmoense. Of special practical interest is the fact that one of the latter three clusters is composed of clinically significant scotochromogenic bacteria that can be misidentified as the nonpathogenic organism Mycobacterium gordonae if insufficient biochemical tests are performed. C1 CHUBU CHEST HOSP,OBU,AICHI,JAPAN. STATE HLTH LAB SERV,BRISBANE,AUSTRALIA. INST TROP MED,ANTWERP,BELGIUM. INST PASTEUR,F-75724 PARIS 15,FRANCE. VET ADM MED CTR,W HAVEN,CT 06516. NIDR,BETHESDA,MD 20205. CTR DIS CONTROL,ATLANTA,GA 30333. TB FORSCHUNGSINST,BORSTEL,GERMANY. RP WAYNE, LG (reprint author), VET ADM MED CTR,LONG BEACH,CA 90822, USA. NR 41 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1991 VL 41 IS 4 BP 463 EP 472 PG 10 WC Microbiology SC Microbiology GA GK447 UT WOS:A1991GK44700001 PM 1742195 ER PT J AU GRAU, O LAIGRET, F CARLE, P TULLY, JG ROSE, DL BOVE, JM AF GRAU, O LAIGRET, F CARLE, P TULLY, JG ROSE, DL BOVE, JM TI IDENTIFICATION OF A PLANT-DERIVED MOLLICUTE AS A STRAIN OF AN AVIAN PATHOGEN, MYCOPLASMA-IOWAE, AND ITS IMPLICATIONS FOR MOLLICUTE TAXONOMY SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID PULSED-FIELD ELECTROPHORESIS; DNA; SEROTYPES; SIZES AB Strain PPAV, a filamentous but nonhelical mollicute, was isolated from aborted apple seeds in France in late 1979. This organism grew well in SP-4 broth, fermented glucose, and required sterol for growth, and most of its properties suggested that it belonged to the genus Mycoplasma. However, it was serologically distinct; in addition, unlike other Mycoplasma species, genome measurements consistently yielded values of about 1,000 MDa (ca. 1,500 kbp), and the organism had a growth temperature optimum of 43-degrees-C. A comparison of strain PPAV 16S rRNA sequences with those of other mollicutes revealed a high degree of sequence similarity to a strain of Mycoplasma iowae, which is commonly encountered in poultry. This relationship was confirmed by performing a restriction endonuclease pattern analysis and DNA-DNA hybridization tests. The genome size of type strain 695 of M. iowae was determined to be about 1,000 MDa (1,500 kbp) by renaturation kinetics, a value which is much higher than any other value known in the genus. Additional measurements by pulsed-field gel electrophoresis yielded values of 1,300 kbp for both strain PPAV and M. iowae. Subsequent phenotypic comparisons supported this relationship. Serologic tests with strain PPAV and other strains of M. iowae confirmed the findings of other investigators that this species is serologically heterogeneous. The high optimum temperature for growth of strain PPAV was also shared by a number of M. iowae isolates. Genome size is an inappropriate character for taxonomic assignment to the family Mycoplasmataceae because strain PPAV and other established species in this famfly are now known to have genomes ranging in size from 1,000 to 1,400 kbp. C1 INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. NIH,FREDERICK CANC RES & DEV CTR,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. UNIV BORDEAUX 2,F-33076 BORDEAUX,FRANCE. NR 35 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1991 VL 41 IS 4 BP 473 EP 478 PG 6 WC Microbiology SC Microbiology GA GK447 UT WOS:A1991GK44700002 PM 1720652 ER PT J AU PITTMAN, KF WALCZAK, CA LOCK, CM AF PITTMAN, KF WALCZAK, CA LOCK, CM TI CODES AND ABBREVIATIONS FOR APPROVED OR EFFECTIVELY PUBLISHED NAMES OF GENERA OF BACTERIA PUBLISHED FROM JANUARY 1980 TO DECEMBER 1990 SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Note ID LISTS AB Lists of abbreviations for genus names of bacteria are expanded to accommodate 103 new entries which are names that have been validly published since the publication of an updated list by Rogosa et al. in 1986 (Int. J. Syst. Bacteriol. 36:464-472). These abbreviations are provided to serve the need for appropriate codified abbreviations for use in processing or indexing of information on computers. C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,MICROBIAL SYSTEMAT SECT,BETHESDA,MD 20892. RP PITTMAN, KF (reprint author), BIOSIS INC,DEPT SPECIAL ANAL,PHILADELPHIA,PA 19103, USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1991 VL 41 IS 4 BP 571 EP 579 PG 9 WC Microbiology SC Microbiology GA GK447 UT WOS:A1991GK44700019 PM 1742201 ER PT J AU BERKOWITZ, BA SATO, Y WILSON, CA DEJUAN, E AF BERKOWITZ, BA SATO, Y WILSON, CA DEJUAN, E TI BLOOD RETINAL BARRIER BREAKDOWN INVESTIGATED BY REAL-TIME MAGNETIC-RESONANCE-IMAGING AFTER GADOLINIUM-DIETHYLENETRIAMINEPENTAACETIC ACID INJECTION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MAGNETIC RESONANCE IMAGING; BLOOD-RETINAL BARRIER; GADOLINIUM; PANRETINAL PHOTOCOAGULATION; RABBIT ID CONTRAST AGENT; DTPA AB Recent magnetic resonance imaging (MRI) studies show that gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) entry into the vitreous space can be used as a qualitative marker of blood-retinal barrier (BRB) disruption. To determine if a more quantitative measurement of BRB breakdown could be obtained, the utility of acquiring real-time, T1-weighted proton images was studied after Gd-DTPA injection. Two days before the MRI experiment, panretinal photocoagulation was done. The mean signal intensity over selected regions-of-interest (ROI) in the vitreous and anterior chamber was followed before and after (0, 10, 20, 30, 45, and 60 min) Gd-DTPA injection (1.0 mmol/kg, intravenously). At every laser power setting used in this study (0, 200, 400, 600, and 800 mW), the change in the mean signal intensity could be approximated by a simple exponential equation. However, the time constants determined for these curves were too imprecise to be useful as correlates between laser power and BRB breakdown. The slope of the line fit to the data in the first 20 min postinjection (ie, an initial-rate analysis) was a more precise correlate between BRB breakdown and laser power. This slope represented the rate of change in mean signal intensity in the ROI as a result of the entry of Gd-DTPA, and it was called the "leakiness" parameter. The leakiness parameter reflected changes in the permeability surface area product of the BRB if the blood flow and the Gd-DTPA arterial concentration immediately after injection were approximately the same between animals. C1 DUKE UNIV,CTR EYE,DURHAM,NC 27706. RP BERKOWITZ, BA (reprint author), NIEHS,MAIL DROP HA-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NEI NIH HHS [R01 EY07576] NR 9 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1991 VL 32 IS 11 BP 2854 EP 2860 PG 7 WC Ophthalmology SC Ophthalmology GA GL407 UT WOS:A1991GL40700002 PM 1917389 ER PT J AU KITAGAWA, Y GREINER, DL REYNOLDS, CW ORTALDO, JR TOCCAFONDI, R HANDLER, ES VANDERMEIDE, PH MORDES, JP ROSSINI, AA AF KITAGAWA, Y GREINER, DL REYNOLDS, CW ORTALDO, JR TOCCAFONDI, R HANDLER, ES VANDERMEIDE, PH MORDES, JP ROSSINI, AA TI ISLET CELLS BUT NOT THYROCYTES ARE SUSCEPTIBLE TO LYSIS BY NK CELLS SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; AUTOIMMUNE THYROID-DISEASE; CYTOPLASMIC GRANULES; BB RAT; ANTIGEN EXPRESSION; IODIDE TRANSPORT; LYMPHOCYTES-T; CYTO-TOXICITY C1 NCI,FREDERICK CTR RES FACIL,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA 01655. UNIV CONNECTICUT,DEPT PATHOL,STORRS,CT 06268. UNIV FLORENCE,MED CLIN 3,METAB RES SECT,I-50121 FLORENCE,ITALY. TNO,INST EXPTL GERONTOL,CTR PRIMATE,RIJSWIJK,NETHERLANDS. FU NIDDK NIH HHS [DK36024, DK25306, DK41235] NR 71 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD OCT PY 1991 VL 4 IS 5 BP 703 EP 716 DI 10.1016/0896-8411(91)90167-B PG 14 WC Immunology SC Immunology GA GL078 UT WOS:A1991GL07800001 PM 1797021 ER PT J AU GOLDING, A WEICKERT, MJ TOKESON, JPE GARGES, S ADHYA, S AF GOLDING, A WEICKERT, MJ TOKESON, JPE GARGES, S ADHYA, S TI A MUTATION DEFINING ULTRAINDUCTION OF THE ESCHERICHIA-COLI GAL OPERON SO JOURNAL OF BACTERIOLOGY LA English DT Note ID MAP AB Tn10 insertion in the galS (ultrainduction factor) gene of Escherichia coli allows the gal operon to be constitutively expressed at a very high leve, equal to that seen in a DELTA-galR strain in the presence of an inducer. The insertion has been mapped by criss-cross Hfr matings and by marker rescue into Kohara phages at 46 min on the E. coli chromosome. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 11 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1991 VL 173 IS 19 BP 6294 EP 6296 PG 3 WC Microbiology SC Microbiology GA GH455 UT WOS:A1991GH45500047 PM 1655705 ER PT J AU WOJCIECHOWSKI, MF PETERSON, KR LOVE, PE AF WOJCIECHOWSKI, MF PETERSON, KR LOVE, PE TI REGULATION OF THE SOS RESPONSE IN BACILLUS-SUBTILIS - EVIDENCE FOR A LEXA REPRESSOR HOMOLOG SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RECA PROTEIN ANALOG; ESCHERICHIA-COLI; DNA-DAMAGE; DEOXYRIBONUCLEIC-ACID; RESTRICTION FRAGMENTS; INDUCIBLE RESPONSES; MOLECULAR-CLONING; GENE-PRODUCT; MUTAGENESIS; CLEAVAGE AB The inducible SOS response for DNA repair and mutagenesis in the bacterium Bacillus subtilis resembles the extensively characterized SOS system of Escherichia coli. In this report, we demonstrate that the cellular repressor of the E. coli SOS system, the LexA protein, is specifically cleaved in B. subtilis following exposure of the cells to DNA-damaging treatments that induce the SOS response. The in vivo cleavage of LexA is dependent upon the functions of the E. coli RecA protein homolog in B. subtilis (B. subtilis RecA) and results in the same two cleavage fragments as produced in E. coli cells following the induction of the SOS response. We also show that a mutant form of the E. coli RecA protein (RecA430) can partially substitute for the nonfunctional cellular RecA protein in the B. subtilis recA4 mutant, in a manner consistent with its known activities and deficiencies in E. coli. RecA430 protein, which has impaired repressor cleaving (LexA, UmuD, and bacteriophage lambda-cI) functions in E. coli, partially restores genetic exchange to B. subtilis recA4 strains but, unlike wild-type E. coli RecA protein, is not capable of inducing SOS functions (expression of DNA damage-inducible [din::Tn917-lacZ] operons or RecA synthesis) in B. subtilis in response to DNA-damaging agents or those functions that normally accompany the development of physiological competence. Our results provide support for the existence of a cellular repressor in B. subtilis that is functionally homologous to the E. coli LexA repressor and suggest that the mechanism by which B. subtilis RecA protein (like RecA of E. coli) becomes activated to promote the induction of the SOS response is also conserved. C1 NICHHD,MAMMALIAN GENES & DEV LABS,BETHESDA,MD 20892. RP WOJCIECHOWSKI, MF (reprint author), UNIV ARIZONA,DEPT ECOL & EVOLUT BIOL,TUCSON,AZ 85721, USA. FU NCRR NIH HHS [S07RR07002]; NIGMS NIH HHS [GM36410] NR 57 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1991 VL 173 IS 20 BP 6489 EP 6498 PG 10 WC Microbiology SC Microbiology GA GK772 UT WOS:A1991GK77200025 PM 1917874 ER PT J AU TILLY, K AF TILLY, K TI INDEPENDENCE OF BACTERIOPHAGE-N-15 LYTIC AND LINEAR PLASMID REPLICATION FROM THE HEAT-SHOCK PROTEINS DNAJ, DNAK, AND GRPE SO JOURNAL OF BACTERIOLOGY LA English DT Note ID ESCHERICHIA-COLI DNAK; GENE; IDENTIFICATION; ENDS; TEMPERATURES; MUTANTS; GROWTH AB The chromosome of the temperature bacteriophage N15 replicates as a linear plasmid with covalently closed ends (or hairpins) when it forms a lysogen. I found that, in contrast to the cases for lambda and the low-copy-number plasmids F and P1, both phage and plasmid replication of N15 are independent of the heat shock proteins DnaJ, DnaK, and GrpE. RP TILLY, K (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 28 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1991 VL 173 IS 20 BP 6639 EP 6642 PG 4 WC Microbiology SC Microbiology GA GK772 UT WOS:A1991GK77200044 PM 1917885 ER PT J AU HENDLER, RW AF HENDLER, RW TI CAN FERRICYANIDE OXIDIZE CARBON MONOXIDE-LIGANDED CYTOCHROME-A3 SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE REDOX POTENTIALS; CYTOCHROME OXIDASE; ELECTRON TRANSPORT ID C-OXIDASE; HEART-MITOCHONDRIA; INVISIBLE COPPER; REDOX PROPERTIES; SPECTROSCOPY; BIOENERGETICS; COMPONENTS; REDUCTION; OXIDATION; SPECTRA AB Evidence for the oxidation of CO-liganded cytochrome a3 by ferricyanide has been published recently. These observations conflict with the long-held belief that ferricyanide is thermodynamically incapable of oxidizing the CO complex. The present paper examines the facts on which the earlier idea was based. It is concluded that the earlier evidence did not establish that ferricyanide was incompetent as an oxidant for CO-liganded cytochrome a3. RP HENDLER, RW (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD OCT PY 1991 VL 23 IS 5 BP 805 EP 817 DI 10.1007/BF00786002 PG 13 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA GP529 UT WOS:A1991GP52900007 PM 1660874 ER PT J AU CHARNEY, E CHEN, HH RAU, DC AF CHARNEY, E CHEN, HH RAU, DC TI THE FLEXIBILITY OF A-FORM DNA SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID TRANSIENT ELECTRIC BIREFRINGENCE; TRANSCRIPTION FACTOR-IIIA; RESTRICTION FRAGMENTS; PERSISTENCE LENGTH; LINEAR DICHROISM; BINDING-SITE; B-FORM; POLARIZABILITY; HELIX AB We have determined the rise per base pair and persistence length of A-form DNA in trifluoroethanol solutions for fragments 350-900 base pairs in length that best describe rotational diffusion coefficients determined by transient electric birefringence. The 2.6 A spacing between base pairs found in crystal and fiber A-form structures is preserved in solution. The persistence length is about 1500 A, or about three times longer than for B-form DNA. There is no apparent electrostatic contribution to the persistence length in the salt concentration range 0.2-2.0 mM Na cacodylate. This suggests an even closer association between DNA and its neutralizing counterions than predicted by condensation theory, perhaps due to a sheath of trifluoroethanol excluded water surrounding the A-form helix. C1 GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. NIDDK,BIOCHEM METAB LAB,BETHESDA,MD 20892. RP CHARNEY, E (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 36 TC 16 Z9 16 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD OCT PY 1991 VL 9 IS 2 BP 353 EP 362 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GL928 UT WOS:A1991GL92800012 PM 1741967 ER PT J AU DOMINGUEZ, P IBARAKI, K ROBEY, PG HEFFERAN, TE TERMINE, JD YOUNG, MF AF DOMINGUEZ, P IBARAKI, K ROBEY, PG HEFFERAN, TE TERMINE, JD YOUNG, MF TI EXPRESSION OF THE OSTEONECTIN GENE POTENTIALLY CONTROLLED BY MULTIPLE CIS-ACTING AND TRANS-ACTING FACTORS IN CULTURED BONE-CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR AP-2; ALPHA-1(I) COLLAGEN GENE; 1ST INTRON; MESSENGER-RNA; INSITU HYBRIDIZATION; REGULATORY ELEMENTS; BASEMENT-MEMBRANE; PROTEIN SPARC; RETINOIC ACID; PROMOTER AB The cis-acting regulatory elements of the osteonectin gene have been studied using a chloramphenicol acetyl-transferase (CAT) promoter assay in osteonectin-expressing and nonexpressing cultured cells. When various stretches of the promoter were transiently transfected into fetal bovine bone cells, a positive element was detected in the DNA located between bases -504 and 11 (1 being the start of transcription) and a negative element between bases -900 and -504. The positive element of the promoter also conferred preferential expression of the gene, showing more activity in cells with higher levels of osteonectin mRNA expression. A 1.2 kb fragment of intron 1 displayed a negative effect on CAT expression when inserted 5' to the promoter. An additional regulatory element was found in DNA encoding exon 1, which significantly influenced expression of the gene in fetal bovine bone cells. Gel shift analysis using positive genomic elements located 5' to the start of transcription indicated that one of the nuclear proteins that interacts with the osteonectin promoter may be related to the transcription factor AP2. C1 NIDR,BONE RES BRANCH,BLDG 30,RM 106,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011; Dominguez, Pedro/A-8266-2012 OI Robey, Pamela/0000-0002-5316-5576; Dominguez, Pedro/0000-0003-4788-1071 NR 45 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1991 VL 6 IS 10 BP 1127 EP 1136 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GN792 UT WOS:A1991GN79200014 PM 1796760 ER PT J AU KULESZALIPKA, D BAINES, IC BRZESKA, H KORN, ED AF KULESZALIPKA, D BAINES, IC BRZESKA, H KORN, ED TI IMMUNOLOCALIZATION OF MYOSIN-I HEAVY-CHAIN KINASE IN ACANTHAMOEBA-CASTELLANII AND BINDING OF PURIFIED KINASE TO ISOLATED PLASMA-MEMBRANES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID COFACTOR PROTEIN; ACTIN ACTIVATION; 3RD ISOFORM; PHOSPHORYLATION; LOCALIZATION; PURIFICATION; CLEAVAGE; SITES AB The actin-activated Mg2+-ATPase activities of Acanthamoeba myosins I are known to be maximally expressed only when a single threonine (myosin IA) or serine (myosins IB and IC) is phosphorylated by myosin I heavy chain kinase. The purified kinase is highly activated by autophosphorylation and the rate of autophosphorylation is greatly enhanced by the presence of acidic phospholipids. In this paper, we show by immunofluorescence and immunoelectron microscopy of permeabilized cells that myosin I heavy chain kinase is highly concentrated, but not exclusively, at the plasma membrane. Judged by their electrophoretic mobilities, kinase associated with purified plasma membranes may differ from the cytoplasmic kinase, possibly in the extent of its phosphorylation. Purified kinase binds to highly purified plasma membranes with an apparent K(D) of approximately 17 nM and a capacity of approximately 0.8 nmol/mg of plasma membrane protein, values that are similar to the affinity and capacity of plasma membranes for myosins I. Binding of kinase to membranes is inhibited by elevated ionic strength and by extensive autophosphorylation but not by substrate-level concentrations of ATP. Membrane-bound kinase autophosphorylates to a lesser extent than free kinase and does not dissociate from the membranes after autophosphorylation. The co-localization of myosin I heavy chain kinase and myosin I at the plasma membrane is of interest in relation to the possible functions of myosin I especially as phospholipids increase kinase activity. RP NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 31 TC 15 Z9 15 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1991 VL 115 IS 1 BP 109 EP 119 DI 10.1083/jcb.115.1.109 PG 11 WC Cell Biology SC Cell Biology GA GH249 UT WOS:A1991GH24900010 PM 1655799 ER PT J AU YAMAGATA, M YAMADA, KM YAMADA, SS SHINOMURA, T TANAKA, H NISHIDA, Y OBARA, M KIMATA, K AF YAMAGATA, M YAMADA, KM YAMADA, SS SHINOMURA, T TANAKA, H NISHIDA, Y OBARA, M KIMATA, K TI THE COMPLETE PRIMARY STRUCTURE OF TYPE-XII COLLAGEN SHOWS A CHIMERIC MOLECULE WITH REITERATED FIBRONECTIN TYPE-III MOTIFS, VONWILLEBRAND FACTOR-A MOTIFS, A DOMAIN HOMOLOGOUS TO A NONCOLLAGENOUS REGION OF TYPE-IX COLLAGEN, AND SHORT COLLAGENOUS DOMAINS WITH AN ARG-GLY-ASP SITE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID AMINO-ACID SEQUENCE; CHICK-EMBRYO; PLASMA FIBRONECTIN; CHAIN REVEALS; PROTEOGLYCAN; PROTEIN; COMPONENT; FRAGMENTS; BINDING; CDNA AB Extracellular matrix molecules are generally categorized as collagens, elastin, proteoglycans, or other noncollagenous structural/cell interaction proteins. Many of these extracellular proteins contain distinctive repetitive modules, which can sometimes be found in other proteins. We describe the complete primary structure of an alpha-1 chain of type XII collagen from chick embryonic fibroblasts. This large, structurally chimeric molecule identified by cDNA analysis combines previously unrelated molecular domains into a single large protein 3,124 residues long (approximately 340 kD). The deduced chicken type XII collagen sequence starts at the amino terminus with one unit of the type III motif of fibronectin, which is followed by one unit homologous to the von Willebrand factor A domain, then one more fibronectin type III module, a second A domain from von Willebrand factor, 6 units of type III motif and a third A domain, 10 consecutive units of type III motif and a fourth A domain, a domain homologous to the NC4 domain peptide of type IX collagen, and finally two short collagenous regions previously described as part of the partially sequenced collagen type XII molecule; an Arg-Gly-Asp potential cell adhesive recognition sequence is present in a hydrophilic region at the terminus of one collagenous domain. Antibodies raised to type XII collagen synthesized in a bacterial expression system recognized not only previously reported bands (220 kD et cetera) in tendons, but also bands with apparently different molecular sizes in fibroblasts and 4-d embryos. The antibodies stained a wide variety of extracellular matrices in embryos in patterns distinct from those of fibronectin or interstitial collagens. They prominently stained extracellular matrix associated with certain neuronal tissues, such as axons from dorsal root ganglia and neural tube. These studies identify a novel chimeric type of molecule that contains both adhesion molecule and collagen motifs in one protein. Its structure blurs current classification schemes for extracellular proteins and underscores the potentially large diversity possible in these molecules. C1 AICHI MED UNIV, INST MOLEC SCI MED, NAGAKUTE, AICHI 48011, JAPAN. INST PHYS & CHEM RES RIKEN, TSUKUBA LIFE SCI CTR, CELL BIOL LAB, TSUKUBA 305, JAPAN. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. GUNMA UNIV, DEPT PHARMACOL, MAEBASHI, GUNMA 371, JAPAN. AICHI CANC CTR, RES INST, DEPT EXPTL RADIOL, NAGOYA, AICHI 464, JAPAN. RI Yamagata, Masahito/H-6695-2016 OI Yamagata, Masahito/0000-0001-8193-2931 NR 54 TC 100 Z9 103 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1991 VL 115 IS 1 BP 209 EP 221 DI 10.1083/jcb.115.1.209 PG 13 WC Cell Biology SC Cell Biology GA GH249 UT WOS:A1991GH24900019 PM 1918137 ER PT J AU LEIKIN, S AF LEIKIN, S TI ON THE THEORY OF ELECTROSTATIC INTERACTION OF NEUTRAL LIPID BILAYERS SEPARATED BY THIN WATER FILM SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HYDRATION FORCE; ORIENTABLE DIPOLES; SURFACES; MODEL; MOBILE AB A simple analytical solution is obtained for the screened Coulombic force between neutral lipid bilayers separated by thin water film within a model formally analogous to the "spherical model" for Ising systems. This model accounts for constraints on the surface charge density fluctuations imposed by the structure of lipid bilayers. The force is attractive at low and repulsive at high temperatures. A relationship between the system parameters and the temperature of the transition from the repulsion to attraction is established. At room temperature predicted force can be repulsive as well as attractive depending on the system parameters and on the assumptions. C1 NIDDK,LBM,BETHESDA,MD 20892. AN FRUMKIN ELECTROCHEM INST,MOSCOW,USSR. RP LEIKIN, S (reprint author), NIH,PSL,DIV COMP RES & TECHNOL,BLDG 12A,ROOM 2007,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 28 TC 13 Z9 13 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 1 PY 1991 VL 95 IS 7 BP 5224 EP 5229 DI 10.1063/1.461693 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA GH356 UT WOS:A1991GH35600053 ER PT J AU LILLIOJA, S NYOMBA, BL SAAD, MF FERRARO, R CASTILLO, C BENNETT, PH BOGARDUS, C AF LILLIOJA, S NYOMBA, BL SAAD, MF FERRARO, R CASTILLO, C BENNETT, PH BOGARDUS, C TI EXAGGERATED EARLY INSULIN RELEASE AND INSULIN RESISTANCE IN A DIABETES-PRONE POPULATION - A METABOLIC COMPARISON OF PIMA-INDIANS AND CAUCASIANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PULSATILE SECRETION; MELLITUS; OBESITY; INVIVO; RESPONSES; RECEPTOR; HYPERINSULINEMIA; RELATIVES; DISPOSAL AB Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P < 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P < 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P < 0.0001), 38% higher 10 min after the end of a meal (P < 0.0001), and 20% higher 30 min after an oral glucose load (P < 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease. RP LILLIOJA, S (reprint author), PHOENIX INDIAN MED CTR, NIDDKD, CLIN DIABET & NUTR SECT, 4212 N 16TH ST, ROOM 541, PHOENIX, AZ 85016 USA. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 65 TC 125 Z9 126 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1991 VL 73 IS 4 BP 866 EP 876 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GF684 UT WOS:A1991GF68400029 PM 1890157 ER PT J AU BURCH, RM MAHAN, LC AF BURCH, RM MAHAN, LC TI OLIGONUCLEOTIDES ANTISENSE TO THE INTERLEUKIN-1 RECEPTOR MESSENGER-RNA BLOCK THE EFFECTS OF INTERLEUKIN-1 IN CULTURED MURINE AND HUMAN FIBROBLASTS AND IN MICE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INFLAMMATION; DERMATITIS; NEUTROPHIL INFILTRATION ID ARACHIDONIC-ACID METABOLISM; IL-1 RECEPTOR; T-CELLS; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; BINDING; INHIBITION; ANTAGONIST; CLONING AB Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1 stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3-mu-M-30-mu-M) fashion. Murine sense oligonucleotide and an oligonucleotide antisense to human IL-1 receptor were without effect. Moreover, murine antisense oligonucleotides did not affect tumor necrosis factor- or bradykinin-stimulated PGE2 synthesis by murine fibroblasts. Similarly, antisense oligonucleotides to the human, but not the murine, IL-1 receptor inhibited IL-1-stimulated PGE2 synthesis by cultured human fibroblasts. The attenuation of the cellular response to IL-1 caused by the antisense oligonucleotides correlated with a loss in cell surface receptors for IL-1, without any change in the number of bradykinin receptors on these cells. When antisense oligonucleotides were encapsulated in liposomes, they blocked completely the appearance of newly synthesized IL-1 receptors and IL-1-stimulated PGE2 synthesis. In mice, subcutaneous injection with an oligonucleotide antisense to the murine IL-1 receptor markedly inhibited the infiltration of neutrophils in response to subsequent injection of IL-1. These data suggest that antisense oligodeoxynucleotides may share a role in the design of antiinflammatory therapeutics. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP BURCH, RM (reprint author), NOVA PHARMACEUT CORP,6200 FREEPORT CTR,BALTIMORE,MD 21224, USA. NR 39 TC 72 Z9 73 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1991 VL 88 IS 4 BP 1190 EP 1196 DI 10.1172/JCI115421 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GJ508 UT WOS:A1991GJ50800018 PM 1833422 ER PT J AU LIMAYE, AP ABRAMS, JS SILVER, JE AWADZI, K FRANCIS, HF OTTESEN, EA NUTMAN, TB AF LIMAYE, AP ABRAMS, JS SILVER, JE AWADZI, K FRANCIS, HF OTTESEN, EA NUTMAN, TB TI INTERLEUKIN-5 AND THE POSTTREATMENT EOSINOPHILIA IN PATIENTS WITH ONCHOCERCIASIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE INTERLEUKIN-5; EOSINOPHILIA; ONCHOCERCIASIS; MAZZOTTI REACTION; DIETHYLCARBAMAZINE ID BANCROFTS FILARIASIS; BONE-MARROW; INFECTION; BLOOD; ANTIBODY; MANSONI; CELLS; MICE AB To understand the role of the eosinophilopoietic cytokine IL-5 in humans, the posttreatment eosinophilic response in a group of microfilaria (mf)-positive patients with onchocerciasis (n = 10) was examined before and after treatment with diethylcarbamazine (6 mg/kg for 7 d). Sequential blood samples were assessed at 24 and 1 h before treatment (baseline values), then at frequent intervals over the next 14 d. Symptom scores, skin microfilariae (mf), and peripheral blood eosinophil counts were recorded as a function of time after treatment, and serum levels of IL-5 were quantitated by a highly sensitive (sensitivity greater-than-or-equal-to 20 pg/ml) monoclonal-based ELISA. Pretreatment eosinophil counts ranged from 240 to 1,186 eosinophils/mu-l (geometric mean, 675), and the mf counts from 10 to 218 per mg skin (geometric mean, 79). After an initial decline in the peripheral eosinophil count to 28 +/- 8% of pretreatment levels at 8 h after beginning treatment, the eosinophil counts steadily increased over the next 2 wk, reaching a maximum at 14 d (257 +/- 38% of pretreatment levels). Serum levels of IL-5 rose sharply from pretreatment levels to a peak of 70.5 +/- 11 pg/ml by 24 h after treatment. Serum IL-5 remained elevated over the next 2-3 d and declined toward baseline by approximately 6 d after treatment, at which time the eosinophil levels were steadily increasing. IL-3 and granulocyte macrophage colony-stimulating factor, two other cytokines implicated in eosinophilopoeisis, were not detectable in the serum at any time before or after treatment. The rise in serum IL-5 before the posttreatment eosinophilia seen in this group of patients with onchocerciasis demonstrates a temporal relationship between IL-5 and the subsequent development of eosinophilia and implicates IL-5 as an important mediator of eosinophilia in humans. C1 NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. ONCHOCERCIASIS CHEMOTHERAPEUT RES CTR,TAMALE,GHANA. NR 16 TC 40 Z9 40 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1991 VL 88 IS 4 BP 1418 EP 1421 DI 10.1172/JCI115449 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GJ508 UT WOS:A1991GJ50800046 PM 1918387 ER PT J AU BEHETS, F DISASI, A RYDER, RW BISHAGARA, K PIOT, P KASHAMUKA, M KAMENGA, M NZILA, N LAGA, M VERCAUTEREN, G BATTER, V BROWN, C QUINN, T AF BEHETS, F DISASI, A RYDER, RW BISHAGARA, K PIOT, P KASHAMUKA, M KAMENGA, M NZILA, N LAGA, M VERCAUTEREN, G BATTER, V BROWN, C QUINN, T TI COMPARISON OF 5 COMMERCIAL ENZYME-LINKED IMMUNOSORBENT ASSAYS AND WESTERN IMMUNOBLOTTING FOR HUMAN-IMMUNODEFICIENCY-VIRUS ANTIBODY DETECTION IN SERUM SAMPLES FROM CENTRAL AFRICA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HIV INFECTION; BLOOD-DONORS; HTLV-III; ELISA; KITS; IMMUNOASSAYS; SENSITIVITY; ANTI-HIV-1; TESTS; EIA AB Detection by five different enzyme-linked immunosorbent assays (ELISAs) of antibody to human immunodeficiency virus (HIV) in sera from three Zairian populations consisting of 1,998 individuals with various risks for HIV infection was evaluated. Sera that were reactive by at least one assay and 10% of the nonreactive serum samples were analyzed by Western blot (immunoblot) by using . U.S. Public Health Service interpretation criteria. Sera which were positive by ELISA for detection of antibody to HIV-1 and HIV-2 and negative or indeterminate by HIV-1 Western blot were also analyzed by HIV-2 Western blot. Overall, 443 (22.2%) serum specimens were HIV-1 Western blot positive, 390 (19.5%) had indeterminate HIV-1 Western blot patterns, and no samples were HIV-2 Western blot positive. The sensitivity of the ELISAs ranged from 97.5 to 99.8%, and the specificity ranged from 51.7 to 98.4%. By population group, the negative predictive value ranged from 97.1 to 100%, in contrast to the positive predictive value, which varied from 6.6 to 100%. Follow-up results for sera which were indeterminate for antibody to HIV-1 documented only four seroconversions (6.0%) among 67 individuals at high risk for HIV-1 infection and no seroconversions among 202 individuals at relatively low risk for HIV-1 infection. This study demonstrates the importance of evaluating commercial ELISAs with sera from appropriate geographical regions in order to select the most cost-effective and practical assay for use in that region. Furthermore, the high frequency of indeterminate Western blots for African sera emphasizes the continual need for improved confirmatory assays and interpretation criteria. C1 PROJET SIDA,KINSHASA,ZAIRE. INST TROP MED,DEPT MICROBIOL,ANTWERP,BELGIUM. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. CTR DIS CONTROL,AIDS PROGRAM,ATLANTA,GA 30333. NR 16 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1991 VL 29 IS 10 BP 2280 EP 2284 PG 5 WC Microbiology SC Microbiology GA GG963 UT WOS:A1991GG96300035 PM 1939584 ER PT J AU ALLEGRA, CJ AF ALLEGRA, CJ TI BIOCHEMICAL MODULATION - A MODALITY THAT HAS COME OF THERAPEUTIC AGE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID METASTATIC COLORECTAL-CARCINOMA; HIGH-DOSE LEUCOVORIN; FOLINIC ACID; BREAST-CANCER; PHASE-II; FLUOROURACIL; 5-FLUOROURACIL; INTERFERON; INFUSION; MECHANISM RP ALLEGRA, CJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 27 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1991 VL 9 IS 10 BP 1723 EP 1726 PG 4 WC Oncology SC Oncology GA GH456 UT WOS:A1991GH45600002 PM 1919622 ER PT J AU GREM, JL MCATEE, N MURPHY, RF BALIS, FM STEINBERG, SM HAMILTON, JM SORENSEN, JM SARTOR, O KRAMER, BS GOLDSTEIN, LJ GAY, LM CAUBO, KM GOLDSPIEL, B ALLEGRA, CJ AF GREM, JL MCATEE, N MURPHY, RF BALIS, FM STEINBERG, SM HAMILTON, JM SORENSEN, JM SARTOR, O KRAMER, BS GOLDSTEIN, LJ GAY, LM CAUBO, KM GOLDSPIEL, B ALLEGRA, CJ TI A PILOT-STUDY OF INTERFERON ALFA-2A IN COMBINATION WITH FLUOROURACIL PLUS HIGH-DOSE LEUCOVORIN IN METASTATIC GASTROINTESTINAL CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED COLORECTAL-CARCINOMA; POLYINOSINIC-POLYCYTIDYLIC ACID; FOLINIC ACID; ONCOLOGY-GROUP; CONTINUOUS INFUSION; RANDOMIZED TRIAL; COLON-CARCINOMA; CELL-LINES; 5-FLUOROURACIL; MODULATION C1 UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,BETHESDA,MD 20814. NCI,DIV HYG & PUBL HLTH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NIH,CLIN CTR PHARM,CANC NURSING SERV,BETHESDA,MD 20892. RP GREM, JL (reprint author), NCI,DIV HYG & PUBL HLTH,CLIN ONCOL PROGRAM,MED BRANCH,GASTROINTESTINAL TUMOR SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 38 TC 112 Z9 112 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1991 VL 9 IS 10 BP 1811 EP 1820 PG 10 WC Oncology SC Oncology GA GH456 UT WOS:A1991GH45600015 PM 1919632 ER PT J AU URBA, WJ KOPP, WC CLARK, JW SMITH, JW STEIS, RG HUBER, C COGGIN, D LONGO, DL AF URBA, WJ KOPP, WC CLARK, JW SMITH, JW STEIS, RG HUBER, C COGGIN, D LONGO, DL TI THE INVIVO IMMUNOMODULATORY EFFECTS OF RECOMBINANT INTERFERON GAMMA PLUS RECOMBINANT TUMOR NECROSIS FACTOR-ALFA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; PHASE-I TRIAL; HUMAN-MONOCYTES; ENDOTHELIAL-CELLS; EXPRESSION; MACROPHAGES; SYNERGISM; NEOPTERIN; INDUCTION; MELANOMA C1 UNIV MAINZ,DEPT HAEMATOL,W-6500 MAINZ,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP URBA, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,CLIN IMMUNOL SERV,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 42 TC 6 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 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1991 VL 9 IS 10 BP 1831 EP 1839 PG 9 WC Oncology SC Oncology GA GH456 UT WOS:A1991GH45600017 PM 1919633 ER PT J AU KETTER, TA POST, RM WORTHINGTON, K AF KETTER, TA POST, RM WORTHINGTON, K TI PRINCIPLES OF CLINICALLY IMPORTANT DRUG-INTERACTIONS WITH CARBAMAZEPINE .2. SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review ID EPILEPTIC PATIENTS; VALPROIC ACID; PLASMA-CONCENTRATIONS; SERUM CONCENTRATIONS; ANTICONVULSANT TREATMENT; ANTIEPILEPTIC DRUGS; AFFECTIVE-ILLNESS; SODIUM VALPROATE; ANTI-CONVULSANTS; THYROID-HORMONES C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 159 TC 39 Z9 39 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1991 VL 11 IS 5 BP 306 EP 312 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA GG423 UT WOS:A1991GG42300006 PM 1765573 ER PT J AU ABBOTT, BD PRATT, RM AF ABBOTT, BD PRATT, RM TI RETINOIC ACID ALTERS EPITHELIAL DIFFERENTIATION DURING PALATOGENESIS SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Article DE 13-CIS-RETINOIC ACID; ALL-TRANS-RETINOIC ACID; EPIDERMAL GROWTH FACTOR; EGF; CLEFT PALATE; PALATAL EPITHELIUM ID EPIDERMAL GROWTH-FACTOR; SECONDARY PALATE FORMATION; VITAMIN-A; MOUSE DEVELOPMENT; FACTOR RECEPTORS; ORGAN-CULTURE; FACTOR-ALPHA; RESPONSIVE ELEMENT; LIMB DEVELOPMENT; SHELVES PRIOR AB Retinoids are teratogenic in humans and animals, producing a syndrome of craniofacial malformations that includes cleft palate. This study investigates the mechanism through which retinoic acid induces cleft palate. Murine palatogenesis after exposure to retinoic acid in utero is compared to normal development and to alterations observed after exposure in organ culture to retinoic acid or epidermal growth factor (EGF). Human embryonic palatal shelves were placed in the organ culture system and the responses to retinoic acid and EGF were compared to those of the murine palatal shelves. Growth factors play a role in normal development and are found in the embryonic palate. In other cell culture systems, retinoids alter the expression of EGF receptors. Our results suggest that in the medial epithelial cells of the palate, retinoic acid sustains the expression of the EGF receptor and the binding of EGF at a time when the expression in control medial cells has declined, and these control cells subsequently undergo programmed cell death. The continued DNA synthesis, proliferation, survival, and shift in phenotype of the medial cells is believed to interfere with the adhesion and fusion of opposing palatal shelves, resulting in cleft palate. C1 NIEHS,REPROD & DEV TOXICOL LAB,EXPTL TERATOGENESIS SECT,RES TRIANGLE PK,NC 27709. NR 71 TC 16 Z9 16 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD OCT-DEC PY 1991 VL 11 IS 4 BP 315 EP 325 PG 11 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA GX043 UT WOS:A1991GX04300015 PM 1812132 ER PT J AU YAMADA, Y HORTON, W MIYASHITA, T SAVAGNER, P HASSELL, J DOEGE, K AF YAMADA, Y HORTON, W MIYASHITA, T SAVAGNER, P HASSELL, J DOEGE, K TI EXPRESSION AND STRUCTURE OF CARTILAGE PROTEINS SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Article DE CHONDROCYTES; COLLAGEN; II; AGGRECAN; LINK PROTEIN ID PROTEOGLYCAN CORE PROTEIN; IX COLLAGEN-PROTEOGLYCAN; II GENE AB Cartilage has unique physical characteristics attributable to the presence of an unusually high content of proteoglycan embedded in the network of collagen fibrils. Advances in understanding the structure of these components and how their synthesis is regulated have been greatly assisted by the application of molecular biology. For example, an immortalized rat chondrocyte cell line was obtained by infection with a recombinant retrovirus encoding the myc gene product. Several positive and negative DNA regulatory elements of the collagen II gene have been identified that appear to be important in the regulation of this gene in chondrocytes. The complete primary structure of the cartilage proteoglycan (aggrecan) core protein deduced from cDNA sequence displays a complex multidomain structure including numerous repeats of Ser-Gly sequences and sequence homologies with link protein and animal lectins. Such studies advance our understanding of normal morphogenetic events and lay the groundwork for determining the basis of molecular and genetic defects. RP YAMADA, Y (reprint author), NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892, USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD OCT-DEC PY 1991 VL 11 IS 4 BP 350 EP 356 PG 7 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA GX043 UT WOS:A1991GX04300018 PM 1812134 ER PT J AU BROWN, KS YAMADA, Y ABRAMCZUK, J KIMATA, K AF BROWN, KS YAMADA, Y ABRAMCZUK, J KIMATA, K TI NEW GENETIC APPROACHES TO CRANIOFACIAL GROWTH AND MALFORMATION IN THE MOUSE SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Article DE TRANSGENIC MICE; COLLAGEN-II ID TRANSGENIC MICE; STRAIN ANALYSIS; PROTEOGLYCAN; PHENOTYPE; CARTILAGE; PROTEIN AB New genetic tools that have been developed in the mouse for the study of genetic variation and molecular biology can be applied to the study of craniofacial growth and malformation. D.W. Bailey (Journal of Heredity, 76:107-114, 1985, 77:17-25, 1986) has used congenic and recombinant inbred strains to identify a large number of genes that result in growth variation in local regions of the mandible. The function of "morphogenes" have not been characterized, but they may act as switches that regulate already recognized structural genes. We have studied the cartilage matrix deficiency (cmd/cmd) mutant mouse and found that their chondrocytes fail to synthesize the cartilage-specific proteoglycan at both protein and mRNA levels. In vitro experiments demonstrate biochemical feedback control in the formation of the cartilage extracellular matrix. Abnormalities of cartilage matrix result in facial clefts and in dental malocclusion in mice. A recombinant plasmid containing the type II collagen promoter and enhancer fused to a reporter gene, chloramphenicol acetyl transferase, has been used to produce transgenic mice. These mice reveal that the type II collagen enhancer controls the high level of tissue-specific expression of the gene. The transgenic mice provide a potential test system for study of development and teratogenesis at the gene level. RP BROWN, KS (reprint author), NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892, USA. NR 14 TC 3 Z9 3 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD OCT-DEC PY 1991 VL 11 IS 4 BP 357 EP 365 PG 9 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA GX043 UT WOS:A1991GX04300019 PM 1812135 ER PT J AU TOWNSLEY, JD AF TOWNSLEY, JD TI RESEARCH ADVANCES IN PRENATAL CRANIOFACIAL DEVELOPMENT - PREFACE SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Editorial Material RP TOWNSLEY, JD (reprint author), NIDR,CRANIOFACIAL ANOMALIES PAIN CONTROL & BEHAN RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD OCT-DEC PY 1991 VL 11 IS 4 BP R5 EP R5 PG 1 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA GX043 UT WOS:A1991GX04300002 ER PT J AU FRANKEL, RA POTTALA, EW BOWSER, RW BAILEY, JJ AF FRANKEL, RA POTTALA, EW BOWSER, RW BAILEY, JJ TI A FILTER TO SUPPRESS ECG BASE-LINE WANDER AND PRESERVE ST-SEGMENT ACCURACY IN A REAL-TIME ENVIRONMENT SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE ECG; MONITOR; REAL-TIME; FILTER; BASE-LINE; ST-SEGMENTS AB Accurate monitoring of the ST-segment displacements in real-time environments can be distorted by the nonlinear phase response of a baseline filter such as the single-pole, high-pass (0.5 Hz) filter that is standard in the industry today. The authors have previously constructed a four-pole null phase (1.0 Hz) filter that is nearly ideal in suppressing baseline wander while preserving ST-segment accuracy; however, this foreward/backward filter requires capture of a large ECG segment before filtering, thereby producing a delay that is unacceptable in a real-time environment. As a practical compromise, a two-pole, phase-compensated (1.0 Hz) filter was constructed while introducing a small time delay (160 ms). It performs much better than the "standard filter" and almost as well as the "ideal" filter in several tests, namely (1) suppression of baseline wander in a series of ECGs, (2) suppression of artificial baseline, (3) response to a triangular impulse wave (American Heart Association test), and (4) J-point displacement in several ECGs. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. MED COLL OHIO,DEPT PHYSIOL & BIOPHYS,TOLEDO,OH 43699. CREIGHTON UNIV,CTR CARDIAC,OMAHA,NE 68178. NR 11 TC 7 Z9 7 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD OCT PY 1991 VL 24 IS 4 BP 315 EP 323 DI 10.1016/0022-0736(91)90014-D PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GK156 UT WOS:A1991GK15600003 PM 1836004 ER PT J AU SANT, AJ HENDRIX, LR COLIGAN, JE MALOY, WL GERMAIN, RN AF SANT, AJ HENDRIX, LR COLIGAN, JE MALOY, WL GERMAIN, RN TI DEFECTIVE INTRACELLULAR-TRANSPORT AS A COMMON MECHANISM LIMITING EXPRESSION OF INAPPROPRIATELY PAIRED CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ALPHA/BETA CHAINS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CELL-SURFACE EXPRESSION; MHC CLASS-II; CHONDROITIN SULFATE PROTEOGLYCAN; INFLUENZA-VIRUS HEMAGGLUTININ; MEDIATED GENE-TRANSFER; MOUSE L-CELLS; INVARIANT CHAIN; IA ANTIGENS; BETA-CHAIN; HLA-DR AB Distinct combinations of class II major histocompatibility complex (MHC) alpha and beta-chains show widely varying efficiencies of cell surface expression in transfected cells. Previous studies have analyzed the regions of the class II chains that are critically involved in this phenomenon of variable expression and have shown a predominant effect of the NH2-terminal domains comprising the peptide-binding site. The present experiments attempt to identify the post-translational defects responsible for this variation in surface class II molecule expression for both interisotypic alpha/beta-combinations failing to give rise to any detectable cell membrane molecules (e.g., E-alpha-A-beta-k) and intraisotypic pairs with inefficient surface expression (e.g., A-alpha-dA-beta-k). The results of metabolic labeling and immunoprecipitation experiments using L cell transfectants demonstrate that in both of these cases, the alpha and beta-chains form substantial amounts of stable intracellular dimers. However, the isotype- and allele-mismatched combinations do not show the typical post-translational increases in molecular weight that accompany muturation of the N-linked glycans of class II MHC molecules. Studies with endoglycosidase H reveal that no or little progression to endoglycosidase H resistance occurs for these mismatched dimers. These data are consistent with active or passive retention of relatively stable and long-lived mismatched dimers in a pre-medial-Golgi compartment, possibly in the endoplasmic reticulum itself. This retention accounts for the absent or poor surface expression of these alpha/beta-combinations, and suggests that conformational effects of the mismatching in the NH2-terminal domain results in a failure of class II molecules to undergo efficient intracellular transport. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NR 56 TC 55 Z9 55 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1991 VL 174 IS 4 BP 799 EP 808 DI 10.1084/jem.174.4.799 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GJ109 UT WOS:A1991GJ10900007 PM 1919435 ER PT J AU VANSEVENTER, GA NEWMAN, W SHIMIZU, Y NUTMAN, TB TANAKA, Y HORGAN, KJ GOPAL, TV ENNIS, E OSULLIVAN, D GREY, H SHAW, S AF VANSEVENTER, GA NEWMAN, W SHIMIZU, Y NUTMAN, TB TANAKA, Y HORGAN, KJ GOPAL, TV ENNIS, E OSULLIVAN, D GREY, H SHAW, S TI ANALYSIS OF T-CELL STIMULATION BY SUPERANTIGEN PLUS MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES OR BY CD3 MONOCLONAL-ANTIBODY - COSTIMULATION BY PURIFIED ADHESION LIGANDS VCAM-1, ICAM-1, BUT NOT ELAM-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN LYMPHOCYTES-T; ENDOTHELIAL-CELLS; B-CELLS; ANTIGEN PRESENTATION; INTERFERON-GAMMA; ACCESSORY CELLS; IFN-GAMMA; IA EXPRESSION; ACTIVATION AB Many ligands of adhesion molecules mediate costimulation of T cell activation. The generality of this emerging concept is best determined by using model systems which exploit physiologically relevant ligands. We developed such an "antigen-specific" model system for stimulation of resting CD4+ human T cells using the following purified ligands: (a) major histocompatibility complex class II plus the superantigen Staphylococcus enterotoxin A, to engage the T cell receptor (TCR); (b) adhesion proteins vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1), to provide potential cell surface costimulatory signals; and (c) recombinant interleukin 1-beta (rIL-1-beta)/rIL-6 as costimulatory cytokines. In this biochemically defined system, we find that resting CD4+ T cells require costimulation in order to respond to TCR engagement. This costimulation can be provided by VCAM-1 or ICAM-1; however adhesion alone is not sufficient since ELAM-1 mediates adhesion but not costimulation. The cytokines IL-1-beta and IL-6 by themselves cannot mediate costimulation, but augment the adhesion ligand-mediated costimulation. Direct comparison with the model of TCR/CD3 engagement by CD3 monoclonal antibody demonstrated comparable costimulatory requirements in both system, thereby authenticating the commonly used CD3 model. The costimulation mediated by the activation-dependent interaction of the VLA-4 and LFA-1 integrins with their respective ligands VCAM-1 and ICAM-1 leads to increased IL-2R-alpha (CD25) expression and proliferation in both CD45RA+ CD4+ and CD45RO+ CD4+ T cells. The integrins also regulate the secretion of IL-2, IL-4, and granulocyte/macrophage colony-stimulating factor. In contrast the activation-independent adhesion of CD4+ T cell to ELAM-1 molecules does not lead to T cell stimulation as measured by proliferation, IL-2R-alpha expression, or cytokine release. These findings imply that adhesion per se is not sufficient for costimulation, but rather that the costimulation conferred by the VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions reflects specialized accessory functions of these integrin pathways. The new finding that VLA-4/VCAM-1 mediates costimulation adds significance to observations that VCAM-1 is expressed on a unique set of potential antigen-presenting cells in vivo. C1 OTSUKA AMER PHARMACEUT INC,DEPT ENDOTHELIAL CELL BIOL,ROCKVILLE,MD 20850. OTSUKA AMER PHARMACEUT INC,DEPT MOLEC BIOL,ROCKVILLE,MD 20850. UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. CYTEL CORP,LA JOLLA,CA 92037. RP VANSEVENTER, GA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. OI Shimizu, Yoji/0000-0001-9760-0288 FU NIAID NIH HHS [AI-31126-01] NR 69 TC 332 Z9 333 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1991 VL 174 IS 4 BP 901 EP 913 DI 10.1084/jem.174.4.901 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GJ109 UT WOS:A1991GJ10900019 PM 1717633 ER PT J AU CURRAN, MJ BRODWICK, MS AF CURRAN, MJ BRODWICK, MS TI IONIC CONTROL OF THE SIZE OF THE VESICLE MATRIX OF BEIGE MOUSE MAST-CELLS SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID CATION-EXCHANGE; MULTIMODAL DISTRIBUTION; MOLECULAR MECHANISM; GRANULES VESICLES; COMMON MECHANISM; BIOGENIC-AMINES; MUCIN SECRETION; RELEASE; EXOCYTOSIS; STORAGE AB Isolated matrices of the giant secretory vesicles of mast cells of the beige mouse were reliably produced by the osmotic lysis of isolated vesicles. These matrices maintained their form, and their sizes were easily measured using Nomarski optics. The size of the matrix depended on the ionic composition of the bathing solution. The physiologically relevant ions, histamine and serotonin, contracted the matrix. Multivalent cations condensed the matrix relative to univalents. Ag+, acid pH (below 5), and basic pH (above 9) expanded the matrix. In the presence of 10 mM histamine, lowering the pH from 9 to 5 contracted the matrix more than can be attributed to the pH-dependent matrix contraction in zero histamine. The nontitratable organic cation, dimethonium, contracts the matrix with little effect of pH in the range of 5-9. These results suggest that histamine acts as a matrix contractor in the divalent form. The dose-response (contraction) relation for histamine was gradual from micromolar to 316 mM (millimolar) histamine. Experiments with mixtures of histamine and sodium show antagonistic effects on the matrix but are inconsistent with either a model where ions compete for identical sites or a parallel model where ions interact with separate independent sites. In vigorous histamine washoff experiments, the half time for vesicle expansion in 10(-4) M pH buffer was approximately 4 s; in isotonic NaCl solution, it was 0.5 s. When 1 M histamine was presented to closely apposed matrices, fusion resulted. The matrix material returned to its initial shape after being mechanically deformed with a glass probe. These results suggest that the matrix size is controlled by its ion exchange properties. The matrix expansion can quantitatively account for the vesicular size increase observed upon exocytosis (as a postfusional event) and the osmotic nonideality of intact vesicles. The mechanical expansion is probably significant in the widening of the exocytotic pore and the dispersal of the vesicular contents. C1 UNIV TEXAS,MED BRANCH,DEPT PHYSIOL & BIOPHYS,GALVESTON,TX 77550. NIH,BETHESDA,MD 20892. NR 40 TC 66 Z9 67 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD OCT PY 1991 VL 98 IS 4 BP 771 EP 790 DI 10.1085/jgp.98.4.771 PG 20 WC Physiology SC Physiology GA GK907 UT WOS:A1991GK90700006 PM 1960530 ER PT J AU PETERS, D HORNFELDT, AB GRONOWITZ, S AF PETERS, D HORNFELDT, AB GRONOWITZ, S TI SYNTHESIS OF VARIOUS 5-ARYLSUBSTITUTED CYTOSINES SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID NUCLEOSIDES; ANALOGS; URACIL AB Some Pd-catalyzed coupling reactions have been evaluated for the synthesis of 5-substituted cytosines. A large number of 5-arylcytosines were prepared in good yields by using 2,4-O,N-bis-trimethylsilyl-5-iodocytosine with various aryl tin compounds. The use of trimethylsilyl groups proved to be essential for the reaction, attempted coupling of 5-iodocytosine and 2-trimethylstannylthiazole was not successful. One convenient alternative, which unfortunately was not successful, would have been to reverse the coupling functionalities and couple commercial arylhalides with 5-trimethylstannyl- or 5-tributylstannyl-derivatives or the corresponding 2,4-O,N-bis-trialkylsilylcytosines. C1 NIH,BETHESDA,MD 20892. RP PETERS, D (reprint author), CHEM CTR LUND,BOX 124,S-22100 LUND,SWEDEN. NR 31 TC 19 Z9 19 U1 0 U2 1 PU HETERO CORPORATION PI TAMPA PA BOX 20285, TAMPA, FL 33622-0285 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD OCT PY 1991 VL 28 IS 6 BP 1613 EP 1617 PG 5 WC Chemistry, Organic SC Chemistry GA HU846 UT WOS:A1991HU84600026 ER PT J AU HIRSCH, R ARCHIBALD, J GRESS, RE AF HIRSCH, R ARCHIBALD, J GRESS, RE TI DIFFERENTIAL T-CELL HYPORESPONSIVENESS INDUCED BY INVIVO ADMINISTRATION OF INTACT OR F(AB')2 FRAGMENTS OF ANTI-CD3 MONOCLONAL-ANTIBODY - F(AB')2 FRAGMENTS INDUCE A SELECTIVE T-HELPER DYSFUNCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; TUMOR-NECROSIS-FACTOR; ALLOGRAFT-REJECTION; BIOLOGICAL-ACTIVITY; INTERLEUKIN-2; MICE; ACTIVATION; OKT3; TRANSPLANTATION; RECEPTOR AB Induction of peripheral T cell anergy associated with stimulation through the TCR complex in vivo has been described in mice using chemically modified APC, staphylococcal enterotoxin B, and intact anti-CD3 mAb. In the latter two models, T cell proliferation, IL-2R expression, and lymphokine production have been demonstrated before subsequent induction of hyporesponsiveness, whereas in the former model, these events have not been observed. To further investigate the relationship between mitogenicity and induction of peripheral hyporesponsiveness, mice were treated with either mitogenic intact anti-CD3 mAb or nonmitogenic F(ab')2 fragments of anti-CD3 mAb. T cells from F(ab')2-treated mice demonstrated a selective decrease in helper functions, with minimal effect on CTL function. Specifically, a marked reduction in ability of Th cells to secrete IL-2 when challenged in vitro with mitogen or alloantigen was observed, which persisted for at least 2 mo after mAb administration and which was independent of T cell depletion. Proliferative function was decreased in CD4+ T cells and could not be fully restored with addition of exogenous IL-2. A helper defect was also evident in vivo, in that F(ab')2-treated mice were deficient in their ability to reject MHC-disparate skin grafts, and in vivo administration of IL-2 reconstituted their ability to reject skin grafts normally. In contrast, T cells from mice treated with intact mAb demonstrated a significant decrease in both CTL and helper functions. A long term reduction in TCR expression on CD4+ cells from F(ab')2-treated mice, and on both CD4+ and CD8+ cells from intact mAb-treated mice was observed. These findings demonstrate that peripheral T cell hyporesponsiveness can be induced in vivo by binding an identical epitope on the TCR complex in the presence or absence of initial proliferation, lymphokine secretion, or IL-2R expression, and that binding to the same epitope can result in varying long term effects on T cell function. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 27 TC 48 Z9 49 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2088 EP 2093 PG 6 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400004 PM 1833451 ER PT J AU BLAYLOCK, BL KOUCHI, Y COMMENT, CE CORSINI, E ROSENTHAL, GJ LUSTER, MI AF BLAYLOCK, BL KOUCHI, Y COMMENT, CE CORSINI, E ROSENTHAL, GJ LUSTER, MI TI PENTAMIDINE ISOTHIONATE REDUCES IA EXPRESSION AND ANTIGEN PRESENTATION BY LANGERHANS CELLS AND INHIBITS THE CONTACT HYPERSENSITIVITY REACTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; LYMPH-NODES; T-CELLS; PRESENTING CELLS; SKIN; MICE; UNRESPONSIVENESS; DEPLETION; INDUCTION; COMPLEX AB The mechanism of action of pentamidine isethionate, a diamidino compound used in the treatment of Pneumocystis carinii pneumonia, is unknown. We recently reported that this drug may inhibit the release of inflammatory mediators from alveolar macrophages, which may be associated with its antiparasite activity. As a potential anti-inflammatory agent, we report that topically applied pentamidine reduces ear swelling in the contact hypersensitivity reaction to oxazolone in B6C3F1 mice. The application of pentamidine must occur within 1 h, at the challenge site, to be effective. Topical application appears necessary, because i.v. injection had no effect on reduction of ear swelling. In dose-response studies, a 50% reduction in ear swelling was achieved with as little as 20-mu-g of pentamidine. Pentamidine did not affect Ag transport from the challenge site to the draining lymph nodes, as measured by FITC transport. However, there was a 30 to 40% reduction in epidermal cells expressing Ia Ag from pentamidine-treated mouse ears, compared with control. Ia expression is almost exclusively limited to Langerhans cells in the normal epidermis. This reduction in Ia expression was not due to simple depletion of Langerhans cells by pentamidine, because CD45 expression was unaffected. Concurrent with reduced Ia expression, Ag presentation by pentamidine-treated Langerhans cells was also reduced. Taken together, a mechanism of action for pentamidine in inhibition of the contact hypersensitivity reaction appears to be via a reduction in Ag presentation by decreasing Ia+ Langerhans cells. C1 NIEHS,NATL TOXICOL PROGRAM,SYST TOX BRANCH,IMMUNOTOXICOL GRP,MD C1-04,POB 12233,RES TRIANGLE PK,NC 27709. TAIHO PHARMACEUT CO LTD,TOKUSHIMA,JAPAN. UNIV MILAN,INST PHARMACOL SCI,I-20122 MILAN,ITALY. RP BLAYLOCK, BL (reprint author), NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. RI Corsini, Emanuela/B-5602-2011 NR 40 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2116 EP 2121 PG 6 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400008 PM 1833452 ER PT J AU JANOFF, EN HARDY, WD SMITH, PD WAHL, SM AF JANOFF, EN HARDY, WD SMITH, PD WAHL, SM TI HUMORAL RECALL RESPONSES IN HIV-INFECTION - LEVELS, SPECIFICITY, AND AFFINITY OF ANTIGEN-SPECIFIC IGG SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; B-CELL ACTIVATION; MEMORY T-CELLS; ANTIBODY-RESPONSES; LYMPHOCYTES-B; LYMPHOTROPIC VIRUS; TETANUS; AIDS; ADULTS AB To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p < 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36-mu-g/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT-specific IgG (p < 0.05). Peak levels correlated directly with the number of CD4+ T cells (p < 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (K(d) = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time. C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,DEPT MED,AIDS CLIN RES CTR,LOS ANGELES,CA 90024. RP JANOFF, EN (reprint author), VET AFFAIRS MED CTR,DEPT MED,INFECT DIS SECT IIIF,1 VE DR,MINNEAPOLIS,MN 55417, USA. NR 53 TC 75 Z9 76 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2130 EP 2135 PG 6 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400010 PM 1918947 ER PT J AU SCHNEERSON, R FATTOM, A SZU, SC BRYLA, D ULRICH, JT RUDBACH, JA SCHIFFMAN, G ROBBINS, JB AF SCHNEERSON, R FATTOM, A SZU, SC BRYLA, D ULRICH, JT RUDBACH, JA SCHIFFMAN, G ROBBINS, JB TI EVALUATION OF MONOPHOSPHORYL LIPID-A (MPL) AS AN ADJUVANT - ENHANCEMENT OF THE SERUM ANTIBODY-RESPONSE IN MICE TO POLYSACCHARIDE-PROTEIN CONJUGATES BY CONCURRENT INJECTION WITH MPL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; T-CELL ACTIVITY; CAPSULAR POLYSACCHARIDE; TREHALOSE DIMYCOLATE; IMMUNOGENICITY; VACCINES; INACTIVATION; CHILDREN; VI AB Concurrent injection of monophosphoryl lipid A (MPL) in saline or as an oil-in-water emulsion enhanced both the primary and secondary serum antibody responses to the capsular polysaccharide (CP) components of seven conjugates: the enhanced responses were Ag-specific. In contrast, MPL did not enhance the serum antibody response to five of the six unconjugated CP. MPL and trehalose dimycolate injected concurrently with the unconjugated Vi CP of Salmonella typhi (Vi) enhanced the serum antibody response to that Ag. MPL further enhanced the Vi antibody levels when injected with conjugates of this CP. The serum antibody responses to Pseudomonas aeruginosa exotoxin A, used as the carrier p2rotein for the Staphylococcus aureus types 5 and 8 conjugates, were also enhanced by MPL. MPL in oil-in-water emulsion was generally more effective than when administered in saline. C1 NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. SUNY DOWNSTATE MED CTR,DEPT MICROBIOL & IMMUNOL,BROOKLYN,NY 11203. RIBI IMMUNOCHEM RES INC,HAMILTON,MT 59840. NR 30 TC 36 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2136 EP 2140 PG 5 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400011 PM 1918948 ER PT J AU YOSHIMURA, T TAKEYA, M TAKAHASHI, K KURATSU, JI LEONARD, EJ AF YOSHIMURA, T TAKEYA, M TAKAHASHI, K KURATSU, JI LEONARD, EJ TI PRODUCTION AND CHARACTERIZATION OF MOUSE MONOCLONAL-ANTIBODIES AGAINST HUMAN MONOCYTE CHEMOATTRACTANT PROTEIN-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD MONONUCLEAR LEUKOCYTES; AMINO-ACID SEQUENCE; SMOOTH-MUSCLE CELLS; CHEMOTACTIC FACTOR; GROWTH-FACTOR; GENE JE; PURIFICATION; CLONING; GLIOMA; ACTIVATION AB We developed five different hybridoma cell lines that produced mAb against human monocyte chemoattractant protein-1 (MCP-1). The subclass of all five antibodies was IgG1. All five mAb formed complexes with metabolically labeled MCP-1 that could be demonstrated by immunoprecipitation. The antibodies were specific for MCP-1. They did not cross-react by immunoprecipitation with structurally related host defense cytokines present in metabolically labeled PHA- or LPS-stimulated mononuclear cell culture fluids, nor did they cross-react in a direct ELISA with neutrophil attractant/activation protein-1, with crude platelet lysate proteins, or with pure platelet proteins that have amino acids sequences similar to that of MCP-1. The mAb also reacted with rMCP-1 expressed in Escherichia coli, suggesting that they recognize protein structure rather than the glycosylated portion of human MCP-1. When the mAb were mixed with MCP-1, the monocyte chemotactic response to MCP-1 was inhibited. A sandwich ELISA was developed to detect MCP-1 in biologic fluids containing relatively high concentrations of other proteins. The sensitivity was 300 pg/ml, or 30 pg/ELISA well. An anti-MCP-1 mAb column was used in an improved method of MCP-1 purification. Approximately 240-mu-g of MCP-1 were purified from 5 liters of FCS-containing U-105MG cell culture supernatant. The yield was at least 60%. In addition to two forms of MCP-1 reported previously by us, two more forms of MCP-1 were found in a mixture of culture supernatants of PHA- and LPS-stimulated human PBMC. C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,KUMAMOTO 860,JAPAN. RP YOSHIMURA, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702, USA. NR 25 TC 58 Z9 58 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2229 EP 2233 PG 5 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400025 PM 1918959 ER PT J AU BRESSLER, P PANTALEO, G DEMARIA, A FAUCI, AS AF BRESSLER, P PANTALEO, G DEMARIA, A FAUCI, AS TI ANTI-CD2 RECEPTOR ANTIBODIES ACTIVATE THE HIV LONG TERMINAL REPEAT IN LYMPHOCYTES-T SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; TUMOR NECROSIS FACTOR; NF-KAPPA-B; NUCLEAR FACTOR BINDING; FACTOR-ALPHA; GENE-EXPRESSION; INDUCTION; CELLS; CD2; TRANSCRIPTION AB The CD2 T lymphocyte glycoprotein surface molecule mediates both cell to cell adhesion and T cell activation, two processes that are involved in the spread of HIV infection. Treatment of chronically HIV-infected PBMC with anti-CD2 mAb has been shown to induce the expression of infectious virus from these cultures. In this study we investigated the mechanisms whereby anti-CD2 antibodies stimulate viral production. We demonstrate that treatment of transiently transfected T lymphocytes with anti-CD2 antibodies results in activation of the HIV long terminal repeat. Furthermore, CAT assays using mutated HIV long terminal repeat-CAT constructs and gel shift assays demonstrate that this activation is dependent on the NF-(k)B enhancer. These studies suggest that interaction of CD2 with its natural ligand, LFA-3, may play a role in regulation of HIV expression. RP BRESSLER, P (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 30 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2290 EP 2294 PG 5 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400034 PM 1680914 ER PT J AU HAKIM, FT GAZZINELLI, RT DENKERS, E HIENY, S SHEARER, GM SHER, A AF HAKIM, FT GAZZINELLI, RT DENKERS, E HIENY, S SHEARER, GM SHER, A TI CD8+ T-CELLS FROM MICE VACCINATED AGAINST TOXOPLASMA-GONDII ARE CYTOTOXIC FOR PARASITE-INFECTED OR ANTIGEN-PULSED HOST-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; CIRCUMSPOROZOITE PROTEIN; INTERFERON-GAMMA; IMMUNITY; LYT-2+; TROPHOZOITES; RESISTANCE; ANTIBODY; MALARIA; INVITRO AB Mice vaccinated with a live temperature sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to subsequent challenge with a highly virulent Toxoplasma strain (RH). Because CD8+ T cells have been demonstrated to be critical to this protective immunity in vivo, the involvement of cytotoxic T lymphocytes in the killing of infected cells in vaccinated mice was investigated. After re-stimulation in vitro, splenic T cells from vaccinated mice of either the BALB/c or C57BL/6 strains were found to kill syngeneic bone marrow-derived macrophages infected with TS-4 tachyzoites or preincubated with soluble T. gondii Ag. Unimmunized control mice or mice vaccinated with heat-killed TS-4 tachyzoites failed to generate significant CTL activity in vitro. Moreover, the observed lytic reaction was found to be target specific, not killing uninfected or unpulsed macrophages even when included as bystanders in the assay. Target lysis did not depend on the production by the effector cells of either a cytotoxic supernatant factor or IFN-gamma. Depletion of CD8+ cells from the splenic effector cell population, however, abrogated the cytotoxic activity, whereas depletion of CD4+ cells had little effect. The MHC restriction of the Toxoplasma-specific cytolytic reaction was confirmed in studies using effector cells from BALB/c mice and targets from congenic or mutant haplotype strains. These experiments indicated that target killing is primarily restricted by genes mapping within the H-2D/L(d) loci. Together, these results establish MHC-restricted cytolysis as a major parameter of CD8+ effector function against T. gondii and indicate that, in the case of this protozoan, Ag presentation to CD8+ lymphocytes can occur as a result of either processing within infected cells or exogenous uptake of parasite Ag. C1 NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. RP HAKIM, FT (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 147 Z9 151 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2310 EP 2316 PG 7 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400037 PM 1918963 ER PT J AU CHEN, YMA ZHANG, XQ DAHL, CE SAMUEL, KP SCHOOLEY, RT ESSEX, M PAPAS, TS AF CHEN, YMA ZHANG, XQ DAHL, CE SAMUEL, KP SCHOOLEY, RT ESSEX, M PAPAS, TS TI DELINEATION OF TYPE-SPECIFIC REGIONS ON THE ENVELOPE GLYCOPROTEINS OF HUMAN T-CELL LEUKEMIA VIRUSES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; MEDIATED CYTO-TOXICITY; HTLV-II INFECTION; LYMPHOTROPIC VIRUS; ANTIGENIC DETERMINANTS; MONOCLONAL-ANTIBODY; C RETROVIRUS; PROTEIN; GENE AB Two different approaches were used to map the type-specific regions on human T cell leukemia virus (HTLV) envelope glycoproteins. 1) Antibody reactivities of polymerase chain reaction-confirmed HTLV-I or HTLV-II carriers' sera were analyzed by Western blot assay with seven recombinant proteins containing different regions of HTLV-I or HTLV-II envelope proteins. 2) Rabbits antibodies elicited by nine HTLV-I Env synthetic peptides were used to react with the native HTLV envelope glycoproteins in an antibody-dependent cellular cytotoxicity (ADCC) assay. The results of the Western blot analysis showed that RP-B2, which contains amino acid residues 166 to 213 from HTLV-II exterior glycoprotein, was specifically reactive with 90.6% (48 of 53) of the HTLV-II carriers' sera but not with any of the HTLV-I carriers' serum (0 of 71). In contrast, RP-B, which contains amino acid residues 166 to 229 from HTLV-I exterior glycoprotein, was reactive with 85.1% (114 of 134) of the HTLV-I carriers' sera but not with any HTLV-II carrier serum (0 of 62). Furthermore, anti-HTLV-I Env synthetic peptide antibody-mediated ADCC identified several distinguishing HTLV-I ADCC epitopes in the middle region (amino acid residues 177 to 257) of the HTLV-I exterior glycoprotein. Therefore, HTLV type-specific epitopes reside mainly in a 69-amino acid sequence bounded by two cysteine residues (amino acids 157 and 225 for HTLV-I and 153 and 221 for HTLV-II), in the middle region of the exterior envelope glycoproteins. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702. UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80262. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DUNCORP,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. NR 52 TC 28 Z9 28 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2368 EP 2376 PG 9 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400045 PM 1717557 ER PT J AU SVETIC, A FINKELMAN, FD JIAN, YC DIEFFENBACH, CW SCOTT, DE MCCARTHY, KF STEINBERG, AD GAUSE, WC AF SVETIC, A FINKELMAN, FD JIAN, YC DIEFFENBACH, CW SCOTT, DE MCCARTHY, KF STEINBERG, AD GAUSE, WC TI CYTOKINE GENE-EXPRESSION AFTER INVIVO PRIMARY IMMUNIZATION WITH GOAT ANTIBODY TO MOUSE IGD ANTIBODY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER T-CELLS; GROWTH-FACTOR ACTIVITY; MURINE IMMUNE-SYSTEM; COLONY-STIMULATING FACTOR; IFN-GAMMA; POLYCLONAL ACTIVATION; INTERFERON-GAMMA; LYMPHOCYTES-T; MESSENGER-RNA; CDNA CLONES AB Cytokines are important mediators of effector lymphoid cell function during an immune response, but their expression during an in vivo immune response has not been well documented. We anlayzed the kinetics of cytokine gene expression during the course of an in vivo primary immune response to goat antibody to mouse IgD antibody. Total RNA was purified from spleens taken from freshly killed BALB/c mice 1 to 7 days after immunization. The reverse transcriptase polymerase chain reaction was used to evaluate the expression of seven cytokine genes, all of which encode cytokines that are secreted by T cells and are important in T and/or B cell activation and differentiation. These were IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-9, and IL-10. IL-2 and IL-9 exhibited an early elevated expression at days 2 to 3, and declined as the expression of IL-4, IL-6, IL-10, and IFN-gamma increased. In contrast, IL-5 gene expression showed little change, exhibiting a similar pattern to the housekeeping gene, hypoxanthine-guanine phosphoribosyl transferase. Cell sorting of CD4+ and CD4- cells at day 3 and day 5 after immunization revealed that CD4+ cells were the predominant source of the elevated cytokines (with the exception of IL-6). Our results demonstrate a specific and highly reproducible cytokine gene expression pattern during the course of a primary in vivo immune response that is marked by an absence of a clear-cut Th1/Th2 dichotomy. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. NIAMS,ARTHRITIS & RHEUMATISM BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. ARMED FORCES RADIOBIOL RES INST,DEPT RADIAT BIOCHEM,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. FU NIAID NIH HHS [AI26150, AI21328] NR 63 TC 287 Z9 288 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2391 EP 2397 PG 7 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400048 PM 1717559 ER PT J AU BECKWITH, M URBA, WJ FERRIS, DK FRETER, CE KUHNS, DB MORATZ, CM LONGO, DL AF BECKWITH, M URBA, WJ FERRIS, DK FRETER, CE KUHNS, DB MORATZ, CM LONGO, DL TI ANTI-IGM-MEDIATED GROWTH-INHIBITION OF A HUMAN B-LYMPHOMA CELL-LINE IS INDEPENDENT OF PHOSPHATIDYLINOSITOL TURNOVER AND PROTEIN-KINASE-C ACTIVATION AND INVOLVES TYROSINE PHOSPHORYLATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-B; SIGNAL TRANSDUCTION; MEMBRANE IMMUNOGLOBULIN; CROSS-LINKING; RECEPTOR COMPLEX; IDIOTYPE THERAPY; PHORBOL ESTER; INDUCE DEATH; ANTIBODIES; WEHI-231 AB The RL cell line is an EBV-negative, surface IgM, IgD-positive B lymphoma line, which is significantly growth arrested in the presence of acrylamide-linked antibodies to the surface IgM receptor. We demonstrate here that activation of protein kinase C (PKC) with PMA abrogates anti-IgM-induced phosphoinositide turnover and Ca2+ mobilization; however, growth inhibition is not affected. In addition, inhibitors of PKC are unable to reverse the anti-IgM-mediated growth inhibition. Two-dimensional gel electrophoresis reveals a different pattern of protein phosphorylation after treatment of RL with PMA or anti-IgM. These data strongly suggest that anti-IgM-induced growth inhibition does not rely on phospholipase C-mediated phosphoinositide turnover, Ca2+ mobilization, or PKC activation. On the other hand, the phosphatase inhibitor orthovanadate results in an augmentation of proteins phosphorylated on tyrosine and the growth inhibition which follows anti-IgM treatment. Furthermore, protein tyrosine kinase inhibitors, genistein and herbimycin A, are able to reverse the anti-IgM-induced inhibition of growth. These data demonstrate that multiple signaling pathways are activated by the interaction of anti-IgM with its ligand, and suggest that tyrosine kinase activation is a critical component of the inhibitory response. C1 NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. GEORGETOWN UNIV HOSP,LOMBARDI CANC CTR,WASHINGTON,DC 20007. RP BECKWITH, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BLDG 567,ROOM 204,POB B,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102] NR 47 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1991 VL 147 IS 7 BP 2411 EP 2418 PG 8 WC Immunology SC Immunology GA GH524 UT WOS:A1991GH52400051 PM 1918971 ER PT J AU SMITH, JW URBA, WJ CLARK, JW LONGO, DL FARRELL, M CREEKMORE, SP CONLON, KC JAFFE, H STEIS, RG AF SMITH, JW URBA, WJ CLARK, JW LONGO, DL FARRELL, M CREEKMORE, SP CONLON, KC JAFFE, H STEIS, RG TI PHASE-I EVALUATION OF RECOMBINANT TUMOR-NECROSIS-FACTOR GIVEN IN COMBINATION WITH RECOMBINANT INTERFERON-GAMMA SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE TUMOR NECROSIS FACTOR; INTERFERON-GAMMA; PHASE-I TRIAL; COMBINATION IMMUNOTHERAPY; OUTPATIENT IMMUNOTHERAPY ID HUMAN CELL-LINES; FACTOR-ALPHA; CANCER-PATIENTS; WEIGHT-LOSS; IFN-GAMMA; PROCOAGULANT ACTIVITY; TRANSFORMED-CELLS; RECEPTORS; EXPRESSION; INTERLEUKIN-1 AB In light of in vitro and preclinical animal model data suggesting potential additive or synergistic antitumor effects from the combined use of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), we conducted a phase I study employing escalating doses of each agent in 36 patients with solid tumors to determine the maximum tolerated dose (MTD). Patients were given an intramuscular (i.m.) injection of IFN-gamma, followed 5 min later by an i.m. injection of TNF-alpha, each agent in different sites, every other day for ten doses over 20 days. Patients received 10, 50, or 100-mu-g/m2 of each agent throughout the treatment course. No dose modifications were made. Patients suffering serious toxicity had therapy stopped and were considered to be off-study. All patients experienced fatigue, and 36% spent over half their time in bed on treatment days. Fever and chills were nearly universal. Mild to moderate elevations in serum transaminase levels were noted in 44% of patients, and 44% developed transient microscopic hematuria. Although 81% of patients had anorexia, only 17% of patients lost more than 3 kg of body wt during the 3 weeks of therapy. Because two of three patients receiving 100-mu-g/m2 of both agents developed serious toxicity (one fever > 105-degrees-F, one thrombocytopenia 43,000/mm3), the MTD was established to be 100-mu-g/m2 of IFN-gamma plus 50-mu-g/m2 of TNF-alpha. The use of aspirin did not significantly alter the toxic effects of the agents. One patient with melanoma had a mixed response and one patient with mesothelioma transiently cleared his ascites of malignant cells. C1 NCI,FCRDC,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21701. RP SMITH, JW (reprint author), NCI,FCRDC,CLIN RES BRANCH,BIOL RESPONSE MODIFERS PROGRAM,SUITE 3,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N0I-CO-74102] NR 52 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1991 VL 10 IS 5 BP 355 EP 362 DI 10.1097/00002371-199110000-00007 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA GH358 UT WOS:A1991GH35800007 PM 1790143 ER PT J AU SHERRY, RM ROSENBERG, SA YANG, JC AF SHERRY, RM ROSENBERG, SA YANG, JC TI RELAPSE AFTER RESPONSE TO INTERLEUKIN-2-BASED IMMUNOTHERAPY - PATTERNS OF PROGRESSION AND RESPONSE TO RETREATMENT SO JOURNAL OF IMMUNOTHERAPY LA English DT Note DE IMMUNOTHERAPY; INTERLEUKIN-2; METASTATIC MELANOMA; METASTATIC RENAL CELL CANCER ID ACTIVATED KILLER CELLS; TUMOR-INFILTRATING LYMPHOCYTES; HIGH-DOSE INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; MELANOMA AB The initial site of disease relapse was identified for 79 patients with metastatic renal cell cancer (RCC), melanoma, colon cancer, or non-Hodgkin's lymphoma (NHL), who had achieved partial or complete responses to one of five IL-2-based immunotherapy regimens. The initial site of relapse was evenly distributed between pre-existing sites of disease (33%), new sites of disease (38%), or both (29%). There was no difference in the distribution of recurrences between patients with partial or complete responses. Fifty-one patients with prior complete or partial responses were retreated with additional IL-2-based therapy following tumor progression. Five of 51 patients retreated following relapse developed new partial responses. There were no complete responses. Three patients with NHL were retreated with IL-2 and LAK cells and all achieved a second response, while only 2 of 48 patients with other histologic diagnoses reresponded. It is concluded that after a partial or complete response to IL-2-based immunotherapy, patients who relapse do so equally at new and pre-existing sites of disease. A response to retreatment following tumor progression may be attained in patients with NHL, while a new response is unlikely for patients with melanoma and RCC. RP SHERRY, RM (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1991 VL 10 IS 5 BP 371 EP 375 DI 10.1097/00002371-199110000-00009 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA GH358 UT WOS:A1991GH35800009 PM 1790145 ER PT J AU LUCEY, DR MELCHER, GP HENDRIX, CW ZAJAC, RA GOETZ, DW BUTZIN, CA CLERICI, M WARNER, RD ABBADESSA, S HALL, K JASO, R WOOLFORD, B MILLER, S STOCKS, NI SALINAS, CM WOLFE, WH SHEARER, GM BOSWELL, RN AF LUCEY, DR MELCHER, GP HENDRIX, CW ZAJAC, RA GOETZ, DW BUTZIN, CA CLERICI, M WARNER, RD ABBADESSA, S HALL, K JASO, R WOOLFORD, B MILLER, S STOCKS, NI SALINAS, CM WOLFE, WH SHEARER, GM BOSWELL, RN TI HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IN THE UNITED-STATES AIR-FORCE - SEROCONVERSIONS, CLINICAL STAGING, AND ASSESSMENT OF A T HELPER-CELL FUNCTIONAL ASSAY TO PREDICT CHANGE IN CD4+ T-CELL COUNTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; SEROPOSITIVE HOMOSEXUAL MEN; HIV-INFECTION; IMMUNE-DEFICIENCY; LYMPHOCYTE COUNTS; AIDS; TYPE-1; COHORT; ARMY; ANTIBODIES AB As of January 1990, 933 persons with human immunodeficiency virus type 1 (HIV-1) infection were clinically evaluated at Wilford Hall US Air Force (USAF) Medical Center. The Walter Reed HIV staging system was used in these evaluations to describe disease status and progression. Most persons were diagnosed through mandatory HIV testing in the USAF and were asymptomatic at the time of diagnosis. As of May 1990, 161 HIV-positive seroconverters (estimated overall seroconversion rate of 0.156/1000 person-years between 30 June 1988 and 1 July 1990) had been identified among active-duty USAF personnel, as they had previously tested negative for antibody to HIV. Men constitute 95% of the USAF HIV-positive population. An in vitro T helper cell functional assay was assessed to predict rate of CD4+ T cell decline over the subsequent year (mean, 15 months) in patients with > 200 CD4+ T cells/mm3. This assay may prove useful for prognostication and comparisons of patients in clinical trials of anti-HIV interventions. C1 WILFORD HALL USAF MED CTR,DEPT MED,LACKLAND AFB,TX 78236. WILFORD HALL USAF MED CTR,CLIN INVEST DIRECTORATE,LACKLAND AFB,TX 78236. ARMSTRONG LAB,EPIDEMIOL RES DIV,DIV HUMAN SYST,BROOKS AFB,TX. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 53 TC 83 Z9 83 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1991 VL 164 IS 4 BP 631 EP 637 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GF805 UT WOS:A1991GF80500001 PM 1680134 ER PT J AU FRANCIS, CL JERSE, AE KAPER, JB FALKOW, S AF FRANCIS, CL JERSE, AE KAPER, JB FALKOW, S TI CHARACTERIZATION OF INTERACTIONS OF ENTEROPATHOGENIC ESCHERICHIA-COLI O127-H6 WITH MAMMALIAN-CELLS INVITRO SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TISSUE-CULTURE CELLS; HEP-2 CELLS; LINE CACO-2; CLASSIC SEROTYPES; SHIGELLA-FLEXNERI; ADHERENCE FACTOR; PLASMID; ADHESION; EXPRESSION; DIARRHEA AB Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic "pedestal" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by, eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation. C1 UNIV MARYLAND,SCH MED,CTR VACCINE DEV,DIV GEOG MED,BALTIMORE,MD 21201. NIAID,PATHOL LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. RP FRANCIS, CL (reprint author), STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,FAIRCHILD SCI BLDG D309,STANFORD,CA 94305, USA. OI Kaper, James/0000-0003-0715-2907 FU NIAID NIH HHS [AI-07328, AI-26195, R37 AI021657]; NIDDK NIH HHS [DK-38707] NR 38 TC 82 Z9 82 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1991 VL 164 IS 4 BP 693 EP 703 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GF805 UT WOS:A1991GF80500009 PM 1680136 ER PT J AU DARBAN, H ENRIQUEZ, J STERLING, CR LOPEZ, MC CHEN, G ABBASZADEGAN, M WATSON, RR AF DARBAN, H ENRIQUEZ, J STERLING, CR LOPEZ, MC CHEN, G ABBASZADEGAN, M WATSON, RR TI CRYPTOSPORIDIOSIS FACILITATED BY MURINE RETROVIRAL INFECTION WITH LP-BM5 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MICE; INDUCTION; ANTIBODIES; COLOSTRUM; DISEASE; MAIDS; CELLS AB LP-BM5 murine leukemia virus infection caused alterations in splenic T cell subsets in adult C57BL/6 female mice. Prolonged infection resulted in increased immunosuppression and a concomitant decreased resistance to Cryptosporidium parvum infection. Significant Cryptosporidium colonization of the intestinal villi was seen 10 days after oral challenge in mice infected with murine retrovirus for 3 months but not in non-virally infected controls. Parasite numbers per villus of retrovirally infected mice were 20-fold higher than in controls, which showed only occasional parasites. Feces from most virally infected mice but none from controls contained oocysts. Cryptosporidium infection in mice after 4 and 5 months of retroviral infection was accompanied by severe immunosuppression and parasite levels 50-5000 times higher than in controls. A high level of infection persisted 21 days after Cryptosporidium challenge in virally infected mice, while controls cleared their transient and marginal infection. These results further characterize LP-BM5 infection as a murine model of retrovirally induced acquired immune deficiency. C1 UNIV ARIZONA,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85724. UNIV ARIZONA,NATL INST ALCOHOLISM,BIOTECHNOL RESOURCES CTR,DEPT VET SCI,TUCSON,AZ 85721. UNIV ARIZONA,ALCOHOL ABUSE SPECIALIZED ALCOHOL RES CTR,TUCSON,AZ 85721. UNIV ARIZONA,NUTR SCI PROGRAM,TUCSON,AZ 85721. FU NIAAA NIH HHS [AA-08037]; NIAID NIH HHS [AI-30223]; NIDA NIH HHS [DA-04827] NR 31 TC 47 Z9 47 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1991 VL 164 IS 4 BP 741 EP 745 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GF805 UT WOS:A1991GF80500015 PM 1654357 ER PT J AU TALSINGER, R SEIDELDUGAN, C FRIES, L HUEMER, HP EISENBERG, RJ COHEN, GH FRIEDMAN, HM AF TALSINGER, R SEIDELDUGAN, C FRIES, L HUEMER, HP EISENBERG, RJ COHEN, GH FRIEDMAN, HM TI HERPES-SIMPLEX VIRUS GLYCOPROTEIN C IS A RECEPTOR FOR COMPLEMENT COMPONENT IC3B SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TYPE-1 INFECTION; CELLS; C3B; BINDING AB Herpes simplex virus type 1-infected cells bind C3b and iC3b, but not C3d, at the cell surface. Herpes simplex virus type 2 (HSV-2)-infected cells bind none of these C3 fragments. A transfection assay was used to demonstrate that binding of iC3b was to gC1. Although iC3b did not bind to HSV-2-infected cells, it did bind to mammalian cells transfected with the gC2 gene. Using linker insertion mutants, three domains on gC2 that are important for binding iC3b were mapped; these regions were similar to previously defined regions involved in binding C3b. These results suggest that some of the functions served by gC may be similar to those of CR3, the mammalian receptor for iC3b. C1 UNIV PENN,CHILDRENS HOSP,SCH DENT MED,CTR ORAL HLTH RES,PHILADELPHIA,PA 19104. UNIV PENN,CHILDRENS HOSP,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. NIAID,CLIN INVEST LAB,BETHESDA,MD. UNIV PENN,CHILDRENS HOSP,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,CHILDRENS HOSP,DEPT MICROBIOL,PHILADELPHIA,PA 19104. FU NHLBI NIH HHS [HL-28220] NR 15 TC 33 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1991 VL 164 IS 4 BP 750 EP 753 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GF805 UT WOS:A1991GF80500017 PM 1654359 ER PT J AU MIDTHUN, K HALSEY, NA JETTGOHEEN, M CLEMENTS, ML STEINHOFF, M KING, JC KARRON, R WILSON, M BURNS, B PERKIS, V SAMORODIN, R KAPIKIAN, AZ AF MIDTHUN, K HALSEY, NA JETTGOHEEN, M CLEMENTS, ML STEINHOFF, M KING, JC KARRON, R WILSON, M BURNS, B PERKIS, V SAMORODIN, R KAPIKIAN, AZ TI SAFETY AND IMMUNOGENICITY OF HUMAN ROTAVIRUS VACCINE STRAIN M37 IN ADULTS, CHILDREN, AND INFANTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NEUTRALIZATION; INFECTIONS; DIARRHEA AB Rotavirus vaccine strain M37 (serotype 1), recovered from the stool of an asymptomatic newborn infant and serially passaged in cell culture, was given orally to adults, children, and infants. Serologic responses were detected by neutralization assay or EIA in 59% of 17 adults (10(5)-pfu dose), 55%-60% of 21 infants and children (10(4)-pfu dose), and 70% of 10 infants (10(5)-pfu dose); vaccine virus was shed by 24%, 20%-36%, and 70%, respectively. In adults, neutralizing antibody rises to strain M37 and the related serotype 1 strain Wa occurred with equal frequency (41% vs. 47%). In pediatric subjects, the former were more frequent (36%-40%) than the latter (10%18%). This was also true of 8 infants who received two doses of vaccine. Mild gastrointestinal illnesses occurred with equal frequency in pediatric subjects who received vaccine or placebo. Thus, strain M37 was well tolerated and immunogenic in young infants, but elicited primarily vaccine-strain-specific rather than serotype-specific neutralizing antibody responses. C1 NIAID,INFECT DIS LAB,BETHESDA,MD. RP MIDTHUN, K (reprint author), JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,DEPT INT HLTH,624 N BROADWAY,ROOM 125,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-62515] NR 15 TC 17 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1991 VL 164 IS 4 BP 792 EP 796 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GF805 UT WOS:A1991GF80500028 PM 1654365 ER PT J AU FALANGA, V QIAN, SW DANIELPOUR, D KATZ, MH ROBERTS, AB SPORN, MB AF FALANGA, V QIAN, SW DANIELPOUR, D KATZ, MH ROBERTS, AB SPORN, MB TI HYPOXIA UP-REGULATES THE SYNTHESIS OF TGF-BETA-1 BY HUMAN DERMAL FIBROBLASTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PROGRESSIVE SYSTEMIC-SCLEROSIS; EXPRESSION; CELLS; GENE; SKIN AB In this report, we have investigated the secretion and synthesis of transforming growth factor-beta-1 (TGF-beta-1) by human dermal fibroblast cultures in response to hypoxia (2% oxygen), and have compared it to standard oxygen culture conditions (15% oxygen at the cell surface). Sandwich enzyme-linked immunosorbent assay (SELISA) showed a selective and progressive increase in secretion of the TGF-beta-1 isoform in response to hypoxia, up to ninefold after cultures were exposed to low oxygen for 72 h; TGF-beta-2 peptide levels were not increased. We then investigated the transcriptional regulation of the TGF-beta-1 gene in response to low and standard oxygen tensions. In the first 24-48 h, TGF-beta-1 mRNA levels decreased steadily in both oxygen environments. This mRNA decline continued for up to 72 h in standard oxygen but not in cultures exposed to low oxygen tension. At 72 h, steady-state TGF-beta-1 mRNA levels were 8 times greater in low compared to standard oxygen, and this increase was reversible upon re-exposure of fibroblast cultures to standard oxygen tension for 24 h. Elevated TGF-beta-1 m-RNA levels in both low and standard oxygen declined steadily and with the same half-life after the addition of actinomycin D, suggesting that hypoxia increased TGF-beta-1 transcription rather than mRNA stability. We conclude that low oxygen tension upregulates the synthesis of TGF-beta-1 by human dermal fibroblasts, and leads to increased secretion of this peptide. C1 UNIV MIAMI,SCH MED,DEPT DERMATOL & CUTANEOUS SURG,MIAMI,FL 33101. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR 39658] NR 19 TC 186 Z9 194 U1 1 U2 7 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1991 VL 97 IS 4 BP 634 EP 637 DI 10.1111/1523-1747.ep12483126 PG 4 WC Dermatology SC Dermatology GA GH451 UT WOS:A1991GH45100006 PM 1940433 ER PT J AU GUND, TM SHUKLA, K SU, TP AF GUND, TM SHUKLA, K SU, TP TI MOLECULAR MODELING OF SIGMA RECEPTOR LIGANDS - A MODEL OF BINDING BASED ON CONFORMATIONAL AND ELECTROSTATIC CONSIDERATIONS SO JOURNAL OF MATHEMATICAL CHEMISTRY LA English DT Article ID ANTIPSYCHOTIC-DRUGS; PHENCYCLIDINE; SITES; AFFINITY; AGONISTS; BRAIN AB We have performed molecular modeling studies on four representative sigma receptor specific ligands, (+)haloperidol, (+)3-PPP, (+)pentazocine and progesterone, to develop a model for sigma receptor-ligand binding. The modeling studies have investigated the conformational and electrostatic properties of the ligands. Based on the complementarity of the conformational and electrostatic properties of the ligands, a model of binding has been proposed which shows that the four ligands can fit a common receptor site. Unlike the binding model for haloperidol that was previously proposed by Manallack and Andrews, our model binds haloperidol in the gauche conformation. The first site binds the fluorophenyl group and the second site the lone pair of the piperidine nitrogen. This pharmacophore can be presented by (+)3-PPP and (+)pentazocine, but for progesterone the binding model requires the ring junction of the cyclohexenyl ring A and ring B to fit the fluorophenyl region, while the lone pair of the acetylcarbonyl oxygen at ring D emulates the nitrogen lone pair of the piperidine ring. Calculations were performed using RCG5 for generating conformations, molecular mechanics for calculating steric energies, quantum mechanical methods for generating charges, and ARCHEM for calculating electrostatic potentials on the Van der Waals surface. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD 21224. RP GUND, TM (reprint author), NEW JERSEY INST TECHNOL,DEPT CHEM CHEM ENGN & ENVIRONM SCI,323 MARTIN LUTHER KING JR BLVD,NEWARK,NJ 07102, USA. NR 33 TC 9 Z9 9 U1 0 U2 1 PU BALTZER SCI PUBL BV PI AMSTERDAM PA ASTERWEG 1A, 1031 HL AMSTERDAM, NETHERLANDS SN 0259-9791 J9 J MATH CHEM JI J. Math. Chem. PD OCT PY 1991 VL 8 IS 4 BP 309 EP 325 DI 10.1007/BF01166945 PG 17 WC Chemistry, Multidisciplinary; Mathematics, Interdisciplinary Applications SC Chemistry; Mathematics GA GL450 UT WOS:A1991GL45000001 ER PT J AU APPLETON, CC BOINSKI, S AF APPLETON, CC BOINSKI, S TI A PRELIMINARY PARASITOLOGICAL ANALYSIS OF FECAL SAMPLES FROM A WILD POPULATION OF COSTA RICAN SQUIRREL-MONKEYS (SAIMIRI-OERSTEDI) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE ENDOPARASITES; FECAL SAMPLES; SQUIRREL MONKEY; SAIMIRI-OERSTEDI ID PARASITES; BEHAVIOR; HABITAT AB Fecal samples (n = 18) were obtained from a wild population of squirrel monkeys, Saimiri oerstedi, in Costa Rica. The parasite cysts, eggs, and larvae recovered from these samples are described. C1 UNIV NATAL,DEPT ZOOL & ENTOMOL,PIETERMARITZBURG 3200,SOUTH AFRICA. NIH,CTR ANIM,COMPARAT ETHOL LAB,POOLESVILLE,MD. NR 12 TC 8 Z9 9 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 1991 VL 20 IS 8 BP 402 EP 403 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HD571 UT WOS:A1991HD57100005 PM 1803011 ER PT J AU ERDMAN, DD USHER, MJ TSOU, C CAUL, EO GARY, GW KAJIGAYA, S YOUNG, NS ANDERSON, LJ AF ERDMAN, DD USHER, MJ TSOU, C CAUL, EO GARY, GW KAJIGAYA, S YOUNG, NS ANDERSON, LJ TI HUMAN PARVOVIRUS B19 SPECIFIC IGG, IGA, AND IGM ANTIBODIES AND DNA IN SERUM SPECIMENS FROM PERSONS WITH ERYTHEMA-INFECTIOSUM SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE ENZYME IMMUNOASSAY; PCR; ERYTHEMA-INFECTIOSUM ID LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODIES; APLASTIC CRISIS; ELISA; ARTHRITIS; ANEMIA AB To determine the diagnostic use of different markers of acute parvovirus B19 infection, serum specimens obtained from 128 persons with erythema infectiosum were tested for specific immunoglobulin G (IgG), IgA, and IgM antibodies by capture enzyme immunoassay (EIA) using Chinese hamster ovary (CHO) cell-expressed B19 antigen, and tested for circulating B19 DNA by polymerase chain reaction (PCR). A significant rise in specific IgG and IgA antibodies was detected in 87% and 77%, respectively, of persons from whom acute- and convalescent-phase serum specimens were available. Specific IgA antibodies were detected in single serum specimens from 90% of cases and were present in 22 (18%) of 120 persons from a control group without a history of recent exposure to B19. Specific IgM antibodies were detected in 97% of cases and one person (1%) from the control group. B19 DNA was detected in 94% of cases and was absent in 20 persons from the control group positive for both IgG and IgA antibodies. Serum specimens obtained between 4 and 6 months after onset of illness from six additional persons were also tested. All had specific IgG antibodies, four (67%) had IgA, five (83%) had IgM, and none had detectable B19 DNA. Our data indicate that 1) specific IgA antibodies are too persistent to be a useful indicator of recent B19 infection; 2) specific IgM antibodies are the most sensitive indicator of acute B19 infection in immunologically normal persons but can persist up to 6 months; and 3) B19 DNA can often be detected up to 2 months after onset of illness even in immunologically normal hosts and might be a useful adjunct test for diagnosis of acute B19 infection. C1 NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. REG VIRUS & PUBL HLTH LAB,BRISTOL,ENGLAND. RP ERDMAN, DD (reprint author), CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RESP & ENTEROVIRUS BRANCH,ATLANTA,GA 30333, USA. NR 23 TC 75 Z9 78 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD OCT PY 1991 VL 35 IS 2 BP 110 EP 115 DI 10.1002/jmv.1890350207 PG 6 WC Virology SC Virology GA GK124 UT WOS:A1991GK12400006 PM 1765775 ER PT J AU RADESCA, L BOWEN, WD DIPAOLO, L DECOSTA, BR AF RADESCA, L BOWEN, WD DIPAOLO, L DECOSTA, BR TI SYNTHESIS AND RECEPTOR-BINDING OF ENANTIOMERIC N-SUBSTITUTED CIS-N-[2-(3,4-DICHLOROPHENYL)ETHYL]-2-(1-PYRROLIDINYL)CYCLOHEXYLAMINES AS HIGH-AFFINITY SIGMA RECEPTOR LIGANDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG; ABSOLUTE-CONFIGURATION; RAT; PHENCYCLIDINE; AGONIST; DRUGS; SITES; BRAIN; INHIBITION; DOPAMINE AB N-Alkyl-substituted derivatives of (+)- and (-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine have been synthesized in nine steps in a stereospecific manner starting from cyclohexene oxide. The key step in the reaction sequence involved catalytic hydrogenation of oxime 8 in the presence of PtO2 and AcOH to give the cis diamine (+/-)-7. Most of the compounds in this series exhibited very high affinity at sigma-receptors when tested against [H-3]-(+)-3-PPP, and in general it was observed that the 1R,2S enantiomers bound more potently to sigma-receptors than their corresponding 1S,2R enantiomers. The most potent sigma-ligand found in this class was the unsubstituted derivative (1R,2S)-(-)-4, which exhibited an affinity constant of 0.49 nM. This compound was also found to be very selective for sigma-receptors. It exhibited little or no affinity for kappa-opioid, PCP, and dopamine-D2 receptors. It was also demonstrated that the cis configuration as opposed to the trans configuration of (+)- and (-)-5 was necessary for a higher sigma-receptor affinity. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. BROWN UNIV,DIV BIOL & MED,BIOCHEM SECT,PROVIDENCE,RI 02912. FU NIDA NIH HHS [DA04988]; NINDS NIH HHS [NS26746] NR 33 TC 51 Z9 51 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT PY 1991 VL 34 IS 10 BP 3058 EP 3065 DI 10.1021/jm00114a015 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GK473 UT WOS:A1991GK47300015 PM 1656044 ER PT J AU DVORAK, JA MUDD, CP DVORAK, VK SCHUETTE, WH AF DVORAK, JA MUDD, CP DVORAK, VK SCHUETTE, WH TI AN ELECTRONIC INTERFACE FOR MICROCOMPUTER-BASED FLOW-CYTOMETRY - DESIGN, OPERATION AND PERFORMANCE-CHARACTERISTICS SO JOURNAL OF MICROCOMPUTER APPLICATIONS LA English DT Article C1 DAVID TAYLOR RES CTR,DEPT ELECTROMAGNET SIGNATURES,BETHESDA,MD 20084. NIH,DIV RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0745-7138 J9 J MICROCOMPUT APPL JI J. Microcomput. Appl. PD OCT PY 1991 VL 14 IS 4 BP 327 EP 341 DI 10.1016/0745-7138(91)90019-N PG 15 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA GN586 UT WOS:A1991GN58600002 ER PT J AU BRANDON, DD MARKWICK, AJ FLORES, M DIXON, K ALBERTSON, BD LORIAUX, DL AF BRANDON, DD MARKWICK, AJ FLORES, M DIXON, K ALBERTSON, BD LORIAUX, DL TI GENETIC-VARIATION OF THE GLUCOCORTICOID RECEPTOR FROM A STEROID-RESISTANT PRIMATE SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; COMPLEMENTARY-DNA; FUNCTIONAL DOMAINS; VITAMIN-D; EXPRESSION; CLONING; CDNA; SEQUENCE; BINDING; VIRUS AB The neotropical cotton-top marmoset (Saguinus oedipus) is a New World primate known to have markedly increased total and free plasma cortisol concentrations when compared with Old World primates including man. The relative end-organ 'resistance' to glucocorticoids found in various New World primates has been attributed to a glucocorticoid receptor (GR) with diminished affinity for glucocorticoids. It has been demonstrated that the marmoset GR has approximately tenfold lower binding affinity for dexamethasone when compared with the human GR. We have examined the primary structure of the marmoset GR by molecular cloning and sequencing of GR functional domains. A library of cDNA clones was constructed in the phage vector lambda-gt10 using poly(A)+ RNA from a marmoset-derived lymphoid cell line, and screened using the human GR cDNA. DNA sequencing determined 76 individual nucleotide substitutions in the coding region of the marmoset GR. Comparison of the marmoset GR nucleotide sequence with the human GR cDNA coding region indicated an overall sequence homology of about 97%. Thirty of the nucleotide substitutions lead to alterations in the predicted amino acid sequence (28 amino acid substitutions) of the marmoset GR. The size of the marmoset GR predicted from the 778 amino acids is approximately 90 000 which is in agreement with previous size estimates of the human and marmoset GRs. Alterations of amino acid sequence in the marmoset GR were greatest towards the amino terminus, including the tau-1 domain putatively involved in transcriptional activation. The DNA-binding domain contained an additional codon (arginine). Comparison of the DNA-binding domain of the marmoset GR with other members of the steroid receptor superfamily indicates that the additional arginine occurs in the same position as other amino acid insertions within the interfinger region of the human androgen receptor and the erb-A proto-oncogene. There are only four missense substitutions within the steroid-binding domain. Two of these substitutions occur within the transducing site which has been associated with binding of the GR to a 90 kDa heat shock protein. These data suggest that diminished GR affinity for glucocorticoids in the marmoset may be due to alterations in the primary structure of one or more functional domains of the GR gene. In addition, other important regulatory functions, such as transcriptional activation, DNA binding and receptor transduction, may also be affected. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RP BRANDON, DD (reprint author), OREGON HLTH SCI UNIV,DEPT MED,DIV ENDOCRINOL DIABET CLIN NUTR,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 33 TC 45 Z9 45 U1 0 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD OCT PY 1991 VL 7 IS 2 BP 89 EP 96 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH976 UT WOS:A1991GH97600001 PM 1930628 ER PT J AU VANCOMPERNOLLE, K VANDEKERCKHOVE, J BUBB, M KORN, E AF VANCOMPERNOLLE, K VANDEKERCKHOVE, J BUBB, M KORN, E TI INTERFACES BETWEEN ACTIN AND ACANTHAMOEBA ACTOBINDIN - IDENTIFICATION OF A NEW ACTIN-BINDING MOTIF SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 STATE UNIV GHENT,PHYSIOL CHEM LAB,B-9000 GHENT,BELGIUM. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD OCT PY 1991 VL 12 IS 5 BP 484 EP 485 PG 2 WC Cell Biology SC Cell Biology GA GG037 UT WOS:A1991GG03700023 ER PT J AU LOVINGER, DM AF LOVINGER, DM TI INHIBITION OF 5-HT3 RECEPTOR-MEDIATED ION CURRENT BY DIVALENT METAL-CATIONS IN NCB-20 NEUROBLASTOMA-CELLS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURO-BLASTOMA CELLS; METHYL-D-ASPARTATE; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; GABA RESPONSES; BRAIN-TISSUE; ZINC; RELEASE; LINES; ANTAGONISTS AB 1. The effect of micromolar concentrations of divalent metal cations on ion current activated by 5-hydroxytryptamine (5-HT) was investigated in NCB-20 neuroblastoma cells by the use of the whole-cell, patch-clamp technique. 2. Ion current activated by 5-HT in these cells was mimicked by 5-HT3 receptor agonists, blocked by nanomolar concentrations of selective 5-HT3 receptor antagonists and reversed polarity at approximately 0 mV. These properties indicate that this current is carried primarily if not exclusively by the nonspecific cation channel activated by the 5-HT3 receptor. 3. The Group IIb metal cations Cd2+ and Zn2+ and the Group Ib cation Cu2+ inhibited 5-HT-activated current with inhibition increasing in a concentration-dependent manner over micromolar concentrations of the ions. The order of potency of the ions for inhibiting 5-HT-activated current was Zn2+ (IC50 = 20-mu-M) greater-than-or-equal-to Cu2+ (IC50 = 25-mu-M) > Cd2+ (IC50 = 75-mu-M) at -50 mV. The other divalent metal cations tested (Ba2+, Co2+, Mg2+, Mn2+, and Ni2+) produced little or no inhibition of 5-HT-activated current at concentrations up to 200-mu-M. 4. Inhibition of 5-HT-activated current by Cd2+ and Zn2+ was dependent on membrane potential with the Kd increasing e-fold per 72 and 52 mV, respectively. Inhibition by Cu2+ was much less voltage dependent with the Kd increasing e-fold per 233 mV. 5. Inhibition by all three cations decreased with increasing concentration of agonist over a range of 5-HT concentrations from 1 to 10-mu-M. The apparent potency of 5-HT was reduced by all three cations. 6. These observations indicate that certain divalent metal cations are potent inhibitors of ion current mediated by 5-HT3 receptors. The action of these cations appears to decrease the affinity of 5-HT for its recognition site. Inhibition by Cd2+ and Zn2+ may take place at a site within the receptor-linked nonspecific cation channel. Alternatively, these cations may interact with a conformation of the receptor that is preferentially adopted at negative membrane potentials. Inhibition by CU2+ does not appear to result from an action within the channel and may result from an action on the extracellular surface of the receptor. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. NR 29 TC 38 Z9 38 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1991 VL 66 IS 4 BP 1329 EP 1337 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GK793 UT WOS:A1991GK79300017 PM 1722246 ER PT J AU LEVEY, AI KITT, CA SIMONDS, WF PRICE, DL BRANN, MR AF LEVEY, AI KITT, CA SIMONDS, WF PRICE, DL BRANN, MR TI IDENTIFICATION AND LOCALIZATION OF MUSCARINIC ACETYLCHOLINE-RECEPTOR PROTEINS IN BRAIN WITH SUBTYPE-SPECIFIC ANTIBODIES SO JOURNAL OF NEUROSCIENCE LA English DT Article ID RAT-BRAIN; AUTORADIOGRAPHIC LOCALIZATION; BINDING-PROPERTIES; MESSENGER-RNAS; ANTAGONIST; EXPRESSION; CELLS; PIRENZEPINE; RELEASE; DNA AB mRNAs encoding five genetically distinct muscarinic ACh receptors are present in the CNS. Because of their pharmacological similarities, it has not been possible to detect the individual encoded proteins; thus, their physiological functions are not well defined. To characterize the family of proteins, a panel of subtype-selective antibodies was generated against recombinant muscarinic receptor proteins and shown to bind specifically to each of the cloned receptors. Using immunoprecipitation, three receptor proteins (m1, m2, and m4) accounted for the vast majority of the total solubilized muscarinic binding sites in rat brain. These receptor subtypes had marked differences in regional and cellular localization as shown by immunocytochemistry. The m1-protein was present in cortex and striatum and was localized to cell bodies and neurites, consistent with its role as a major postsynaptic muscarinic receptor. The m2-receptor protein was abundant in basal forebrain, scattered striatal neurons, mesopontine tegmentum, and cranial motor nuclei; this distribution is similar to that of cholinergic neurons and suggests that m2 is an autoreceptor. However, m2 was also present in noncholinergic cortical and subcortical structures, providing evidence that this subtype may presynaptically modulate release of other neurotransmitters and/or function postsynaptically. The m4-receptor was enriched in neostriatum, olfactory tubercle, and islands of Calleja, indicating an important role in extrapyramidal function. These results clarify the roles of these genetically defined receptor proteins in cholinergic transmission in brain. Since the nonselective muscarinic drugs used in the treatment of patients with neurological disease produce many side effects, the characterization of receptor subtypes, including cellular and subcellular localization, will be of great value in defining the targets for the development of more effective and specific therapeutic agents. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. RP LEVEY, AI (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,509 PATHOL BLDG,600 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIA NIH HHS [AG 03359, AG 05146]; NINDS NIH HHS [NS 10580] NR 47 TC 671 Z9 680 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT PY 1991 VL 11 IS 10 BP 3218 EP 3226 PG 9 WC Neurosciences SC Neurosciences & Neurology GA GL292 UT WOS:A1991GL29200022 PM 1941081 ER PT J AU MURPHY, VA SMITH, QR RAPOPORT, SI AF MURPHY, VA SMITH, QR RAPOPORT, SI TI SATURABLE TRANSPORT OF CA INTO CSF IN CHRONIC HYPOCALCEMIA AND HYPERCALCEMIA SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE RAT, TRANSFER COEFFICIENT; CHOROID PLEXUS; CEREBROSPINAL FLUID; CALCIUM; SATURABLE TRANSPORT ID CEREBROSPINAL-FLUID CALCIUM; BLOOD-BRAIN-BARRIER; CHOROID-PLEXUS; PERMEABILITY; PLASMA; INTESTINE; CHLORIDE; RATS AB To further characterize possible saturable transport of Ca into CSF during chronic plasma [Ca] changes, weanling rats were fed diets differing in Ca for 10 weeks. Transfer coefficients for unidirectional uptake of Ca-45 and Cl-36 into CSF (K(csf)) were determined 3 or 10 min after intravenous tracer injection in unanesthetized animals. In rats fed low Ca diet, K(csf)s for Ca-45 and Cl-36 were elevated above control, but the Ca-45/Cl-36 ratio for K(csf), a more specific measure of Ca transport, was also increased. In animals fed high Ca diet, K(csf)s of both radiotracers were not statistically different from control, but the Ca-45/Cl-36 ratio was decreased. Injection of CaCl2 into hypocalcemic rats elevated plasma [Ca], depressed Ca-45 K(csf), and returned the Ca-45/Cl-36 ratio to the control value. The inverse relationship between plasma ionized [Ca] and Ca-45 K(csf) was fitted to saturation kinetics with K(m) less-than-or-equal-to 0.53-mu-mol/ml, maximal Ca influx for the saturable component between 27 and 67 x 10(-5)-mu-mol.g-1.s-1, and the passive component of K(csf) less-than-or-equal-to 15 X 10(-5) ml.g-1.s-1. We conclude that Ca transport into CSF is saturable and this transport is important in the regulation of CSF [Ca]. C1 NIA,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892. NR 20 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 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 1991 VL 30 IS 2 BP 421 EP 426 DI 10.1002/jnr.490300218 PG 6 WC Neurosciences SC Neurosciences & Neurology GA GM665 UT WOS:A1991GM66500017 PM 1798059 ER PT J AU UAUY, RD FANAROFF, AA KORONES, SB PHILLIPS, EA PHILIPS, JB WRIGHT, LL AF UAUY, RD FANAROFF, AA KORONES, SB PHILLIPS, EA PHILIPS, JB WRIGHT, LL TI NECROTIZING ENTEROCOLITIS IN VERY-LOW-BIRTH-WEIGHT INFANTS - BIODEMOGRAPHIC AND CLINICAL CORRELATES SO JOURNAL OF PEDIATRICS LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; INTESTINE; THERAPY; AGE AB We studied the occurrence of necrotizing enterocolitis in 2681 very low birth weight infants during an 18-month period to characterize the biodemographic and clinical correlates. Proven necrotizing enterocolitis (Bell stage II and beyond) occurred in 10.1% of study infants; necrotizing enterocolitis was suspected in 17.2% of study infants. Positivity of blood cultures was related to necrotizing enterocolitis staging. The mortality rate increased only for stage III necrotizing enterocolitis (54% died). Logistic regression identified medical center of birth, race, gender, birth weight, maternal hemorrhage, duration of ruptured membranes, and cesarean section as significant risk factors. For one center the odds ratio was 3.7, whereas for another center it was only 0.3. For black boys, the odds ratio was 2.3 relative to nonblack boys; for girls, race did not affect prevalence of necrotizing enterocolitis. Age at onset was related to birth weight and gestational age. Intercenter differences in necrotizing enterocolitis prevalence were related to time required to regain birth weight and other indicators of fluid management. Gram-positive organisms predominated in positive blood cultures for stage I and II necrotizing enterocolitis; enteric bacteria were isolated more frequently in infants with stage III disease. We conclude that necrotizing enterocolitis prevalence varies greatly among centers; this may be related to early clinical practices of neonatal care. C1 CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. UNIV TENNESSEE, CTR HLTH SCI, MEMPHIS, TN 38163 USA. GEORGE WASHINGTON UNIV, WASHINGTON, DC 20052 USA. UNIV ALABAMA, BIRMINGHAM, AL 35294 USA. NICHHD, BETHESDA, MD 20892 USA. RP UAUY, RD (reprint author), UNIV TEXAS, SW MED CTR, DEPT PEDIAT, 5323 HARRY HINES BLVD, DALLAS, TX 75235 USA. NR 35 TC 227 Z9 236 U1 2 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1991 VL 119 IS 4 BP 630 EP 638 DI 10.1016/S0022-3476(05)82418-7 PG 9 WC Pediatrics SC Pediatrics GA GK017 UT WOS:A1991GK01700021 PM 1919897 ER PT J AU LOE, H BROWN, LJ AF LOE, H BROWN, LJ TI EARLY ONSET PERIODONTITIS IN THE UNITED-STATES-OF-AMERICA SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE PERIODONTITIS, JUVENILE EPIDEMIOLOGY; ORAL HEALTH SURVEYS; ADOLESCENTS ID LOCALIZED JUVENILE PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BONE LOSS; PREVALENCE; DISEASE; ATTACHMENT; POPULATION; RATIOS; AGE AB A NATIONAL SURVEY OF THE ORAL HEAlTH OF U.S. children aged 5 to 17 was conducted by the National Institute of Dental Research during the 1986-87 school year. Eleven thousand and seven adolescents aged 14 to 17 years received a periodontal assessment. Their patterns of loss of periodontal attachment as assessed by probing at mesial sites were used to classify adolescents as cases of early onset periodontitis. Approximately 0.53% of adolescents nation-wide were estimated to have localized juvenile periodontitis (UP), 0.13% to have generalized juvenile periodontitis (GJP), and 1.61% to have incidental loss of attachment (LA) (greater-than-or-equal-to 3 mm on 1 or more teeth). The total number of adolescents affected were not trivial. Close to 70,000 adolescents in the U.S. were estimated to have UP in 1986-87. More destructive GJP affected an estimated 17,000 adolescents. Another 212,000 adolescents were estimated to have incidental LA. Blacks were at much greater risk for all forms of early onset periodontitis than whites. Males were clearly more likely (4.3 to 1) to have GJP than females when other variables were statistically controlled. Gender associations were more complicated for LJP because gender interacted with race. Black males were 2.9 times as likely to have LJP as black females. In contrast, white females were more likely than white males to have the disease by about the same odds. When interactions among demographic variables exist, caution must be taken in comparing results from different studies. RP LOE, H (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BLDG 31,ROOM 2C-39-NIH,BETHESDA,MD 20892, USA. NR 46 TC 178 Z9 183 U1 1 U2 5 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 1991 VL 62 IS 10 BP 608 EP 616 DI 10.1902/jop.1991.62.10.608 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GK464 UT WOS:A1991GK46400004 PM 1770420 ER PT J AU ROGAWSKI, MA YAMAGUCHI, SI JONES, SM RICE, KC THURKAUF, A MONN, JA AF ROGAWSKI, MA YAMAGUCHI, SI JONES, SM RICE, KC THURKAUF, A MONN, JA TI ANTICONVULSANT ACTIVITY OF THE LOW-AFFINITY UNCOMPETITIVE N-METHYL-D-ASPARTATE ANTAGONIST (+/-)-5-AMINOCARBONYL-10,11-DIHYDRO-5H-DIBENZO[A,D]CYCLOHEPTEN-5, 10-IMINE (ADCI) - COMPARISON WITH THE STRUCTURAL ANALOGS DIZOCILPINE (MK-801) AND CARBAMAZEPINE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AMINO-ACID ANTAGONISTS; AMYGDALOID-KINDLED SEIZURES; RECEPTOR-IONOPHORE COMPLEX; NON-COMPETITIVE ANTAGONIST; SELECTIVE NMDA-ANTAGONIST; RAT HIPPOCAMPAL-NEURONS; DEPENDENT BLOCK; SPINAL-CORD; PHENCYCLIDINE; EPILEPSY AB (+/-)-5-Aminocarbonyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (ADCl), a tricyclic compound structurally related to dizocilpine (MK-801) and carbamazepine, was a potent anti-convulsant in the mouse maximal electroshock seizure test when administered i.p. (ED50, 8.9 mg/kg) or p.o. (ED50, 23.5 mg/kg), but failed to cause motor impairment except at substantially higher doses (TD50 values, 49.2 mg/kg i.p. and 293 mg/kg p.o.). ADCl was also protective against chemically induced seizures in mice, including those produced by 4-aminopyridine (ED50, 7.1 mg/kg s.c.) and pentylenetetrazol (ED50, 37.4 mg/kg s.c.). In addition, ADCl antagonized the behavioral effects and lethality of s.c. administered N-methyl-D-aspartate (NMDA; ED50, 15.2 mg/kg), but was a weaker antagonist of kainate-induced clonic seizures (ED50, 33.0 mg/kg), indicating that the drug is a selective functional NMDA antagonist. In common with other NMDA antagonists, ADCl retarded the development of amygdaloid kindled seizures in rats, but failed to attenuate the afterdischarge duration in fully kindled animals. Whole cell voltage clamp recordings from cultured hippocampal neurons demonstrated that ADCI selectively blocks inward current responses to NMDA in a use-dependent fashion without affecting responses to kainate or quisqualate, indicating that ADCI is a selective open channel (uncompetitive) blocker of the NMDA receptor-ionophore complex. ADCI blocked NMDA-evoked inward current responses with a potency (IC50, 14-mu-M) similar to that with which it displaces [H-3]-1-[1-(2-thienyl)-cyclohexyl]piperidine from binding to NMDA receptor channels in rat brain homogenates (IC50, 11.3-mu-M). In contrast, dizocilpine (MK-801) was a high potency antagonist of NMDA responses (IC50 approximately 10 nM) whereas carbamazepine only minimally affected NMDA responses even at high concentrations (IC50 > 300-mu-M). We conclude that ADCl is a low-affinity uncompetitive NMDA antagonist which, like other NMDA antagonists, has a broad spectrum of anticonvulsant activity in animal seizure models. However, in contrast to conventional (high affinity) NMDA antagonists whose propensity to cause neurological side effects may limit their therapeutic usefulness, ADCI has a therapeutic index [maximal electroshock ED50/TD50, 5.5 (i.p.) or 12.5 (p.o.) in the mouse] comparable to that of the widely used antiepileptic drug carbamazepine. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD. RP ROGAWSKI, MA (reprint author), NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITABLE SECT,BLDG 10,ROOM 5N-248,BETHESDA,MD 20892, USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 56 TC 65 Z9 66 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1991 VL 259 IS 1 BP 30 EP 37 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK924 UT WOS:A1991GK92400005 PM 1920122 ER PT J AU PRITCHARD, JB WALDEN, R OIKARI, A AF PRITCHARD, JB WALDEN, R OIKARI, A TI DEHYDROABIETIC ACID, A MAJOR ANIONIC CONTAMINANT OF PULP-MILL EFFLUENT, REDUCES BOTH ACTIVE PARA-AMINOHIPPURATE TRANSPORT AND PASSIVE MEMBRANE-PERMEABILITY IN ISOLATED RENAL MEMBRANES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TROUT SALMO-GAIRDNERI; RAINBOW-TROUT; BASOLATERAL MEMBRANE; RESIN ACIDS; KRAFT PULP; CELL-MEMBRANE; PAPER-MILL; WATER; LIVER; VESICLES AB The renal organic anion transport system plays a pivotal role in elimination of potentially toxic anions. This system is driven by indirect coupling to the sodium gradient at the basolateral membrane, i.e., the organic anion enters the cell in exchange for internal alpha-ketoglutarate (alpha-KG) and the in > out alpha-KG gradient is regenerated by Na+/alpha-KG cotransport. The resin acid, dehydroabietic acid (DHAA), is one of several anionic xenobiotics which enter the environment secondary to pulp and paper processing. Because it is largely ionized at neutral pH (pK(a), 5.7), DHAA should share the organic anion system. Indeed, Na+/glutarate-coupled p-aminohippurate (PAH) uptake by renal basolateral membrane vesicles was inhibited competitively by DHAA (K(i) congruent-to 150-mu-M). Despite the reduced rate of PAH uptake, a substantial, but delayed, overshoot was observed, suggesting additional effects. Passive permeabilities to mannitol, PAH and sodium were all decreased by DHAA, consistent with a general tightening of the membrane. Decreased permeability extended the effective lifetime of imposed ion gradients. Thus, sodium driven glutarate uptake was stimulated by 200-mu-M DHAA, prolonging and more than doubling its overshoot. Because the immediate driving force for PAH uptake into basolateral membrane vesicles is the magnitude of the glutarate gradient, DHAA increased the driving force for PAH uptake and permitted a substantial overshoot despite the reduced rate of PAH uptake. These data indicate that DHAA has several distinctly different effects on the membrane. RP PRITCHARD, JB (reprint author), NIEHS,COMPARAT MEMBRANE PHARMACOL SECT,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 21 Z9 21 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1991 VL 259 IS 1 BP 156 EP 163 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK924 UT WOS:A1991GK92400022 PM 1920114 ER PT J AU NIKODIJEVIC, O SARGES, R DALY, JW JACOBSON, KA AF NIKODIJEVIC, O SARGES, R DALY, JW JACOBSON, KA TI BEHAVIORAL-EFFECTS OF A1-SELECTIVE AND A2-SELECTIVE ADENOSINE AGONISTS AND ANTAGONISTS - EVIDENCE FOR SYNERGISM AND ANTAGONISM SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LOCOMOTOR-ACTIVITY; RECEPTOR AGONIST; CYCLIC-AMP; ANALOGS; CAFFEINE; BRAIN; MICE; RAT; METHYLXANTHINES; ACCUMULATION AB The locomotor effects in mice of selective A1 and A2 adenosine agonists, antagonists and combinations of agonists were investigated using a computerized activity monitor. The A2-selective agonist 2-[(2-aminoethylamino)carbonylethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine (APEC), an amine derivative of 2-(carboxyethylphenylethylamino)adenosine-5'-carboxamide, was a more potent locomoter depressant than its amide conjugates. The rank order of potency after i.p. injection for adenosine agonists was 5'-N-ethylcarboxamidoadenosine (NECA) (ED50, 5.8 nmol/kg) > APEC (ED50, 25 nmol/kg) > N6-cyclohexyladenosine (CHA) (ED50, 270 nmol/kg). An A1-selective, centrally acting, adenosine antagonist, 8-cyclopentyltheophylline (10 mg/kg), completely reversed the locomoter depressant effects of CHA (A1-selective) and NECA (nonselective) at doses of agonists as high as twice the ED50, and shifted the dose-response curves to the right, suggesting a primary involvement of A1 receptors. 8-cyclopentyltheophylline did not affect the depressant effects of APEC at the ED50, consistent with the A2-selectivity of APEC. The locomotor effects of APEC and CHA were completely reversed by theophylline, but not by the peripherally active 8-p-sulfophenyltheophylline, indicating central action of the adenosine agonists. The depressant effects of APEC, but not of NECA or CHA, were reversed significantly by an A2-selective adenosine receptor antagonist, 4-amino-8-chloro-1-phenyl-[1,2,4]triazol[4,3-a]quinoxaline. Low or subthreshold doses of CHA potentiated the depressant effects of APEC. A subthreshold dose of CHA did not alter the depressant effect of NECA, whereas a subthreshold dose of APEC increased the depressant effects of low doses of NECA. Thus, it appears that A1- and A2-selective adenosine agonists have separate central depressant effects, which can be potentiative. The relatively high potency of NECA in vivo could be due to a synergism between central A1 and A2 receptor activation by this nonselective agonist. C1 NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-17,BETHESDA,MD 20892. PFIZER INC,PFIZER CENT RES,GROTON,CT 06340. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 37 TC 101 Z9 102 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1991 VL 259 IS 1 BP 286 EP 294 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK924 UT WOS:A1991GK92400041 PM 1920121 ER PT J AU BELCHEVA, MM BARG, J MCHALE, RJ GAO, XM CHUANG, DM COSCIA, CJ AF BELCHEVA, MM BARG, J MCHALE, RJ GAO, XM CHUANG, DM COSCIA, CJ TI UP-REGULATION OF DELTA-OPIOID RECEPTORS IN NEUROBLASTOMA HYBRID-CELLS - EVIDENCE FOR DIFFERENCES IN THE MECHANISMS OF ACTION OF SODIUM-BUTYRATE AND NALTREXONE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MUSCARINIC CHOLINERGIC RECEPTORS; INDUCED DOWN-REGULATION; OPIATE RECEPTORS; LYSOSOMAL-ENZYMES; GUANINE-NUCLEOTIDES; ADENYLATE-CYCLASE; BINDING PROTEINS; CHRONIC MORPHINE; PERTUSSIS TOXIN; NCB-20 CELLS AB Opioid binding in subcellular fractions from neurohybrid cells was assessed using two models of up-regulation. Homologous up-regulation was achieved by treating NG108-15 cells with the opioid antagonist naltrexone. Na butyrate was added to NCB-20 cell cultures to affect heterologous up-regulation. In both paradigms light and heavy membranes were resolved by concanavalin A (con A) pretreatment of cells followed by density centrifugation. [H-3][D-Ala2,D-Leu5]enkephalin (DADLE) and [H-3] diprenorphine B(max) values for these fractions increased without changes in affinity. In contrast to 48 h of antagonist treatment, 5 min of exposure to naltrexone down-regulated heavy membrane delta sites. Under both conditions of up-regulation, inhibition of LM [H-3]DADLE specific binding by 5'-guanylylimidodiphosphate was enhanced suggesting greater receptor coupling to guanine nucleotide binding regulatory proteins. Although attenuated by addition of cycloheximide, [H-3]DADLE binding to total homogenates increased upon naltrexone treatment of NG108-15 cells. Heavy membrane B(max) values were also augmented in the presence of cycloheximide and naltrexone for 48 h. Activities of beta-glucuronidase and beta-hexoseaminidase were diminished in total homogenates and subcellular fractions from naltrexone-treated cells, suggesting an opioid-induced alteration in lysosomal enzyme trafficking. Comparable receptor down- and up-regulation and attenuation of lysosomal enzyme activity were elicited by the delta-selective opioid peptide antagonist (allyl)2Tyr-Aib-Aib-Phe-Leu-OH. These results suggest that homologous up-regulation entails initial down-regulation and blockade of receptor degradation. C1 ST LOUIS UNIV,SCH MED,EA DOISY DEPT BIOCHEM & MOLEC BIOL,1402 S GRAND BLVD,ST LOUIS,MO 63104. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 51 TC 34 Z9 35 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1991 VL 259 IS 1 BP 302 EP 309 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK924 UT WOS:A1991GK92400043 PM 1656025 ER PT J AU KIM, SG PHILPOT, RM NOVAK, RF AF KIM, SG PHILPOT, RM NOVAK, RF TI PYRIDINE EFFECTS ON P450IIE1, IIB AND IVB EXPRESSION IN RABBIT LIVER - CHARACTERIZATION OF HIGH-AFFINITY AND LOW-AFFINITY PYRIDINE N-OXYGENASES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HEPATIC-MICROSOMAL CYTOCHROME-P-450; SPECIES-DEPENDENT EXPRESSION; RAT-LIVER; -LABELED PYRIDINE; 3-SUBSTITUTED PYRIDINES; CIGARETTE-SMOKE; OXIDATION; INDUCTION; IMIDAZOLE; INVITRO AB The effects of pyridine exposure on expression of cytochromes P450IIE1, IIB and IVB in rabbit hepatic microsomes and their respective role in pyridine N-oxide production has been examined. Immunoblot analysis revealed that pyridine administration caused a substantial increase in P450IIE1 levels, failed to affect P450IIB content and marginally increased the expression of P450IVB. In an effort to implicate specific forms of P450 in pyridine N-oxide production, the kinetics of pyridine N-oxide formation in uninduced and induced rabbit hepatic microsomal preparations were obtained. Pyridine-induced microsomes exhibited a single low K(m) value of 81-mu-M with a approximately 2.5-fold increase in V(max) (2.44 nmol/min/mg protein) relative to uninduced microsomes. Interestingly, pyridine N-oxide production in phenobarbital-induced microsomes was also monophasic, exhibiting a single, high K(m) value of 949-mu-M and a V(max) of 3.3 nmol/min/mg protein, a approximately 10-fold increase over the uninduced preparations. In contrast, uninduced and isosafrole-induced rabbit hepatic microsomes both exhibited biphasic kinetics; uninduced microsomes gave K(m) values of 85 and 973-mu-M, whereas isosafrole-induced microsomes yielded K(m) values of 229 and 1733-mu-M, respectively, with a V(max) somewhat less than uninduced microsomes. When kinetic data were normalized for P450 content, a pronounced substrate specificity was detected for both pyridine- and phenobarbital-induced microsomes. para-Nitrophenol hydroxylase activity was enhanced approximately 6-fold in pyridine-induced microsomes consistent with elevated levels of P450IIE1. para-Nitrophenol competitively inhibited (K(i) = 13-mu-M) the production of pyridine N-oxide in pyridine-induced microsomes. Immunochemical titration experiments revealed only approximately 15% inhibition of pyridine N-oxide production by goat antirabbit P450IIB IgG in phenobarbital-induced rabbit liver microsomes. In contrast, goat antirabbit P450IVB IgG decreased pyridine N-oxide production by 80% in phenobarbital-induced rabbit liver microsomes, suggesting that P450IVB is highly active in the catalysis of pyridine N-oxide production. This is supported further by data obtained from rabbit lung microsomes. The rate of pyridine N-oxide production in lung microsomes, catalyzed by constitutively expressed enzymes, is approximately 3-fold as great as compared to untreated hepatic microsomes. Anti-P450IVB immunoglobulin G addition to lung microsomes resulted in approximately 90% inhibition of pyridine N-oxide formation. These results support the conclusion that P450IIE1 is the principal high-affinity catalyst of pyridine N-oxide formation in rabbit hepatic microsomes at low substrate concentration, whereas P450IVB is the low-affinity form active in pyridine N-oxide production at elevated (e.g., > 2 mM) pyridine concentrations. The low K(m) and elevated V(max) values associated with P450IIE1-catalyzed N-oxide production may be important in the metabolism of low levels of nitrogen-heterocycle-containing agents, which proceed through a similar pathway. The metabolism of volatile heterocyclic aromatic amines to N-oxides, however, may be greatest in lung tissue given the concentration of P450IVB present in this tissue. C1 WAYNE STATE UNIV,INST CHEM TOXICOL,2727 2ND AVE,ROOM 4000,DETROIT,MI 48201. NIEHS,DEPT CELULAR & MOLEC PHARMACOL,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES03656] NR 35 TC 39 Z9 39 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1991 VL 259 IS 1 BP 470 EP 477 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK924 UT WOS:A1991GK92400066 PM 1920133 ER PT J AU CSERR, HF DEPASQUALE, M NICHOLSON, C PATLAK, CS PETTIGREW, KD RICE, ME AF CSERR, HF DEPASQUALE, M NICHOLSON, C PATLAK, CS PETTIGREW, KD RICE, ME TI EXTRACELLULAR VOLUME DECREASES WHILE CELL-VOLUME IS MAINTAINED BY ION UPTAKE IN RAT-BRAIN DURING ACUTE HYPERNATREMIA SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ACUTE HYPEROSMOLALITY; DIFFUSION; FLUID AB 1. Regulation of brain extracellular and intracellular water content, regarded as volume, and electrolytes in response to 90 min of hypernatremia has been studied in the cerebral cortex of rats under urethane anaesthetic. 2. Total tissue electrolytes and water were partitioned between extracellular and intracellular compartments based on measurements made in two series of experiments. In one, tissue samples were collected and analysed for total water, Na+, K+ and Cl-. In the other, tissue extracellular volume fraction, [Na+] and [K+] were measured in situ using ion-selective microelectrodes. 3. Osmotically induced water loss from cerebral cortex was less than that predicted for ideal osmotic behaviour, revealing a degree of volume regulation, and this regulation was associated with net tissue uptake of Na+, Cl- and K+. 4. Total water content was 3.77 g H2O (g dry weight)-1 in control cortex and this decreased by 7% after 30 min of hypernatremia and then remained relatively stable at this value. Control extracellular water content, based on an extracellular volume fraction of 0.18, was 0.88 g H2O (g dry weight)-1. Control intracellular water content, estimated as the difference between total and extracellular water contents, was 2.89 g H2O (g dry weight)-1. After 30 min of hypernatremia, extracellular water content decreased by an average of 27% but intracellular water did not change. This indicates selective regulation of cell volume. By 90 min the extracellular water content had decreased by 47% and the loss in extracellular water content appeared to be accompanied by a roughly equivalent increase in intracellular water content. The intracellular volume increase, however, was not statistically significant. The tortuosity of the extracellular space averaged 1.57 and increased to 1.65 during the hypernatremia. 5. Brain extracellular fluid and plasma [Na+] were roughly equal in control tissue. Both increased by 30-mu-equiv (g H2O)-1 as a result of the hypernatremia, although extracellular [Na+] lagged behind the plasma value during much of the first 60 min of hypernatremia. Extracellular [K+] was homeostatically regulated at 3-mu-equiv (g H2O)-1 independent of changes in plasma electrolytes. 6. Estimates of extracellular and intracellular ion content (mu-equiv (g dry weight)-1) indicate that extracellular Na+, Cl- and K+ content decreased during hypernatremia, by 32, 21 and 42% respectively, whereas intracellular ion content increased by 100, 169 and 5% respectively. 7. It is concluded that during acute hypernatremia the extracellular space decreases in volume through the loss of water and electrolytes while the intracellular compartment maintains its water content and gains electrolytes. The shift of extracellular Na+, Cl- and K+ into the intracellular compartment accounts in part for the decrease in extracellular electrolytes and contributes to the selective regulation of brain cell volume. C1 NYU MED CTR,DEPT PHYSIOL & BIOPHYS,NEW YORK,NY 10016. SUNY STONY BROOK,DEPT NEUROSURG,STONY BROOK,NY 11794. NIMH,DIV BIOMETRY & APPL SCI,BETHESDA,MD 20892. RP CSERR, HF (reprint author), BROWN UNIV,PHYSIOL SECT,PROVIDENCE,RI 02912, USA. FU NINDS NIH HHS [NS-11050, NS-07745, NS-13742] NR 30 TC 117 Z9 119 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT PY 1991 VL 442 BP 277 EP 295 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GK914 UT WOS:A1991GK91400016 PM 1798030 ER PT J AU LANDIS, WJ SONG, MJ AF LANDIS, WJ SONG, MJ TI EARLY MINERAL DEPOSITION IN CALCIFYING TENDON CHARACTERIZED BY HIGH-VOLTAGE ELECTRON-MICROSCOPY AND 3-DIMENSIONAL GRAPHIC IMAGING SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID COLLAGEN FIBRILLOGENESIS INSITU; RAT-TAIL TENDON; NEUTRON-DIFFRACTION; FIBRILS; BONE; MATRIX; RECONSTRUCTION; CALCIFICATION; CRYSTALS; TURKEY C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,HIGH VOLTAGE ELECTRON MICROSCOPY RESOURCE,ALBANY,NY 12201. HARVARD UNIV,SCH MED,DEPT ORTHOPED SURG,BOSTON,MA 02115. RP LANDIS, WJ (reprint author), CHILDRENS HOSP MED CTR,ENDERS BLDG,ROOM 284,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAMS NIH HHS [AR 34078, AR 34081]; NICHD NIH HHS [HD 22400] NR 31 TC 45 Z9 45 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 1991 VL 107 IS 2 BP 116 EP 127 DI 10.1016/1047-8477(91)90015-O PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GM774 UT WOS:A1991GM77400003 PM 1807348 ER PT J AU STEINERT, PM AF STEINERT, PM TI ORGANIZATION OF COILED-COIL MOLECULES IN NATIVE MOUSE KERATIN 1/KERATIN-10 INTERMEDIATE FILAMENTS - EVIDENCE FOR ALTERNATING ROWS OF ANTIPARALLEL IN-REGISTER AND ANTIPARALLEL STAGGERED MOLECULES SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID BOVINE EPIDERMAL KERATIN; TRANSMISSION ELECTRON-MICROSCOPY; NEUROFILAMENT-L PROTEIN; AMINO-ACID-SEQUENCE; ASSEMBLED INVITRO; II KERATINS; SUBUNIT; MICROFIBRIL; VIMENTIN; CELLS RP STEINERT, PM (reprint author), NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,SKIN BIOL LAB,BETHESDA,MD 20892, USA. NR 52 TC 47 Z9 47 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 1991 VL 107 IS 2 BP 157 EP 174 DI 10.1016/1047-8477(91)90019-S PG 18 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GM774 UT WOS:A1991GM77400007 PM 1725489 ER PT J AU STEINERT, PM AF STEINERT, PM TI ANALYSIS OF THE MECHANISM OF ASSEMBLY OF MOUSE KERATIN 1/KERATIN-10 INTERMEDIATE FILAMENTS INVITRO SUGGESTS THAT INTERMEDIATE FILAMENTS ARE BUILT FROM MULTIPLE OLIGOMERIC UNITS RATHER THAN A UNIQUE TETRAMERIC BUILDING BLOCK SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID TRANSMISSION ELECTRON-MICROSCOPY; MOLECULAR-INTERACTIONS; VIMENTIN SUBUNITS; NUCLEAR LAMINA; COILED-COILS; NF-L; CELLS; PROTEINS; EXPRESSION; REVEALS RP STEINERT, PM (reprint author), NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,SKIN BIOL LAB,BETHESDA,MD 20892, USA. NR 50 TC 68 Z9 69 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD OCT PY 1991 VL 107 IS 2 BP 175 EP 188 DI 10.1016/1047-8477(91)90020-W PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GM774 UT WOS:A1991GM77400008 PM 1725490 ER PT J AU BOWERS, GM REDDI, AH AF BOWERS, GM REDDI, AH TI REGENERATING THE PERIODONTIUM IN ADVANCED PERIODONTAL-DISEASE SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GUIDED TISSUE REGENERATION; ATTACHMENT APPARATUS FORMATION; HISTOLOGIC EVALUATION; INACTIVATION; HUMANS; OSTEOGENIN; DEFECTS; PROTEIN; VIRUS; DOGS AB Current techniques can benefit patients with advanced periodontal disease and oral injuries. Future technology offers even greater promise for regenerating periodontal tissue. C1 NIDR,BONE BIOL SECT,BETHESDA,MD 20892. RP BOWERS, GM (reprint author), UNIV MARYLAND,SCH DENT,DEPT PERIODONT,666 W BALTIMORE ST,BALTIMORE,MD 21201, USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1991 VL 122 IS 11 BP 45 EP 48 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GJ659 UT WOS:A1991GJ65900012 PM 1744346 ER PT J AU GUCKES, AD BRAHIM, JS MCCARTHY, GR RUDY, SF COOPER, LF AF GUCKES, AD BRAHIM, JS MCCARTHY, GR RUDY, SF COOPER, LF TI USING ENDOSSEOUS DENTAL IMPLANTS FOR PATIENTS WITH ECTODERMAL DYSPLASIA SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ANODONTIA AB Congenitally missing teeth and poorly developed or absent alveolar ridges are signs often associated with various types of ectodermal dysplasia. Endosseous dental implants may be used to support fixed mandibular prostheses in patients with ectodermal dysplasia. Anatomical factors and age considerations require careful attention to treatment planning. RP GUCKES, AD (reprint author), NIDR,PATIENT CARE & CLIN INVEST SECT,BLDG 10,ROOM 1N-13,BETHESDA,MD 20892, USA. NR 27 TC 55 Z9 55 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1991 VL 122 IS 11 BP 59 EP 62 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GJ659 UT WOS:A1991GJ65900014 PM 1744347 ER PT J AU SILKS, LA PENG, J ODOM, JD DUNLAP, RB AF SILKS, LA PENG, J ODOM, JD DUNLAP, RB TI SYNTHESIS OF (4S,5R)-(-)-4-METHYL-5-PHENYLOXAZOLIDINE-2-SELONE - A CHIRAL AUXILIARY REAGENT CAPABLE OF DETECTING THE ENANTIOMERS OF (R,S)-LIPOIC ACID BY SE-77 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID SELENIUM DOUBLE-BONDS; ORGANOSELENIUM COMPOUNDS; ALPHA-CHYMOTRYPSIN; NMR; ISOCYANIDES; C=SE AB (4S,5R)-(-)-4-Methyl-5-phenyloxazolidine-2-selone was constructed in 5 steps on the 10-gram scale. Se-77 NMR spectroscropic studies revealed that this selone served as a remarkably sensitive chiral auxiliary agent which readily distinguished the selone-coupled (R,S)-lipoic acid (DELTA-delta 0.119 ppm), even though its chiral centre was separated by 8 bonds from the observed nucleus. C1 UNIV S CAROLINA,DEPT CHEM,COLUMBIA,SC 29208. RP SILKS, LA (reprint author), NIH,LOS ALAMOS NATL LAB,STABLE ISOTOPES RESOURCE,INC-4,MS C-345,LOS ALAMOS,NM 87545, USA. NR 45 TC 31 Z9 31 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD OCT PY 1991 IS 10 BP 2495 EP 2498 DI 10.1039/p19910002495 PG 4 WC Chemistry, Organic SC Chemistry GA GK057 UT WOS:A1991GK05700030 ER PT J AU ROBERTSON, MN MIYAZAWA, M MORI, S CAUGHEY, B EVANS, LH HAYES, SF CHESEBRO, B AF ROBERTSON, MN MIYAZAWA, M MORI, S CAUGHEY, B EVANS, LH HAYES, SF CHESEBRO, B TI PRODUCTION OF MONOCLONAL-ANTIBODIES REACTIVE WITH A DENATURED FORM OF THE FRIEND MURINE LEUKEMIA-VIRUS GP70 ENVELOPE PROTEIN - USE IN A FOCAL INFECTIVITY ASSAY, IMMUNOHISTOCHEMICAL STUDIES, ELECTRON-MICROSCOPY AND WESTERN BLOTTING SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE MONOCLONAL ANTIBODY; RETROVIRUS; IMMUNOHISTOCHEMISTRY; ELECTRON MICROSCOPY ID ENV GENE; PLAQUE ASSAY; CELL-LINES; WILD MICE; C-VIRUS; DNA; MCF; ERYTHROLEUKEMIA; RECOMBINANT; RETROVIRUS AB Four monoclonal antibodies were selected for their ability to recognize the envelope protein of Friend murine leukemia virus (F-MuLV) in methanol-fixed tissue culture cells. Each of these monoclonal antibodies was found to react only with F-MuLV. By using recombinant retroviruses, it was determined that each of the monoclonal antibodies recognized the C-terminal one-third of the F-MuLV gp70 envelope protein. The monoclonal antibodies were effective in radioimmunoprecipitation of F-MuLV proteins, and one of the antibodies, 720, was also effective in Western blotting. The ability of antibody 720 to react with F-MuLV in methanol-fixed cells facilitated the use of a sensitive immunoperoxidase method with a focal virus infectivity assay. In immunohistochemical studies using light microscopy, antibody 720 could specifically label F-MuLV-infected cells in acetone-fixed tissue sections from F-MuLV-infected animals. Finally, in immuno-gold labelling studies using electron microscopy, antibody 720 could be used to distinguish F-MuLV from amphotropic MuLV. C1 NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,903 S 4TH ST,HAMILTON,MT 59840. NIAID,VECTORS & PATHOGENS LAB,ROCKY MT LABS,HAMILTON,MT 59840. NR 34 TC 93 Z9 93 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD OCT PY 1991 VL 34 IS 3 BP 255 EP 271 DI 10.1016/0166-0934(91)90105-9 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA GP283 UT WOS:A1991GP28300004 PM 1744218 ER PT J AU NAGPAL, S OSTROVE, JM AF NAGPAL, S OSTROVE, JM TI CHARACTERIZATION OF A POTENT VARICELLA-ZOSTER VIRUS-ENCODED TRANS-REPRESSOR SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; HUMAN IMMUNODEFICIENCY VIRUS; LONG TERMINAL REPEAT; SV40 GENE-EXPRESSION; T-ANTIGEN; TRANSCRIPTIONAL ACTIVATION; CELLULAR PROTEINS; RESPONSE ELEMENT; MESSENGER-RNAS; LEUCINE ZIPPER AB Using a transient expression assay in Vero cells, we have shown that the protein product from gene 61 of varicella-zoster virus (VZV) can repress the function of the VZV encoded trans-activators on putative viral immediate-early, early, and late gene promoters. The repression is exerted at the transcriptional level and requires functional gene 61 protein. This trans-repressor is the herpes simplex type 1 ICP0 (a trans-activator) homolog, as defined by gene location, the sharing of a cysteine-rich putative zinc-binding finger in the amino-terminal region, and limited amino acid homology. Open reading frame 61 (ORF61)-mediated trans-repression appears to be specific for VZV-encoded trans-activators in that it has no effect on simian virus 40 and Rous sarcoma virus promoters. Moreover, it does not inhibit trans-activation of the human T-lymphotropic virus type I and human immunodeficiency virus long terminal repeats by tax and tat genes, respectively. We constructed plasmids with mutations in ORF61 and tested them for their ability to inhibit trans-activator (VZV genes 4 and 62)-mediated activation of the viral thymidine kinase promoter-chloramphenicol acetyltransferase construct. Mutants containing interruptions in ORF61 lost their trans-repressing ability, as demonstrated at both the protein and steady-state RNA levels. These results suggest that the ORF61 protein product can mediate down-regulation of VZV gene expression. C1 NIAID,MED VIROL SECT,CLIN INVEST LAB,BETHESDA,MD 20892. RI Nagpal, Sunil/A-8007-2009 NR 49 TC 62 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5289 EP 5296 PG 8 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700020 PM 1654442 ER PT J AU GITLIN, SD BOSSELUT, R GEGONNE, A GHYSDAEL, J BRADY, JN AF GITLIN, SD BOSSELUT, R GEGONNE, A GHYSDAEL, J BRADY, JN TI SEQUENCE-SPECIFIC INTERACTION OF THE ETS1 PROTEIN WITH THE LONG TERMINAL REPEAT OF THE HUMAN T-LYMPHOTROPIC VIRUS TYPE-I SO JOURNAL OF VIROLOGY LA English DT Article ID CELL LEUKEMIA-VIRUS; TRANSCRIPTIONAL CONTROL REGION; TROPICAL SPASTIC PARAPARESIS; ENCODING NUCLEAR PROTEINS; DNA-BINDING ACTIVITY; C-ETS; RESPONSIVE ELEMENT; TRANSFORMING GENE; LYMPHOID-CELLS; E26 RETROVIRUS AB We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T-lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expression of Ets1 with reporter plasmids containing ERR-1 or ERR-2 upstream of a basal promoter resulted in an increase in transcriptional activity. By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region. By DNase I footprint, gel mobility shift, and methylation interference analyses, ERR-1 was found to contain two Ets1 binding sites, ERE-A and ERE-B. A recombinant Ets1 protein was found to bind with higher affinity to ERE-A than to ERE-B. Binding of Ets1 to these sites appears to result in a specific and sequential protection of a 37-nucleotide sequence of the HTLV-I LTR from -154 to -118. In view of the high-level expression of Ets1 in lymphoid cells, the c-ets proto-oncogenes encode transcription factors which could play an important role in both basal and Tax1-mediated HTLV-I transcription. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. INST CURIE,BIOL SECT,ONCOL VIRALE & CELLULAIRE LAB,F-91405 ORSAY,FRANCE. RI GHYSDAEL, Jacques/F-3377-2013 NR 77 TC 76 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5513 EP 5523 PG 11 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700048 PM 1895400 ER PT J AU HARDY, ME WOODE, GN XU, ZC GORZIGLIA, M AF HARDY, ME WOODE, GN XU, ZC GORZIGLIA, M TI COMPARATIVE AMINO-ACID-SEQUENCE ANALYSIS OF VP4 FOR VP7 SEROTYPE-6 BOVINE ROTAVIRUS STRAINS NCDV, B641, AND UK SO JOURNAL OF VIROLOGY LA English DT Note ID COMPLETE NUCLEOTIDE-SEQUENCE; CALF DIARRHEA VIRUS; NEUTRALIZATION EPITOPES; ANTIGENIC RELATIONSHIPS; MONOCLONAL-ANTIBODIES; TRYPSIN ENHANCEMENT; ANIMAL ROTAVIRUSES; GNOTOBIOTIC CALVES; PORCINE ROTAVIRUS; RHESUS ROTAVIRUS AB In a previous study (S. Zheng, G. N. Woode, D. R. Melendy, and R. F. Ramig, J. Clin. Microbiol. 27:1939-1945, 1989), it was predicted that the VP7 serotype 6 bovine rotavirus strains NCDV and B641 do not share antigenically similar VP4s. In this study, gene 4 and the VP7 gene of B641 were sequenced, and the amino acid sequences were deduced and compared with those of NCDV and bovine rotavirus strain UK. Amino acid sequence homology in VP7 between the three strains was > 94%, confirming their relationship as VP7 serotype 6 viruses. VP4 of B641 showed amino acid homology to UK of 94% but only 73% homology to NCDV. Sequence comparison of a variable region of VP8 demonstrated amino acid homology of 53% between B641 and NCDV, whereas B641 and UK were 89% homologous in this region. These results confirm the earlier prediction that although the same serotype by VP7 reactivity, B641 and NCDV represent different VP4 serotypes. This difference in VP4 may have contributed to the lack of homotypic protection observed in calves, implicating VP4 as an important antigen in the active immune response to rotavirus infection in bovines. C1 TEXAS A&M UNIV SYST,COLL VET MED,DEPT VET PATHOBIOL,COLLEGE STN,TX 77843. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 32 TC 38 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5535 EP 5538 PG 4 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700051 PM 1654450 ER PT J AU JOSEPHS, SF ABLASHI, DV SALAHUDDIN, SZ JAGODZINSKI, LL WONGSTAAL, F GALLO, RC AF JOSEPHS, SF ABLASHI, DV SALAHUDDIN, SZ JAGODZINSKI, LL WONGSTAAL, F GALLO, RC TI IDENTIFICATION OF THE HUMAN HERPESVIRUS-6 GLYCOPROTEIN-H AND PUTATIVE LARGE TEGUMENT PROTEIN GENES SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CYTOMEGALO-VIRUS; LONG TERMINAL REPEAT; EPSTEIN-BARR-VIRUS; VARICELLA-ZOSTER VIRUS; TYPE-1 REPLICATION; TRANS-ACTIVATION; EXANTHEM SUBITUM; CELL-LINES; T-CELLS AB Determination of the nucleotide sequences of two molecular clones of human herpesvirus 6 (HHV-6) (strain GS) and comparison with those of human cytomegalovirus (HCMV) has allowed the identification of the genes for the glycoprotein H (gH) and the putative large tegument protein of HHV-6. Two molecular clones of fragments of HHV-6, the BamHI-G fragment (7,981 bp) of the clone termed pZVB43 and a HindIII fragment (8,717 bp) of the clone termed pZVH14, represent approximately 10% of the HHV-6 genome (16,689). An open reading frame within the BamHI-G fragment was designated the gH gene of HHV-6 because of the extensive sequence similarity of its predicted product (79,549 Da) to the HCMV gH gene product. The predicted product (239,589 Da) of an open reading frame within clone pZVH14 showed homology to the predicted product of the proposed gene of HCMV representing the large tegument protein. Computer analyses indicated a closer relationship of the predicted peptides of these HHV-6 genes to those of HCMV than to those of the other human herpesviruses Epstein-Barr virus, herpes simplex virus type 1, and varicella-zoster virus. The gH gene was more conserved among the human herpesvirus group, while significant sequence similarity of the tegument gene could be found only with that of HCMV. The data reported here with one conserved gene (gH) and a more divergent gene (tegument) support previous reports that HHV-6 and HCMV are more closely related to each other than to the other well-characterized human herpesviruses. C1 NCI,DIV CANC ETIOL,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. CAMBRIDGE BIOTECH INC,ROCKVILLE,MD 20850. NR 50 TC 62 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5597 EP 5604 PG 8 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700064 PM 1654455 ER PT J AU KRAUSE, PR OSTROVE, JM STRAUS, SE AF KRAUSE, PR OSTROVE, JM STRAUS, SE TI THE NUCLEOTIDE-SEQUENCE, 5' END, PROMOTER DOMAIN, AND KINETICS OF EXPRESSION OF THE GENE ENCODING THE HERPES-SIMPLEX VIRUS TYPE-2 LATENCY-ASSOCIATED TRANSCRIPT SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN TRIGEMINAL GANGLIA; MESSENGER-RNA; INFECTION; MICE; DELETION; NEURONS; REGION; GENOME; MUTANT; PHASE AB The sequence of the herpes simplex virus type 2 (HSV-2) latency-associated transcript (LAT) region resembles that of HSV-1 only where the LATs overlap ICP0 and in the putative promoter region. Otherwise, the LAT 5' ends, kinetics of expression, and promoter elements are mostly conserved between HSV-1 and HSV-2. The remaining differences between the LATs could contribute to each virus's distinctive pattern of reactivation. C1 NIAID,MED VIROL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N228,BETHESDA,MD 20892. NR 28 TC 30 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5619 EP 5623 PG 5 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700068 PM 1654458 ER PT J AU REMENICK, J RADONOVICH, MF BRADY, JN AF REMENICK, J RADONOVICH, MF BRADY, JN TI HUMAN-IMMUNODEFICIENCY-VIRUS TAT TRANSACTIVATION - INDUCTION OF A TISSUE-SPECIFIC ENHANCER IN A NONPERMISSIVE CELL-LINE SO JOURNAL OF VIROLOGY LA English DT Note ID LONG-TERMINAL REPEAT; POLYOMAVIRUS JC-VIRUS; TRANS-ACTIVATOR GENE; HUMAN-BRAIN CELLS; HIV-1 TAT; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATION; REGULATORY REGION; HTLV-III; PROTEIN AB The enhancer of the human neurotropic papovavirus JC virus (JCV) restricts viral transcription to glial cells. We utilized the tissue specificity of the JCV enhancer as a tool to investigate the function of human immunodeficiency virus (HIV) Tat in transcriptional activation. The reporter plasmid pJCTAR-CAT was constructed by inserting the HIV type 1 Tat-responsive element, TAR, between the JCV promoter and the chloramphenicol acetyltransferase (CAT) gene. Cotransfection of pJCTAR-CAT and pSV-Tat, an expression vector for Tat, resulted in a 50-fold increase in JCV promoter activity in cells nonpermissive for JCV expression. Both the 98-bp JCV enhancer and the HIV TAR sequences were required for transactivation of pJCTAR-CAT in nonpermissive cells. The transactivation by Tat occurred at the level of transcription, as the increase in CAT activity paralleled an increase in the steady-state levels of CAT mRNA in S1 nuclease and nuclear run-on analyses. In the presence of Tat, the JCV enhancer is functional in cells normally nonpermissive for JCV expression; therefore, our results provide unique evidence that HIV type 1 Tat may regulate the activity of specific transcription factors. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 46 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1991 VL 65 IS 10 BP 5641 EP 5646 PG 6 WC Virology SC Virology GA GF097 UT WOS:A1991GF09700072 PM 1654461 ER PT J AU MASSRY, SG FADDA, GZ ZHOU, XJ CHANDRASOMA, P CHENG, L FILBURN, CR AF MASSRY, SG FADDA, GZ ZHOU, XJ CHANDRASOMA, P CHENG, L FILBURN, CR TI IMPAIRED INSULIN-SECRETION OF AGING - ROLE OF RENAL-FAILURE AND HYPERPARATHYROIDISM SO KIDNEY INTERNATIONAL LA English DT Article ID PARATHYROID-HORMONE; GLUCOSE-INTOLERANCE; ISOLATED ISLETS; BETA-CELL; AGE; RAT; RELEASE; METABOLISM; PROINSULIN; CLEARANCE AB Available data indicate that insulin secretion is impaired with aging. Almost all the studies that examined insulin secretion by old animals did not take into consideration the state of renal function or the blood levels of parathyroid hormone (PTH). Old animals may have chronic renal failure (CRF) and secondary hyperparathyroidism, and both of these conditions impair insulin secretion. It is possible, therefore, that the impaired insulin secretion of aging is not due to old age per se, but rather to associated CRF and excess PTH. The present study examined this issue in adult (6 month old) and senescent rats (2 years old) with and without CRF and excess PTH. Senescent rats without CRF had normal renal function and normal blood levels of PTH, and the values were not different from those observed in adult rats. Creatinine clearance in senescent rats with CRF was significantly (P < 0.01) lower and serum levels of PTH were significantly (P < 0.01) higher than in senescent animals without CRF and than in the adult rats as well. Only the senescent rats with CRF displayed glucose intolerance during intravenous glucose tolerance test. For any given level of blood glucose, plasma insulin levels were lower in senescent rats with CRF than in the adult rat or senescent animals without CRF. Both initial phase (139 +/- 45 pg/islet . 8 min) and total (808 +/- 216 pg/islet . 33 min) insulin secretion from pancreatic islets of the senescent rats with CRF and excess PTH were significantly lower than those in senescent rats with normal renal function (658 +/- 117 pg/islet .8 min and 3294 +/- 290 pg/islet . 33 min, respectively) or in adult rats (710 +/- 134 pg/islet . 8 min and 3183 +/- 366 pg/islet . 33 min, respectively). There were no significant differences in insulin secretion between the adult rats and the senescent ones with normal renal function. The data demonstrate that the impaired insulin secretion by the pancreatic islets in old rats is not necessarily related to the higher age per se, but is due to the associated CRF and secondary hyperparathyroidism that develops in many, but not all old animals. Our results indicate that studies examining the effect of aging on body function should take into consideration the level of renal function and of the serum PTH, since both CRF and excess PTH adversely affect the functional integrity of many organs. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. RP MASSRY, SG (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,DIV NEPHROL,2025 ZONAL AVE,LOS ANGELES,CA 90033, USA. FU NIDDK NIH HHS [DK-29955] NR 37 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1991 VL 40 IS 4 BP 662 EP 667 DI 10.1038/ki.1991.258 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA GT736 UT WOS:A1991GT73600010 PM 1745015 ER PT J AU RAY, PE AGUILERA, G KOPP, JB HORIKOSHI, S KLOTMAN, PE AF RAY, PE AGUILERA, G KOPP, JB HORIKOSHI, S KLOTMAN, PE TI ANGIOTENSIN-II RECEPTOR-MEDIATED PROLIFERATION OF CULTURED HUMAN FETAL MESANGIAL CELLS SO KIDNEY INTERNATIONAL LA English DT Article ID SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; VASOPRESSIN; EXPRESSION; STIMULATION; CALCIUM; SYSTEM; KIDNEY; SITES; CA-2+ AB Accumulating evidence suggests that angiotensin II (Ang II) may play an important role in renal growth and glomerular development. During nephrogenesis, a complex relationship between the capillary and renal mesangium develops. Since the mesangial cell is a centrally-located pericyte with contractile, endocrine, and immune modulating functions, it may play a unique role in maintaining normal glomerular function. Therefore, we examined whether Ang II affects proliferation of human fetal mesangial cells in vitro and compared these findings to mesangial cells isolated from adult kidney. In these primary isolates, we studied the relationship between Ang II receptors and the mitogenic activity of angiotensin. Scatchard analysis of the binding of I-125[Sar1, Ile8]Ang II to subconfluent cultured human fetal mesangial cells revealed the presence of one class of binding sites with a Kd of 1.25 nM and a B(max) of 70 fmol/1 x 10(5) cells. Ang II receptors on adult mesangial cells had similar binding kinetics with a Kd of 1.6 nM and B(max) of 65 fmol/10(5) cells in subconfluent culture. In subconfluent culture of fetal mesangial cells, Ang II increased [H-3]thymidine incorporation by 130% (P < 0.005). In subconfluent culture of adult mesangial cells, Ang II increased [H-3]thymidine incorporation by only 35% (P < 0.05). In confluent culture of fetal mesangial cells, Ang II receptor number and mitogenic response were reduced. The Ang II antagonist [Sar1,Ile8]Ang II (1-mu-M) inhibited the mitogenic response of fetal mesangial cells to Ang II. Ang II increased fetal mesangial cell number by 25% (after 4 days) in serum-free medium supplemented with insulin or supplemented with insulin and 1% Nutridoma (P < 0.005). Thus, Ang II is mitogenic for fetal mesangial cells but, in contrast, Ang II is only weakly mitogenic for adult mesangial cells. These results are consistent with a role for Ang II in glomerular development as well as in disease states in which there is a change from the adult to the fetal phenotype. C1 NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC. RP RAY, PE (reprint author), NIDR,DEV BIOL LAB,MOLEC MED SECT,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 40 TC 128 Z9 129 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1991 VL 40 IS 4 BP 764 EP 771 DI 10.1038/ki.1991.273 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA GT736 UT WOS:A1991GT73600025 PM 1745028 ER PT J AU ZWEIG, MH AF ZWEIG, MH TI ROC ANALYSIS - ASSESSMENT OF DIAGNOSTIC-ACCURACY IN THE LABORATORY SO LABORATORY MEDICINE LA English DT Article AB The intrinsic ability of a diagnostic test or system to discriminate between two states of health constitutes its accuracy in the purest sense. Information about this accuracy can be readily obtained by the laboratorian using receiver (or relative) operating characteristic curve analysis, and may be helpful in making some of the decisions normally encountered in laboratory practice. RP ZWEIG, MH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0007-5027 J9 LAB MED JI Lab. Med. PD OCT PY 1991 VL 22 IS 10 BP 708 EP 711 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA GF438 UT WOS:A1991GF43800003 ER PT J AU BERKOWITZ, BA WILSON, CA HATCHELL, DL LONDON, RE AF BERKOWITZ, BA WILSON, CA HATCHELL, DL LONDON, RE TI QUANTITATIVE-DETERMINATION OF THE PARTIAL OXYGEN-PRESSURE IN THE VITRECTOMIZED RABBIT EYE INVIVO USING F-19 NMR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID BLOOD SUBSTITUTE; SURFACE COILS; SPECTROSCOPY; RELAXATION; INVERSION; TENSION; LIQUIDS C1 DUKE UNIV,CTR EYE,DURHAM,NC 27710. VET ADM MED CTR,DURHAM,NC 27710. RP BERKOWITZ, BA (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. FU NEI NIH HHS [R01 EY02903] NR 22 TC 45 Z9 45 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD OCT PY 1991 VL 21 IS 2 BP 233 EP 241 DI 10.1002/mrm.1910210208 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GH820 UT WOS:A1991GH82000007 PM 1745122 ER PT J AU PEKAR, J LIGETI, L RUTTNER, Z LYON, RC SINNWELL, TM VANGELDEREN, P FIAT, D MOONEN, CTW MCLAUGHLIN, AC AF PEKAR, J LIGETI, L RUTTNER, Z LYON, RC SINNWELL, TM VANGELDEREN, P FIAT, D MOONEN, CTW MCLAUGHLIN, AC TI INVIVO MEASUREMENT OF CEREBRAL OXYGEN-CONSUMPTION AND BLOOD-FLOW USING O-17 MAGNETIC-RESONANCE-IMAGING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note ID CAT BRAIN; P-31 NMR C1 NIAAA,ROCKVILLE,MD 20852. SEMMELWEIS UNIV MED,H-1085 BUDAPEST 8,HUNGARY. DELFT UNIV TECHNOL,DEPT APPL PHYS,DELFT,NETHERLANDS. UNIV ILLINOIS,DEPT PERFORMING ARTS,CHICAGO,IL 60680. RP PEKAR, J (reprint author), NIH,INVIVO NMR RES CTR,BLDG 10,ROOM B1D-125,BETHESDA,MD 20892, USA. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 12 TC 86 Z9 87 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD OCT PY 1991 VL 21 IS 2 BP 313 EP 319 DI 10.1002/mrm.1910210217 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GH820 UT WOS:A1991GH82000016 PM 1745131 ER PT J AU MORGAN, PF AF MORGAN, PF TI IS QUINOLINIC ACID AN ENDOGENOUS EXCITOTOXIN IN ALCOHOL-WITHDRAWAL SO MEDICAL HYPOTHESES LA English DT Article ID STRIATAL EXTRACELLULAR FLUID; CENTRAL NERVOUS-SYSTEM; TRYPTOPHAN OXYGENASE; NMDA RECEPTORS; AMINO-ACID; RAT; METABOLITES; BRAIN; LIVER; ETHANOL AB Levels of tryptophan in brain are increased by the action of chronic ethanol, particularly in the event of compromised hepatic function. This is likely to result in elevated brain levels of the potent excitotoxin quinolinic acid (quinolinate) since levels of this tryptophan metabolite can be elevated considered by tryptophan loading. Ethanol may also selectively increase the activity of enzymes important in the synthesis of quinolinic acid such as tryptophan oxygenase. It is concluded that ethanol may generate significant levels of the NMDA receptor agonist, quinolinic acid, possibly even toxic levels in localized brain areas, especially during ethanol withdrawal and when associated with acute or chronic hepatotoxicity. RP MORGAN, PF (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,ROOM 3C-102,BETHESDA,MD 20892, USA. NR 25 TC 11 Z9 11 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 1991 VL 36 IS 2 BP 118 EP 121 DI 10.1016/0306-9877(91)90251-S PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GR021 UT WOS:A1991GR02100005 PM 1664036 ER PT J AU LINDBERG, DAB SIEGEL, ER AF LINDBERG, DAB SIEGEL, ER TI ON ASSESSING THE IMPACT OF MEDICAL INFORMATION - DOES MEDLINE MAKE A DIFFERENCE SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material RP LINDBERG, DAB (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 2 TC 16 Z9 16 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD OCT PY 1991 VL 30 IS 4 BP 239 EP 240 PG 2 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA GR511 UT WOS:A1991GR51100001 PM 1762577 ER PT J AU MIZUNO, K GONZALEZ, FJ KIMURA, S AF MIZUNO, K GONZALEZ, FJ KIMURA, S TI THYROID-SPECIFIC ENHANCER-BINDING PROTEIN (T/EBP) - CDNA CLONING, FUNCTIONAL-CHARACTERIZATION, AND STRUCTURAL IDENTITY WITH THYROID TRANSCRIPTION FACTOR TTF-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROGLOBULIN GENE-EXPRESSION; COMPLETE NUCLEOTIDE-SEQUENCE; TISSUE-SPECIFIC EXPRESSION; PEROXIDASE GENE; MOLECULAR-CLONING; GEL-ELECTROPHORESIS; RIBONUCLEIC-ACID; VACCINIA VIRUS; FACTOR-I; CELLS AB A cDNA clone encoding a thyroid-specific enhancer-binding protein (T/EBP) was isolated from a rat thyroid-derived FRTL-5 cell lambda-gt 11 expression library, using a double-stranded oligonucleotide probe. This oligonucleotide was previously demonstrated to have the strongest binding affinity among three cis-acting DNA elements within the thyroid-specific enhancer region located 5.5 kbp upstream of the human thyroid peroxidase gene transcription start site. Nucleotide and deduced amino acid sequences of the cDNA revealed that T/EBP is identical to the previously reported thyroid-specific transcription factor 1 (TTF-1), which binds to the promoter of the rat thyroglobulin gene and controls its thyroid-specific expression. Expression of the T/EBP cDNA under control of the human cytomegalovirus major immediate-early gene promoter conferred thyroid-specific enhancer activity of as high as 26-fold to nonpermissive human hepatoma HepG2 cells when cotransfected with a vector containing 6.3 kbp of upstream sequence of the human thyroid peroxidase gene connected to a luciferase reporter gene. T/EBP was further expressed in HepG2 cells by using the vaccinia virus expression system. The expressed protein was partially purified by using sequence-specific affinity column chromatography and was further shown, by gel mobility shift experiments, to specifically bind to the enhancer-derived double-stranded oligonucleotide. These results clearly indicate that the binding of T/EBP (TTF-1) to the specific cis-acting enhancer element is largely responsible for thyroid-specific enhancer activity. C1 NCI, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. NR 48 TC 106 Z9 106 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1991 VL 11 IS 10 BP 4927 EP 4933 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GJ401 UT WOS:A1991GJ40100014 PM 1922026 ER PT J AU KIM, SJ WINOKUR, TS LEE, HD DANIELPOUR, D KIM, KY GEISER, AG CHEN, LS SPORN, MB ROBERTS, AB JAY, G AF KIM, SJ WINOKUR, TS LEE, HD DANIELPOUR, D KIM, KY GEISER, AG CHEN, LS SPORN, MB ROBERTS, AB JAY, G TI OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IN TRANSGENIC MICE CARRYING THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I TAX GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; LEUKEMIA-VIRUS; INTERLEUKIN-2 RECEPTOR; MESSENGER-RNA; ADULT TISSUES; P40X PROTEIN; EXPRESSION; ACTIVATION; FACTOR-BETA-1; PROMOTER AB Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta-1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta-1 promoter. To understand further the regulation of TGF-beta-1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta-1 mRNA and protein. Moreover, TGF-beta-1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta-1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo. C1 AMER RED CROSS,JEROME H HOLLAND LAB,VIROL LAB,ROCKVILLE,MD 20855. RP KIM, SJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. RI Jay, Gregory/C-6346-2013 FU NCI NIH HHS [CA51779-01] NR 34 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1991 VL 11 IS 10 BP 5222 EP 5228 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GJ401 UT WOS:A1991GJ40100045 PM 1922042 ER PT J AU EIDEN, MV MACARTHUR, L OKAYAMA, H AF EIDEN, MV MACARTHUR, L OKAYAMA, H TI SUPPRESSION OF THE CHEMICALLY TRANSFORMED PHENOTYPE OF BHK CELLS BY A HUMAN CDNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2A; INTERMEDIATE FILAMENTS; HUMAN VIMENTIN; GENE; CHROMOSOME-10; CARCINOGENS; ONCOGENES; MUTATION; GROWTH AB Transformation of the baby hamster kidney cell line BHK SN-10 by chemical carcinogens such as nitrosylmethylurea (NMU) is mediated by the loss of a gene product critical for the suppression of malignant transformation. Somatic cell hybrids between chemically transformed BHK SN-10 cells and either normal hamster kidney or human fibroblast cells are nontransformed; therefore, a recessive mechanism underlies the malignant transformation of BHK SN-10 cells after chemical carcinogenesis (A. Stoler and N.P. Bouck, Proc. Natl. Acad. Sci. USA 82:570-574, 1985). A human fibroblast cDNA library was constructed and introduced into NMU-transformed BHK SN-10 cells (NMU 34m) in order to identify a human cDNA capable of suppressing cellular transformation. NMU-transformed BHK cells were analyzed for reversion to an anchorage-dependent normal cellular phenotype after transfection with human cDNA. The human cDNA capable of inducing stable reversion of NMU 34m cells encodes the intermediate filament protein vimentin, which is apparently required for maintenance of the normal phenotype in BHK SN-10 cells. RP EIDEN, MV (reprint author), NIMH,CELL BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1991 VL 11 IS 10 BP 5321 EP 5329 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GJ401 UT WOS:A1991GJ40100056 PM 1922047 ER PT J AU WILLIAMS, AO MUTINGA, J RODGERS, M AF WILLIAMS, AO MUTINGA, J RODGERS, M TI LEISHMANIASIS IN A DOMESTIC GOAT IN KENYA SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE LEISHMANIASIS; GOAT; DNA AMPLIFICATION (PCR); ISOENZYMES ID KINETOPLAST DNA; KALA-AZAR; IDENTIFICATION; DIAGNOSIS; AMPLIFICATION; INFECTIONS; RESERVOIRS; DISTRICT; MALARIA; DOGS C1 INT CTR INSECT PHYSIOL & ECOL,NAIROBI,KENYA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP WILLIAMS, AO (reprint author), NIH,FOGARTY INT CTR,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 1991 VL 5 IS 5 BP 319 EP 325 DI 10.1016/S0890-8508(06)80002-2 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA GH383 UT WOS:A1991GH38300001 PM 1791852 ER PT J AU WONG, M RIUS, RA LOH, YP AF WONG, M RIUS, RA LOH, YP TI CHARACTERIZATION OF XENOPUS-LAEVIS PROENKEPHALIN GENE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE PROENKEPHALIN; XENOPUS; PROENKEPHALIN GENE ID CYCLIC-AMP; POSTERIOR PITUITARY; IDENTIFICATION; EXPRESSION; DNA; TRANSCRIPTION; SEQUENCES; ELEMENT; REGION; CELLS AB Enkephalins are opiate peptides found in a variety of tissues including brain and pituitary. In brain, they function as neurotransmitters, neuromodulators and neurohormones. Recent studies show that proenkephalin mRNA is expressed early in development both in mammals and the amphibian, suggesting that enkephalins may play a unique role in embryogenesis. In order to characterize factors which regulate the onset and patterning of expression of this gene in adult and developing frog embryos, the proenkephalin A gene was cloned from Xenopus laevis. The clones have been characterized by DNA sequencing and restriction endonuclease mapping. The gene is made up of three exons which span approximately 12 kb. Exon I encodes the 5' untranslated region of the mRNA. Exon II contains the signal peptide and the N terminus of the mature protein. Biologically active opioid peptides are generated from exon III. Comparison to mammalian proenkephalin genomic sequence indicated that nucleotide sequences of the 5' flanking region, noncoding exon I and exon II were not well conserved but exon III was highly conserved. Primer extension and RNase protection assay analyses of the RNA transcripts revealed two major 5' ends. The putative TATA box, CAAT box, CRE and Pit 1 elements have been identified on this gene by sequence homology to published consensus sequences. To assay for sequences that could potentially regulate Xenopus proenkephalin expression, we transfected constructs that contained upstream genomic sequences linked to the CAT reporter gene into various eukaryotic cell lines. The expression of the fusion gene constructs were detected and could be induced 10- to 30-fold upon treatment with forskolin. Although the Xenopus proenkephalin gene promoter does not share sequence homology with the mammalian promoter, it was found to be transcriptionally active upon transfection into mammalian cell lines, indicating that at least some of the transacting factors required for expression are conserved through evolution. RP WONG, M (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,RM 2A21,BETHESDA,MD 20892, USA. NR 30 TC 17 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1991 VL 11 IS 3-4 BP 197 EP 205 DI 10.1016/0169-328X(91)90028-V PG 9 WC Neurosciences SC Neurosciences & Neurology GA GM373 UT WOS:A1991GM37300002 ER PT J AU SHINODA, H NADI, NS SCHWARTZ, JP AF SHINODA, H NADI, NS SCHWARTZ, JP TI ALTERATIONS IN SOMATOSTATIN AND PROENKEPHALIN MESSENGER-RNA IN RESPONSE TO A SINGLE AMYGDALOID STIMULATION VERSUS KINDLING SO MOLECULAR BRAIN RESEARCH LA English DT Article DE SOMATOSTATIN MESSENGER RNA; PROENKEPHALIN MESSENGER RNA; KINDLING; INSITU HYBRIDIZATION; ELECTRICAL STIMULATION; HIPPOCAMPUS; OLFACTORY CORTEX ID IMMUNOREACTIVE SOMATOSTATIN; ELECTRICAL-STIMULATION; GENE-EXPRESSION; RAT HIPPOCAMPUS; INCREASES; BRAIN; HYBRIDIZATION; ENKEPHALIN; SEIZURES; BIOSYNTHESIS AB Previous studies have shown changes in both somatostatin (SS)- and proenkephalin(PE)-derived peptides in the brains of amygdaloid-kindled rats, suggesting possible roles for the peptides in the kindling process. In this study, we have extended this analysis by looking at the time course of changes in SS and PE mRNAs at various times after kindling, in comparison with a single non-convulsive stimulation. Blot analysis of total RNA showed increases in SS mRNA in striatum, frontal cortex and hippocampus of animals receiving only a single stimulation as well as kindled animals - the increase occurred 1-3 days following stimulation and levels were back to basal by 1 week. PE mRNA did not change. In situ hybridization analysis, one day after the last kindling stimulation, showed significant elevations of SS mRNA in CA1, CA2 and dentate gyrus of hippocampus and of PE mRNA in olfactory cortex that were specific to kindling. However, both a single stimulation and kindling increased PE mRNA in olfactory tubercle and arcuate nucleus. In contrast, a single electrical stimulus increased PE mRNA in ventral striatum and SS mRNA in cingulate cortex and olfactory tubercle. These data support the idea that changes of SS mRNA in hippocampus and of PE mRNA in olfactory cortex may be related to kindling, and point out the importance of using animals which receive a single electrical stimulus, rather than sham-operated animals, as controls. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 9,ROOM 1W115,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 25 TC 43 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1991 VL 11 IS 3-4 BP 221 EP 226 DI 10.1016/0169-328X(91)90030-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA GM373 UT WOS:A1991GM37300004 ER PT J AU PEREZ, N SUGAR, J CHARYA, S JOHNSON, G MERRIL, C BIERER, L PERL, D HAROUTUNIAN, V WALLACE, W AF PEREZ, N SUGAR, J CHARYA, S JOHNSON, G MERRIL, C BIERER, L PERL, D HAROUTUNIAN, V WALLACE, W TI INCREASED SYNTHESIS AND ACCUMULATION OF HEAT-SHOCK 70 PROTEINS IN ALZHEIMERS-DISEASE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE HEAT SHOCK PROTEIN; ALZHEIMERS DISEASE; GENE EXPRESSION; POLYSOME; STRESS RESPONSE; PROTEIN SYNTHESIS; COTRANSLATIONAL PROCESSING ID MESSENGER-RNA; BRAIN; PHOSPHORYLATION; TRANSLATION; PRECURSOR; UBIQUITIN; CELLS AB Postmortem cortical tissues from Alzheimer's disease cases were found to contain significantly higher levels of the heat shock proteins hsp 72 and hsp 73 than control cortical tissues. This elevation was associated with the disease pathology in that it was not observed in Alzheimer's disease cerebella and was not correlated with perimortem characteristics such as age or cause of death of the patient or postmortem interval of the brain tissue. Examination of polysome translation products on two dimensional gels and by immunoprecipitation indicated that the syntheses of hsp 72/73 were increased in Alzheimer's disease tissues. In addition, immunoprecipitation of newly synthesized hsp 72 showed that numerous other nascent polypeptides were co-precipitated, which indicates an irreversible cotranslational association with the hsp 72. These results indicate that induction of specific heat shock proteins is associated with Alzheimer's disease and that cotranslational processes are affected by this induction. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,MACK LAB,1 GUSTAVE LEVY PL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,ARTHUR FISHBERG CTR NEUROBIOL,NEW YORK,NY 10029. NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. NR 35 TC 99 Z9 101 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1991 VL 11 IS 3-4 BP 249 EP 254 DI 10.1016/0169-328X(91)90033-T PG 6 WC Neurosciences SC Neurosciences & Neurology GA GM373 UT WOS:A1991GM37300007 ER PT J AU KITAMURA, M BUCZKO, E DUFAU, ML AF KITAMURA, M BUCZKO, E DUFAU, ML TI DISSOCIATION OF HYDROXYLASE AND LYASE ACTIVITIES BY SITE-DIRECTED MUTAGENESIS OF THE RAT P45017-ALPHA SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SIDE-CHAIN CLEAVAGE; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; MICROSOMAL CYTOCHROME-P-450; P-45017-ALPHA CDNA; MEMBRANE; TESTIS; SEQUENCE; EXPRESSION; ENZYMES; GENE AB Site-directed mutagenesis of the arginine-rich region within the putative active site of the rat testicular P450(17-alpha) (17-alpha-hydroxylase cytochrome P-450, the product of P450XVII gene) was performed to identify specific amino acids that contribute to either the hydroxylase or lyase activities catalyzed by this enzyme. The conversion of Arg346 to alanine differentially abolished lyase activity without affecting hydroxylase activity, resulting in an accumulation of the 17-alpha-hydroxylated intermediate, and partial lyase activity was recovered by conversion of this mutant to Lys346. Similar results were obtained with the conversion of Arg357 to alanine, although this mutant also diminished hydroxylase activity, and full lyase and hydroxylase activities were recovered with a lysine in this position. Major reductions in hydroxylase activity were apparent with the conversion of Arg363 to Ala, and this inhibition was reversed by a lysine at position 363. In contrast, differential effects were not observed with the mutants Arg361Ala, Arg361Lys, or Tyr334Phe. Both mutations at the Arg361 position resulted in a total loss of hydroxylase and lyase activities, and mutation at the Tyr334 position had no effect on either activity. The identification of specific amino acids that are essential for either the hydroxylase or lyase reaction indicates that the steroid substrate-protein interaction changes during the course of the two consecutive reactions and reveals the potential for separation of the two activities by chemical and biological modulators within the active site region of the P450(17-alpha). C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BLDG 10,ROOM B1-L400,BETHESDA,MD 20892. NR 34 TC 62 Z9 62 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1991 VL 5 IS 10 BP 1373 EP 1380 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GL389 UT WOS:A1991GL38900003 PM 1723139 ER PT J AU BELLAND, RJ AF BELLAND, RJ TI H-DNA FORMATION BY THE CODING REPEAT ELEMENTS OF NEISSERIAL OPA GENES SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEINS; PHASE VARIATION; GONOCOCCUS INFECTION; ESCHERICHIA-COLI; COLONY OPACITY; GONORRHOEAE; SEQUENCE; REGION; EXPRESSION; PLASMIDS AB The coding repeat region of opa genes from Neisseria gonorrhoeae and Neisseria meningitidis determines the expression state of their respective genes through high-frequency addition or deletion of pentanucleotide coding repeat units (CRs; CTTCT). In vitro analyses of cloned opa gene CR regions using single-strand specific nucleases, oligonucleotide protection experiments, and modifications of non-B-DNA residues indicate that the regions form structures resembling H-DNA under acidic conditions in the presence of negative supercoiling. The purine/pyrimidine strand bias and H-palindromic nature of the repeat region are consistent with sequence requirements for H-DNA formation. Sequences flanking the repeat elements are required to form the H-DNA structure in vitro as judged by the pattern of exposed non-B-DNA residues in CR sequences synthesized as oligonucleotides to form beta-galactosidase::CR translational fusions. The fusions phase vary by addition and deletion of CR elements and the rate of phase variation increases upon induction of the fusion genes. The opa gene CR region is the first reported bacterial H-DNA structure and is unique in that it lies within the coding sequence for the gene. RP BELLAND, RJ (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 48 TC 19 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1991 VL 5 IS 10 BP 2351 EP 2360 DI 10.1111/j.1365-2958.1991.tb02081.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GL954 UT WOS:A1991GL95400008 PM 1791751 ER PT J AU GILMORE, RD CIEPLAK, W POLICASTRO, PF HACKSTADT, T AF GILMORE, RD CIEPLAK, W POLICASTRO, PF HACKSTADT, T TI THE 120 KILODALTON OUTER-MEMBRANE PROTEIN (ROMP-B) OF RICKETTSIA-RICKETTSII IS ENCODED BY AN UNUSUALLY LONG OPEN READING FRAME - EVIDENCE FOR PROTEIN PROCESSING FROM A LARGE PRECURSOR SO MOLECULAR MICROBIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; SPOTTED-FEVER; FILAMENTOUS HEMAGGLUTININ; BORDETELLA-PERTUSSIS; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; STRAINS; PROWAZEKII; VIRULENCE; ANTIGENS AB A Rickettsia rickettsii outer surface membrane protein (rOmp B), of an apparent molecular mass of 120 kilodaltons, is a major surface antigen of the Rickettsiae that displays genus, species, and sub-species specific antigenic determinants. The 5' portion of this gene was found to be unstable in plasmids, but was stably cloned in a lambda vector. The nucleotide sequence of the 5' terminus has been determined, thus completing the DNA sequence of the entire gene. Genetic analysis revealed an unusually large open reading frame with the capacity to encode a product much larger than the mature protein. A 32 kilodalton peptide from purified rickettsiae was isolated and the amino terminus was sequenced, which revealed that the peptide is encoded by the 3' portion of this large open reading frame. This suggests a role for post-translational processing of rOmp B from a large precursor molecule. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. RP GILMORE, RD (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 35 TC 70 Z9 74 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1991 VL 5 IS 10 BP 2361 EP 2370 DI 10.1111/j.1365-2958.1991.tb02082.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GL954 UT WOS:A1991GL95400009 PM 1724278 ER PT J AU HIDE, M ALI, H PRICE, SR MOSS, J BEAVEN, MA AF HIDE, M ALI, H PRICE, SR MOSS, J BEAVEN, MA TI GTP-BINDING PROTEIN-G-ALPHA-Z - ITS DOWN-REGULATION BY DEXAMETHASONE AND ITS CREDENTIALS AS A MEDIATOR OF ANTIGEN-INDUCED RESPONSES IN RBL-2H3 CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; CATALYZED ADP-RIBOSYLATION; BETA-ADRENERGIC RECEPTORS; ISLET-ACTIVATING PROTEIN; PERTUSSIS TOXIN; CHOLERA-TOXIN; MAST-CELLS; PHOSPHOLIPASE-C; HISTAMINE-RELEASE; SYNERGISTIC SIGNALS AB We have investigated the possible role of guanine nucleotide-binding proteins in the process of antigen-induced exocytosis in a cultured rat mast cell line, RBL-2H3 cells. The mRNAs for the alpha-subunits of the guanine nucleotide-binding proteins G-alpha-s (short and long forms), G-alpha-i-2, G-alpha-i-3, and G-alpha-z were detected by hybridization with G-alpha-specific oligonucleotide probes. The corresponding proteins were identified in membranes of RBL-2H3 cells on the basis of size, immunoreactivity with specific antibodies, and their ability to serve as substrates for ADP-ribosylation by cholera toxin or pertussis toxin. Treatment of cells with as little as 10(-9) to 10(-7) M dexamethasone markedly decreased the amount of G-alpha-z mRNA and membrane G-alpha-z, as well as the responsiveness of the cells to antigen stimulation. In the same cells, the exposure to dexamethasone caused an increase in the amounts of certain other G-alpha subunits, particularly G-alpha-i-3, and in the responsiveness of the cells to an adenosine analog, N(ethylcarboxamido)-adenosine. Because of the apparent decrease in G-alpha-z mRNA and protein in dexamethasone-treated cells and the fact that neither cholera toxin nor pertussis toxin inhibits the stimulatory signals to antigen [J. Biol. Chem, 265:745-753 (1990)], we suggest that G-alpha-z is a potential candidate for regulating the early signals in antigen-stimulated RBL-2H3 cells. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N114,BETHESDA,MD 20892. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 52 TC 36 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1991 VL 40 IS 4 BP 473 EP 479 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK821 UT WOS:A1991GK82100003 PM 1921983 ER PT J AU LELONG, IH GUZIKOWSKI, AP HAUGLAND, RP PASTAN, I GOTTESMAN, MM WILLINGHAM, MC AF LELONG, IH GUZIKOWSKI, AP HAUGLAND, RP PASTAN, I GOTTESMAN, MM WILLINGHAM, MC TI FLUORESCENT VERAPAMIL DERIVATIVE FOR MONITORING ACTIVITY OF THE MULTIDRUG TRANSPORTER SO MOLECULAR PHARMACOLOGY LA English DT Article ID RESISTANT HUMAN-CELLS; ASCITES TUMOR-CELLS; CARCINOMA-CELLS; CYTO-TOXICITY; DRUG ACCUMULATION; MEMBRANE-VESICLES; CROSS-RESISTANCE; P-GLYCOPROTEIN; VINBLASTINE; RHODAMINE-123 AB Multidrug resistance to amphipathic natural product chemotherapeutic drugs is conferred on cancer cells by expression of the MDR1 gene, which encodes the 170-kDa multidrug transporter known as P glycoprotein. The P glycoprotein-mediated efflux of toxic chemotherapeutic drugs can be reversed by agents such as verapamil, which is a substrate for the multidrug transporter and appears to be a competitive inhibitor of the efflux pump. In this study, Bodipy-verapamil, a fluorescent derivative of verapamil, has been shown to be a substrate for the efflux pump activity of P glycoprotein. Single-cell fluorescence analysis reveals that Bodipy-verapamil accumulates in lysosomes of drug-sensitive NIH3T3 and KB cells but is rapidly effluxed from multidrug-resistant derivatives of these cell lines. Although Bodipy-verapamil is a substrate for the multidrug transporter, it is not an efficient inhibitor of the pump and does not reverse resistance to vinblastine and colchicine as effectively as does verapamil. This new derivative may be a useful tool for imaging of lysosomes in drug-sensitive cells and for rapid screening for the multidrug-resistant phenotype in other cell types. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM IB22,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. MOLEC PROBES INC,EUGENE,OR 97402. NR 26 TC 45 Z9 45 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1991 VL 40 IS 4 BP 490 EP 494 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GK821 UT WOS:A1991GK82100005 PM 1681415 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI CLINICAL IMMUNOLOGY - PAST, PRESENT AND FUTURE CHALLENGES AND PROSPECTS SO NETHERLANDS JOURNAL OF MEDICINE LA English DT Article DE CLINICAL IMMUNOLOGY; CLINICAL RESEARCH; ENZYME DEFICIENCY; GENE TRANSFER; IMMUNODEFICIENCY; IMMUNOTHERAPY; INTERLEUKIN; IL-2 RECEPTOR ID ADENOSINE-DEAMINASE DEFICIENCY; T-CELLS; IMMUNOGLOBULIN GENES; IMMUNOTHERAPY; LYMPHOCYTES; DISEASE; MYELOMA AB Over the past four decades, immunology has undergone a revolution changing from a largely phenomenological science into a deeply analytical and technical field. Questions concerning the primary cell involved in cell-mediated immunity, the mechanisms responsible for antibody diversity as well as the molecules used by the network of immunological cells to communicate with one another that could barely be asked in the 1950s, have been definitely answered. A major contributor to this revolution in immunological knowledge has been the scientist focussing on patient-oriented clinical immunology, a form of clinical research requiring the presence of the patient or materials freshly derived from the patient. This type of research has led to the discovery of new diseases, the definition of new infectious agents causing disease and the delineation of functional defects using applied variables on mononuclear cells removed from the patient. Moreover, this type of research is absolutely required to test hypotheses concerning the pathogenesis of disease in humans and to provide the scientific basis for the development of new approaches to therapy. As I look to the future, there are great threats to patient-oriented clinical research. The road ahead seems long and daunting. Nevertheless, I am encouraged that the patient-oriented clinical research scientist in the future will make major contributions to the use of the immune system in preventing human disease, in the development of immunological methods for diagnosis, and in the use of immune intervention to provide a new perspective for the prevention of allograft rejection, and for the treatment of neoplastic, immunodeficiency, and autoimmune disease. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0300-2977 J9 NETH J MED JI Neth. J. Med. PD OCT PY 1991 VL 39 IS 3-4 BP 322 EP 328 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GN657 UT WOS:A1991GN65700027 PM 1791894 ER PT J AU RAY, P MONROE, FL BERMAN, JD FIEDLER, J AF RAY, P MONROE, FL BERMAN, JD FIEDLER, J TI CYANIDE SENSITIVE AND INSENSITIVE BIOENERGETICS IN A CLONAL NEUROBLASTOMA X GLIOMA HYBRID CELL-LINE SO NEUROCHEMICAL RESEARCH LA English DT Article DE NG108-15 CELLS; CYANIDE; 2-DEOXY GLUCOSE; ATP DEPLETION; METABOLIC INHIBITION; CYANIDE ANTIDOTE ID INTOXICATION; CULTURE; ANTAGONISM; MECHANISMS AB The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which posses numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG): cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06 - 0.18 mM) for 5 min prevented the depression of both [H-3]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. RP RAY, P (reprint author), WALTER REED ARMY MED CTR,DEPT BIOL,DIV EXPTL THERAPEUT,WASHINGTON,DC 20307, USA. RI Fiedler, Jenny/I-5617-2016 NR 21 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD OCT PY 1991 VL 16 IS 10 BP 1121 EP 1124 DI 10.1007/BF00966589 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GK148 UT WOS:A1991GK14800003 PM 1795758 ER PT J AU RAPOPORT, SI PETTIGREW, KD SCHAPIRO, MB AF RAPOPORT, SI PETTIGREW, KD SCHAPIRO, MB TI DISCORDANCE AND CONCORDANCE OF DEMENTIA OF THE ALZHEIMER TYPE (DAT) IN MONOZYGOTIC TWINS INDICATE HERITABLE AND SPORADIC FORMS OF ALZHEIMERS-DISEASE SO NEUROLOGY LA English DT Article ID IDENTICAL-TWINS; CHROMOSOME-21; GENETICS; MARKERS; FEATURES; LINKAGE AB Monozygotic (MZ) twin pairs concordant for dementia of the Alzheimer type (DAT) or for proven Alzheimer's disease (AD) have a significantly higher frequency of a positive family history (DAT or AD in at least one first-degree relative, p < 0.002) than do discordant MZ twin pairs, consistent with a lesser predicted distribution of proportions of surviving first-degree relatives without DAT (or AD) (p < 0.001). The results suggest that concordant MZ twin pairs with DAT (or AD) have a heritable form of disease. AD in discordant twins may result from environmental influences or from a somatic chromosomal change following zygotic division. C1 NIMH,DIV BIOMETRY & APPL SCI,BETHESDA,MD 20892. RP RAPOPORT, SI (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892, USA. NR 43 TC 37 Z9 37 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1991 VL 41 IS 10 BP 1549 EP 1553 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA GK878 UT WOS:A1991GK87800004 PM 1922794 ER PT J AU BASER, SM MEER, J POLINSKY, RJ HALLETT, M AF BASER, SM MEER, J POLINSKY, RJ HALLETT, M TI SUDOMOTOR FUNCTION IN AUTONOMIC FAILURE SO NEUROLOGY LA English DT Article ID MULTIPLE SYSTEM ATROPHY; SYMPATHETIC SKIN-RESPONSE; AXON REFLEX TEST; ORTHOSTATIC HYPOTENSION; NERVOUS-SYSTEM AB We measured sweat production to direct gland stimulation with intradermal methacholine in patients with autonomic failure and in normal subjects. The sympathetic skin response (SSR) to electrical stimulation was assessed in some of the same subjects. Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) produced significantly less sweat than controls. None of the patients manifested greater than normal sweat production. Impaired sweat gland function does not differentiate MSA and PAF. The SSR did not correlate with sweat response to methacholine. An SSR can occur in the absence of normal sweat gland function. The diminished production of sweat in response to intradermal methacholine in PAF suggests that human sweat glands do not develop chronic denervation supersensitivity. Intradermal methacholine is a simple method to assess sweat gland function. C1 NINCDS,CLIN NEUROSCI BRANCH,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. CARMEL HOSP,DEPT NEUROL,HAIFA,ISRAEL. NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NR 29 TC 48 Z9 50 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1991 VL 41 IS 10 BP 1564 EP 1566 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA GK878 UT WOS:A1991GK87800008 PM 1922796 ER PT J AU KURTZKE, JF FLATEN, TP MURPHY, FM AF KURTZKE, JF FLATEN, TP MURPHY, FM TI DEATH RATES FROM PARKINSONS-DISEASE IN NORWAY REFLECT INCREASED SURVIVAL SO NEUROLOGY LA English DT Note AB Age-specific death-rate curves for Parkinson's disease in Norway for 1970 to 1974 and 1980 to 1985 were very similar in configuration to those at like periods in the United States and Denmark. As with the United States and Denmark, the pattern of a steady, progressive increase with age in the 1980s reverted to the earlier configurations, which showed maximal rates near ages 80, when the Norwegian rates were recalculated by attributing all deaths to ages 5 years younger. C1 VET AFFAIRS MED CTR,NEUROEPIDEMIOL RES PROGRAM,WASHINGTON,DC 20422. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. UNIV TRONDHEIM,AVH,DEPT CHEM,TRONDHEIM,NORWAY. RP KURTZKE, JF (reprint author), VET AFFAIRS MED CTR,NEUROL SERV,WASHINGTON,DC 20422, USA. RI Flaten, Trond Peder/I-3756-2013 NR 6 TC 14 Z9 14 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1991 VL 41 IS 10 BP 1665 EP 1667 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA GK878 UT WOS:A1991GK87800027 PM 1922813 ER PT J AU STENT, GS AF STENT, GS TI BRIDGING THE GAP BETWEEN TOP-DOWN AND BOTTOM-UP WILSON,ALLAN,C. 1934-1991 SO NEW BIOLOGIST LA English DT Editorial Material RP STENT, GS (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD OCT PY 1991 VL 3 IS 10 BP 911 EP 913 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GL955 UT WOS:A1991GL95500001 PM 1768649 ER PT J AU BAILLON, JG NASHED, NT KUMAR, A WILSON, SH JERINA, DM AF BAILLON, JG NASHED, NT KUMAR, A WILSON, SH JERINA, DM TI A LEUCINE ZIPPER-LIKE MOTIF MAY MEDIATE HIV REVERSE-TRANSCRIPTASE SUBUNIT BINDING SO NEW BIOLOGIST LA English DT Letter ID COMPLETE NUCLEOTIDE-SEQUENCE; CELL LEUKEMIA-VIRUS; AIDS VIRUS; IMMUNODEFICIENCY-VIRUS; PROTEIN CONFORMATION; RNASE-H; DOMAIN; DNA; RETROVIRUS; PEPTIDES C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 39 TC 31 Z9 31 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD OCT PY 1991 VL 3 IS 10 BP 1015 EP 1019 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GL955 UT WOS:A1991GL95500015 PM 1722701 ER PT J AU GOLDENBERG, RL TAMURA, T CLIVER, SP CUTTER, GR HOFFMAN, HJ DAVIS, RO AF GOLDENBERG, RL TAMURA, T CLIVER, SP CUTTER, GR HOFFMAN, HJ DAVIS, RO TI MATERNAL SERUM ALPHA2-MACROGLOBULIN AND FETAL GROWTH-RETARDATION SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ALPHA-2-MACROGLOBULIN DEFICIENCY; GESTATIONAL-AGE AB Maternal serum alpha-2-macroglobulin levels were measured twice, at approximately 18 and 30 weeks' gestation, in 289 pregnant women who later delivered at or after 37 weeks. Levels were elevated as early as 18 weeks' gestation in women destined to have a growth-retarded infant, and this elevation persisted through 30 weeks' gestational age. Furthermore, levels were higher in white women than black, in smokers than in non-smokers, and in thin than in heavier women. When the effect of alpha-2-macroglobulin on birth weight was evaluated in a multiple regression analysis adjusting for gestational age, race, body size, smoking, fetal sex, and a history of a low birth weight infant, high alpha-2-macroglobulin levels were associated with a statistically significant decrease in birth weight. The effect was greater in women who smoked. This relationship did not appear to be associated with differences in serum zinc or hematocrit levels. C1 UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. RP GOLDENBERG, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,UNIV STN,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 15 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1991 VL 78 IS 4 BP 594 EP 599 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA GH117 UT WOS:A1991GH11700005 PM 1717906 ER PT J AU BENNETT, WP HOLLSTEIN, MC HE, A ZHU, SM RESAU, JH TRUMP, BF METCALF, RA WELSH, JA MIDGLEY, C LANE, DP HARRIS, CC AF BENNETT, WP HOLLSTEIN, MC HE, A ZHU, SM RESAU, JH TRUMP, BF METCALF, RA WELSH, JA MIDGLEY, C LANE, DP HARRIS, CC TI ARCHIVAL ANALYSIS OF P53 GENETIC AND PROTEIN ALTERATIONS IN CHINESE ESOPHAGEAL CANCER SO ONCOGENE LA English DT Article ID CELLULAR TUMOR-ANTIGEN; TRANSFORMED-CELLS; BREAST-CANCER; SV40-TRANSFORMED CELLS; MATE DRINKING; LUNG-CANCER; WILD-TYPE; KI-RAS; MUTATIONS; EXPRESSION AB A strategy and methods for archival analysis of genetic and protein alterations in the p53 tumor-suppressor gene are presented. The tumor series includes 43 paraffin-embedded esophageal carcinomas from two high-incidence regions in the People's Republic of China. More than half contained elevated p53 protein levels which were detected by a high-titer polyclonal antiserum and a sensitive immunohistochemical method. To estimate the frequency of underlying mutations, DNA was isolated from conventional paraffin sections, amplified by the polymerase chain reaction, and examined by dideoxy termination sequencing. Analysis of exons 5-8 in a subset of 10 tumors revealed mis-sense point mutations in 4 out of 5 immunostain-positive tumors and a mutation encoding a stop codon in 1 of 5 immunostain-negative tumors. In this report of archival material, we conclude that detectable levels of p53 protein correlate closely with the occurrence of mis-sense mutations. Furthermore, these methods render large repositories of paraffin-embedded tumor and non-tumor tissues accesible to analysis. Immunohistochemical screening for elevated protein levels followed by sequence analysis represents an efficient strategy for the evaluation of the p53 mutational spectrum. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892. CHINA MED UNIV,CANC RES INST,SHENYANG,PEOPLES R CHINA. SUN YAT-SAN UNIV MED SCI,GUANGZHOU,PEOPLES R CHINA. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. UNIV DUNDEE,INST MED SCI,CANC RES CAMPAIGN LAB,DUNDEE DD1 4HN,SCOTLAND. RI Lane, David/C-4920-2008 NR 54 TC 202 Z9 203 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1991 VL 6 IS 10 BP 1779 EP 1784 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX118 UT WOS:A1991GX11800009 PM 1923503 ER PT J AU PEREGO, R RON, D KRUH, GD AF PEREGO, R RON, D KRUH, GD TI ARG ENCODES A WIDELY EXPRESSED 145 KDA PROTEIN TYROSINE KINASE SO ONCOGENE LA English DT Note ID CHRONIC MYELOGENOUS LEUKEMIA; C-ABL; PHILADELPHIA-CHROMOSOME; GENE-PRODUCT; ONCOGENE; PHOSPHORYLATION; TRANSDUCTION; ACTIVATION; CELLS; K562 AB Arg encodes a protein highly related to the c-abl gene product with regard to overall structural architecture as well as the amino acid sequences of their tyrosine kinase, and src-homologous 2 and 3 domains. The two genes form a distinct subfamily of non-receptor tyrosine kinases and share a common homolog in Drosophila. In this study we characterized the arg protein product by expression of its coding sequence in bacteria. The recombinant arg protein was detected in bacterial lysates by immunoblotting and exhibited a molecular mass of 145 kDa. Phosphoamino acid analysis of the arg gene product following an immune complex autokinase reaction revealed tyrosine phosphorylation and established that it possesses tyrosine kinase activity. High-titer antibody capable of detecting the cellular arg gene product was generated by expressing a carboxy-terminal segment of arg in bacteria and using the recombinant protein as an immunogen. The arg gene product was identified in cultured human cells as a 145 kDa protein that exhibited autokinase activity. Analysis of arg expression in murine tissues revealed that arg, like c-abl, is widely expressed, further extending the similarities between the two genes, and suggesting that arg probably functions in signaling pathways fundamental to many cell types. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV MILAN,INST GEN PATHOL,I-20122 MILAN,ITALY. CNR,CTR RES CELL PATHOL,I-20133 MILAN,ITALY. TECHNION ISRAEL INST TECHNOL,FAC BIOL,IL-32000 HAIFA,ISRAEL. NR 24 TC 39 Z9 39 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1991 VL 6 IS 10 BP 1899 EP 1902 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX118 UT WOS:A1991GX11800025 PM 1923513 ER PT J AU DUBNER, R AF DUBNER, R TI A CALL FOR MORE SCIENCE, NOT MORE RHETORIC, REGARDING OPIOIDS AND NEUROPATHIC PAIN SO PAIN LA English DT Editorial Material ID TOOTH-PULP SENSATIONS; INTENSITY RP DUBNER, R (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 1991 VL 47 IS 1 BP 1 EP 2 DI 10.1016/0304-3959(91)90002-F PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA GM053 UT WOS:A1991GM05300001 PM 1771084 ER PT J AU DIAMOND, LS AF DIAMOND, LS TI VIRUSES OF PARASITIC PROTOZOA SO PARASITOLOGY TODAY LA English DT Letter ID ENTAMOEBA-HISTOLYTICA RP DIAMOND, LS (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD OCT PY 1991 VL 7 IS 10 BP 276 EP 276 DI 10.1016/0169-4758(91)90094-5 PG 1 WC Parasitology SC Parasitology GA GJ032 UT WOS:A1991GJ03200007 PM 15463388 ER PT J AU KURINIJ, N SHIONO, PH AF KURINIJ, N SHIONO, PH TI EARLY FORMULA SUPPLEMENTATION OF BREAST-FEEDING SO PEDIATRICS LA English DT Article DE BREAST-FEEDING; INFANT FORMULA; SUPPLEMENTATION ID DURATION AB Factors influencing early formula supplementation in breast-fed neonates were examined among 726 women who were delivered of their first child in one of three metropolitan Washington, DC, hospitals. Thirty-seven percent of breast-fed neonates were given supplementary formula in the hospital. Mothers who gave birth at a university hospital were more likely to breast-feed exclusively (adjusted odds ratio 3.5; 95% confidence limit 2.1 to 5.9), after adjustment for maternal demographics, hospital factors (such as time of first breast-feed, demand feeding, delivery type, and rooming-in), and the maternal breast-feeding commitment. Aside from delivery hospital, a strong predictor of formula use was the time between birth and initiation of the first breast-feed. The longer a mother waited to initiate breast-feeding the more likely she was to use formula; the adjusted odds ratios for women who initiated breast-feeding 2 to 6 hours, 7 to 11 hours, and 12 or more hours postpartum were 1.1, 0.5, and 0.2, respectively. Feeding the baby on demand, having a vaginal delivery, deciding to breast-feed before pregnancy, having a college education, and being married also were moderately, though significantly, predictive of exclusive breast-feeding. The findings suggest that hospital influences can promote formula use and indirectly shorten breast-feeding duration, particularly those hospital practices that delay early initiation of breast-feeding. C1 DAVID & LUCILLE PACKARD FDN,CTR FUTURE CHILDREN,LOS ALTOS,CA. RP KURINIJ, N (reprint author), NEI,COLLABORAT CLIN RES BRANCH,BETHESDA,MD 20892, USA. NR 14 TC 61 Z9 62 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1991 VL 88 IS 4 BP 745 EP 750 PG 6 WC Pediatrics SC Pediatrics GA GY801 UT WOS:A1991GY80100011 PM 1896277 ER PT J AU CAPORASO, N LANDI, MT VINEIS, P AF CAPORASO, N LANDI, MT VINEIS, P TI RELEVANCE OF METABOLIC POLYMORPHISMS TO HUMAN CARCINOGENESIS - EVALUATION OF EPIDEMIOLOGIC EVIDENCE SO PHARMACOGENETICS LA English DT Review AB Genetic modulation of environmental exposures associated with common malignancies (lung and bladder) is an attractive mechanism to explain differential susceptibility to tobacco or occupation related carcinogens in the population. Epidemiologic studies to test the hypothesis of such associations and to evaluate evidence for a causal role for genetic factors in the etiology of chemically-induced tumors are challenging and require the close collaboration of epidemiologists, clinicians and laboratory investigators. In this work we review the evidence for an association of three polymorphisms of drug or xenobiotic metabolism with human cancers. Methodologic considerations and data relevant to evaluating a causal role for each polymorphism are considered. Fair to good support for both an association of the acetylation phenotype with occupationally-related bladder cancer and for an association of the debrisoquine metabolic phenotype and lung cancer is found, although in neither case is the evidence completely convincing. Epidemiologic evidence for the association of aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of difficulties in the assay and subsequent confounding factors. DNA based assays are at various stages of development for each of the genotypes and promise to simplify future studies while introducing new methodologic pitfalls. Further studies in all three areas are warranted as each has important implications for the understanding of the carcinogenic process, etiology and the public health aspects of common malignancies. RP CAPORASO, N (reprint author), NCI,EPIDEMIOL & BIOSTAT BRANCH,FAMILY STUDIES SECT,439 EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 0 TC 157 Z9 157 U1 1 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1991 VL 1 IS 1 BP 4 EP 19 DI 10.1097/00008571-199110000-00003 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA LG848 UT WOS:A1991LG84800002 PM 1844821 ER PT J AU SZEKELY, JI SHARPE, LG JAFFE, JH AF SZEKELY, JI SHARPE, LG JAFFE, JH TI INDUCTION OF PHENCYCLIDINE-LIKE BEHAVIOR IN RATS BY DEXTRORPHAN BUT NOT DEXTROMETHORPHAN SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE DEXTROMETHORPHAN; DEXTRORPHAN; DRUG ABUSE; PHENCYCLIDINE; LOCOMOTOR ACTIVITY; STEREOTYPY ID INDUCED STEREOTYPED BEHAVIOR; GUINEA-PIG BRAIN; BINDING-SITES; AFFINITY; RECEPTOR; OPIOIDS; METABOLITES; CONVULSIONS; GLUTAMATE; MEMBRANES AB The behavioral effects of dextromethorphan (DM), dextrorphan (DO) and phencyclidine (PCP) were compared in rats. DO (15-120 mg/kg) was similar to PCP (1.25-20 mg/kg) in including dose-dependent locomotor hyperactivity, streotypy and ataxia. 15-120 mg/kg) induced moderate hyperactivity only at the higher doses about 45 min after treatment. DM and DO modified the locomotor facilitation induced by 10 mg/kg PCP in opposite directions. Pretreatment with DO facilitated, whereas DM dose-dependently inhibited PCP-elicited hyperactivity. Although the metabolism of DM in rats is unknown, the recently reported abuse of DM in humans may occur by its conversion to DO in the organism, i.e., to a metabolite which produces PCP-like effects. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. NR 32 TC 53 Z9 53 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 1991 VL 40 IS 2 BP 381 EP 386 DI 10.1016/0091-3057(91)90569-N PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GQ882 UT WOS:A1991GQ88200031 PM 1805242 ER PT J AU ROTHMAN, RB MELE, A REID, AA AKUNNE, HC GREIG, N THURKAUF, A DECOSTA, BR RICE, KC PERT, A AF ROTHMAN, RB MELE, A REID, AA AKUNNE, HC GREIG, N THURKAUF, A DECOSTA, BR RICE, KC PERT, A TI GBR12909 ANTAGONIZES THE ABILITY OF COCAINE TO ELEVATE EXTRACELLULAR LEVELS OF DOPAMINE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE COCAINE; DOPAMINE; MICRODIALYSIS; DOPAMINE TRANSPORT ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; INVIVO MICRODIALYSIS; HEALTHY-VOLUNTEERS; NOMIFENSINE; INCREASE; AMPHETAMINE; PHENCYCLIDINE; INHIBITORS; BUPROPION AB Rats were administered various IP doses of the high-affinity dopamine (DA) reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[phenylpropyl]piperazine (GBR12909). The caudate nuclei were removed 60 min after drug administration and stored at -70-degrees-C. Striatal membranes were prepared later. The results demonstrated that GBR12909 produced a dose-dependent decrease in the binding of [H-3]cocaine or [H-3]GBR12935 to the DA transporter (ED50 about 10 mg/kg). Saturation binding studies with [H-3]GBR12935 showed that this was due to both an increase in the K(d), due to residual drug, and to a decrease in the B(max). At a dose of 25 mg/kg IP, GBR12909 produced a 50% decrease in the B(max), and a 3.4-fold increase in the K(d). In the in vivo microdialysis studies, GBR12909 (25 mg/kg IP) produced a modest, long-lasting and stable elevation of extracellular DA. Administration of cocaine through the microdialysis probe to rats pretreated with either saline or GBR12909 (25 mg/kg IP) produced a dose-dependent increase in extracellular DA in both groups. GBR12909 inhibited cocaine-induced increases in extracellular DA by about 50% at all doses. These data collectively indicate that at a dose sufficient to decrease by 50% the B(max) of [H-3]GBR12935 binding sites, GBR12909 antagonizes the ability of cocaine to elevate extracellular DA by 50%. Further studies will be needed to evaluate a possible role for GBR12909 in the medical treatment of cocaine addiction. C1 NIDDK,MED CHEM LAB,RECEPTOR STUDIES UNIT,BLDG 10-3D41,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIDDK,MED CHEM LAB,DRUG DESIGN & SYNTH SECT,BETHESDA,MD 20892. RI Mele, Andrea/E-7741-2015 NR 49 TC 130 Z9 130 U1 7 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 1991 VL 40 IS 2 BP 387 EP 397 DI 10.1016/0091-3057(91)90570-R PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GQ882 UT WOS:A1991GQ88200032 PM 1839568 ER PT J AU GARCIAPEREZ, A BURG, MB AF GARCIAPEREZ, A BURG, MB TI RENAL MEDULLARY ORGANIC OSMOLYTES SO PHYSIOLOGICAL REVIEWS LA English DT Review ID ALDOSE REDUCTASE INHIBITOR; CHOLINE DEHYDROGENASE-ACTIVITY; HAMSTER SMALL-INTESTINE; CELL-VOLUME REGULATION; COLLECTING DUCT CELLS; ASCITES TUMOR-CELLS; SALT-LOADED RATS; INNER MEDULLA; MESSENGER-RNA; ALDEHYDE REDUCTASE RP GARCIAPEREZ, A (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 253 TC 467 Z9 471 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 1991 VL 71 IS 4 BP 1081 EP 1115 PG 35 WC Physiology SC Physiology GA GK696 UT WOS:A1991GK69600005 PM 1924548 ER PT J AU ROCK, CD HEATH, TG GAGE, DA ZEEVAART, JAD AF ROCK, CD HEATH, TG GAGE, DA ZEEVAART, JAD TI ABSCISIC ALCOHOL IS AN INTERMEDIATE IN ABSCISIC-ACID BIOSYNTHESIS IN A SHUNT PATHWAY FROM ABSCISIC ALDEHYDE SO PLANT PHYSIOLOGY LA English DT Article ID TOMATO MUTANTS FLACCA; ZEA-MAYS-L; WILTY MUTANTS; ARABIDOPSIS-THALIANA; DEFICIENT MUTANTS; MOLECULAR-OXYGEN; ABA-ALDEHYDE; METABOLISM; XANTHOXIN; ACCUMULATION AB It has previously been shown that the abscisic acid (ABA)-deficient flacca and sitiens mutants of tomato are impaired in ABA-aldehyde oxidation and accumulate trans-ABA-alcohol as a result of the biosynthetic block (IB Taylor, RST Linforth, RJ Al-Naieb, WR Bowman, BA Marples [1988] Plant Cell Environ 11:739-745). Here we report that the flacca and sitiens mutants accumulate trans-ABA and trans-ABA glucose ester and that this accumulation is due to trans-ABA biosynthesis. O-18 labeling of water-stressed wild-type and mutant tomato leaves and analysis of [O-18]ABA by tandem mass spectrometry show that the tomato mutants synthesize a significant percentage of their ABA and trans-ABA as [O-18]ABA with two O-18 atoms in the carboxyl group. We further show, by feeding experiments with [H-2(6)]ABA-alcohol and O-18(2), that this doubly-carboxyl-labeled ABA is synthesized from [O-18]ABA-alcohol with incorporation of molecular oxygen. In vivo inhibition of [H-2(6)]ABA-alcohol oxidation by carbon monoxide establishes the involvement of a P-450 monooxygenase. Likewise, carbon monoxide inhibits the synthesis of doubly-carboxyl-labeled ABA in O-18-labeling experiments. This minor shunt pathway from ABA-aldehyde to ABA-alcohol to ABA operates in all plants examined. For the ABA-deficient mutants impaired in ABA-aldehyde oxidation, this shunt pathway is an important source of ABA and is physiologically significant. C1 MICHIGAN STATE UNIV,US DOE,PLANT RES LAB,E LANSING,MI 48824. MICHIGAN STATE UNIV,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. NR 30 TC 42 Z9 42 U1 0 U2 1 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD OCT PY 1991 VL 97 IS 2 BP 670 EP 676 DI 10.1104/pp.97.2.670 PG 7 WC Plant Sciences SC Plant Sciences GA GM057 UT WOS:A1991GM05700029 PM 16668451 ER PT J AU BROSSI, A AF BROSSI, A TI MAMMALIAN ALKALOIDS - CONVERSIONS OF TETRAHYDROISOQUINOLINE-1-CARBOXYLIC ACIDS DERIVED FROM DOPAMINE SO PLANTA MEDICA LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON BIOLOGY AND CHEMISTRY OF ACTIVE NATURAL SUBSTANCES CY JUL 17-22, 1990 CL BONN, GER DEM REP DE MAMMALIAN ALKALOIDS; TETRAHYDROISOQUINOLINES; 0-METHYLATION; MORPHINE BIOSYNTHESIS; DOPAMINE; PICTET-SPENGLER CYCLIZATION; QUINONEMETHIDES ID ABSOLUTE-CONFIGURATION; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; O-METHYLATION; MORPHINE; URINE; IDENTIFICATION; BIOSYNTHESIS; TETRAHYDROPAPAVEROLINE; (S)-NORCOCLAURINE AB Racemic and optically active mammalian 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids derived from dopamine, and quinonemethides obtained from them by oxidative decarboxylation at physiological pH 7-9, are methylated by S-adenosyl-L-methionine in the presence of catechol-O-methyl-transferase in vitro exclusively at the OH-group at C-7. It can, therefore, be stated that these acids are unlikely intermediates in the biosynthesis of isoquinolines en route to morphine. Enantiospecific and regioselective O-methylations observed with (S)- and (R)-norcoclaurines, leading in the (S)-series predominantly to compounds methylated at the hydroxy group at C-6, and in the (R)-series to isomers methylated at the hydroxy group at C-7, respectively, are in full accord with similar reactions occurring in the plant biosynthesis of morphine. Since the same methylation pattern is ascertained in reactions catalyzed by mammalian enzymes, it is suggested that mammals might be capable of synthesizing morphine from the same isoquinoline precursors. RP BROSSI, A (reprint author), NATL INST DIABET & DIGEST & KIDNEY DIS,STRUCT BIOL LAB,NAT PROD SECT,BETHESDA,MD 20892, USA. NR 51 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD OCT PY 1991 VL 57 SU 1 BP S93 EP S100 DI 10.1055/s-2006-960235 PG 8 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA GP684 UT WOS:A1991GP68400014 PM 1956963 ER PT J AU CHAMPOUX, M METZ, B SUOMI, SJ AF CHAMPOUX, M METZ, B SUOMI, SJ TI BEHAVIOR OF NURSERY PEER-REARED AND MOTHER-REARED RHESUS-MONKEYS FROM BIRTH THROUGH 2 YEARS OF AGE SO PRIMATES LA English DT Note DE RHESUS MACAQUE; BEHAVIOR; REARING; INFANT; JUVENILE AB The behavior of 8 nursery/peer-reared and 16 mother-only reared rhesus macaques was observed between birth and 5 months of age, with follow-up studies conducted when the animals were 10-21 months old and living in large social groups. Nursery-reared neonates were more awake, active, and irritable than mother-only reared monkeys. From 1 to 5 months of age the nursery/peer-reared animals exhibited a greater variety of behaviors than the mother-only reared infants, which spent the majority of the time in ventral contact with mothers. As juveniles the groups were indistinguishable with the exception of more self-directed behaviors observed in the nursery/peer-reared monkeys. Both rearing conditions, by virtue of their atypicality, imposed restrictions on social development. The behavioral similarity of the juveniles while in the large social group may be a function of maturation or due to the rehabilitative effect of the large social group. C1 UNIV WISCONSIN,MADISON,WI 53706. RP CHAMPOUX, M (reprint author), NICHHD,CTR ANIM,COMPARAT ETHOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 12 TC 23 Z9 23 U1 0 U2 10 PU JAPAN MONKEY CENTRE PI INUYAMA AICHI PA PRIMATES, EDITORIAL OFFICE, INUYAMA AICHI 484, JAPAN SN 0032-8332 J9 PRIMATES JI Primates PD OCT PY 1991 VL 32 IS 4 BP 509 EP 514 DI 10.1007/BF02381941 PG 6 WC Zoology SC Zoology GA GX003 UT WOS:A1991GX00300008 ER PT J AU HORISBERGER, JD JAUNIN, P GOOD, PJ ROSSIER, BC GEERING, K AF HORISBERGER, JD JAUNIN, P GOOD, PJ ROSSIER, BC GEERING, K TI COEXPRESSION OF ALPHA-1 WITH PUTATIVE BETA-3 SUBUNITS RESULTS IN FUNCTIONAL NA+/K+ PUMPS IN XENOPUS OOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALPHA-1 ISOFORM; BETA-1 ISOFORM; NA+/K+-ATPASE; ELECTROGENIC TRANSPORT; VOLTAGE DEPENDENCE ID NERVOUS-SYSTEM; K+-ATPASE; NA/K PUMP; NA,K-ATPASE; EXPRESSION; LAEVIS; DEPENDENCE; TRANSPORT; RNA AB The active Na+/K+ pump is composed of an alpha and beta subunit. Until now, three putative isoforms of the beta subunit have been identified that share sequence similarity. We have expressed the beta-1 and beta-3 isoforms of Xenopus laevis Na+/K+-ATPase in Xenopus oocytes to compare functional properties of the Na+/K+ pump, including either of these two isoforms. Na+/K+ pump current, estimated as K+-induced outward current in voltage-clamped oocytes, was doubled by coexpression of alpha-1 subunits with either isoform of the beta subunit compared to expression of alpha-1 subunits alone. The kinetics of activation by external K+ and the voltage dependence of the electrogenic activity of the Na+/K+ pump were similar with both beta isoforms, indicating that both beta-1 and beta-3 isoforms can support expression at the oocyte surface of an active Na+/K+ pump with similar functional properties. C1 NICHHD, MOLEC GENET LAB, BETHESDA, MD 20892 USA. RP HORISBERGER, JD (reprint author), UNIV LAUSANNE, INST PHARMACOL & TOXICOL, BUGNON 27, CH-1005 LAUSANNE, SWITZERLAND. RI Horisberger, Jean-Daniel/A-2538-2009 NR 26 TC 49 Z9 49 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 OCT PY 1991 VL 88 IS 19 BP 8397 EP 8400 DI 10.1073/pnas.88.19.8397 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500024 PM 1717977 ER PT J AU BURKITT, MJ MASON, RP AF BURKITT, MJ MASON, RP TI DIRECT EVIDENCE FOR INVIVO HYDROXYL-RADICAL GENERATION IN EXPERIMENTAL IRON OVERLOAD - AN ESR SPIN-TRAPPING INVESTIGATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IRON POISONING; FREE RADICALS; IRON AUTOXIDATION ID LIPID-PEROXIDATION; RATS; MITOCHONDRIA; PHAGOCYTES; TRANSPORT; DAMAGE AB Although the hydroxyl radical is often implicated as the species responsible for the initiation of oxidative damage in iron-overload conditions, no ESR evidence for the formation of the radical in vivo has been reported. We have employed a secondary radical-trapping technique in which the hydroxyl radical reacts with dimethyl sulfoxide to form the methyl radical, which is then detected as its adduct of the spin trap N-t-butyl-alpha-phenylnitrone in the bile of animals given an intragastric dose of ferrous sulfate. The identity of this adduct was verified by isotope-substitution techniques. We show that unless measures are taken to inactivate the iron excreted in the bile of treated animals, reactions between iron, oxygen, dimethyl sulfoxide, N-t-butyl-alpha-phenylnitrone, and bile components lead to the formation of artifacts during sample collection. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 36 TC 169 Z9 171 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8440 EP 8444 DI 10.1073/pnas.88.19.8440 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500033 PM 1656444 ER PT J AU AXLEY, MJ BOCK, A STADTMAN, TC AF AXLEY, MJ BOCK, A STADTMAN, TC TI CATALYTIC PROPERTIES OF AN ESCHERICHIA-COLI FORMATE DEHYDROGENASE MUTANT IN WHICH SULFUR REPLACES SELENIUM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SELENOCYSTEINE; SELENOENZYMES; TGA CODON; KINETICS ID GLUTATHIONE-PEROXIDASE; HYDROGEN-LYASE; TRANSFER-RNA; UGA CODON; SELENOCYSTEINE; IDENTIFICATION; METABOLISM; COMPONENT; GENE; SITE AB Formate dehydrogenase H of Escherichia coli contains selenocysteine as an integral amino acid. We have purified a mutant form of the enzyme in which cysteine replaces selenocysteine. To elucidate the essential catalytic role of selenocysteine, kinetic and physical properties of the mutant enzyme were compared with those of wild type. The mutant and wild-type enzymes displayed similar pH dependencies with respect to activity and stability, although the mutant enzyme profiles were slightly shifted to more alkaline pH. Both enzymes were inactivated by reaction with iodoacetamide; however, addition of the substrate, formate, was necessary to render the enzymes susceptible to alkylation. Alkylation-induced inactivation was highly dependent on pH, with each enzyme displaying an alkylation vs. pH profile suggestive of an essential selenol or thiol. Both forms of the enzyme use a ping-pong bi-bi kinetic mechanism. The mutant enzyme binds formate with greater affinity than does the wild-type enzyme, as shown by reduced values of K(m) and K(d). However, the mutant enzyme has a turnover number which is more than two orders of magnitude lower than that of the native selenium-containing enzyme. The lower turnover number results from a diminished reaction rate for the initial step of the overall reaction, as found in kinetic analyses that employed the alternative substrate deuterioformate. These results indicate that the selenium of formate dehydrogenase H is directly involved in formate oxidation. The observed differences in kinetic properties may help explain the evolutionary conservation of selenocysteine at the enzyme's active site. C1 UNIV MUNICH,LEHRSTUHL MIKROBIOL,W-8000 MUNICH 19,GERMANY. RP AXLEY, MJ (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 141 Z9 145 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8450 EP 8454 DI 10.1073/pnas.88.19.8450 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500035 PM 1924303 ER PT J AU SKALNIK, DG DORFMAN, DM PERKINS, AS JENKINS, NA COPELAND, NG ORKIN, SH AF SKALNIK, DG DORFMAN, DM PERKINS, AS JENKINS, NA COPELAND, NG ORKIN, SH TI TARGETING OF TRANSGENE EXPRESSION TO MONOCYTE MACROPHAGES BY THE GP91-PHOX PROMOTER AND CONSEQUENT HISTIOCYTIC MALIGNANCIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MYELOID DIFFERENTIATION; CIS-REGULATORY ELEMENTS; NEUTROPHIL CYTOCHROME-B ID CHRONIC GRANULOMATOUS-DISEASE; NEUTROPHIL CYTOCHROME-B; MONOCLONAL-ANTIBODY; CHROMOSOMAL LOCATION; LIGHT CHAIN; GENE; MICE; CELL; ONCOGENES; PROTEIN AB A component of a heterodimeric cytochrome b, designated gp91-phox, is required for the microbicidal activity of phagocytic cells and is expressed exclusively in differentiated myelomonocytic cells (granulocytes; monocyte/macrophages). In an attempt to identify cis-elements responsible for this restricted pattern of expression, we produced transgenic mice carrying reporter genes linked to the human gp91-phox promoter. Immunohistochemical and RNA analyses indicate that 450 base pairs of the proximal gp91-phox promoter is sufficient to target reporter expression to a subset of monocyte/macrophages. Mice expressing simian virus 40 large tumor antigen under control of the gp91-phox promoter develop monocyte/macrophage-derived malignancies with complete penetrance at 6-12 mo of age and provide an animal model of true histiocytic lymphoma. As these transgenes are inactive in most phagocytic cells that express the endogenous gp91-phox-encoding gene, we infer that additional genomic regulatory elements are necessary for appropriate targeting to the full complement of phagocytes in vivo. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,HOWARD HUGHES MED INST,DEPT PEDIAT,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD 18661] NR 36 TC 54 Z9 55 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8505 EP 8509 DI 10.1073/pnas.88.19.8505 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500046 PM 1656446 ER PT J AU MERTZ, LM CATT, KJ AF MERTZ, LM CATT, KJ TI ADRENOCORTICOTROPIN RECEPTORS - FUNCTIONAL EXPRESSION FROM RAT ADRENAL MESSENGER-RNA IN XENOPUS-LAEVIS OOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADRENAL CORTEX; ZONA-FASCICULATA; ADENYLATE CYCLASE; CYCLIC AMP ID STEROIDOGENESIS-ACTIVATOR POLYPEPTIDE; ADENYLATE-CYCLASE; HORMONE RECEPTORS; CYCLIC-AMP; CELLS; CORTICOTROPIN; ACTH; AFFINITY; PROTEIN; CALCIUM AB The adrenocorticotropin (ACTH) receptor, which binds corticotropin and stimulates adenylate cyclase and steroidogenesis in adrenocortical cells, was expressed in Xenopus laevis oocytes microinjected with rat adrenal poly(A)+ RNA. Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand-stimulated cAMP production. Injection of 5-40 ng of adrenal mRNA caused dose-dependent increases in ACTH-responsive cAMP production. These were detected at 48 h and reached a maximum 72 h after microinjection of 20-40 ng of adrenal mRNA. In response to 1-mu-M ACTH, total cAMP production increased within 2.5 min and reached half-maximal and maximal levels (5-fold greater than basal) at 10 and 75 min, respectively, and then remained elevated for up to 5 h. Extracellular cAMP levels were much lower but showed prominent linear increases from almost undectectable levels, with 70- and 150-fold increases evident at 1 and 2 h, respectively. The half-maximal concentration (ED50) for stimulation of cAMP formation was 5 x 10(-8) M ACTH-(1-24); the ED50 for ACTH-(1-17) was 5 x 10(-7) M, and no response was observed with ACTH-(1-10). Size fractionation of rat adrenal poly(A)+ RNA by sucrose density-gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1.1- to 2.0-kilobase fraction. These data indicate that ACTH receptors can be expressed from adrenal mRNA in Xenopus oocytes and are fully functional in terms of ligand specificity and signal generation. The extracellular cAMP response to ACTH is a sensitive and convenient index of receptor expression. This system should permit more complete characterization and expression cloning of the ACTH receptor. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,ROOM B1L-400,BETHESDA,MD 20892. NR 28 TC 9 Z9 9 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8525 EP 8529 DI 10.1073/pnas.88.19.8525 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500050 PM 1656448 ER PT J AU BRINKMANN, U PAI, LH FITZGERALD, DJ WILLINGHAM, M PASTAN, I AF BRINKMANN, U PAI, LH FITZGERALD, DJ WILLINGHAM, M PASTAN, I TI B3(FV)-PE38KDEL, A SINGLE-CHAIN IMMUNOTOXIN THAT CAUSES COMPLETE REGRESSION OF A HUMAN CARCINOMA IN MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MONOCLONAL ANTIBODY B3; SINGLE-CHAIN ANTIGEN-BINDING PROTEIN; PSEUDOMONAS EXOTOXIN; CANCER THERAPY ID PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; RECOGNITION DOMAIN; ESCHERICHIA-COLI; POLYMERASE; PROTEINS; CONTAINS; SEQUENCE; ANTIGEN; GENES AB The genes encoding the heavy- and light-chain Fv regions of the monoclonal murine antibody B3, which recognizes a carbohydrate antigen on the surface of many human carcinomas, were cloned by PCR techniques and used to generate single-chain immunotoxins containing Pseudomonas exotoxin (PE). The light and heavy chains were connected by a flexible linker to form a single-chain antigen-binding protein, B3(Fv), which was in turn fused to truncated forms of PE lacking the cell-binding domain. The single-chain Fv and two different B3(Fv) immunotoxins, B3(Fv)-PE40 and B3(Fv)-PE38KDEL, were expressed in Escherichia coli and the single-chain immunotoxins were purified to near homogeneity. Both recombinant immunotoxins were shown to be cytotoxic specifically to carcinoma cell lines that express the B3 antigen on their surface; B3(Fv)-PE38KDEL was significantly more active. Furthermore, intravenous administration of B3(Fv)-PE-38KDEL caused complete regression of human epidermoid carcinomas growing subcutaneously in immunodeficient mice. C1 NCI,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 23 TC 225 Z9 230 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8616 EP 8620 DI 10.1073/pnas.88.19.8616 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500069 PM 1924323 ER PT J AU DEMOTZ, S SETTE, A SAKAGUCHI, K BUCHNER, R APPELLA, E GREY, HM AF DEMOTZ, S SETTE, A SAKAGUCHI, K BUCHNER, R APPELLA, E GREY, HM TI SELF PEPTIDE REQUIREMENT FOR CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ALLORECOGNITION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIGEN PRESENTATION; ANTIGEN-IA COMPLEXES; ALLOREACTIVITY ID T-CELL CLONES; ANTIGEN RECOGNITION; MOLECULAR-BASIS; ALLOREACTIVITY; SPECIFICITY; ACTIVATION; HYBRIDOMAS; RECEPTOR; H-2 AB Using a dinitrophenylated and biotinylated peptide antigen, we have developed an affinity chromatography procedure to purify complexes of a given peptide species and a given class II major histocompatibility complex antigen away from class II molecules occupied by other peptides. We show that hen egg lysozyme peptide-I-E(d) complexes purified according to this procedure have a greatly enhanced capacity to activate hen egg lysozyme-specific T cells but have lost the capacity to activate three different alloreactive T-cell hybridomas. These data demonstrate that the class II molecule in and of itself is not sufficient to activate alloreactive T cells. Rather, the data suggest that recognition of specific complexes formed between allo-class II and particular autologous peptides may be required. Alternatively, alloreactive T cells may be recognizing "empty" major histocompatibility complex molecules. C1 CYTEL,3525 JOHN HOPKINS COURT,SAN DIEGO,CA 92121. NCI,BETHESDA,MD 20892. FU NIAID NIH HHS [AI18634] NR 22 TC 36 Z9 37 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8730 EP 8734 DI 10.1073/pnas.88.19.8730 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500092 PM 1924332 ER PT J AU WEISSINGER, EM MISCHAK, H LARGAESPADA, DA KAEHLER, DA MITCHELL, T SMITHGILL, SJ RISSER, R MUSHINSKI, JF AF WEISSINGER, EM MISCHAK, H LARGAESPADA, DA KAEHLER, DA MITCHELL, T SMITHGILL, SJ RISSER, R MUSHINSKI, JF TI INDUCTION OF PLASMACYTOMAS SECRETING ANTIGEN-SPECIFIC MONOCLONAL-ANTIBODIES WITH A RETROVIRUS EXPRESSING V-ABL AND C-MYC SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; PRIMED BALB/C MICE; B-CELL; RAPID INDUCTION; PRISTANE; GENE; SEQUENCES; ONCOGENE; RAF AB ABL-MYC, a recombinant murine retrovirus that expresses v-abl and c-myc, rapidly induces transplantable mono- or oligoclonal plasmacytomas in BALB/c mice. To determine if the targets for transformation of this retrovirus are antigen-committed B lymphocytes and to explore this system as an alternative technique for producing antigen-specific monoclonal antibodies, plasmacytomas were induced in mice that had been immunized with two different types of immunogens, hen egg white lysozyme and sheep red blood cells. The majority of these plasmacytomas secreted immunogen-specific antibodies. Plasmacytomas induced in unimmunized mice did not react with hen egg white lysozyme or sheep red blood cells. The specific antibodies were comparable in concentration, specificity, and affinity to monoclonal antibodies obtained with conventional hybridoma technology, but, in addition to IgGs and IgMs, they included specific IgA antibodies, which are rare among splenic-derived hybridomas. Our results demonstrate that a principal target for ABL-MYC is an antigen-committed B lymphocyte. In addition this procedure provides an alternative method for the production of monoclonal antibodies, without a requirement for heterocaryon formation by cell fusion techniques. C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. RP WEISSINGER, EM (reprint author), NCI,MOLEC GENET SECT,GENET LAB,BETHESDA,MD 20892, USA. RI Mischak, Harald/E-8685-2011; Largaespada, David/C-9832-2014; Mitchell, Thomas/B-4193-2013 NR 30 TC 19 Z9 20 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8735 EP 8739 DI 10.1073/pnas.88.19.8735 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500093 PM 1924333 ER PT J AU WANG, YH CITRON, BA RIBEIRO, P KAUFMAN, S AF WANG, YH CITRON, BA RIBEIRO, P KAUFMAN, S TI HIGH-LEVEL EXPRESSION OF RAT PC12 TYROSINE-HYDROXYLASE CDNA IN ESCHERICHIA-COLI - PURIFICATION AND CHARACTERIZATION OF THE CLONED ENZYME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHEOCHROMOCYTOMA; MOLECULAR CLONING; PROTEIN PHOSPHORYLATION ID BOVINE ADRENAL-MEDULLA; PHOSPHORYLATING CONDITIONS; ACTIVATION; CELLS; PROTEINS AB A rat cDNA containing the complete coding sequence for rat tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 1.14.16.2) was isolated from a rat PC12 cDNA library and subcloned in a bacterial expression plasmid, and large amounts of functional enzyme were produced in Escherichia coli. The recombinant enzyme was purified approximately 20-fold to a final specific activity of 1.8-mu-mol/min per mg of protein, with a yield of 30%. As much as 1 mg of pure protein could be obtained from 1 g of wet bacterial cells. The purified hydroxylase was shown to be homogeneous by denaturing polyacrylamide electrophoresis and isoelectric focusing. Amino acid analysis of the N terminus (25 residues) revealed 100% identity with rat PC12 tyrosine hydroxylase, as deduced from its cDNA sequence. Several of the kinetic properties of the recombinant enzyme resembled those of the native PC12 hydroxylase. However, in contrast to the native enzyme, the purified recombinant hydroxylase was shown to be in an activated form. Phosphorylation with cAMP-dependent protein kinase resulted in stoichiometric incorporation of phosphate, but the kinetic profile of the recombinant enzyme was unaffected. Several clues to these differences are considered that may provide insight into the structural features important to the regulation of tyrosine hydroxylase. RP WANG, YH (reprint author), NIMH,NEUROCHEM LAB,ROOM 3D30,BLDG 36,BETHESDA,MD 20892, USA. NR 40 TC 35 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 19 BP 8779 EP 8783 DI 10.1073/pnas.88.19.8779 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH805 UT WOS:A1991GH80500102 PM 1681542 ER PT J AU LETOURNEUR, F KLAUSNER, RD AF LETOURNEUR, F KLAUSNER, RD TI T-CELL AND BASOPHIL ACTIVATION THROUGH THE CYTOPLASMIC TAIL OF T-CELL-RECEPTOR ZETA-FAMILY PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODY; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; IMMUNOGLOBULIN-E; COMPLEX; CHAIN; FC AB The zeta-chain of the T-cell antigen receptor is the prototype of a family of proteins that exist as disulfide-linked dimers and are subunits of the T-cell antigen receptor and both IgE and IgG binding Fc receptors. Two related genes encode the zeta and gamma-proteins. In this study we examine the ability of chimeric proteins consisting of the extracellular domain of the alpha-chain of the interleukin 2 receptor (Tac) and the cytoplasmic domain of either zeta or gamma to activate cells when expressed in either T cells or rat basophilic leukemia cells. The zeta and gamma-chimera were effective at eliciting interleukin 2 production in T cells and serotonin release in rat basophilic leukemia cells when externally cross-linked. Cytoplasmic-tail deletion mutants of zeta and gamma were constructed and used to verify the specificity of cell activation by these chimeric proteins. Signaling potencies of complementary mutants having the zeta-tail truncated in position 108 or deleted from positions 66 through 114 suggested the presence of several functional domains in zeta. RP LETOURNEUR, F (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 46 TC 263 Z9 265 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 8905 EP 8909 DI 10.1073/pnas.88.20.8905 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600009 PM 1833767 ER PT J AU CHU, E KOELLER, DM CASEY, JL DRAKE, JC CHABNER, BA ELWOOD, PC ZINN, S ALLEGRA, CJ AF CHU, E KOELLER, DM CASEY, JL DRAKE, JC CHABNER, BA ELWOOD, PC ZINN, S ALLEGRA, CJ TI AUTOREGULATION OF HUMAN THYMIDYLATE SYNTHASE MESSENGER-RNA TRANSLATION BY THYMIDYLATE SYNTHASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IRON-RESPONSIVE ELEMENT; R17 COAT PROTEIN; BINDING-SITE; DIHYDROFOLATE REDUCTASE; NUCLEOTIDE-SEQUENCE; SECONDARY STRUCTURE; MOUSE FIBROBLASTS; MOLECULAR-CLONING; ESCHERICHIA-COLI; CELL-LINE AB Thymidylate synthase (TS; 5,10-methylene-tetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) is essential for the de novo synthesis of thymidylate, a precursor of DNA. Previous studies have shown that the cellular level of this protein is regulated at both the transcriptional and posttranscriptional levels. The regulation of human TS mRNA translation was studied in vitro with a rabbit reticulocyte lysate system. The addition of purified human recombinant TS protein to in vitro translation reactions inhibited translation of TS mRNA. This inhibition was specific in that recombinant TS protein had no effect on the in vitro translation of mRNA for human chromogranin A, human folate receptor, preplacental lactogen, or total yeast RNA. The inclusion of dUMP, 5-fluoro-dUMP, or 5,10-methylene-tetrahydrofolate in in vitro translation reactions completely relieved the inhibition of TS mRNA translation by TS protein. Gel retardation assays confirmed a specific interaction between TS protein and its corresponding mRNA but not with unrelated mRNAs, including human placenta, human beta-actin, and yeast tRNA. These studies suggest that translation of TS mRNA is controlled by its own protein end product, TS, in an autoregulatory manner. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP CHU, E (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 48 TC 291 Z9 294 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 8977 EP 8981 DI 10.1073/pnas.88.20.8977 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600024 PM 1924359 ER PT J AU ABELES, AL AUSTIN, SJ AF ABELES, AL AUSTIN, SJ TI ANTIPARALLEL PLASMID PLASMID PAIRING MAY CONTROL P1-PLASMID REPLICATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INVITRO REPLICATION; PLASMID INCOMPATIBILITY; REPEATED SEQUENCES; ORIGIN CONTROL ID UNIT-COPY MINIPLASMIDS; NEGATIVE CONTROL; DNA-REPLICATION; DAUGHTER CELLS; SEQUENCES; SEQUESTRATION; SUFFICIENT; PARTITION; PROTEIN; VECTORS AB The copy number of the P1 plasmid replicon is stringently controlled, giving only one or two copies per newborn cell. Control is achieved by the action of the copy-control locus incA, which contains nine repeats of the 19-base-pair binding site for the plasmid-encoded initiator protein RepA. A set of five similar repeats are present in the replication origin where RepA acts to trigger initiation. Using an in vitro replication system consisting of an Escherichia coli extract, the P1 origin as a template, and purified RepA protein, we show that supercoiled DNA circles containing the incA locus block origin function in trans. Shutdown becomes complete at a 1:1 ratio of origin to incA sequences. This is not due to titration of the RepA protein, as an excess of RepA can be added without restoring activity. Rather, the incA sequences appear to block the origin by direct contact in a plasmid-plasmid pairing event. When both the origin and the incA locus are present on one plasmid, trans contacts with daughter molecules appear to predominate over cis looping. The results are consistent with a model for replication control where daughter plasmids block their own replication by a pairing in which each origin is in contact with the incA locus of its partner. RP ABELES, AL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 27 TC 34 Z9 34 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 9011 EP 9015 DI 10.1073/pnas.88.20.9011 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600031 PM 1924364 ER PT J AU MATTHEWS, W JORDAN, CT GAVIN, M JENKINS, NA COPELAND, NG LEMISCHKA, IR AF MATTHEWS, W JORDAN, CT GAVIN, M JENKINS, NA COPELAND, NG LEMISCHKA, IR TI A RECEPTOR TYROSINE KINASE CDNA ISOLATED FROM A POPULATION OF ENRICHED PRIMITIVE HEMATOPOIETIC-CELLS AND EXHIBITING CLOSE GENETIC-LINKAGE TO C-KIT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEMATOPOIETIC STEM CELL; PROTEIN-TYROSINE KINASE ID STEM-CELLS; W-LOCUS; DEVELOPMENTAL EXPRESSION; PROTO-ONCOGENE; FAMILY; SEQUENCES; DOMAINS AB We have cloned a receptor tyrosine kinase cDNA, designated fetal liver kinase 1 (Flk-1), from mouse cell populations enriched for hematopoietic stem and progenitor cells. Sequence analysis of this clone reveals strong homology to the c-Kit subfamily of receptor kinases, and in particular to the Flt gene product. Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked. Flk-1 mRNA is expressed in primitive and more mature hematopoietic cells as well as in a wide variety of nonhematopoietic tissues. C1 PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [CA45339, N01-CO-74101]; NIDDK NIH HHS [DK42989] NR 29 TC 421 Z9 433 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 9026 EP 9030 DI 10.1073/pnas.88.20.9026 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600034 PM 1717995 ER PT J AU MIZUUCHI, M BAKER, TA MIZUUCHI, K AF MIZUUCHI, M BAKER, TA MIZUUCHI, K TI DNASE PROTECTION ANALYSIS OF THE STABLE SYNAPTIC COMPLEXES INVOLVED IN MU TRANSPOSITION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MUA PROTEIN; CLEAVED DONOR COMPLEX; STRAND-TRANSFER COMPLEX; BACTERIOPHAGE MU ID LAMBDA INTEGRATIVE RECOMBINATION; SITE-SPECIFIC RECOMBINATION; BACTERIOPHAGE-MU; PROTEIN; ENHANCER; ENDS; TRANSPOSOSOMES; PURIFICATION AB Several critical steps in phage Mu transposition involve specialized protein-DNA complexes. Cleavage of Mu donor DNA by MuA protein leads to the formation of the stable cleaved donor complex (CDC), in which the two Mu DNA ends are held together by MuA. In the subsequent strand-transfer reaction the CDC attacks a target DNA to generate the strand-transfer complex, in which the donor and the target DNAs are covalently joined. We have carried out DNase I protection experiments on these protein-DNA complexes and found that only three MuA binding sites (L1, R1, and R2 of the six total) at the two Mu ends are stably bound by MuA to maintain the paired Mu end structure. The protection extends beyond the ends of the Mu sequence for different lengths (7-20 nucleotides) depending on the strand and the type of complex. After formation of the CDC, the other MuA binding sites (L2, L3, and R3) and internal activation sequence become dispensable for the subsequent strand-transfer reaction. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 24 TC 65 Z9 65 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 9031 EP 9035 DI 10.1073/pnas.88.20.9031 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600035 PM 1656459 ER PT J AU MOORE, SP ERDILE, L KELLY, T FISHEL, R AF MOORE, SP ERDILE, L KELLY, T FISHEL, R TI THE HUMAN HOMOLOGOUS PAIRING PROTEIN HPP-1 IS SPECIFICALLY STIMULATED BY THE COGNATE SINGLE-STRANDED BINDING-PROTEIN HRP-A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENETIC RECOMBINATION; RECOMBINATION COMPLEX; DNA REPAIR; DNA REPLICATION ID SIMIAN VIRUS-40 DNA; RECA-PROTEIN; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; HUMAN-CELLS; HETERODUPLEX DNA; EXCHANGE; REPLICATION; RECOMBINATION; PURIFICATION AB Homologous pairing and strand exchange of DNA are catalyzed by the human homologous pairing protein HPP-1 in a magnesium-dependent, ATP-independent reaction that requires homologous DNA substrates and stoichiometric quantities of HPP-1. Here we show that the addition of the purified human single-strand binding (SSB) protein hRP-A to the reaction mixture stimulates the rate of homologous pairing 70-fold and reduces the amount of HPP-1 required for the reaction at least 10-fold. The identification of hRP-A as a stimulatory factor of HPP-1-catalyzed reaction was facilitated by its recognition as a member of a high molecular weight complex of recombination components. Neither the Escherichia coli SSB protein, bacteriophage T4 gene 32 protein, nor the highly conserved Saccharomyces cerevisiae yRP-A SSB protein could substitute for hRP-A in this stimulation. Because only the cognate SSB was capable of stimulating HPP-1, these results suggest that eukaryotes depend on unique and specific interactions between DNA recombination components. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. FU NCI NIH HHS [N01-CO-74101] NR 34 TC 94 Z9 94 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 9067 EP 9071 DI 10.1073/pnas.88.20.9067 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600043 PM 1924369 ER PT J AU KWON, BS CHINTAMANENI, C KOZAK, CA COPELAND, NG GILBERT, DJ JENKINS, N BARTON, D FRANCKE, U KOBAYASHI, Y KIM, KK AF KWON, BS CHINTAMANENI, C KOZAK, CA COPELAND, NG GILBERT, DJ JENKINS, N BARTON, D FRANCKE, U KOBAYASHI, Y KIM, KK TI A MELANOCYTE-SPECIFIC GENE, PMEL-17, MAPS NEAR THE SILVER COAT COLOR LOCUS ON MOUSE CHROMOSOME-10 AND IS IN A SYNTENIC REGION ON HUMAN CHROMOSOME-12 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PIGMENTATION; SILVER LOCUS ID PROTO-ONCOGENE; GROWTH-FACTOR; OCULOCUTANEOUS ALBINISM; INTERSPECIFIC BACKCROSS; INSITU HYBRIDIZATION; TYROSINASE GENE; W-LOCUS; LOCALIZATION; LINKAGE; BIOSYNTHESIS AB Melanocytes preferentially express an mRNA species, Pmel 17, whose protein product cross-reacts with anti-tyrosinase antibodies and whose expression correlates with the melanin content. We have now analyzed the deduced protein structure and mapped its chromosomal location in mouse and human. The amino acid sequence deduced from the nucleotide sequence of the Pmel 17 cDNA showed that the protein is composed of 645 amino acids with a molecular weight of 68,600. The Pmel 17 protein contains a putative leader sequence and a potential membrane anchor segment, which indicates that this may be a membrane-associated protein in melanocytes. The deduced protein contains five potential N-glycosylation sites and relatively high levels of serine and threonine. Three repeats of a 26-amino acid motif appear in the middle of the molecule. The human Pmel 17 gene, designated D12S53E, maps to chromosome 12, region 12pter-q21; and the mouse homologue, designated D12S53Eh, maps to the distal region of mouse chromosome 10, a region also known to carry the coat color locus si (silver). C1 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. RP KWON, BS (reprint author), INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202, USA. RI Kim, Kack-Kyun/C-5031-2012; OI Kim, Kack-Kyun/0000-0002-1279-5387; Barton, David E/0000-0002-2031-9719 FU NIAMS NIH HHS [AR-40248] NR 40 TC 135 Z9 137 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT PY 1991 VL 88 IS 20 BP 9228 EP 9232 DI 10.1073/pnas.88.20.9228 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK676 UT WOS:A1991GK67600077 PM 1924386 ER PT J AU VITIELLO, B HILL, JL MOLCHAN, SE MARTINEZ, RA MARTINSON, HJ SUNDERLAND, T AF VITIELLO, B HILL, JL MOLCHAN, SE MARTINEZ, RA MARTINSON, HJ SUNDERLAND, T TI LACK OF SEASONAL-VARIATION IN THE BIRTHS OF PATIENTS WITH DEMENTIA OF THE ALZHEIMER TYPE SO PSYCHIATRY RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; BIRTH DATE; SEASONALITY ID DISEASE; RISK AB Seasonal variation in the birth rates of patients suffering from dementia of the Alzheimer type (DAT) was investigated in 150 patients, aged 42-88 years, and in 132 normal control subjects of comparable age and gender. No seasonal variation or cyclic trend could be demonstrated in the DAT patients compared with control subjects. The exclusion from the analysis of the patients with a positive family history did not change the results of the study, which further suggests that a seasonality in DAT birth rates is unlikely. C1 NIMH,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,BETHESDA,MD 20892. RP VITIELLO, B (reprint author), NIMH,CLIN SCI LAB,BIOSTAT UNIT,9000 ROCKVILLE PIKE,10-3D-41,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT PY 1991 VL 39 IS 1 BP 21 EP 24 DI 10.1016/0165-1781(91)90004-9 PG 4 WC Psychiatry SC Psychiatry GA GR623 UT WOS:A1991GR62300003 PM 1771206 ER PT J AU FREED, WJ AF FREED, WJ TI SUBSTANTIA-NIGRA GRAFTS AND PARKINSONS-DISEASE - FROM ANIMAL-EXPERIMENTS TO HUMAN THERAPEUTIC TRIALS SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Review DE SUBSTANTIA-NIGRA; DOPAMINE; PARKINSONS DISEASE; TRANSPLANTATION; BRAIN GRAFT ID RECOVERY FOLLOWING TRANSPLANTATION; DOPAMINE-DENERVATED STRIATUM; ADRENAL-MEDULLA GRAFTS; BRAIN-TISSUE TRANSPLANTATION; CENTRAL NERVOUS-SYSTEM; ADULT 6-OHDA LESIONS; RAT CAUDATE-NUCLEUS; BEHAVIORAL RECOVERY; NEONATAL RATS; NIGROSTRIATAL PATHWAY AB During the decade since the first reports of functional effects of substantia nigra (SN) transplantation in animal models of Parkinson's disease, the procedure has progressed to human clinical trials. There is evidence that SN grafts can produce some alleviation of the manifestations of SN lesions in animal models, and by several measures these grafts appear to function in a manner similar to the normal SN. There do, however, appear to be limitations on the efficacy of SN allografts in rodent models, that may be related to an inability of fetal SN transplants to fully integrate into the host brain structure. No method of overcoming this limitation has yet been found. Studies of transplantation of human fetal SN to immunosuppressed rat hosts suggest that human donor tissue exerts proportionately greater effects than rat tissue, and is similarly effective when transplanted as solid tissue fragments or as dissociated cells. Only recently, a few controlled studies have obtained evidence for positive effects of SN grafts in primate models of Parkinson's disease. In the few clinical studies reported thus far, there are indications that some clinical improvements can be produced by SN grafts, although there is little or no evidence that the clinical changes found so far are larger than the changes that have been seen after adrenal medulla grafts. The possibility of a role of striatal injury in the clinical changes has not been resolved. It is noteworthy that nearly all of the studies of SN transplantation in rodents, primates, and humans have employed methodologies similar to those developed in the course of the first few reports on SN transplantation, and that the effects obtained by these methods are limited, even in rats. The possibility is raised that fundamental advances in SN transplantation techniques may be important for the development of a more efficacious clinical procedure. RP NIMH, CTR NEUROSCI, NEUROPSYCHIAT BRANCH, PRECLIN NEUROSCI SECT, 2700 MARTIN LUTHER KING AVE, WASHINGTON, DC 20032 USA. NR 185 TC 68 Z9 68 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 EI 1878-3627 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PD OCT PY 1991 VL 3 IS 3 BP 109 EP 134 PG 26 WC Neurosciences SC Neurosciences & Neurology GA GJ665 UT WOS:A1991GJ66500001 PM 21551873 ER PT J AU STEVENS, JR AF STEVENS, JR TI SCHIZOPHRENIA - STATIC OR PROGRESSIVE PATHOPHYSIOLOGY SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT SATELLITE MEETING OF THE AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY : LONGITUDINAL PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA CY DEC 08, 1990 CL SAN JUAN, PR SP AMER COLL NEUROPSYCHOPHARM ID BASAL GANGLIA; LIMBIC SYSTEM; BRAIN; GLIOSIS; VOLUME RP STEVENS, JR (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1991 VL 5 IS 3 BP 184 EP 186 DI 10.1016/0920-9964(91)90061-U PG 3 WC Psychiatry SC Psychiatry GA GP342 UT WOS:A1991GP34200002 PM 1760384 ER PT J AU CASANOVA, MF AF CASANOVA, MF TI ASTROCYTOSIS AND SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT SATELLITE MEETING OF THE AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY : LONGITUDINAL PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA CY DEC 08, 1990 CL SAN JUAN, PR SP AMER COLL NEUROPSYCHOPHARM ID GLIOSIS RP CASANOVA, MF (reprint author), NIMH,ST ELIZABETHS HOSP,CBDB,NEUROSCI CTR,BRAIN BANK UNIT,WASHINGTON,DC 20032, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1991 VL 5 IS 3 BP 186 EP 187 DI 10.1016/0920-9964(91)90062-V PG 2 WC Psychiatry SC Psychiatry GA GP342 UT WOS:A1991GP34200003 PM 1760385 ER PT J AU WYATT, RJ AF WYATT, RJ TI EARLY INTERVENTION WITH NEUROLEPTICS MAY DECREASE THE LONG-TERM MORBIDITY OF SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT SATELLITE MEETING OF THE AMERICAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY : LONGITUDINAL PERSPECTIVES ON THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA CY DEC 08, 1990 CL SAN JUAN, PR SP AMER COLL NEUROPSYCHOPHARM RP WYATT, RJ (reprint author), NIMH,CTR NEUROSCI,2700 MARTIN LUTHER KING JR AVE,WASHINGTON,DC 20032, USA. NR 3 TC 56 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1991 VL 5 IS 3 BP 201 EP 202 DI 10.1016/0920-9964(91)90073-Z PG 2 WC Psychiatry SC Psychiatry GA GP342 UT WOS:A1991GP34200014 PM 1684719 ER PT J AU ABI-DARGHAM, A JASKIW, G SUDDATH, RL WEINBERGER, DR AF ABI-DARGHAM, A JASKIW, G SUDDATH, RL WEINBERGER, DR TI EVIDENCE AGAINST PROGRESSION OF INVIVO ANATOMICAL ABNORMALITIES IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article ID VENTRICULAR ENLARGEMENT RP ABI-DARGHAM, A (reprint author), ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1991 VL 5 IS 3 BP 210 EP 210 DI 10.1016/0920-9964(91)90078-6 PG 1 WC Psychiatry SC Psychiatry GA GP342 UT WOS:A1991GP34200019 PM 1760399 ER PT J AU COGGIANO, MA ALEXANDER, RC KIRCH, DG WYATT, RJ KULAGA, H AF COGGIANO, MA ALEXANDER, RC KIRCH, DG WYATT, RJ KULAGA, H TI THE CONTINUED SEARCH FOR EVIDENCE OF RETROVIRAL INFECTION IN SCHIZOPHRENIC-PATIENTS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE RETROVIRUS; (SCHIZOPHRENIA) ID HUMAN IMMUNODEFICIENCY VIRUS; T-CELL LEUKEMIA; NEUROLOGICAL DISORDERS; REVERSE-TRANSCRIPTASE; AIDS; ONSET; HYPOTHESIS; ANTIBODIES; PSYCHOSIS; GENE AB Retroviral infection has been proposed as an etiologic factor in schizophrenia. In an effort to unmask a latent retrovirus, short term cultures of peripheral lymphocytes from 15 schizophrenic subjects and nine normal controls were exposed to ionizing radiation and co-cultured with indicator cells. Reverse transcriptase activity. a marker of retroviral infection, could not be detected in any of the cultures. Our findings are further evidence against a role for retroviral infection in the etiology of schizophrenia. RP COGGIANO, MA (reprint author), NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN L KING JR AVE,WASHINGTON,DC 20032, USA. NR 32 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1991 VL 5 IS 3 BP 243 EP 247 DI 10.1016/0920-9964(91)90082-3 PG 5 WC Psychiatry SC Psychiatry GA GP342 UT WOS:A1991GP34200023 PM 1662066 ER PT J AU LANE, HC AF LANE, HC TI THE ROLE OF ALPHA-INTERFERON IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO SEMINARS IN ONCOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; KAPOSI-SARCOMA; SYNDROME AIDS; A INTERFERON; ZIDOVUDINE; INVITRO RP LANE, HC (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-09,BETHESDA,MD 20892, USA. NR 13 TC 19 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1991 VL 18 IS 5 SU 7 BP 46 EP 52 PG 7 WC Oncology SC Oncology GA GN575 UT WOS:A1991GN57500009 PM 1948129 ER PT J AU KNUDHANSEN, CR DALLABETTA, GA REICHART, C PABST, KM HOOK, EW WASSERHEIT, JN AF KNUDHANSEN, CR DALLABETTA, GA REICHART, C PABST, KM HOOK, EW WASSERHEIT, JN TI SURROGATE METHODS TO DIAGNOSE GONOCOCCAL AND CHLAMYDIAL CERVICITIS - COMPARISON OF LEUKOCYTE ESTERASE DIPSTICK, ENDOCERVICAL GRAM STAIN, AND CULTURE SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SCREENING-TEST; MUCOPURULENT CERVICITIS; ADOLESCENT MALE; URETHRITIS; TRACHOMATIS; INFECTIONS; URINE AB This study compared leukocyte esterase dipsticks (LED) and endocervical Gram stains (EGS) as surrogates for culture diagnosis of gonococcal and chlamydial cervicitis in 495 STD clinic patients. Overall, gonorrhea prevalence was 15.7%; chlamydia prevalence (in the subgroup that was tested) was 17.8%. In diagnosing gonorrhea, LED and EGS performed similarly, with sensitivities of 68% and 76%, respectively, and identical specificities of 44%. In diagnosing gonococcal or chlamydial cervicitis, LED and EGS sensitivities fell to 48% and 47%, respectively, whereas specificities increased to 55% and 75%. These data suggest that, although both tests are imperfect surrogates for gonococcal and chlamydial culture, LED sacrifices little in sensitivity compared with EGS. Because LED does not require ancillary supplies, equipment, electricity, or trained personnel, its use may be feasible when Gram-stain diagnosis is impossible. Modifications of LED technology and specimen preparation should be sought to improve LED performance. C1 NIAID,STD BRANCH,WESTWOOD BLDG,ROOM 749,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. CALBOT CTY HLTH DEPT,EASTON,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. FU PHS HHS [R30-CCR302723] NR 16 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD OCT-DEC PY 1991 VL 18 IS 4 BP 211 EP 216 DI 10.1097/00007435-199110000-00003 PG 6 WC Infectious Diseases SC Infectious Diseases GA GQ726 UT WOS:A1991GQ72600003 PM 1722912 ER PT J AU KOTLOFF, KL TACKET, CO WASSERMAN, SS BRIDWELL, MW COWAN, JE CLEMENS, JD BROTHERS, TA ODONNELL, SA QUINN, TC AF KOTLOFF, KL TACKET, CO WASSERMAN, SS BRIDWELL, MW COWAN, JE CLEMENS, JD BROTHERS, TA ODONNELL, SA QUINN, TC TI A VOLUNTARY SEROSURVEY AND BEHAVIORAL RISK ASSESSMENT FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AMONG COLLEGE-STUDENTS SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; HOMOSEXUAL MEN; HIV INFECTION; TRANSMISSION; POPULATION; PREVALENCE; HEALTH; WOMEN AB The authors conducted a voluntary serosurvey and educational campaign among 3394 undergraduate students attending the University of Maryland at College Park to determine the prevalence of and risk factors for human immunodeficiency virus type 1 (HIV-1) infection. Two students were seropositive (0.06%, 95% confidence interval 0-0.15%). Both were homosexual men with multiple sexual partners. Despite the low prevalence of infection, potential risk factors for transmission of HIV-1 were common, as assessed by a self-administered anonymous questionnaire. These included a previous sexually transmitted disease (12.6%), male homosexual intercourse (4.8% of men), heterosexual anal intercourse (25.3%), heterosexual intercourse with a person at risk (an HIV-1 infected person, a bisexual man, a parenteral drug user, a female prostitute, or a hemophiliac) (5.2%), multiple sexual partners (21% reported 10 or more lifetime partners), and intravenous drug use (1.3%). Assessment of the efficacy of our program by comparing responses on pre- and post-test questionnaires showed gains in knowledge about heterosexual transmission of HIV-1 and an increase in the reported frequency of condom use 1-2 months after participating in the survey. The authors conclude that HIV-1 infections are occurring among college students but in our study group remain confined to persons with known high-risk behavior; however, practices that may support transmission are common, and programs designed to diminish these behaviors among college students are needed. C1 UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV INFECT DIS,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT GEOG MED,DIV TROP PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,CTR HLTH,COLLEGE PK,MD 20742. NIAID,IMMUNOREGUL LAB,BETHESDA,MD 20892. RP KOTLOFF, KL (reprint author), UNIV MARYLAND,SCH MED,CTR VACCINE DEV,DEPT MED,10 S PINE ST,BALTIMORE,MD 21201, USA. RI kotloff, karen/E-7768-2012 OI kotloff, karen/0000-0003-1808-6431 FU NIAID NIH HHS [AI-28711] NR 20 TC 20 Z9 20 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD OCT-DEC PY 1991 VL 18 IS 4 BP 223 EP 227 DI 10.1097/00007435-199110000-00005 PG 5 WC Infectious Diseases SC Infectious Diseases GA GQ726 UT WOS:A1991GQ72600005 PM 1771475 ER PT J AU OHTA, T ANDO, K IWATA, T OZAKI, N KAYUKAWA, Y TERASHIMA, M OKADA, T KASAHARA, Y AF OHTA, T ANDO, K IWATA, T OZAKI, N KAYUKAWA, Y TERASHIMA, M OKADA, T KASAHARA, Y TI TREATMENT OF PERSISTENT SLEEP-WAKE SCHEDULE DISORDERS IN ADOLESCENTS WITH METHYLCOBALAMIN (VITAMIN-B12) SO SLEEP LA English DT Article DE DELAYED SLEEP PHASE SYNDROME; HYPERNYCHTHEMERAL SYNDROME; METHYLCOBALAMIN; ADOLESCENT; VITAMIN-B12 ID PHASE SYNDROME; CARBACHOL MIMICS; CIRCADIAN-RHYTHM; LIGHT; INSOMNIA; CYCLE AB Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B-12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000-mu-g/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B-12 deficiency or hypothyroidism (which can cause B-12 deficiency). Serum concentrations of vitamin B-12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B-12 and its metabolites is discussed. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RP OHTA, T (reprint author), NAGOYA UNIV,SCH MED,DEPT PSYCHIAT,65 TSURUMA CHO,SHOWA KU,NAGOYA,AICHI 466,JAPAN. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 23 TC 46 Z9 47 U1 2 U2 6 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD OCT PY 1991 VL 14 IS 5 BP 414 EP 418 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GP009 UT WOS:A1991GP00900007 PM 1759094 ER PT J AU BLETTNER, M BOICE, JD AF BLETTNER, M BOICE, JD TI RADIATION-DOSE AND LEUKEMIA RISK - GENERAL RELATIVE RISK TECHNIQUES FOR DOSE-RESPONSE MODELS IN A MATCHED CASE-CONTROL STUDY SO STATISTICS IN MEDICINE LA English DT Article AB Generalized relative risk functions were used to model radiation dose-response information from a large matched case-control study of leukaemia occurring after treatment for cervical cancer. Models suggested by radiobiological theory were investigated and compared to standard analyses of categorical dose-response to the linear model. Local radiation doses to each of fourteen bone marrow compartments for each patient were incorporated into the models, and the corresponding risks were summed. Conditional maximum likelihood methods were used to estimate risk parameters. Unique features of the analysis include modelling both induction and reduction of risk as a function of radiation dose absorbed by different parts of the body within individuals. Detailed statistical aspects of these analyses are presented and discussed. RP BLETTNER, M (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 14 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT PY 1991 VL 10 IS 10 BP 1511 EP 1526 DI 10.1002/sim.4780101004 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA GH687 UT WOS:A1991GH68700003 PM 1947508 ER PT J AU PILOTTE, NS MITCHELL, WM SHARPE, LG DESOUZA, EB DAX, EM AF PILOTTE, NS MITCHELL, WM SHARPE, LG DESOUZA, EB DAX, EM TI CHRONIC COCAINE ADMINISTRATION AND WITHDRAWAL OF COCAINE MODIFY NEUROTENSIN BINDING IN RAT-BRAIN SO SYNAPSE LA English DT Article DE MESOCORTICOLIMBIC SYSTEM; SENSITIZATION; PREFRONTAL CORTEX ID VENTRAL TEGMENTAL AREA; DOPAMINERGIC-NEURONS; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; INVIVO MICRODIALYSIS; SUBSTANTIA NIGRA; LOCALIZATION; RECEPTORS; RELEASE; SYSTEMS AB Neurotensin (NT) is a peptide colocalized with dopamine (DA) within some mesocorticolimbic DA neurons that are affected by cocaine. We assessed whether chronic treatment with cocaine and withdrawal from cocaine would alter NT binding within these and other areas in the brain. Rats were given infusions repeatedly of isotonic saline or cocaine (1 mg/kg i.v. every 12 min for 2 hr over 10 days) and then were killed within 15 min of the last treatment session ("cocaine" or "saline") or 10 days later ("withdrawal"). Brains were processed for NT receptor autoradiography. Cocaine affected NT binding in the mesocortical regions differently from other areas. Within the mesocorticolimbic system, NT binding in the parabrachial pigmented nucleus of the ventral tegmental area (VTA) was 67% lower in cocaine-treated rats killed immediately after or 10 days after their final infusion than in rats given saline. In contrast to the perikaryal region, significantly more NT binding occurred postsynaptically in the terminal areas of the VTA (prefrontal cortex [PFC] and substantia nigra, pars compacta) 10 days after withdrawal of cocaine than in the saline controls. NT binding in the nucleus accumbens was unaffected by cocaine or its withdrawal. Cocaine also decreased NT binding in non-mesocorticolimbic areas, including the dorsal hypothalamic area and the zona incerta, but binding returned toward control levels 10 days after withdrawal from cocaine. These data suggest that in central areas poor in DA uptake sites such as the PFC, NT may be a critical element in the inactivation of DA. Chronic cocaine treatment and its withdrawal appear to uncouple the normal NT-DA interaction at both the cell bodies and terminals. This may increase dopaminergic neurotransmission, a process that may be important to the development of behavioral sensitization. RP PILOTTE, NS (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 43 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 1991 VL 9 IS 2 BP 111 EP 120 DI 10.1002/syn.890090205 PG 10 WC Neurosciences SC Neurosciences & Neurology GA GN590 UT WOS:A1991GN59000004 PM 1821482 ER PT J AU POLLI, JW KINCAID, RL TORRIS, J BILLINGSLEY, ML AF POLLI, JW KINCAID, RL TORRIS, J BILLINGSLEY, ML TI EXPRESSION OF CALMODULIN-DEPENDENT ENZYMES IN DEVELOPING RAT STRIATUM IS NOT AFFECTED BY PERTURBATION OF DOPAMINERGIC SYSTEMS SO SYNAPSE LA English DT Article DE CALMODULIN-BINDING PROTEINS; TRANSSYNAPTIC REGULATION; DOPAMINE; CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE (CALCINEURIN); CALMODULIN-DEPENDENT PROTEIN KINASE-II; CALMODULIN-DEPENDENT PHOSPHODIESTERASE ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; POSTSYNAPTIC DENSITY PROTEIN; DEVELOPMENTAL EXPRESSION; TYROSINE-HYDROXYLASE; BINDING PROTEINS; SENSITIVE METHOD; DARPP-32; BRAIN; KINASE; CALCINEURIN AB Transsynaptic regulation is one mechanism that controls expression of several calmodulin (CaM)-dependent enzymes. This observation and the demonstration that expression of several CaM-dependent enzymes in developing striatum occurred with a spatial and temporal pattern similar to that seen for dopamine and tyrosine hydroxylase suggested that the nigrostriatal pathway may influence the expression of CaM-binding proteins (CaM-BPs) during striatal development. Therefore, the possible role of nigrostriatal dopamine systems regulating the expression of CaM-dependent enzymes was studied in Sprague-Dawley rats by using surgical hemitransections of brain, 6-hydroxydopamine lesions, and chronic haloperidol treatments. Alterations in CaM-BP expression following perturbation of the developing nigrostriatal tract were analyzed by using immunoblots, biotinylated CaM overlays, and enzyme assays. The extent of nigrostriatal lesions was assessed by using depletion of immunoreactive tyrosine hydroxylase levels in striatum. All three experimental paradigms failed to alter the normal developmental expression of CaM-dependent enzymes. From these results we conclude that the increased expression of CaM-dependent enzymes during striatal development is not directly dependent on synaptic input from the nigrostriatal dopamine system. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,CTR CELL & MOLEC BIOL,HERSHEY,PA 17033. NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,IMMUNOL SECT,ROCKVILLE,MD 20852. RP POLLI, JW (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033, USA. FU NIA NIH HHS [R01-AG06377]; NIEHS NIH HHS [R01-ES05450] NR 35 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 1991 VL 9 IS 2 BP 136 EP 143 DI 10.1002/syn.890090208 PG 8 WC Neurosciences SC Neurosciences & Neurology GA GN590 UT WOS:A1991GN59000007 PM 1821485 ER PT J AU HOLLADAY, SD LINDSTROM, P BLAYLOCK, BL COMMENT, CE GERMOLEC, DR HEINDELL, JJ LUSTER, MI AF HOLLADAY, SD LINDSTROM, P BLAYLOCK, BL COMMENT, CE GERMOLEC, DR HEINDELL, JJ LUSTER, MI TI PERINATAL THYMOCYTE ANTIGEN EXPRESSION AND POSTNATAL IMMUNE DEVELOPMENT ALTERED BY GESTATIONAL EXPOSURE TO TETRACHLORODIBENZO-P-DIOXIN (TCDD) SO TERATOLOGY LA English DT Article ID DIBENZO-PARA-DIOXINS; PRE-B-CELL; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; MATURE THYMOCYTES; MURINE THYMOCYTES; CYCLOSPORINE-A; STEM-CELL; MOUSE; THYMUS; FETAL AB In utero exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was found to alter expression of murine thymocyte fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 1.5, or 3.0-mu-g TCDD/kg/day in corn oil on gestational days (gd) 6-14. Offspring were examined on gd 18 and postnatally on d6, d14, and d21, and at 7, 8, and 10 weeks of age. Severe thymic atrophy and cellular depletion were found both pre- and postnatally in TCDD-exposed mice. Immunocytochemical localization of the Thy 1.2 antigen on gd 18 thymocytes revealed no TCDD-related changes in cellular distribution. Flow cytometric analysis, however, indicated that the TCDD treatment resulted in a significant decrease in the percentage of CD4+8+ fetal thymocytes, as well as significantly increased CD4-8- and CD4-8+ thymocytes. The increased CD4-8+ population after TCDD was not from induction of T(s) cells. At 7-8 weeks postnatally, no differences existed between control and treatment groups in mitogen responses and antibody plaque response. However, altered thymocyte antigen expression was found to correlate with altered postnatal immune function, as evidenced by decreased cytotoxic T lymphocyte response at 8 weeks of age. Taken together, these results indicate that immunosuppression following prenatal exposure to TCDD can be readily detected by qualitative and quantitative changes in the cell surface phenotype of fetal thymocytes. Furthermore, the observed altered distribution suggests that TCDD inhibits normal thymocyte maturational processes. C1 NIEHS,NATL TOXICOL PROGRAM,REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,IMMUNOTOXICOL GRP,RES TRIANGLE PK,NC 27709. RP HOLLADAY, SD (reprint author), NIEHS,NATL TOXICOL PROGRAM,DEV GRP,POB 12233,MD E1-02,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 92 Z9 94 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD OCT PY 1991 VL 44 IS 4 BP 385 EP 393 DI 10.1002/tera.1420440405 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA GE314 UT WOS:A1991GE31400004 PM 1683717 ER PT J AU YUAN, J JAMESON, CW GOEHL, TJ COLLINS, BJ PURDIE, W JUDD, L AF YUAN, J JAMESON, CW GOEHL, TJ COLLINS, BJ PURDIE, W JUDD, L TI APPLICATION OF MOLECULAR ENCAPSULATION FOR TOXICOLOGY STUDIES - TOXICOKINETICS OF P-CHLORO-ALPHA,ALPHA,ALPHA-TRIFLUOROTOLUENE IN ALPHA-CYCLODEXTRIN OR CORN-OIL VEHICLES IN MALE F344 RATS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID PROLIFERATIVE LESIONS; LYMPHATIC ABSORPTION; EXOCRINE PANCREAS; TOXICITY; GAVAGE; ACID C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. NR 27 TC 2 Z9 2 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1991 VL 111 IS 1 BP 107 EP 115 DI 10.1016/0041-008X(91)90139-6 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GN684 UT WOS:A1991GN68400012 PM 1949027 ER PT J AU KU, WW CHAPIN, RE MOSEMAN, RF BRINK, RE PIERCE, KD ADAMS, KY AF KU, WW CHAPIN, RE MOSEMAN, RF BRINK, RE PIERCE, KD ADAMS, KY TI TISSUE DISPOSITION OF BORON IN MALE FISCHER RATS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID BORIC-ACID; BORATE; WATER C1 RADIAN CORP,MORRISVILLE,NC 27560. RP KU, WW (reprint author), NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-75199] NR 31 TC 55 Z9 58 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1991 VL 111 IS 1 BP 145 EP 151 DI 10.1016/0041-008X(91)90143-3 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GN684 UT WOS:A1991GN68400016 PM 1949031 ER PT J AU KEDDERIS, LB DILIBERTO, JJ LINKO, P GOLDSTEIN, JA BIRNBAUM, LS AF KEDDERIS, LB DILIBERTO, JJ LINKO, P GOLDSTEIN, JA BIRNBAUM, LS TI DISPOSITION OF 2,3,7,8-TETRABROMODIBENZO-P-DIOXIN AND 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN THE RAT - BILIARY-EXCRETION AND INDUCTION OF CYTOCHROMES CYP1A1 AND CYP1A2 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ETHOXYRESORUFIN O-DEETHYLASE; DIBENZO-PARA-DIOXINS; HEPATIC-METABOLISM; 2-HYDROXYLASE ACTIVITY; TISSUE DISTRIBUTION; FLAME RETARDANTS; LIVER MICROSOMES; AH RECEPTOR; BINDING; INVIVO C1 US EPA,DIV ENVIRONM TOXICOL,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27711. NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP KEDDERIS, LB (reprint author), UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599, USA. RI Goldstein, Joyce/A-6681-2012 NR 41 TC 63 Z9 64 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 1991 VL 111 IS 1 BP 163 EP 172 DI 10.1016/0041-008X(91)90145-5 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GN684 UT WOS:A1991GN68400018 PM 1949032 ER PT J AU MISRA, M RODRIGUEZ, RE NORTH, SL KASPRZAK, KS AF MISRA, M RODRIGUEZ, RE NORTH, SL KASPRZAK, KS TI NICKEL-INDUCED RENAL LIPID-PEROXIDATION IN DIFFERENT STRAINS OF MICE - CONCURRENCE WITH NICKEL EFFECT ON ANTIOXIDANT DEFENSE SYSTEMS SO TOXICOLOGY LETTERS LA English DT Article DE NICKEL; LIPID PEROXIDATION; GLUTATHIONE; ANTIOXIDANT ENZYMES ID CULTURED MAMMALIAN-CELLS; GLUTATHIONE; TOXICITY; RATS; INVITRO; MALONALDEHYDE; CHLORIDE; RADICALS; ACETATE; ENZYMES AB Lipid peroxidation (LPO) and active oxygen-detoxifying enzymes, atalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD), as well as glutathione (GSH) and some related enzymes, glutathione-S-transferase (GST) and glutathione reductase (GSSG-R) were assayed in kidneys of BALB/cAnNCr (BALB/c), C3H/HeNCr-MTV- (C3H), B6C3F1, and C57BL/6NCr (C57BL) mice 3-48 h after a single intraperitoneal injection of 170-mu-mol nickel (II) acetate (NiAcet)/kg body wt. In control mice that received 340-mu-mol sodium acetate/kg, the levels of enzymes and GSH did not significantly vary in time but were different in various strains. The basal activities of CAT and SOD in the controls were highest in BALB/c and lowest in C57BL mice (1.8:1.0 and 1.4:1.0 respectively) in contrast to that of GSH-Px which was highest in B6C3F1 and lowest in BALB/c (1.3:1.0; P < 0.05). The strain ranking of control concentrations of renal GSH was B6C3F1 > C3H greater-than-or-equal-to C57BL > BALB/c (2.8:2.4:2.3:1.0), and that of GSSG-R was C3H greater-than-or-equal-to C3H greater-than-or-equal-to BALB/c > B6C3F1 greater-than-or-equal-to C57BL (1.5:1.4:1.1:1.0). The basal activity of renal GST in control mice was 25% lower in C3H than in any of the other 3 strains. The renal LPO levels in the control mice did not vary among strains. Nickel treatment transiently increased renal LPO in the BALB/c mice by 100%, in B6C3F1 by 30%, and in C57BL by 20% (P < 0.05), with no significant effect in C3H mice. Thus, the magnitude of nickel-induced renal LPO was greatest in the strain that is lowest in GSH and GSH-Px, but not in CAT and SOD. Nickel effects on GSH and the enzymes were time-dependent and included transient inhibition or enhancement of different proportions with no apparent strain- and/or base level-related patterns, or concurrence with LPO. The results emphasize the importance of GSH and GSH-Px for preventing nickel-induced oxidative cell damage. RP MISRA, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 35 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT PY 1991 VL 58 IS 2 BP 121 EP 133 DI 10.1016/0378-4274(91)90166-4 PG 13 WC Toxicology SC Toxicology GA GM141 UT WOS:A1991GM14100001 PM 1949071 ER PT J AU ALTER, HJ TEGTMEIER, GE JETT, BW QUAN, S SHIH, JW BAYER, WL POLITO, A AF ALTER, HJ TEGTMEIER, GE JETT, BW QUAN, S SHIH, JW BAYER, WL POLITO, A TI THE USE OF A RECOMBINANT IMMUNOBLOT ASSAY IN THE INTERPRETATION OF ANTI-HEPATITIS-C VIRUS REACTIVITY AMONG PROSPECTIVELY FOLLOWED PATIENTS, IMPLICATED DONORS, AND RANDOM DONORS SO TRANSFUSION LA English DT Note ID NON-B-HEPATITIS; NON-A; RECIPIENTS AB Samples from prospectively followed recipients, their respective donors, and a cohort of random donors were used to evaluate the specificity and efficacy of a recombinant immunoblot assay (RIBA) as an adjunct to anti-hepatitis C virus (HCV) testing by enzyme immunoassay (EIA). RIBA reacted (RIBA+) in 100 percent of patients who developed hepatitis associated with anti-HCV seroconversion documented by EIA and in 100 percent of the EIA-positive (EIA+) donors implicated in these cases. In contrast, RIBA reacted in none of 10 recipients who were EIA+ but did not develop hepatitis, in none of 7 EIA+ patients with hepatitis B or cytomegalovirus infection, in 33 percent of EIA+ donors who were not implicated in hepatitis transmission, and in 37 percent of EIA+ random donors. Hence, the vast majority of EIA+ individuals who have ancillary evidence of HCV infection react on RIBA, whereas the majority of EIA+ individuals in low-risk settings do not react (RIBA-negative, or RIBA-). There was a strong association between RIBA reactivity and the presence of a surrogate marker (elevated alanine aminotransferase [ALT] and/or antibody to hepatitis B core antigen); 43 percent of RIBA+ implicated donors had a surrogate marker as compared to none of 14 EIA+, RIBA- donors. Among EIA+ random donors, 77 percent of those with a surrogate marker were RIBA+, as compared with 29 percent of those without a surrogate marker. In addition, in EIA+ donors, RIBA reactivity correlated with the extent of ALT elevation; 86 percent of those with an ALT > 135 IU per L were RIBA+ compared with 18 percent of those with an ALT < 30 IU per L. Among recipients of an EIA+, RIBA+ blood unit, 73 percent developed hepatitis C and an additional 6 percent developed hepatitis, but were not positive for anti-HCV. None of 13 recipients of an EIA+, RIBA- unit developed hepatitis (p < 0.001). By using linked donor-recipient sets, a RIBA+ donor was found in association with 75 percent of hepatitis C cases, which implies that these cases could have been prevented if anti-HCV screening had been available at the time of the prospective study. Although considered supplemental rather than a confirmatory assay, RIBA correlates well with HCV infectivity and with surrogate markers of viral hepatitis. Its ability to distinguish probable true-positive EIA reactions from probable false-positive reactions makes it a valuable adjunct to blood donor notification, and it should be used prior to such notification whenever possible. C1 CHIRON CORP,DIAGNOST DEV,EMERYVILLE,CA. COMMUNITY BLOOD CTR GREATER KANSAS CITY,RES,KANSAS CITY,MO. RP ALTER, HJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 12 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1991 VL 31 IS 8 BP 771 EP 776 DI 10.1046/j.1537-2995.1991.31892023507.x PG 6 WC Hematology SC Hematology GA GL386 UT WOS:A1991GL38600019 PM 1656553 ER PT J AU TURMAN, MA CASALI, P NOTKINS, AL BACH, FH PLATT, JL AF TURMAN, MA CASALI, P NOTKINS, AL BACH, FH PLATT, JL TI POLYREACTIVITY AND ANTIGEN-SPECIFICITY OF HUMAN XENOREACTIVE MONOCLONAL AND SERUM NATURAL ANTIBODIES SO TRANSPLANTATION LA English DT Article ID B-CELL REPERTOIRE; CD5+ LYMPHOCYTE-B; RHEUMATOID-FACTOR; NEWBORN MICE; AUTOANTIBODIES; FREQUENCY; LINEAGE; TRANSPLANTATION; AUTOIMMUNE; GENERATION AB Naturally occurring antibodies that react with xenogeneic antigens are a clinically important subset of antibodies because they initiate hyperacute rejection of organs transplanted between disparate species. This currently precludes the use of nonprimate organs for human transplantation. Most antibodies that arise after immunization are monoreactive, i.e., bind only to the immunogen. Similarly, some "natural" antibodies, e.g., isohemagglutinins, bind in a monoreactive manner. In contrast, other natural antibodies, e.g., those that bind to actin, are polyreactive (i.e., bind to multiple ligands). Such polyreactive antibodies may be derived predominantly from CD5+ B cells. In this study, we demonstrate that the majority of xenoreactive natural antibodies in human serum are polyreactive, as indicated by the ability of ssDNA and thyroglobulin (ligands commonly used as targets of polyreactive antibodies) to block the binding of the antibodies to xenogeneic antigens, whereas these ligands could not block the binding of antitetanus antibodies to tetanus toxoid. Furthermore, we compared the ability of 8 polyreactive and 7 monoreactive human mAb to bind to porcine antigens. All of the polyreactive mAb reacted with porcine antigens at mAb concentrations < 3-mu-g/ml, while none of the monoreactive mAb reacted at concentrations < 3-mu-g/ml. Each polyreactive mAb reacted with partially overlapping, but distinct sets of porcine cell surface moieties. These results indicate that human polyreactive mAb can bind to multiple xenogeneic antigens in a selective manner and that xenoreactive natural antibodies in human serum are largely polyreactive. C1 UNIV MINNESOTA,IMMUNOBIOL RES CTR,BOX 724,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. NIDR,ORAL MED LAB,BETHESDA,MD 20892. RI Casali, Paolo/F-6579-2010 NR 35 TC 64 Z9 64 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT PY 1991 VL 52 IS 4 BP 710 EP 717 DI 10.1097/00007890-199110000-00024 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GK378 UT WOS:A1991GK37800024 PM 1926349 ER PT J AU PEITSCH, MC BOGUSKI, MS AF PEITSCH, MC BOGUSKI, MS TI THE 1ST LIPOCALIN WITH ENZYMATIC-ACTIVITY SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note ID RETINOL-BINDING-PROTEIN C1 NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20892 USA. RP UNIV LAUSANNE, INST BIOCHIM, CH-1066 EPALINGES, SWITZERLAND. NR 8 TC 51 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 1991 VL 16 IS 10 BP 363 EP 363 DI 10.1016/0968-0004(91)90149-P PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK379 UT WOS:A1991GK37900004 PM 1723819 ER PT J AU GERSHON, ES AF GERSHON, ES TI GENETIC-MAPPING OF MANIC-DEPRESSIVE ILLNESS - REPLY SO TRENDS IN GENETICS LA English DT Letter ID LINKAGE RP GERSHON, ES (reprint author), NIMH,CLIN NEUROGENET BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1991 VL 7 IS 10 BP 311 EP 312 DI 10.1016/0168-9525(91)90189-W PG 2 WC Genetics & Heredity SC Genetics & Heredity GA GG258 UT WOS:A1991GG25800005 ER PT J AU GUPTA, RK RELYVELD, EH AF GUPTA, RK RELYVELD, EH TI ADVERSE REACTIONS AFTER INJECTION OF ADSORBED DIPHTHERIA PERTUSSIS TETANUS (DPT) VACCINE ARE NOT DUE ONLY TO PERTUSSIS ORGANISMS OR PERTUSSIS COMPONENTS IN THE VACCINE SO VACCINE LA English DT Review DE ADVERSE REACTIONS; PERTUSSIS VACCINE; ALUMINUM ADJUVANTS; TETANUS AND DIPHTHERIA TOXOIDS ID PARENTERAL-NUTRITION; ANTIBODY-RESPONSES; WHOOPING-COUGH; BONE-DISEASE; GUINEA-PIGS; WHOLE-CELL; ALUMINUM; INFANTS; GLUTARALDEHYDE; IMMUNIZATION AB Reactions to adsorbed diphtheria-pertussis-tetanus (DPT) vaccine have mostly been attributed to the pertussis organisms or pertussis components in the vaccine. Nevertheless reactions may also be due to other factors such as sensitization induced by aluminium adjuvants and impurities present in crude toxoids that cannot be removed by purification of toxoids after formalinization. Aluminium compounds such as aluminium phosphate and aluminium hydroxide are the most commonly used adjuvants with vaccines for human use. Due to the increasing concern about the toxicity of aluminium, other adjuvants like calcium phosphate may be evaluated as an alternative to aluminium adjuvants. To minimize reactions after immunization with DPT vaccine due to impurities in the toxoids, the use of toxoided purified toxins is suggested. C1 INST PASTEUR FDN,F-92430 MARNES COQUETTE,FRANCE. RP GUPTA, RK (reprint author), NIH,BLDG 6,RM 1A06,BETHESDA,MD 20892, USA. NR 81 TC 33 Z9 34 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD OCT PY 1991 VL 9 IS 10 BP 699 EP 702 DI 10.1016/0264-410X(91)90283-C PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GH044 UT WOS:A1991GH04400001 PM 1759487 ER PT J AU SIBER, GR THAKRAR, N YANCEY, BA HERZOG, L TODD, C COHEN, N SEKURA, RD LOWE, CU AF SIBER, GR THAKRAR, N YANCEY, BA HERZOG, L TODD, C COHEN, N SEKURA, RD LOWE, CU TI SAFETY AND IMMUNOGENICITY OF HYDROGEN PEROXIDE-INACTIVATED PERTUSSIS TOXOID IN 18-MONTH-OLD CHILDREN SO VACCINE LA English DT Article DE PERTUSSIS; HYDROGEN PEROXIDE-INACTIVATED; INFANTS ID ADVERSE REACTIONS; BORDETELLA-PERTUSSIS; CLINICAL-TRIAL; VACCINE; INFANTS; STANDARDIZATION; IMMUNIZATION; TOXIN AB The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50-mu-g (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p < 0.05 for 10-mu-g dose and p < 0.01 for 50-mu-g dose) and pertussis antitoxin responses (p < 0.01 for 50-mu-g dose) than DTP. The 50-mu-g dose gave slightly higher (though not significantly) antibody responses than the 10-mu-g dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10-mu-g PTxd, 12% with 50-mu-g PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10-mu-g PTxd, in none after 50-mu-g PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p < 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis. C1 CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. NICHHD,BETHESDA,MD 20892. STATE LAB INST,MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. RP SIBER, GR (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115, USA. NR 26 TC 27 Z9 27 U1 1 U2 3 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD OCT PY 1991 VL 9 IS 10 BP 735 EP 740 DI 10.1016/0264-410X(91)90289-I PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GH044 UT WOS:A1991GH04400007 PM 1759491 ER PT J AU NOIMAN, S YANIV, A TSACH, T MIKI, T TRONICK, SR GAZIT, A AF NOIMAN, S YANIV, A TSACH, T MIKI, T TRONICK, SR GAZIT, A TI THE TAT PROTEIN OF EQUINE INFECTIOUS-ANEMIA VIRUS IS ENCODED BY AT LEAST 3 TYPES OF TRANSCRIPTS SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; AUG INITIATOR CODON; NUCLEOTIDE-SEQUENCE; GENE-EXPRESSION; VISNA VIRUS; MUTATIONAL ANALYSIS; FUNCTIONAL DOMAINS; TRANS-ACTIVATION; PROVIRAL DNA; TRANSLATION C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NR 30 TC 23 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1991 VL 184 IS 2 BP 521 EP 530 DI 10.1016/0042-6822(91)90422-8 PG 10 WC Virology SC Virology GA GH254 UT WOS:A1991GH25400006 PM 1653485 ER PT J AU ABLASHI, DV BALACHANDRAN, N JOSEPHS, SF HUNG, CL KRUEGER, GRF KRAMARSKY, B SALAHUDDIN, SZ GALLO, RC AF ABLASHI, DV BALACHANDRAN, N JOSEPHS, SF HUNG, CL KRUEGER, GRF KRAMARSKY, B SALAHUDDIN, SZ GALLO, RC TI GENOMIC POLYMORPHISM, GROWTH-PROPERTIES, AND IMMUNOLOGICAL VARIATIONS IN HUMAN HERPESVIRUS-6 ISOLATES SO VIROLOGY LA English DT Article ID EXANTHEM SUBITUM; T-CELLS; VIRUS; HHV-6; REPLICATION; SALIVA; HBLV; IDENTIFICATION; DNA; HIV C1 UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66103. PHARMACIA DIAGNOST INC,SILVER SPRING,MD 20904. UNIV COLOGNE,INST PATHOL,W-5000 COLOGNE 41,GERMANY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90003. RP ABLASHI, DV (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,RM 1E24,BETHESDA,MD 20892, USA. FU DRS NIH HHS [BRSG-SO7PR05373-28]; NIAID NIH HHS [AI24224] NR 34 TC 243 Z9 250 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1991 VL 184 IS 2 BP 545 EP 552 DI 10.1016/0042-6822(91)90424-A PG 8 WC Virology SC Virology GA GH254 UT WOS:A1991GH25400008 PM 1653487 ER PT J AU QIAN, Y JIANG, BM SAIF, LJ KANG, SY OJEH, CK GREEN, KY AF QIAN, Y JIANG, BM SAIF, LJ KANG, SY OJEH, CK GREEN, KY TI MOLECULAR ANALYSIS OF THE GENE-6 FROM A PORCINE GROUP-C ROTAVIRUS THAT ENCODES THE NS34 EQUIVALENT OF GROUP-A ROTAVIRUSES SO VIROLOGY LA English DT Note ID NUCLEOTIDE-SEQUENCE; DIARRHEA; SUBGROUP; PROTEIN; VIRUS; OUTBREAK C1 NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892. OHIO STATE UNIV,OHIO AGR RES & DEV CTR,FOOD ANIM HLTH RES PROGRAM,WOOSTER,OH 44691. NR 27 TC 33 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1991 VL 184 IS 2 BP 752 EP 757 DI 10.1016/0042-6822(91)90446-I PG 6 WC Virology SC Virology GA GH254 UT WOS:A1991GH25400030 PM 1653496 ER PT J AU CRYSTAL, RG AF CRYSTAL, RG TI OXIDANTS AND RESPIRATORY-TRACT EPITHELIAL INJURY - PATHOGENESIS AND STRATEGIES FOR THERAPEUTIC INTERVENTION SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT SYMP ON OXIDANTS AND ANTIOXIDANTS : PATHOPHYSIOLOGIC DETERMINANTS AND THERAPEUTIC AGENTS CY OCT 26-27, 1990 CL MARBELLA, SPAIN SP ZAMBON GRP ID CYSTIC-FIBROSIS GENE; IDIOPATHIC PULMONARY FIBROSIS; HIV-SEROPOSITIVE INDIVIDUALS; INTERSTITIAL LUNG-DISEASES; LINING FLUID; GLUTATHIONE DEFICIENCY; ALVEOLAR MACROPHAGES; CIGARETTE SMOKERS; BRONCHOALVEOLAR LAVAGE; CHRONIC INFLAMMATION RP CRYSTAL, RG (reprint author), NHLBI,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 55 TC 31 Z9 32 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 30 PY 1991 VL 91 SU 3C BP S39 EP S44 DI 10.1016/0002-9343(91)90282-3 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GM012 UT WOS:A1991GM01200006 PM 1928210 ER PT J AU CRYSTAL, RG AF CRYSTAL, RG TI OXIDANTS AND ANTIOXIDANTS - PATHOPHYSIOLOGIC DETERMINANTS AND THERAPEUTIC AGENTS - SUMMARY SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material RP CRYSTAL, RG (reprint author), NHLBI,PULM BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 30 PY 1991 VL 91 SU 3C BP S145 EP S145 DI 10.1016/0002-9343(91)90298-C PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM012 UT WOS:A1991GM01200022 ER PT J AU CRYSTAL, RG AF CRYSTAL, RG TI OXIDANTS AND ANTIOXIDANTS - PATHOPHYSIOLOGIC DETERMINANTS AND THERAPEUTIC AGENTS - SYMPOSIUM HELD ON OCTOBER 26-27, 1990 IN MARBELLA, SPAIN SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material RP CRYSTAL, RG (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 30 PY 1991 VL 91 SU 3C BP S1 EP S1 DI 10.1016/0002-9343(91)90277-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM012 UT WOS:A1991GM01200001 ER PT J AU PUTNEY, JW BIRD, GSJ HORSTMAN, DA HUGHES, AR MENNITI, FS NOGIMORI, K OBIE, J OLIVER, KG SUGIYA, H TAKEMURA, H AF PUTNEY, JW BIRD, GSJ HORSTMAN, DA HUGHES, AR MENNITI, FS NOGIMORI, K OBIE, J OLIVER, KG SUGIYA, H TAKEMURA, H TI ROLE OF INOSITOL PHOSPHATES IN THE ACTIONS OF SUBSTANCE-P ON NK1 RECEPTORS IN EXOCRINE GLAND-CELLS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PAROTID ACINAR-CELLS; PROTEIN-KINASE-C; SEA-URCHIN EGGS; INTRACELLULAR CALCIUM RELEASE; PLASMA-MEMBRANE VESICLES; CYTOSOLIC FREE CALCIUM; PHORBOL ESTER; PHOSPHOLIPASE-C; TRISPHOSPHATE FORMATION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE RP PUTNEY, JW (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL, CALCIUM REGULAT SECT, RES TRIANGLE PK, NC 27709 USA. OI Menniti, Frank/0000-0003-2612-9534 NR 69 TC 14 Z9 14 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD SEP 30 PY 1991 VL 632 BP 94 EP 102 DI 10.1111/j.1749-6632.1991.tb33097.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM203 UT WOS:A1991JM20300010 PM 1719914 ER PT J AU SZOLCSANYI, J SZALLASI, A SZALLASI, Z JOO, F BLUMBERG, PM AF SZOLCSANYI, J SZALLASI, A SZALLASI, Z JOO, F BLUMBERG, PM TI RESINIFERATOXIN - AN ULTRAPOTENT NEUROTOXIN OF CAPSAICIN-SENSITIVE PRIMARY AFFERENT NEURONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SENSORY NEURONS C1 NCI, BETHESDA, MD 20892 USA. NINCDS, BETHESDA, MD 20892 USA. RP SZOLCSANYI, J (reprint author), MED UNIV PECS, DEPT PHARMACOL, H-7643 PECS, HUNGARY. NR 6 TC 22 Z9 22 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD SEP 30 PY 1991 VL 632 BP 473 EP 475 DI 10.1111/j.1749-6632.1991.tb33161.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM203 UT WOS:A1991JM20300074 PM 1952635 ER PT J AU SNOW, JB AF SNOW, JB TI INTERNATIONAL-SYMPOSIUM ON THE GENETICS OF HEARING IMPAIRMENT - INTRODUCTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material RP SNOW, JB (reprint author), NIDCD,ROOM B2C-02,BLDG 31,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 1 EP 2 DI 10.1111/j.1749-6632.1991.tb19569.x PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400001 ER PT J AU CHO, H YAMADA, Y YOO, TJ AF CHO, H YAMADA, Y YOO, TJ TI ULTRASTRUCTURAL-CHANGES OF COCHLEA IN MICE WITH HEREDITARY CHONDRODYSPLASIA (CHO/CHO) SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NIDR,BETHESDA,MD 20892. RP CHO, H (reprint author), UNIV TENNESSEE CTR HLTH SCI,DEPT MED MICROBIOL & IMMUNOL,OTOIMMUNOL LAB,956 COURT,MEMPHIS,TN 38163, USA. NR 1 TC 8 Z9 9 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 259 EP 261 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400030 PM 1952599 ER PT J AU CHO, H BUCHANAN, J STRONG, D YAMADA, Y YOO, TJ AF CHO, H BUCHANAN, J STRONG, D YAMADA, Y YOO, TJ TI THE MOLECULAR AND STRUCTURAL BASIS OF HEARING IMPAIRMENT IN MICE WITH THE CPK MUTANT-GENE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NIDR,BETHESDA,MD 20892. RP CHO, H (reprint author), UNIV TENNESSEE CTR HLTH SCI,DEPT MED MICROBIOL & IMMUNOL,OTOIMMUNOL LAB,956 COURT,MEMPHIS,TN 38163, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 262 EP 264 DI 10.1111/j.1749-6632.1991.tb19599.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400031 PM 1952600 ER PT J AU YOO, TJ CHO, H YAMADA, Y AF YOO, TJ CHO, H YAMADA, Y TI HEARING IMPAIRMENT IN MICE WITH THE CMD/CMD (CARTILAGE MATRIX DEFICIENCY) MUTANT-GENE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NIDR,BETHESDA,MD 20892. RP YOO, TJ (reprint author), UNIV TENNESSEE CTR HLTH SCI,DEPT MED MICROBIOL & IMMUNOL,OTOIMMUNOL LAB,956 COURT,MEMPHIS,TN 38163, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 265 EP 267 DI 10.1111/j.1749-6632.1991.tb19600.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400032 PM 1952601 ER PT J AU PARRY, DM KAISERKUPFER, MI SHERMAN, JL PIKUS, A ELDRIDGE, R AF PARRY, DM KAISERKUPFER, MI SHERMAN, JL PIKUS, A ELDRIDGE, R TI NEUROFIBROMATOSIS-2 (BILATERAL ACOUSTIC OR CENTRAL NEUROFIBROMATOSIS), A TREATABLE CAUSE OF DEAFNESS - RECOMMENDATIONS FOR SCREENING AND FOLLOW-UP BASED ON STUDY OF ONE LARGE KINDRED SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. WASHINGTON IMAGING CTR,KENSINGTON,MD 20895. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIDCD,BETHESDA,MD 20892. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. RP PARRY, DM (reprint author), NCI,CLIN EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 400,BETHESDA,MD 20892, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 305 EP 307 DI 10.1111/j.1749-6632.1991.tb19615.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400047 PM 1952615 ER PT J AU PIKUS, A AF PIKUS, A TI AUDIOLOGICAL PROFILE IN NIEMANN-PICK-C SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article RP PIKUS, A (reprint author), NIDCD,AUDIOL CLIN,BLDG 10,ROOM 5C306,BETHESDA,MD 20892, USA. NR 2 TC 7 Z9 8 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD SEP 30 PY 1991 VL 630 BP 313 EP 314 DI 10.1111/j.1749-6632.1991.tb19618.x PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM204 UT WOS:A1991JM20400050 PM 1952618 ER PT J AU BIRCH, NP TRACER, HL HAKES, DJ LOH, YP AF BIRCH, NP TRACER, HL HAKES, DJ LOH, YP TI COORDINATE REGULATION OF MESSENGER-RNA LEVELS OF PROOPIOMELANOCORTIN AND THE CANDIDATE PROCESSING ENZYMES PC2 AND PC3, BUT NOT FURIN, IN RAT PITUITARY INTERMEDIATE LOBE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INSITU HYBRIDIZATION; DOPAMINERGIC REGULATION; CONVERTING ENZYME; BETA-LIPOTROPIN; CDNA; GENE; SEQUENCE; PROHORMONE; EXPRESSION; PROTEASE C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 FU NIDDK NIH HHS [DK 18849] NR 36 TC 41 Z9 41 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1991 VL 179 IS 3 BP 1311 EP 1319 DI 10.1016/0006-291X(91)91716-P PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GH295 UT WOS:A1991GH29500027 PM 1843617 ER PT J AU RAMPINO, NJ JOHNSTON, PG AF RAMPINO, NJ JOHNSTON, PG TI MICROFLUOROMETRIC SIZE MEASUREMENTS OF HUMAN AND PHAGE DNA CORRELATE WITH THE DEGREE OF INVITRO CISPLATIN TREATMENT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID QUANTITATION; ADDUCTS; CELLS C1 NCI,DCT,MED BRANCH,BETHESDA,MD 20892. RP RAMPINO, NJ (reprint author), NICHHD,LTPB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1991 VL 179 IS 3 BP 1344 EP 1351 DI 10.1016/0006-291X(91)91721-N PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GH295 UT WOS:A1991GH29500032 PM 1930179 ER PT J AU VISWANATHAN, M TSUTSUMI, K CORREA, FMA SAAVEDRA, JM AF VISWANATHAN, M TSUTSUMI, K CORREA, FMA SAAVEDRA, JM TI CHANGES IN EXPRESSION OF ANGIOTENSIN RECEPTOR SUBTYPES IN THE RAT AORTA DURING DEVELOPMENT SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; RENIN; DUP-753; SYSTEM RP VISWANATHAN, M (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 23 TC 192 Z9 193 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1991 VL 179 IS 3 BP 1361 EP 1367 DI 10.1016/0006-291X(91)91723-P PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GH295 UT WOS:A1991GH29500034 PM 1930181 ER PT J AU LESTER, DS COLLIN, C ETCHEBERRIGARAY, R ALKON, DL AF LESTER, DS COLLIN, C ETCHEBERRIGARAY, R ALKON, DL TI ARACHIDONIC-ACID AND DIACYLGLYCEROL ACT SYNERGISTICALLY TO ACTIVATE PROTEIN-KINASE-C INVITRO AND INVIVO SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RAT-BRAIN; CURRENTS; AUTOPHOSPHORYLATION RP LESTER, DS (reprint author), NIH,NEURAL SYST SECT,PK 5 BLDG,RM 435,BETHESDA,MD 20892, USA. NR 24 TC 104 Z9 104 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 30 PY 1991 VL 179 IS 3 BP 1522 EP 1528 DI 10.1016/0006-291X(91)91745-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GH295 UT WOS:A1991GH29500056 PM 1930192 ER PT J AU HILDESHEIM, A MANN, V BRINTON, LA SZKLO, M REEVES, WC RAWLS, WE AF HILDESHEIM, A MANN, V BRINTON, LA SZKLO, M REEVES, WC RAWLS, WE TI HERPES-SIMPLEX VIRUS TYPE-2 - A POSSIBLE INTERACTION WITH HUMAN PAPILLOMAVIRUS TYPES-16/18 IN THE DEVELOPMENT OF INVASIVE CERVICAL-CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INFECTION; EPIDEMIOLOGY; TRANSFORMATION; CONTRACEPTION; NEOPLASIA; SMOKING; SERA; RISK; DNA AB A case-control study of 766 histologically confirmed incident cases of invasive cervical cancer and 1,532 hospital and community controls was conducted in Latin America to evaluate the etiologic role of herpes simplex virus type 2 (HSV-2) and to examine whether HSV-2 interacts with other risk factors. In addition to a personal interview, all subjects were asked to donate blood samples and cervical swabs for assessment of exposure to HSV-2 and human papillomaviruses (HPVs) respectively. Ninety-eight percent of cases and 91% of controls agreed to the interview and blood collection. Women testing positive for HSV-2 antibodies were found to have a 60% increased risk of cervical cancer compared with seronegative women (95% Cl = 1.3, 1.9). Control for education, sexual and reproductive behavior, prior Pap-smear screening, smoking, oral contraceptive use, HPV-6/11 DNA, or HPV-16/18 DNA detection did not materially affect this estimate. No effect modification of HSV-2 by age, HPV-6/11 DNA, pregnancies, oral contraceptive use or cigarette smoking was observed. However, a significant interaction was detected between HSV-2 and HPV-16/18. Compared with women testing negative to both virus types, those positive for HSV-2 alone had a RR of 1.2 (95% Cl = 0.9, 1.6), those positive for HPV-16/18 DNA alone had a RR of 4.3 (95% Cl = 3.0, 6.0), and those positive for both viruses had a RR of 8.8 (95% Cl = 5.9, 13.0). These findings corroborate recent laboratory evidence of a possible biological interaction between HSV-2 and HPV-16/18 in the development of cervical cancer. Further confirmatory studies are needed, given concerns with potential misclassification of exposure by the laboratory assays utilized. C1 CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. MCMASTER UNIV,DEPT PATHOL,MOLEC & IMMUNOL PROGRAM,HAMILTON L8S 4L8,ONTARIO,CANADA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. RP HILDESHEIM, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 31 TC 99 Z9 102 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 30 PY 1991 VL 49 IS 3 BP 335 EP 340 DI 10.1002/ijc.2910490304 PG 6 WC Oncology SC Oncology GA GH846 UT WOS:A1991GH84600003 PM 1655658 ER PT J AU YAMAGUCHI, T WINSKY, L JACOBOWITZ, DM AF YAMAGUCHI, T WINSKY, L JACOBOWITZ, DM TI CALRETININ, A NEURONAL CALCIUM-BINDING PROTEIN, INHIBITS PHOSPHORYLATION OF A 39 KDA SYNAPTIC MEMBRANE-PROTEIN FROM RAT-BRAIN CEREBRAL-CORTEX SO NEUROSCIENCE LETTERS LA English DT Article DE CALRETININ; CALCIUM BINDING PROTEIN; PROTEIN PHOSPHORYLATION; BRAIN PROTEIN; SYNAPTIC MEMBRANE PROTEIN AB The neuronal calcium binding protein calretinin was studied for possible effects on brain protein phosphorylation. Calretinin (100 nm) inhibited the appearance of a calcium stimulated 39 kDa phosphoprotein within a synaptic membrane fraction following sucrose density centrifugation. Calmodulin or a specific protein kinase C inhibitor had no effect on either the phosphorylation of the 39 kDa protein or the inhibition produced by calretinin. At the same concentration, calretinin produced a slight increase in the phosphorylation of several other synaptic membrane proteins which appeared additive with the stimulation produced by either calmodulin or phosphatidylserine in the presence of calcium. C1 NIMH,CLIN SCI LAB,BLDG 10,RM 3D-48,BETHESDA,MD 20892. NR 17 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 30 PY 1991 VL 131 IS 1 BP 79 EP 82 DI 10.1016/0304-3940(91)90341-P PG 4 WC Neurosciences SC Neurosciences & Neurology GA GK153 UT WOS:A1991GK15300019 PM 1791982 ER PT J AU MERVIS, J HEALY, B AF MERVIS, J HEALY, B TI HEALY SEIZES THE REINS OF AUTHORITY AS NIHS NEW DIRECTOR SO SCIENTIST LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. RP MERVIS, J (reprint author), SCIENTIST,3501 MARKET ST,PHILADELPHIA,PA 19104, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD SEP 30 PY 1991 VL 5 IS 19 BP 11 EP & PG 0 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA GG437 UT WOS:A1991GG43700008 ER PT J AU JOHNSON, KA PICKLE, LW AF JOHNSON, KA PICKLE, LW TI SCREENING FOR PROSTATIC-CANCER SO LANCET LA English DT Letter C1 NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP JOHNSON, KA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 28 PY 1991 VL 338 IS 8770 BP 819 EP 819 DI 10.1016/0140-6736(91)90702-Q PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GG979 UT WOS:A1991GG97900034 PM 1681183 ER PT J AU BARONTI, F CONANT, KE GIUFFRA, M DAVIS, TL BRUGHITTA, G IADAROLA, MJ BERRETTINIW, H CHASE, TN MOURADIAN, MM AF BARONTI, F CONANT, KE GIUFFRA, M DAVIS, TL BRUGHITTA, G IADAROLA, MJ BERRETTINIW, H CHASE, TN MOURADIAN, MM TI OPIOID-PEPTIDES IN PARKINSON DISEASE - EFFECTS OF DOPAMINE REPLETION SO BRAIN RESEARCH LA English DT Article DE PARKINSON; ENKEPHALIN; DYNORPHIN; LEVODOPA; STRIATUM; SPINAL FLUID ID BASAL GANGLIA; MET-ENKEPHALIN; SUBSTANCE-P; HUMAN-BRAIN; METHIONINE-ENKEPHALIN; CEREBROSPINAL-FLUID; GENE-EXPRESSION; HUNTINGTONS-DISEASE; MOTOR FLUCTUATIONS; LEU-ENKEPHALIN AB Neurotransmitters other than dopamine, including neuropeptides, could have important pathophysiologic and therapeutic roles in Parkinson's disease. Both Met-enkephalin, the main transmitter of the striatopallidal pathway, and dynorphin, one of the co-transmitters of the striatonigral pathway display complex anatomic and biochemical interactions with the basal ganglionic dopamine system. In this study, the cerebrospinal fluid content of a proenkephalin derivative, Met5 enkephalin-Arg6-Gly7-Leu8 (MERGL), was found in significantly low concentrations in parkinsonian patients following overnight withdrawal of all medications compared with control subjects, and failed to change after at least 16 h of steady-state, optimal doses of levodopa infusion intravenously. MERGL levels increased with advancing age among normal individuals but not among patients with Parkinson's disease. In contrast, dynorphin A(1-8) levels were not different between the two study groups, did not change with levodopa therapy, and failed to correlate with age or any indices of disease progression. These observations, consistent with post-mortem studies on Parkinson brains and contrary to findings in animal models of Parkinsonism, suggest that abnormality of the enkephalin system in this disease is due to involvement of these striatal neurons in the primary pathologic process. C1 NINCDS,EXPTL THERAPEUT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 5C207,BETHESDA,MD 20892. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NR 39 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 27 PY 1991 VL 560 IS 1-2 BP 92 EP 96 DI 10.1016/0006-8993(91)91219-Q PG 5 WC Neurosciences SC Neurosciences & Neurology GA GM832 UT WOS:A1991GM83200013 PM 1684735 ER PT J AU DECHESNE, CJ WINSKY, L KIM, HN GOPING, G VU, TD WENTHOLD, RJ JACOBOWITZ, DM AF DECHESNE, CJ WINSKY, L KIM, HN GOPING, G VU, TD WENTHOLD, RJ JACOBOWITZ, DM TI IDENTIFICATION AND ULTRASTRUCTURAL-LOCALIZATION OF A CALRETININ-LIKE CALCIUM-BINDING PROTEIN (PROTEIN-10) IN THE GUINEA-PIG AND RAT INNER-EAR SO BRAIN RESEARCH LA English DT Article DE PROTEIN-10; CALRETININ; INNER EAR; CALCIUM-BINDING PROTEIN; IMMUNOCYTOCHEMISTRY; GUINEA PIG; RAT ID VESTIBULAR HAIR-CELLS; SYNAPTOPHYSIN; COCHLEAR; NEURONS; SYSTEM; IMMUNOREACTIVITY; PARVALBUMIN; APPEARANCE; VESICLES; NERVE AB Calretinin has been identified as a brain specific calcium-binding protein which appears as a prominent protein in the cochlear nucleus. We identified and localized calretinin in the guinea pig and rat inner ear using polyclonal antibodies. Immunoblot analyses of guinea pig and rat auditory nerve homogenates revealed an immunoreactive band migrating with the same molecular weight as the purified protein, at M(r) = 29 k. Immunocytochemistry was carried out at the light and electron microscope levels. In the guinea pig cochlea, inner hair cells, Deiters' cells, Hensen's cells and interdental cells of the spiral limbus were stained. Most of the cochlear ganglion cells were immunostained. In the guinea pig vestibular organs, the staining was exclusively neuronal and localized in large nerve fibers and nerve calices of the apex of the cristae. Only some vestibular ganglion cells were stained. In the rat cochlea, inner hair cells and most of the ganglion neurons were immunoreactive. In the rat vestibule, large nerve fibers and calices were stained as were some type II hairs cells. Only some vestibular ganglion cells were reactive. Electron microscopic observations of immunostained guinea pig cochlea and vestibule showed that the staining was cytosolic. In addition, specific sub-localization was also found in the apical portion of the nerve calices in association with microvesicles. These results describe the discrete localization of calretinin in the cochlea and in the vestibular receptors and suggest a function associated with biochemical regulations at the level of microvesicles in vestibular afferent neurons. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIDCD,NEUROCHEM SECT,MOLEC ONCOL LAB,BETHESDA,MD. RP DECHESNE, CJ (reprint author), UNIV SCI & TECHNOL LANGUEDOC,INSERM,UZ54,NEUROPHYSIOL SENSORIELLE LAB,PL BATAILLON,F-34095 MONTPELLIER 5,FRANCE. NR 30 TC 84 Z9 85 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 27 PY 1991 VL 560 IS 1-2 BP 139 EP 148 DI 10.1016/0006-8993(91)91224-O PG 10 WC Neurosciences SC Neurosciences & Neurology GA GM832 UT WOS:A1991GM83200018 PM 1722130 ER PT J AU DRAISCI, G KAJANDER, KC DUBNER, R BENNETT, GJ IADAROLA, MJ AF DRAISCI, G KAJANDER, KC DUBNER, R BENNETT, GJ IADAROLA, MJ TI UP-REGULATION OF OPIOID GENE-EXPRESSION IN SPINAL-CORD EVOKED BY EXPERIMENTAL NERVE INJURIES AND INFLAMMATION SO BRAIN RESEARCH LA English DT Article DE OPIOID GENE; DYNORPHIN; NEUROPATHIC PAIN; NOCICEPTION; INFLAMMATION ID EXPERIMENTAL ANESTHESIA DOLOROSA; DORSAL HORN; C-FOS; OCTAPEPTIDE MET5-ENKEPHALIN-ARG6-GLY7-LEU8; PERIPHERAL MONONEUROPATHY; PROJECTION NEURONS; RAT MODEL; DYNORPHIN; PAIN; HYPERALGESIA AB Opioid systems modulate nociceptive input at several levels of the CNS. At the spinal cord level neurons are present that express the genes coding for the precursors of the dynorphin and enkephalin opioid peptide families. We found that two conditions in rats, a chronic constriction injury to the sciatic nerve and peripheral inflammation, have a common consequence centrally: they evoke a large, rapid and sustained up-regulation of preprodynorphin mRNA. Both are also characterized by signs of hyperalgesia and increased primary afferent input. In contrast, there is little or no up-regulation of preprodynorphin mRNA following complete transection of the sciatic nerve or sciatic nerve crush. Furthermore, only minor alterations in the levels of preproenkephalin mRNA occur in any of the conditions, except for inflammation where the elevation is relatively small compared to that of preprodynorphin mRNA. These data imply that specific regulatory processes that include stimulation of opioid gene expression are strongly engaged in the spinal cord in certain types of peripheral nerve injuries and inflammation, but not in others. Marked and sustained up-regulation of the spinal cord dynorphin system distinguishes the chronic constriction injury model from other nerve injury models of pain. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BLDG 30, ROOM B-20, BETHESDA, MD 20892 USA. OI DRAISCI, Gaetano/0000-0003-0148-5073 NR 45 TC 126 Z9 128 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 27 PY 1991 VL 560 IS 1-2 BP 186 EP 192 DI 10.1016/0006-8993(91)91231-O PG 7 WC Neurosciences SC Neurosciences & Neurology GA GM832 UT WOS:A1991GM83200025 PM 1684729 ER PT J AU OLDFIELD, EH DOPPMAN, JL NIEMAN, LK CHROUSOS, GP MILLER, DL KATZ, DA CUTLER, GB LORIAUX, DL AF OLDFIELD, EH DOPPMAN, JL NIEMAN, LK CHROUSOS, GP MILLER, DL KATZ, DA CUTLER, GB LORIAUX, DL TI PETROSAL SINUS SAMPLING WITH AND WITHOUT CORTICOTROPIN-RELEASING HORMONE FOR THE DIFFERENTIAL-DIAGNOSIS OF CUSHINGS-SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STIMULATION TEST; PITUITARY-GLAND; CLINICAL-APPLICATIONS; COMPUTED-TOMOGRAPHY; ADRENAL-TUMORS; DISEASE; ACTH; CT; DEXAMETHASONE; MICROADENOMAS AB Background. Measurement of adrenocorticotropin levels in plasma from the inferior petrosal sinuses of patients with Cushing's syndrome can distinguish adrenocorticotropin-secreting pituitary tumors (Cushing's disease) from other causes of the syndrome, principally ectopic adrenocorticotropin secretion from an occult tumor, However, it is unknown whether such measurement consistently identifies patients with Cushing's disease and whether testing with corticotropin-releasing hormone (CRH) enhances the value of the procedure. Methods. We prospectively studied 281 patients with Cushing's syndrome to evaluate the diagnostic efficacy of the procedure. Bilateral sampling was successfully accomplished in 278 patients, with no major morbidity; 262 of these patients underwent sampling before and after administration of ovine CRH. The adrenocorticotropin levels in the samples were used to calculate the ratio of the concentration in plasma from the inferior petrosal sinuses to the concentration in peripheral-blood plasma (the IPS:P ratio). Results. The diagnosis of 246 patients was confirmed surgically as Cushing's disease in 215, as ectopic adrenocorticotropin syndrome in 20, and as primary adrenal disease in 11. An IPS:P ratio greater-than-or-equal-to 2.0 in basal samples identified 205 of the 215 patients with Cushing's disease (sensitivity, 95 percent), with no false positive results (specificity, 100 percent). A peak IPS:P ratio greater-than-or-equal-to 3.0 after CRH administration identified all 203 of the patients with Cushing's disease who received CRH (sensitivity, 100 percent), with no false positive results (specificity, 100 percent). The sensitivity was much lower when the adrenocorticotropin concentrations in the samples from one sinus were considered alone. In patients with Cushing's disease a difference of greater-than-or-equal-to 1.4-fold between the concentrations in the two sinuses (the adrenocorticotropin gradient) predicted the location of the microadenoma in 68 percent of 104 patients during basal sampling and in 71 percent of 105 patients after CRH administration Conclusions. Simultaneous bilateral sampling of plasma from the inferior petrosal sinuses, with the adjunctive use of CRH, distinguishes patients with Cushing's disease from those with ectopic adrenocorticotropin secretion with high diagnostic accuracy. C1 NICHHD,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RP OLDFIELD, EH (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,RM 5D37,BETHESDA,MD 20892, USA. NR 49 TC 523 Z9 540 U1 0 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 1991 VL 325 IS 13 BP 897 EP 905 DI 10.1056/NEJM199109263251301 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA GF856 UT WOS:A1991GF85600001 PM 1652686 ER PT J AU SACEDA, M KNABBE, C DICKSON, RB LIPPMAN, ME BRONZERT, D LINDSEY, RK GOTTARDIS, MM MARTIN, MB AF SACEDA, M KNABBE, C DICKSON, RB LIPPMAN, ME BRONZERT, D LINDSEY, RK GOTTARDIS, MM MARTIN, MB TI POSTTRANSCRIPTIONAL DESTABILIZATION OF ESTROGEN-RECEPTOR MESSENGER-RNA IN MCF-7 CELLS BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MAMMARY-CARCINOMA CELLS; GROWTH-FACTOR RECEPTOR; BREAST-CANCER-CELLS; GENE-TRANSCRIPTION; TUMOR PROMOTERS; PHORBOL ESTERS; SIGNAL-TRANSDUCTION; SEQUENCE; LINE AB The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the regulation of the estrogen receptor (ER) was investigated in this study. After treatment with 100 nM TPA the concentration of receptor protein was measured using an enzyme immunoassay. By 24 h the receptor protein declined by about 80% from a level of approximately 236 fmol of ER/mg of protein in control cells to 50 fmol of ER/mg of protein in cells treated with TPA. Similar results were obtained with an estrogen receptor ligand binding assay. After removal of TPA, the level of ER returned to control values. 4-alpha-Phorbol, a compound related to TPA, had no effect on ER. The effects of TPA on ER expression appear to be mediated by activation of protein kinase C as H-7, an inhibitor of protein kinase C, blocks these effects. In addition to the effect on ER protein, TPA treatment also resulted in a decrease in the steady-state level of ER mRNA as determined by a RNase protection assay. The metabolic inhibitor cycloheximide was unable to prevent the TPA-induced decrease in ER mRNA. Transcription run-off experiments demonstrated that TPA had no effect on ER gene transcription. A half-life study demonstrated that TPA decreased ER mRNA half-life by a factor of 6 from approximately 4 h in control cells to 40 min in TPA-treated cells. These data suggest that the decline in ER expression is mediated by post-transcriptional destabilization of ER mRNA. C1 GEORGETOWN UNIV,VINCENT T LOMBARDI CANC RES CTR,S-LEVEL,3800 RESERVOIR RD NW,WASHINGTON,DC 20007. UNIV HAMBURG,CLIN EPPENDORF,W-2000 HAMBURG 13,GERMANY. NCI,CLIN TRIALS EVALUAT PROGRAM,BETHESDA,MD 20892. RI Saceda, Miguel/A-1581-2008 FU NCI NIH HHS [R01 CA50445-02, U01 CA51908-01] NR 38 TC 94 Z9 94 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 17809 EP 17814 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300018 PM 1917923 ER PT J AU REINLIB, L HOMAIDAN, F WATSON, A BREDT, DS SHARP, GWG ZAHNISER, D DONOWITZ, M AF REINLIB, L HOMAIDAN, F WATSON, A BREDT, DS SHARP, GWG ZAHNISER, D DONOWITZ, M TI UNCOUPLING OF PHOSPHOLIPASE-C FROM RECEPTOR REGULATION OF [CA2+]I IN T84 COLONIC CELLS BY PROLONGED EXPOSURE TO PHORBOL DIBUTYRATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; INOSITOL 1,4,5-TRISPHOSPHATE; CHLORIDE SECRETION; 2ND MESSENGER; LINE; CALCIUM; CA-2+; TRISPHOSPHATE; PHOSPHATES; MECHANISMS AB The T84 colonic cell line, a cultured Cl- secretory cell, elevates intracellular free Ca2+ ([Ca2+]i) in a concentration-dependent manner when exposed to carbachol or histamine. As determined with a fluorescence microscope imaging system, exposure of T84 cells to 100-mu-M carbachol or histamine resulted in an immediate [Ca2+]i rise of approximately 50-80 nM in all cells. Preincubation of monolayers for 1 h or longer with 0.4-mu-M phorbol 12,13-dibutyrate (PDB) reduced the number of cells which responded to histamine or carbachol and reduced the magnitude of the increase in the responding cells. This effect reached its maximum after 2 h and persisted for at least 24 h of PDB incubation. Binding of quinuclidinyl benzilate, a cholinergic receptor antagonist, indicated that down-regulation of external receptors was not an explanation for this effect. Examination of phospholipase C activity in T84 cell membranes showed increased basal activity in PDB-treated compared with control cells. Measurement of inositol phosphates generated by intact cells using myo-[H-3]inositol incorporation or receptor binding assays showed that 2 h of incubation with PDB elevated basal levels of inositol 1,4,5-trisphosphate and prevented any further carbachol-induced generation of inositol trisphosphate. Probably as a consequence, both total cell calcium and Ca2+ ionophore-releasable calcium were decreased after 2 h of PDB incubation. Membrane-associated protein kinase C activity was elevated after a 2 h exposure to PDB but was below the level of detection after 24 h with PDB. Protein kinase C antagonists neither duplicated nor blocked the uncoupling of carbachol receptors induced by long term treatment with PDB. The results suggest that prolonged PDB incubation caused uncoupling and elevation of phospholipase C activity from cholinergic and histaminergic receptor regulation resulting in increased basal levels of inositol 1,4,5-trisphosphate. Protein kinase C apparently is not involved directly in the mechanism that leads to these effects. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL & NEUROSCI,BALTIMORE,MD 21205. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. NEW ENGLAND MED CTR HOSP,BOSTON,MA 02111. CORNELL UNIV,COLL VET MED,DEPT PHARMACOL,ITHACA,NY 14853. RP REINLIB, L (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Bredt, David/J-4872-2012 FU NIDDK NIH HHS [DK31667, P01 DK39428, R01 DK26523] NR 24 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 17904 EP 17911 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300032 PM 1917930 ER PT J AU HINTON, DM AF HINTON, DM TI TRANSCRIPTION FROM A BACTERIOPHAGE-T4 MIDDLE PROMOTER USING T4 MOTA PROTEIN AND PHAGE-MODIFIED RNA-POLYMERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOST-VIRUS INTERACTIONS; TABC RHO MUTANTS; ESCHERICHIA-COLI; DNA-REPLICATION; INVITRO SYSTEM; T4-PREREPLICATIVE TRANSCRIPTION; ADP-RIBOSYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; REGULATORY PROTEIN; EXPRESSED PROTEIN AB The bacteriophage T4 motA protein is required for transcription from T4 middle promoters. These promoters, which contain the Escherichia coli promoter consensus sequence at the -10 region (TATAAT) but a unique sequence centered at -30 ((a/t)(a/t)TGCTT(t/c)A) (Guild, N., Gayle, M., Sweeney, R., Hollingsworth, T., Modeer, T., and Gold, L. (1988) J. Mol. Biol. 199, 241-258), become active about 2 min after infection, a time when the host RNA polymerase has been modified by phage proteins. This paper shows that motA protein binds to a T4 middle promoter in vitro and that the addition of the motA protein allows in vitro transcription from this promoter by T4-modified RNA polymerase. The T4 motA gene was cloned into a multicopy plasmid that complemented T4 motA mutants in vivo. MotA protein, partially purified from cells containing a motA+ plasmid, specifically retarded the electrophoretic mobility of an oligomer containing the T4 middle promoter located 195 bases upstream of uvsX (P(uvsX)). RNA polymerase isolated from infected cells during T4 middle gene expression supported in vitro transcription from P(uvsX) only when fractions containing the motA protein were added. In contrast, unmodified host RNA polymerase catalyzed the synthesis of minor amounts of RNA from P(uvsX), but this synthesis was not motA dependent. Thus, the in vitro transcription system described here provides the basis for a detailed study of the phage and host factors needed to regulate T4 middle gene expression. RP HINTON, DM (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,NUCLEIC ACID BIOCHEM SECT,BLDG 8,ROOM 2A-13,BETHESDA,MD 20892, USA. NR 67 TC 53 Z9 53 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 18034 EP 18044 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300052 PM 1917941 ER PT J AU HIGUCHI, S TAMURA, J GIRI, PR POLLI, JW KINCAID, RL AF HIGUCHI, S TAMURA, J GIRI, PR POLLI, JW KINCAID, RL TI CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE FROM NEUROSPORA-CRASSA - MOLECULAR-CLONING AND EXPRESSION OF RECOMBINANT CATALYTIC SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCINEURIN-A; DOMAIN; BRAIN; PHOSPHODIESTERASE; IDENTIFICATION; PURIFICATION; ROLES AB A cDNA for the catalytic subunit of a calmodulin (CaM)-dependent protein phosphatase was cloned from Neurospora crassa. The open reading frame of 1557 base pairs encoded a protein of M(r) almost-equal-to 59,580 and was followed by a 3'-untranslated region of 363 base pairs including the poly(A) tail. Based on primer extension analysis, the mRNA transcript in vivo was 2403 base pairs. Expression of this CaM-protein phosphatase mRNA was developmentally regulated, being highest during early mycelial growth; production of the corresponding protein followed mRNA with a time lag of 8-12 h. Polymerase chain reaction amplification of genomic DNA revealed three small introns, the positions of which coincided with those in the mouse gene, indicating evolutionary conservation of these structures. The deduced sequence showed almost-equal-to 75% identity with the mammalian homologue, calcineurin, in aligned regions. A region of 40 amino acids preceding the CaM-binding domain was essentially unchanged, suggesting conservation of a crucial interaction site. Three small segments in the carboxyl half of the protein were unrelated to the mammalian gene and may constitute "variable regions" that confer substrate specificity to the enzyme. An active recombinant catalytic subunit was expressed in bacteria and purified by CaM-Sepharose chromatography. This preparation was stimulated 2-3-fold by CaM and showed a p-nitrophenol phosphatase activity equal to that of the bovine brain holoenzyme, although its dephosphorylation of phosphoprotein substrates was markedly different. These findings demonstrate that the catalytic subunit of this phosphatase can exhibit high activity in the absence of its intrinsic Ca2+-binding subunit. RP HIGUCHI, S (reprint author), NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,IMMUNOL SECT,ROCKVILLE,MD 20852, USA. NR 32 TC 54 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 18104 EP 18112 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300061 PM 1655737 ER PT J AU CAUGHEY, B RAYMOND, GJ AF CAUGHEY, B RAYMOND, GJ TI THE SCRAPIE-ASSOCIATED FORM OF PRP IS MADE FROM A CELL-SURFACE PRECURSOR THAT IS BOTH PROTEASE-SENSITIVE AND PHOSPHOLIPASE-SENSITIVE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; NEURO-BLASTOMA CELLS; GERSTMANN-STRAUSSLER SYNDROME; PRION-PROTEIN; FIBRIL PROTEIN; INCUBATION PERIOD; EUKARYOTIC CELLS; CULTURED-CELLS; MESSENGER-RNA; MOUSE-BRAIN AB A common feature of scrapie and related transmissible spongiform encephalopathies is the accumulation of an abnormal protease-resistant form of PrP which may be the major component of the infectious agent. While it is known that both the normal (protease-sensitive) PrP and protease-resistant PrP are encoded by the same endogenous gene, the nature of the disease-associated modification of PrP is not understood. To study the cellular events leading to the formation of protease-resistant PrP, we have compared its biosynthesis to that of its normal isoform in scrapie-infected mouse neuroblastoma cells. In pulse-chase labeling experiments, the protease-resistant PrP was synthesized and degraded much more slowly than the normal PrP, suggesting that protease-resistant PrP is made from a protease-sensitive precursor. More significantly, we found that the precursor of protease-resistant PrP was eliminated from intact cells by treatments with phosphatidylinositol-specific phospholipase C and trypsin. This demonstrated that, unlike the protease-resistant PrP itself, the precursor is phospholipase- and protease-sensitive and at least transiently found on the cell surface. By these criteria, the precursor of protease-resistant PrP is indistinguishable from the normal PrP isoform. These results indicate that the conversion of PrP to the protease- and phospholipase-resistant state is a post-translational event that occurs after the precursor reaches the cell surface. RP CAUGHEY, B (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 56 TC 518 Z9 528 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 18217 EP 18223 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300076 PM 1680859 ER PT J AU FUKAYAMA, M KANNO, T BRODY, SL KIRBY, M CRYSTAL, RG AF FUKAYAMA, M KANNO, T BRODY, SL KIRBY, M CRYSTAL, RG TI RESPIRATORY-TRACT GENE-TRANSFER - TRANSPLANTATION OF GENETICALLY MODIFIED LYMPHOCYTES-T DIRECTLY TO THE RESPIRATORY EPITHELIAL SURFACE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; RETROVIRAL EXPRESSION; CELLS; THERAPY; GROWTH; MOUSE; LINE; TUMORIGENICITY; TRANSDUCTION; MIGRATION AB To evaluate the strategy for potentially treating respiratory disorders with genetically modified T-lymphocytes, the interleukin-2 (IL-2)-dependent murine T-cell line, CTLL2, was genetically altered with the Escherichia coli beta-galactosidase (beta-gal) gene (lacZ) in vitro with a retroviral vector and the modified T-cells were transplanted directly to the respiratory epithelial surface of syngeneic C57Bl/6 mice. Southern and Northern analyses confirmed that the neomycin-selected modified T-cells contained and expressed the lacZ gene. The fate of the modified T-cells (CTLL2/lacZ) was followed by flow cytometry with T-cell surface marker Thy1.2 and fluorescent beta-gal analysis. One day after transplantation (7.5 x 10(5) CTLL2/lacZ T-cells/g of body weight), 95 +/- 3% of the Thy1.2+ T-cells recovered from respiratory epithelial lining fluid (ELF) were beta-gal+. Importantly, the modified T-cells remained in the lung for some time; at 3 days, Thy1.2+ beta-gal+ T-cells represented 63 +/- 12% of ELF Thy1.2+ T-cells and 59 +/- 6% of Thy1.2+ T-cells recovered from the whole lung. At 7 days, 33 +/- 8% of the Thy 1.2+ cells in ELF and 75 +/- 6% of the Thy1.2+ cells in whole lung were Thy1.2+ beta-gal+. In contrast, the proportion of the Thy1.2+ beta-gal+ T-cells in the spleen, the major extrapulmonary lymphatic organ, never rose above 3 +/- 1% of the total Thy1.2+ cells. The number of Thy1.2+ beta-gal+ T-cells in the lung could be modified by the systemic administration of IL-2, with whole lung Thy1.2+ beta-gal+ T-cells increasing 4.6-fold 3 days after transplantation, compared with non-IL-2-treated animals. These studies suggest that direct transplantation of genetically modified T-cells into the lung is feasible and represents a viable strategy for lung-specific gene transfer. C1 NHLBI, PULM BRANCH, BLDG 10, RM 6D03, BETHESDA, MD 20892 USA. NR 36 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1991 VL 266 IS 27 BP 18339 EP 18344 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG553 UT WOS:A1991GG55300094 PM 1717448 ER PT J AU SZABO, A ZWANZIG, R AF SZABO, A ZWANZIG, R TI CHRONOAMPEROMETRIC CURRENT AT A RANDOM ENSEMBLE OF MICRODISK ELECTRODES SO JOURNAL OF ELECTROANALYTICAL CHEMISTRY LA English DT Note ID DISK ELECTRODES; DIFFUSION RP SZABO, A (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 12 TC 24 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0022-0728 J9 J ELECTROANAL CHEM JI J. Electroanal. Chem. PD SEP 25 PY 1991 VL 314 IS 1-2 BP 307 EP 311 DI 10.1016/0022-0728(91)85444-T PG 5 WC Chemistry, Analytical; Electrochemistry SC Chemistry; Electrochemistry GA GM428 UT WOS:A1991GM42800021 ER PT J AU ARAKI, H HAMATAKE, RK MORRISON, A JOHNSON, AL JOHNSTON, LH SUGINO, A AF ARAKI, H HAMATAKE, RK MORRISON, A JOHNSON, AL JOHNSTON, LH SUGINO, A TI CLONING DPB3, THE GENE ENCODING THE 3RD SUBUNIT OF DNA POLYMERASE-II OF SACCHAROMYCES-CEREVISIAE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HEAT-SHOCK PROTEIN; NUCLEOTIDE-SEQUENCE; CELL-CYCLE; CDC2 GENE; YEAST; EXPRESSION; PURIFICATION; TEMPERATURE; PRIMASE; DELTA AB DNA polymerase II purified from Saccharomyces cerevisiae contains polypeptides with apparent molecular masses of > 200, 80, 34, 30 and 29 kDa, the two largest of which (subunits A and B) are encoded by the essential genes POL2 and DPB2. By probing a lambda-gt11 expression library of yeast DNA with antiserum against DNA polymerase II, we isolated a single gene, DPB3, that encodes both the 34- and 30-kDa polypeptides (subunit C and C'). The nucleotide sequence of DPB3 contained an open reading frame encoding a 23-kDa protein, significantly smaller than the observed molecular masses, 34- or 30-kDa, which might represent post-translationally modified forms of the DPB3 product. The predicted amino acid sequence contained a possible NTP-binding motif and a glutamate-rich region. A dpb3 deletion mutant (dpb3-DELTA) was viable and yielded a DNA polymerase II lacking the 34- and 30-kDa polypeptides. dpb3-DELTA strains exhibited an increased spontaneous mutation rate, suggesting that the DPB3 product is required to maintain fidelity of chromosomal replication. Since a fifth, 29-kDa polypeptide was present in DNA polymerase II preparations from wild-type cell extracts throughout purification, the subunit composition appears to be A, B, C (or C and C') and D. The 5' nontranscribed region of DPB3 contained the Mlul-related sequence ACGCGA, while the 0.9-kb DPB3 transcript accumulated periodically during the cell cycle and peaked at the G1/S boundary. The level of DPB3 transcript thus appears to be under the same cell cycle control as those of POL2, DPB2 and other DNA replication genes. DPB3 was mapped to chromosome II, 30 cM distal to his7. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NATL INST MED RES,CELL PROPAGAT LAB,LONDON NW7 1AA,ENGLAND. RP ARAKI, H (reprint author), OSAKA UNIV,FAC ENGN,DEPT BIOTECHNOL,2-1 YAMADAOKA,SUITA,OSAKA 565,JAPAN. NR 36 TC 77 Z9 78 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 25 PY 1991 VL 19 IS 18 BP 4867 EP 4872 DI 10.1093/nar/19.18.4867 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GH660 UT WOS:A1991GH66000007 PM 1923754 ER PT J AU SUSSMAN, DJ CHUNG, J LEDER, P AF SUSSMAN, DJ CHUNG, J LEDER, P TI INVITRO AND INVIVO ANALYSIS OF THE C-MYC RNA POLYMERASE-III PROMOTER SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION INITIATION; TRANS-ACTIVATION; BINDING-PROTEIN; TATA ELEMENTS; U2 SNRNA; GENE; EXPRESSION; CELLS; DIFFERENTIATION; TRANSFORMATION AB The c-myc promoter has the unusual property of displaying both RNA polymerase II (Pol II) and RNA polymerase III (Pol III) activities. Both Pol II and Pol III utilize the same transcription initiation site. We have now examined the effects of mutations in crucial regions of the c-myc promoter to assess their effects on both transcriptional activities. In doing this we show that both Pol II and Pol III activities require sequences that are located within the stronger of the two principal c-myc promoter regions (P2). Further, we show that the Pol III activity using this initiation site does not require an A box or distal upstream sequences. Like the Pol II activity, it does require an intact TATA sequence and alterations at this site result in the simultaneous loss of both Pol II and Pol III activities. The superimposition of two apparently inseparable promoter activities makes it possible to consider common features, possible common protein elements in each holoenzyme complex, as well as a potential role for each enzyme in the regulated expression of the c-myc gene. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SUSSMAN, DJ (reprint author), W ALTON JONES CELL SCI CTR,10 OLD BARN RD,LAKE PLACID,NY 12946, USA. NR 41 TC 23 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 25 PY 1991 VL 19 IS 18 BP 5045 EP 5052 DI 10.1093/nar/19.18.5045 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GH660 UT WOS:A1991GH66000034 PM 1923771 ER PT J AU WILMANNS, M HYDE, CC DAVIES, DR KIRSCHNER, K JANSONIUS, JN AF WILMANNS, M HYDE, CC DAVIES, DR KIRSCHNER, K JANSONIUS, JN TI STRUCTURAL CONSERVATION IN PARALLEL BETA/ALPHA-BARREL ENZYMES THAT CATALYZE 3 SEQUENTIAL REACTIONS IN THE PATHWAY OF TRYPTOPHAN BIOSYNTHESIS SO BIOCHEMISTRY LA English DT Article ID SPINACH GLYCOLATE OXIDASE; N-(5'-PHOSPHORIBOSYL)ANTHRANILATE ISOMERASE-INDOLE-3-GLYCEROL-PHOSPHATE SYNTHASE; RIBULOSE 1,5-BISPHOSPHATE CARBOXYLASE; MUCONATE LACTONIZING ENZYME; PROTEIN CODING REGIONS; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; TRIOSEPHOSPHATE ISOMERASE; CRYSTAL-STRUCTURE; SALMONELLA-TYPHIMURIUM AB Three successive steps in tryptophan biosynthesis are catalyzed by single-domain proteins, each folded as a parallel-beta/alpha-barrel, as observed in the crystal structures of the bienzyme (phosphoribosyl)-anthranilate isomerase:indoleglycerolphosphate synthase from Escherichia coli [Priestle, J. P., Grutter, M. G., White, J. L., Vincent, M. G., Kania, M., Wilson, E., Jardetzky, T. S., Kirschner, K., & Jansonius, J. N. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5690-5694] and the alpha-subunit of the tetrameric bienzyme tryptophan synthase from Salmonella typhimurium [Hyde, C. C., Ahmed, S. A., Padlan, E. A., Miles, E. W., & Davies, D. R. (1988) J. Biol. Chem. 263, 17857-17871]. Recent refinement of the crystal structures of these enzymes at atomic resolution revealed that they contain a common phosphate group binding site in the beta/alpha-barrel, created by residues of the loop between beta-strand 7 and alpha-helix 7 and the N-terminus of an additional helix 8'. The close similarities of their beta/alpha-barrel structures permitted the alignment of 50-75% of their respective amino acid sequences. Considerable sequence similarity was detected in the regions spanning the phosphate binding sites, whereas the percentage of identical residues was barely significant for the remaining parts of the enzymes. These observations suggest divergent evolution of these three beta/alpha-barrel enzymes involved in tryptophan biosynthesis. The same phosphate binding site was also observed in six other beta/alpha-barrel enzymes that are functionally unrelated to those involved in tryptophan biosynthesis: triosephosphate isomerase, ribulose-1,5-bisphosphate carboxylase/oxygenase, glycolate oxidase, flavocytochrome b2, trimethylamine dehydrogenase, and tentatively also fructosebisphosphate aldolase. This observation indicates that a much larger number of beta/alpha-barrel enzymes, not restricted to the three tryptophan biosynthesis enzymes, might be evolutionarily related. Whether these beta/alpha-barrel enzymes or domains of enzymes evolved from the same ancestor or, in part, from each other remains open. C1 UNIV BASEL, BIOCTR, DEPT STRUCT BIOL, KLINGELBERGSTR 70, CH-4056 BASEL, SWITZERLAND. NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV BASEL, BIOCTR, DEPT BIOPHYS CHEM, CH-4056 BASEL, SWITZERLAND. NR 65 TC 142 Z9 144 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 24 PY 1991 VL 30 IS 38 BP 9161 EP 9169 DI 10.1021/bi00102a006 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG430 UT WOS:A1991GG43000006 PM 1892826 ER PT J AU IKURA, M SPERA, S BARBATO, G KAY, LE KRINKS, M BAX, A AF IKURA, M SPERA, S BARBATO, G KAY, LE KRINKS, M BAX, A TI SECONDARY STRUCTURE AND SIDE-CHAIN H-1 AND C-13 RESONANCE ASSIGNMENTS OF CALMODULIN IN SOLUTION BY HETERONUCLEAR MULTIDIMENSIONAL NMR-SPECTROSCOPY SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CHEMICAL-SHIFTS; 3D NMR; STAPHYLOCOCCAL NUCLEASE; COUPLING-CONSTANTS; TRYPTIC FRAGMENTS; PRACTICAL ASPECTS; CALCIUM-BINDING; ROTATING-FRAME; NOESY-HMQC AB Heteronuclear 2D and 3D NMR experiments were carried out on recombinant Drosophila calmodulin (CaM), a protein of 148 residues and with molecular mass of 16.7 kDa, that is uniformly labeled with N-15 and C-13 to a level of > 95%. Nearly complete H-1 and C-13 side-chain assignments for all amino acid residues are obtained by using the 3D HCCH-COSY and HCCH-TOCSY experiments that rely on large heteronuclear one-bond scalar couplings to transfer magnetization and establish through-bond connectivities. The secondary structure of this protein in solution has been elucidated by a qualitative interpretation of nuclear Overhauser effects, hydrogen exchange data, and 3J(HNH-alpha) coupling constants. A clear correlation between the C-13-alpha chemical shift and secondary structure is found. The secondary structure in the two globular domains of Drosophila CaM in solution is essentially identical with that of the X-ray crystal structure of mammalian CaM [Babu, Y., Bugg, C. E., & Cook, W. J. (1988) J. Mol. Biol. 204, 191-204], which consists of two pairs of a "helix-loop-helix" motif in each globular domain. The existence of a short antiparallel beta-sheet between the two loops in each domain has been confirmed. The eight alpha-helix segments identified from the NMR data are located at Glu-6 to Phe-19, Thr-29 to Ser-38, Glu-45 to Glu-54, Phe-65 to Lys-77, Glu-82 to Asp-93, Ala-102 to Asn-111, Asp-118 to Glu-127, and Tyr-138 to Thr-146. Although the crystal structure has a long "central helix" from Phe-65 to Phe-92 that connects the two globular domains, NMR data indicate that residues Asp-78 to Ser-81 of this central helix adopt a nonhelical conformation with considerable flexibility. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Barbato, Gaetano/G-4904-2011 NR 64 TC 172 Z9 174 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 24 PY 1991 VL 30 IS 38 BP 9216 EP 9228 DI 10.1021/bi00102a013 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG430 UT WOS:A1991GG43000013 PM 1909892 ER PT J AU SINHA, BK ELIOT, HM AF SINHA, BK ELIOT, HM TI ETOPOSIDE-INDUCED DNA DAMAGE IN HUMAN TUMOR-CELLS - REQUIREMENT FOR CELLULAR ACTIVATING FACTORS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE DNA DAMAGE; DRUG RESISTANCE; TOPOISOMERASE-II; DAMAGE FACTOR ID TOPOISOMERASE-II; P-GLYCOPROTEIN; STRAND BREAKS; MULTIDRUG RESISTANCE; DRUG-RESISTANCE; CYTO-TOXICITY; CANCER-CELLS; VP-16-213; MECHANISM; BINDING AB Previous studies with the multidrug-resistant human HL60 cell line have shown a 3-4-fold decrease in VP-16 accumulation compared to the sensitive cell line, while the degree of resistance to VP-16 was 300-fold, indicating that other mechanisms of resistance are also operative. Since VP-16 has been shown to interfere with topoisomerase II activity, we have evaluated VP-16-dependent DNA strand break formation in the drug-sensitive and -resistant HL60 cells. Studies reported here show that the drug-resistant HL60 cells are extremely resistant to VP-16-dependent DNA cleavage compared to the sensitive cells. This decrease in DNA cleavage activity in the presence of VP-16 was, in part, related to a 2-3-fold decrease in both the amount and activity of topoisomerase II in the resistant cell line compared to the sensitive cells. Nuclei from the resistant cell line were markedly more resistant to VP-16-dependent DNA cleavage than the WT cell nuclei. Interestingly, WT nuclei were found to be relatively more resistant to VP-16-induced DNA cleavage than the intact WT cells. Addition of WT cytosolic proteins to WT nuclei, however, significantly stimulated VP-16-dependent DNA cleavage and slightly increased DNA cleavage in resistant cell nuclei. In contrast, cytosolic proteins from the resistant cells had no effect on DNA cleavage in nuclei isolated from either cell line. These observations indicate that a decrease in the amount and activity of topoisomerase II in resistant HL60 cells translates into a decrease in VP-16-dependent DNA breakage and contributes to the resistance to VP-16. Furthermore, the cytosolic fraction from WT cells contains some factor, not present in the resistant cells, which is necessary for the maximal drug-induced DNA cleavage. RP SINHA, BK (reprint author), NCI,GENET & PLANT BREEDING PROGRAM,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 29 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD SEP 23 PY 1991 VL 1097 IS 2 BP 111 EP 116 DI 10.1016/0925-4439(91)90093-O PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GK947 UT WOS:A1991GK94700004 PM 1655044 ER PT J AU LOREAL, O LEVAVASSEUR, F RESCAN, PY YAMADA, Y GUILLOUZO, A CLEMENT, B AF LOREAL, O LEVAVASSEUR, F RESCAN, PY YAMADA, Y GUILLOUZO, A CLEMENT, B TI DIFFERENTIAL EXPRESSION OF LAMININ CHAINS IN HEPATIC LIPOCYTES SO FEBS LETTERS LA English DT Article DE LAMININ; LIPOCYTE; LIVER; CELL CULTURE; MESSENGER RNA ID FAT-STORING CELLS; NORMAL RAT-LIVER; BASEMENT-MEMBRANES; MULTIDOMAIN PROTEIN; ENDOTHELIAL-CELLS; GENE-EXPRESSION; PRIMARY CULTURE; IV COLLAGEN; B-CHAINS; HEPATOCYTES AB The lipocyte is an important source of laminin in the normal liver. We have investigated the expression of the 3 chains of laminin in isolated rat lipocytes. Both B1 and B2 chains, but not A, were found in medium from 5-day-old lipocyte primary cultures by immunoblotting and immunoprecipitation of S-35-labeled proteins after reducing SDS-polyacrylamide gel gel electrophoresis. An additional polypeptide of m(r) = 380 000 was identified by immunoprecipitation. Under non-reducing conditions only one M(r) = 900 000 band was revealed. High levels of B1 and B2 mRNAs were also demonstrated in 5-day-old cultured lipocytes while at the time of seeding, only B2 chain mRNAs were clearly detectable. A chain mRNA was constantly absent. These results suggest that lipocytes produce a variant form of laminin in primary culture and that the M(r) = 380 000 polypeptide could be unrelated to the A chain of laminin. C1 HOP PONTCHAILLOU,INSERM,U49,UNITE RECH HEPATOL,F-35033 RENNES,FRANCE. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. RI Loreal, Olivier/G-3366-2013; Clement, Bruno/E-5546-2016 NR 33 TC 23 Z9 23 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 SEP 23 PY 1991 VL 290 IS 1-2 BP 9 EP 12 DI 10.1016/0014-5793(91)81213-R PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GJ553 UT WOS:A1991GJ55300003 PM 1915898 ER PT J AU BIRCH, NP ESTIVARIZ, FE BENNETT, HPJ LOH, YP AF BIRCH, NP ESTIVARIZ, FE BENNETT, HPJ LOH, YP TI DIFFERENTIAL GLYCOSYLATION OF N-POMC1-77 REGULATES THE PRODUCTION OF GAMMA-3-MSH BY PURIFIED PROOPIOMELANOCORTIN CONVERTING ENZYME - A POSSIBLE MECHANISM FOR TISSUE-SPECIFIC PROCESSING SO FEBS LETTERS LA English DT Article DE NEUROPEPTIDE; MATURATION; PROOPIOMELANOCORTIN PROCESSING; O-LINKED GLYCOSYLATION ID CENTRAL NERVOUS-SYSTEM; PITUITARY PEPTIDES; BOVINE; PROENKEPHALIN; CHROMATOGRAPHY; PROTEOLYSIS; SEQUENCE AB The amino terminus of bovine pro-opiomelanocortin (N-POMC1-77) is partially processed in the intermediate lobe of the pituitary to N-POMC1-49 and lys-gamma-3-melanotropin. Two pools of N-POMC1-77 were isolated which were differentially glycosylated at threonine45, while N-POMC1-49 isolated from bovine intermediate lobe extracts existed in a non-glycosylated form. This suggested that differential O-linked glycosylation of N-POMC1-77 may regulate cleavage at the Arg49-Lys50 processing site. We tested this hypothesis by incubating N-POMC1-77 glycoforms with purified proopiomelanocortin converting enzyme. Only non-O-glycosylated N-POMC1-77 and O-glycosylated N-POMC1-77 with truncated oligosaccharide sidechains were sensitive to cleavage and generated predominantly lys-gamma-3-melanotropin, identified by high-performance liquid chromatography. These data provide the first functional evidence to support a role for differential O-linked glycosylation in the regulation of the processing of the N-terminus of bovine POMC. C1 NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,BLDG 36,RM 2A21,BETHESDA,MD 20892. ROYAL VICTORIA HOSP,MONTREAL H3A 1A1,QUEBEC,CANADA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 21 TC 32 Z9 32 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 SEP 23 PY 1991 VL 290 IS 1-2 BP 191 EP 194 DI 10.1016/0014-5793(91)81257-9 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GJ553 UT WOS:A1991GJ55300047 PM 1655531 ER PT J AU COHN, KH WANG, FS DESOTOLAPAIX, F SOLOMON, WB PATTERSON, LG ARNOLD, MR WEIMAR, J FELDMAN, JG LEVY, AT LEONE, A STEEG, PS AF COHN, KH WANG, FS DESOTOLAPAIX, F SOLOMON, WB PATTERSON, LG ARNOLD, MR WEIMAR, J FELDMAN, JG LEVY, AT LEONE, A STEEG, PS TI ASSOCIATION OF NM23-H1 ALLELIC DELETIONS WITH DISTANT METASTASES IN COLORECTAL-CARCINOMA SO LANCET LA English DT Note ID INDICATORS AB A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p < 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value. C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT SURG,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT PREVENT MED & COMMUNITY HLTH,BROOKLYN,NY. NCI,PATHOL LAB,BETHESDA,MD 20892. VET ADM MED CTR,DEPT PATHOL,BROOKLYN,NY 11209. RP COHN, KH (reprint author), VET ADM MED CTR,DEPT SURG 112,800 POLY PL,BROOKLYN,NY 11209, USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 10 TC 153 Z9 163 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 21 PY 1991 VL 338 IS 8769 BP 722 EP 724 DI 10.1016/0140-6736(91)91444-Y PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GG104 UT WOS:A1991GG10400005 PM 1679868 ER PT J AU GERSHON, PD AHN, BY GARFIELD, M MOSS, B AF GERSHON, PD AHN, BY GARFIELD, M MOSS, B TI POLY(A) POLYMERASE AND A DISSOCIABLE POLYADENYLATION STIMULATORY FACTOR ENCODED BY VACCINIA VIRUS SO CELL LA English DT Article ID THYMIDINE KINASE GENE; EARLY TRANSCRIPTION FACTOR; RNA-CAPPING ENZYME; MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; BINDING-PROTEIN; FOWLPOX VIRUS; ACID; DNA AB mRNA made in eukaryotic cells typically has a 3' poly(A) tail that is added posttranscriptionally. To investigate mechanisms by which 3' poly(A) is formed, we identified the genes for the two vaccinia virus-encoded polypeptides, VP55 and VP39. Primer-dependent polyadenylation activity was associated exclusively with purified VP55-VP39 heterodimer, which, although stable to column chromatography and glycerol gradient sedimentation, was readily dissociated by antibody to an N-terminal peptide of VP55. Poly(A) polymerase activity was associated with immunopurified VP55, but not with immunopurified or chromatographically purified VP39. VP39 was, however, required for the formation of long poly(A) molecules, in conjunction with either purified VP55 or low concentrations of the heterodimer, and was shown to bind free poly(A). Thus, a catalytic polypeptide and a dissociable poly(A)-binding stimulatory factor each contribute to poly(A) tail formation. No prokaryotic or eukaryotic homologs of either polypeptide were detected in sequence data bases, consistent with the absence of previously reported poly(A) polymerase genes from any source. C1 NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP GERSHON, PD (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 50 TC 108 Z9 111 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 20 PY 1991 VL 66 IS 6 BP 1269 EP 1278 DI 10.1016/0092-8674(91)90048-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GG552 UT WOS:A1991GG55200020 PM 1670500 ER PT J AU CASASFINET, JR KARPEL, RL MAKI, AH KUMAR, A WILSON, SH AF CASASFINET, JR KARPEL, RL MAKI, AH KUMAR, A WILSON, SH TI PHYSICAL STUDIES OF TYROSINE AND TRYPTOPHAN RESIDUES IN MAMMALIAN-A1 HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN - SUPPORT FOR A SEGMENTED STRUCTURE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; DETECTED MAGNETIC-RESONANCE; HELIX-DESTABILIZING PROTEIN; TRIPLET-STATE PROPERTIES; RNA-BINDING PROTEINS; GENE 32 PROTEIN; ESCHERICHIA-COLI; CALF THYMUS; OPTICAL-DETECTION; UNWINDING PROTEINS C1 UNIV CALIF DAVIS, DEPT CHEM, DAVIS, CA 95616 USA. NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. RP UNIV MARYLAND, DEPT CHEM & BIOCHEM, CATONSVILLE, MD 21228 USA. FU NIEHS NIH HHS [ES 02662] NR 62 TC 20 Z9 20 U1 0 U2 1 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 SEP 20 PY 1991 VL 221 IS 2 BP 693 EP 709 DI 10.1016/0022-2836(91)80081-5 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GH947 UT WOS:A1991GH94700026 PM 1656054 ER PT J AU HADLEY, SW AF HADLEY, SW TI OSI PROCEDURES SO NATURE LA English DT Letter RP HADLEY, SW (reprint author), NIH,OFF SCI POLICY & LEGISLAT,OFF DIRECTOR,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 19 PY 1991 VL 353 IS 6341 BP 204 EP 204 DI 10.1038/353204b0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GF674 UT WOS:A1991GF67400022 PM 1896067 ER PT J AU BONOW, RO AF BONOW, RO TI PROGNOSTIC APPLICATIONS OF EXERCISE TESTING SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; MEDICALLY TREATED PATIENTS; CATHETERIZATION; DEATH RP BONOW, RO (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 19 PY 1991 VL 325 IS 12 BP 887 EP 888 DI 10.1056/NEJM199109193251211 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GF616 UT WOS:A1991GF61600011 PM 1875976 ER PT J AU KEISER, HR AF KEISER, HR TI SURREPTITIOUS SELF-ADMINISTRATION OF EPINEPHRINE RESULTING IN PHEOCHROMOCYTOMA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FACTITIOUS ILLNESS RP KEISER, HR (reprint author), NHLBI,BLDG 10,ROOM 8C-103,BETHESDA,MD 20892, USA. NR 13 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 18 PY 1991 VL 266 IS 11 BP 1553 EP 1555 DI 10.1001/jama.266.11.1553 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GE458 UT WOS:A1991GE45800037 PM 1880888 ER PT J AU FISHER, B REDMOND, C AF FISHER, B REDMOND, C TI NEW PERSPECTIVE ON CANCER OF THE CONTRALATERAL BREAST - A MARKER FOR ASSESSING TAMOXIFEN AS A PREVENTIVE AGENT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TRIAL C1 UNIV PITTSBURGH,SCH MED,DEPT BIOSTAT,PITTSBURGH,PA 15261. RP FISHER, B (reprint author), UNIV PITTSBURGH,SCH MED,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,HEADQUARTERS,ROOM 914,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [CA-37377, CA-12027, CA-39086] NR 12 TC 91 Z9 91 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 18 PY 1991 VL 83 IS 18 BP 1278 EP 1280 DI 10.1093/jnci/83.18.1278 PG 3 WC Oncology SC Oncology GA GF670 UT WOS:A1991GF67000001 PM 1832192 ER PT J AU SCHWEITZER, J HANDLEY, FG EDWARDS, J HARRIS, WF GREVER, MR SCHEPARTZ, SA CRAGG, G SNADER, K BHAT, A AF SCHWEITZER, J HANDLEY, FG EDWARDS, J HARRIS, WF GREVER, MR SCHEPARTZ, SA CRAGG, G SNADER, K BHAT, A TI SUMMARY OF THE WORKSHOP ON DRUG DEVELOPMENT, BIOLOGICAL DIVERSITY, AND ECONOMIC-GROWTH SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,EXECUT PLAZA N,SUITE 843,ROCKVILLE,MD 20892. US AGCY INT DEV,SCI & TECHNOL BRANCH,WASHINGTON,DC 20523. NATL SCI FDN,BIOL BEHAV & SOCIAL SCI DIRECTORATE,WASHINGTON,DC 20550. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. FOGARTY INT CTR,INT COORDINAT & LIAISON BRANCH,BETHESDA,MD. NR 0 TC 20 Z9 20 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 18 PY 1991 VL 83 IS 18 BP 1294 EP 1298 DI 10.1093/jnci/83.18.1294 PG 5 WC Oncology SC Oncology GA GF670 UT WOS:A1991GF67000010 PM 1679460 ER PT J AU REDDY, PG GRAHAM, GM DATTA, S GUARINI, L MOULTON, TA JIANG, HP GOTTESMAN, MM FERRONE, S FISHER, PB AF REDDY, PG GRAHAM, GM DATTA, S GUARINI, L MOULTON, TA JIANG, HP GOTTESMAN, MM FERRONE, S FISHER, PB TI EFFECT OF RECOMBINANT FIBROBLAST INTERFERON AND RECOMBINANT IMMUNE INTERFERON ON GROWTH AND THE ANTIGENIC PHENOTYPE OF MULTIDRUG-RESISTANT HUMAN GLIOBLASTOMA-MULTIFORME CELLS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-MELANOMA CELLS; BETA-SER-INTERFERON; GAMMA-INTERFERON; TYPE-5 ADENOVIRUS; TRANSCRIPTIONAL INDUCTION; MONOCLONAL-ANTIBODIES; RECEPTOR EXPRESSION; MALIGNANT GLIOMAS; CARCINOMA-CELLS; GENE-EXPRESSION AB To study the effect of drug resistance on the response of stage IV astrocytomas to interferon, a human glioblastoma multiforme cell line, GBM-18, was transfected with an expression-vector plasmid containing a human multidrug resistance (MDR) gene (pHaMDR1/A), and clones surviving in colchicine were isolated. GBM-18 multidrug-resistant subclones displayed cross-resistance to other chemotherapeutic agents, including vincristine, doxorubicin, and dactinomycin. The multidrug-resistant phenotype was reversible when GBM-18 multidrug-resistant cells were cultured in colchicine and the calcium-channel blocker verapamil. The level of the MDR1 gene (also known as PGY1) message was increased in GBM-18 multidrug-resistant cells selected for increased resistance to colchicine, and this effect was not correlated with an amplification of the MDR1 gene. In both parental GBM-18 and GBM-18 multidrug-resistant cells, growth was suppressed to a greater degree when cultures were treated with the combination of fibroblast interferon (IFN-beta) and immune interferon (IFN-gamma). Parental cells and multidrug-resistant subclones varied in their de novo and/or interferon-modulated expression of HLA class I and class II antigens, a high-molecular-weight melanoma-associated antigen, and intercellular adhesion molecule 1 (ICAM-1). Of the antigens tested, ICAM-1 and HLA class I antigens were the most sensitive to enhanced expression induced by IFN-beta and IFN-gamma when used alone or in combination. The results of the present study indicate that multidrug-resistant human glioblastoma multiforme cells retain their increased sensitivity to the antiproliferative activity of the combination of IFN-beta plus IFN-gamma, and differences in antigenic phenotype are apparent in independent multidrug-resistant glioblastoma multiforme clones. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,650 W 168TH ST,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT UROL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROSURG,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DIV HEMATOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,INST CANC RES,CTR COMPREHENS CANC,NEW YORK,NY 10032. NCI,DIV CANC BIOL & DIAG,CELL BIOL LAB,BETHESDA,MD 20892. NEW YORK MED COLL,DEPT MICROBIOL & IMMUNOL,VALHALLA,NY 10595. FU NCI NIH HHS [CA-39559, CA-35675, CA-37959] NR 61 TC 27 Z9 27 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 18 PY 1991 VL 83 IS 18 BP 1307 EP 1315 DI 10.1093/jnci/83.18.1307 PG 9 WC Oncology SC Oncology GA GF670 UT WOS:A1991GF67000012 PM 1653364 ER PT J AU JOHNSON, ES AF JOHNSON, ES TI NESTED CASE-CONTROL STUDY OF LUNG-CANCER IN THE MEAT INDUSTRY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID SLAUGHTERHOUSE WORKERS; BUTCHERS; MORTALITY RP JOHNSON, ES (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA-30410] NR 15 TC 32 Z9 32 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 18 PY 1991 VL 83 IS 18 BP 1337 EP 1339 DI 10.1093/jnci/83.18.1337 PG 3 WC Oncology SC Oncology GA GF670 UT WOS:A1991GF67000017 PM 1886160 ER PT J AU HENDERSON, DK AF HENDERSON, DK TI POSTEXPOSURE CHEMOPROPHYLAXIS FOR OCCUPATIONAL EXPOSURE TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - CURRENT STATUS AND PROSPECTS FOR THE FUTURE SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 3RD DECENNIAL INTERNATIONAL CONF ON NOSOCOMIAL INFECTIONS - PREVENTING NOSOCOMIAL INFECTIONS : PROGRESS IN THE 1980S ; PLANS FOR THE 1990S CY JUL 31-AUG 03, 1990 CL ATLANTA, GA SP NATL FDN INFECTIOUS DIS, CTR DIS CONTROL ID CONTROLLED TRIAL; ZIDOVUDINE; 3'-AZIDO-3'-DEOXYTHYMIDINE; SUPPRESSION; INFECTION; INVITRO; CELLS; AZT AB Occupational exposures to the human immunodeficiency virus (HIV) continue to occur in the health care setting. Each such exposure is associated with risk for occupational infection. Although occupational HIV infections have been uncommon in health care workers, the occurrence of even one such infection is traumatic for the health care worker and his or her institution. To attempt to prevent infection following occupational exposures, some institutions and investigators have elected to offer postexposure chemoprophylaxis with zidovudine. Unfortunately, data describing the use of nucleoside analogues in animals and humans as antiviral chemoprophylaxis are quite limited and data simply do not exist that definitively support or refute their use in this setting. One can mount an equally reasonable argument for or against the use of these agents in this setting in 1990. This article reviews the available data regarding postexposure chemoprophylaxis, summarizes the clinical experience with zidovudine use for postexposure chemoprophylaxis to date, and evaluates prospects for additional chemoprophylaxis options in the future. RP HENDERSON, DK (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BLDG 10,ROOM 2C146,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 19 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP 16 PY 1991 VL 91 SU 3B BP S312 EP S319 DI 10.1016/0002-9343(91)90388-E PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GH803 UT WOS:A1991GH80300055 PM 1928185 ER PT J AU VENTURA, C GUARNIERI, C STEFANELLI, C CIRIELLI, C LAKATTA, EG CAPOGROSSI, MC AF VENTURA, C GUARNIERI, C STEFANELLI, C CIRIELLI, C LAKATTA, EG CAPOGROSSI, MC TI COMPARISON BETWEEN ALPHA-ADRENERGICMEDIATED AND K-OPIOIDERGIC-MEDIATED INOSITOL(1,4,5)P3 INOSITOL(1,3,4,5)P4 FORMATION IN ADULT CULTURED RAT VENTRICULAR CARDIOMYOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INOSITOL PHOSPHATES; CARDIAC MYOCYTES; CA-2+; RECEPTOR; RELEASE; 1,4,5-TRISPHOSPHATE; ADRENOCEPTORS; ACCOMPANIES; STIMULATION; INCREASE C1 UNIV BOLOGNA,DEPT BIOCHEM,I-40126 BOLOGNA,ITALY. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP VENTURA, C (reprint author), UNIV SASSARI,INST BIOCHEM,VIALE S PIETRO 43-B,I-07100 SASSARI,ITALY. NR 25 TC 38 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 16 PY 1991 VL 179 IS 2 BP 972 EP 978 DI 10.1016/0006-291X(91)91913-W PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GF218 UT WOS:A1991GF21800039 PM 1898416 ER PT J AU WEIHE, E HORSCH, D EIDEN, LE HARTSCHUH, W AF WEIHE, E HORSCH, D EIDEN, LE HARTSCHUH, W TI DUAL PRESENCE OF CHROMOGRANIN-A-LIKE IMMUNOREACTIVITY IN A POPULATION OF ENDOCRINE-LIKE CELLS AND IN NERVE-FIBERS IN THE HUMAN ANAL-CANAL SO NEUROSCIENCE LETTERS LA English DT Article DE ANAL CANAL; ANAL TRANSITIONAL ZONE; ANAL GLAND; EPITHELIUM; SKIN; INNERVATION; ENDOCRINE CELL; PARACRINE CELL; MERKEL CELL; DIFFUSE NEUROENDOCRINE SYSTEM; CHROMOGRANIN-A; PEPTIDE ID PEPTIDES; PANCREASTATIN; SECRETION; WIDESPREAD AB Light microscopic immunohistochemistry was used to investigate the presence and distribution of chromogranin A-like immunoreactivity in the human anal canal. In the anal transitional zone (ATZ), anal duct and anal gland epithelium, a varied number of mostly elongated cells strongly stained for CGA, using an antibody directed to a highly species-conserved region of the CGA molecule or the monoclonal antibody LK2H10. The density of CGA-immunoreactive (ir) cells strikingly increased from the ATZ epithelium towards the anal gland epithelium. CGA-ir cells possessed single processes running perpendicularly to reach the epithelial surface and exhibited basal ramifications that extended parallel to the basal lamina. The number of CGA-ir cells in anal glands exceeded CGA-ir cells in the crypt-bearing colorectal-type mucosa. The abundant population of CGA-ir cells in the anal canal most likely represents a population of specialized endocrine or paracrine cells. CGA-like immunoreactivity was also present in anocutaneous Merkel cells. A sparse number of vascular and non-vascular CGA-ir varicose nerve fibers was present throughout the layers and rostrocaudal divisions of the anal canal and in the perianal skin. Proposed functions of CGA in neuroendocrine cells and nerves of the anal canal include calcium binding and regulation, secretory granule matrix formation, and generation of bioactive peptides. C1 NIMH,MOLEC BIOL UNIT,BETHESDA,MD 20892. UNIV CLIN HEIDELBERG,DEPT DERMATOL,HEIDELBERG,GERMANY. RP WEIHE, E (reprint author), UNIV MAINZ,INST ANAT,SAARSTR 19-21,W-6500 MAINZ,GERMANY. OI Eiden, Lee/0000-0001-7524-944X NR 18 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 16 PY 1991 VL 130 IS 2 BP 190 EP 194 DI 10.1016/0304-3940(91)90394-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA GG575 UT WOS:A1991GG57500013 PM 1795880 ER PT J AU SILVERTON, JV QUINN, FR HAUGWITZ, RD AF SILVERTON, JV QUINN, FR HAUGWITZ, RD TI STRUCTURE OF ISOPROPYL 2-CHLORO-5-(2-METHYL-1,4-OXATHIIN-3-YLCARBONYLAMINO)-BENZOATE, OXATHIIN CARBOXANILIDE SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Article AB C16H18ClNO4S, M(r) = 355.8, monoclinic, P2(1)/a, a = 8.784 (1), b = 20.342 (1), c = 9.522 (1) angstrom, beta = 98.61 (1)-degrees, V = 1682.3 angstrom 3, Z = 4, D(x) = 1.404 g cm-3, lambda(Cu K-alpha) = 1.5418 angstrom, mu = 33.5 cm-1, F(000) = 744, T = 295 K, final R = 0.044 for 2156 observed reflections. The crystal structure and conformation are reported for this new potential AIDS drug whose mode of action differs from that of the dideoxynucleosides. The molecules are hydrogen bonded and form infinite chains along the a axis. The crystal packing leads to parallel stacking of the rings of the molecules. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP SILVERTON, JV (reprint author), NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD SEP 15 PY 1991 VL 47 BP 1911 EP 1913 DI 10.1107/S0108270191002664 PN 9 PG 3 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA GH168 UT WOS:A1991GH16800046 ER PT J AU COATES, RJ ELEY, JW BLOCK, G GUNTER, EW SOWELL, AL GROSSMAN, C GREENBERG, RS AF COATES, RJ ELEY, JW BLOCK, G GUNTER, EW SOWELL, AL GROSSMAN, C GREENBERG, RS TI AN EVALUATION OF A FOOD FREQUENCY QUESTIONNAIRE FOR ASSESSING DIETARY-INTAKE OF SPECIFIC CAROTENOIDS AND VITAMIN-E AMONG LOW-INCOME BLACK-WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLACKS; CAROTENE; CAROTENOIDS; DIET; NUTRITIONAL STATUS; QUESTIONNAIRES; SMOKING; VITAMIN-E ID ALPHA-TOCOPHEROL LEVELS; BETA-CAROTENE; PLASMA RETINOL; DETERMINANTS; CHOLESTEROL; METABOLISM; SMOKING; ADULTS AB The National Cancer Institute diet questionnaire was evaluated for use in a low-income black population. Data were collected from 91 women aged 30-69 years who were hospital outpatients in Atlanta, Georgia, June through August, 1988. Six ethnic and regional foods added to the questionnaire were found to be important contributors to intakes of several nutrients. Although 17 records were identified as containing probable recording or reporting errors, intakes of carotenes, alpha-carotene, beta-carotene, cryptoxanthin, and vitamin E were significantly and positively associated with serum levels of their referent nutrients. Among nonsmokers, correlation coefficients ranged from 0.32 to 0.45, adjusted for age, body mass index, alcohol and calorie intakes, medications and vitamin supplement use, and serum cholesterol and triglycerides. When questionnaires containing identified errors were omitted, correlations ranged from 0.30 to 0.54. There were no correlations between dietary intakes of lycopene and lutein and blood levels (-0.06 to 0.09). Among smokers, diet-serum correlations were reduced (0.00 to 0.32). These correlations are similar to those reported in research on vitamin E and carotenoids in other populations. These results suggest that the questionnaire is as valid for use in this population as it is in other populations. C1 CTR DIS CONTROL,CTR CHRON DIS PREVENT & HLTH PROMOT,DIV NUTR,ATLANTA,GA 30333. EMORY UNIV,SCH MED,WINSHIP CANC CTR,ATLANTA,GA 30322. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. CTR DIS CONTROL,CTR ENVIRONM HLTH & INJURY CONTROL,HANES LAB,ATLANTA,GA 30333. RP COATES, RJ (reprint author), EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,1599 CLIFTON RD NE,ATLANTA,GA 30329, USA. RI Block, Gladys/E-3304-2010 FU NCI NIH HHS [CA17998-15] NR 38 TC 159 Z9 159 U1 1 U2 5 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1991 VL 134 IS 6 BP 658 EP 671 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GL646 UT WOS:A1991GL64600011 PM 1951269 ER PT J AU MOLCHAN, SE LAWLOR, BA HILL, JL MELLOW, AM DAVIS, CL MARTINEZ, R SUNDERLAND, T AF MOLCHAN, SE LAWLOR, BA HILL, JL MELLOW, AM DAVIS, CL MARTINEZ, R SUNDERLAND, T TI THE TRH STIMULATION TEST IN ALZHEIMERS-DISEASE AND MAJOR DEPRESSION - RELATIONSHIP TO CLINICAL AND CSF MEASURES SO BIOLOGICAL PSYCHIATRY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; PRIMARY DEGENERATIVE DEMENTIA; CEREBROSPINAL-FLUID; SENILE DEMENTIA; ENDOGENOUS-DEPRESSION; GENDER DIFFERENCES; ELDERLY CONTROLS; SCALE; TSH; NEUROPEPTIDES AB A blunted thyroid-stimulating hormone (TSH) reponse to exogenous thyrotropin-releasing hormone (TRH) has been reported to occur consistently in patients with major depression and less consistently in patients with Alzheimer's disease (AD). In this study we compared the TSH response to TRH in a large group (n = 40) of AD patients, elderly patients with major depression (n = 17), and age-matched controls (n = 14) to further characterize how it may relate to clinical variables, baseline thyroid function tests, and cerebrospinal fluid measures. Comparisons of TRH stimulation test response across all three groups revealed that patients with major depression had lower stimulated TSH levels (DELTA-maxTSH) (p < 0.02) and higher (though still within normal limits) mean thyroxine (T4) levels (p < 0.05) than the AD patients or controls. AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p < 0.03) and tended to be more severely demented (p < 0.01) than those with a nonblunted response. C1 NIMH,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,DIV GEROPSYCHIAT,NEW YORK,NY 10029. UNIV MICHIGAN,MED CTR,DEPT PSYCHIAT,ANN ARBOR,MI 48109. NR 38 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1991 VL 30 IS 6 BP 567 EP 576 DI 10.1016/0006-3223(91)90026-I PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GF821 UT WOS:A1991GF82100004 PM 1932406 ER PT J AU GOLD, JM EGAN, MF KIRCH, DG GOLDBERG, TE DANIEL, DG BIGELOW, LB WYATT, RJ AF GOLD, JM EGAN, MF KIRCH, DG GOLDBERG, TE DANIEL, DG BIGELOW, LB WYATT, RJ TI TARDIVE-DYSKINESIA - NEUROPSYCHOLOGICAL, COMPUTERIZED TOMOGRAPHIC, AND PSYCHIATRIC SYMPTOM FINDINGS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID ABNORMAL INVOLUNTARY MOVEMENTS; COGNITIVE DYSFUNCTION; NEGATIVE SYMPTOMS; BASAL GANGLIA; MEDICATED SCHIZOPHRENICS; IMPAIRMENT; DISEASE; PERFORMANCE; ASSOCIATION; CIRCUITS AB Prior studies have suggested that schizophrenic patients with tardive dyskinesia (TD) have an unusual incidence of cognitive impairment, structural brain abnormalities, and negative symptoms. Twenty-seven schizophrenic patients with TD and an equal number of age-, gender-, and education-matched schizophrenic controls were studied. Each patient received neuropsychological testing, psychiatric symptom ratings, and most had cerebral computed tomography (CT) scans. Patients with TD significantly differed from controls on only 1 of 23 cognitive measures, and the overall group performance profiles were highly similar. No differences were observed on symptom ratings. Patients with TD had significantly smaller ventricular-brain ratios (VBRs) than controls. These data fail to support an association of TD with global measures of "organicity." Abnormal movements may result from specific dysfunction within the more purely motor circuits of the basal ganglia without compromising other neural systems involved in cognitive processing. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,CLIN & RES SERV BRANCH,WASHINGTON,DC 20032. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP GOLD, JM (reprint author), NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 48 TC 15 Z9 15 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1991 VL 30 IS 6 BP 587 EP 599 DI 10.1016/0006-3223(91)90028-K PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GF821 UT WOS:A1991GF82100006 PM 1681948 ER PT J AU SPANGRUDE, GJ SMITH, L UCHIDA, N IKUTA, K HEIMFELD, S FRIEDMAN, J WEISSMAN, IL AF SPANGRUDE, GJ SMITH, L UCHIDA, N IKUTA, K HEIMFELD, S FRIEDMAN, J WEISSMAN, IL TI MOUSE HEMATOPOIETIC STEM-CELLS SO BLOOD LA English DT Article ID TYROSINE KINASE RECEPTOR; GROWTH-FACTOR; BONE-MARROW; W-LOCUS; PROTO-ONCOGENE; W/WV MICE; SI-LOCUS; CFU-S; LIGAND; PURIFICATION C1 STANFORD UNIV,MED CTR,SCH MED,HOWARD HUGHES MED INST,DEPT PATHOL,STANFORD,CA 94305. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. STANFORD UNIV,MED CTR,SCH MED,HOWARD HUGHES MED INST,DEPT DEV BIOL,STANFORD,CA 94305. CELLPRO,BOTHELL,WA. NR 56 TC 211 Z9 212 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1991 VL 78 IS 6 BP 1395 EP 1402 PG 8 WC Hematology SC Hematology GA GF444 UT WOS:A1991GF44400001 PM 1884012 ER PT J AU KARP, JE BRODER, S AF KARP, JE BRODER, S TI ACQUIRED-IMMUNODEFICIENCY-SYNDROME AND NON-HODGKINS-LYMPHOMAS SO CANCER RESEARCH LA English DT Review ID EPSTEIN-BARR-VIRUS; C-MYC ONCOGENE; RETINOBLASTOMA SUSCEPTIBILITY GENE; BONE-MARROW TRANSPLANTATION; HUMAN HEMATOPOIETIC-CELLS; NERVOUS-SYSTEM LYMPHOMA; B-CELL; ANTISENSE OLIGODEOXYNUCLEOTIDE; LYMPHOPROLIFERATIVE DISORDERS; CHROMOSOMAL-ABNORMALITIES C1 NCI,OFF DIRECTOR,9000 ROCKVILLE PK,BLDG 31,ROOM 11A48,BETHESDA,MD 20892. NR 116 TC 74 Z9 74 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4743 EP 4756 PG 14 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300001 PM 1893369 ER PT J AU VANOSDOL, W FUJIMORI, K WEINSTEIN, JN AF VANOSDOL, W FUJIMORI, K WEINSTEIN, JN TI AN ANALYSIS OF MONOCLONAL-ANTIBODY DISTRIBUTION IN MICROSCOPIC TUMOR NODULES - CONSEQUENCES OF A BINDING-SITE BARRIER SO CANCER RESEARCH LA English DT Article ID HUMAN-COLON; CARCINOEMBRYONIC ANTIGEN; LYMPHATIC CAPILLARIES; MODELING ANALYSIS; SOLID TUMORS; BLOOD-FLOW; PHARMACOKINETICS; PERMEABILITY; TRANSPORT; SPHEROIDS AB Rational in vivo application of monoclonal antibodies for diagnosis and therapy of cancer requires an understanding of both the global and microscopic pharmacology of macromolecular ligands. Here, we introduce a new mathematical model for antibody distribution into small, prevascular, densely packed nodules (representing either primary or metastatic tumor). For the analysis, we link together several aspects of antibody pharmacology: the global (whole body) pharmacokinetics; transcapillary transport into normal tissue interstitium surrounding the nodule; diffusion into the nodule; nonspecific binding and/or partitioning; specific binding to tumor antigen; metabolism; and lymphatic outflow from the tissue space. Input parameter values are estimated from experimental studies in vitro, in animals, and in clinical trials. Our aim is to explore the sensitivity of antibody localization to variation in three of the important parameters of this model: the rate of transcapillary transport; the rate of lymphatic outflow; and the antigen density. Predictions based on this analysis include the following: (a) High rates of transcapillary transport influx or low rates of lymphatic efflux will enhance antibody percolation into the tumor nodule at early times after injection and increase the average antibody concentration in the tumor at all times; (b) Changes in antibody influx rate will affect the antibody distribution in the tumor at earlier times than do changes in the efflux rate; (c) Reducing the antigen concentration will increase the uniformity of antibody penetration but lower the average concentration in the tumor at all times after injection; and (d) Counter to intuition, lowering the antigen concentration can increase the peak concentrations achieved toward the center of the nodule. If, in addition, there is any metabolism of bound antibody, the concentration-time integral (i.e., the "area under the curve") for the center of the nodule will also be increased by decreasing the antigen concentration. These predictions directly reflect the "binding site barrier" hypothesis of Weinstein et al. (Ann. NY Acad. Sci., 507: 199-210, 1987) and Fujimori et al. (Cancer Res., 49: 5656-5663, 1989; J. Nucl. Med., 31: 1191-1198, 1990). In general, and perhaps surprisingly until one considers the problem carefully, the parameters governing antibody percolation can have opposite effects on the uniformity of antibody distribution at early and late times. These calculations, using the PERC program set, were done for antibodies, but we believe that the "binding site barrier" will also prove important for other injected macromolecules, for at least some highly bindable injected small molecules, for lymphokines and cytokines released from transfected cells injected in vivo, and, indeed, for endogenous species such as the autocrine-paracrine factors. C1 HOKKAIDO UNIV, SCH MED, DEPT NUCL MED, KITA KU, SAPPORO, HOKKAIDO 060, JAPAN. RP VANOSDOL, W (reprint author), NCI, MATH BIOL LAB, BLDG 10, ROOM 4B-56, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 48 TC 117 Z9 118 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4776 EP 4784 PG 9 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300005 PM 1893370 ER PT J AU POTISCHMAN, N BRINTON, LA LAIMING, VA REEVES, WC BRENES, MM HERRERO, R TENORIO, F DEBRITTON, RC GAITAN, E AF POTISCHMAN, N BRINTON, LA LAIMING, VA REEVES, WC BRENES, MM HERRERO, R TENORIO, F DEBRITTON, RC GAITAN, E TI A CASE-CONTROL STUDY OF SERUM FOLATE LEVELS AND INVASIVE CERVICAL-CANCER SO CANCER RESEARCH LA English DT Article ID ORAL-CONTRACEPTIVE THERAPY; LATIN-AMERICA; FOLIC-ACID; RISK; WOMEN; DIET; EPIDEMIOLOGY; METABOLISM; DYSPLASIA AB Although small intervention trials have suggested that folate supplementation reduces cervical dysplasia, the association of blood folate concentrations with invasive cervical cancer risk has not been investigated in well-controlled epidemiological studies. A study was conducted with newly diagnosed Stage I and II invasive cervical cancer cases and controls in 4 Latin American countries. Ninety-five % of subjects donated blood samples, resulting in 330 case and 565 control serum samples analyzed for folate concentrations by radioassay. Cases did not differ significantly from controls in mean levels of folate (5.00 and 4.90 ng/ml, respectively). No associations were observed between quartiles of serum folate and risk of cervical cancer after adjustment for other risk factors, and no interactions with established risk factors were observed. Folate levels were also unrelated to risk among women who might have compromised folate status because of recent or extended oral contraceptive usage or multiple pregnancies. Further, mean levels of folate were similar by stage of disease, arguing against an effect of disease progression on serum values. These results do not support a role for serum folate in the etiology of invasive cervical cancer. C1 MICROBIOL ASSOCIATES INC,BETHESDA,MD 20016. CTR DIS CONTROL,ATLANTA,GA 30333. GORGAS MEM LAB,PANAMA CITY,PANAMA. CAJA COSTARRICENSE SEGURO SOCIAL,UNIDAD NACL CANCEROL,SAN JOSE,COSTA RICA. INST MEXICANO SEGURO SOCIAL,HOSP ONCOL NACL,MEXICO CITY 7,DF,MEXICO. INST ONCOL NACL,PANAMA CITY,PANAMA. INST NACL CANCEROL,BOGOTA,COLOMBIA. RP POTISCHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [R01-CA-42042, N01-CP-41026] NR 33 TC 44 Z9 44 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4785 EP 4789 PG 5 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300006 PM 1893371 ER PT J AU FUJIMORI, K FISHER, DR WEINSTEIN, JN AF FUJIMORI, K FISHER, DR WEINSTEIN, JN TI INTEGRATED MICROSCOPIC-MACROSCOPIC PHARMACOLOGY OF MONOCLONAL-ANTIBODY RADIOCONJUGATES - THE RADIATION-DOSE DISTRIBUTION SO CANCER RESEARCH LA English DT Article ID SOLID TUMORS; INTERSTITIAL PRESSURE; MODELING ANALYSIS; BLOOD-FLOW; MACROMOLECULES; PERMEABILITY; RADIOIMMUNOTHERAPY; MICROVASCULATURE; XENOGRAFTS; THERAPY AB Accurate dosimetry is essential for the assessment of radioimmunotherapy. Most often studied to date has been the macroscopic dosimetry related to organ and tumor distribution of the radiolabeled antibody, but the question of microscopic dose heterogeneity is also important. To address the latter issue, we have taken an integrated approach to the pharmacology, taking into account whole-body distribution, transcapillary transport, percolation through the tumor interstitial space, antigen-antibody interaction, and antibody metabolism. The first step is to simulate the spatial antibody concentration profile in a tumor as a function of time after i.v. (e.g., bolus) injection, using reasonable values for the parameters involved. The second step is to calculate, also as a function of time, the absorbed radiation dose distribution resulting from each concentration profile. Parameter values for IgG pharmacology and a radiation point source function for I-131 are used to explore the effect of antibody distribution profiles on absorbed dose in the tumor. The geometry simulated corresponds to a spherical nodule of densely packed tumor cells. Absorbed doses are calculated for radiation from a single nodule (e.g., a micrometastasis or prevascular primary tumor) and for a cubic lattice of such nodules (e.g., corresponding to nodular lymphoma). As noted in our previous studies, there is a "binding site barrier." Binding to antigen retards antibody percolation into the nodules; high antibody affinity tends to decrease percolation and give a higher absorbed dose near the surface of each nodule. Heterogeneous antibody distribution results in a heterogeneous absorbed dose. This is more apparent in the case of radiation from a single nodule than it is for radiation from within an array of nodules. Dehalogenation results in a lower absorbed dose over time, and the effect is more apparent at later times after injection. PERC-RAD, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of macroscopic and microscopic parameters on the distribution of radioimmunoconjugates and on the consequent profile of absorbed radiation dose in tumors. This mathematical model and the general principles developed here can be applied as well to other radiolabeled biological ligands. C1 NCI, MATH BIOL LAB, BLDG 10, ROOM 4B-56, BETHESDA, MD 20892 USA. PACIFIC NW LAB, RICHLAND, WA 99352 USA. FU NCI NIH HHS [CA44991] NR 34 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4821 EP 4827 PG 7 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300012 PM 1893374 ER PT J AU CROUCH, GD HELMAN, LJ AF CROUCH, GD HELMAN, LJ TI ALL-TRANS-RETINOIC ACID INHIBITS THE GROWTH OF HUMAN RHABDOMYOSARCOMA CELL-LINES SO CANCER RESEARCH LA English DT Article ID CHICK LIMB BUD; VITAMIN-A; PROMYELOCYTIC LEUKEMIA; BINDING PROTEINS; FACTOR-II; RECEPTOR; DIFFERENTIATION; EXPRESSION; GENE; IDENTIFICATION AB We have been evaluating the role of all-trans-retinoic acid (RA) in the differentiation and growth of human rhabdomyosarcoma (RMS) cell lines. Treatment of both embryonal (RD) and alveolar (RH30) human RMS cell lines with all-trans-RA resulted in a dose-dependent inhibition of cell growth with a maximal inhibition of 92 and 66%, respectively, at 5 x 10(-6) M. When 13-cis-RA was used under identical experimental conditions, maximal growth inhibition was 41 and 37%, respectively. This stereo-specific growth inhibition was not associated with morphological or biochemical evidence of myogenic differentiation. Furthermore, all-trans-RA demonstrated no evidence of competition with binding of insulin-like growth factor II (IGF-II), an autocrine growth factor in RMS, to its membrane receptor as evaluated by an [I-125]IGF-I receptor-binding assay. Attempts to rescue all-trans-RA growth-inhibited RMS cells with exogenous IGF-II resulted in no increase in growth compared to cells treated with all-trans-RA alone. We conclude that RA inhibits the growth of human RMS cell lines in a dose-dependent, stereo-specific manner, is not associated with differentiation, and does not appear to be directly related to IGF-II. C1 NCI,MOLEC GENET SECT,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 38 TC 37 Z9 37 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4882 EP 4887 PG 6 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300021 PM 1893378 ER PT J AU MITSUDOMI, T STEINBERG, SM OIE, HK MULSHINE, JL PHELPS, R VIALLET, J PASS, H MINNA, JD GAZDAR, AF AF MITSUDOMI, T STEINBERG, SM OIE, HK MULSHINE, JL PHELPS, R VIALLET, J PASS, H MINNA, JD GAZDAR, AF TI RAS GENE-MUTATIONS IN NON-SMALL-CELL LUNG CANCERS ARE ASSOCIATED WITH SHORTENED SURVIVAL IRRESPECTIVE OF TREATMENT INTENT SO CANCER RESEARCH LA English DT Note ID ONCOGENE ACTIVATION; ADENOCARCINOMA; AMPLIFICATION; RESISTANCE AB We analyzed 66 non-small cell lung cancer cell lines for mutations at codons 12, 13, and 61 of all three ras genes and correlated the findings with patient survival. We used designed restriction fragment-length polymorphisms to detect mutations after amplification of ras-specific sequences by the polymerase chain reaction. We found 19 mutations of ras genes (29%), and 11 of these 19 (58%) were at codon 12 of the K-ras gene. By univariate analysis, the presence of any ras mutation in cell lines from patients who received curative intent treatment was associated with a shorter survival (P2 = 0.002). For patients who received only palliative treatment, detection of K-ras mutations at codon 12 was associated with a shortened survival (P2 = 0.0103), but this analysis was not statistically significant for the group with any ras mutation (P2 = 0.093). The Cox proportional hazards model also predicted a higher risk for patients with any type of ras mutations. We conclude that ras mutations, present in a subset of non-small cell lung cancers, are independently associated with the shortened survival of patients, irrespective of treatment intent. C1 NCI, USN, MED ONCOL BRANCH, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 27 TC 230 Z9 232 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 BP 4999 EP 5002 PG 4 WC Oncology SC Oncology GA GE303 UT WOS:A1991GE30300039 PM 1654209 ER PT J AU HARRIS, CC AF HARRIS, CC TI CHEMICAL AND PHYSICAL CARCINOGENESIS - ADVANCES AND PERSPECTIVES FOR THE 1990S SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 82ND ANNUAL MEETING OF THE AMERICAN ASSOC FOR CANCER RESEARCH CY MAY 15, 1991 CL HOUSTON, TX SP AMER ASSOC CANC RES ID BRONCHIAL EPITHELIAL-CELLS; DIOL-EPOXIDE-DNA; HARVEY-RAS ONCOGENE; PROTEIN-KINASE-C; POLYCYCLIC AROMATIC-HYDROCARBONS; NEUROFIBROMATOSIS TYPE-1 GENE; PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN COLORECTAL-CARCINOMA; SPONTANEOUS MUTATION-RATES; MOUSE SKIN CARCINOGENESIS AB Carcinogenesis is a multistage process driven by carcinogen-induced genetic and epigenetic damage in susceptible cells that gain a selective growth advantage and undergo clonal expansion as the result of activation of protooncogenes and/or inactivation of tumor suppressor genes. Therefore, the mutational spectra of chemical and physical carcinogens in these critical genes are of interest to define endogenous and exogenous mutational mechanisms. The p53 tumor suppressor gene is ideally suited for analysis of the mutational spectrum. Such an analysis has revealed evidence for both exogenous and endogenous molecular mechanisms of carcinogenesis. For example, an informative p53 mutational spectrum of frequent G --> T transversions in codon 249 is found in hepatocellular carcinomas from either Qidong, People's Republic of China, or southern Africa. This observation links exposure to aflatoxin B1, a known cancer risk factor in these geographic regions, with a specific mutation in a cancer-related gene. Other studies indicate that abnormalities in genes controlling the cell cycle may cause genomic instability and increase the probability of neoplastic transformation. Finally, mechanistic understanding of carcinogenesis is leading to improved cancer risk assessment and to the identification of individuals at high cancer risk. RP HARRIS, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892, USA. NR 469 TC 497 Z9 504 U1 3 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 SU S BP S5023 EP S5044 PG 22 WC Oncology SC Oncology GA GE627 UT WOS:A1991GE62700004 ER PT J AU HOWLEY, PM AF HOWLEY, PM TI ROLE OF THE HUMAN PAPILLOMAVIRUSES IN HUMAN CANCER SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 82ND ANNUAL MEETING OF THE AMERICAN ASSOC FOR CANCER RESEARCH CY MAY 15, 1991 CL HOUSTON, TX SP AMER ASSOC CANC RES ID CARCINOMA CELL-LINES; CONTAINS SEPARATE DOMAINS; KINASE-II PHOSPHORYLATION; SIMPLEX TYPE-2 VIRUS; CERVICAL-CARCINOMA; ADENOVIRUS E1A; LARGE-T; TUMOR-ANTIGEN; TRANSCRIPTIONAL ANALYSIS; MUTATIONAL ANALYSIS AB The papillomaviruses associated with human anogenital carcinomas encode two transforming genes, E6 and E7. The oncoprotein products of these two genes complex with the tumor suppressor gene products p53 and pRB, respectively. The loss of the normal function of these tumor suppressor gene products, either as a consequence of their association with E6 and E7 or by mutation, appears to be a common event in human cervical carcinogenesis. RP HOWLEY, PM (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. NR 60 TC 241 Z9 242 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 SU S BP S5019 EP S5022 PG 4 WC Oncology SC Oncology GA GE627 UT WOS:A1991GE62700003 PM 1653110 ER PT J AU LIOTTA, LA STETLERSTEVENSON, WG AF LIOTTA, LA STETLERSTEVENSON, WG TI TUMOR INVASION AND METASTASIS - AN IMBALANCE OF POSITIVE AND NEGATIVE REGULATION SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 82ND ANNUAL MEETING OF THE AMERICAN ASSOC FOR CANCER RESEARCH CY MAY 15, 1991 CL HOUSTON, TX SP AMER ASSOC CANC RES ID RECONSTITUTED BASEMENT-MEMBRANE; HUMAN AMNIOTIC MEMBRANE; HUMAN-BREAST TUMORS; NIH 3T3 CELLS; TISSUE INHIBITOR; IV COLLAGENASE; PLASMINOGEN-ACTIVATOR; INTERSTITIAL COLLAGENASE; GENE-EXPRESSION; ENDOTHELIAL-CELLS AB A group of coordinated cellular processes, not just one gene product, is responsible for invasion and metastasis, the most life-threatening aspect of cancer. It is now recognized that negative factors may be just as important as positive elements. Genetic changes causing an imbalance of growth regulation lead to uncontrolled proliferation necessary for both primary tumor and metastasis expansion. However, unrestrained growth does not, by itself, cause invasion and metastasis. This phenotype may require additional genetic changes. Thus, tumorigenicity and metastatic potential have both overlapping and separate features. Invasion and metastasis can be facilitated by proteins which stimulate tumor cell attachment to host cellular or extracellular matrix determinants, tumor cell proteolysis of host barriers, such as the basement membrane, tumor cell locomotion, and tumor cell colony formation in the target organ for metastasis. Facilitory proteins may act at many levels both intracellularly or extracellularly but are counterbalanced by factors which can block their production, regulation, or action. A common theme has emerged. In addition to loss of growth control, an imbalanced regulation of motility and proteolysis appears to be required for invasion and metastasis. RP LIOTTA, LA (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 95 TC 702 Z9 729 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 SU S BP S5054 EP S5059 PG 6 WC Oncology SC Oncology GA GE627 UT WOS:A1991GE62700006 ER PT J AU MITCHELL, JB GLATSTEIN, E AF MITCHELL, JB GLATSTEIN, E TI RADIATION ONCOLOGY - PAST ACHIEVEMENTS AND ONGOING CONTROVERSIES SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 82ND ANNUAL MEETING OF THE AMERICAN ASSOC FOR CANCER RESEARCH CY MAY 15, 1991 CL HOUSTON, TX SP AMER ASSOC CANC RES ID OXYGEN ENHANCEMENT RATIO; BREAST CANCER-CELLS; BUTHIONINE SULFOXIMINE; ADRIAMYCIN RESISTANCE; THERAPY; GLUTATHIONE; RADIOTHERAPY; TUMOR; CARCINOMA; SURVIVAL AB With the development of megavoltage treatment and computerized treatment planning the quality and precision of radiation oncology has steadily improved. Likewise, these developments have contributed to better local control for some cancers; however, micrometastatic lesions beyond the radiation treatment field and ineffective systemic treatments for many malignancies hamper efforts at the most important oncological end point, survival. Major advances in cancer therapy are therefore likely to come with improved combined modality treatment representing integration of local modalities with the systemic. These advances, in our opinion, will come from biological developments that address the problems that the modern oncologist faces at the cellular level. The biological developments will incorporate modern molecular biology, continued probing for biochemical mechanisms, and an intensified effort to learn more about the complexities of human tumor physiology. C1 NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892. NR 63 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 SU S BP S5065 EP S5073 PG 9 WC Oncology SC Oncology GA GE627 UT WOS:A1991GE62700008 ER PT J AU ROSENBERG, SA AF ROSENBERG, SA TI IMMUNOTHERAPY AND GENE-THERAPY OF CANCER SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 82ND ANNUAL MEETING OF THE AMERICAN ASSOC FOR CANCER RESEARCH CY MAY 15, 1991 CL HOUSTON, TX SP AMER ASSOC CANC RES ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; PURIFIED HUMAN INTERLEUKIN-2; HIGH-DOSE INTERLEUKIN-2; MURINE TUMOR; RECOMBINANT INTERLEUKIN-2; ANTITUMOR-ACTIVITY; ADOPTIVE IMMUNOTHERAPY; INVIVO DISTRIBUTION AB In the past decade, immunotherapies have been developed that are capable of causing prolonged cancer regressions in selected patients with advanced metastatic disease. In the past year, attempts at the gene therapy of cancer have begun. These experimental cancer treatments deserve vigorous exploration. RP ROSENBERG, SA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 43 TC 181 Z9 181 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1991 VL 51 IS 18 SU S BP S5074 EP S5079 PG 6 WC Oncology SC Oncology GA GE627 UT WOS:A1991GE62700009 PM 1884383 ER PT J AU SU, TP AF SU, TP TI SIGMA-RECEPTORS - PUTATIVE LINKS BETWEEN NERVOUS, ENDOCRINE AND IMMUNE-SYSTEMS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review ID GUINEA-PIG BRAIN; STIMULATED PHOSPHOINOSITIDE METABOLISM; POSSIBLE THERAPEUTIC IMPORTANCE; DEXTROMETHORPHAN BINDING-SITES; POTENTIAL ANTIPSYCHOTIC DRUG; ETORPHINE-INACCESSIBLE SITES; INDUCED NEURONAL ACTIVATION; RAT-BRAIN; PHENCYCLIDINE RECEPTORS; HIGH-AFFINITY AB The sigma-receptor is a neuronal substrate that binds several psychoactive compounds. These include cocaine, some steroids, dextromethorphan, phencyclidine (PCP), and benzomorphans such as pentazocine and N-allyl-normatezocine (SKF-10047). Many newer atypical antipsychotic drugs also bind to the sigma-receptor. The sigma-receptor, however, is not the PCP receptor. The sigma-receptor exists in the central nervous system, endocrine, immune and certain peripheral tissues. Progesterone and certain steroids have been shown to represent endogenous ligands for the sigma-receptor. The sigma-receptor resides likely in the nonsynaptic region of the plasma membrane. The sigma-receptor exists in two forms: high-affinity and low-affinity. The solubilized sigma-receptor retains all of the pharmacological characteristics of a membrane-bound receptor. A major physiological role of the sigma-receptor may involve the modulation of a tonic potassium channel. RP SU, TP (reprint author), NIDA,ADDICT RES CTR,NEUROPHARMACOL LAB,NEUROCHEM UNIT,POB 5180,BALTIMORE,MD 21224, USA. NR 129 TC 145 Z9 147 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD SEP 15 PY 1991 VL 200 IS 3 BP 633 EP 642 DI 10.1111/j.1432-1033.1991.tb16226.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF511 UT WOS:A1991GF51100004 PM 1655424 ER PT J AU RENSHAW, RW GONDA, MA CASEY, JW AF RENSHAW, RW GONDA, MA CASEY, JW TI STRUCTURE AND TRANSCRIPTIONAL STATUS OF BOVINE SYNCYTIAL VIRUS IN CYTOPATHIC INFECTIONS SO GENE LA English DT Article DE RECOMBINANT DNA; RETROVIRUS; SPUMAVIRUS; FOAMY VIRUS; MOLECULAR CLONES; LINEAR VIRAL DNA; SINGLE-STRANDED GAP IN DNA; PHAGE-LAMBDA-VECTOR; BSV, LENTIVIRUSES ID HUMAN SPUMARETROVIRUS; NUCLEOTIDE-SEQUENCE; FOAMY VIRUS; POL GENES; DNA; VISNA; RETROVIRUSES; GENOME; ACID; AIDS AB The genomic structure of bovine syncytial virus (BSV), a virus commonly infecting cattle, was examined in order to gain in sights into the nature of viral DNA (vDNA) intermediates and the transcriptional status of the virus in cytopathic infections. In dog Cf2Th cells, the DNA intermediate of BSV was found to exist predominantly as linear unintegrated vDNA (uvD) molecules. The uvD molecules were cloned directly from total cellular DNA by addition of EcoRI linkers and subsequent ligation into the phage lambda-EMBL4 vector. Of the eleven clones characterized, seven were full length as judged by restriction fragment analysis. The remaining four clones showed varying degrees of heterogeneity in the form of internal deletions or terminal truncations. Heat denaturation and S1 nuclease analyses were used to show that vDNA isolated from Cf2Th cells contains a single-stranded (ss) gap structure located in the central region of the genome. In addition. a double-stranded (ds) 1.3-kb fragment is observed in this vDNA population. Northern-blot analysis revealed the presence of virus-specific transcripts of 11.0, 6.4, 2.8, and 2.4 kb. This suggests that BSV is similar in complexity to the lentiviruses in terms of linear intermediates containing ss gap structures, and the presence of several RNA transcripts which may direct complex regulatory functions. C1 CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,602 VRT,ITHACA,NY 14853. NCI,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 20 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 15 PY 1991 VL 105 IS 2 BP 179 EP 184 DI 10.1016/0378-1119(91)90149-6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GM936 UT WOS:A1991GM93600006 PM 1657718 ER PT J AU STADTMAN, ER BERLETT, BS AF STADTMAN, ER BERLETT, BS TI FENTON CHEMISTRY - AMINO-ACID OXIDATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MIXED-FUNCTION OXIDATION; COLI GLUTAMINE-SYNTHETASE; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; OXYGEN RADICALS; XANTHINE-OXIDASE; PROTEIN DAMAGE; CATALYZED OXIDATION; HYDROXYL RADICALS AB The oxidation of amino acids by Fenton reagent (H2O2 + Fe(II)) leads mainly to the formation of NH4+, alpha-ketoacids, CO2, oximes, and aldehydes or carboxylic acids containing one less carbon atom. Oxidation is almost completely dependent on the presence of bicarbonate ion and is stimulated by iron chelators at levels which are substoichiometric with respect to the iron concentration but is inhibited at higher concentrations. The stimulatory effect of chelators is not due merely to solubilization of catalytically inactive polymeric forms of Fe(OH)3 nor to the conversion of Fe(II) to complexes incapable of scavenging hydroxyl radicals. The results suggest that an iron chelate and another as yet unidentified form of iron are both required for maximal rates of amino acid oxidation. The metal ion-catalyzed oxidation of amino acids is likely a "caged" process, since the oxidation is not inhibited by hydroxyl radical scavengers, and the relative rates of oxidation of various amino acids by the Fenton system as well as the distribution of products formed (especially products of aromatic amino acids) are significantly different from those reported for amino acid oxidation by ionizing radiation. Several iron-binding proteins, peptides, and hemoglobin degradation products can replace Fe(II) or Fe(III) in the bicarbonate-dependent oxidation of amino acids. In view of their ability to sequester metal ions and their susceptibility to oxidation by H2O2 in the presence of physiological concentrations of bicarbonate, amino acids may serve an important role in antioxidant defense against tissue damage. RP STADTMAN, ER (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,RM 222,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 61 TC 224 Z9 230 U1 3 U2 26 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1991 VL 266 IS 26 BP 17201 EP 17211 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF445 UT WOS:A1991GF44500037 PM 1894614 ER PT J AU SEETHARAM, S CHAUDHARY, VK FITZGERALD, D PASTAN, I AF SEETHARAM, S CHAUDHARY, VK FITZGERALD, D PASTAN, I TI INCREASED CYTOTOXIC ACTIVITY OF PSEUDOMONAS EXOTOXIN AND 2 CHIMERIC TOXINS ENDING IN KDEL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ENDOPLASMIC-RETICULUM; BREFELDIN-A; INTRACELLULAR-TRANSPORT; SECRETORY PROTEINS; RAT HEPATOCYTES; FUSION PROTEIN; DOMAIN-II; CELLS; IMMUNOTOXIN AB Pseudomonas exotoxin (PE) is a 66,000 molecular weight protein secreted by Pseudomonas aeruginosa. PE is made up of three domains, and PE40 is a form of PE which lacks domain Ia (amino acids 1-252) and has very low cytotoxicity because it cannot bind to target cells. The sequence Arg-Glu-Asp-Leu-Lys (REDLK) at the carboxyl terminus of Pseudomonas exotoxin has been shown to be important for its cytotoxic activity (Chaudhary, V. K., Jinno, Y., FitzGerald, D. J., and Pastan, I. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 308-312). In this study, we tested the effect of altering the carboxyl sequence of PE from REDLK to the characteristic endoplasmic reticulum retention sequence, KDEL, or to KDEL repeated three times (KDEL)3. We also made similar changes at the carboxyl terminus of two chimeric toxins in which domain I of PE (amino acids 1-252) was either replaced with transforming growth factor-alpha (TGF-alpha) to make TGF-alpha-PE40 or with a single chain antibody (anti-Tac) reacting with the human interleukin 2 receptor to make anti-Tac(Fv)-PE40. Statistical analyses of our results demonstrate that PE and its derivatives ending in KDEL or (KDEL)3 are significantly more active than PE or derivatives ending in REDLK. We have also found that brefeldin A, which is known to perturb the endoplasmic reticulum, inhibits the cytotoxic action of PE. Our results suggest that the altered carboxyl terminus may enable the toxin to interact more efficiently with a cellular component involved in translocation of the toxin to the cytosol. C1 NCI,DIV CANC BIOL DIAGNOSIS & CENTERS,MOLEC BIOL LAB,BLDG 37,RM 4E16,BETHESDA,MD 20892. NR 31 TC 174 Z9 180 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1991 VL 266 IS 26 BP 17376 EP 17381 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF445 UT WOS:A1991GF44500061 PM 1910044 ER PT J AU NAPOLITANO, M MODI, WS CEVARIO, SJ GNARRA, JR SEUANEZ, HN LEONARD, WJ AF NAPOLITANO, M MODI, WS CEVARIO, SJ GNARRA, JR SEUANEZ, HN LEONARD, WJ TI THE GENE ENCODING THE ACT-2 CYTOKINE - GENOMIC STRUCTURE, HTLV-I TAX RESPONSIVENESS OF 5' UPSTREAM SEQUENCES, AND CHROMOSOMAL LOCALIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; TRANSACTIVATOR GENE; ACTIVATION; IDENTIFICATION; PROTEIN; SUPERFAMILY; MEMBERS; CULTURE; ELEMENT AB Act-2 is a cytokine that belongs to a superfamily of structurally related proteins. Act-2 expression is rapidly induced in T cells, B cells, and monocytes upon mitogenic stimulation. The Act-2 genomic locus is on chromosome 17q. The exons and exon/intron splice junctions have been sequenced, as have the sequences upstream of exon 1. A classical TATA box is located immediately upstream of the transcription initiation site. The upstream sequences possess promoter activity and can be functionally activated after treatment of Jurkat T cells with phythohemagglutinin plus phorbol myristrate acetate. In addition, Act-2 promoter chloramphenicol acetyltransferase constructs are expressed in human T cell lymphotropic virus type I (HTLV-I)-infected MT-2 cells and in Jurkat cells which can be induced to express the transactivator gene (tax) product of HTLV-I. C1 PROGRAM RESOURCES INC,FREDERICK CANC RES FACIL,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP NAPOLITANO, M (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74102] NR 28 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1991 VL 266 IS 26 BP 17531 EP 17536 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF445 UT WOS:A1991GF44500082 PM 1894635 ER PT J AU WU, YJ NOGUCHI, CT AF WU, YJ NOGUCHI, CT TI ACTIVATION OF GLOBIN GENE-EXPRESSION BY CDNAS FROM INDUCED K562 CELLS - EVIDENCE FOR INVOLVEMENT OF FERRITIN IN GLOBIN GENE-EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IRON-RESPONSIVE ELEMENT; MAMMALIAN-CELLS; MESSENGER-RNA; ERYTHROLEUKEMIA-CELLS; MOLECULAR-CLONING; BINDING PROTEINS; LEUKEMIC-CELL; HEAVY-CHAIN; TRANSCRIPTION; DNA AB We have isolated non-globin cDNA clones specific for erythroid differentiation from K562 human erythroleukemia cells and have identified those that may regulate globin gene transcription. A cDNA library was constructed from K562 cells induced by hemin for production of embryonic and fetal hemoglobins and screened against cDNA from uninduced K562 cells. Full-length clones specific for induced K562 cells were ligated into a eukaryotic expression vector and transfected into HeLa cells to allow for production of the corresponding coded polypeptide. The ability to increase epsilon- or gamma-globin promoter activity was identified using cotransfection with a second vector containing a globin gene promoter fused to a reporter gene. Six of the induced K562-specific clones exhibited the ability to increase the levels of the reporter genes, bacterial chloramphenicol acetyltransferase and human growth hormone. Sequencing analyses of these clones indicated that five were homologous to ferritin heavy and light chains and one had no homology with known DNA or protein sequences. The ferritin light chain cDNA had the greatest effect on globin gene promoter activation, increasing the gamma-globin promoter activity by 6-8-fold. The activation of the globin gene promoter in the absence of globin gene translation suggests that ferritin (or iron) may have a direct role in globin gene transcription. The subtractive library cloning strategy has enabled us to isolate cDNA clones that activate specific gene promoters without the requirement of direct DNA binding. This approach may allow further identification of the genes encoding proteins that are involved in the control of erythropoiesis. C1 NIDDKD,CHEM BIOL LAB,BLDG 10,RM 9N307,BETHESDA,MD 20892. NR 49 TC 15 Z9 16 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1991 VL 266 IS 26 BP 17566 EP 17572 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF445 UT WOS:A1991GF44500087 PM 1840594 ER PT J AU RAMSDELL, F JENKINS, M DINH, Q FOWLKES, BJ AF RAMSDELL, F JENKINS, M DINH, Q FOWLKES, BJ TI THE MAJORITY OF CD4+8- THYMOCYTES ARE FUNCTIONALLY IMMATURE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL T-CELLS; CYTOLYTIC LYMPHOCYTES-T; ADULT MURINE THYMUS; MONOCLONAL-ANTIBODY; MATURE THYMOCYTES; ANTIGEN; MOUSE; EXPRESSION; PROLIFERATION; ACTIVATION AB The thymus is the major site of T cell development and repertoire selection. During these processes, T cells segregate into two subsets that express either CD4 or CD8 accessory molecules, the phenotype of peripheral T cells. Analysis of CD4+8- thymocytes revealed that the majority of these cells express the heat-stable Ag (HSA) but not the nonclassical class I Ag, Qa-2. This HSA+, Qa-2- phenotype is similar to that of the less mature, CD4+8+ thymocytes. The remaining CD4+8- thymocytes possess the HSA-, Qa-2+ phenotype of peripheral T cells. To determine whether the Qa-2-, CD4+8- thymic subset is fully mature, we have analyzed the functional status of these CD4+8- subpopulations. The results indicate that only those thymocytes which express Qa-2 are fully responsive to anti-TCR stimulation in a manner analogous to peripheral T cells. The Qa-2- subset is nonresponsive to stimulation by anti-TCR antibodies that have been immobilized to plastic, even in the presence of lymphokines or syngeneic APC. This subset is, however, capable of proliferating to allogeneic cells or to anti-TCR on the surface of syngeneic APC, although not to the levels achieved by Qa-2+ thymocytes. Thus, the Qa-2- subset appears to require additional interactions which are not necessary for peripheral T cells or Qa-2+ thymocytes. Relevant to this issue, the Qa-2+ thymocyte subset does not appear until relatively late in development, and does not reach adult frequencies until several weeks after birth. These results would suggest that there is a progression from HSA+, Qa-2- to HSA-, Qa-2+ which parallels the maturation of functional responsiveness. These findings are important to understanding T cell selection since thymocytes with such a decreased responsiveness may have a differential capacity for tolerance induction. The results presented suggest that the bulk of CD4+8- thymocytes are not fully mature and that Qa-2 may serve as a marker for T cells with a more complete functional competence. C1 UNIV MINNESOTA,DEPT MICROBIOL,MINNEAPOLIS,MN 55455. RP RAMSDELL, F (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BLDG 4,ROOM 334,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 NR 40 TC 132 Z9 134 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1991 VL 147 IS 6 BP 1779 EP 1785 PG 7 WC Immunology SC Immunology GA GG108 UT WOS:A1991GG10800008 PM 1679836 ER PT J AU JOHNS, LD FLANDERS, KC RANGES, GE SRIRAM, S AF JOHNS, LD FLANDERS, KC RANGES, GE SRIRAM, S TI SUCCESSFUL TREATMENT OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS WITH TRANSFORMING GROWTH FACTOR-BETA-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS FACTOR-ALPHA; FACTOR TYPE-BETA; T-CELL LINES; LYMPHOCYTES-T; ENCEPHALITOGENIC DETERMINANT; CLONES; LOCALIZATION; MICE AB Transforming growth factor-beta-1 (TGF-beta-1) is a multifunctional cytokine with immunosuppressive effects on T cells in vitro. Experimental allergic encephalomyelitis is an archetypal T cell-mediated autoimmune demyelinating disease of the central nervous system that often serves as a model for multiple sclerosis. In vivo administration of TGF-beta-1 into SJL mice was successful in reducing the incidence of clinical disease and the histologic severity of inflammation and demyelination in the brain and spinal cord. Immunohistochemical studies performed on control animals showed that TGF-beta-1, -2, and -3 were present in inflammatory perivascular lesions in the brain. The use of a naturally occurring cytokine with immunoregulatory functions in the treatment of an autoimmune disease is novel. However, potential long term complications of such therapy must be addressed before its use in human autoimmune disease such as multiple sclerosis. C1 UNIV VERMONT,DEPT NEUROL,BURLINGTON,VT 05405. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. MILES RES CTR,W HAVEN,CT 06516. FU NINDS NIH HHS [NS22654] NR 43 TC 226 Z9 230 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1991 VL 147 IS 6 BP 1792 EP 1796 PG 5 WC Immunology SC Immunology GA GG108 UT WOS:A1991GG10800010 PM 1716279 ER PT J AU MOXEYMIMS, MM SIMMS, HH FRANK, MM LIN, EY GAITHER, TA AF MOXEYMIMS, MM SIMMS, HH FRANK, MM LIN, EY GAITHER, TA TI THE EFFECTS OF IL-1, IL-2, AND TUMOR-NECROSIS-FACTOR ON POLYMORPHONUCLEAR LEUKOCYTE FC-GAMMA RECEPTOR-MEDIATED PHAGOCYTOSIS - IL-2 DOWN-REGULATES THE EFFECT OF TUMOR-NECROSIS-FACTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-NEUTROPHILS; FACTOR-ALPHA; INTERFERON-GAMMA; DE-GRANULATION; RECEIVING INTERLEUKIN-2; SUPEROXIDE PRODUCTION; BACTERIAL-INFECTIONS; ACUTE-INFLAMMATION; RESPIRATORY BURST; FACTOR-BETA AB It has been reported that the Fc-gamma-R-mediated phagocytic activity of polymorphonuclear leukocytes (PMN) from patients with acute bacterial infections is markedly enhanced when compared with healthy controls. Inasmuch as several potent cytokines are known to be involved in inflammatory and infectious processes, we studied the effects of three such cytokines (IL-1-beta, IL-2, and TNF-alpha) on normal PMN Fc-gamma-R-mediated phagocytosis. IL-1-beta and TNF-alpha both caused a significant increase in the ingestion of EIgG by adherent PMN. In combination, IL-1-beta and TNF-alpha had an additive effect, even when each was used at its optimal concentration. In contrast to the enhancing effects mediated by IL-1-beta and TNF-alpha, IL-2 alone had no significant effect on PMN phagocytosis. Notably, however, IL-2 at a concentration of 10(4) U/ml partially inhibited TNF-alpha-mediated enhancement of phagocytosis by decreasing TNF binding to the PMN cell surface. This inhibitory effect of IL-2 on TNF was reversed by anti-IL-2 antibody and mAb directed against the low affinity IL-2R (anti-Tac), whereas mAb directed against the intermediate affinity receptor (mik-beta-1) had no such effect. These findings may have important physiologic implications, because patients receiving IL-2 therapy have been shown to have increased susceptibility to infection. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 55 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1991 VL 147 IS 6 BP 1823 EP 1830 PG 8 WC Immunology SC Immunology GA GG108 UT WOS:A1991GG10800015 PM 1890305 ER PT J AU WONG, HL WELCH, GR BRANDES, ME WAHL, SM AF WONG, HL WELCH, GR BRANDES, ME WAHL, SM TI IL-4 ANTAGONIZES INDUCTION OF FC-GAMMA-RIII (CD16) EXPRESSION BY TRANSFORMING GROWTH-FACTOR-BETA ON HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; HUMAN MONONUCLEAR PHAGOCYTES; HUMAN PERIPHERAL-BLOOD; DIFFERENTIAL REGULATION; SUPEROXIDE PRODUCTION; CELL-GROWTH; IFN-GAMMA; TGF-BETA; B-CELLS; INTERLEUKIN-4 AB The multifunctional cytokines, transforming growth factor (TGF)-beta-1 and beta-2, have the capability of inducing human peripheral blood monocytes to express the type III receptor for the Fc portion of IgG (Fc-gamma-RIII/CD16). In this study we show that the T cell-derived cytokine, IL-4, antagonizes the ability of TGF-beta to induce the expression of CD16. Furthermore, this ability to down-regulate expression of CD16 is completely abrogated after treatment with polyclonal anti-IL-4, suggesting that IL-4 is solely responsible for the observed inhibition. The mechanism for negating the effect of TGF-beta is not due to decreased expression of surface receptors for TGF-beta, but appears to occur at the mRNA level. Nuclear run-off assays indicate that regulation occurs predominantly through a posttranscriptional mechanism(s), although a transcriptional process cannot be ruled out. Normally, CD16 appears on only a small population of circulating monocytes, however, expression is apparent on the majority of mature tissue and inflammatory macrophages likely due to the release of TGF-beta in these sites. Inasmuch as this receptor binds immune complexes and opsonized particles, it is associated with enhanced immunophagocytosis. Suppression of CD16 expression and its ability to suppress a number of other monocyte functions suggests that IL-4 may play an important role in the resolution of inflammatory and tissue repair responses. RP WONG, HL (reprint author), NIDR,IMMUNOL LAB,BLDG 30,ROOM 334,BETHESDA,MD 20892, USA. NR 47 TC 39 Z9 39 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1991 VL 147 IS 6 BP 1843 EP 1848 PG 6 WC Immunology SC Immunology GA GG108 UT WOS:A1991GG10800018 PM 1653804 ER PT J AU CUNNINGHAM, ML MATTHEWS, HB AF CUNNINGHAM, ML MATTHEWS, HB TI RELATIONSHIP OF HEPATOCARCINOGENICITY AND HEPATOCELLULAR PROLIFERATION INDUCED BY MUTAGENIC NONCARCINOGENS VS CARCINOGENS .2. 1-NITROPROPANE VS 2-NITROPROPANE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; SPRAGUE-DAWLEY RATS; CELL-PROLIFERATION; DI(2-ETHYLHEXYL)PHTHALATE DEHP; CHEMICAL CARCINOGENESIS; LIVER CARCINOGENESIS; POTASSIUM SUPEROXIDE; PRENEOPLASTIC CELLS; GENOTOXIC ACTIVITY; MICRONUCLEUS TEST RP CUNNINGHAM, ML (reprint author), NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 49 TC 37 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 15 PY 1991 VL 110 IS 3 BP 505 EP 513 DI 10.1016/0041-008X(91)90050-O PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GH709 UT WOS:A1991GH70900012 PM 1949017 ER PT J AU NARIAI, T DEGEORGE, JJ LAMOUR, Y RAPOPORT, SI AF NARIAI, T DEGEORGE, JJ LAMOUR, Y RAPOPORT, SI TI INVIVO BRAIN INCORPORATION OF [1-C-14]ARACHIDONATE IN AWAKE RATS, WITH OR WITHOUT CHOLINERGIC STIMULATION, FOLLOWING UNILATERAL LESIONING OF NUCLEUS BASALIS MAGNOCELLULARIS SO BRAIN RESEARCH LA English DT Article DE NUCLEUS BASALIS MAGNOCELLULARIS; ARACHIDONIC ACID; LIPID METABOLISM; PHOSPHOLIPID; PHOSPHATIDYLINOSITOL; ARECOLINE; ALZHEIMERS DISEASE; BRAIN ID M2 MUSCARINE RECEPTORS; PLASMA C-14 PALMITATE; C62B GLIOMA-CELLS; ALZHEIMERS-DISEASE; SENILE DEMENTIA; CEREBRAL-CORTEX; PHOSPHOINOSITIDE HYDROLYSIS; ACETYLCHOLINE-RECEPTOR; UNANESTHETIZED RATS; ARACHIDONIC-ACID AB Regional brain incorporation of a radiolabeled unsaturated fatty acid, [1-C-14]arachidonic acid (C-14-AA), was measured in awake rats following unilateral lesioning of the nucleus basalis magnocellularis (NBM). Right-sided lesions were produced in 3-month-old, male rats by stereotaxic injection of 10-mu-g ibotenic acid. Two weeks after lesioning, rats were subjected to one of two protocols: (1) 5 min intravenous infusion of C-14-AA (170-mu-Ci/kg); or (2) i.p. injection of arecoline (5 mg/kg), a cholinergic agonist, followed by 5 min intravenous infusion of C-14-AA. All animals were killed 15 min postinfusion. Brains were frozen and sectioned for quantitative autoradiography or were stained for acetylcholinesterase (AChE). Animals with unilateral NBM lesions displayed reduced AChE staining in prefrontal, frontal and parietal cortices of the lesioned side, but there was no right-left difference in incorporation of C-14-AA without cholinergic stimulation. Arecoline administration increased C-14-AA incorporation into the prefrontal and frontal cortices ipsilateral to the NBM lesion as compared to the contralateral side and the increase was most prominent in deeper cortical layers such as layers IV and V. Right-left differences in incorporation were not apparent in parietal, temporal, or occipital cortices, where reduction of AChE activity was minimal or absent, nor in subcortical structures. The results suggest that the intravenous C-14-AA technique combined with cholinergic stimulation can be used to detect compensatory regulation of phospholipid-coupled signal transduction caused by a deficit in cholinergic input into the cerebral cortex. C1 NIA,NEUROSCI LAB,BLDG 10,RM 6C-103,BETHESDA,MD 20892. NR 58 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 13 PY 1991 VL 559 IS 1 BP 1 EP 9 DI 10.1016/0006-8993(91)90279-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA GH083 UT WOS:A1991GH08300001 PM 1723641 ER PT J AU MURPHY, PM TIFFANY, HL AF MURPHY, PM TIFFANY, HL TI CLONING OF COMPLEMENTARY-DNA ENCODING A FUNCTIONAL HUMAN INTERLEUKIN-8 RECEPTOR SO SCIENCE LA English DT Article ID PHAGOCYTIC CELL RECEPTORS; ACTIVATING FACTOR; XENOPUS OOCYTES; HUMAN-NEUTROPHILS; PROTEIN; GENES; CDNA; C5A AB Interleukin-8 (IL-8) is an inflammatory cytokine that activates neutrophil chemotaxis, degranulation, and the respiratory burst. Neutrophils express receptors for IL-8 that are coupled to guanine nucleotide-binding proteins (G proteins); binding of IL-8 to its receptor induces the mobilization of intracellular calcium stores. A cDNA clone from HL-60 neutrophils, designated p2, has now been isolated that encodes a human IL-8 receptor. When p2 is expressed in oocytes from Xenopus laevis, the oocytes bind I-125-labeled IL-8 specifically and respond to IL-8 by mobilizing calcium stores with an EC50 of 20 nM. This IL-8 receptor has 77% amino acid identity with a second human neutrophil receptor isotype that binds IL-8 with higher affinity. It also exhibits 69% an-amino acid identity with a protein reported to be an N-formyl peptide receptor from rabbit neutrophils, but less than 30% identity with all other known G protein-coupled receptors, including the human N-formyl peptide receptor. RP MURPHY, PM (reprint author), NIAID,HOST DEF LAB,BETHESDA,MD 20892, USA. NR 27 TC 785 Z9 803 U1 2 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 13 PY 1991 VL 253 IS 5025 BP 1280 EP 1283 DI 10.1126/science.1891716 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GE689 UT WOS:A1991GE68900041 PM 1891716 ER PT J AU GERMAIN, RN HENDRIX, LR AF GERMAIN, RN HENDRIX, LR TI MHC CLASS-II STRUCTURE, OCCUPANCY AND SURFACE EXPRESSION DETERMINED BY POST-ENDOPLASMIC RETICULUM ANTIGEN-BINDING SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; B-CELL ALLOANTIGENS; HLA-DR ANTIGENS; INVARIANT CHAIN; MONOCLONAL-ANTIBODIES; T-CELLS; IMMUNOGENIC PEPTIDES; IA ANTIGENS; MOLECULES; RECOGNITION AB Class II major histocompatibility complex molecules undergo a change in structure upon stable binding of peptide antigen. Analysis of the site and extent of this change among class II molecules of splenic antigen-presenting cells reveals the preference of class II for peptide acquisition outside the endoplasmic reticulum and indicates that the class II presentation system is not saturated with self peptides. There are numerous empty class II molecules on the cell surface and peptide antigen is evidently important in regulating surface class II expression. RP GERMAIN, RN (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892, USA. NR 63 TC 398 Z9 400 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 12 PY 1991 VL 353 IS 6340 BP 134 EP 139 DI 10.1038/353134a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GE731 UT WOS:A1991GE73100043 PM 1891045 ER PT J AU SADEGHNASSERI, S GERMAIN, RN AF SADEGHNASSERI, S GERMAIN, RN TI A ROLE FOR PEPTIDE IN DETERMINING MHC CLASS-II STRUCTURE SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SEPARATE ALPHA-CHAINS; IMMUNOGENIC PEPTIDES; ANTIGENIC PEPTIDES; LYMPHOCYTE-T; BETA-CHAINS; MOLECULES; BINDING; IA; RECOGNITION AB T LYMPHOCYTES recognize antigen-derived peptides associated with major histocompatibility complex (MHC) class I or class II proteins 1,2. Peptide is critical in class I heavy folding and/or stable association with beta-2-Microglobulin 3-6. Although data exist suggesting a relationship between class II structure and peptide association 7-9, no equivalent positive contribution of peptide to the folding state or stability of class II dimers has yet been demonstrated. We report here that most purified E-alpha(k)E-beta-k molecules leaving low pH in the absence of specific peptide lack a compact, stable dimeric structure. Brief exposure to the appropriate peptide just before and during neutralization promotes this specific conformation in proportion to stably bound peptide, indicating that peptide is important in determining class II MHC structure. Our results also indicate that efficient generation of long-lived peptide-class II complexes involves two stages: initial peptide binding in an acidic environment, which enhances the ability of class II to enter a conformation, from which stabilization upon neutralization results in high-affinity binding of previously associated peptide. RP SADEGHNASSERI, S (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892, USA. OI Sadegh-Nasseri, Scheherazade/0000-0002-8127-1720 NR 26 TC 279 Z9 282 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 12 PY 1991 VL 353 IS 6340 BP 167 EP 170 DI 10.1038/353167a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GE731 UT WOS:A1991GE73100054 PM 1653903 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN DIHYDROFOLATE-REDUCTASE PSI-2 PSEUDOGENE (DHFRP2) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, ROOM 131, 2700 MARTIN LUTHER KING AVE, WASHINGTON, DC 20032 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 11 PY 1991 VL 19 IS 17 BP 4792 EP 4792 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF998 UT WOS:A1991GF99800054 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN PROSTATIC ACID-PHOSPHATASE (ACPP) GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, ROOM 131, 2700 MARTIN LUTHER KING AVE, WASHINGTON, DC 20032 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 11 PY 1991 VL 19 IS 17 BP 4792 EP 4792 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF998 UT WOS:A1991GF99800053 ER PT J AU MCDANIEL, T CARBONE, D TAKAHASHI, T CHUMAKOV, P CHANG, EH PIROLLO, KF YIN, J HUANG, Y MELTZER, SJ AF MCDANIEL, T CARBONE, D TAKAHASHI, T CHUMAKOV, P CHANG, EH PIROLLO, KF YIN, J HUANG, Y MELTZER, SJ TI THE MSPI POLYMORPHISM IN INTRON-6 OF P53 (TP53) DETECTED BY DIGESTION OF PCR PRODUCTS SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. UNIV MARYLAND,MOLEC & CELL BIOL PROGRAM,BALTIMORE,MD 21201. DEPT VET AFFAIRS HOSP,BALTIMORE,MD 21201. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. RI Takahashi, Takashi/I-7262-2014 NR 2 TC 77 Z9 77 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 11 PY 1991 VL 19 IS 17 BP 4796 EP 4796 DI 10.1093/nar/19.17.4796-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF998 UT WOS:A1991GF99800062 PM 1716362 ER PT J AU CAENAZZO, L HOEHE, MR HSIEH, WT BERRETTINI, WH BONNER, TI GERSHON, ES AF CAENAZZO, L HOEHE, MR HSIEH, WT BERRETTINI, WH BONNER, TI GERSHON, ES TI HINDIII IDENTIFIES A 2 ALLELE DNA POLYMORPHISM OF THE HUMAN CANNABINOID RECEPTOR GENE (CNR) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 1 TC 16 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 11 PY 1991 VL 19 IS 17 BP 4798 EP 4798 DI 10.1093/nar/19.17.4798-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF998 UT WOS:A1991GF99800066 PM 1679930 ER PT J AU STARKEBAUM, G LOUGHRAN, TP WATERS, CA RUSCETTI, FW AF STARKEBAUM, G LOUGHRAN, TP WATERS, CA RUSCETTI, FW TI ESTABLISHMENT OF AN IL-2 INDEPENDENT, HUMAN T-CELL LINE POSSESSING ONLY THE P70 IL-2 RECEPTOR SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LEUKEMIA-LYMPHOMA VIRUS; INTERLEUKIN-2 FUSION PROTEIN; BETA-CHAIN; AUTOCRINE GROWTH; HTLV-I; GENE-PRODUCT; EXPRESSION; TAC; PATIENT; LYMPHOCYTES AB A continuous cell line was established from the blood of a patient (HH) with an aggressive cutaneous T-cell leukemia/lymphoma who lacked antibodies to human T lymphotrophic virus, type I. The immunophenotype of the cultured cells was CD2+, CD3+, CD4+, CD5+, CD8-, DR+ and CD25- (Tac, IL-2 receptor alpha-chain). Southern-blot hybridization analysis of T-cell-receptor beta-chain DNA demonstrated the same rearrangement in freshly isolated blood cells and cultured cells, indicating that the cell line was derived from the patient's malignant clone. Since cultured T-cells grew in complete medium without added IL-2, we investigated whether HH cells could be producing and responding to IL-2 in an autocrine fashion. However, no IL-2 was detectable in supernatant from the cell line, while antibodies to IL-2, or to the IL-2 receptor alpha or beta-chains did not inhibit cell growth. In addition, no mRNA message for IL-2 was detectable in these cells. The results appear to exclude an autocrine IL-2-dependent mechanism of cell growth for this T-cell line. Although cultured HH cells lacked detectable IL-2 receptor alpha-chain, they did show increased proliferation to exogenous IL-2. Binding studies with I-125-IL-2 demonstrated an intermediate affinity receptor for IL-2, K(D) = 1.7nM, with 6400 binding sites per cell, suggesting the presence of an IL-2 receptor beta-chain. Consistent with these findings I-125-IL-2 cross-linking studies demonstrated a single receptor calculated to be 75kDa. Also, the beta-chain of the IL-2 receptor was detected by immunofluorescence using specific monoclonal antibodies (MAbs). Nanomolar concentrations of an IL-2-diphteria toxin fusion protein inhibited cellular protein synthesis, an effect abrogated by native IL-2. These findings indicate that the IL-2 receptor beta-chain was functional. This novel mature T-cell line may be useful in studies of IL-2 receptor regulation and in analysis of the mechanism of T-cell leukemogenesis. C1 UNIV WASHINGTON,DEPT MED,DIV RHEUMATOL,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. SERAGEN,HOPKINTON,MA. RP STARKEBAUM, G (reprint author), VET ADM MED CTR,DEPT MED,ARTHRITIS SECT 111,1660 SO COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 43 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1991 VL 49 IS 2 BP 246 EP 253 DI 10.1002/ijc.2910490218 PG 8 WC Oncology SC Oncology GA GE544 UT WOS:A1991GE54400017 PM 1879969 ER PT J AU PALLERONI, AV VARESIO, L WRIGHT, RB BRUNDA, MJ AF PALLERONI, AV VARESIO, L WRIGHT, RB BRUNDA, MJ TI TUMORICIDAL ALVEOLAR MACROPHAGE AND TUMOR INFILTRATING MACROPHAGE CELL-LINES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONONUCLEAR PHAGOCYTES; MONOCLONAL-ANTIBODY; IMMORTALIZATION; EXPRESSION; ANTIGEN; TRANSFORMATION; RETROVIRUS; PERITONEAL; ORIGIN; VIRUS AB Continuous alveolar macrophage (AM) and tumor-infiltrated (TIM) cell lines have been generated from C57B16J mice by in vitro infection with the J2 retrovirus carrying the v-raf and v-myc oncogens. Four cloned AM cell lines (AMJ2-C8, AMJ2-C10, AMJ2-C11, AMJ2-C20) and 3 cloned TIM cell lines (TIMJ2-C4, TIMJ2-C7 and TIMJ2-C15) were expanded for further characterization. Flow cytometry detected the product of the raf gene in the cytoplasm of all these cell lines. Studies on the tumoricidal properties of these AM and TIM cell lines demonstrated differences in their response to a panel of known macrophage activators. Four of these cell lines (AMJ2-C8, AMJ2-C10, TIMJ2-C7 and TIMJ2-C15) were activated following exposure to recombinant murine interferon gamma (rMuIFN-gamma) but not lipopolysaccharide (LPS) or muramyl dipeptide (MDP). AMJ2-C20 was only activated by incubation with rMuIFN-gamma plus LPS. AMJ2-C11 and TIMJ2-C4 are the cell lines that most closely resembled the response pattern of the parental AM and TIM, since they could be activated by either the combination of rMuIFN-gamma plus LPS or rMuIFN-gamma plus MDP. Constitutive expression of MHC-class-II antigens was low on AMJ2-C11 or TIMJ2-C4 but was increased following exposure to rMuIFN-gamma. Neither cell line secreted substantial amounts of IL-1 or TNF but both secreted large amounts of IL-6. Thus these cell lines could be powerful tools to study AM and TIM activation and cytotoxicity. C1 NCI,FREDERICK,MD 21701. RP PALLERONI, AV (reprint author), HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT ONCOL,NUTLEY,NJ 07110, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 27 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 9 PY 1991 VL 49 IS 2 BP 296 EP 302 DI 10.1002/ijc.2910490226 PG 7 WC Oncology SC Oncology GA GE544 UT WOS:A1991GE54400025 PM 1879973 ER PT J AU ZORETIC, PA WENG, XY CASPAR, ML DAVIS, DG AF ZORETIC, PA WENG, XY CASPAR, ML DAVIS, DG TI STEREOSPECIFIC TETRACYCLIZATION OF ICOSATETRAENES VIA MN(III) PROMOTED OXIDATIVE FREE-RADICAL CYCLIZATION SO TETRAHEDRON LETTERS LA English DT Article AB A stereospecific oxidative free-radical cyclization of polyene 10a to the D-homo-5-alpha-androstane system 11a containing seven asymmetric centers is reported. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP ZORETIC, PA (reprint author), E CAROLINA UNIV,DEPT CHEM,GREENVILLE,NC 27858, USA. NR 10 TC 40 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD SEP 9 PY 1991 VL 32 IS 37 BP 4819 EP 4822 DI 10.1016/S0040-4039(00)93469-5 PG 4 WC Chemistry, Organic SC Chemistry GA GF755 UT WOS:A1991GF75500002 ER PT J AU GUTFREUND, H CHOCK, PB AF GUTFREUND, H CHOCK, PB TI SUBSTRATE CHANNELING AMONG GLYCOLYTIC-ENZYMES - FACT OR FICTION SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; LACTATE-DEHYDROGENASE; MECHANISM; ALDOLASE; NADH C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP GUTFREUND, H (reprint author), UNIV BRISTOL,DEPT BIOCHEM,BRISTOL BS8 1TD,AVON,ENGLAND. NR 11 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD SEP 7 PY 1991 VL 152 IS 1 BP 117 EP 121 DI 10.1016/S0022-5193(05)80524-7 PG 5 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA GF744 UT WOS:A1991GF74400025 PM 1753754 ER PT J AU HILLER, S AF HILLER, S TI A BETTER WAY TO MAKE THE MEDICINE GO DOWN SO SCIENCE LA English DT Editorial Material RP HILLER, S (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 6 PY 1991 VL 253 IS 5024 BP 1095 EP 1096 DI 10.1126/science.1679567 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GD808 UT WOS:A1991GD80800020 PM 1679567 ER PT J AU STADTMAN, TC AF STADTMAN, TC TI BIOSYNTHESIS AND FUNCTION OF SELENOCYSTEINE-CONTAINING ENZYMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CLOSTRIDIAL GLYCINE REDUCTASE; FORMATE-HYDROGEN-LYASE; AMINO-ACID-SEQUENCE; GLUTATHIONE-PEROXIDASE; ESCHERICHIA-COLI; TRANSFER-RNA; SELENIUM METABOLISM; PROTEIN-COMPONENTS; TRANSLATION FACTOR; HUMAN-PLASMA RP STADTMAN, TC (reprint author), NHLBI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 64 TC 152 Z9 152 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16257 EP 16260 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500001 PM 1832153 ER PT J AU JUVONEN, RO IWASAKI, M NEGISHI, M AF JUVONEN, RO IWASAKI, M NEGISHI, M TI STRUCTURAL FUNCTION OF RESIDUE-209 IN COUMARIN 7-HYDROXYLASE (P450COH) - ENZYME-KINETIC STUDIES AND SITE-DIRECTED MUTAGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER; STEROID 15-ALPHA-HYDROXYLASE; SUBSTRATE-SPECIFICITY; II P-45015-ALPHA; AMINO-ACID; CYTOCHROME-P-450; CDNA; 7-ETHOXYCOUMARIN; CYTOCHROMES-P450; IDENTIFICATION AB Residue-209 plays a critical role in determining the substrate and product specificity of cytochrome P450coh. In order to investigate further the structural function of residue-209 in coumarin 7-hydroxylase reaction, we measured the enzyme-kinetic properties of wild-type P450coh and its mutants in which residue-209 was substituted with various amino acids. In general, the K(m) and V(max) values for coumarin increased as the size of residue-209 became smaller and V(max) values decreased. The size of residue-209, therefore, was a principle factor determining K(m), K(d), and V(max) values of P450coh. Although the polarity and charge also increased the K(m) value consistently, they altered V(max) and K(d) values in an irregular manner. The substitution of serine for residue-209 increased the V(max), while the substitution of lysine decreased it. Coumarin 7-hydroxylase activity was inhibited weakly by indan, but competitively and strongly by 2-coumaranone. Moreover, K(i) values for the inhibitor were similar to K(m) values of the corresponding, mutated P450s. The results indicate, therefore, that residue-209 is localized in a proposed substrate-binding sequence 1 which binds to the 2-keto group of coumarin and directs its 7-position toward the sixth ligand of heme. Consequently, the identity of residue-209 determines not only the binding of coumarin in P450coh, but also the other reaction step(s) of coumarin 7-hydroxylation. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,POB 12233,RES TRIANGLE PK,NC 27709. NR 22 TC 67 Z9 67 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16431 EP 16435 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500033 PM 1885576 ER PT J AU COY, DH JIANG, NY KIM, SH MOREAU, JP LIN, JT FRUCHT, H QIAN, JM WANG, LW JENSEN, RT AF COY, DH JIANG, NY KIM, SH MOREAU, JP LIN, JT FRUCHT, H QIAN, JM WANG, LW JENSEN, RT TI COVALENTLY CYCLIZED AGONIST AND ANTAGONIST ANALOGS OF BOMBESIN AND RELATED PEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SWISS 3T3 CELLS; RECEPTOR ANTAGONISTS; ANTIMITOTIC ACTIVITY; PANCREATIC ACINAR; POTENT AB During a search for possible cyclization points in shortened, potent bombesin agonists and antagonists, it was found that the joining of amino acid residues in positions 6 and 14 by various means resulted in retention of significant binding affinity for rat pancreatic acini and murine Swiss 3T3 cells. In one series of analogues, Cys residues in these positions were used for bridging via a disulfide bond. (D)-C-Q-W-A-V-G-H-L-C-NH2 retained significant binding affinity for rat pancreatic acini cells and was a full amylase releasing agonist (EC50 187 nM). Potency was markedly increased by substituting D-Ala for Gly (EC50 67 nM compared to 10 nM for its linear counterpart) and was decreased by substituting L-Cys for D-Cys in this analogue (EC50 214 nM), thus strongly suggesting stabilization of peptide folding by the D residues. Elimination of the COOH-terminal amino acid produces competitive antagonists in the linear analogues; however, (D)-C-Q-W-A-V-G-H-C-NH2 Was devoid of activity. Likewise, cyclization to position 13 with the 14 amino acids intact to give (D)-C-Q-W-A-V-G-H-C-L-NH2 resulted in an almost inactive peptide. On the other hand, as in the linear series, the reduced peptide bond analogue, (D)-C-Q-W-A-V-(D)-A-H-L-psi(CH2NH)-C-NH2, was a receptor antagonist (IC50 5.7 mM), albeit much weaker than the corresponding linear analogues, but with no residual agonist activity. Direct head-to-tail cyclization was also tried. Both cyclo[(D)-F-Q-W-A-V-G-H-L-L] (EC50 346 mM) and the shorter cyclo[Q-W-A-V-G-H-L-L] (EC50 1236 mM) were full agonists. Elimination of the COOH-terminal residue in cyclo[(D)-p-Cl-F-Q-W-A-V-(D)-A-H-L-] produced an agonist (EC50 716 nM) rather than an antagonist. These results provide support for the proposal that both bombesin agonists and antagonists adopt a folded conformation at their receptor (s). Furthermore, the retention of appreciable potencies using several cyclization strategies and chain lengths suggests that further optimization of these structures both in terms of potency and ring size is possible. Since these peptides have increased conformational restriction, they should begin to serve as useful substrates for NMR and molecular modeling studies aimed at comparing the obviously subtle differences between agonist and antagonist structures. C1 BIOMEASURE INC,HOPKINTON,MA 01748. NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP COY, DH (reprint author), TULANE UNIV,SCH MED,DEPT MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70112, USA. FU NCI NIH HHS [CA-45153] NR 28 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16441 EP 16447 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500035 PM 1715866 ER PT J AU NOGIMORI, K HUGHES, PJ GLENNON, MC HODGSON, ME PUTNEY, JW SHEARS, SB AF NOGIMORI, K HUGHES, PJ GLENNON, MC HODGSON, ME PUTNEY, JW SHEARS, SB TI PURIFICATION OF AN INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE 3-PHOSPHATASE ACTIVITY FROM RAT-LIVER AND THE EVALUATION OF ITS SUBSTRATE-SPECIFICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 1,3,4-TRISPHOSPHATE PHOSPHORYLATION; HUMAN-PLATELETS; METABOLISM; PHOSPHATES; 1,3,4,5-TETRAKISPHOSPHATE; 1,4,5-TRISPHOSPHATE; CELLS; HEXAKISPHOSPHATE; BRAIN; 1,3,4,5,6-PENTAKISPHOSPHATE AB Hepatic inositol (1,3,4,5)-tetrakisphosphate 3-phosphatase activity was detected in a 100,000 x g soluble fraction and a detergent-solubilized particulate fraction. Activity in both fractions increased up to 40-fold after anion-exchange chromatography due to removal of endogenous inhibitors (Hodgson, M. E., and Shears, S. B. (1990) Biochem. J. 267, 831-834); at this stage the detergent-solubilized particulate activity comprised over 90% of total activity. The particulate phosphatase was further purified by affinity chromatography using heparin-agarose and red-agarose. The latter column resolved two peaks of enzyme activity (designated 1 and 2 by their order of elution from the column). Their proportions varied between experiments, but peak 2 generally predominated and so this was further purified by hydroxylapatite chromatography. The final preparation was typically 38,000-fold purified with a 7% yield. The apparent molecular mass of this enzyme was 66 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration. The enzyme had little or no affinity for the following: inositol (1,3,4,6)-tetrakisphosphate, inositol (1,3,4)-trisphosphate, inositol (1,3)-bisphosphate, inositol (3,4)-bisphosphate, and para-nitrophenylphosphate. At pH 7.4 the K(m) for inositol (1,3,4,5)-tetrakisphosphate was 130 nM and the V(max) was 4250 nmol/mg protein/min. The purified enzyme also dephosphorylated inositol (1,3,4,5,6)-pentakisphosphate to inositol (1,4,5,6)-tetrakisphosphate (K(m) = 40 nM, V(max) = 211 nmol/mg protein/min), and inositol hexakisphosphate to at least five isomers of inositol pentakisphosphate (K(m) = 0.3 nM, V(max) = 12 nmol/mg protein/min). The latter affinity is the highest yet defined for an enzyme involved in inositol phosPhate metabolism. Determinations of IC50 values, and Dixon plots, revealed that with the (1,3,4,5)-tetrakisphosphate as substrate, the pentakis- and hexakisphosphates were potent competitive inhibitors; the K(i) values (25 and 0.5 nM, respectively) were similar to their substrate K(m) values. The kinetic properties of this enzyme, as well as estimates of the cellular levels of its potential substrates, indicate that inositol pentakisphosphate and inositol hexakisphosphate are likely to be the preferred substrates in vivo. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. OI Hodgson, Elizabeth/0000-0002-2089-2689 NR 36 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16499 EP 16506 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500044 PM 1653239 ER PT J AU ASHIZAWA, K WILLINGHAM, MC LIANG, CM CHENG, SY AF ASHIZAWA, K WILLINGHAM, MC LIANG, CM CHENG, SY TI INVIVO REGULATION OF MONOMER-TETRAMER CONVERSION OF PYRUVATE-KINASE SUBTYPE-M2 BY GLUCOSE IS MEDIATED VIA FRUCTOSE-1,6-BISPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3,3',5-TRIIODO-L-THYRONINE BINDING-PROTEIN; THYROID-HORMONE BINDING; MONOCLONAL-ANTIBODIES; RAT AB The activity of pyruvate kinase, subtype M2 (PKM2), is known to be increased by fructose 1,6-bisphosphate (Fru-1,6-P2), one of the metabolites in the glycolytic pathway. Recently, we have shown that in vitro, Fru-1,6-P2 activated the association of monomer to form the tetrameric PKM2. To ascertain whether this mode of regulation also occurs in vivo, we prepared monomer-specific monoclonal antibody and quantified the monomer formation in situ in cultured cells by immunocytochemistry. The intracellular Fru-1,6-P2 was manipulated by the glucose concentration in the media. At the physiological concentration of glucose (4-6 mM), 30-35% of PK existed as a monomer. However, PKM2 was dissociated into monomer within minutes after cells were deprived of glucose. The maximal level of monomer was detected after 1 h at 37-degrees-C. Monomer was rapidly (within minutes) converted to tetramer after addition of glucose. Furthermore, when cells cultured in 10 mm of glucose were treated with cytochalasin B, an inhibitor of the glucose transporter, a maximal level of monomer was detected within 20-30 min. Determination of Fru-1,6-P2 indicated that its intracellular concentration decreased concomitantly with the reduction in glucose concentration in the medium. These results indicate that monomer-tetramer interconversion is a major in vivo cellular regulatory mechanism in response to changes in the extracellular glucose concentration via Fru-1,6-P2. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,ROOM 4B09,BETHESDA,MD 20892. US FDA,DIV BLOOD & BLOOD PROD,BETHESDA,MD 20014. NR 14 TC 79 Z9 82 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16842 EP 16846 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500094 PM 1885610 ER PT J AU VOSTAL, JG JACKSON, WL SHULMAN, NR AF VOSTAL, JG JACKSON, WL SHULMAN, NR TI CYTOSOLIC AND STORED CALCIUM ANTAGONISTICALLY CONTROL TYROSINE PHOSPHORYLATION OF SPECIFIC PLATELET PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETICULUM CA-2+-ATPASE; CA-2+ POOL; THROMBIN; THAPSIGARGIN; AGGREGATION; INDICATORS; GENISTEIN; PROTEASE; VANADATE; KINASE AB Depletion of intracellular calcium stores appears to increase plasma membrane permeability for calcium by an as yet obscure mechanism. We found that the Ca2+ ionophore, A23187, and thrombin elevate cytosolic calcium ([Ca2+]i) equally and cause tyrosine phosphorylation of a 130-kDa protein and to a lesser extent 80- and 60-kDa proteins. Chelation of [Ca2+]i by 1,2bis(2-aminophenoxyethane)N,N,N',N'-tetraacetic acid/acetomethoxy ester decreased thrombin-induced tyrosine phosphorylation responses. These results suggested that [Ca2+]i elevation promotes tyrosine phosphorylation. Tyrosine phosphorylation persisted in the presence or absence of extracellular calcium after thrombin stimulation but subsided rapidly after A23187 addition if extracellular calcium was present. When Ca2+/ATPase activity, which is apparently required to maintain calcium stores, is inhibited by low temperature, tyrosine phosphorylation of the 130-kDa protein occurs. Rewarming platelets reverses tyrosine phosphorylation only if extracellular calcium is present. Thapsigargin, a calcium ATPase inhibitor, also induces tyrosine phosphorylation of the 130-kDa protein and prevents dephosphorylation of this protein when added prior to rewarming. These observations suggest that homeostatic levels of calcium in storage compartments favor tyrosine dephosphorylation of specific proteins. Thus the levels of [Ca2+]i and stored calcium appear to control tyrosine phosphorylation antagonistically. Tyrosine phosphorylation may play a role in regulating calcium channel function. RP VOSTAL, JG (reprint author), NIDDKD,CLIN HEMATOL BRANCH,BLDG 10,RM 8C-101,BETHESDA,MD 20892, USA. NR 38 TC 171 Z9 173 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1991 VL 266 IS 25 BP 16911 EP 16916 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD635 UT WOS:A1991GD63500105 PM 1832159 ER PT J AU CLORE, GM GRONENBORN, AM AF CLORE, GM GRONENBORN, AM TI COMPARISON OF THE SOLUTION NUCLEAR-MAGNETIC-RESONANCE AND X-RAY CRYSTAL-STRUCTURES OF HUMAN RECOMBINANT INTERLEUKIN-1-BETA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE INTERLEUKIN-1-BETA; SOLUTION STRUCTURE; X-RAY STRUCTURE; NUCLEAR MAGNETIC RESONANCE ID DYNAMICS; PROTEINS; SPECTROSCOPY; RESOLUTION; REFINEMENT; ENERGY RP CLORE, GM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 18 TC 42 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 5 PY 1991 VL 221 IS 1 BP 47 EP 53 DI 10.1016/0022-2836(91)90802-D PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG372 UT WOS:A1991GG37200009 PM 1920417 ER PT J AU BENDELAC, A SCHWARTZ, RH AF BENDELAC, A SCHWARTZ, RH TI CD4+ AND CD8+ T-CELLS ACQUIRE SPECIFIC LYMPHOKINE SECRETION POTENTIALS DURING THYMIC MATURATION SO NATURE LA English DT Article ID MONOCLONAL-ANTIBODIES; MOUSE THYMOCYTES; STEM-CELLS; EXPRESSION; IL-4; SUBSETS; PRECURSORS; DEFINITION; RECEPTORS; PROFILES AB PERIPHERAL CD4+ and CD8+ T lymphocytes carry out different functions during immune reactions, partly as a result of the distinct patterns of lymphokines that they secrete upon stimulation. Using thymic cells from adult and newborn mice as well as from fetal organ cultures, we show here that this functional differentiation occurs inside the thymus and is completed during the single positive stage by the time the T-cell receptor becomes fully coupled to the intracellular activation pathways leading to lymphokine secretion. Surprisingly, CD4+8- thymocytes differ from their immediate progeny, naive peripheral CD4+ cells, in that they secrete a broader range of lymphokines, including interleukins 4, 5 and 10 and gamma-interferon, and more closely resemble immunologically experienced (activated or memory) CD4+ lymphocytes. RP BENDELAC, A (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 171 Z9 172 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 5 PY 1991 VL 353 IS 6339 BP 68 EP 71 DI 10.1038/353068a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GD805 UT WOS:A1991GD80500059 PM 1831881 ER PT J AU HEALY, B AF HEALY, B TI COPPER FOUND TO INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS PROTEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1991 VL 266 IS 9 BP 1185 EP 1185 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GC858 UT WOS:A1991GC85800004 ER PT J AU HEALY, B AF HEALY, B TI INSULIN REVERSES DEFECT IN TISSUE AFFINITY FOR GLUCOSE IN TYPE-II DIABETES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1991 VL 266 IS 9 BP 1185 EP 1185 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GC858 UT WOS:A1991GC85800007 ER PT J AU HEALY, B AF HEALY, B TI CHEMOSENSORY DYSFUNCTIONS ARE OFTEN INDICATIVE OF UNDERLYING DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1991 VL 266 IS 9 BP 1185 EP 1185 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GC858 UT WOS:A1991GC85800006 ER PT J AU HEALY, B AF HEALY, B TI IMPROVED METHOD FOR MAGNETIC-RESONANCE-IMAGING OF THE KNEE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1991 VL 266 IS 9 BP 1185 EP 1185 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GC858 UT WOS:A1991GC85800005 ER PT J AU FERRIS, FL AF FERRIS, FL TI PHOTOCOAGULATION FOR DIABETIC-RETINOPATHY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP FERRIS, FL (reprint author), NEI, BIOMETRY & EPIDEMIOL PROGRAM, CLIN TRIALS BRANCH, BLDG 31, ROOM 6A24, BETHESDA, MD 20892 USA. NR 10 TC 7 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1991 VL 266 IS 9 BP 1263 EP 1265 DI 10.1001/jama.266.9.1263 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GC858 UT WOS:A1991GC85800037 PM 1870253 ER PT J AU HAYES, HM TARONE, RE CANTOR, KP JESSEN, CR MCCURNIN, DM RICHARDSON, RC AF HAYES, HM TARONE, RE CANTOR, KP JESSEN, CR MCCURNIN, DM RICHARDSON, RC TI CASE-CONTROL STUDY OF CANINE MALIGNANT-LYMPHOMA - POSITIVE ASSOCIATION WITH DOG OWNERS USE OF 2,4-DICHLOROPHENOXYACETIC ACID HERBICIDES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-HODGKINS-LYMPHOMA; LYMPHOSARCOMA; RISK; SASKATCHEWAN; PATTERNS; LEUKEMIA; CANCER AB A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the hostology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV MINNESOTA,COLL VET MED,ST PAUL,MN 55108. COLORADO STATE UNIV,VET TEACHING HOSP,COLL VET MED,FT COLLINS,CO 80523. PURDUE UNIV,SCH VET MED,W LAFAYETTE,IN 47907. NR 37 TC 102 Z9 103 U1 2 U2 12 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 1991 VL 83 IS 17 BP 1226 EP 1231 DI 10.1093/jnci/83.17.1226 PG 6 WC Oncology SC Oncology GA GD152 UT WOS:A1991GD15200011 PM 1870148 ER PT J AU SIMON, R AF SIMON, R TI EVALUATING THE DIFFERENTIAL EFFECT OF DIET ON RAT CARCINOGENESIS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP SIMON, R (reprint author), NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,EPN 739,BETHESDA,MD 20892, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 1991 VL 83 IS 17 BP 1261 EP 1262 DI 10.1093/jnci/83.17.1261 PG 2 WC Oncology SC Oncology GA GD152 UT WOS:A1991GD15200019 PM 1870154 ER PT J AU KEREN, G LEON, MB AF KEREN, G LEON, MB TI CHARACTERIZATION OF ATHEROSCLEROTIC LESIONS BY INTRAVASCULAR ULTRASOUND - POSSIBLE ROLE IN UNSTABLE CORONARY SYNDROMES AND IN INTERVENTIONAL THERAPEUTIC PROCEDURES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MORPHOMETRIC ANALYSIS; VASCULAR-DISEASE; ANGINA-PECTORIS; PLAQUES; THROMBOSIS; MORPHOLOGY; INVITRO; DEATH C1 WASHINGTON HOSP CTR,110 IRVING ST,WASHINGTON,DC 20010. NHLBI,BETHESDA,MD 20892. NR 30 TC 11 Z9 14 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 3 PY 1991 VL 68 IS 7 BP B85 EP B91 DI 10.1016/0002-9149(91)90389-3 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GE530 UT WOS:A1991GE53000013 PM 1892072 ER PT J AU ROBERTS, WC KRAGEL, AH GERTZ, SD ROBERTS, CS KALAN, JM AF ROBERTS, WC KRAGEL, AH GERTZ, SD ROBERTS, CS KALAN, JM TI THE HEART IN FATAL UNSTABLE ANGINA-PECTORIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EPICARDIAL CORONARY-ARTERIES; ACUTE MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC PLAQUES; MORPHOMETRIC ANALYSIS; NECROPSY PATIENTS; DEATH; WEIGHT AB Compared to patients with sudden coronary death and acute myocardial infarction, relatively little morphologic data has been reported in patients with unstable angina pectoris. This article reviews necropsy data collected from one laboratory on unstable angina pectoris. From these data, several observations are appropriate: (1) Patients with unstable angina as a group have more coronary narrowing by atherosclerotic plaque than do patients with sudden coronary death or acute or healed myocardial infarction. (2) Patients with unstable angina have a much higher frequency of severe narrowing of the left main coronary artery than do patients in other coronary subsets. (3) The coronary atherosclerotic plaques in unstable angina consist primarily of fibrous tissue, and they are more similar to those found in patients with sudden coronary death than in patients with acute myocardial infarction. (4) The frequency of acute coronary lesions (thrombi, plaque rupture, and plaque hemorrhage) is similar to that observed in patients with sudden coronary death and significantly less than that observed in acute myocardial infarction. (5) The frequency of multiluminal channels throughout the major coronary arteries is significantly higher in unstable angina compared to sudden coronary death or acute myocardial infarction. (6) The major epicardial arteries and the heart are smaller in patients with unstable angina than in patients with sudden coronary death or acute myocardial infarction. (7) The left ventricular cavity is usually of normal size in patients with unstable angina and therefore left ventricular function is usually normal. RP ROBERTS, WC (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N-258,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 3 PY 1991 VL 68 IS 7 BP B22 EP B27 DI 10.1016/0002-9149(91)90381-T PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GE530 UT WOS:A1991GE53000005 PM 1892064 ER PT J AU ABEYGUNAWARDANA, C BUSH, CA CISAR, JO AF ABEYGUNAWARDANA, C BUSH, CA CISAR, JO TI COMPLETE STRUCTURE OF THE CELL-SURFACE POLYSACCHARIDE OF STREPTOCOCCUS-ORALIS-C104 - A 600-MHZ NMR-STUDY SO BIOCHEMISTRY LA English DT Article ID ACTINOMYCES-VISCOSUS T14V; SPIN COUPLING-CONSTANTS; MULTIPLE QUANTUM NMR; VIRIDANS STREPTOCOCCI; CORRELATED SPECTROSCOPY; ORALIS BRIDGE; SNEATH 1982; PROTON; PHASE; OLIGOSACCHARIDES AB Specific lectin-carbohydrate interactions between certain oral streptococci and actinomyces contribute to the microbial colonization of teeth. The receptor molecules of Streptococcus oralis, 34, ATCC 10557, and Streptococcus mitis J22 for the galactose and N-acetylgalactosamine reactive fimbrial lectins of Actinomyces viscosus and Actinomyces naeslundii are antigenically distinct polysaccharides, each formed by a different phosphodiester-linked oligosaccharide repeating unit. These streptococci all coaggregated strongly with both A. viscosus and A. naeslundii strains, whereas S. oralis C104 interacted preferentially with certain strains of the latter species. Receptor polysaccharide was isolated from S. oralis C104 cells and was shown to contain galactose, N-acetylgalactosamine, ribitol, and phosphate with molar ratios of 4:1:1:1. The H-1 NMR spectrum of the polysaccharide shows that it contains a repeating structure. The individual sugars in the repeating unit were identified by H-1 coupling constants observed in E-COSY and DQF-COSY spectra. NMR methods included complete resonance assignments (H-1 and C-13) by various homonuclear and heteronuclear correlation experiments that utilize scalar couplings. Sequence and linkage assignments were obtained from the heteronuclear multiple-bond correlation (HMBC) spectrum. This analysis shows that the receptor polysaccharide of S. oralis C104 is a ribitol teichoic acid polymer composed of a linear hexasaccharide repeating unit containing two residues each of galactopyranose and galactofuranose and a residue each of GalNAc and ribitol joined end to end by phosphodiester linkages with the following structure. [--> 6)Gal(f)(beta-1 --> 3)Gal(p)(beta-1 --> 6)Gal(f)(beta-1 --> 6)Gal(p)NAc(beta-1 --> 3)Gal(p)(alpha-1 --> 1)ribitol(5 --> PO4-]n C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228. NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [RR-02301]; NIDCR NIH HHS [DE-09445] NR 38 TC 47 Z9 47 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 3 PY 1991 VL 30 IS 35 BP 8568 EP 8577 DI 10.1021/bi00099a012 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GD733 UT WOS:A1991GD73300012 PM 1888724 ER PT J AU JONES, SVP CHOI, OH BEAVEN, MA AF JONES, SVP CHOI, OH BEAVEN, MA TI CARBACHOL INDUCES SECRETION IN A MAST-CELL LINE (RBL-2H3) TRANSFECTED WITH THE M1 MUSCARINIC RECEPTOR GENE SO FEBS LETTERS LA English DT Article DE CLONED M1 MUSCARINIC RECEPTOR; EXPRESSION (RBL-2H3 CELL); INTRACELLULAR SIGNAL; EXOCYTOSIS ID RELEASE; CALCIUM AB The possibility that the m1 muscarinic receptor subtype can induce release of intracellular granules and transmitters was studied by transfecting a cultured mast cell line, RBL-2H3 cells, with the m1 receptor gene. Comparisons were made between carbachol- and antigen-induced activation of various secretory responses. Like antigen, carbachol stimulated inositol phospholipid hydrolysis and release of arachidonic acid with concomitant dose-dependent secretion of granular contents. Carbachol also stimulated a biphasic increase in intracellular calcium, as measured by single cell fura-2 measurements. Although the kinetics of the carbachol-induced rise in intracellular calcium differed from that induced by antigen, they both utilized the same intracellular pool of calcium, and the second phase of the rise in intracellular calcium was dependent on extracellular calcium in both cases. Thus, the m1 muscarinic receptor activates release of granules by a mechanism ostensibly similar to that of antigen. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N114,BETHESDA,MD 20892. UNIV VERMONT,DEPT PSYCHIAT,BURLINGTON,VT 05405. NINCDS,BIOPHYS & MOLEC BIOL LAB,BURLINGTON,VT 05405. NR 19 TC 63 Z9 63 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 2 PY 1991 VL 289 IS 1 BP 47 EP 50 DI 10.1016/0014-5793(91)80905-I PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GE523 UT WOS:A1991GE52300012 PM 1832647 ER PT J AU HOEFER, M COOK, JC AF HOEFER, M COOK, JC TI PURIFICATION AND PARTIAL CHARACTERIZATION OF UBIQUITIN-ACTIVATING ENZYME FROM SACCHAROMYCES-CEREVISIAE SO FEBS LETTERS LA English DT Article DE YEAST; UBIQUITIN-ACTIVATING ENZYME ID PROTEIN LIGASE SYSTEM; AFFINITY PURIFICATION; RESOLUTION; MECHANISM; BINDING; YEAST; ATP AB Ubiquitin-activating enzyme was purified from the yeast Saccharomyces cerevisiae by covalent affinity chromatography on ubiquitin-Sepharose followed by HPLC anion-exchange chromatography. Enzyme activity was monitored by the ubiquitin-dependent ATP: 32PP(i) exchange assay. The purified enzyme has a specific activity of 1.5-mu-mol 32PP(i) incorporated into ATP.min-1.mg-1 at 37-degrees-C and pH 7.0 under standard conditions for substrate concentrations as described by Ciechanover et al. (1982) J. Biol. Chem. 257, 2537-2542. The catalytic activity showed a maximum at pH 7.0. Its molecular weight both in non-denaturing and in SDS-gel electrophoresis was estimated to be 115 kDa, suggesting a monomeric form. The isoelectric point determined by gel electrofocusing was approximately 4.7. Two protein bands differing slightly in electrophoretic mobility could be distinguished when SDS gels were loaded with very small amounts of purified E1 and immunoblotted, the one with higher molecular weight being clearly predominant. The same two bands were also found in anti-E1 immunoblots of crude yeast lysates prepared under broad protease inhibition. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV FREIBURG,INST BIOCHEM,W-7800 FREIBURG,GERMANY. NR 23 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 2 PY 1991 VL 289 IS 1 BP 54 EP 58 DI 10.1016/0014-5793(91)80907-K PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GE523 UT WOS:A1991GE52300014 PM 1894008 ER PT J AU GINSBERG, L GERSHFELD, NL AF GINSBERG, L GERSHFELD, NL TI MEMBRANE BILAYER INSTABILITY AND THE PATHOGENESIS OF DISORDERS OF MYELIN SO NEUROSCIENCE LETTERS LA English DT Article DE MYELIN; MEMBRANE; METACHROMATIC LEUKODYSTROPHY; MULTIPLE SCLEROSIS; LIPID BILAYER ID METACHROMATIC LEUKODYSTROPHY; MULTIPLE-SCLEROSIS; WHITE MATTER; OLIGODENDROCYTES; TEMPERATURE; COMPLEMENT; STATE AB We have previously shown that total lipid extracts from normal nervous tissues spontaneously form a structure in vitro resembling the cell membrane bilayer, but only at a critical temperature, T*, equal to the 'physiological' temperature of the original tissues. In the present study, we found T* for normal human myelin lipids was 37-degrees-C, in agreement with the concept that lipid metabolic pools maintain a critical composition in vivo which permits spontaneous formation of the (myelin) membrane bilayer at normal body temperature. But T* for myelin lipids from a patient with metachromatic leukodystrophy was < 30-degrees-C. Thus, myelin lipid composition was inappropriate for normal bilayer stability at this patient's core temperature, suggesting a mechanism whereby defective lipid metabolism in this disease could produce pathological myelin. The shift in T* in this patient was unlikely to be simply secondary to myelin destruction, as myelin lipids from a patient with advanced multiple sclerosis yielded a normal value for T* of 37-degrees-C, even when extracted from areas of extensive demyelination. C1 NIAMS,PHYS BIOL LAB,BLDG 6,ROOM 139,BETHESDA,MD 20892. RI Ginsberg, Lionel/C-8704-2009 NR 27 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 2 PY 1991 VL 130 IS 1 BP 133 EP 136 DI 10.1016/0304-3940(91)90245-O PG 4 WC Neurosciences SC Neurosciences & Neurology GA GE330 UT WOS:A1991GE33000033 PM 1749512 ER PT J AU HEALY, B NOVELLO, AC VARMUS, H BIRNEY, D AF HEALY, B NOVELLO, AC VARMUS, H BIRNEY, D TI THE CRUCIAL LINK BETWEEN LABORATORY-ANIMAL RESEARCH AND HUMAN HEALTH SO ACADEMIC MEDICINE LA English DT Article RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1991 VL 66 IS 9 BP 526 EP 530 DI 10.1097/00001888-199109000-00006 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA GF337 UT WOS:A1991GF33700006 PM 1883448 ER PT J AU SOLOMON, D AF SOLOMON, D TI NOMENCLATURE FOR THE CYTODIAGNOSIS OF CERVICAL INTRAEPITHELIAL LESIONS - REPLY SO ACTA CYTOLOGICA LA English DT Letter ID TERM FOLLOW-UP; DYSPLASIA; BEHAVIOR RP SOLOMON, D (reprint author), NCI,CYTOPATHOL SECT,BLDG 10,ROOM 2A19,900 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 1991 VL 35 IS 5 BP 658 EP 659 PG 2 WC Pathology SC Pathology GA GG709 UT WOS:A1991GG70900022 ER PT J AU MOLLER, H KNELLER, RW BOICE, JD OLSEN, JH AF MOLLER, H KNELLER, RW BOICE, JD OLSEN, JH TI CANCER INCIDENCE FOLLOWING HOSPITALIZATION FOR MULTIPLE-SCLEROSIS IN DENMARK SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE MULTIPLE SCLEROSIS; CANCER INCIDENCE; COHORT STUDY; RECORD LINKAGE; HOSPITAL DISCHARGE ID HODGKINS-DISEASE; ANTIBODY; VIRUS; TUMOR AB Incidence of various cancers was evaluated in a cohort of 5359 multiple sclerosis (MS) patients, identified through hospital discharge records between 1977 and 1987 and followed for an average of 5.2 years. Computerized linkage with the Danish Cancer Registry uncovered 210 cancer cases which was significantly more than expected based on national rates (relative risk (RR) = 1.29). Over half of the excess, however, was observed for non-melanoma skin cancer and tumors of the urinary tract, which may be related to increased medical surveillance among MS patients compared to the Danish population as a whole. There was a significant excess of nasopharyngeal carcinomas in the cohort (RR = 17.3), but based on only 3 cases and seen only among women. Hematologic and lymphatic malignancies were not increased, adding little support to previous suggestions of a possible association of these malignancies with MS. An excess of brain tumors, seen only in women, may represent situations where the tumor caused symptoms which were interpreted as MS. Overall, the data suggest that a patient with MS is not at unusual risk for subsequent cancer development, but the relatively short follow-up of the population is a limitation of the investigation. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MOLLER, H (reprint author), DANISH CANC SOC,INST CANC EPIDEMIOL,DANISH CANC REGISTRY,ROSENVAENGETS HOVEDVEJ 35,POB 839,DK-2100 COPENHAGEN 0,DENMARK. OI Moller, Henrik/0000-0001-8200-5929 NR 31 TC 50 Z9 50 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD SEP PY 1991 VL 84 IS 3 BP 214 EP 220 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA GH479 UT WOS:A1991GH47900009 PM 1950464 ER PT J AU DSOUZA, MP DURDA, P HANSON, CV MILMAN, G AF DSOUZA, MP DURDA, P HANSON, CV MILMAN, G TI EVALUATION OF MONOCLONAL-ANTIBODIES TO HIV-1 BY NEUTRALIZATION AND SEROLOGICAL ASSAYS - AN INTERNATIONAL COLLABORATION SO AIDS LA English DT Article DE HIV-1; MONOCLONAL ANTIBODIES; NEUTRALIZATION; SEROLOGY; STANDARDIZATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIGENS; RETROVIRUSES; GENERATION; MICROASSAY; PEPTIDES; EPITOPE AB In a National Institutes of Health (NIH)/World Health Organization (WHO)-sponsored collaboration, 26 laboratories characterized a coded panel of monoclonal antibodies (MAb) to HIV-1 envelope protein. The MAb were evaluated by serological [radioimmunoprecipitation, immunoblot, enzyme-linked immunosorbent assay (ELISA) and peptide mapping] and neutralization assays. Although laboratories used diverse neutralization assays that vary considerably in sensitivity, qualitatively similar data were obtained. The MAb were classified into three neutralization specificities: type-specific for MN and SF2, type-specific for IIIB, and group-specific for MN, SF2, and IIIB. The group-specific MAb displayed much lower neutralizing titers than the type-specific MAb. The specificity of MAb for neutralization was greater than for serological recognition of gp120 protein or peptide epitopes. Some MAb that bound to the same or closely overlapping linear epitopes had very different neutralization properties. The distinction between serological recognition and neutralization may result from differences in affinity of the MAb or may indicate that MAb can neutralize by interactions at a site distinct from the antibody binding site. C1 CALIF DEPT HLTH SERV,BERKELEY,CA 94704. DUPONT CO,N BILLERICA,MA. RP DSOUZA, MP (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 37 TC 53 Z9 53 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1991 VL 5 IS 9 BP 1061 EP 1070 DI 10.1097/00002030-199109000-00001 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GF841 UT WOS:A1991GF84100002 PM 1718320 ER PT J AU VITKOVIC, L WOOD, GP MAJOR, EO FAUCI, AS AF VITKOVIC, L WOOD, GP MAJOR, EO FAUCI, AS TI HUMAN ASTROCYTES STIMULATE HIV-1 EXPRESSION IN A CHRONICALLY INFECTED PROMONOCYTE CLONE VIA INTERLEUKIN-6 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TUMOR NECROSIS FACTOR; CENTRAL NERVOUS-SYSTEM; HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; FACTOR-ALPHA; CEREBROSPINAL-FLUID; BRAIN; INDUCTION; CELLS; LIPOPOLYSACCHARIDE AB Human promonocyte cells chronically infected with human immunodeficiency virus type (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by human astrocytes and glioma cell lines U251 and 253. HIV-1 expression was assessed by measuring reverse transcriptase activity. All media conditioned by unstimulated and lipopolysaccharide (LPS) stimulated glial cells induced HIV-1 expression and contained detectable levels of interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha). An antibody against IL-6, but not against TNF-alpha, reduced the induction of HIV-1 by the conditioned media in a concentration-dependent manner. The magnitude of HIV-1 induction by the conditioned media was proportional to the concentration of IL-6 in them. The data indicate that normal and transformed human astrocytes are capable of stimulating HIV-1 expression in chronically infected promonocytic cells by secreting IL-6. The results demonstrate that cytokines secreted by neural cells could play an important role in regulating HIV-1 expression in the brain. C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RP VITKOVIC, L (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 28 TC 30 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1991 VL 7 IS 9 BP 723 EP 727 DI 10.1089/aid.1991.7.723 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GG140 UT WOS:A1991GG14000002 PM 1742078 ER PT J AU FRUCHT, DM LAMPERTH, L VICENZI, E BELCHER, JH MARTIN, MA AF FRUCHT, DM LAMPERTH, L VICENZI, E BELCHER, JH MARTIN, MA TI ULTRAVIOLET-RADIATION INCREASES HIV-LONG TERMINAL REPEAT-DIRECTED EXPRESSION IN TRANSGENIC MICE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; DNA DAMAGE; INDUCTION; CELLS; TYPE-1; KERATINOCYTES; IRRADIATION; ACTIVATION; GENOMES; GENE AB Previously described FVB/N mice harboring a human immunodeficiency virus (HIV) long terminal repeat (LTR)/chloramphenicol acetyl transferase (CAT) transgene were treated with varying amounts of 254 nm UV-C radiation or 312 nm UV-B radiation. At optimal exposure periods, a 20-fold increase in HIV-LTR-directed expression was observed in ear specimens collected 24 h following UV-C exposure; a fourfold increase in expression was induced by UV-B exposure. Investigation of the kinetics of UV-C induction in vivo revealed that LTR-directed gene expression began to increase 2 hours after exposure and reached a maximum on Day 3 following exposure (> 30-fold induction). In experiments examining the kinetics of UV-B activation, the maximum level of CAT activity in the ears of irradiated transgenic animals was fivefold above levels in unirradiated transgenic controls (Day 5). Furthermore, CAT activity was not induced in fur-bearing skin following UV exposure; however, a fourfold increase in HIV-LTR-directed expression could be elicited when hair was removed by shaving prior to UV-B treatment. C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NIAID,MED NEUROL BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. OI Vicenzi, Elisa/0000-0003-0051-3968 NR 20 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1991 VL 7 IS 9 BP 729 EP 733 DI 10.1089/aid.1991.7.729 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GG140 UT WOS:A1991GG14000003 PM 1742079 ER PT J AU RAHMATHULLAH, L UNDERWOOD, BA THULASIRAJ, RD MILTON, RC AF RAHMATHULLAH, L UNDERWOOD, BA THULASIRAJ, RD MILTON, RC TI DIARRHEA, RESPIRATORY-INFECTIONS, AND GROWTH ARE NOT AFFECTED BY A WEEKLY LOW-DOSE VITAMIN-A SUPPLEMENT - A MASKED, CONTROLLED FIELD TRIAL IN CHILDREN IN SOUTHERN INDIA SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE MORBIDITY; DIARRHEA; RESPIRATORY INFECTIONS; VITAMIN-A; GROWTH; VITAMIN-A DEFICIENCY ID PRESCHOOL-CHILDREN; MILD VITAMIN; NUTRITIONAL-STATUS; TRACT INFECTIONS; INCREASED RISK; DEFICIENCY; MORBIDITY; MALNUTRITION; MORTALITY; COMMUNITY AB Incidence, duration, and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15 419 children 6-60 mo of age in a randomized, placebo-controlled, masked clinical trial conducted in southern India. Half the children received weekly doses of 8.7-mu-mol (2500-mu-g) vitamin A and 46-mu-mol (20 mg) vitamin E (treated) and the other half, 46-mu-mol vitamin E (control). Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention. Ocular examinations also were obtained after 26 wk. Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother's recall of daily morbidity of her child during the previous week. Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11% xerophthalmia and 72% undernutrition. Weekly treatment with the low-dose vitamin A supplement did not influence the incidence, severity, or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth. C1 NEI,OFF INT PROGRAMS,BLDG 31,ROOM 6A-17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. ARAVIND CHILDRENS HOSP,MADURAI,INDIA. ARAVIND EYE HOSP,MADURAI,INDIA. NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD. NR 42 TC 93 Z9 95 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1991 VL 54 IS 3 BP 568 EP 577 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GD041 UT WOS:A1991GD04100019 PM 1877512 ER PT J AU COSSMAN, J GARRETT, CT HANSON, LO JAFFE, E AF COSSMAN, J GARRETT, CT HANSON, LO JAFFE, E TI GENE REARRANGEMENTS IN THE DIAGNOSIS OF LYMPHOMA LEUKEMIA - REPLY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. ONCOR INC,GAITHERSBURG,MD. NIH,BETHESDA,MD 20892. RP COSSMAN, J (reprint author), GEORGETOWN UNIV,WASHINGTON,DC 20057, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1991 VL 96 IS 3 BP 437 EP 437 PG 1 WC Pathology SC Pathology GA GD045 UT WOS:A1991GD04500029 ER PT J AU KNEKT, P JARVINEN, R SEPPANEN, R RISSANEN, A AROMAA, A HEINONEN, OP ALBANES, D HEINONEN, M PUKKALA, E TEPPO, L AF KNEKT, P JARVINEN, R SEPPANEN, R RISSANEN, A AROMAA, A HEINONEN, OP ALBANES, D HEINONEN, M PUKKALA, E TEPPO, L TI DIETARY ANTIOXIDANTS AND THE RISK OF LUNG-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE DIET; LONGITUDINAL STUDIES; LUNG NEOPLASMS; SELENIUM; VITAMIN-A; VITAMIN-C; VITAMIN-E ID VITAMIN-A; FINNISH MEN; SELENIUM; ADULTS AB The relation between the intake of retinoids, carotenoids, vitamin E, vitamin C, and selenium and the subsequent risk of lung cancer was studied among 4,538 initially cancer-free Finnish men aged 20-69 years. During a follow-up of 20 years beginning in 1966-1972, 117 lung cancer cases were diagnosed. Inverse gradients were observed between the intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers, for whom the age-adjusted relative risks of lung cancer in the lowest tertile of intake compared with that in the highest tertile were 2.5 (p value for trend = 0.04), 3.1 (p = 0.12), and 3.1 (p < 0.01) for the three intakes, respectively. Adjustment for various potential confounding factors did not materially alter the results, and the associations did not seem to be due to preclinical cancer. In the total cohort, there was an inverse association between intake of margarine and fruits and risk of lung cancer. The relative risk of lung cancer for the lowest compared with the highest tertile of margarine intake was 4.0 (p < 0.001), and that for fruits was 1.8 (p = 0.01). These associations persisted after adjustment for the micronutrient intakes and were stronger among nonsmokers. The results suggest that carotenoids, vitamin E, and vitamin C may be protective against lung cancer among nonsmokers. Food sources rich in these micronutrients may also have other constituents with independent protective effects against lung cancer. C1 UNIV HELSINKI,DEPT FOOD CHEM & TECHNOL,SF-00100 HELSINKI 10,FINLAND. FINNISH CANC REGISTRY,HELSINKI,FINLAND. NATL PUBL HLTH INST,SF-00280 HELSINKI 28,FINLAND. UNIV KUOPIO,DEPT CLIN NUTR,SF-70101 KUOPIO 10,FINLAND. NCI,BETHESDA,MD 20892. RP KNEKT, P (reprint author), SOCIAL INSURANCE INST,SOCIAL SECUR RES INST,POB 78,SF-00381 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 44 TC 149 Z9 152 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1991 VL 134 IS 5 BP 471 EP 479 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GH065 UT WOS:A1991GH06500006 PM 1897503 ER PT J AU TAYLOR, JO CORNONIHUNTLEY, J CURB, JD MANTON, KG OSTFELD, AM SCHERR, P WALLACE, RB AF TAYLOR, JO CORNONIHUNTLEY, J CURB, JD MANTON, KG OSTFELD, AM SCHERR, P WALLACE, RB TI BLOOD-PRESSURE AND MORTALITY RISK IN THE ELDERLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGING; BLOOD PRESSURE; CARDIOVASCULAR DISEASES; HYPERTENSION; LONGITUDINAL STUDIES; MORTALITY ID CORONARY HEART-DISEASE; SERUM-CHOLESTEROL LEVELS; PREDICTING RISK; HYPERTENSION; TRIAL; MEN; SURVIVAL; AUTOPSY; CARE; OLD AB Blood pressure was assessed between 1981 and 1983 in all persons over age 65 years in three communities (East Boston, Massachusetts; New Haven, Connecticut; and lowa and Washington counties, Iowa), and cause-specific mortality was monitred annually over the subsequent 5 years as part of the National Institute on Aging-sponsored Established Populations for Epidemiologic Studies of the Elderly. Each community had 80% or more participation: in East Boston, 3,809 persons with 903 deaths, in New Haven, 2,812 persons with 804 deaths, and in Iowa, 3,673 persons with 763 deaths. At 2 years, odds of death from all causes were higher in the low (< 130 mmHg) than the middle (130-159 mmHg) systolic blood pressure group for persons aged 65-79 years in all three populations. By 5 years, cardiovascular death increased with increasing systolic pressure in all three communities and reached significance in Iowa. Cancer death was highest in the low systolic pressure stratum in all three centers. All-cause, cardiovascular death, and cancer mortality was highest in the low (< 75 mmHg) diastolic blood pressure group in East Boston, even at 5 years. Blood pressures obtained 9 years earlier in 2,079 (68%) of the East Boston participants showed a significantly higher risk of cardiovascular death with increasing systolic pressure and no relation between diastolic pressure and mortality risk. In the elderly, excess mortality at lower levels of blood pressure during early follow-up may in part be due to the effects of illness and disability present at baseline. This may obscure the usual rise in mortality with increasing systolic pressure. There is no consistent relation between diastolic pressure and mortality. C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06510. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CHANNING LAB,DEPT MED,BOSTON,MA 02115. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV HAWAII MANOA,SCH PUBL HLTH,HONOLULU,HI 96822. UNIV MASSACHUSETTS,DEPT PREVENT MED & ENVIRONM HLTH,AMHERST,MA 01003. DUKE UNIV,CTR DEMOG STUDIES,DURHAM,NC 27706. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2107, N01-AG-0-2106] NR 39 TC 105 Z9 105 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1991 VL 134 IS 5 BP 489 EP 501 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GH065 UT WOS:A1991GH06500009 PM 1897505 ER PT J AU SHIONO, PH KLEBANOFF, MA AF SHIONO, PH KLEBANOFF, MA TI THE EFFECT OF 2 MAILING STRATEGIES ON THE RESPONSE TO A SURVEY OF PHYSICIANS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Note DE HEALTH SURVEYS; PHYSICIANS; PHYSICIANS, WOMEN; POSTAL SERVICE; SURVEY METHODS AB In 1989, the authors tested the effectiveness of two response-enhancing techniques, a postage stamped or franked return envelope and a prenotification letter, in a survey of pregnancy among 10,047 resident physicians in the United States. The techniques were randomly assigned using a factorial design. No significant interactions were observed between the techniques. After two mailings, those who received a stamped return envelope had a response of 71.2%, compared with 68.2% for those who received a franked return envelope (95% confidence interval 1.3-4.9%). Men who received the stamped envelope had a 5.9% greater response than those who received the franked envelope (p < 0.001), but the type of postage did not influence response among women (p = 0.84); this interaction was statistically significant (p = 0.006). Physicians who received a prenotification letter had a response of 69.0%, compared with 70.5% for those who did not receive the letter (95% confidence interval -3.3 to 0.2%). The authors conclude that seemingly minor changes in survey design could have saved from 12% to 19% of the total cost of the study. C1 DAVID & LUCILE PACKARD FDN,CTR FUTURE CHILDREN,LOS ALTOS,CA. NICHHD,DIV PREVENT RES,EPN 640,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-9-2923] NR 12 TC 37 Z9 36 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1991 VL 134 IS 5 BP 539 EP 542 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GH065 UT WOS:A1991GH06500014 PM 1897510 ER PT J AU JOHNSTON, PG RUSCETTI, FW CONNAGHAN, DG SULLIVAN, FJ LONGO, DL AF JOHNSTON, PG RUSCETTI, FW CONNAGHAN, DG SULLIVAN, FJ LONGO, DL TI TRANSIENT REVERSAL OF BONE-MARROW APLASIA ASSOCIATED WITH LYMPHOCYTE DEPLETED HODGKINS-DISEASE AFTER COMBINATION CHEMOTHERAPY SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE APLASTIC MARROW; MOPP CHEMOTHERAPY; APLASTIC ANEMIA; LYMPHOCYTE DEPLETED; HODGKINS DISEASE ID RED-CELL APLASIA; T-CELLS; ANEMIA; INVITRO; COMPLICATIONS; INTERLEUKIN-1; SUPPRESSION; GENERATION; INTERFERON; DISORDERS AB This report describes a patient with lymphocyte depleted Hodgkin's disease who presented with bone marrow aplasia. The aplastic marrow reverted to normal after initiation of MOPP chemotherapy; however, 4 months after completion of therapy, bone marrow aplasia recurred in the absence of recurrent Hodgkin's disease. The patient remains free of Hodgkin's disease 34 months after completion of chemotherapy. Bone marrow abnormalities in Hodgkin's disease are reviewed and the current understanding of the pathological mechanisms leading to aplastic anemia is discussed. C1 NIH,CTR CLIN,DEPT CLIN PATHOL,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. RP JOHNSTON, PG (reprint author), NCI,MED BRANCH,BLD 10,RM12N226,BETHESDA,MD 20892, USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 1991 VL 38 IS 1 BP 54 EP 60 DI 10.1002/ajh.2830380109 PG 7 WC Hematology SC Hematology GA GF622 UT WOS:A1991GF62200008 PM 1897515 ER PT J AU DONO, R MONTUORI, N ROCCHI, M DEPONTIZILLI, L CICCODICOLA, A PERSICO, MG AF DONO, R MONTUORI, N ROCCHI, M DEPONTIZILLI, L CICCODICOLA, A PERSICO, MG TI ISOLATION AND CHARACTERIZATION OF THE CRIPTO AUTOSOMAL GENE AND ITS X-LINKED RELATED SEQUENCE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; LDL RECEPTOR; GLOBIN GENE; PROMOTER; HYBRIDIZATION; PROTEINS; ACID; RNA; EMBRYOGENESIS; RETROPOSON AB We have previously reported on the identification of a cDNA clone encoding a novel human growth factor, named "CRIPTO," that is abundantly expressed in undifferentiated human NTERA-2 clone D1 (NT2/D1) and mouse (F9) teratocarcinoma cells. We now report the organization and nucleotide sequence of two related genomic sequences. One (CR-1) corresponds to the structural gene encoding the human CRIPTO protein expressed in the undifferentiated human teratocarcinoma cells, and the other (CR-3) corresponds-to a complete copy of the mRNA containing seven base substitutions in the coding region representing both silent and replacement substitutions. The 440 bp 5' to the CAP site of CR-1 are preserved in CR-3. CR-1 maps to chromosome 3, and CR-3 maps to Xq21-q22. Southern blot analysis reveals that multiple CRIPTO-related DNA sequences are present in the human as well as in the mouse genome. C1 CNR,INT INST GENET & BIOPHYS,VIA MARCONI 10,I-80125 NAPLES,ITALY. IST GIANNINA GASLINI,MOLEC BIOL LAB,I-16148 GENOA,ITALY. NIDDK,MOLEC BIOL LAB,BETHESDA,MD. RI Montuori, Nunzia/J-8542-2013; DONO, ROSANNA/I-7821-2016; OI Montuori, Nunzia/0000-0001-8697-986X NR 36 TC 51 Z9 53 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1991 VL 49 IS 3 BP 555 EP 565 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA GE367 UT WOS:A1991GE36700008 PM 1882841 ER PT J AU DEAN, M LUCASDERSE, S BOLOS, A OBRIEN, SJ KIRKNESS, EF FRASER, CM GOLDMAN, D AF DEAN, M LUCASDERSE, S BOLOS, A OBRIEN, SJ KIRKNESS, EF FRASER, CM GOLDMAN, D TI GENETIC-MAPPING OF THE BETA-I GABA RECEPTOR GENE TO HUMAN CHROMOSOME-4, USING A TETRANUCLEOTIDE REPEAT POLYMORPHISM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID C-III GENE; FUNCTIONAL EXPRESSION; SUBUNIT; SEQUENCE; HETEROGENEITY; LOCALIZATION; ANTAGONIST; DISEASE AB As more coding loci for functional human genes are described, there is a growing need to identify DNA polymorphisms in specific genes. By examining DNA sequences within the introns of the beta-1 subunit of the gamma-aminobutyric acid receptor gene, GABARB1, we found a tetranucleotide repeat sequence (GATA). Amplification of this region by using PCR revealed seven alleles and a high degree of polymorphism (PIC = .75) in human populations. DNAs from the CEPH families were typed for the GABARB1 intron polymorphism and were analyzed with respect to 20 linked markers on chromosome 4. The results permit placement of GABARB1 on the linkage map of chromosome 4, between D4S104 and ALB. These results affirm that sequence analysis of noncoding segments included within or adjacent to functional genes has value as a strategy to detect highly informative polymorphisms. C1 PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NIAAA,CLIN STUDIES LAB,BETHESDA,MD. NIAAA,PHARMACOL STUDIES LAB,ROCKVILLE,MD 20852. RP DEAN, M (reprint author), NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 FU NCI NIH HHS [N01-CO-74102] NR 29 TC 39 Z9 39 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1991 VL 49 IS 3 BP 621 EP 626 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GE367 UT WOS:A1991GE36700015 PM 1652891 ER PT J AU MCLAUGHLIN, JK MEHL, ES AF MCLAUGHLIN, JK MEHL, ES TI A COMPARISON OF OCCUPATIONAL DATA FROM DEATH CERTIFICATES AND INTERVIEWS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE DEATH CERTIFICATE DATA; OCCUPATION AND INDUSTRY EQUIVOCATIONS; SURROGATE RESPONSES ID INDUSTRY DATA; INFORMATION; MORTALITY; ACCURACY; RECORDS; CANCER AB A comparison was made of the occupational data reported on the death certificates of 586 men with their employment history obtained by interviews. Agreement was assessed for 19 occupational and 14 industrial categories of usual employment, with the highest levels of concordance (greater-than-or-equal-to 80%) found for agricultural, medical, and public administration activities. Between the two sources of information, there was overall agreement of 56% for usual occupation and 51% for usual industry of employment. Concordance was highest among the 68 self-respondents (usual occupation 66%; usual industry 53%). Among the 518 surrogates, spousal agreement was highest (58% for occupation and 51% for industry). For other surrogate types, agreement was 49% for both industry and occupation. Agreement varied by duration of employment and by level of education, with concordance tending to increase as length of employment and educational attainment rose. These relationships remained when examined by respondent type. Evaluation of agreement levels by age and other study subject characteristics showed little effect on concordance. Review of verbatim data from the interviews and death certificates revealed that most disagreements could be attributed to coding problems caused by vague or misleading information on the death certificates, although some disconcordance was due to uncodable and missing information in the interview history. Based on results from this and prior studies, the value of occupational data derived from death certificates in epidemiologic studies may be limited, although the addition of explicit instructions on the death certificate itself may aid in providing more useful and complete information for usual employment. C1 WESTAT CORP,1650 RES BLVD,ROCKVILLE,MD. NCI,BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL EPIDEMIOL,BETHESDA,MD 20892, USA. NR 15 TC 13 Z9 13 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 1991 VL 20 IS 3 BP 335 EP 342 DI 10.1002/ajim.4700200306 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GC246 UT WOS:A1991GC24600005 PM 1928110 ER PT J AU KAPLAN, MH HALL, WW SUSIN, M PAHWA, S SALAHUDDIN, SZ HEILMAN, C FETTEN, J CORONESI, M FARBER, BF SMITH, S AF KAPLAN, MH HALL, WW SUSIN, M PAHWA, S SALAHUDDIN, SZ HEILMAN, C FETTEN, J CORONESI, M FARBER, BF SMITH, S TI SYNDROME OF SEVERE SKIN-DISEASE, EOSINOPHILIA, AND DERMATOPATHIC LYMPHADENOPATHY IN PATIENTS WITH HTLV-II COMPLICATING HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID T-CELL LEUKEMIA; PERSISTENT GENERALIZED LYMPHADENOPATHY; CHRONIC PROGRESSIVE MYELOPATHY; TROPICAL SPASTIC PARAPARESIS; AIDS-RELATED LYMPHADENOPATHY; HOMOSEXUAL MEN; MYCOSIS-FUNGOIDES; LYMPHOPROLIFERATIVE DISORDERS; CONCOMITANT INFECTION; CULTURED LYMPHOCYTES AB Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemis virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1. C1 N SHORE UNIV HOSP,CORNELL UNIV MED COLL,DEPT PATHOL,MANHASSET,NY 11030. N SHORE UNIV HOSP,CORNELL UNIV MED COLL,DEPT PEDIAT,MANHASSET,NY 11030. NCI,TUMOR & CELL BIOL LAB,BETHESDA,MD 20892. DUPONT CO,WILMINGTON,DE 19898. UNIV MED & DENT NEW JERSEY,DEPT PATHOL,NEWARK,NJ 07103. UNIV MED & DENT NEW JERSEY,DEPT MED,NEWARK,NJ 07103. VET ADM MED CTR,E ORANGE,NJ 07019. RP KAPLAN, MH (reprint author), N SHORE UNIV HOSP,CORNELL UNIV MED COLL,DEPT MED,300 COMMUNITY DR,MANHASSET,NY 11030, USA. NR 72 TC 52 Z9 52 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1991 VL 91 IS 3 BP 300 EP 309 DI 10.1016/0002-9343(91)90132-H PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA GG130 UT WOS:A1991GG13000016 PM 1892151 ER PT J AU STRAUS, SE AF STRAUS, SE TI INTRAVENOUS IMMUNOGLOBULIN TREATMENT OF CHRONIC FATIGUE SYNDROME - REPLY SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter RP STRAUS, SE (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1991 VL 91 IS 3 BP 320 EP 320 DI 10.1016/0002-9343(91)90140-S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GG130 UT WOS:A1991GG13000024 ER PT J AU HOFFMAN, GS LEAVITT, RY FAUCI, AS AF HOFFMAN, GS LEAVITT, RY FAUCI, AS TI PULSE CYCLOPHOSPHAMIDE THERAPY FOR WEGENERS GRANULOMATOSIS - REPLY SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter RP HOFFMAN, GS (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1991 VL 91 IS 3 BP 322 EP 322 DI 10.1016/0002-9343(91)90145-N PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GG130 UT WOS:A1991GG13000029 ER PT J AU MASON, DY CRAMER, EM MASSE, JM CRYSTAL, R BASSOT, JM BRETONGORIUS, J AF MASON, DY CRAMER, EM MASSE, JM CRYSTAL, R BASSOT, JM BRETONGORIUS, J TI ALPHA1-ANTITRYPSIN IS PRESENT WITHIN THE PRIMARY GRANULES OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FAST-FREEZE FIXATION; HUMAN-NEUTROPHILS; ULTRASTRUCTURAL-LOCALIZATION; MONOCLONAL-ANTIBODY; IMMUNOGOLD; ELASTASE; ALPHA-1-ANTITRYPSIN; MYELOPEROXIDASE; GENE AB Elastase is a potent proteolytic enzyme found within human neutrophil primary granules. Its major inhibitor in the serum is alpha-1-antitrypsin, a protein that is synthesized by hepatocytes but which has recently also been shown to be synthesized by circulating neutrophils. The authors have therefore carried out an immunocytochemical study at the light microscopic and ultrastructural level to determine the intracellular localization of alpha-1-antitrypsin. Double labeling with colloidal gold showed that alpha-1-antitrypsin is localized at the same site as neutrophil elastase, i.e., within primary granules. Secondary granules (detected by labeling for lactoferrin) were unstained for alpha-1-antitrypsin. Elastase and its major inhibitor therefore coexist within the same granule population within human neutrophils. Some difference in their intraorganelle distribution existed at the ultrastructural level (in that elastase tended to be localized at the periphery of the granules whereas alpha-1-antitrypsin was usually diffusely present in the matrix of the granules), but further studies are required to determine whether the two molecules are already complexed with each other within the neutrophil. C1 CHU HENRI MONDOR,INSERM,U91,F-94010 CRETEIL,FRANCE. NHLBI,BETHESDA,MD 20892. LAB TECHNOL APPL MICROSCOPIE,PARIS,FRANCE. RP MASON, DY (reprint author), JOHN RADCLIFFE HOSP,DEPT HAEMATOL,OXFORD OX3 9DU,ENGLAND. NR 16 TC 35 Z9 37 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1991 VL 139 IS 3 BP 623 EP 628 PG 6 WC Pathology SC Pathology GA GE846 UT WOS:A1991GE84600017 PM 1887864 ER PT J AU DEHAYE, JP TURNER, RJ AF DEHAYE, JP TURNER, RJ TI ISOLATION AND CHARACTERIZATION OF RAT SUBMANDIBULAR INTRALOBULAR DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SALIVARY DUCTS; KALLIKREIN; AMYLASE; STIMULUS-SECRETION COUPLING; INTRACELLULAR CALCIUM, ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE ID SUBSTANCE-P; GLANDS; STIMULATION; TRANSPORT; SECRETION; BINDING; PEPTIDE; CALCIUM; PERCOLL; CA-2+ AB Intralobular (granular) salivary ducts were purified by isopycnic centrifugation after collagenase/hyaluronidase digestion of the rat submandibular gland. The resulting ductal fraction (density, 1.056 +/- 0.003) was highly enriched in kallikrein (a ductal cell marker) and contained little amylase activity (an acinar cell marker). The resting intracellular calcium level in the ductal preparation was 103 +/- 4 nM. Increased intracellular calcium concentrations (2-3 times resting levels) were observed in response to muscarinic (carbachol) and alpha-adrenergic (epinephrine) agonists, but little response was observed to substance P, suggesting the absence of substance P peptidergic receptors on rat submandibular ducts. Intracellular adenosine 3',5'-cyclic monophosphate levels were increased 35-fold in response to beta-adrenergic stimulation (isoproterenol) and forskolin. The ducts secreted kallikrein in response to epinephrine, carbachol, and isoproterenol but not in response to substance P. Epinephrine was the most potent inducer of kallikrein release with a K0.5 of approximately 3 mu-M and a maximal secretory rate approximately nine times unstimulated levels. Taken together, these results provide strong evidence for the functional integrity of the ductal preparation. This preparation should prove useful for the further elucidation of the properties of intralobular salivary ducts, structures which heretofore have only been studied indirectly. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1A06,BETHESDA,MD 20892. FREE UNIV BRUSSELS,INST PHARM,DEPT GEN & HUMAN BIOCHEM,B-1050 BRUSSELS,BELGIUM. NR 28 TC 52 Z9 53 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP C490 EP C496 PN 1 PG 7 WC Physiology SC Physiology GA GE637 UT WOS:A1991GE63700014 PM 1716052 ER PT J AU RAVUSSIN, E HARPER, IT RISING, R BOGARDUS, C AF RAVUSSIN, E HARPER, IT RISING, R BOGARDUS, C TI ENERGY-EXPENDITURE BY DOUBLY LABELED WATER - VALIDATION IN LEAN AND OBESE SUBJECTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE INDIRECT CALORIMETRY; RESPIRATORY CHAMBER; OBESITY ID TOTAL-BODY WATER; CO2 PRODUCTION; EXCHANGEABLE HYDROGEN; INFANTS; HUMANS; DILUTION; ANIMALS; ERRORS; OXYGEN AB The doubly labeled water ((H2O)-H-2-O-18) method to assess energy expenditure in free-living conditions has been successfully validated against gas exchange measurements in lean healthy volunteers in both sedentary conditions and during sustained heavy exercise. However, no data are available on obese subjects. We therefore compared the (H2O)-H-2-O-18 method with indirect calorimetry (respiratory chamber) in 12 male subjects covering a wide range of body weight and composition (61-190 kg, 7-41% fat). Isotope pool sizes and elimination rates were calculated from O-18 and H-2 enrichments in baseline urine samples and in 7-h, 11.5-h, and daily postdose urine samples using the multipoint slope/intercept method. Results were corrected for isotopic fractionation. Mean 7-day energy expenditure in the respiratory chamber varied from 1,851 to 4,105 kcal/day. The doubly labeled water method tended to underestimate energy expenditure (-2.5 +/- 5.8%, not-equal 0, range -14 to +4%), with the larger underestimate observed in heavier and fatter subjects (r = -0.82 and -0.68, P < 0.02, respectively). The underestimation in heavier subjects might be related to larger sequestration of deuterium during fat synthesis. In conclusion, the doubly labeled water method is a suitable and accurate method to measure energy expenditure in free-living conditions but might provide a slightly underestimated figure in fatter subjects. RP RAVUSSIN, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016, USA. NR 35 TC 82 Z9 82 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP E402 EP E409 PN 1 PG 8 WC Physiology SC Physiology GA GE637 UT WOS:A1991GE63700038 PM 1909495 ER PT J AU BRUGGEMAN, LA HORIGAN, EA HORIKOSHI, S RAY, PE KLOTMAN, PE AF BRUGGEMAN, LA HORIGAN, EA HORIKOSHI, S RAY, PE KLOTMAN, PE TI THROMBOXANE STIMULATES SYNTHESIS OF EXTRACELLULAR-MATRIX PROTEINS INVITRO SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE LAMININ; COLLAGEN; FIBRONECTIN; GLOMERULOSCLEROSIS; GENE EXPRESSION ID MESSENGER-RNA LEVELS; NECROSIS FACTOR-ALPHA; PROSTAGLANDIN ENDOPEROXIDES; COLLAGEN-SYNTHESIS; GLOMERULAR CELLS; MESANGIAL CELL; RAT; INTERLEUKIN-1; KIDNEY; ACID AB The vasoconstrictor eicosanoid thromboxane plays an important role in the pathogenesis of several renal diseases. As an autacoid, its local release alters blood flow and induces platelet aggregation. We report a direct stimulatory effect of thromboxane on extracellular matrix protein production and gene expression in vitro. Treatment of two cell types, differentiated mouse teratocarcinoma cells (F9+) and human glomerular mesangial cells, with two different thromboxane analogues resulted in increased production of components of the extracellular matrix including fibronectin and the basement membrane proteins laminin and type IV collagen. These responses to thromboxane were not the result of a mitogenic effect of thromboxane nor the result of an increase in total cellular protein. The increased production of extracellular matrix proteins was, at least in part, due to an increase in the steady-state level of mRNA for these genes. Furthermore, the effect of thromboxane was markedly inhibited by cotreatment with a thromboxane-receptor antagonist. These results suggest a new potential role for thromboxane as a mediator of the sclerotic and fibrotic responses to injury. C1 NIDR,MOLEC MED SECT,DEV BIOL LAB,BLDG 30,RM 433,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 40 TC 58 Z9 58 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP F488 EP F494 PN 2 PG 7 WC Physiology SC Physiology GA GE638 UT WOS:A1991GE63800101 PM 1887910 ER PT J AU LANKFORD, SP CHOU, CL TERADA, Y WALL, SM WADE, JB KNEPPER, MA AF LANKFORD, SP CHOU, CL TERADA, Y WALL, SM WADE, JB KNEPPER, MA TI REGULATION OF COLLECTING DUCT WATER PERMEABILITY INDEPENDENT OF CAMP-MEDIATED AVP RESPONSE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE URINARY CONCENTRATION; ISOLATED PERFUSED TUBULE; UREA PERMEABILITY; OSMOTIC WATER PERMEABILITY; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; FREEZE-FRACTURE ELECTRON MICROSCOPY; RAT ID INTRAMEMBRANOUS PARTICLE CLUSTERS; PAPILLARY SURFACE EPITHELIUM; ANTIDIURETIC-HORMONE; INNER MEDULLA; VASOPRESSIN; UREA; TRANSPORT; RATS; MEMBRANE; ADH AB We have used the isolated perfused tubule technique, measurements of adenosine 3',5'-cyclic monophosphate (cAMP) content in single tubules, and freeze-fracture electron microscopy to study the basis of high vasopressin-independent (basal) osmotic water permeability (P(f)) in the terminal inner medullary collecting duct (IMCD) of the rat. The results confirmed the observation that the basal P(f) of the terminal IMCD is considerably higher than that of the initial IMCD. They also showed that the basal P(f) of the terminal IMCD is regulated by in vivo factors related to water intake, such that a very high vasopressin-independent P(f) can be induced in isolated tubules by prior in vivo thirsting. Tubules from thirsted rats did not display elevated urea permeabilities, nor did they exhibit measurable cAMP levels in the absence of exogenous vasopressin, indicating that the high basal P(f) was not due to residual binding of vasopressin to its receptors. Freeze-fracture studies in thirsted rats demonstrated the presence of intramembrane particle (IMP) clusters in both initial and terminal IMCD, with more in the latter. Water loading of the rats suppressed the incidence of clusters almost entirely but did not fully suppress the basal P(f) in the terminal IMCD, raising the possibility that a component of transepithelial water transport may occur independently of the vasopressin-regulated IMP clusters. On the basis of these results, we conclude that the vasopressin-independent P(f) in the terminal IMCD can be stably elevated to very high levels in response to in vivo thirsting. This elevation appears to be due to a chronic conditioning effect mediated by unknown in vivo factors and is not due to the short-term cAMP-mediated regulatory effect of vasopressin. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. FU NIDDK NIH HHS [DK-32839] NR 49 TC 95 Z9 96 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP F554 EP F566 PN 2 PG 13 WC Physiology SC Physiology GA GE638 UT WOS:A1991GE63800109 PM 1653534 ER PT J AU MENOZZI, D GU, ZF MATON, PN BUNNETT, NW AF MENOZZI, D GU, ZF MATON, PN BUNNETT, NW TI INHIBITION OF PEPTIDASES POTENTIATES ENKEPHALIN-STIMULATED CONTRACTION OF GASTRIC MUSCLE-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ENKEPHALINASE; AMINOPEPTIDASE; PEPTIDE DEGRADATION; NEUROPEPTIDASE ID BESTATIN-SENSITIVE AMINOPEPTIDASE; AMINO-ACID SEQUENCE; OPIATE RECEPTORS; MET5 ENKEPHALIN; SUBSTANCE-P; METABOLISM; ENDOPEPTIDASE-24.11; INACTIVATION; STOMACH AB Cell surface peptidases degrade enkephalins and thereby restrict the number of molecules available to activate receptors. The effects of peptidase inhibitors on degradation of enkephalins and on enkephalin-stimulated contraction of gastric smooth muscle cells were examined. Muscle cells dispersed from the guinea pig stomach degraded [Tyr1-H-3][Leu5]enkephalin (41.6 +/- 9.0% degradation at 60 min incubation, mean +/- SD, n = 4 animals). Amastatin (10-mu-M, an aminopeptidase inhibitor) inhibited degradation by 72.1 +/- 1.5%. The residual peptidase activity was inhibited by phosphoramidon (1-mu-M, an endopeptidase EC 3.4.24.11 inhibitor) by 58.0 +/- 11.0%. [Tyr1-I-125][Met5]enkephalin was similarly degraded. Phosphoramidon (1-mu-M) inhibited the degradation of the aminopeptidase-resistant peptide [Tyr1-H-3][D-Ala2]-[Leu5]enkephalin by > 95%. [Met5]enkephalin, incubated with cells for 30 s, stimulated contraction [50% maximal contraction (EC50) 120 +/- 50 nM, n = 6]. Pretreatment of cells with phosphoramidon alone, amastatin alone, or phosphoramidon plus amastatin, caused 20-fold (EC50 6.5 +/- 1.1 nM), 2-fold (EC50 63 +/- 23 nM), and 100-fold (EC50 1.1 +/- 0.3 nM) increase in potency of [Met5]enkephalin, respectively. The results show that endopeptidase EC 3.4.24.11 and aminopeptidases contribute to degradation of enkephalins by gastric muscle cells. The rapidity and magnitude of the potentiating effects of the inhibitors on enkephalin-stimulated contraction suggest a close physical relationship between the peptidases and the enkephalin receptors. C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK-35597] NR 24 TC 18 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP G476 EP G484 PN 1 PG 9 WC Physiology SC Physiology GA GE637 UT WOS:A1991GE63700054 PM 1679601 ER PT J AU TSUTSUMI, K SAAVEDRA, JM AF TSUTSUMI, K SAAVEDRA, JM TI CHARACTERIZATION OF AT2 ANGIOTENSIN-II RECEPTORS IN RAT ANTERIOR CEREBRAL-ARTERIES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ANGIOTENSIN RECEPTOR SUBTYPES; DUP-753; CGP-42112-A; BRAIN RENIN-ANGIOTENSIN SYSTEM; CEREBRAL CIRCULATION; ANGIOTENSIN RECEPTOR DEVELOPMENT ID ACTIVE ANTIHYPERTENSIVE AGENT; ATRIAL-NATRIURETIC-PEPTIDE; BRAIN MICROVESSELS; CAROTID LIGATION; MORTALITY-RATE; BINDING-SITES; BLOOD-FLOW; ANTAGONISTS; SUBTYPES; DUP-753 AB Quantitative autoradiography using the agonist I-125-Sar1-angiotensin II was used to localize and characterize angiotensin II (AT) receptors in the anterior cerebral artery of the male rat. This artery showed a moderately high number of AT receptors, localized throughout the arterial wall. The number of receptors was higher (125 +/- 7 fmol/mg protein) in arteries from young 2-wk-old rats compared with those in adult 8-wk-old rats (43 +/- 2 fmol/mg protein). In the anterior cerebral artery, AT binding was insensitive to displacement with the selective AT1 antagonist DuP 753 but was readily displaced by the selective AT2 antagonist CGP-42112 A (concentration eliciting 50% of maximum inhibition: 6 +/- 1 x 10(-10) M). This indicated that the AT receptors in the cerebral artery were of the AT2 subtype. Our observations suggest that AT may exert its effects on cerebral circulation by stimulation of AT2 receptors and that these receptors may play a role during cerebrovascular development. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 28 TC 84 Z9 84 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1991 VL 261 IS 3 BP H667 EP H670 PN 2 PG 4 WC Physiology SC Physiology GA GE638 UT WOS:A1991GE63800010 PM 1887916 ER PT J AU MAIMAN, LA GREENLAND, P HILDRETH, NG COX, C AF MAIMAN, LA GREENLAND, P HILDRETH, NG COX, C TI PATTERNS OF PHYSICIANS TREATMENTS FOR REFERRAL PATIENTS FROM PUBLIC CHOLESTEROL SCREENING SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Current interest in high blood cholesterol and attendance at public cholesterol screening programs has raised the issue of whether physicians are responding to referrals according to existing national assessment and treatment recommendations. This study assessed the relationship of characteristics of referrals from a series of public blood cholesterol screenings to physicians' treatment practices. For this analysis, the sample was restricted to 1,324 subjects, from the 2,109 referred, who reported seeking physician care. At five months after screening, 75% of subjects reported their physician prescribed a diet; 16% of physicians prescribed medication. Multiple logistic regression, adjusted for sociodemographic characteristics and other coronary heart disease (CHD) risk factors, indicated that screening cholesterol risk level, prior history of high blood cholesterol levels, and type of medical contact were consistently related to receipt of diet and medication treatment, but other CHD risk factors were underutilized. "Moderate" risk subjects with no history of high blood cholesterol were less likely to have received dietary advice, but a screening-risk level interaction did not occur for medication. The results imply that current treatment guidelines may not be working and suggest the need for continued physician education in the management of hypercholesterolemia. RP MAIMAN, LA (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,6130 EXECUT PLAZA N,ROOM 640,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL34895, HL00982]; NICHD NIH HHS [HD00538] NR 0 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP-OCT PY 1991 VL 7 IS 5 BP 273 EP 279 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA HH029 UT WOS:A1991HH02900004 PM 1790032 ER PT J AU KORN, EL GRAUBARD, BI AF KORN, EL GRAUBARD, BI TI EPIDEMIOLOGIC STUDIES UTILIZING SURVEYS - ACCOUNTING FOR THE SAMPLING DESIGN SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NUTRITION EXAMINATION SURVEY; UNITED-STATES POPULATION; ORAL-CONTRACEPTIVE USE; EXAMINATION SURVEY-I; 1ST NATIONAL-HEALTH; BLOOD LEAD LEVELS; BODY IRON STORES; BREAST-CANCER; NUTRIENT INTAKE; NHANES-II AB Background. Since large-scale healthy surveys usually have complicated sampling schemes, there is often a question as to whether the sampling design must be considered in the analysis of the data. A recent disagreement concerning the analysis of a body iron stores-cancer association found in the first National Health and Nutrition Examination Survey and its follow-up is used to highlight the issues. Methods. We explain and illustrate the importance of two aspects of the sampling design: clustering and weighting of observations. The body iron stores-cancer data are reanalyzed by utilizing or ignoring various aspects of the sampling design. Simple formulas are given to describe how using the sampling design of a survey in the analysis will affect the conclusions of that analysis. Results. The different analyses of the body iron stores-cancer data lead to very different conclusions. Application of the simple formulas suggests that utilization of the sample clustering in the analysis is appropriate, but that a standard utilization of the sample weights leads to an uninformative analysis. The recommended analysis incorporates the sampling weights in a nonstandard way and the sample clustering in the standard way. Conclusions. Which particular aspects of the sampling design to use in the analysis of complex survey data and how to use them depend on certain features of the design. We give some guidelines for when to use the sample clustering and sample weights in the analysis. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,EXECUT PLAZA N,ROOM 739,BETHESDA,MD 20892, USA. NR 72 TC 273 Z9 277 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1991 VL 81 IS 9 BP 1166 EP 1173 DI 10.2105/AJPH.81.9.1166 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GJ839 UT WOS:A1991GJ83900014 PM 1951829 ER PT J AU STETLERSTEVENSON, WG TALANO, JA GALLAGHER, ME KRUTZSCH, HC LIOTTA, LA AF STETLERSTEVENSON, WG TALANO, JA GALLAGHER, ME KRUTZSCH, HC LIOTTA, LA TI INHIBITION OF HUMAN TYPE-IV COLLAGENASE BY A HIGHLY CONSERVED PEPTIDE SEQUENCE DERIVED FROM ITS PROSEGMENT SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE TYPE-IV COLLAGENASE; PROENZYME; PROFRAGMENT; INHIBITOR PEPTIDES ID RHEUMATOID SYNOVIAL FIBROBLASTS; HUMAN-SKIN; MATRIX METALLOPROTEINASE; MAMMALIAN COLLAGENASES; SUBSTRATE-SPECIFICITY; TISSUE INHIBITOR; NEUTRAL PROTEASE; CYSTEINE SWITCH; GENE FAMILY; RAT UTERUS AB The proenzyme fragment of the 72 kDa type IV collagenase contains a conserved amino acid sequence, MRKPRCGN(V)PDV, that is shared with other members of the matrix metalloproteinase family, such as interstitial collagenase and stromelysin. This sequence is lost upon the autocatalytic removal of the 80-84 amino acids from the amino terminus of these proenzymes following enzyme activation. The loss of this profragment converts the latent proenzyme species into a stable active enzyme species. In the present study, we demonstrate that this conserved prosegment sequence is an inhibitor of these enzymes and plays a critical role in maintenance of the latent state of the matrix metalloproteinases. Peptides containing the conserved sequence, MRKPRCGNPDV, were capable of inhibiting activated enzyme. Free cysteine was also an effective inhibitor, whereas reduced glutathione was a less effective inhibitor. Oxidized glutathione was not inhibitory. The 72 kDa type IV collagenase holoproenzyme preparations did not contain a free cysteinyl side chain that reacted with the sulfhydryl substitution reagent 5, 5'-dithiobis(2-nitrobenzoic acid) (Ellman's reagent). However, addition of ethylenediaminetetraacetic acid to the reaction mixture to generate the apoenzyme form resulted in the detection of titrable sulfhydryl side chains. Based on these data, we postulate that in the latent enzyme state the conserved profragment sequence interacts with the metal atom at the active site through a sulfhydryl-metal atom coordination that is further stabilized by the amino acyl residues surrounding the essential 73Cys residue. Disturbance of this interaction results in enzyme activation This provides an explanation for the activation mechanism of enzymes of the collagenase family. RP STETLERSTEVENSON, WG (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASES SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 43 TC 28 Z9 28 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 1991 VL 302 IS 3 BP 163 EP 170 DI 10.1097/00000441-199109000-00009 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GF560 UT WOS:A1991GF56000009 PM 1656751 ER PT J AU HOMEIDA, MA ELTOM, I NASH, T BENNETT, JL AF HOMEIDA, MA ELTOM, I NASH, T BENNETT, JL TI ASSOCIATION OF THE THERAPEUTIC ACTIVITY OF PRAZIQUANTEL WITH THE REVERSAL OF SYMMERS FIBROSIS INDUCED BY SCHISTOSOMA-MANSONI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PERIPORTAL FIBROSIS; CHEMOTHERAPY; INFECTIONS; MORBIDITY; SUDAN AB The impact of antischistosomal chemotherapy on the most important complication of intestinal schistosomiasis, Symmers' periportal fibrosis, has not been determined. Since abdominal ultrasonography has proven to be an effective tool in assessing the extent of Symmers' fibrosis in patients, we monitored the effect of chemotherapy, which involved the annual administration of praziquantel, on 48 Sudanese villagers having varying degrees of Symmers' fibrosis. Results indicate no significant differences in the fibrotic status of the 48 patients between 1986 and 1987, but test statistics (both the Wilcoxon signed rank test and Friedman's block/treatment test), indicated a significant decrease between the fibrotic status of the patients in 1986 and their fibrotic status in 1988 and 1989. Thus, after three years of therapy, 12 of the 48 patients no longer had detectable Symmers' fibrosis, while another 16 patients experienced a reduction in the amount of fibrosis in their livers. When coupled with our previous study, which demonstrated that annual treatment of children with praziquantel prevents the appearance of Symmers' fibrosis, it now appears that praziquantel may reverse this schistosomal-induced pathology. C1 UNIV KHARTOUM,FAC MED,DEPT PATHOL,KHARTOUM,SUDAN. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT PHARMACOL TOXICOL,E LANSING,MI 48824. RP HOMEIDA, MA (reprint author), UNIV KHARTOUM,FAC MED,DEPT MED,KHARTOUM,SUDAN. FU NIAID NIH HHS [AI-16312-11] NR 16 TC 64 Z9 66 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 1991 VL 45 IS 3 BP 360 EP 365 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA GK409 UT WOS:A1991GK40900011 PM 1928571 ER PT J AU LESHNER, AI AF LESHNER, AI TI PSYCHOLOGY RESEARCH AND NIMH - OPPORTUNITIES AND CHALLENGES SO AMERICAN PSYCHOLOGIST LA English DT Article RP LESHNER, AI (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD SEP PY 1991 VL 46 IS 9 BP 977 EP 979 PG 3 WC Psychology, Multidisciplinary SC Psychology GA GE042 UT WOS:A1991GE04200011 PM 1958017 ER PT J AU KRAMER, MR DENNING, DW MARSHALL, SE ROSS, DJ BERRY, G LEWISTON, NJ STEVENS, DA THEODORE, J AF KRAMER, MR DENNING, DW MARSHALL, SE ROSS, DJ BERRY, G LEWISTON, NJ STEVENS, DA THEODORE, J TI ULCERATIVE TRACHEOBRONCHITIS AFTER LUNG TRANSPLANTATION - A NEW FORM OF INVASIVE ASPERGILLOSIS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID BRONCHOCENTRIC GRANULOMATOSIS; IMMUNOCOMPROMISED PATIENTS; PULMONARY COMPLICATIONS; BRONCHIAL ASPERGILLOSIS; MARROW TRANSPLANTATION; ITRACONAZOLE THERAPY; HEART; RECIPIENTS; CYCLOSPORINE; INFECTIONS AB Invasive aspergillosis is frequently a fatal disease in the setting of immunosuppression, including organ transplant recipients. The fungus usually affects lung parenchyma and may disseminate from there. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. This apparently new form of invasive disease is initially limited to the anastomosis site and large airways. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. In two patients subsequent disseminated aspergillosis occurred with a fatal outcome. In the two single-lung recipients, disease was limited to the transplanted side emphasizing the importance of abnormal local defense mechanisms in the airways of lung transplant recipients. Routine bronchoscopic examination of the airways is important in early detection of this complication. Oral therapy with the new, antifungal agent itraconazole was successful in five of the six patients, with fatal relapse in one. A classification of the various forms of saprophytic, allergic, and invasive forms of aspergillus tracheobronchitis, to include this new entity, is proposed. C1 UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,DEPT MED,LOS ANGELES,CA 90048. CALIF INST MED RES,SAN JOSE,CA. NIAID,MYCOSES STUDY GRP,BETHESDA,MD 20892. STANFORD UNIV,CTR MED,DEPT MED,DIV RESP MED,STANFORD,CA 94305. STANFORD UNIV,CTR MED,DEPT PATHOL,DIV INFECT DIS,STANFORD,CA 94305. STANFORD UNIV,CTR MED,DEPT PEDIAT,DIV ALLERGY IMMUNOL & RESP DIS,STANFORD,CA 94305. SANTA CLARA VALLEY MED CTR,DEPT PATHOL,CLIN MICROBIOL LAB,SAN JOSE,CA 95128. SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,751 S BASCOM AVE,SAN JOSE,CA 95128. OI Denning, David/0000-0001-5626-2251 FU NHLBI NIH HHS [HL-13108]; NIAID NIH HHS [AI-52562, AI-82570] NR 34 TC 183 Z9 193 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD SEP PY 1991 VL 144 IS 3 BP 552 EP 556 PG 5 WC Respiratory System SC Respiratory System GA GF551 UT WOS:A1991GF55100015 PM 1654038 ER PT J AU TOLLERUD, DJ BROWN, LM BLATTNER, WA MANN, DL PANKIWTROST, L HOOVER, RN AF TOLLERUD, DJ BROWN, LM BLATTNER, WA MANN, DL PANKIWTROST, L HOOVER, RN TI T-CELL SUBSETS IN HEALTHY BLACK SMOKERS AND NONSMOKERS - EVIDENCE FOR ETHNIC-GROUP AS AN IMPORTANT RESPONSE MODIFIER SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID FLOW-CYTOMETRY; MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN LEVELS; CIGARETTE-SMOKING; LUNG-CANCER; DISEASE; WHITE; RISK AB The influence of cigarette smoking on T cell subsets has been studied in white subjects, but comparable data are not available for blacks. We analyzed peripheral blood mononuclear cell subsets in a population-based, stratified, random sample of healthy black adults using monoclonal antibodies and flow cytometry. The study population consisted of 94 men and 79 women. including 73 smokers (CS) and 100 nonsmokers (NS). Cigarette smoking was associated with a significant elevation in leukocyte (WBC) count (CS 7,270 +/- 230 cells/mm3 versus NS 6,260 +/- 160 cells/mm3; p = 0.001), although WBC counts for both groups were substantially lower than those reported for white smokers and nonsmokers. Smokers had a significantly lower proportion of CD4, cells then nonsmokers (CS 55.4 +/- 0.9% versus NS 58.7 +/- 0.9; p = 0.01), adjusting for age and gender. No significant smoking-related changes were observed for CD8+ cells, the CD4/CD8 ratio, or total T cells (CD3+), monocytes (CD14+), or natural killer cells (CD16+). Among black smokers, a significant dose-related decrease in CD4+ cells was observed as the number of cigarettes smoked per day increased. Among black ex-smokers, the level of WBC and CD4+ cells returned to the level observed in never smokers within 2 to 5 yr after smoking cessation. These results contrast sharply with the previously reported increase In CD4+ cells and decrease in natural killer cells associated with cigarette smoking in whites. The data suggest that the immunologic effects of cigarette smoking may be significantly modified by ethnic characteristics. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP TOLLERUD, DJ (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH A-718,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [YO1-CP-30500] NR 24 TC 40 Z9 40 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD SEP PY 1991 VL 144 IS 3 BP 612 EP 616 PG 5 WC Respiratory System SC Respiratory System GA GF551 UT WOS:A1991GF55100026 PM 1892301 ER PT J AU KALINER, MA AF KALINER, MA TI HUMAN NASAL RESPIRATORY SECRETIONS AND HOST DEFENSE SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article; Proceedings Paper CT 6TH TRANSATLANTIC AIRWAY CONF : AIRWAY MUCIN CY JAN, 1991 CL KEY BISCAYNE, FL SP BOEHRINGER INGELHEIM ID INDUCED ALLERGIC RHINITIS; PATHO-PHYSIOLOGY; LAVAGE FLUID; PROTEIN; MUCOSA; BRADYKININ; CHALLENGE; ANTIGEN; PEPTIDE; MUCUS AB The largest human body surface is the lining of the respiratory tract, gastrointestinal tract, and reproductive system each of which is covered by mucous membranes, named for their capacity to secrete mucus. Recent studies of mucus have defined some of the physiologic and pharmacologic controls of secretions. However, the constituents that are found in mucus and their roles in human health and disease are still in the initial phase of exploration. Human nasal respiratory secretions provide one convenient source of mucous membrane secretions. Nasal secretions include a variety of proteins, which appear to serve important functions in host-defense. Most, if not all, of the antiphlogistic products are synthesized and secreted by serous cells in the submucous glands, and it appears that the serous cell is the resident antimicrobial cell in mucous membranes. RP KALINER, MA (reprint author), NIAID,ALLERG DIS SECT,BLDG 10,ROOM 11C205,BETHESDA,MD 20892, USA. NR 40 TC 46 Z9 46 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD SEP PY 1991 VL 144 IS 3 SU S BP S52 EP S56 PG 5 WC Respiratory System SC Respiratory System GA GG424 UT WOS:A1991GG42400013 PM 1892328 ER PT J AU BUSBY, J TOBIN, J ETTINGER, W ROADARMEL, K PLATO, CC AF BUSBY, J TOBIN, J ETTINGER, W ROADARMEL, K PLATO, CC TI A LONGITUDINAL-STUDY OF OSTEOARTHRITIS OF THE HAND - THE EFFECT OF AGE SO ANNALS OF HUMAN BIOLOGY LA English DT Article ID JOINT DISEASES; HAVEN SURVEY; PREVALENCE AB Osteoarthritis is the most ubiquitous rheumatic disease worldwide. Although its prevalence in various populations has been well documented, few studies have evaluated the longitudinal radiographic progression of the disease, especially as it is expressed in the interphalangeal joints of the hand. In this longitudinal study, left hand-wrist X-rays of 386 white male participants of the Baltimore Longitudinal Study of Aging followed for at least 5 years with two or more visits were examined for prevalence and progression of osteoarthritis of the distal and proximal interphalangeal joints of the hand. As other studies have shown, we found that the prevalence of osteoarthritis in both distal and proximal interphalangeal joints becomes progressively higher as the age of the subjects increases. Using the life table method of analysis we studied the progression of osteoarthritis as defined by the following criteria: (1) an increase in the severity of radiographic changes of the joints previously affected and (2) an increase in the number of new joints affected. The results indicated that osteoarthritis in both the distal and proximal interphalangeal joints progresses at a faster rate in the older population than in individuals < 60 years of age. Furthermore, osteoarthritis in the interphalangeal joints progresses at the same rate whether the starting point was a Kellgren grade of 0 (no disease) or 1 (doubtful). We therefore conclude that grade 1 is an intermediate step in the inexorable progression of osteoarthritis of the interphalangeal joints and not synonymous with grade 0, as it has been customarily interpreted. C1 FRANCIS SCOTT KEY MED CTR,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. RP BUSBY, J (reprint author), NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,APPL PHYSIOL SECT,BETHESDA,MD 20892, USA. FU NIA NIH HHS [K08 AG0038302] NR 19 TC 23 Z9 23 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0301-4460 J9 ANN HUM BIOL JI Ann. Hum. Biol. PD SEP-OCT PY 1991 VL 18 IS 5 BP 417 EP 424 DI 10.1080/03014469100001712 PG 8 WC Anthropology; Biology; Public, Environmental & Occupational Health SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public, Environmental & Occupational Health GA GC822 UT WOS:A1991GC82200004 PM 1952799 ER PT J AU REED, T FABSITZ, RR SELBY, JV CARMELLI, D AF REED, T FABSITZ, RR SELBY, JV CARMELLI, D TI GENETIC INFLUENCES AND GRIP STRENGTH NORMS IN THE NHLBI TWIN STUDY MALES AGED 59-69 SO ANNALS OF HUMAN BIOLOGY LA English DT Article ID MUSCLE MORPHOLOGY AB Maximal grip strength was measured in kilograms using a hand dynamometer on 344 unrelated males between the ages of 59 and 70 participating in the third examination of the NHLBI Twin Study. There was a significant linear decline in mean grip strength over this age range. Mean grip strength and grip strength per kilogram weight are presented for age 59, ages 60-64 and 65-69. Genetic analysis using 127 pairs of identical (MZ) twins and 130 pairs of fraternal (DZ) twins indicated significant genetic effects for absolute grip strength and grip strength per kilogram weight. The largest estimate of heritability (65%) was obtained for grip strength adjusted for significant effects of weight, height, age, and various anthropometric measures of fatness, muscle mass, and frame size. C1 NHLBI,CLIN & GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. KAISER FDN RES INST,OAKLAND,CA. SRI INT,DEPT BEHAV MED,MENLO PK,CA 94025. RP REED, T (reprint author), INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46202, USA. NR 37 TC 60 Z9 62 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0301-4460 J9 ANN HUM BIOL JI Ann. Hum. Biol. PD SEP-OCT PY 1991 VL 18 IS 5 BP 425 EP 432 DI 10.1080/03014469100001722 PG 8 WC Anthropology; Biology; Public, Environmental & Occupational Health SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public, Environmental & Occupational Health GA GC822 UT WOS:A1991GC82200005 PM 1952800 ER PT J AU DALONZO, GE BARST, RJ AYRES, SM BERGOFSKY, EH BRUNDAGE, BH DETRE, KM FISHMAN, AP GOLDRING, RM GROVES, BM KERNIS, JT LEVY, PS PIETRA, GG REID, LM REEVES, JT RICH, S VREIM, CE WILLIAMS, GW WU, M AF DALONZO, GE BARST, RJ AYRES, SM BERGOFSKY, EH BRUNDAGE, BH DETRE, KM FISHMAN, AP GOLDRING, RM GROVES, BM KERNIS, JT LEVY, PS PIETRA, GG REID, LM REEVES, JT RICH, S VREIM, CE WILLIAMS, GW WU, M TI SURVIVAL IN PATIENTS WITH PRIMARY PULMONARY-HYPERTENSION - RESULTS FROM A NATIONAL PROSPECTIVE REGISTRY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HYPERTENSION, PULMONARY; VENTRICULAR FUNCTION, RIGHT; ATRIAL FUNCTION, RIGHT; RAYNAUDS DISEASE; HEART-LUNG TRANSPLANTATION ID UNUSUALLY LONG DURATION; NATURAL-HISTORY AB Objective: To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. Design: Registry with prospective follow-up. Setting: Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. Patients: Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. Measurements: At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. Main Results: The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DL(CO)). Drug therapy at entry or discharge was not associated with survival duration. Conclusions: Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources. C1 NHLBI,DIV LUNG DIS,WESTWOOD BLDG,ROOM 6A09,BETHESDA,MD 20892. UNIV TEXAS,MED CTR,DIV PULM,HOUSTON,TX 77030. BABYS HOSP S,NEW YORK,NY 10032. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. SUNY STONY BROOK,HLTH SCI CTR,DIV PULM CRIT CARE,STONY BROOK,NY 11794. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,TORRANCE,CA 90509. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15261. UNIV PENN,DEPT PHYS MED & REHABIL,PHILADELPHIA,PA 19104. NYU,DEPT MED,NEW YORK,NY 10016. UNIV HOSP DENVER,DIV CARDIOL,DENVER,CO 80262. UNIV ILLINOIS,SCH PUBL HLTH,CHICAGO,IL 60680. HOSP UNIV PENN,DEPT PATHOL & MED,PHILADELPHIA,PA 19104. CHILDRENS HOSP MED CTR,MED CTR,DEPT PATHOL,BOSTON,MA 02115. UNIV COLORADO,HLTH SCI CTR,CARDIOVASC PULM RES LAB,DENVER,CO 80262. UNIV ILLINOIS,DEPT MED,CARDIOL SECT,CHICAGO,IL 60680. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NIH,DIV HEART LUNG & BLOOD INST,MATH & STAT BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HR-14000] NR 24 TC 1836 Z9 1917 U1 5 U2 42 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1991 VL 115 IS 5 BP 343 EP 349 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GC065 UT WOS:A1991GC06500002 PM 1863023 ER PT J AU KIYOSAWA, K SODEYAMA, T TANAKA, E NAKANO, Y FURUTA, S NISHIOKA, K PURCELL, RH ALTER, HJ AF KIYOSAWA, K SODEYAMA, T TANAKA, E NAKANO, Y FURUTA, S NISHIOKA, K PURCELL, RH ALTER, HJ TI HEPATITIS-C IN HOSPITAL EMPLOYEES WITH NEEDLESTICK INJURIES SO ANNALS OF INTERNAL MEDICINE LA English DT Note DE HEPATITIS VIRAL, NON-A, NON-B; HEPATITIS-C VIRUS; ACCIDENTS, OCCUPATIONAL; NEEDLESTICK INJURY; OCCUPATIONAL EXPOSURE ID NON-A; B VIRUS AB Of 357 needlestick accidents occurring at a university hospital between 1981 and 1989, 200 involved 196 health care workers who were then prospectively followed for 6 months; 110 of these 196 workers were exposed to blood from antibody to the hepatitis C virus (anti-HCV). Only 4 of these 110 exposed persons (4%; 95% CI, 1% to 9%) developed non-A, non-B hepatitis. Hepatitis was accompanied by anti-HCV seroconversion in 3 of these 4 persons. Three of the four were icteric, and each had a peak alanine aminotransferase level exceeding 8.5-mu-kat/L. There was no instance of anti-HCV seroconversion among the 106 recipients of an anti-HCV-positive needlestick who did not manifest biochemical or clinical evidence of hepatitis. This study documents that HCV-related non-A, non-B hepatitis can be transmitted infrequently by needlestick injury. C1 JAPANESE RED CROSS SOC,CENT BLOOD CTR,SHIBUYA KU,TOKYO 150,JAPAN. NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP KIYOSAWA, K (reprint author), SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,3-1-1 ASAHI,MATSUMOTO,NAGANO 390,JAPAN. NR 10 TC 289 Z9 291 U1 2 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1991 VL 115 IS 5 BP 367 EP 369 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GC065 UT WOS:A1991GC06500006 PM 1907441 ER PT J AU ROBERTS, CS ROBERTS, WC AF ROBERTS, CS ROBERTS, WC TI COMBINED THORACIC AORTIC DISSECTION AND ABDOMINAL AORTIC FUSIFORM ANEURYSM SO ANNALS OF THORACIC SURGERY LA English DT Article ID COMPUTED-TOMOGRAPHY AB Certain clinical and autopsy findings are described in 13 patients who had both aortic dissection (AD) and fusiform abdominal aortic aneurysm (AAA). All 13 patients had severe and extensive aortic atherosclerosis. The AAA was diagnosed clinically in 9 patients, and 5 had the AAA resected. The AD was diagnosed clinically in 5 patients, and 2 underwent attempted operative repair. Two patients who had the AAA resected because of suspected rupture were found later to have ruputured a more proximal AD. Thus, AD occurs occasionally in patients who have AAA. In older persons with suspected rupture of an AAA, a more proximal rupture of an AD should be ruled out. When both AAA and AD are present in the same patient, the AD is more likely the cause of cardiovascular collapse than is rupture of the AAA. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. RP ROBERTS, CS (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 8 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1991 VL 52 IS 3 BP 537 EP 540 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA GG679 UT WOS:A1991GG67900021 PM 1845108 ER PT J AU TOSHIMORI, K ARAKI, S OURA, C EDDY, EM AF TOSHIMORI, K ARAKI, S OURA, C EDDY, EM TI LOSS OF SPERM SURFACE SIALIC-ACID INDUCES PHAGOCYTOSIS - AN ASSAY WITH A MONOCLONAL-ANTIBODY T21, WHICH RECOGNIZES A 54K SIALOGLYCOPROTEIN SO ARCHIVES OF ANDROLOGY LA English DT Article DE MOUSE; SPERM; EPIDIDYMAL MATURATION; SIALIC ACID; PHAGOCYTOSIS ID MATURATION ANTIGEN; EPIDIDYMAL SPERMATOZOA; PLASMA-MEMBRANE; RAT SPERMATOZOA; MOUSE; GLYCOPROTEINS; PROTEIN; BINDING; LOCALIZATION; ASSOCIATION AB Using a monoclonal antibody T21, we reported that a mouse sperm maturation-associated antigen sialoglycoprotein of 54000 daltons (54K sialoglycoprotein) was secreted at the distal caput to proximal corpus epididymidis and that the 54K sialoglycoprotein had a hidden determinant (cryptodeterminant), which could be eliminated by sialidase treatment (Toshimori et al. (1988): Histochemistry 90:195-200; (1990a): Biol Reprod 42:151-160; (1990b): Arch Histol Cytol 53:339-349). This study evaluated the mouse sperm susceptibility to phagocytosis by macrophage in vitro. Comparisons were made between sperm from the caput epididymidis (caput sperm) incubated in modified Krebs Ringer's solution (MKR) and caput sperm incubated in MKR containing cauda fluid, and between sialylated (sialidase-untreated) sperm from the corpus and cauda epididymidis (corpus/cauda sperm) and desialylated (sialidase-treated) corpus/cauda sperm. The results showed that macrophages were least actively engaged in phagocytosis for caput sperm incubated in MKR containing cauda fluid, and most active for desialylated corpus/cauda sperm. Incubation of caput sperm in MKR containing cauda fluid revealed that the 54K sialoglycoprotein in cauda fluid could be bound to the flagellar surface of caput sperm. These results together with previous findings strongly suggest that the 54K sialoglycoprotein bound to immature sperm during maturation in the epididymis is implicated in the protection of sperm from phagocytosis with the aid of sialic acid residues. C1 MIYAZAKI MED COLL,DEPT ANAT,MIYAZAKI 88916,JAPAN. NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. NR 40 TC 23 Z9 24 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0148-5016 J9 ARCH ANDROLOGY JI Arch. Androl. PD SEP-OCT PY 1991 VL 27 IS 2 BP 79 EP 86 PG 8 WC Andrology SC Endocrinology & Metabolism GA GF796 UT WOS:A1991GF79600003 PM 1953200 ER PT J AU CLIMENT, I LEVINE, RL AF CLIMENT, I LEVINE, RL TI OXIDATION OF THE ACTIVE-SITE OF GLUTAMINE-SYNTHETASE - CONVERSION OF ARGININE-344 TO GAMMA-GLUTAMYL SEMIALDEHYDE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MIXED-FUNCTION OXIDATION; METAL-CATALYZED OXIDATION; PROTEIN-TURNOVER; COVALENT MODIFICATION; ESCHERICHIA-COLI; INACTIVATION; RESIDUES; DERIVATIZATION; ENZYMES C1 NHLBI,BIOCHEM LAB,BLDG 3,ROOM 106,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 25 TC 28 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP PY 1991 VL 289 IS 2 BP 371 EP 375 DI 10.1016/0003-9861(91)90425-I PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GA870 UT WOS:A1991GA87000025 PM 1680314 ER PT J AU BURKE, KC BURKE, JD RAE, DS REGIER, DA AF BURKE, KC BURKE, JD RAE, DS REGIER, DA TI COMPARING AGE AT ONSET OF MAJOR DEPRESSION AND OTHER PSYCHIATRIC-DISORDERS BY BIRTH COHORTS IN 5 UNITED-STATES COMMUNITY POPULATIONS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CATCHMENT-AREA SITES; LIFETIME PREVALENCE; MENTAL-DISORDERS; RATES; RELIABILITY; RELATIVES; INTERVIEW; HEALTH; TRENDS; PERIOD AB Using data collected in the National Institute of Mental Health (Rockville, Md) Epidemiologic Catchment Area Program, we examined the proposed hypothesis that there has been a shift in major depression to younger ages at onset, or increased prevalence in younger age periods, for recent birth cohorts. Life-table survival methods were used to examine the hazard rates for major depression as well as for other specific mental disorders. The findings are consistent with a gradual shift to increased rates for major depression between the ages of 15 and 19 years for Epidemiologic Catchment Area respondents born more recently. The findings also suggest a similar shift for drug abuse/dependence; similar but less pronounced changes were found for alcohol abuse/dependence and obsessive-compulsive disorder. However, in this study, bipolar disorder, panic disorder, and phobias did not exhibit a consistent increase in onset at younger ages. Further research is required to determine if the shifts in major depression, drug abuse/dependence, and possibly alcohol abuse/dependence are linked. It is important to note that these shifts to adolescent onset are occurring when nearly half the 31 million Americans without health insurance are aged 24 years or younger. C1 NIMH,OFF INST DIRECTOR,ROCKVILLE,MD 20857. NIMH,DIV APPL & SERV RES,ROCKVILLE,MD 20857. NIMH,DIV CLIN RES,ROCKVILLE,MD 20857. RI Burke, Jack/I-4440-2012 OI Burke, Jack/0000-0001-5868-1695 FU NIMH NIH HHS [U01 MH-33870, U01 MH-33883, U01 MH-34224] NR 40 TC 160 Z9 160 U1 22 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 789 EP 795 PG 7 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300001 PM 1929768 ER PT J AU PRIEN, RF CARPENTER, LL KUPFER, DJ AF PRIEN, RF CARPENTER, LL KUPFER, DJ TI THE DEFINITION AND OPERATIONAL CRITERIA FOR TREATMENT OUTCOME OF MAJOR DEPRESSIVE DISORDER - A REVIEW OF THE CURRENT RESEARCH LITERATURE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID ADJUSTMENT; ALPRAZOLAM; RECOVERY; RELAPSE; THERAPY AB A review of research articles published in nine journals over a 2-year period was conducted to determine how critical changes in the clinical course of depressive disorder are defined in the research literature. These change points, labeled by terms such as response, recovery, and relapse, are critical for evaluation and communication of study results. The review focused on studies of unipolar depression that used a criterion-based diagnostic system and involved some form of therapeutic maneuver. The review showed significant inconsistency in the labeling and definition of change points and indicated the need for more precise conceptual definitions and operational criteria to enhance comparison, generalization, and application of results from clinical studies of depression. C1 WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA 15261. RP PRIEN, RF (reprint author), NIMH,DIV CLIN RES,ROOM 10C24 PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 28 TC 145 Z9 147 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 796 EP 800 PG 5 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300002 PM 1929769 ER PT J AU LEONARD, HL LENANE, MC SWEDO, SE RETTEW, DC RAPOPORT, JL AF LEONARD, HL LENANE, MC SWEDO, SE RETTEW, DC RAPOPORT, JL TI A DOUBLE-BLIND COMPARISON OF CLOMIPRAMINE AND DESIPRAMINE TREATMENT OF SEVERE ONYCHOPHAGIA (NAIL BITING) SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO; PAIN; CHLORIMIPRAMINE; ADOLESCENTS; MAPROTILINE; RELAXATION; CROSSOVER; MIANSERIN; CHILDREN AB Twenty-five adult subjects with severe morbid onychophagia (nail biting) and no history of obsessive-compulsive disorder were enrolled in a 10-week double-blind crossover trial of clomipramine hydrochloride and desipramine hydrochloride. For the 14 subjects who completed the study, clomipramine hydrochloride (mean +/- SD dose, 120 +/- 48 mg/d) was superior to desipramine hydrochloride (mean +/- SD dose, 135 +/- 53 mg/d) in decreasing nail biting as measured by a repeated-measures analysis of variance on the Nail Biting Severity, Nailbiting Impairment, and Clinical Progress scales. The high dropout rate at every stage of the study was in sharp contrast to that seen with psychiatric populations. From a neuroethologic perspective, similar biologic systems are hypothesized to mediate a spectrum of grooming behaviors, including onychophagia, trichotillomania, and obsessive-compulsive disorder. RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 66 TC 76 Z9 77 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 821 EP 827 PG 7 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300006 PM 1929772 ER PT J AU SWEDO, SE RAPOPORT, JL LEONARD, HL SCHAPIRO, MB RAPOPORT, SI GRADY, CL AF SWEDO, SE RAPOPORT, JL LEONARD, HL SCHAPIRO, MB RAPOPORT, SI GRADY, CL TI REGIONAL CEREBRAL GLUCOSE-METABOLISM OF WOMEN WITH TRICHOTILLOMANIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; RATES; CLOMIPRAMINE AB Positron emission tomography and 18-F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 10 adult women with trichotillomania and 20 age-matched female controls. As a group, the patients with trichotillomania showed significantly increased global (mean gray matter) and normalized right and left cerebellar and right superior parietal glucose metabolic rates. Contrary to expectation, this pattern differed from that seen in our previous investigation of obsessive-compulsive disorder. Clomipramine hydrochloride-induced improvement was negatively correlated with anterior cingulate and orbital frontal metabolism, of particular interest because similar results had been obtained for obsessive-compulsive disorder. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 91 Z9 92 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 828 EP 833 PG 6 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300007 PM 1929773 ER PT J AU FRANK, E PRIEN, RF JARRETT, RB KELLER, MB KUPFER, DJ LAVORI, PW RUSH, AJ WEISSMAN, MM AF FRANK, E PRIEN, RF JARRETT, RB KELLER, MB KUPFER, DJ LAVORI, PW RUSH, AJ WEISSMAN, MM TI CONCEPTUALIZATION AND RATIONALE FOR CONSENSUS DEFINITIONS OF TERMS IN MAJOR DEPRESSIVE DISORDER - REMISSION, RECOVERY, RELAPSE, AND RECURRENCE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material AB In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery, relapse, and recurrence. In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments. C1 BROWN UNIV,BUTLER HOSP,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. COLUMBIA UNIV COLL PHYS & SURG,DIV CLIN GENET EPIDEMIOL,NEW YORK,NY 10032. NIMH,DIV CLIN RES,ROCKVILLE,MD 20857. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,DALLAS,TX 75235. RP FRANK, E (reprint author), UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,SCH MED,DEPT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. OI Rush, Augustus/0000-0003-2004-2382; Weissman, Myrna/0000-0003-3490-3075 FU NIMH NIH HHS [MH30915, MH41115, R01 MH025478] NR 11 TC 1304 Z9 1329 U1 3 U2 57 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 851 EP 855 PG 5 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300010 PM 1929776 ER PT J AU PIGOTT, TA MURPHY, DL AF PIGOTT, TA MURPHY, DL TI ARE EFFECTIVE ANTIOBSESSIONAL DRUGS INTERCHANGEABLE - REPLY SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID OBSESSIVE-COMPULSIVE DISORDER RP PIGOTT, TA (reprint author), NIMH,CLIN SCI LAB,BLDG 10-3D41,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1991 VL 48 IS 9 BP 858 EP 859 PG 2 WC Psychiatry SC Psychiatry GA GF523 UT WOS:A1991GF52300013 ER PT J AU NELSON, RG KNOWLER, WC PETTITT, DJ SAAD, MF CHARLES, MA BENNETT, PH AF NELSON, RG KNOWLER, WC PETTITT, DJ SAAD, MF CHARLES, MA BENNETT, PH TI ASSESSMENT OF RISK OF OVERT NEPHROPATHY IN DIABETIC-PATIENTS FROM ALBUMIN EXCRETION IN UNTIMED URINE SPECIMENS SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PIMA-INDIANS; KIDNEY-FUNCTION; INCIPIENT NEPHROPATHY; CREATININE RATIOS; CIRCADIAN-RHYTHM; PROTEINURIA; MICROALBUMINURIA; MELLITUS; EXERCISE; SAMPLES AB The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ. RP NELSON, RG (reprint author), CLEVELAND CLIN EDUC FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44106, USA. RI Nelson, Robert/B-1470-2012 NR 50 TC 99 Z9 101 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP PY 1991 VL 151 IS 9 BP 1761 EP 1765 DI 10.1001/archinte.151.9.1761 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GE534 UT WOS:A1991GE53400011 PM 1888242 ER PT J AU FINK, JK RAVIN, PD FILLINGKATZ, M ARGOFF, CE HALLETT, M AF FINK, JK RAVIN, PD FILLINGKATZ, M ARGOFF, CE HALLETT, M TI CLINICAL AND GENETIC-ANALYSIS OF PROGRESSIVE DYSTONIA WITH DIURNAL-VARIATION SO ARCHIVES OF NEUROLOGY LA English DT Article ID TETRAHYDROBIOPTERIN AB We examined 17 patients with progressive dystonia with diurnal variation, a dominantly inherited, generalized dystonia that begins in childhood. Dystonia was typically least severe in the morning, increased as the day continued, and markedly improved with low doses of carbidopa-levodopa. We also studied the patient's parents, children, and siblings from seven families. We observed a spectrum of neurologic involvement, phenotypic variability among siblings, and incomplete genetic penetrance. Progression of motor impairment over several years, which reaches a plateau during late adolescence, is useful in distinguishing progressive dystonia with diurnal variation from cerebral palsy and degenerative disorders. It is important to recognize the subtle, as well the extreme, manifestations ot progressive dystonia with diurnal variation because it is treatable. Genetic counseling must consider that mildly affected parents with little or no disability may have profoundly affected children. Appreciation of the phenotypic variability and degree of genetic penetrance will permit detailed genetic and biochemical analyses. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,DEPT NEUROL,WORCESTER,MA 01605. RP FINK, JK (reprint author), UNIV MICHIGAN,DEPT NEUROL,NEUROSCI LAB 1120-A,ANN ARBOR,MI 48104, USA. NR 15 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 1991 VL 48 IS 9 BP 908 EP 911 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GF745 UT WOS:A1991GF74500007 PM 1953413 ER PT J AU BHATTACHARYYA, AK CONNOR, WE LIN, DS MCMURRY, MM SHULMAN, RS AF BHATTACHARYYA, AK CONNOR, WE LIN, DS MCMURRY, MM SHULMAN, RS TI SLUGGISH SITOSTEROL TURNOVER AND HEPATIC-FAILURE TO EXCRETE SITOSTEROL INTO BILE CAUSE EXPANSION OF BODY POOL OF SITOSTEROL IN PATIENTS WITH SITOSTEROLEMIA AND XANTHOMATOSIS SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE PLANT STEROLS; CHOLESTEROL; TURNOVER; TISSUE ACCUMULATION; XANTHOMATOSIS; ATHEROSCLEROSIS ID DIETARY PLANT STEROLS; CHOLESTEROL-SYNTHESIS; BETA-SITOSTEROLEMIA; PHYTOSTEROLEMIA; METABOLISM; CHOLESTANOLEMIA; DEGRADATION; ABSORPTION; DISEASE; PLASMA AB Sitosterolemia and xanthomatosis are characterized by the development of tendon and tuberous xanthomas at an early age and premature atherosclerosis despite normal plasma cholesterol concentrations. The reason(s) for the xanthoma formation and premature atherosclerosis are not clearly understood. The accumulation of sitosterol in the tissues of these patients could be due to increased uptake of low density lipoprotein (LDL) via LDL receptors because of an expanded sitosterol pool caused by sluggish turnover and decreased excretion of sitosterol into bile and feces coupled with the hyperabsorption of sitosterol. We have studied sitosterol and cholesterol turnovers, the biliary and fecal excretion of neutral and acidic steroids, and the response of plasma sterol (sitosterol and cholesterol) levels to either a sterol-free formula or low plant sterol diet in three patients. The average half-life of the first exponential (t(A)1/2) for sitosterol was 9.2 +/- 3.3 (mean +/- SD) days, which was more than twice that in normal humans. The second exponential (t(B)1/2) was 156 +/- 108 days, which was nearly 10 times longer than that for normal humans. The average cholesterol production rate in pool A was 0.87 g/day, whic is about 40% of that in normal humans. Cholesterol synthesis measured by the sterol balance technique was also found to be about 70% lower than that for normal humans. In two patients fed a sterol-free formula diet, by 25 days their plasma sitosterol and cholesterol levels had decreased by 42% and 36%, respectively. However, in one patient plasma sitosterol and cholesterol concentrations remained unchanged while on the low plant sterol-mixed food diet. The sitosterol to cholesterol ratio in bile (0.05) was extremely low compared with that found in plasma (0.14), indicating low excretion of sitosterol into the bile. Thus, patients with sitosterolemia have a slow turnover of sitosterol, low excretion of sitosterol into the duodenal bile and feces, and low cholesterol synthesis. These metabolic defects have implications in the formation of xanthomas and the development of premature atherosclerosis in these patients. C1 OREGON HLTH SCI UNIV,DEPT MED,DIV ENDOCRINOL METABOL & CLIN NUTR,PORTLAND,OR 97201. UNIV IOWA,COLL MED,CLIN RES CTR,IOWA CITY,IA 52242. LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,NEW ORLEANS,LA 70112. NIH,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV IOWA,COLL MED,DEPT MED,IOWA CITY,IA 52242. RP BHATTACHARYYA, AK (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,1901 PERDIDO ST,NEW ORLEANS,LA 70112, USA. FU NHLBI NIH HHS [HL-08974]; PHS HHS [MO1-FR-59, HE-14239] NR 41 TC 64 Z9 66 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD SEP-OCT PY 1991 VL 11 IS 5 BP 1287 EP 1294 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GH339 UT WOS:A1991GH33900019 PM 1911714 ER PT J AU EVANS, SM GRIFFITHS, RR AF EVANS, SM GRIFFITHS, RR TI DOSE-RELATED CAFFEINE DISCRIMINATION IN NORMAL VOLUNTEERS - INDIVIDUAL-DIFFERENCES IN SUBJECTIVE EFFECTS AND SELF-REPORTED CUES SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE DRUG DISCRIMINATION; CAFFEINE; HUMANS; DISCRIMINATIVE STIMULUS EFFECTS; SUBJECTIVE EFFECTS; INDIVIDUAL DIFFERENCES; WITHDRAWAL ID D-AMPHETAMINE; DRUG DISCRIMINATION; PHYSICAL-DEPENDENCE; STIMULUS PROPERTIES; HUMANS; RAT AB A within subject design was used to study a caffeine versus placebo drug discrimination in five volunteers who were not explicitly instructed that the drug conditions involved caffeine and placebo. The caffeine (200 or 300 mg) versus placebo discrimination was acquired by all subjects and remained stable (78-90% accuracy) throughout the study which spanned 5 to 8.7 months across the subjects. A full caffeine dose-response function (50 to 400 or 600 mg) was determined repeatedly under test conditions in each subject; caffeine produced orderly dose-related increases in caffeine identification in all subjects. The present study evaluated individual subject data to examine the correspondence between the subjective effects of caffeine versus placebo and the cues subjects reported as being important to making the discrimination. Although the subjective effects and self-reported cues differed across subjects, there was a correspondence within subjects. Prominent self-reported cues for caffeine included jittery/nervous/anxious (four subjects) and alert/active (one subject); self-reported cues for placebo included tired and/or headache (three subjects) and absence of drug effect (two subjects). The reporting of tired and headache as cues for the placebo condition suggests that caffeine withdrawal may produce stimulus effects relevant to the caffeine versus placebo discrimination. C1 NIDA, ADDICT RES CTR, POB 5180, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. NR 30 TC 34 Z9 34 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 1991 VL 2 IS 4-5 BP 345 EP 356 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GM735 UT WOS:A1991GM73500011 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI XENOPUS TRANSCRIPTION FACTORS - KEY MOLECULES IN THE DEVELOPMENTAL REGULATION OF DIFFERENTIAL GENE-EXPRESSION SO BIOCHEMICAL JOURNAL LA English DT Review ID 5S RNA GENES; INTERNAL CONTROL REGION; PROTO-ONCOGENE INT-1; ESTROGEN-RECEPTOR; DNA-REPLICATION; LAEVIS OOCYTES; HOMEOBOX GENE; VITELLOGENIN GENES; RIBOSOMAL DNA; MESSENGER-RNA RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892, USA. NR 152 TC 10 Z9 10 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1991 VL 278 BP 313 EP 324 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GF221 UT WOS:A1991GF22100001 PM 1910329 ER PT J AU GURGUIS, GNM MEFFORD, IN UHDE, TW AF GURGUIS, GNM MEFFORD, IN UHDE, TW TI HYPOTHALAMIC PITUITARY ADRENOCORTICAL ACTIVITY IN PANIC DISORDER - RELATIONSHIP TO PLASMA-CATECHOLAMINE METABOLITES SO BIOLOGICAL PSYCHIATRY LA English DT Note ID PERFORMANCE LIQUID-CHROMATOGRAPHY; URINARY FREE CORTISOL; ELECTROCHEMICAL DETECTION; HOMOVANILLIC-ACID; ANXIETY; AGORAPHOBIA; SECRETION; MECHANISMS; YOHIMBINE; ATTACKS C1 NIMH,BIOL PSYCHIAT BRANCH,INTRAMURAL RES PROGRAM,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,NEUROSCI BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NR 27 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 1991 VL 30 IS 5 BP 502 EP 506 DI 10.1016/0006-3223(91)90312-A PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GE872 UT WOS:A1991GE87200010 PM 1657223 ER PT J AU SANG, QX THOMPSON, EW GRANT, D STETLERSTEVENSON, WG BYERS, SW AF SANG, QX THOMPSON, EW GRANT, D STETLERSTEVENSON, WG BYERS, SW TI SOLUBLE LAMININ AND ARGININE-GLYCINE-ASPARTIC ACID CONTAINING PEPTIDES DIFFERENTIALLY REGULATE TYPE-IV COLLAGENASE MESSENGER-RNA, ACTIVATION, AND LOCALIZATION IN TESTICULAR CELL-CULTURE SO BIOLOGY OF REPRODUCTION LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; PLASMA-MEMBRANES; SERTOLI CELLS; PERITUBULAR CELLS; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR; INVITRO; IDENTIFICATION; EXPRESSION; SEQUENCE AB Rat testicular cells in culture produce several metalloproteinases including type IV collagenases (Sang et al. Biol Reprod 1990; 43:946-955, 956-964). We have now investigated the regulation of testicular cell type IV collagenase and other metalloproteinases in vitro. Soluble laminin stimulated Sertoli cell type IV collagenase mRNA levels. However, three peptides corresponding to different domains of the laminin molecule (CSRAKQAASIKVASADR, FALRGDNP, CLQDGDVRV) did not influence type IV collagenase mRNA levels. Zymographic analysis of medium collected from these cultures revealed that neither soluble laminin nor any of the peptides influenced 72-kDa type IV collagenase protein levels. However, peptide FALRGDNP resulted in both, a selective increase in two higher molecular-weight metalloproteinases (83 kDa and 110 kDa and in an activation of the 72-kDa rat type IV collagenase. Interleukin-1, phorbol ester, testosterone, and FSH did not affect collagenase activation. Immunocytochemical studies demonstrated that the addition of soluble laminin resulted in a redistribution of type IV collagenase from intracellular vesicles to the cell-substrate region beneath the cells. Peptide FALRGDNP induced a change from a vesicular to peripheral plasma membrane type of staining pattern. Zymography of plasma membrane preparations demonstrated triton-soluble gelatinases of 76 kDa, 83 kDa, and 110 kDa and a triton-insoluble gelatinase of 225 kDa. These results indicate that testicular cell type IV collagenase mRNA levels, enzyme activation, and distribution are influenced by laminin and RGD-containing peptides. C1 GEORGETOWN UNIV,MED CTR,DEPT ANAT & CELL BIOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Thompson, Erik/A-1425-2009; Stetler-Stevenson, William/H-6956-2012 OI Thompson, Erik/0000-0002-9723-4924; Stetler-Stevenson, William/0000-0002-5500-5808 NR 30 TC 19 Z9 19 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 1991 VL 45 IS 3 BP 387 EP 394 DI 10.1095/biolreprod45.3.387 PG 8 WC Reproductive Biology SC Reproductive Biology GA GC911 UT WOS:A1991GC91100002 PM 1664247 ER PT J AU DIXON, DO SIMON, R AF DIXON, DO SIMON, R TI BAYESIAN SUBSET ANALYSIS SO BIOMETRICS LA English DT Article DE CLINICAL TRIAL; EXCHANGEABILITY; INTERACTIONS; MULTIPLE TESTING ID PATIENT SUBSETS; THERAPY AB As a means of assessing the importance of variation in treatment effect among patient subsets, we derived posterior distributions for subset-specific treatment effects. The effects are represented by combinations of terms for treatment and treatment-by-covariate interaction effects in familiar regression models. Exchangeability among the interactions is a key assumption; thus, the results are of interest primarily in the context of examining a collection of subsets with no definite a priori distinction relative to treatment effect. Exchangeability leads to a shrinking of the posterior distributions of the interaction terms toward the natural origin of 0, offsetting the tendency of the estimated effects to disperse. The method is applied to parameter estimates from a proportional hazards regression analysis of survival data from a clinical trial, invoking the approximate multivariate normal distribution of the estimates. No subjective prior distributions are required. Vague priors are used for all of the regression coefficients except the treatment-by-covariate interactions, which are assumed to follow a normal distribution. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOMATH,HOUSTON,TX 77030. NCI,DCT,CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA11430] NR 16 TC 52 Z9 52 U1 1 U2 12 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1991 VL 47 IS 3 BP 871 EP 881 DI 10.2307/2532645 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA GG509 UT WOS:A1991GG50900006 PM 1742443 ER PT J AU KITADE, Y ALSTER, DK PABUCCUOGLU, A TORRENCE, PF AF KITADE, Y ALSTER, DK PABUCCUOGLU, A TORRENCE, PF TI URIDINE ANALOGS OF 2',5'-OLIGOADENYLATES - ON THE BIOLOGICAL ROLE OF THE MIDDLE BASE OF 2-5A TRIMER SO BIOORGANIC CHEMISTRY LA English DT Article ID BINDING; ACTIVATION; RNASE; CELLS C1 NIDDKD,ANALYT CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. NR 22 TC 12 Z9 12 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD SEP PY 1991 VL 19 IS 3 BP 283 EP 299 DI 10.1016/0045-2068(91)90054-S PG 17 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GE386 UT WOS:A1991GE38600006 ER PT J AU HAMRELL, MR CHEW, NJ AF HAMRELL, MR CHEW, NJ TI CLINICAL-TRIALS FOR AIDS TREATMENTS SO BIOPHARM-THE TECHNOLOGY & BUSINESS OF BIOPHARMACEUTICALS LA English DT Editorial Material C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NJC ENTERPRISES LTD,NEW YORK,NY 10014. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 1040-8304 J9 BIOPHARM-TECHNOL BUS JI Biopharm-Technol. Bus. Biopharm. PD SEP PY 1991 VL 4 IS 8 BP 22 EP & PG 0 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA GD313 UT WOS:A1991GD31300002 ER PT J AU FAJER, PG FAJER, EA SCHOENBERG, M THOMAS, DD AF FAJER, PG FAJER, EA SCHOENBERG, M THOMAS, DD TI ORIENTATIONAL DISORDER AND MOTION OF WEAKLY ATTACHED CROSS-BRIDGES SO BIOPHYSICAL JOURNAL LA English DT Article ID SPIN-LABELED MYOSIN; ELECTRON-PARAMAGNETIC RESONANCE; MICROSECOND ROTATIONAL MOTIONS; LOW IONIC-STRENGTH; MUSCLE-FIBERS; RELAXED MUSCLE; ACTOMYOSIN; HEADS; CONTRACTION; ACTIN AB In a relaxed muscle fiber at low ionic strength, the cross-bridges may well be in states comparable to the one that precedes the cross-bridge power stroke (Schoenberg, M. 1988. Adv. Exp. Med. Biol. 226:189-202). Using electron paramagnetic resonance (EPR) and (saturation transfer) electron paramagnetic resonance (ST-EPR) techniques on fibers labeled with maleimide spin label, under low ionic strength conditions designed to produce a majority of weakly-attached heads, we have established that (a) relaxed labeled fibers show a speed dependence of chord stiffness identical to that of unlabeled, relaxed fibers, suggesting similar rapid dissociation and reassociation of cross-bridges: (b) the attached relaxed heads at low ionic strength are nearly as disordered as in relaxation at physiological ionic strength where most of the heads are detached from actin; and (c) the microsecond rotational mobility of the relaxed heads was only slightly restricted compared to normal ionic strength, implying great motional freedom despite attachment. The differences in head mobility between low and normal ionic strength scale with filament overlap and are thus due to actomyosin interactions. The spectra can be modeled in terms of two populations: one identical to relaxed heads at normal ionic strength (83%), the other representing a more oriented population of heads (17%). The spectrum of the latter is centered at approximately the same angle as the spectrum in rigor but exhibits larger (40-degrees) axial probe disorder with respect to the fiber axis. Alternatively, assuming that the chord stiffness is proportional to the fraction of attached crossbridges, the attached fraction must be even more disordered than 40-degrees, with rotational mobility nearly as great as for detached cross-bridges. C1 UNIV MINNESOTA,SCH MED,DEPT BIOCHEM,MINNEAPOLIS,MN 55455. NIH,PHYS PHYSIOL LAB,BETHESDA,MD 20892. RI Thomas, David/B-4257-2012 FU NCRR NIH HHS [RR4300]; NIAMS NIH HHS [AR32961] NR 40 TC 35 Z9 35 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1991 VL 60 IS 3 BP 642 EP 649 PG 8 WC Biophysics SC Biophysics GA GD082 UT WOS:A1991GD08200011 PM 1657230 ER PT J AU ZWANZIG, R SZABO, A AF ZWANZIG, R SZABO, A TI TIME-DEPENDENT RATE OF DIFFUSION-INFLUENCED LIGAND-BINDING TO RECEPTORS ON CELL-SURFACES SO BIOPHYSICAL JOURNAL LA English DT Article ID BOUND RECEPTORS; CHEMORECEPTION AB The theory of the kinetics of binding of ligands to a sphere partially covered by receptors is extended to provide the full time dependence of the reactive flux. The ligands diffuse to the receptors; the receptors are either fully or partially absorbing. The total flux into the sphere with many receptors is expressed analytically in terms of the flux into a single isolated receptor on the sphere. At steady state, the Berg-Purcell formula is generalized to the case where the binding to a single receptor is only partially diffusion controlled. At short times, the receptors behave independently and the total flux is the sum of the fluxes to the isolated receptors. RP ZWANZIG, R (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 12 TC 93 Z9 93 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1991 VL 60 IS 3 BP 671 EP 678 PG 8 WC Biophysics SC Biophysics GA GD082 UT WOS:A1991GD08200014 PM 1657231 ER PT J AU SCHOENBERG, M AF SCHOENBERG, M TI EQUILIBRIUM MUSCLE CROSS-BRIDGE BEHAVIOR THEORETICAL CONSIDERATIONS .2. MODEL DESCRIBING THE BEHAVIOR OF STRONGLY-BINDING CROSS-BRIDGES WHEN BOTH HEADS OF MYOSIN BIND TO THE ACTIN FILAMENT SO BIOPHYSICAL JOURNAL LA English DT Article ID SKELETAL-MUSCLE; CROSSBRIDGE DETACHMENT; SUBFRAGMENT-1; FIBERS; KINETICS; ANALOGS; RABBIT; RIGOR AB A model has been developed for characterizing the interaction between strongly-binding myosin cross-bridges and actin in muscle fibers under equilibrium conditions where both heads of the myosin cross-bridge bind to actin. The model, that of Anderson and Schoenberg (1987. Biophys. J. 52:1077-1082) is quite similar to that of Schoenberg (1985. Biophys. J. 48:467-475), except that explicit account is taken of the fact that each crossbridge has two heads which can bind to actin. The key assumption that allows this model to explain a large body of data unexplained by the Schoenberg (1985) model is that the two crossbridge heads are not totally independent of one another after attachment. After the first head attaches, the second head is then free to attach only to an actin site distal to the first head. This means that when the more distally attached head subsequently detaches and reattaches (as the heads continually do), it will not reattach in a position of lesser strain and reduce the force it supports, but instead will remain attached in its strained position until the proximally attached head also detaches. This model gives an explanation for two important and otherwise unexplained observations made previously: it explains why at ionic strengths in the range of 50-120 mM, (a) the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and (b) why in the presence of analogues or in rigor the rate constant of force decay after a small stretch is significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution. RP SCHOENBERG, M (reprint author), NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1991 VL 60 IS 3 BP 679 EP 689 PG 11 WC Biophysics SC Biophysics GA GD082 UT WOS:A1991GD08200015 PM 1932554 ER PT J AU SCHOENBERG, M AF SCHOENBERG, M TI EFFECT OF IONIC-STRENGTH ON SKINNED RABBIT PSOAS FIBERS IN THE PRESENCE OF MAGNESIUM PYROPHOSPHATE SO BIOPHYSICAL JOURNAL LA English DT Article ID SKELETAL-MUSCLE FIBERS; MYOSIN SUBFRAGMENT-1; CROSSBRIDGE DETACHMENT; F-ACTIN; BINDING; COMPLEX; DISSOCIATION; ACTOMYOSIN; FILAMENTS; DYNAMICS AB The effect of ionic strength on the kinetics of myosin cross-bridges in the presence of the ATP analogue PP(i) has been examined. It was found that increasing ionic strength from moderate values (mu-approximately 100 mM) to high values (mu-approximately 200 mM) has three effects. It causes a big decrease in the half time for the force decay after a small stretch, it causes a significant decrease in the sigmoidicity of the nucleotide analogue concentration dependence of the "apparent rate constant" of force decay after a small stretch, and it causes a big decrease in the range of rate constants necessary to describe the multiexponential force decay. It causes the last of these by causing a much larger increase in the slowest rate constants of the decay than in the fastest rate constants. The results suggest that whereas the behavior of cross-bridges in the presence of ATP is well-described by the simple independent-head equilibrium cross-bridge model of Schoenberg (1985. Biophys. J. 48:467-475), cross-bridges in the presence of the ATP analogue PP(i) require the more complicated double-headed equilibrium cross-bridge model of Anderson and Schoenberg (1987. Biophys. J. 52:1077-1082) to describe their behavior. RP SCHOENBERG, M (reprint author), NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1991 VL 60 IS 3 BP 690 EP 696 PG 7 WC Biophysics SC Biophysics GA GD082 UT WOS:A1991GD08200016 PM 1657232 ER PT J AU KATSANIS, E ANDERSON, PM FILIPOVICH, AH HASZ, DE RICH, ML LOEFFLER, CM OCHOA, AC WEISDORF, DJ AF KATSANIS, E ANDERSON, PM FILIPOVICH, AH HASZ, DE RICH, ML LOEFFLER, CM OCHOA, AC WEISDORF, DJ TI PROLIFERATION AND CYTOLYTIC FUNCTION OF ANTI-CD3 + INTERLEUKIN-2 STIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS FOLLOWING BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACTIVATED KILLER CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; VERSUS-HOST DISEASE; RECOMBINANT INTERLEUKIN-2; SUBSEQUENT REMISSION; CYTO-TOXICITY; LAK CELLS; GRAFT C1 UNIV MINNESOTA,DEPT INTERNAL MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT LAB MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,BONE MARROW TRANSPLANT PROGRAM,MINNEAPOLIS,MN 55455. NCI,PROGRAM RESOURCES INC,FREDERICK,MD 21701. RP KATSANIS, E (reprint author), UNIV MINNESOTA,DEPT PEDIAT,BOX 484 UMHC,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [CA 21737] NR 32 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1991 VL 78 IS 5 BP 1286 EP 1291 PG 6 WC Hematology SC Hematology GA GD499 UT WOS:A1991GD49900021 PM 1831682 ER PT J AU LAJEUNESSE, D KIEBZAK, GM FRONDOZA, C SACKTOR, B AF LAJEUNESSE, D KIEBZAK, GM FRONDOZA, C SACKTOR, B TI REGULATION OF OSTEOCALCIN SECRETION BY HUMAN PRIMARY BONE-CELLS AND BY THE HUMAN OSTEOSARCOMA CELL-LINE MG-63 SO BONE AND MINERAL LA English DT Article DE HUMAN NORMAL OSTEOBLAST-LIKE CELL; HUMAN OSTEOSARCOMA CELL LINE MG-63; OSTEOCALCIN SECRETION; PARATHYROID HORMONE ID OSTEO-SARCOMA CELLS; PARATHYROID-HORMONE; ADENYLATE-CYCLASE; CYCLIC-AMP; 1,25-DIHYDROXYVITAMIN-D3; CALCIUM; PROTEIN; INVITRO; CAMP; MOUSE AB We present evidence that the regulation of osteocalcin secretion by PTH and PGE2 in normal human bone cells can be produced in the human osteoblast-like cell line MG-63. Both cell cultures showed time- and dose-dependent stimulation of osteocalcin secretion in response to 1,25(OH)2D3. Bovine parathyroid hormone (PTH) amino acid fragment 1-34 (40 nM) and prostaglandin E2 (PGE2, 5 nM) significantly inhibited 1,25(OH)2D3-induced osteocalcin secretion by these cells. The inhibition reached 20 and 36%, respectively. In contrast, PTH 3-34 had no effect on osteocalcin secretion. Both cell cultures produced cAMP in response to PTH. Dexamethasone (Dex) (100 nM) potentiated PTH-induced (40 nM) cAMP synthesis in subconfluent MG-63 cells (1.5-fold increase, P < 0.05). This treatment with Dex resulted in a greater inhibition of 1,25(OH)2D3-induced osteocalcin secretion (-30%, P < 0.005) by PTH in MG-63 cells as compared to cells exposed to PTH and 1,25(OH)2D3 alone. Pretreatment of subconfluent MG-63 cells with Dex (100 nM) for 48 h also increased 1,25(OH)2D3-induced osteocalcin secretion by 40% (P < 0.025). In contrast, treatments of confluent MG-63 cells with Dex inhibited osteocalcin secretion regardless of the 1,25(OH)2D3 doses used. Forskolin (10(-7)-10(-5) M) and dibutyryl cAMP (10(-6)-10(-3) M) both reproduced the effects observed with PTH and PGE2 in the two cell cultures. Forskolin's action was time-dependent: addition of forskolin (10(-6) M) 12 h after 1,25(OH)2D3 (50 nM) resulted in a progressively weaker inhibition of osteocalcin secretion. Increasing the extracellular calcium concentration of the incubation media resulted in a dose-dependent increase in osteocalcin secretion (P < 0.01). These results indicate that PTH and PGE2 inhibit osteocalcin secretion by a mechanism involving cAMP production. In contrast, an increase in extracellular calcium stimulated osteocalcin release. Thus the human osteosarcoma cell line MG-63 is a useful osteoblast-like cell model to study the regulation of osteocalcin secretion. Furthermore, a factor (or factors) between hormone-receptor coupling and gene induction can regulate the expression of the osteocalcin gene or affect pre- or posttranslational mechanisms implicated in osteocalcin synthesis and secretion. C1 NIA,GERONTOL RES CTR,FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21218. NR 27 TC 79 Z9 81 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-6009 J9 BONE MINER JI Bone Miner. PD SEP PY 1991 VL 14 IS 3 BP 237 EP 250 DI 10.1016/0169-6009(91)90025-U PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GE515 UT WOS:A1991GE51500005 PM 1657256 ER PT J AU YANO, T PULLMAN, A ANDRADE, R UPPENKAMP, M DEVILLARTAY, JP REAMAN, G CRUSHSTANTON, S COHEN, DI RAFFELD, M COSSMAN, J AF YANO, T PULLMAN, A ANDRADE, R UPPENKAMP, M DEVILLARTAY, JP REAMAN, G CRUSHSTANTON, S COHEN, DI RAFFELD, M COSSMAN, J TI A COMMON V-DELTA-2-D-DELTA-2-D-DELTA-3 T-CELL RECEPTOR GENE REARRANGEMENT IN PRECURSOR-B ACUTE LYMPHOBLASTIC-LEUKEMIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID EARLY THYMOCYTES; DELTA-GENE; CHAIN GENE; LEUKEMIA; LOCUS; DIFFERENTIATION; IDENTIFICATION; NEOPLASMS; DELETION AB Despite their apparent commitment to the B lymphocytic lineage, human precursor B cell acute lymphoblastic leukaemias (ALL) frequently rearrange their T cell antigen receptor (TCR) alpha, beta and gamma-chain genes. Since these three genes are active sites of rearrangement in precursor B cell neoplasms, it seemed that the recently discovered fourth TCR gene, delta, might be similarly rearranged. To investigate this possibility, a series of precursor B cell leukaemias was analysed for rearrangements at the delta-chain gene locus, using probes of the variable, joining, and constant regions of the delta-chain gene. The majority of precursor B cell ALLs in this series (2 5/32, 78%) showed rearrangement or deletion of one or more TCR delta-genes. This contrasts sharply with a series of 16 mature B cell neoplasms (chronic lymphocytic leukaemia) in which no TCR-delta gene rearrangements were detected. An unusual TCR-delta rearrangement, rarely observed in normal or neoplastic T cells, was seen in the majority (14/18) of precursor B cell ALLs with TCR-delta rearrangements. In contrast to the utilization of V-delta-1 in T cell ALL, detailed restriction mapping of precursor B ALL revealed an incomplete rearrangement without involvement of J-delta segments. Direct genomic sequencing was performed on one example and demonstrated a nonproductive V-delta-2-D-delta-2-D-delta-3 recombination in this precursor B ALL. We conclude that the TCR-delta chain gene is an active locus in precursor B cell neoplasia, involves an unusual type of rearrangement and provides a clonal tumour marker for diagnosis of precursor B ALL. C1 GEORGETOWN UNIV,MED CTR,SCH MED,DEPT PATHOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007. NCI,PATHOL LAB,BETHESDA,MD 20892. NIDDKD,CHEM BIOL LAB,BETHESDA,MD. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. MOLEC ONCOL INC,GAITHERSBURG,MD. NR 24 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1991 VL 79 IS 1 BP 44 EP 49 DI 10.1111/j.1365-2141.1991.tb08005.x PG 6 WC Hematology SC Hematology GA GE960 UT WOS:A1991GE96000008 PM 1654993 ER PT J AU BENVENISTE, M MAYER, ML AF BENVENISTE, M MAYER, ML TI STRUCTURE-ACTIVITY ANALYSIS OF BINDING-KINETICS FOR NMDA RECEPTOR COMPETITIVE ANTAGONISTS - THE INFLUENCE OF CONFORMATIONAL RESTRICTION SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE NMDA RECEPTOR; GLUTAMATE; KINETICS, ANTAGONIST, DOSE-RESPONSE ANALYSIS; STRUCTURE-ACTIVITY RELATIONSHIP; AP5, CPP ID METHYL-D-ASPARTATE; CULTURED HIPPOCAMPAL-NEURONS; AMINO-ACID RECEPTORS; XENOPUS-OOCYTES; SPINAL-CORD; RAT-BRAIN; GLYCINE; PHARMACOLOGY; DESENSITIZATION; INHIBITION AB 1 The kinetics of action of 17 structurally related NMDA receptor competitive antagonists were measured under voltage clamp in mouse hippocampal neurones. Analysis of the response to rapid changes in antagonist concentration during constant application of agonist was used to estimate microscopic association (k(on)) and dissociation (k(off)) rate constants for antagonist binding, assuming a two-equivalent site model for competitive antagonism. Dose-inhibition curves were analysed to estimate antagonist equilibrium dissociation constants. 2 For a series of 11-omega-phosphono, alpha-amino acids k(on) and k(off) varied 26 and 107 fold respectively. Rapid association and dissociation rate constants were obtained for flexible antagonist molecules such as D-2-amino-7-phosphonoheptanoic acid (D-AP7): k(on) 1.4 x 10(7) M-1 s-1; k(off) 20.3 s-1. For conformationally restrained molecules such as 3S,4aR,6S,8aR-6-phosphonomethyl-decahydroisoquinoline-3-carboxylic acid (LY 235959), association and dissociation rate constants were much slower: k(on) 1.1 x 10(6) M-1 s-1; k(off) 0.2 s-1. For the D- and L-isomers of 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) estimates for k(on) were similar, but for the L-isomer k(off) was 10 fold faster than for the D-isomer. 3 For 2-amino-5-phosphonopentanoic acid (AP5) and its piperidine derivative cis-4-(phosphonomethyl) piperidine-2-carboxylic acid (CGS 19755), an increase in chain length of two methylene groups between the omega-phosphono and alpha-carboxylate moieties caused a 1.6 to 1.8 fold decrease in k(on) with little change in k(off). In contrast, for AP5, CPP and its omega-carboxylate analogue, addition of a double bond close to the phosphonate moiety caused a 1.3 to 1.6 fold increase in k(on). 4 For antagonists with an omega-tetrazole moiety, k(on) and k(off) were 2.8-4.6 times faster than for the parent omega-phosphono compounds. A similar, but smaller increase in k(on) and k(off) was observed for antagonists with an omega-carboxylate moiety. 5 The slow kinetics of action of potent NMDA receptor antagonists were not an artefact of buffered diffusion. In neurones equilibrated with 200-mu-M D-AP7, 2-mu-M LY 235959 and 10-mu-M NMDA, a transient agonist response was recorded following a rapid switch to D-AP7-free solution. This can only be explained by differences in the binding kinetics of AP7 and LY 235959, since at equilibrium, with these concentrations, either antagonist essentially eliminates the agonist response to 10-mu-M NMDA. 6 For all antagonists studied, the ratio k(off)/k(on) was consistent with equilibrium K(i) values obtained under similar experimental conditions, over a 40 fold range of potency. Comparison of these values with K(i) estimates determined from both agonist ([H-3]-glutamate), and antagonist ([H-3]-CGS 19755 and [H-3]-CPP) radioligand competition studies revealed good correlation between data from voltage clamp and binding experiments. However, K(i) values obtained in antagonist binding assays showed on average 6.5 fold higher affinity than those obtained in voltage clamp experiments; in contrast K(i) values obtained in agonist binding assays showed only 1.4 fold higher affinity. 7 The insights gained from our experiments may be use for predicting the structural features required to generate more potent NMDA receptor antagonists, and suggest that novel acyclic compounds will have greater potential for high potency than derivatives of conformationally rigid compounds with piperazine, piperidine or bicyclic ring structures. C1 NICHHD, NEUROPHYSIOL & BIOPHYS SECT,DEV NEUROBIOL LAB, BLDG 36,ROOM 2A21, BETHESDA, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 42 TC 64 Z9 65 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1991 VL 104 IS 1 BP 207 EP 221 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GD283 UT WOS:A1991GD28300036 PM 1686203 ER PT J AU RICHARDSON, GE LONGO, DL AF RICHARDSON, GE LONGO, DL TI MULTIPLE CAVITATING PULMONARY NODULES IN HODGKINS-DISEASE SO CANCER LA English DT Article ID CHEMOTHERAPY; DIAGNOSIS; LYMPHOMA; MOPP AB Although pulmonary involvement in Hodgkin's disease is common, the presentation with multiple cavitating lung lesions is exceedingly rare, having been described in only five patients. The authors present a case report of a 27-year-old woman with nodular sclerosing Hodgkin's disease treated with conventional chemotherapy and autologous bone marrow transplantation. The patient relapsed with multiple cavitating lung lesions requiring open-lung biopsy for diagnosis. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAMME,FREDERICK,MD 21701. NR 16 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1991 VL 68 IS 5 BP 930 EP 933 DI 10.1002/1097-0142(19910901)68:5<930::AID-CNCR2820680503>3.0.CO;2-1 PG 4 WC Oncology SC Oncology GA GD025 UT WOS:A1991GD02500002 PM 1913488 ER PT J AU SCHAIRER, C BRINTON, LA DEVESA, SS ZIEGLER, RG FRAUMENI, JF AF SCHAIRER, C BRINTON, LA DEVESA, SS ZIEGLER, RG FRAUMENI, JF TI RACIAL-DIFFERENCES IN THE RISK OF INVASIVE SQUAMOUS-CELL CERVICAL-CANCER SO CANCER CAUSES & CONTROL LA English DT Article DE BLACKS, CANCER, CERVIX, RACE, UNITED-STATES, WHITES AB To investigate reasons for the higher rates of invasive squamous-cell cervical carcinoma among Blacks than Whites in the United States, we examined data from a case-control study of cervical cancer conducted in five geographic areas of the US, supplemented by incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, and hysterectomy prevalence data from the Cancer and Steroid Hormone Study. We observed only minor differences between Blacks and Whites in the magnitude of relative risks associated with a long interval since last Pap smear, multiple sexual partners, cigarette smoking, a higher number of births, and low levels of income and education. Thus, differences in the strength of associations contributed little to the higher incidence rate in Blacks, but the prevalence of these risk factors, except for cigarette smoking, was higher in Blacks than Whites. The SEER incidence rate ratio of 2.3 for Blacks compared to whites was increased to 2.7 when incidence rates utilized denominators corrected for prevalence of hysterectomy, while the rate difference increased from 14.9 to 25.8 cases per 100,000 person-years (PY). We estimated further that, after adjustment for prevalence of hysterectomy, the incidence rate for women at the lowest levels of exposure to the risk factors evaluated was 2.2 times higher in Blacks than Whites, but that the corresponding rate difference was only 2.2 cases per 100,000 PYs. Thus, our results suggest that racial differences in the prevalence of exposure to identified risk factors account for most of the difference in incidence rates. It remains to be determined what, as yet unidentified, aspects of lower socioeconomic status contribute to the higher incidence rate in Blacks. RP SCHAIRER, C (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 15 Z9 16 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1991 VL 2 IS 5 BP 283 EP 289 DI 10.1007/BF00051667 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA GF183 UT WOS:A1991GF18300001 PM 1834239 ER PT J AU INSKIP, PD HARVEY, EB BOICE, JD STONE, BJ MATANOSKI, G FLANNERY, JT FRAUMENI, JF AF INSKIP, PD HARVEY, EB BOICE, JD STONE, BJ MATANOSKI, G FLANNERY, JT FRAUMENI, JF TI INCIDENCE OF CHILDHOOD-CANCER IN TWINS SO CANCER CAUSES & CONTROL LA English DT Article DE CANCER, LEUKEMIA, RECORD-LINKAGE, REGISTRIES, TWINS, UNITED-STATES AB The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow-up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristic of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR] = 0.7; 95 percent confidence interval [CI] = 0.5-0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR = 0.8; CI = 0.4-1.4), and all other cancers combined (SIR = 0.6; CI = 0.3-0.9) occurred less often than expected. The deficit was greater among males (SIR = 0.5; CI = 0.2-0.8) than among females (SIR = 0.9; CI = 0.5-1.4) and was especially pronounced among males younger than five years (SIR = 0.2; CI = 0.0-0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an 'effect' of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer. RP INSKIP, PD (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 408,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CPO-1047] NR 0 TC 37 Z9 37 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1991 VL 2 IS 5 BP 315 EP 324 DI 10.1007/BF00051671 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA GF183 UT WOS:A1991GF18300005 PM 1932544 ER PT J AU SREEKANTAIAH, C LI, FP WEIDNER, N SANDBERG, AA AF SREEKANTAIAH, C LI, FP WEIDNER, N SANDBERG, AA TI AN ENDOMETRIAL STROMAL SARCOMA WITH CLONAL CYTOGENETIC ABNORMALITIES SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID UTERINE; REARRANGEMENTS; CHROMOSOMES; TUMORS AB Cytogenetic analysis of a low-grade metastatic endometrial stromal sarcoma in a 58-year-old woman revealed translocations involving both homologues of chromosome 7 with chromosomes 13 and 17, respectively, and an interstitial deletion of the long arm of chromosome 11. The karyotype of the tumor was 46,XX,t(7;13)(q11.1;p13),t(7;17)(p21;q12),del(11)(q13q21). C1 NCI,CLIN STUDIES SECT,CLIN EPIDEMIOL BRANCH,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENETRIX INC,SCOTTSDALE,AZ 85251. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP SREEKANTAIAH, C (reprint author), SW BIOMED RES INST,CTR CANC,6401 E THOMAS RD,TEMPE,AZ 85281, USA. FU NCI NIH HHS [N01-CP-71018] NR 16 TC 32 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1991 VL 55 IS 2 BP 163 EP 166 DI 10.1016/0165-4608(91)90073-4 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GP931 UT WOS:A1991GP93100005 PM 1933818 ER PT J AU SREEKANTAIAH, C LI, FP WEIDNER, N SANDBERG, AA AF SREEKANTAIAH, C LI, FP WEIDNER, N SANDBERG, AA TI MULTIPLE AND COMPLEX ABNORMALITIES IN A CASE OF ALVEOLAR SOFT-PART SARCOMA SO CANCER GENETICS AND CYTOGENETICS LA English DT Article AB Chromosomal analysis of two pulmonary metastases from a 25-year-old male with alveolar soft-part sarcoma of the right lower extremity revealed multiple and complex chromosomal abnormalities. The rearrangements included deletions and translocations affecting chromosomes 1, 2, 3, 10, 11, 14, 15, and 16. Trisomy of chromosome 12 and loss of chromosome 17 was also observed. C1 SW BIOMED RES INST,CTR CANC,6401 E THOMAS RD,TEMPE,AZ 85281. NCI,CLIN STUDIES SECT,CLIN EPIDEMIOL BRANCH,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENETRIX INC,SCOTTSDALE,AZ 85251. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [N01-CP-71018] NR 11 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1991 VL 55 IS 2 BP 167 EP 171 DI 10.1016/0165-4608(91)90074-5 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GP931 UT WOS:A1991GP93100006 PM 1933819 ER PT J AU GREENWELL, A FOLEY, JF MARONPOT, RR AF GREENWELL, A FOLEY, JF MARONPOT, RR TI AN ENHANCEMENT METHOD FOR IMMUNOHISTOCHEMICAL STAINING OF PROLIFERATING CELL NUCLEAR ANTIGEN IN ARCHIVAL RODENT TISSUES SO CANCER LETTERS LA English DT Article DE IMMUNOHISTOCHEMISTRY; ANTIGEN RETRIEVAL; FORMALIN-FIXED TISSUE; PARAFFIN SECTIONS; MICROWAVE; PROLIFERATING CELL NUCLEAR ANTIGEN; CELL PROLIFERATION ID DNA POLYMERASE-DELTA; CYCLIN PCNA; AUXILIARY PROTEIN; S-PHASE; CARCINOGENESIS; TOO AB An enhanced immunohistochemical procedure to detect proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, has been successfully applied to formalin-fixed, paraffin-embedded archival rat and mouse tissues. The procedure involves microwave oven heating of tissue sections in a commercially available antigen retrieval solution of heavy metal salts. Successful immunohistochemical staining of PCNA can be consistently obtained in tissues fixed for over 24 months in formalin and in sections made from paraffin blocks stored in our tissue archives for up to 19 months. Use of this technique will allow retrospective staining of rodent tissues for identification of S phase cells as an indication of DNA replicative activity in previously conducted toxicity and carcinogenicity studies. RP GREENWELL, A (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 176 Z9 177 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD SEP PY 1991 VL 59 IS 3 BP 251 EP 256 DI 10.1016/0304-3835(91)90149-C PG 6 WC Oncology SC Oncology GA GG157 UT WOS:A1991GG15700010 PM 1680544 ER PT J AU CZERWINSKI, M MCLEMORE, TL PHILPOT, RM NHAMBURO, PT KORZEKWA, K GELBOIN, HV GONZALEZ, FJ AF CZERWINSKI, M MCLEMORE, TL PHILPOT, RM NHAMBURO, PT KORZEKWA, K GELBOIN, HV GONZALEZ, FJ TI METABOLIC-ACTIVATION OF 4-IPOMEANOL BY COMPLEMENTARY DNA-EXPRESSED HUMAN CYTOCHROMES P-450 - EVIDENCE FOR SPECIES-SPECIFIC METABOLISM SO CANCER RESEARCH LA English DT Article ID CDNA-DIRECTED EXPRESSION; CARCINOMA CELL-LINES; HUMAN-LIVER; VACCINIA VIRUS; LUNG-CANCER; TOXICITY; IDENTIFICATION; SEQUENCE; SUBFAMILY; PRODUCT AB 4-Ipomeanol is a pulmonary toxin in cattle and rodents that is metabolically activated by cytochromes P-450 (P-450s). P-450-mediated activation of 4-ipomeanol to DNA binding metabolites was evaluated using a vaccinia virus complementary DNA-expression system and an in situ DNA-binding assay. Twelve human P450s and two rodent P450s were expressed in human hepatoma Hep G2 cells and examined for their abilities to metabolically activate this toxin. Three forms, designated CYP1A2, CYP3A3, and CYP3A4, were able to catalyze significant production of DNA-bound metabolites of 20-, 8-, and 5-fold, respectively, above binding catalyzed by Hep G2 cells infected with wild-type vaccinia virus. These enzymes, with highest activities, are not known to be expressed in human or rodent lung. CYP2F1 and CYP4B1, two enzymes that are expressed in lung, display only modest 3- and 2-fold respective increased abilities to metabolically activate 4-ipomeanol. Two human forms were inactive and seven other human forms showed activities ranging from 0.5- to 2-fold above control level. Surprisingly, rabbit complementary DNA-expressed CYP4B1 was the most active enzyme (180-fold above control) among all P-450s tested in producing DNA-binding metabolites from this mycotoxin. These studies demonstrate a species difference in 4-ipomeanol metabolism and suggest caution when attempting to extrapolate rodent data to humans. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NIEHS,PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP CZERWINSKI, M (reprint author), NCI,DIV CANC ETIOL,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 20 TC 69 Z9 72 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1991 VL 51 IS 17 BP 4636 EP 4638 PG 3 WC Oncology SC Oncology GA GC743 UT WOS:A1991GC74300023 PM 1651809 ER PT J AU DLUGOSZ, AA YUSPA, SH AF DLUGOSZ, AA YUSPA, SH TI STAUROSPORINE INDUCES PROTEIN-KINASE-C AGONIST EFFECTS AND MATURATION OF NORMAL AND NEOPLASTIC MOUSE KERATINOCYTES INVITRO SO CANCER RESEARCH LA English DT Article ID ORNITHINE DECARBOXYLASE INDUCTION; EPIDERMAL GROWTH-FACTOR; ESTER-CAUSED INDUCTION; PHORBOL ESTERS; TUMOR PROMOTION; RETINOIC ACID; POTENT INHIBITOR; TERMINAL DIFFERENTIATION; CORNIFIED ENVELOPE; CELLS AB Staurosporine is a potent but nonselective inhibitor of protein kinase C (PKC) and blocks responses to 12-O-tetradecanoylphorbol-13-acetate (TPA) in several cell types in vitro. In cultured primary mouse keratinocytes, however, staurosporine fails to inhibit TPA-mediated keratinocyte maturation and itself elicits responses that are similar to TPA (T. Sako et al., Cancer Res., 48: 4646-4650, 1988). After exposure to 10 nM staurosporine for 24 h, essentially all keratinocytes undergo morphological differentiation, whereas 160 nM TPA induces this response in about 50% of epidermal cells. These concentrations of staurosporine and TPA cause a 4-5-fold induction of epidermal transglutaminase activity and cornified envelopes, both markers of the terminal stage of keratinocyte differentiation. Staurosporine, but not TPA, also induces morphological and biochemical maturation in 2 neoplastic mouse keratinocyte cell lines, 308 and SP-1. The ability of staurosporine to elicit the same responses as TPA suggested that it may be functioning paradoxically as a PKC agonist in intact keratinocytes. In support of this hypothesis, staurosporine induces ornithine decarboxylase activity, inhibits I-125-labeled epidermal growth factor binding, and induces expression of c-fos mRNA. Down-regulation of PKC by pretreatment of primary keratinocytes with 60 nM bryostatin partially blocks staurosporine-mediated induction of cornified envelopes and inhibition of I-125-labeled epidermal growth factor binding, implicating PKC in these responses. The ability of staurosporine to mimic and/or enhance certain responses to TPA suggests that this agent is acting as a functional PKC agonist in cultured keratinocytes. RP DLUGOSZ, AA (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BLDG 37,BETHESDA,MD 20892, USA. NR 60 TC 80 Z9 80 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1991 VL 51 IS 17 BP 4677 EP 4684 PG 8 WC Oncology SC Oncology GA GC743 UT WOS:A1991GC74300030 PM 1678684 ER PT J AU KAUFMANN, WK RICE, JM MACKENZIE, SA SMITH, GJ WENK, ML DEVOR, D QAQISH, BF KAUFMAN, DG AF KAUFMANN, WK RICE, JM MACKENZIE, SA SMITH, GJ WENK, ML DEVOR, D QAQISH, BF KAUFMAN, DG TI PROLIFERATION OF CARCINOGEN-DAMAGED HEPATOCYTES DURING CELL-CYCLE-DEPENDENT INITIATION OF HEPATOCARCINOGENESIS IN THE RAT SO CARCINOGENESIS LA English DT Article ID METHYL-N-NITROSOUREA; PARTIAL-HEPATECTOMY; QUANTITATIVE RELATIONSHIP; DEFICIENT ISLANDS; SINGLE TREATMENT; DNA-SYNTHESIS; LIVER; INDUCTION; METHYL(ACETOXYMETHYL)NITROSAMINE; INVIVO AB Hepatocyte proliferation and damage to DNA were characterized during the initiation phase of carcinogenesis in livers of rats that had received a single administration of the methylating agent methyl(acetoxymethyl)nitrosamine (DMN-OAc). Quiescent non-proliferating hepatocytes in intact livers did not appear to be susceptible to initiation by DMN-OAc, whereas proliferating hepatocytes in the S phase appeared to have greatest risk. To characterize the phenomenology of S-phase-depednece initiation further, the fractions of hepatocytes in the S and M phases of the cell cycle were enumerated at various times after treatment with DMN-OAc. Hepatocytes treated when in G1 experienced a delay of up to 20 h in the onset of S phase and a reduced rate of entry into the S and M cycle phases. Hepatocytes treated when in S phase experienced considerable delay in progression to mitosis due in part to inhibition of DNA replication. Hepatocytes treated when in late S/G2 also demonstrated a delay in progression into mitosis. The levels of 7-methylguanine and O6-methyldeoxyguanosine were quantified in the nuclear DNA of proliferating hepatocytes. The kinetics of removal of these lesions appeared to be first-order (half-life = 24 h). Hepatocyte risk of initiation was modeled by a function which summed over time the product of the fraction of hepatocytes in the S phase and the fraction of residual, unrepaired damage to DNA. For hepatocytes treated when in early G1, the time-weighted frequency of premutagenic DNA damage that was present during DNA replication was estimated to be less than half of that for hepatocytes treated when in early S. The results suggest that cell-cycle-dependent variation in sensitivity to initiation of hepatocarcinogenesis may be, in part, due to efficient removal of potentially carcinogenic lesions from DNA during an extended G1. The apparent high sensitivity of hepatocytes in late S/G2 suggests the contribution of additional factors. C1 UNIV N CAROLINA CHAPEL HILL,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. NCI FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. MICROBIOL ASSOCIATES INC,BETHESDA,MD 20816. UNIV N CAROLINA CHAPEL HILL,DEPT BIOSTAT,CHAPEL HILL,NC 27699. RP KAUFMANN, WK (reprint author), UNIV N CAROLINA CHAPEL HILL,DEPT PATHOL,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA32238, CA31129, CA42765] NR 45 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1991 VL 12 IS 9 BP 1587 EP 1593 DI 10.1093/carcin/12.9.1587 PG 7 WC Oncology SC Oncology GA GG045 UT WOS:A1991GG04500010 PM 1893518 ER PT J AU LEE, E YUSPA, SH AF LEE, E YUSPA, SH TI CHANGES IN INOSITOL PHOSPHATE-METABOLISM ARE ASSOCIATED WITH TERMINAL DIFFERENTIATION AND NEOPLASIA IN MOUSE KERATINOCYTES SO CARCINOGENESIS LA English DT Article ID PROTEIN-KINASE-C; ESTER TUMOR PROMOTERS; EPIDERMAL GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; PHOSPHOLIPASE-C; PHORBOL ESTERS; PHOSPHOINOSITIDE HYDROLYSIS; QUANTITATIVE MEASUREMENT; SIGNAL TRANSDUCTION; ANGIOTENSIN-II AB Cultured murine keratinocytes respond to specific Ca2+ levels in medium (Ca0) by expressing markers of terminal differentiation. A Ca0 of 0.05 mM selects for a basal cell phenotype, whereas spinous cell characteristics occur in 0.12 mM Ca2+ and cornified envelopes develop in 1.0 mM Ca2+. An increase in inositol phosphate (InsP) metabolism is associated with higher Ca2+ in the medium. The magnitude of Ca2+-stimulated InsP turnover is Ca0-dependent, whereby Ca0 of 0.05, 0.12 or 1.4 mM resulted in a graded, sustained (> 24 h) increase in InsPs. Diacylglycerol (DAG) levels similarly increased in a graded manner. The major inositol trisphosphate (InsP3) to accumulate was Ins-1,3,4-P3 while Ins-1,4,5-P3 increased transiently. Neoplastic keratinocyte cell lines, 308 and SP-1, which produce benign tumors and have a mutated c-ras(Ha) gene, do not express markers of differentiation in response to Ca2+. Basal InsP and DAG are 2- and 5-fold higher respectively in the neoplastic cells relative to normal keratinocytes. However, the metabolic profiles of InsPs were similar in normal and neoplastic cells. In neoplastic cells, InsP metabolism was stimulated even further following a Ca2+ increase, and this was graded to the Ca0. The unusual, sustained Ca2+-graded InsP response in normal cells is consistent with the turnover of InsP contributing to the signals controlling expression of markers of differentiation. Very high InsP turnover and DAG levels, as in neoplastic cells, may be inhibitory to marker expression. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 52 TC 61 Z9 61 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1991 VL 12 IS 9 BP 1651 EP 1658 DI 10.1093/carcin/12.9.1651 PG 8 WC Oncology SC Oncology GA GG045 UT WOS:A1991GG04500020 PM 1893524 ER PT J AU HRUSZKEWYCZ, AM CANELLA, KA DIPPLE, A AF HRUSZKEWYCZ, AM CANELLA, KA DIPPLE, A TI DNA POLYMERASE-MEDIATED NUCLEOTIDE INCORPORATION ADJACENT TO HYDROCARBON DEOXYADENOSINE AND HYDROCARBON DEOXYGUANOSINE ADDUCTS SO CARCINOGENESIS LA English DT Article ID CHEMICAL CARCINOGENESIS; NUCLEOSIDE ADDUCTS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BASE-PAIRS; ADENINE; INVITRO; MUTAGENESIS; 1,2-EPOXIDES; TERMINATION AB To examine the effect of DNA adducts on nucleotide incorporation by DNA polymerase at 3' neighboring bases, synthetic oligonucleotides (16mers) containing a purine at position 13 from the 3' end and any one of the four possible bases at position 12 were prepared and reacted with 7-bromomethylbenz[a]anthracene. Using HPLC, unmodified oligonucleotide was separated from oligonucleotide containing a single adduct, at either an adenine or a guanine residue. These products were annealed with a P-32 5'-end labeled primer (11mer) and incubated with modified T7 DNA polymerase (Sequenase, version 2.0) in the presence of deoxyribonucleoside 5'-triphosphates. Analysis by gel electrophoresis showed that unmodified oligonucleotide template allowed the primer to be rapidly extended to the entire length of the template. However, the presence of an adduct caused primer extension to stop at the base 3' to the adduct. While correct base pairing occurred at this termination site with most adducted templates, there was a high frequency of misincorporation of guanine opposite a thymine located 3' to an adenine adduct. This result suggests that some bulky carcinogen-DNA adducts may lead to base mismatches at neighboring bases. RP HRUSZKEWYCZ, AM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 45 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1991 VL 12 IS 9 BP 1659 EP 1663 DI 10.1093/carcin/12.9.1659 PG 5 WC Oncology SC Oncology GA GG045 UT WOS:A1991GG04500021 PM 1893525 ER PT J AU PEGG, AE WIEST, L MUMMERT, C STINE, L MOSCHEL, RC DOLAN, ME AF PEGG, AE WIEST, L MUMMERT, C STINE, L MOSCHEL, RC DOLAN, ME TI USE OF ANTIBODIES TO HUMAN 06-ALKYLGUANINE-DNA ALKYLTRANSFERASE TO STUDY THE CONTENT OF THIS PROTEIN IN CELLS TREATED WITH 06-BENZYLGUANINE OR N-METHYL-N'-NITRO-N-NITROSOGUANIDINE SO CARCINOGENESIS LA English DT Article ID ALKYLATING-AGENTS; MAMMALIAN-CELLS; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; ADAPTIVE RESPONSE; TUMOR-CELLS; REPAIR; CARCINOGENESIS; INACTIVATION; INDUCTION AB Antisera raised in rabbits to three peptides corresponding to amino acid sequences found in human O6 -alkylguanine-DNA alkyltransferase were used to study the fate of the alkyltransferase protein in human colon tumor cells after exposure to N-methyl-N'-nitro-N-nitrosoguanidine or to O6-benzylguanidine. Under these conditions, the alkyltransferase protein becomes inactivated, presumably by the conversion of its cysteine acceptor site to S-methylcysteine or S-benzylcysteine respectively. It was found that the protein was rapidly degraded after such inactivation both in intact cells and in cell-free extracts. It is probable that a conformational change in the protein is brought about by conversion of the alkyltransferase to the inactive form by alkylation of the cysteine acceptor site. This change may render the protein very sensitive to proteolytic degradation. The rapid degradation of the inactive form of the protein may serve as a signal for its resynthesis but in the short term ensures that its reactivation by regeneration of the cysteine acceptor site is unlikely to occur to any significant extent. The short half-life of the inactivated alkyltranferase protein makes it probable that measurement of the content of the alkyltransferase protein by immunohistochemistry, which is likely to measure the sum of the active and inactivated forms of the protein, will nevertheless yield an accurate estimation of the cellular capacity to repair O6-methylguanine provided that procedures with sufficient specificity and affinity can be developed. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS INC,BASIC RES PROGRAM,FREDERICK,MD 21701. UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. RP PEGG, AE (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,POB 850,HERSHEY,PA 17033, USA. FU NCI NIH HHS [CA-18137, N01-CO-74101, CA-47228] NR 23 TC 66 Z9 66 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1991 VL 12 IS 9 BP 1679 EP 1683 DI 10.1093/carcin/12.9.1679 PG 5 WC Oncology SC Oncology GA GG045 UT WOS:A1991GG04500024 PM 1893528 ER PT J AU ORTALDO, JR WINKLERPICKETT, RT YAGITA, H YOUNG, HA AF ORTALDO, JR WINKLERPICKETT, RT YAGITA, H YOUNG, HA TI COMPARATIVE-STUDIES OF CD3- AND CD3+ CD56+ CELLS - EXAMINATION OF MORPHOLOGY, FUNCTIONS, T-CELL RECEPTOR REARRANGEMENT, AND PORE-FORMING PROTEIN EXPRESSION SO CELLULAR IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; LARGE GRANULAR LYMPHOCYTES; PERIPHERAL-BLOOD; INTERLEUKIN-2; ANTIGEN; GAMMA; GENE C1 JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN. RP ORTALDO, JR (reprint author), NCI,FCRDC,FREDERICK CANC RES FACIL,DIV CANC,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. NR 17 TC 77 Z9 86 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1991 VL 136 IS 2 BP 486 EP 495 DI 10.1016/0008-8749(91)90369-M PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GC074 UT WOS:A1991GC07400019 PM 1714795 ER PT J AU Armstrong, E Curtis, M Buxhoeveden, DP Fregoe, C Zilles, K Casanova, MF McCarthy, WF AF Armstrong, Este Curtis, Maria Buxhoeveden, Daniel P. Fregoe, Carolyn Zilles, Karl Casanova, Manuel F. McCarthy, William F. TI Cortical Gyrification in the Rhesus Monkey: A Test of the Mechanical Folding Hypothesis SO CEREBRAL CORTEX LA English DT Article AB A quantitative measure of the degree of cortical folding was used to test the mechanical hypothesis of cortical folding and to analyze structural properties of the rhesus monkey cortex. The rhesus monkey cortex has both its maximal degree of cortical folding and the largest ratios of supragranular laminae to the lower granular and infragranular layers in the caudal cortex, over the posterior parietal-anterior occipital regions. Low values for cortical folding and for the ratios of inner and outer cortical layers characterize frontal regions. Topographically intermediate regions are intermediate in both sets of values. Ratios of the amounts of white and gray matter have a topographic pattern that differs from those of cortical folding, suggesting that the sizes of subcortical axonal bundles are not directly associated with the degree of cortical folding. Whereas differences in mean degrees of cortical folding are correlated with brain weights among species of primates, the amount of folding is not associated with brain weight within the species. C1 [Armstrong, Este; Curtis, Maria; Buxhoeveden, Daniel P.; Fregoe, Carolyn] Armed Forces Inst Pathol, Amer Registry Pathol, Washington, DC 20306 USA. [McCarthy, William F.] Armed Forces Inst Pathol, Dept Biostat, Washington, DC 20306 USA. [Armstrong, Este; Curtis, Maria] Uniformed Serv Univ Hlth Sci, Dept Anat, Bethesda, MD 20814 USA. [Buxhoeveden, Daniel P.] Univ Chicago, Dept Anthropol, Chicago, IL 60637 USA. [Zilles, Karl] Univ Cologne, Inst Anat, D-5000 Cologne 41, Germany. [Casanova, Manuel F.] St Elizabeth Hosp, Clin Brain Disorders Branch, NIMH, Washington, DC 20032 USA. RP Armstrong, E (reprint author), Armed Forces Inst Pathol, Amer Registry Pathol, Washington, DC 20306 USA. RI Zilles, Karl/J-9704-2013 OI Zilles, Karl/0000-0001-9296-9959 FU USPHS [NSF 8820485, NIMH MH45594]; American Registry of Pathology, Washington, DC FX We thank Courtney Henderson and Archibald Fobbs for excellent technical assistance. The study was supported in part by USPHS Grants NSF 8820485 (E.A.) and NIMH MH45594 (E.A.) and the American Registry of Pathology, Washington, DC. NR 22 TC 52 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 1991 VL 1 IS 5 BP 426 EP 432 DI 10.1093/cercor/1.5.426 PG 7 WC Neurosciences SC Neurosciences & Neurology GA V19BJ UT WOS:000208047600007 PM 1822750 ER PT J AU WINK, DA NIMS, RW DESROSIERS, MF FORD, PC KEEFER, LK AF WINK, DA NIMS, RW DESROSIERS, MF FORD, PC KEEFER, LK TI A KINETIC INVESTIGATION OF INTERMEDIATES FORMED DURING THE FENTON REAGENT MEDIATED DEGRADATION OF N-NITROSODIMETHYLAMINE - EVIDENCE FOR AN OXIDATIVE PATHWAY NOT INVOLVING HYDROXYL RADICAL SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Note ID HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; RAT-LIVER; DENITROSATION; IRON(II); ADDUCTS C1 NATL INST STAND & TECHNOL,CTR RADIAT RES,GAITHERSBURG,MD 20899. UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. RP WINK, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011; Keefer, Larry/N-3247-2014 OI Ford, Peter/0000-0002-5509-9912; Keefer, Larry/0000-0001-7489-9555 NR 23 TC 39 Z9 40 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1991 VL 4 IS 5 BP 510 EP 512 DI 10.1021/tx00023a002 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA GG363 UT WOS:A1991GG36300002 PM 1665352 ER PT J AU CRESPI, CL GONZALEZ, FJ STEIMEL, DT TURNER, TR GELBOIN, HV PENMAN, BW LANGENBACH, R AF CRESPI, CL GONZALEZ, FJ STEIMEL, DT TURNER, TR GELBOIN, HV PENMAN, BW LANGENBACH, R TI A METABOLICALLY COMPETENT HUMAN CELL-LINE EXPRESSING 5 CDNAS ENCODING PROCARCINOGEN-ACTIVATING ENZYMES - APPLICATION TO MUTAGENICITY TESTING SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CHINESE-HAMSTER-CELLS; HUMAN-LIVER; STABLE EXPRESSION; CYTOCHROME-P-450 ENZYMES; COMPLEMENTARY-DNA; MUTATION ASSAYS; O-DEETHYLASE; RAT; GENE; BIOACTIVATION AB A human B-lymphoblastoid cell line, designated MCL-5, constitutively expressing human cytochrome P-450 CYP1A1 and also expressing five transfected human cDNAs encoding drug-metabolizing enzymes, has been developed. cDNAs encoding CYP1A2, CYP2A6, and microsomal epoxide hydrolase (mEH) were introduced by using a vector conferring hygromycin B resistance, and cDNAs encoding CYP2E1 and CYP3A4 were introduced by using a vector conferring resistance to 1-histidinol. MCL-5 cells stably expressed all five cDNAs and the native CYP1A1 as determined by measurement of form-specific enzyme activity levels. The mutagenicity of seven model procarcinogens to MCL-5 cells was examined at the hypoxanthine guanine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci. Exposure to benzo[a]pyrene (BP), 3-methylcholanthrene (3MC), N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), aflatoxin B1, (AFB1), 2-(acetylamino)fluorene (AAF), or benzidine (BZD) induced a statistically significant increase in mutant frequency. Linear interpolation of the concentration of procarcinogen necessary to produce a doubling of the mutant fraction at the hprt locus in MCL-5 cells and the parent AHH-1 cell line revealed that, for each of the chemicals examined, except BZD, MCL-5 cells were significantly more sensitive than the parent AHH-1 cells. The increase in sensitivity to mutagenicity ranged from 3-fold for AAF to greater than 40 000-fold for NDMA. MCL-5 cells have great potential as a screening system for the analysis of human procarcinogen/promutagen activation. C1 NIEHS,RES TRIANGLE PK,NC 27709. NCI,BETHESDA,MD 20892. RP CRESPI, CL (reprint author), GENTEST CORP,6 HENSHAW ST,WOBURN,MA 01801, USA. FU PHS HHS [N44-71001] NR 42 TC 130 Z9 133 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1991 VL 4 IS 5 BP 566 EP 572 DI 10.1021/tx00023a013 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA GG363 UT WOS:A1991GG36300013 PM 1793807 ER PT J AU BRANTLY, ML WITTES, JT VOGELMEIER, CF HUBBARD, RC FELLS, GA CRYSTAL, RG AF BRANTLY, ML WITTES, JT VOGELMEIER, CF HUBBARD, RC FELLS, GA CRYSTAL, RG TI USE OF A HIGHLY PURIFIED ALPHA-1-ANTITRYPSIN STANDARD TO ESTABLISH RANGES FOR THE COMMON NORMAL AND DEFICIENT ALPHA-1-ANTITRYPSIN PHENOTYPES SO CHEST LA English DT Article ID AUGMENTATION THERAPY; EMPHYSEMA; INHIBITOR; ALPHA1-ANTITRYPSIN; ELASTASES; MUTATIONS; GENE; SZ AB Diagnosis of the hereditary disorder alpha-1-antitrypsin (alpha-1AT) deficiency is critically dependent on quantification of serum levels of alpha-1AT, a 52-kDa antiprotease that serves to protect the lung from destruction by neutrophil elastase. Although the measurement of serum alpha-1AT levels is not difficult, there is no international standard for alpha-1AT, and investigators in the field recognize that widely used commercially available standards vary by as much as 50 percent. To establish accurate ranges for the common normal and deficient alpha-1AT phenotypes, the present study uses a purified alpha-1AT standard to quantify the alpha-1AT serum levels of 443 individuals with common normal and deficient alpha-1AT phenotypes, including MM, ZZ, SS, MZ, MS, and SZ. Based on the observed values, a statistical model was developed to generate predicted frequency distributions of alpha-1AT serum levels for each of these phenotypes. Based on these studies, the ranges (5th to 95th percentile) for alpha-1AT serum levels of the common phenotypes are: MM, 20 to 53-mu-mol/L; SS, 20 to 48-mu-mol/L; ZZ, 3.4 to 7.0-mu-mol/L; MZ, 15 to 42-mu-mol/L; MS, 18 to 52-mu-mol/L; and SZ, 10 to 23-mu-mol/L. This alpha-1AT standard and these ranges are being used for the National alpha-1-Antitrypsin Deficiency Registry organized under the auspices of the National Heart, Lung, and Blood Institute. C1 NHLBI,PULM BRANCH,BLDG 10,RM 6003,BETHESDA,MD 20892. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 37 TC 99 Z9 104 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1991 VL 100 IS 3 BP 703 EP 708 DI 10.1378/chest.100.3.703 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA GD911 UT WOS:A1991GD91100029 PM 1889260 ER PT J AU BROWN, RA MCCORMICK, KA VAITKEVICIUS, PV FLEG, JL AF BROWN, RA MCCORMICK, KA VAITKEVICIUS, PV FLEG, JL TI EFFECT OF POSTURAL STRESS ON LEFT-VENTRICULAR PERFORMANCE USING THE CONTINUOUS-WAVE DOPPLER TECHNIQUE SO CHEST LA English DT Article ID AORTIC BLOOD VELOCITY; HEART-RATE; CARDIAC-OUTPUT; NONINVASIVE EVALUATION; SYSTOLIC FUNCTION; ACCELERATION; EXERCISE; INDEXES; AGE; AFTERLOAD AB To evaluate the effect of postural shifts on continuous-wave Doppler indices of left ventricular performance in normal man, we recorded Doppler signals suprasternally in 69 healthy volunteers, ranging in age from 20 to 86 years, in the supine position and 2 min after assumption of sitting and standing postures. All indices decreased progressively with increasing orthostasis: peak acceleration (PKA): 15.6 +/- 4.5 m/s2 to 14.0 +/- 4.0 m/s2 to 13.6 +/- 4.6 m/s2; peak velocity (PKV): 0.64 +/- 0.18 m/s to 0.58 +/- 0.17 m/s to 0.56 +/- 0.17 m/s; stroke distance (SD): 11.4 +/- 3.7 cm to 9.8 +/- 3.4 cm to 8.0 +/- 2.8 cm; SD x heart rate (VIH): 717 +/- 272 cm to 655 +/- 268 cm to 572 +/- 217 cm, from supine to sitting to standing, respectively (p < 0.001). In contrast, heart rate increased modestly from 62.4 +/- 10.0 bpm supine, to 66.9 +/- 12.4 bpm sitting, to 71.3 +/- 9.9 bpm standing (p < .001). Similar postural changes in Doppler variables were seen in all three age groups (20 to 44 years; 45 to 64 years; and 65 to 86 years). Thus, orthostasis in normal subjects is accompanied by a reduction in all continuous-wave Doppler indices of left ventricular performance, regardless of age. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. WAYNE STATE UNIV,DEPT PHYSIOL,DETROIT,MI 48202. RP BROWN, RA (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1991 VL 100 IS 3 BP 738 EP 743 DI 10.1378/chest.100.3.738 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA GD911 UT WOS:A1991GD91100036 PM 1889267 ER PT J AU DENHAM, SA ZAHNWAXLER, C CUMMINGS, EM IANNOTTI, RJ AF DENHAM, SA ZAHNWAXLER, C CUMMINGS, EM IANNOTTI, RJ TI SOCIAL COMPETENCE IN YOUNG CHILDRENS PEER RELATIONS - PATTERNS OF DEVELOPMENT AND CHANGE SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE MATERNAL DEPRESSION; SOCIAL COMPETENCE; PRESCHOOLERS ID KINDERGARTEN-CHILDREN; BEHAVIOR; DEPRESSION; AGGRESSION; PRESCHOOL; EMOTIONS AB Patterns of developmental change and individual differences in social competence were examined in children of depressed and psychiatrically well mothers, during the toddler-to-late-preschool period. Forty-one children were observed in peer interaction at ages two and five under semi-naturalistic laboratory conditions intended to elicit a range of emotions and social skills. Social competence increased with age, but patterns of developmental change were moderated by maternal diagnosis. Low levels of individual stability were identified in children's social competence. C1 NIMH,BETHESDA,MD 20892. W VIRGINIA UNIV,MORGANTOWN,WV 26506. GEORGETOWN UNIV,WASHINGTON,DC 20057. RP DENHAM, SA (reprint author), GEORGE MASON UNIV,DEPT PSYCHOL,4400 UNIV DR,FAIRFAX,VA 22030, USA. NR 46 TC 23 Z9 23 U1 2 U2 9 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD FAL PY 1991 VL 22 IS 1 BP 29 EP 44 DI 10.1007/BF00706057 PG 16 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA GC225 UT WOS:A1991GC22500003 PM 1748014 ER PT J AU BURKE, GL SAVAGE, PJ SPRAFKA, JM SELBY, JV JACOBS, DR PERKINS, LL ROSEMAN, JM HUGHES, GH FABSITZ, RR AF BURKE, GL SAVAGE, PJ SPRAFKA, JM SELBY, JV JACOBS, DR PERKINS, LL ROSEMAN, JM HUGHES, GH FABSITZ, RR TI RELATION OF RISK FACTOR LEVELS IN YOUNG ADULTHOOD TO PARENTAL HISTORY OF DISEASE - THE CARDIA STUDY SO CIRCULATION LA English DT Article DE EPIDEMIOLOGY; CARDIOVASCULAR DISEASES; FAMILY HISTORY; RISK FACTORS ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; 1ST DEGREE RELATIVES; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; FAMILY HISTORY; MYOCARDIAL-INFARCTION; CHILDREN; AGGREGATION; PLASMA AB Background. The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986). Methods and Results. The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone. Conclusions. These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals. C1 NHLBI,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. KAISER PERMANENTE,DIV RES,OAKLAND,CA. UNIV ALABAMA,SCH PUBL HLTH,DEPT BIOSTAT & BIOMATH,BIRMINGHAM,AL 35233. UNIV ALABAMA,DIV GEN & PREVENT MED,BIRMINGHAM,AL 35233. RP BURKE, GL (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH,300 S HAWTHORNE ST,WINSTON SALEM,NC 27103, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 37 TC 76 Z9 77 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1991 VL 84 IS 3 BP 1176 EP 1187 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF184 UT WOS:A1991GF18400020 PM 1884448 ER PT J AU KLUES, HG ROBERTS, WC MARON, BJ AF KLUES, HG ROBERTS, WC MARON, BJ TI ANOMALOUS INSERTION OF PAPILLARY-MUSCLE DIRECTLY INTO ANTERIOR MITRAL LEAFLET IN HYPERTROPHIC CARDIOMYOPATHY - SIGNIFICANCE IN PRODUCING LEFT-VENTRICULAR OUTFLOW OBSTRUCTION SO CIRCULATION LA English DT Article DE HYPERTROPHIC CARDIOMYOPATHY; ECHOCARDIOGRAPHY; MITRAL VALVE; PAPILLARY MUSCLE; OBSTRUCTION ID DIMENSIONAL ECHOCARDIOGRAPHIC ASSESSMENT; SUBAORTIC STENOSIS; VALVE REPLACEMENT; M-MODE; CLINICAL MANIFESTATIONS; OPERATIVE TREATMENT; PRESSURE-GRADIENT; PATHO-PHYSIOLOGY; MOTION; INTERRELATIONS AB Background. Obstruction to left ventricular outflow in hypertrophic cardiomyopathy (HCM) is usually due to systolic anterior motion of the mitral valve. Occurrence of structural mitral valve abnormalities in HCM and their significance in producing outflow obstruction (even in the absence of typical systolic anterior motion) has not been fully appreciated. Methods and Results. Analysis of 78 mitral valves excised from patients with obstructive HCM showed that 10 (13%) had anomalous insertion of one or both left ventricular papillary muscles directly into the anterior mitral leaflet. This malformation was identified by echocardiography, which demonstrated direct continuity between the hypertrophied papillary muscle and mitral leaflet, resulting in a long rigid area of midcavity narrowing that appeared to be solely or largely responsible for outflow obstruction. Basal subaortic pressure gradients were large (70-150 mm Hg). Mitral valve replacement reduced the outflow gradient substantially to 0-15 mm Hg in four patients with postoperative cardiac catheterization. However, two other patients who underwent septal myotomy/myectomy had persistent symptoms and incomplete relief of obstruction (gradients 60 and 70 mm Hg) because of continued midcavity apposition of papillary muscle and ventricular septum. Conclusions. Anomalous papillary muscle insertion into anterior mitral leaflet represents a mechanism of obstruction to left ventricular outflow in patients with HCM and differs considerably from typical dynamic obstruction caused by mitral valve systolic anterior motion that occurs in many other patients with HCM. Recognition of this malformation emphasizes the diverse morphological expression of HCM and also has important clinical implications for patients requiring operation because the gradient is likely to persist even after adequate myotomy/myectomy; consequently, mitral valve replacement would appear to be the operation of choice in most such patients. C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 37 TC 130 Z9 135 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1991 VL 84 IS 3 BP 1188 EP 1197 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF184 UT WOS:A1991GF18400021 PM 1884449 ER PT J AU BONOW, RO AF BONOW, RO TI RADIONUCLIDE ANGIOGRAPHY IN THE MANAGEMENT OF ASYMPTOMATIC AORTIC REGURGITATION SO CIRCULATION LA English DT Article; Proceedings Paper CT STATE-OF-THE-ART CONF ON NONINVASIVE TESTING IN THE DIAGNOSIS AND MANAGEMENT OF SUSPECTED OR OVERT HEART DISEASE CY SEP 18-20, 1989 CL DALLAS, TX SP COUNCIL CARDIOVASC RADIOL, HEWLETT PACKARD DE AORTIC REGURGITATION; LEFT VENTRICULAR FUNCTION; RADIONUCLIDE ANGIOGRAPHY ID LEFT-VENTRICULAR FUNCTION; VALVULAR HEART-DISEASE; END-SYSTOLIC DIMENSION; SERIAL ECHOCARDIOGRAPHIC EVALUATION; M-MODE ECHOCARDIOGRAPHY; REGIONAL WALL MOTION; VALVE-REPLACEMENT; EJECTION FRACTION; NATURAL-HISTORY; PROGNOSTIC-SIGNIFICANCE AB Left ventricular systolic function is an important determinant of long-term prognosis in patients with chronic aortic regurgitation. In patients undergoing aortic valve replacement, those with preoperative left ventricular dysfunction have a greater risk of postoperative congestive heart failure and death than do those in whom preoperative left ventricular systolic function is normal. However, patients with preoperative left ventricular dysfunction are not a homogeneous group but may be further stratified according to risk on the basis of the severity of symptoms, exercise intolerance, and temporal duration of left ventricular dysfunction. Therefore, asymptomatic patients with reproducible and definite evidence of impaired left ventricular function should undergo operation without waiting for the development of symptoms or more severe left ventricular dysfunction. In addition, among asymptomatic patients with normal systolic function, indexes of left ventricular function are also helpful, especially when measured serially, in predicting the development of symptoms and the need for valve replacement surgery over the course of the next 5 to 10 years. Noninvasive imaging techniques should play a major role in this evaluation, and radionuclide angiography is ideally suited for the quantitative evaluation of systolic function in the volume-overloaded left ventricle. Although the prognostic value of left ventricular ejection fraction at rest is well established, ejection fraction during exercise has little value once age and left ventricular function at rest are accounted for and is of minor importance in formulating patient management decisions. RP BONOW, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 59 TC 3 Z9 4 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1991 VL 84 IS 3 SU S BP I296 EP I302 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF388 UT WOS:A1991GF38800038 PM 1884499 ER PT J AU BONOW, RO AF BONOW, RO TI RADIONUCLIDE ANGIOGRAPHIC EVALUATION OF LEFT-VENTRICULAR DIASTOLIC FUNCTION SO CIRCULATION LA English DT Article; Proceedings Paper CT STATE-OF-THE-ART CONF ON NONINVASIVE TESTING IN THE DIAGNOSIS AND MANAGEMENT OF SUSPECTED OR OVERT HEART DISEASE CY SEP 18-20, 1989 CL DALLAS, TX SP COUNCIL CARDIOVASC RADIOL, HEWLETT PACKARD DE CORONARY ARTERY DISEASE; HYPERTENSION; HYPERTROPHIC CARDIOMYOPATHY; LEFT VENTRICULAR FUNCTION; RADIONUCLIDE ANGIOGRAPHY ID CORONARY-ARTERY DISEASE; PRESSURE-VOLUME RELATIONS; CONGESTIVE HEART-FAILURE; ISOVOLUMIC RELAXATION PERIOD; BETA-ADRENERGIC STIMULATION; EXERCISE-INDUCED ISCHEMIA; BLOOD POOL SCINTIGRAPHY; PEAK FILLING RATE; HYPERTROPHIC CARDIOMYOPATHY; SYSTOLIC FUNCTION AB Left ventricular diastolic function is altered in the majority of patients with cardiac diseases, especially those characterized by myocardial ischemia or hypertrophy. In many circumstances, such abnormalities related to impaired relaxation or reduced distensibility may precede evidence of left ventricular systolic dysfunction. Radionuclide angiography may be adapted to study the rapid filling phase of diastole, the duration of the isovolumic relaxation phase, the relative contributions of rapid filling and atrial systole to left ventricular stroke volume, and the relation between regional nonuniformity of left ventricular function and global filling properties. Technical aspects of data acquisition that must be considered for such studies include the effects of cardiac cycle length fluctuations, temporal resolution, temporal smoothing, and normalization parameters. As noninvasive radionuclide methods (and any other analyses using purely noninvasive techniques) do not permit assessment of the left atrial-left ventricular pressure gradient or the simultaneous evaluation of changes in left ventricular pressure and volume during relaxation and filling, complete clinical interpretation of "abnormal" left ventricular filling indexes, or changes in these indexes after interventions, is not possible. Despite the inherent limitations of noninvasive assessment of left ventricular diastolic function, radionuclide evaluation of left ventricular filling may provide clinically useful insights, especially in patients with congestive heart failure symptoms and normal left ventricular systolic function. RP BONOW, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 90 TC 8 Z9 8 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1991 VL 84 IS 3 SU S BP I208 EP I215 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF388 UT WOS:A1991GF38800028 PM 1884488 ER PT J AU BANAI, S SHOU, M CORREA, R JAKLITSCH, MT DOUEK, PC BONNER, RF EPSTEIN, SE UNGER, EF AF BANAI, S SHOU, M CORREA, R JAKLITSCH, MT DOUEK, PC BONNER, RF EPSTEIN, SE UNGER, EF TI RABBIT EAR MODEL OF INJURY-INDUCED ARTERIAL SMOOTH-MUSCLE CELL-PROLIFERATION - KINETICS, REPRODUCIBILITY, AND IMPLICATIONS SO CIRCULATION RESEARCH LA English DT Article DE SMOOTH MUSCLE CELLS; ACCELERATED ARTERIOSCLEROSIS; NEOINTIMA; RESTENOSIS; ANIMAL MODEL ID BALLOON ANGIOPLASTY; INHIBITION; ATHEROSCLEROSIS; DIPYRIDAMOLE; RESTENOSIS; PLATELETS; HEPARIN; SYSTEM; WALL AB Recently, considerable interest has focused on the vascular smooth muscle cell (SMC) response to injury, particularly as it relates to restenosis after angioplasty. In an effort to find an optimal experimental model of arterial SMC proliferation after injury, we examined the effects of external injury to the central artery of the rabbit ear and assessed the reproducibility, morphological changes, and time course of cellular proliferation after such an injury. With rabbits under general anesthesia, direct pressure was applied at two sites along the central artery of the ears of 19 New Zealand White rabbits. Rabbits were maintained on a diet of 2.4% fat and 0.001% cholesterol throughout the experiment. In seven rabbits examined after 21 days, marked SMC proliferation with neointimal formation was observed at all 28 sites (100%). Mean neointimal area, expressed as a percentage of the area of the tunica media, was 82 +/- 40% (range, 21-203%). Compared with the uninvolved artery displaced 2 mm from the injury site, mechanical crush caused a 38% increase in total vessel area (p < 0.001), a 40% decrease in luminal area (p < 0.002), and no change in the area of the media. Serial histological studies were performed 1-42 days after injury, using light and electron microscopy and bromodeoxyuridine immunohistochemistry. Beginning at day 3, activated medial SMCs were noted to migrate through defects in the internal elastic membrane, with a gradual increase in neointimal area between days 5 and 12. Peak DNA synthesis was identified in the media 5 days after injury, with proliferative activity shifting almost exclusively to the neointima thereafter. We conclude that mechanical crush injury is a potent stimulus for SMC proliferation. The method is simply employed, multiple lesions can be created in a single animal with high yield, and therapeutic end points can be easily quantified. The lesions so produced are superficial and easily accessible; therefore, agents with the potential to prevent SMC proliferation can be targeted locally by subcutaneous injection or topical application. C1 NHLBI,EXPTL PHYSIOL & PHARMACOL LAB,CARDIOL BRANCH,10-7B15,BETHESDA,MD 20892. RI Bonner, Robert/C-6783-2015 NR 21 TC 51 Z9 52 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1991 VL 69 IS 3 BP 748 EP 756 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA GD193 UT WOS:A1991GD19300019 PM 1873869 ER PT J AU HURD, SS AF HURD, SS TI WORKSHOP SUMMARY AND GUIDELINES - INVESTIGATIVE USE OF BRONCHOSCOPY, LAVAGE AND BRONCHIAL BIOPSIES IN ASTHMA AND OTHER AIRWAYS DISEASES SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE; MAST-CELLS; MILD ASTHMA; ALLERGEN CHALLENGE; ANTIGEN CHALLENGE; MEDIATOR RELEASE; INFLAMMATION; EXERCISE; BRONCHOCONSTRICTION; PROSTAGLANDIN-D2 RP HURD, SS (reprint author), NHLBI,DLD,WESTWOOD BLDG,ROOM 6A-15,BETHESDA,MD 20892, USA. NR 40 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD SEP PY 1991 VL 21 IS 5 BP 533 EP 539 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA GH006 UT WOS:A1991GH00600003 ER PT J AU TSOKOS, GC AF TSOKOS, GC TI BIOCHEMICAL AND MOLECULAR ABNORMALITIES IN THE PATHOGENESIS OF SYSTEMIC LUPUS-ERYTHEMATOSUS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review ID PROTO-ONCOGENE EXPRESSION; PERIPHERAL-BLOOD LYMPHOCYTES; CELL DNA METHYLATION; MRL-LPR/LPR MICE; B220+ T-CELLS; B-CELLS; ULTRAVIOLET-RADIATION; RHEUMATOID-ARTHRITIS; MONONUCLEAR-CELLS; IMMUNE FUNCTIONS C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP TSOKOS, GC (reprint author), NIDDKS,KIDNEY DIS SECT,BLDG 10,RM 3N-112,BETHESDA,MD 20892, USA. NR 75 TC 5 Z9 8 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 1991 VL 9 IS 5 BP 533 EP 539 PG 7 WC Rheumatology SC Rheumatology GA GK766 UT WOS:A1991GK76600016 PM 1954706 ER PT J AU COOPMAN, P VERHASSELT, B BRACKE, M DEBRUYNE, G CASTRONOVO, V SOBEL, M FOIDART, JM VANROY, F MAREEL, M AF COOPMAN, P VERHASSELT, B BRACKE, M DEBRUYNE, G CASTRONOVO, V SOBEL, M FOIDART, JM VANROY, F MAREEL, M TI ARREST OF MCF-7 CELL-MIGRATION BY LAMININ INVITRO - POSSIBLE MECHANISMS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article ID RECEPTOR MESSENGER-RNA; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; CANCER-CELLS; EXPRESSION; ATTACHMENT; CARCINOMA; LINE; GLYCOPROTEIN; PENTAPEPTIDE AB Laminin, a major basement membrane component, arrested the migration of MCF-7/AZ human breast adenocarcinoma cells that were not invasive in vitro. Migration of invasive MCF-7/6 cells was not affected by laminin. Both cell types expressed the 67 kD laminin receptor, at both mRNA and protein level, but did not express the alpha-6 subunit of the VLA-6 integrin-type laminin receptor. The presence of YIGSR peptides (100-mu-g/ml), reported to block the interaction between laminin and its 67 kD receptor, did not change the migratory response of MCF-7/AZ or MCF-7/6 cells when meeting laminin lanes. In addition, the migration of these cell types was not affected by the presence of 17-beta-estradiol (10(-6) M) or all-trans retinoic acid (10(-6) M), which were both reported to increase the number of 67 kD receptors. We could therefore not assign an involvement of the 67 kD receptors in migration of MCF-7 cells on laminin, nor did we find evidence that conditioned medium of MCF-7/6 cells contains factors that are able to initiate migration of MCF-7/AZ cells on laminin. C1 STATE UNIV GHENT HOSP,DEPT RADIOTHERAPY & NUCL MED,EXPTL CANCEROL LAB,DE PINTELAAN 185,B-9000 GHENT,BELGIUM. NIH,PATHOL LAB,BETHESDA,MD 20892. STATE UNIV LIEGE,DEPT GEN BIOL,B-4000 LIEGE,BELGIUM. STATE UNIV GHENT,MOLEC BIOL LAB,B-9000 GHENT,BELGIUM. RI van Roy, Frans/C-6123-2009 OI van Roy, Frans/0000-0003-4358-1039 NR 32 TC 6 Z9 6 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP-OCT PY 1991 VL 9 IS 5 BP 469 EP 484 DI 10.1007/BF01785532 PG 16 WC Oncology SC Oncology GA GQ016 UT WOS:A1991GQ01600004 PM 1833108 ER PT J AU LINK, MP GOORIN, AM HOROWITZ, M MEYER, WH BELASCO, J BAKER, A AYALA, A SHUSTER, J AF LINK, MP GOORIN, AM HOROWITZ, M MEYER, WH BELASCO, J BAKER, A AYALA, A SHUSTER, J TI ADJUVANT CHEMOTHERAPY OF HIGH-GRADE OSTEOSARCOMA OF THE EXTREMITY - UPDATED RESULTS OF THE MULTIINSTITUTIONAL OSTEOSARCOMA STUDY SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID OSTEO-SARCOMA; NEOADJUVANT CHEMOTHERAPY; SURVIVAL; TRIAL AB The multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p < 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients. C1 PEDIAT ONCOL GRP, STAT OFF, GAINESVILLE, FL USA. STANFORD UNIV, MED CTR, SCH MED, STANFORD, CA 94305 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. CHILDRENS HOSP, PHILADELPHIA, PA 19104 USA. CHILDRENS HOSP MED CTR, BOSTON, MA 02115 USA. NCI, SURG ONCOL BRANCH, BETHESDA, MD 20892 USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. UNIV FLORIDA, DEPT STAT, GAINESVILLE, FL 32611 USA. UNIV TEXAS, MD ANDERSON HOSP & TUMOR INST, HOUSTON, TX 77030 USA. RP LINK, MP (reprint author), CHILDRENS HOSP STANFORD, 520 SAND HILL RD, PALO ALTO, CA 94304 USA. FU NCI NIH HHS [CA31566, CA33603, CA3713] NR 12 TC 144 Z9 148 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1991 IS 270 BP 8 EP 14 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA GF151 UT WOS:A1991GF15100003 PM 1884563 ER PT J AU GONZALEZ, FJ MEYER, UA AF GONZALEZ, FJ MEYER, UA TI MOLECULAR-GENETICS OF THE DEBRISOQUIN-SPARTEINE POLYMORPHISM SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID OXIDATIVE DRUG-METABOLISM; LUNG-CANCER RISK; HUMAN-LIVER; POOR METABOLIZERS; CYP2D LOCUS; HYDROXYLATION; DEFICIENT; PHENOTYPE; ALLELE; IDENTIFICATION C1 UNIV BASEL,BIOCTR,DEPT PHARMACOL,CH-4056 BASEL,SWITZERLAND. RP GONZALEZ, FJ (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 40 TC 139 Z9 141 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 1991 VL 50 IS 3 BP 233 EP 238 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GH634 UT WOS:A1991GH63400001 PM 1680592 ER PT J AU HARTMAN, NR YARCHOAN, R PLUDA, JM THOMAS, RV WYVILL, KM FLORA, KP BRODER, S JOHNS, DG AF HARTMAN, NR YARCHOAN, R PLUDA, JM THOMAS, RV WYVILL, KM FLORA, KP BRODER, S JOHNS, DG TI PHARMACOKINETICS OF 2',3'-DIDEOXYINOSINE IN PATIENTS WITH SEVERE HUMAN IMMUNODEFICIENCY INFECTION .2. THE EFFECTS OF DIFFERENT ORAL FORMULATIONS AND THE PRESENCE OF OTHER MEDICATIONS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID AIDS-RELATED COMPLEX; PHASE-I TRIAL; GANCICLOVIR; TOXICITY; DISEASE; PANCREATITIS; RANITIDINE; PROFILE; HIV; DDI AB 2',3'-Dideoxyinosine (ddI) has shown activity against human immunodeficiency virus in phase I clinical trials. The drug is rapidly degraded by acid, however, thus raising questions as to the efficiency and reproducibility of its absorption after oral administration. This investigation studies the bioavailability of several oral dosage forms of ddI. When ddI was given to fasting patients as an oral solution with antacid, the bioavailability was 41% +/- 7% (mean +/- SEM). However, when given as buffered tablets, the bioavailability was considerably less (25% +/- 5%). The bioavailability increased slightly when the tablets were given with supplemental antacid (36% +/- 6%). Two enteric-coated preparations had reasonable bioavailability (36% +/- 5% and 26% +/- 5%), but the peak plasma level was much lower and occurred at a much later time than with the oral solution. When ddI was given as a premeasured powder containing sucrose and buffer to be reconstituted by the patient (the "sachet" preparation), the bioavailability was 29% +/- 6%. This was similar to that of the oral solution for this particular group of patients (30% +/- 7%). However, the bioavailability of the sachet was only 17% +/- 4% when administered with food. When the sachet was given to patients receiving ranitidine, no consistent change in bioavailability was noted. Also, no change in ddI pharmacokinetics was noted in patients receiving ganciclovir. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP HARTMAN, NR (reprint author), NCI,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5B22,BETHESDA,MD 20892, USA. NR 15 TC 62 Z9 62 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 1991 VL 50 IS 3 BP 278 EP 285 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GH634 UT WOS:A1991GH63400007 PM 1914362 ER PT J AU COLE, PM AF COLE, PM TI TERRIFYING LOVE - WHY BATTERED WOMEN KILL AND HOW SOCIETY RESPONDS - WALKER,LE SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP COLE, PM (reprint author), NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1991 VL 36 IS 9 BP 768 EP 769 PG 2 WC Psychology, Multidisciplinary SC Psychology GA GC882 UT WOS:A1991GC88200024 ER PT J AU KELLER, BB AF KELLER, BB TI ANXIETY DISORDERS IN CHILDREN - KLEIN,RG, LAST,CG SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP KELLER, BB (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1991 VL 36 IS 9 BP 799 EP 800 PG 2 WC Psychology, Multidisciplinary SC Psychology GA GC882 UT WOS:A1991GC88200056 ER PT J AU NEWCOMER, S AF NEWCOMER, S TI PARENT-TEEN COMMUNICATION - TOWARD THE PREVENTION OF UNINTENDED PREGNANCIES - JACCARD,J, DITTUS,P SO CONTEMPORARY SOCIOLOGY-A JOURNAL OF REVIEWS LA English DT Book Review RP NEWCOMER, S (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0094-3061 J9 CONTEMP SOCIOL JI Contemp. Sociol.-J. Rev. PD SEP PY 1991 VL 20 IS 5 BP 788 EP 788 DI 10.2307/2072274 PG 1 WC Sociology SC Sociology GA GJ935 UT WOS:A1991GJ93500113 ER PT J AU SIBUG, ME DATILES, MB KASHIMA, K MCCAIN, L KRACHER, G AF SIBUG, ME DATILES, MB KASHIMA, K MCCAIN, L KRACHER, G TI SPECULAR MICROSCOPY STUDIES ON THE CORNEAL ENDOTHELIUM AFTER CESSATION OF CONTACT-LENS WEAR SO CORNEA LA English DT Article DE HARD CONTACT LENS; LONG-TERM LENS WEAR; CORNEAL ENDOTHELIUM; SPECULAR MICROSCOPY; POLYMEGETHISM; PLEOMORPHISM AB We performed specular microscopy on the corneal endothelium of 22 long-term hard contact lens wearers (15-32 years duration) and 22 age- and sex-matched controls. We found polymegethism in users as shown by a significant difference in the coefficient of variation in cell area (p < 0.01) and pleomorphism as shown by a significant decrease in the percent of 6-sided cells (hexagonality, p < 0.01). There was no significant difference in cell density and mean cell area between the 2 groups. Contact lens wear was discontinued in five eyes of three patients after they were entered into the study and switched to eye-glasses. Specular micrographs were taken up to 60 months after discontinuation of use of the lenses. Comparison of the above parameters before and after discontinuation of the lenses did not show a significant change. However, there was a trend toward improvement in the coefficient of variation in the eyes that were followed the longest. This finding suggests that the morphological changes induced by long-term use of contact lenses may be slowly reversible after prolonged discontinuation of contact lens wear. C1 NEI,CLIN BRANCH 3,BLDG 10,ROOM 10N-226,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 0 TC 18 Z9 19 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 1991 VL 10 IS 5 BP 395 EP 401 DI 10.1097/00003226-199109000-00007 PG 7 WC Ophthalmology SC Ophthalmology GA GC699 UT WOS:A1991GC69900007 PM 1935137 ER PT J AU MICHIEL, DF GARCIA, GG EVANS, GA FARRAR, WL AF MICHIEL, DF GARCIA, GG EVANS, GA FARRAR, WL TI REGULATION OF THE INTERLEUKIN-2 RECEPTOR COMPLEX TYROSINE KINASE-ACTIVITY INVITRO SO CYTOKINE LA English DT Article DE IL-2; RECEPTOR; PROTEIN KINASES ID P70-75 BETA-SUBUNIT; IL-2 RECEPTOR; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; PROTEIN-KINASES; GROWTH-HORMONE; ALPHA-CHAIN; EXPRESSION; BINDING; PHOSPHORYLATION C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 34 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 1991 VL 3 IS 5 BP 428 EP 438 DI 10.1016/1043-4666(91)90047-H PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA GH858 UT WOS:A1991GH85800009 PM 1751780 ER PT J AU FLANDERS, KC LUDECKE, G ENGELS, S CISSEL, DS ROBERTS, AB KONDAIAH, P LAFYATIS, R SPORN, MB UNSICKER, K AF FLANDERS, KC LUDECKE, G ENGELS, S CISSEL, DS ROBERTS, AB KONDAIAH, P LAFYATIS, R SPORN, MB UNSICKER, K TI LOCALIZATION AND ACTIONS OF TRANSFORMING GROWTH FACTOR-BETA-S IN THE EMBRYONIC NERVOUS-SYSTEM SO DEVELOPMENT LA English DT Article DE IMMUNOHISTOCHEMISTRY; TGF-BETA; CENTRAL NERVOUS SYSTEM; PERIPHERAL NERVOUS SYSTEM; DEVELOPMENT ID DEOXYRIBONUCLEIC-ACID CLONING; PLASMINOGEN-ACTIVATOR; NEURONOTROPHIC FACTOR; MESSENGER-RNA; ADULT TISSUES; CELLS; FACTOR-BETA-1; EXPRESSION; SURVIVAL; NEURONS AB We present evidence for unique localization and specific biological activities for transforming growth factor-beta-s (TGF-beta-s) 2 and 3, as compared to TGF-beta-1, in the nervous system of the 12-18 day mouse embryo. Each TGF-beta isoform was localized immunohistochemically by specific antibodies raised to peptides corresponding to unique sequences in the respective TGF-beta proteins. Staining for TGF-beta-1 was principally in the meninges, while TGF-beta-s 2 and 3 co-localized in neuronal perikarya and axons, as well as in radial glial cells. In the central nervous system, staining was most prominent in zones where neuronal differentiation occurs and less intense in zones of active proliferation, while in the peripheral nervous system, many nerve fibers as well as their cell bodies were strongly immunoreactive for TGF-beta-s 2 and 3. Functionally, we have also found that in the presence of an extract of chick eye tissue, TGF-beta-s 2 and 3 inhibit survival of cultured embryonic chick ciliary ganglionic neurons in a dose-dependent fashion; TGF-beta-1 shows no inhibitory effects. Our data suggest that TGF-beta-s 2 and 3 may play a role in regulation of neuronal migration and differentiation, as well as in glial cell proliferation and differentiation. C1 UNIV MARBURG,DEPT ANAT & CELL BIOL,W-3550 MARBURG,GERMANY. RP FLANDERS, KC (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,BETHESDA,MD 20892, USA. NR 52 TC 339 Z9 343 U1 0 U2 2 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 1991 VL 113 IS 1 BP 183 EP & PG 0 WC Developmental Biology SC Developmental Biology GA GE976 UT WOS:A1991GE97600014 PM 1764993 ER PT J AU SNAPE, AM WINNING, RS SARGENT, TD AF SNAPE, AM WINNING, RS SARGENT, TD TI TRANSCRIPTION FACTOR-AP-2 IS TISSUE-SPECIFIC IN XENOPUS AND IS CLOSELY RELATED OR IDENTICAL TO KERATIN TRANSCRIPTION FACTOR-I (KTF-1) SO DEVELOPMENT LA English DT Article DE XENOPUS; EMBRYO; KERATIN; TRANSCRIPTION FACTOR; AP-2 ID EPIDERMAL DIFFERENTIATION; ENHANCER ELEMENTS; RETINOIC ACID; FACTOR AP-2; GENE; EXPRESSION; LAEVIS; IDENTIFICATION; ACTIVATOR; SEQUENCES AB This paper identifies a new, developmental role for transcription factor AP-2 in the activation of amphibian embryonic epidermal keratin gene expression. Keratin transcription factor KTF-1 is shown by several criteria to be identical or closely related to AP-2. KTF-1/AP-2 is shown to be tissue-specific from its first transcription in Xenopus embryos, and restricted to a small number of adult tissues, including skin. Epidermis-specific keratin transcription closely follows specification of the embryonic ectoderm in Xenopus, and is subject to regulation by growth factors and embryonic induction. We further show that in mouse basal keratinocytes, a KTF-1/AP-2-like factor is present and binds to a DNA sequence previously shown to be important in the regulation of the keratin K14 gene, which is actively expressed in these cells. Thus, the study of AP-2 and its role in the regulation of keratin gene transcription should enhance our understanding of both amphibian embryonic development and mammalian skin differentiation. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 29 TC 85 Z9 85 U1 1 U2 1 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 1991 VL 113 IS 1 BP 283 EP 293 PG 11 WC Developmental Biology SC Developmental Biology GA GE976 UT WOS:A1991GE97600024 PM 1722450 ER PT J AU HOGAN, A HEYNER, S CHARRON, MJ COPELAND, NG GILBERT, DJ JENKINS, NA THORENS, B SCHULTZ, GA AF HOGAN, A HEYNER, S CHARRON, MJ COPELAND, NG GILBERT, DJ JENKINS, NA THORENS, B SCHULTZ, GA TI GLUCOSE TRANSPORTER GENE-EXPRESSION IN EARLY MOUSE EMBRYOS SO DEVELOPMENT LA English DT Article DE MOUSE EMBRYOS; GLUCOSE TRANSPORTERS; POLYMERASE CHAIN REACTION ID ACTIN MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; PLASMA-MEMBRANE; SKELETAL-MUSCLE; GROWTH-FACTORS; INSULIN; PROTEIN; INVITRO; CELL; LOCALIZATION AB The glucose transporter (GLUT) isoforms responsible for glucose uptake in early mouse embryos have been identified. GLUT 1, the isoform present in nearly every tissue examined including adult brain and erythrocytes, is expressed throughout preimplantation development. GLUT 2, which is normally present in adult liver, kidney, intestine and pancreatic beta-cells is expressed from the 8-cell stage onward. GLUT 4, an insulin-recruitable isoform, which is expressed in adult fat and muscle, is not expressed at any stage of preimplantation development or in early postimplantation stage embryos. Genetic mapping studies of glucose transporters in the mouse show that Glut-1 is located on chromosome 4, Glut-2 on chromosome 3, Glut-3 on chromosome 6, and Glut-4 on chromosome 11. C1 NCI,FREDERICK CANC RES LAND DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. UNIV PENN,MED CTR,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. RP SCHULTZ, GA (reprint author), UNIV CALGARY,HLTH SCI CTR,DEPT MED BIOCHEM,3330 HOSP DR NW,CALGARY T2N 4N1,ALBERTA,CANADA. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD 23511]; NIDDK NIH HHS [DK-08101] NR 64 TC 142 Z9 146 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 1991 VL 113 IS 1 BP 363 EP 372 PG 10 WC Developmental Biology SC Developmental Biology GA GE976 UT WOS:A1991GE97600031 PM 1765007 ER PT J AU CORMONT, M MARCHANDBRUSTEL, YL VANOBBERGHEN, E SPIEGEL, AM SHARP, GWG AF CORMONT, M MARCHANDBRUSTEL, YL VANOBBERGHEN, E SPIEGEL, AM SHARP, GWG TI IDENTIFICATION OF G PROTEIN ALPHA-SUBUNITS IN RINM5F CELLS AND THEIR SELECTIVE INTERACTION WITH GALANIN RECEPTOR SO DIABETES LA English DT Article ID INHIBITS INSULIN-SECRETION; NUCLEOTIDE-BINDING PROTEIN; FREE CA-2+ CONCENTRATION; SENSITIVE-G-PROTEIN; PERTUSSIS-TOXIN; MOLECULAR CHARACTERIZATION; GUANINE-NUCLEOTIDES; ADENYLATE-CYCLASE; HIGH-AFFINITY; K+ CHANNELS AB Galanin, an inhibitor of insulin secretion in pancreatic beta-cells, exerts its multiple effects through mechanisms that are sensitive to pertussis toxin (PTX). G proteins have been characterized in RINm5F cells. By ADP ribosylation and immunoblotting, the alpha-subunits of G(i1), G(i2), G(i3), and two forms of G(o) were identified, G(i-alpha-2) being predominant. As expected from a G protein-linked receptor, GTP and its nonhydrolyzable analogue GTP-gamma-S decreased tracer galanin binding to cell membranes. This resulted from a change in receptor affinity without any modification in the number of sites. Selective antibodies against the COOH-terminal decapeptide of the alpha-subunits of the G(i) and G(o) proteins were used to block G protein interaction before we studied galanin binding. Antibody AS, which selectively recognizes G(i-alpha-1), and G(i-alpha-2), decreased tracer galanin binding to membranes at concentrations where there were no effects of other antibodies specifically directed against G(i-alpha-3) or G-alpha-o. These data suggest that G(i1) and/or G(i2) interact with the galanin receptor and probably mediate the effects of galanin in pancreatic beta-cells. C1 CORNELL UNIV,COLL VET MED,DEPT PHARMACOL,ITHACA,NY 14853. FAC MED NICE,NATL INST HLTH & MED RES,UNIT 145,F-06034 NICE,FRANCE. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD. NR 32 TC 50 Z9 50 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1991 VL 40 IS 9 BP 1170 EP 1176 DI 10.2337/diabetes.40.9.1170 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GC611 UT WOS:A1991GC61100014 PM 1718802 ER PT J AU PERANTONI, AO DOVE, LF WILLIAMS, CL AF PERANTONI, AO DOVE, LF WILLIAMS, CL TI INDUCTION OF TUBULES IN RAT METANEPHROGENIC MESENCHYME IN THE ABSENCE OF AN INDUCTIVE TISSUE SO DIFFERENTIATION LA English DT Article ID TRANSFILTER INDUCTION; KIDNEY-TUBULES; ORGAN-CULTURE; EMBRYONIC INDUCTION; EPITHELIAL-CELLS; DEFINED MEDIUM; GROWTH-FACTOR; ETHYLNITROSOUREA; DIFFERENTIATION; ORGANOGENESIS AB Differentiation of metanephrogenic mesenchyme to renal tubular epithelium requires induction by the ureteric bud in vivo or any of several embryonic tissues in vitro. In an effort to eliminate the tissue requirement in embryonic induction, extracellular matrices and soluble factors were analyzed individually or in combination for their ability to stimulate tubulogenesis in uninduced metanephrogenic mesenchyme from 13-gestation-day rat embryos. These evaluations have established that pituitary extract and epidermal growth factor (EGF) in concert with a matrix can promote morphogenesis of mesenchymal rudiments in culture. While type I collagen, laminin, or fibronectin matrices all promoted tubulogenesis in the presence of pituitary extract and EGF, type IV collagen proved the most effective. Under these conditions, tubules were induced in 23/24 mesenchymal rudiments by 9 days in culture. Mesenchyme was not induced prior to explanation since it formed no tubules when cultured in a medium that allowed tubulogenesis in intact embryonic kidneys. Preliminary characterization of the undefined factor in pituitary extract was consistent with a protein of molecular weight > 100 000 but < 300 000. When uninduced metanephrogenic mesenchyme from mouse was used instead of rat tissue, a similar pattern of morphogenesis was not observed, suggesting that the described medium is inappropriate for promoting differentiation in mouse or, less likely, that different mechanisms mediate differentiation in rat and mouse. These studies show that embryonic induction can occur in explanted rat renal mesenchyme in an appropriate environment and does not require the presence of an inductive tissue. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP PERANTONI, AO (reprint author), UNIV COLORADO,SCH MED,DEPT PATHOL,BOX B-216,4200 E 9TH ST,DENVER,CO 80262, USA. NR 35 TC 36 Z9 36 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 1991 VL 48 IS 1 BP 25 EP 31 DI 10.1111/j.1432-0436.1991.tb00239.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GH935 UT WOS:A1991GH93500004 PM 1743431 ER PT J AU DEMIGUEL, C KLIGMAN, D PATEL, J DETERAWADLEIGH, SD AF DEMIGUEL, C KLIGMAN, D PATEL, J DETERAWADLEIGH, SD TI MOLECULAR ANALYSIS OF MICROTUBULE-ASSOCIATED PROTEIN-2 KINASE-CDNA FROM MOUSE AND RAT-BRAIN SO DNA AND CELL BIOLOGY LA English DT Article ID ALZHEIMER NEUROFIBRILLARY TANGLES; ALPHA-FACTOR RECEPTOR; CELL-CYCLE CONTROL; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; S-CEREVISIAE; CALMODULIN-BINDING; FISSION YEAST; HUMAN GAP-43; G1 ARREST AB We have isolated and characterized brain cDNA clones encoding microtubule-associated protein-2 (MAP-2) kinase for rat (rMNK1) and mouse (mMNK1). The nucleotide sequences diverged by only 5% whereas the amino acid sequences were identical except for one conservative residue change. Conservation of the expressed sequence extended into other mammalian species. These findings constitute the first demonstration of a strict evolutionary conservation of MAP-2 kinase. Genomic restriction patterns revealed a single MAP-2 kinase gene that shares homology with other genomic sequences. The 3' terminal half of the gene appears to be encoded by four exons. rMNK1 and mMNK1 differed from a recently reported MAP-2 kinase cDNA, termed ERK1, because of a nonconservative change in position 82, from Gly in ERK1 to Arg in rMNK1. The rMNK1 gene was found to be expressed mainly as a 1.8-kb transcript that was highest in brain and in lung. In contrast to ERK1, rMNK1 showed two equally prominent mRNA species in liver, at 1.8 kb and 5 kb, which imply differential processing of the primary transcript. Results derived from the immunological screening of an expression library showed that MAP-2 kinase might share epitopes with two prominent protein kinase C substrates, MARCKS (an 80-kD protein kinase C substrate) and GAP-43, suggesting the possibility that MAP-2 kinase could interact with kinase C. C1 NIMH,DIV INTRAMURAL RES PROGRAMS,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 58 TC 6 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1991 VL 10 IS 7 BP 505 EP 514 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA GF198 UT WOS:A1991GF19800004 PM 1716439 ER PT J AU HAQUE, SJ PETERSEN, DD NEBERT, DW MACKENZIE, PI AF HAQUE, SJ PETERSEN, DD NEBERT, DW MACKENZIE, PI TI ISOLATION, SEQUENCE, AND DEVELOPMENTAL EXPRESSION OF RAT UGT2B2 - THE GENE ENCODING A CONSTITUTIVE UDP GLUCURONOSYLTRANSFERASE THAT METABOLIZES ETIOCHOLANOLONE AND ANDROSTERONE SO DNA AND CELL BIOLOGY LA English DT Article ID CDNA; DNA; PROMOTER; CLONING; GLUCURONYLTRANSFERASE; ORGANIZATION; ENZYMES; FAMILY; FORM; RNA AB The UDP glucuronosyltransferase gene UGT2B2 is constitutively expressed in rat liver, and the enzyme has been shown to conjugate glucuronic acid with various endogenous steroids, especially etiocholanolone and androsterone. We have cloned and sequenced much of the UGT2B2 gene and 5'-flanking (247 bp) and 3'-flanking (734 bp) regions. The gene contains six exons spanning about 15.3 kb. Translation begins at nucleotide 36 of exon 1 and terminates with 280 coding nucleotides into exon 6, encoding a protein of 530 amino acids (calculated M(r) of the unmodified chain = 60,913). We have determined that the UGT2B2 full-length cDNA is 1,974 bp. Northern hybridization revealed that the hepatic UGT2B2 transcript is detectable 4 days before birth, becomes markedly elevated in the neonate, and is even further increased at 3 and 12 weeks of age in the liver of both male and female rats. C1 NICHHD,DEV PHARMACOL LAB,BETHESDA,MD 20892. NR 29 TC 52 Z9 53 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1991 VL 10 IS 7 BP 515 EP 524 DI 10.1089/dna.1991.10.515 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA GF198 UT WOS:A1991GF19800005 PM 1909872 ER PT J AU DEY, A NEBERT, DW OZATO, K AF DEY, A NEBERT, DW OZATO, K TI THE AP-1 SITE AND THE CAMP- AND SERUM RESPONSE ELEMENTS OF THE C-FOS GENE ARE CONSTITUTIVELY OCCUPIED INVIVO SO DNA AND CELL BIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ELEMENTS; TRANSCRIPTION FACTOR AP-1; EPIDERMAL GROWTH-FACTOR; PROTO-ONCOGENE FOS; LEUCINE ZIPPER; CYCLIC-AMP; 12-O-TETRADECANOYL PHORBOL-13-ACETATE; MEDIATE INDUCTION; COMPLEX-FORMATION; BINDING PROTEIN AB The c-fos proto-oncogene is inducible by cAMP, phorbol esters, serum, and growth factors. The induction by cAMP is mediated by the conserved cAMP response element (CRE), while induction by phorbol esters, serum, and growth factors requires a distal element called the serum response element (SRE). In addition to these elements, a consensus AP-1 transcription factor binding site is located next to SRE. Upstream regions of the mouse and human c-fos genes were footprinted in vivo by the ligation-mediated polymerase chain (PCR). Our results show that all three elements are constitutively protected in mouse liver and lung and in cultured human A431 cells. No major change in the protection profile was detected in A431 cells following stimulation with epidermal growth factor or in mice at birth, when c-fos is known to be induced. These results suggest that the inducible cis elements of the c-fos gene are poised, ready to respond immediately to external signals. C1 NICHHD,DEV & MOLEC IMMUNITY LAB,BLDG 6,ROOM 2A01,BETHESDA,MD 20892. NICHHD,DEV PHARMACOL LAB,BETHESDA,MD 20892. NR 50 TC 25 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1991 VL 10 IS 7 BP 537 EP 544 DI 10.1089/dna.1991.10.537 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA GF198 UT WOS:A1991GF19800007 PM 1832543 ER PT J AU FRIEDMAN, L SCHRON, E YUSUF, S AF FRIEDMAN, L SCHRON, E YUSUF, S TI RISK-BENEFIT ASSESSMENT OF ANTIARRHYTHMIC DRUGS - AN EPIDEMIOLOGIC PERSPECTIVE SO DRUG SAFETY LA English DT Article RP FRIEDMAN, L (reprint author), NHLBI,CLIN TRIALS BRANCH,CAPP,FED BLDG,ROOM 5CO1,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD SEP-OCT PY 1991 VL 6 IS 5 BP 323 EP 331 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA GF817 UT WOS:A1991GF81700002 PM 1930738 ER PT J AU BOCEK, P CHRAMBACH, A AF BOCEK, P CHRAMBACH, A TI ELECTROPHORETIC SIZE SEPARATIONS IN LIQUEFIED AGAROSE OF POLYSTYRENE PARTICLES AND CIRCULAR DNA SO ELECTROPHORESIS LA English DT Article ID GEL ELECTROPHORESIS; POLYACRYLAMIDE AB Polystyrene sulfate particles of 0.37 to 1.78-mu in diameter are retarded in their electrophoretic migration in proportion to the concentration of agarose liquified above its gelling temperature. In the concentration range of 0.02 to 0.2% liquified agarose, the degree of this retardation in electrophoresis at 40-degrees-C is inversely related to particle size. By contrast, mitochondrial DNA (16 kb), plasmid pBR322 DNA (4 kb) and plasmid PSA509 DNA (3 kb) exhibit under the same conditions a degree of retardation which is proportional to their size. This confirms the existence of two divergent mechanisms of size separation similarly observed in other liquid polymer media, i.e. one based on collisions with the gel fiber (molecular sieving) and one based on exclusion from the fiber network (the electrophoretic equivalent of gel permeation). C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NR 14 TC 19 Z9 19 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 1991 VL 12 IS 9 BP 620 EP 623 DI 10.1002/elps.1150120904 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GJ266 UT WOS:A1991GJ26600003 PM 1752241 ER PT J AU DEML, M GARNER, MM CHRAMBACH, A AF DEML, M GARNER, MM CHRAMBACH, A TI ELECTROPHORESIS WITH INTERMITTENT SCANNING OF THE MIGRATION PATH - DETECTION OF RESOLUTION WITHIN SHORTENED TIME SO ELECTROPHORESIS LA English DT Article ID POLYACRYLAMIDE-GEL ELECTROPHORESIS AB Intermittent optical scanning (by detection of optical density or fluorescence) of the electrophoretic migration path was applied to the resolution of two dyes under an arbitrary set of conditions. Scanning at 5-min intervals allows for detection of resolution between the two zones at least 3 times faster than conventional automatic zone detection employing a detector at the end of the migration path. This result promises that replacing stationary by mobile detectors in general would result in a substantial time saving for automated detection of electrophoretic zones. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NR 10 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 1991 VL 12 IS 9 BP 641 EP 645 DI 10.1002/elps.1150120908 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GJ266 UT WOS:A1991GJ26600007 PM 1752244 ER PT J AU HE, CY MERRICK, BA MANSFIELD, BK HITE, MC DALUGE, DR SELKIRK, JK AF HE, CY MERRICK, BA MANSFIELD, BK HITE, MC DALUGE, DR SELKIRK, JK TI COMPARISON OF C-14 AMINO-ACID MIXTURE AND (S-35)METHIONINE LABELING OF CELLULAR PROTEINS FROM MOUSE FIBROBLAST C3H10T1/2 CELLS BY 2-DIMENSIONAL GEL-ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article ID CYCLIN MESSENGER-RNA; ROUS-SARCOMA VIRUS; DIMENSIONAL ELECTROPHORESIS; POSTCONFLUENCE INHIBITION; POLYACRYLAMIDE GELS; GENE-EXPRESSION; MAMMALIAN-CELL; TRANSFORMATION; POLYPEPTIDES; CHROMOSOMES AB Total cellular proteins from mouse C3H10T1/2 fibroblasts were compared by two-dimensional (2-D) gel electrophoresis after radiolabeling with [S-35]methionine (S-35-Met) or C-14-amino acids (C-14-AA). S-35-Met labeling of protein was three to four times greater than C-14-AA incorporation over a 24 h period. Automated comparative analysis of replicate fluorographs after 6, 12, and 24 h of labeling showed considerable homology between radiolabeling methods. More than 88% percent of S-35-Met and C-14-AA-labeled proteins were common at each time point. However, the total number of S-35-Met-labeled proteins dropped from 6 to 24 h while the number of C-14-AA-labeled proteins increased. Additionally, twenty-one proteins were uniquely labeled by C-14-AA that were not detectable by S-35-Met over the labeling period. Densimetric analysis showed that several S-35-Met and C-14-AA-labeled proteins exhibited time-related differences in radiolabel incorporation while most proteins remained relatively constant. Protein patterns of silver-stained gels from 6 to 24 h were highly registered and showed few qualitative differences. Proteins detected in radiolabeled gels were generally, but not always, found in silver-stained gels. Thus, S-35-Met appears better suited for short-term radiolabeling of cellular protein while more comprehensive labeling of protein occurs with C-14-AA during prolonged incubation of cell cultures under present experimental conditions. C1 OAK RIDGE NATL LAB,DIV HLTH & SAFETY RES,OAK RIDGE,TN. RP HE, CY (reprint author), NIEHS,DIV TOXICOL RES & TESTING,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 5 Z9 5 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 1991 VL 12 IS 9 BP 658 EP 666 DI 10.1002/elps.1150120911 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GJ266 UT WOS:A1991GJ26600010 PM 1752247 ER PT J AU KESHET, E LYMAN, SD WILLIAMS, DE ANDERSON, DM JENKINS, NA COPELAND, NG PARADA, LF AF KESHET, E LYMAN, SD WILLIAMS, DE ANDERSON, DM JENKINS, NA COPELAND, NG PARADA, LF TI EMBRYONIC RNA EXPRESSION PATTERNS OF THE C-KIT RECEPTOR AND ITS COGNATE LIGAND SUGGEST MULTIPLE FUNCTIONAL ROLES IN MOUSE DEVELOPMENT SO EMBO JOURNAL LA English DT Article DE DEVELOPMENT; C-KIT; MOUSE; STEEL; WHITE SPOTTING ID CELL GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; PRIMORDIAL GERM-CELLS; STEEL MUTANT MICE; SPOTTING W LOCUS; SI-LOCUS; PROTO-ONCOGENE; PROTOONCOGENE; GUIDANCE; ALLELES AB Mutations at the dominant white spotting (W) and Steel (Sl) loci in mouse exert deleterious effects on three migratory cell lineages (primordial germ cells, melanocytes and hematopoietic stem cells) resulting in loss of pigmentation, reduced fertility and anemia. The W locus encodes the c-kit protein tyrosine kinase (TK) receptor. More recently, the Sl locus has been shown to encode a ligand for c-kit, which is variously known as mast cell growth factor (MGF), stem cell growth factor and c-kit ligand. Here we report an in situ hybridization analysis comparing the expression profiles of MGF and c-kit transcripts during mouse embryogenesis. The data are consistent with the c-kit receptor-ligand complex providing a homing mechanism during stem cell migration in early development and in stem cell proliferation, differentiation, or survival in late development. In the nervous system, an unexpected and complex pattern of expression is uncovered that suggests involvement of the W and Sl gene products in the organization of the neural tube and brain. C1 NCI,FREDERICK CANC RES FACIL,ANIM BIOL LAB,BASIC RES PROGRAM,FREDERICK,MD 21701. IMMUNEX CORP,SEATTLE,WA 98101. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 54 TC 303 Z9 304 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP PY 1991 VL 10 IS 9 BP 2425 EP 2435 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GB448 UT WOS:A1991GB44800012 PM 1714375 ER PT J AU JOHNSON, MC AGUILERA, G AF JOHNSON, MC AGUILERA, G TI ANGIOTENSIN-II RECEPTOR SUBTYPES AND COUPLING TO SIGNALING SYSTEMS IN CULTURED FETAL FIBROBLASTS SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNAS; ADENYLATE-CYCLASE; ALDOSTERONE PRODUCTION; UNTRANSLATED REGION; CELLS; EXPRESSION; BINDING; PROTEIN; INVITRO; FETUS AB Angiotensin-II (AII) receptors and their coupling to signaling transduction systems were studied in fetal skin fibroblasts using the receptor subtype-specific antagonists Dup753 (type 1) and PD123177 (type 2). In primary cultures, total binding per cell remained constant from days 2-6 of culture, but after subculture levels were initially decreased, then increased until the cells reached confluence. In freshly isolated cells more than 90% of the receptors were type 2, and only a minor fraction were type 1, findings that are consistent with autoradiographic analyses and membrane binding assays. The proportions tended to reverse during culture, with type 1 receptors accounting for 60-80% and type 2 for 20-40% by day 6 of culture. In secondary culture, subtype 1 was about 50% on day 1 and increased to 70% by day 6. At subsequent passages, the proportion of receptor subtypes remained constant up to 6 days, with 90% being of the type 1 variety and 10% of type 2. Scatchard analysis of binding in the presence of the selective antagonists showed similar binding affinities for both subtypes, and the changes in receptor subtype during culture were due primarily to changes in receptor number. Treatment of primary cultures with actinomycin-D for 24 h prevented the transition from AII receptor type 2 to type 1 by increasing the absolute number of type 2 receptors, suggesting that receptor synthesis is regulated at the posttranscriptional level. Stimulation of the cells with 100 nM AII resulted in increases in inositol phosphate accumulation, an effect that was prevented by the type 1 antagonist, but not by the type 2 antagonist. In contrast with other systems in which AII inhibits adenylate cyclase, in fetal fibroblasts AII stimulated cAMP production. The increases in cAMP were more pronounced in secondary cultures in which type 1 receptor content is higher, and the effect was prevented by the type 1, but not the type 2, antagonists. These findings demonstrate the presence of both AII receptor subtypes in fetal fibroblasts, but only the type 1 receptors are coupled to a known intracellular signalling system. The changes in AII receptor subtypes may be the consequence of alterations in intercellular communication, endocrine, or paracrine factors during culture. C1 NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NR 37 TC 54 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1991 VL 129 IS 3 BP 1266 EP 1274 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GD333 UT WOS:A1991GD33300020 PM 1651843 ER PT J AU LOPEZ, FJ SANCHEZCRIADO, JE NEGROVILAR, A AF LOPEZ, FJ SANCHEZCRIADO, JE NEGROVILAR, A TI A PHYSIOLOGICAL-ROLE FOR SPORADIC INTERRUPTIONS OF THE DOPAMINERGIC TONE IN THE GENESIS OF BIG MASS PROLACTIN PULSES SO ENDOCRINOLOGY LA English DT Article ID VASOACTIVE INTESTINAL PEPTIDE; THYROTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; HYPOPHYSEAL PORTAL BLOOD; LUTEINIZING-HORMONE; OVARIECTOMIZED RATS; EPISODIC PROLACTIN; GROWTH-HORMONE; ESTROUS-CYCLE; SECRETION AB The present studies were designed to evaluate pulsatile PRL secretion after the establishment of either a continuous dopaminergic input or a complete blockade of the dpaminergic inhibitory tone. Adult female rats on estrus and male rats implanted with indwelling jugular cannulae were bled at 3-min intervals for a 3-h period. Bromocriptine (CB-154) and domperidone (DOM) were administered sc and iv, respectively. The administration protocol used for both treatments produced either a continuous dopaminergic input (CB-154 treatment) or a complete dopaminergic blockade (DOM treatment). Pulse analysis was performed on the data series using the algorithm Detect. In both estrous female and male rats, dopaminergic receptor activation by CB-154 reduced peak and trough values, pulse amplitude, area under the pulse, and mean PRL levels. In contrast, a complete dopamine (DA) receptor blockade by DOM increased these parameters. Domperidone treatment increased pulse frequency and reduced pulse interval and duration. Bromocriptine, however, differentially affected some pulsatility parameters depending on the sex of the rats. In females, CB-154 did not alter any of the qualitative parameters (frequency, pulse interval, and duration) of pulsatile PRL secretion. In contrast, in male rats the treatment reduced frequency and duration while increasing pulse interval. CB-154 reduced basal PRL levels in male rats, whereas in estrous females this parameter was not altered. PRL pulses were further evaluated by frequency distribution analysis, using the area under the pulses divided by the baseline to normalize the data due to treatment-induced differences in baselines. This calculation allows the estimation of the amount of hormone released per pulse over the baseline. In both estrous female and male rats, two classes of PRL pulses were identified. One class corresponded to pulses containing a small mass of hormone [small mass pulses (SM)], while the others were characterized by pulses containing a large mass of hormone [big mass pulses (BM)]. Interestingly, both the dopaminergic agonist CB-154 and the dopaminergic antagonist DOM dramatically diminished BM pulse incidence in both estrous female and male rats. In fact, BM pulses were practically absent in both experimental groups. To further substantiate this notion, animals of each experimental group were assigned to one of the following categories: animals depicting BM and SM pulses or rats presenting solely SM pulses. Statistical analysis using Fisher's test demonstrated that both treatments significantly reduced the number of animals showing both BM and SM pulses, reinforcing the idea that both treatments changed the physiological pattern, i.e. presence of both BM and SM pulses, to a pattern characterized by the presence of only SM PRL pulses. This study indicates that DA is an important inhibitory regulator of pulsatile PRL secretion. The results demonstrate that BM PRL pulses originate from a discontinuous inhibitory dopaminergic tone. This is based on the observation that BM PRL pulses are suppressed by either continuous blockade or activation of the dopaminergic input. SM PRL pulses appear to be DA independent and, thereby, mediated by stimulatory neural inputs that are able to induce PRL secretion even in the presence of a continuous and strong dopaminergic tone. RP LOPEZ, FJ (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 16 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1991 VL 129 IS 3 BP 1471 EP 1480 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GD333 UT WOS:A1991GD33300048 PM 1874184 ER PT J AU LIPOSITS, Z MERCHENTHALER, I WETSEL, WC REID, JJ MELLON, PL WEINER, RI NEGROVILAR, A AF LIPOSITS, Z MERCHENTHALER, I WETSEL, WC REID, JJ MELLON, PL WEINER, RI NEGROVILAR, A TI MORPHOLOGICAL CHARACTERIZATION OF IMMORTALIZED HYPOTHALAMIC NEURONS SYNTHESIZING LUTEINIZING-HORMONE-RELEASING HORMONE SO ENDOCRINOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; IMMUNOCYTOCHEMICAL LOCALIZATION; PREOPTIC AREA; RAT-BRAIN; LHRH PRECURSOR; GNRH NEURONS; PEPTIDE; MOUSE; GENE; PROHORMONE AB An immortalized LHRH cell line has recently been developed by genetically targeting these neurons for tumorigenesis. One of the subclones, the GT1-7 cells, was characterized at both the light and electron microscopic levels to study the cellular and subcellular organization of these cells, particularly as they relate to biosynthesis, processing, and secretion. The cells were fixed onto slides 18-36 h after plating. LHRH and GnRH-associated peptide (GAP) immunoreactivities (IR) were detected by immunocytochemistry using colloidal gold labeling. These cultured cells exhibited the classical neuronal appearance of LHRH neurons, and they established numerous interconnections. Neighboring neurons were coupled by tight junctions, while more distant cells were interconnected with neural axon-like processes and collaterals. This cellular organization is suggestive of a neural network where neuronal activity is coordinated. At the ultrastructural level, the nondividing cells possessed indented nuclei, well developed Golgi complexes, and abundant numbers of ribosomes and secretory granules. Clathrin-coated vesicles were found in fusion with the plasma membrane. The ribosomes and secretory vesicles were particularly prominent, suggestive of high rates of protein biosynthesis and secretion. All of the cells immunostained for both LHRH and GAP; however, GAP IR was always more pronounced than that for LHRH. This finding was corroborated by biochemical data reported in a companion paper. The GAP IR was associated with ribosomes and secretory vesicles. By comparison, LHRH IR was restricted mainly to the secretory vesicles. Using colloidal gold particles of different sizes to denote LHRH or GAP IR, it was determined that both GAP and LHRH IR were colocalized within the same secretory vesicle. Taken together, these data suggest that pro-LHRH is biosynthesized on the ribosomes, packaged as an intact protein into the secretory vesicles, processed to LHRH and GAP-(1-56) within these vesicles, and transported to the periphery of the cell in preparation for secretion. These morphological data emphasize the utility of using these immortalized LHRH neuronal cells to dissect the cellular and subcellular architecture involved in biosynthesis, processing, and secretion. In addition, our results provide the first detailed evidence for the intracellular pathway involved in pro-LHRH biosynthesis, processing, and secretion in these cultured neuronal cells. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI,REPROD NEUROENDOCRINOL,POB 12233,RES TRIANGLE PK,NC 27709. SALK INST BIOL STUDIES,LA JOLLA,CA 92037. UNIV CALIF SAN FRANCISCO,CTR REPROD ENDOCRINOL,SAN FRANCISCO,CA 94143. FU NIDDK NIH HHS [R01 DK044838] NR 28 TC 119 Z9 119 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1991 VL 129 IS 3 BP 1575 EP 1583 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GD333 UT WOS:A1991GD33300060 PM 1874189 ER PT J AU WETSEL, WC MELLON, PL WEINER, RI NEGROVILAR, A AF WETSEL, WC MELLON, PL WEINER, RI NEGROVILAR, A TI METABOLISM OF PRO-LUTEINIZING HORMONE-RELEASING HORMONE IN IMMORTALIZED HYPOTHALAMIC NEURONS SO ENDOCRINOLOGY LA English DT Article ID HYPOPHYSEAL PORTAL BLOOD; RAT HYPOTHALAMUS; MEDIAN-EMINENCE; PEPTIDE GAP; IMMUNOCYTOCHEMICAL LOCALIZATION; MOLECULAR-FORMS; LHRH PRECURSOR; GNRH NEURONS; PITUITARY; PROHORMONE AB An immortalized hypothalamic neuronal cell line was recently developed by genetically targeting the expression of the simian virus-40 large T-antigen in LHRH neurons. These GT1 cells were subcloned to GT1-1, GT1-3, and GT1-7 cells, and they have been shown to express the mRNA for pro-LHRH and secrete LHRH-like immunoreactive (IR) materials into the media. The purpose of our study was to biochemically and immunologically characterize the IR materials within and secreted from these cells. Both LHRH- and GnRH-associated peptide (GAP)-like IR materials were present and were secreted from these four cell lines. Up to 3% of the total cellular protein was composed of LHRH and GAP materials. When materials from the cell lysate and media were separated according to mol wt (M(r)), at least three different pro-LHRH species were detected. These precursors contained both LHRH- and GAP-like IR determinants, and they eluted in the void volume and at approximately 10,000-12,000 and 8,400-8,500 M(r). A material that contained GAP-like IR eluted at approximately 6,500-6,800 M(r). This species is probably mouse GAP-(1-56) because it eluted on a reverse phase column in the approximate position of rat GAP-(1-56). Cell lysates contained a single LHRH-like IR form which coeluted on a size-exclusion column with synthetic LHRH. This material stimulated secretion of LH from anterior pituitary cells in a dose-response manner. By comparison, two different molecular forms of LHRH were detected in media at approximately 1,500 and 540 M(r). HPLC analyses revealed these peaks to be heterogeneous and to contain at least (Gln1)LHRH-(Gly11,Lys12,Arg13), (Gln1)LHRH-(Gly1,Lys12), LHRH-(Gly11), and LHRH. These experiments demonstrate that the cells contain and secrete multiple molecular forms of the pro-LHRH and that processing of the prohormone must involve 1) cleavage by an endopeptidase to give GAP-(1-56) and a C-terminally extended LHRH, 2) removal of C-terminal basic amino acids by a carboxypeptidase, 3) amidation of LHRH-(Gly11) to LHRH, and 4) cyclization of glutamine to pyroglutamate at the N-terminal of LHRH. These results provide the first evidence for intermediates in the metabolic pathway of pro-LHRH to LHRH. C1 SALK INST BIOL STUDIES,LA JOLLA,CA 92037. UNIV CALIF SAN FRANCISCO,CTR REPROD ENDOCRINOL,SAN FRANCISCO,CA 94143. RP WETSEL, WC (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. FU NICHD NIH HHS [HD-08924, HD-20377]; NIDDK NIH HHS [R01 DK044838] NR 46 TC 86 Z9 87 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1991 VL 129 IS 3 BP 1584 EP 1595 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GD333 UT WOS:A1991GD33300061 PM 1714837 ER PT J AU ROSE, DF SATO, S DUCLASOARES, E KUFTA, CV AF ROSE, DF SATO, S DUCLASOARES, E KUFTA, CV TI MAGNETOENCEPHALOGRAPHIC LOCALIZATION OF SUBDURAL DIPOLES IN A PATIENT WITH TEMPORAL-LOBE EPILEPSY SO EPILEPSIA LA English DT Article DE MAGNETOENCEPHALOGRAPHY; TEMPORAL LOBE; SUBDURAL ELECTRODE; CURRENT DIPOLE; NEUROLOGIC DIAGNOSIS ID INTRACRANIAL LOCALIZATIONS; MAGNETIC LOCALIZATION; HUMAN-BRAIN; MODEL; SPIKES; AGREES; FIELD AB We report magnetoencephalographic localization of subdural electrode dipoles placed at the basal and mesial surfaces of the temporal lobe in a patient with temporal lobe epilepsy. The locations of the three dipoles were predicted from their magnetic fields with a computer model of the head as a conducting sphere. The predicted locations were within 1, 3, and 4 mm of the actual locations. These results, obtained in an area of the brain from which epileptiform discharges are frequently recorded, strongly support the capability of magnetoencephalography to accurately localize electrical events in this brain region. C1 NINCDS,MED NEUROL BRANCH,NEUROPHYSIOL UNIT,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 19 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP-OCT PY 1991 VL 32 IS 5 BP 635 EP 641 DI 10.1111/j.1528-1157.1991.tb04702.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA GH340 UT WOS:A1991GH34000006 PM 1915169 ER PT J AU BALISH, M ALBERT, PS THEODORE, WH AF BALISH, M ALBERT, PS THEODORE, WH TI SEIZURE FREQUENCY IN INTRACTABLE PARTIAL EPILEPSY - A STATISTICAL-ANALYSIS SO EPILEPSIA LA English DT Article DE INTRACTABLE PARTIAL EPILEPSY; SEIZURE FREQUENCY; CYCLICITY; VARIABILITY; CLUSTERING ID REGRESSION-MODELS; DISCHARGES AB We examined the seizure records of 13 patients (nine men and four women, ages 27-50 years) with intractable partial epilepsy, maintained with steady antiepileptic drug dosages. Patients recorded daily seizure frequency on calendars. Periods of outpatient observation ranged from 99 to 1,710 days and the number of observed seizures ranged from 18 to over 400, with daily seizure rates of 0.1-4.3 per day. We used the quasi-likelihood regression model to examine the following four departures of the daily seizure counts from a Poisson (random) model: (1) linear increasing or decreasing time trends in expected seizure rates; (2) clustering, where the expected seizure rate on a given day depends on the number of seizures observed on the immediate prior days; (3) monthly cyclicity; and (4) increased variability (overdispersion). Linear time trends were seen in six patients (four increasing and two decreasing), clustering was seen in 10 patients, and a near-monthly cycle appeared in four patients (two of nine men and two of four women). A significant amount of extra variation (overdispersion) relative to a Poisson distribution was observed in all but one of the 13 patients. Departures from a Poisson (random) model appear more common in this population of patients with medically intractable epilepsy than is commonly recognized, and have clinical importance as well as implications for the design of clinical studies. C1 NINCDS,MATH STAT SECT,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. RP BALISH, M (reprint author), NINCDS,MED NEUROL BRANCH,CLIN EPILEPSY SECT,BETHESDA,MD 20892, USA. NR 30 TC 40 Z9 40 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP-OCT PY 1991 VL 32 IS 5 BP 642 EP 649 DI 10.1111/j.1528-1157.1991.tb04703.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA GH340 UT WOS:A1991GH34000007 PM 1915170 ER PT J AU GOLDFARB, LG BROWN, P MITROVA, E CERVENAKOVA, L GOLDIN, L KORCZYN, AD CHAPMAN, J GALVEZ, S CARTIER, L RUBENSTEIN, R GAJDUSEK, DC AF GOLDFARB, LG BROWN, P MITROVA, E CERVENAKOVA, L GOLDIN, L KORCZYN, AD CHAPMAN, J GALVEZ, S CARTIER, L RUBENSTEIN, R GAJDUSEK, DC TI CREUTZFELDT-JAKOB DISEASE ASSOCIATED WITH THE PRNP CODON-200LYS MUTATION - AN ANALYSIS OF 45 FAMILIES SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CREUTZFELDT-JACOB DISEASE; MOLECULAR GENETICS OF TRANSMISSIBLE ENCEPHALOPATHIES; PRNP GENE; POINT MUTATION AB 200Lys mutation in the human PRNP coding region has been identified in 45 of the 55 CJD-affected families thus far presented to our NIH laboratory. These codon 200Lys families have a total of 87 patients, and originate from 7 different countries: Slovakia, Poland, Germany, Tunisia, Greece, Libya, and Chile. Forty-seven patients were neuropathologically verified, and brain tissue from 14 patients transmitted disease to experimental primates. The mutation was found by direct sequencing in 4 patients, and it was detected by restriction endonuclease analysis with BsmA 1 and/or the single nucleotide extension reaction in 36 other patients and 45 of 109 first degree relatives (1 parent, 14 siblings, and 30 children). The mutation is associated with all known geographical clusters of CJD (Slovakia, Libyan Jews, Chile) in which the annual mortality rate is tens or hundreds of times higher than the world average of 1 per million. All patients originating from the cluster areas carried the mutation, but it was seen in only 1 of 103 unrelated control individuals from the same areas, and in none of 102 controls from other areas, indicating a strong association between the mutation and disease. The penetrance of the mutation was estimated to be 0.56. Branches of some families migrating from cluster areas to other countries continue to have CJD over several generations, suggesting that CJD in these families is a genetic disorder, in which the 200Lys mutation is responsible for the disease. RP GOLDFARB, LG (reprint author), NIMH,CNS STUDIES LAB,BETHESDA,MD 20892, USA. RI Korczyn, Amos/C-3461-2017 OI Korczyn, Amos/0000-0003-0125-2579 NR 0 TC 116 Z9 117 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD SEP PY 1991 VL 7 IS 5 BP 477 EP 486 DI 10.1007/BF00143125 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GK106 UT WOS:A1991GK10600008 PM 1684755 ER PT J AU GAJDUSEK, DC AF GAJDUSEK, DC TI THE TRANSMISSIBLE AMYLOIDOSES - GENETIC-CONTROL OF SPONTANEOUS GENERATION OF INFECTIOUS AMYLOID PROTEINS BY NUCLEATION OF CONFIGURATIONAL CHANGE IN HOST PRECURSORS - KURU-CJD-GSS-SCRAPIE-BSE SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE INFECTIOUS AMYLOID PROTEINS; CREUTZFELDT-JAKOB DISEASE; SCRAPIE; BOVINE SPONGIFORM ENCEPHALOATHIES; GERSTMANN; STRAUSSLER SYNDROME AB Kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, scrapie, and bovine spongiform encephalopathy are caused by so-called unconventional viruses which are really replicating proteins which induce by auto nucleation and autopatterning a configurational change in the precursor protein to produce an infectious amyloid form. Crystallography and NMR may eventually determine how amyloid precursor protein is converted to this infectious form by configurational changes in all tertiary and quaternary structure of the normal precursor. Most sporadic cases of CJD arise by de novo spontaneous conversion of the normal precursor to the infectious form, a rare event occurring at the frequency of one per million persons per year (the annual incidence of CJD throughout the world). In the familial forms of CJD and GSS, where the occurrence is an autosomal dominant trait, each family has one of five different mutations causing a single amino acid change or one of five insertions of 5, 6, 7, 8 or 9 octapeptide repeats. Each mutation causes a million-fold increased probability of the spontaneous configurational change to an infectious polypeptide, and appears as an autosomal dominant trait. Thus, the behavior of the transmissible brain amyloidosis parallels completely that of the transthyretin amyloidoses causing familial amyloidotic polyneuropathy, in which there are 19 different point mutations, each one of which increases enormously the likelihood of configurational change of transthyretin prealbumin to amyloid. RP GAJDUSEK, DC (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 33 Z9 33 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD SEP PY 1991 VL 7 IS 5 BP 567 EP 577 DI 10.1007/BF00143141 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GK106 UT WOS:A1991GK10600024 PM 1684758 ER PT J AU BIKOFF, EK OTTEN, GR ROBERTSON, EJ AF BIKOFF, EK OTTEN, GR ROBERTSON, EJ TI DEFECTIVE ASSEMBLY OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES IN AN EMBRYONIC-CELL LINE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; BETA-2-MICROGLOBULIN GENE; BETA-2 MICROGLOBULIN; HEAVY-CHAINS; B-ANTIGENS; HLA-A; MOUSE; INTERFERON AB Developmentally regulated expression of the products of the major histocompatibility complex (MHC) is thought to play a key role in maternal tolerance of the fetal allograft. Here we analyze a cell line (EE2H3), derived from early post-implantation-stage mouse embryos, that is defective for MHC class I assembly. To follow expression of a single well-defined class I product, we introduced the H-2D(d) gene under control of the human beta-actin promoter. We found that the transfected EE2H3 cells expressed abundant levels of H-2D(d) heavy chains and beta-2-microglobulin protein, but only small amounts of H-2D(d) surface protein. Surface expression was rescued by the addition of an appropriate antigenic peptide, or by culturing the cells at low temperature. The phenotype exhibited by EE2H3 is thus remarkably similar to that described for class I-negative somatic cell variants selected using antibodies and complement. However, a striking difference was that surface expression in H-2D(d)-transfected EE2H3 cells was markedly enhanced in response to treatment with interferon. Thus, we have identified a novel class I assembly-defective cell line. Considering that EE2H3 was established from primary cultures of mouse embryo cells without immunoselection, and is therefore likely to represent a cell population normally present in post-implantation-stage embryos, these findings raise the possibility that expression of class I surface antigens during early development may in part be controlled post-translationally at the level of MHC class I assembly. C1 NIAID, IMMUNOL LAB, LYMPHOCYTE BIOL SECT, BETHESDA, MD 20892 USA. COLUMBIA UNIV, DEPT GENET & DEV, NEW YORK, NY 10027 USA. RP BIKOFF, EK (reprint author), CUNY MT SINAI SCH MED, DEPT OBSTET GYNECOL & REPROD SCI, ANNENBERG 20-84, 1 GUSTAVE L LEVY PL, NEW YORK, NY 10029 USA. FU NICHD NIH HHS [HD-25926] NR 53 TC 30 Z9 30 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1991 VL 21 IS 9 BP 1997 EP 2004 DI 10.1002/eji.1830210905 PG 8 WC Immunology SC Immunology GA GF655 UT WOS:A1991GF65500004 PM 1716207 ER PT J AU WIGGERT, B KUTTY, G LONG, KO INOUYE, L GERY, I CHADER, GJ AGUIRRE, GD AF WIGGERT, B KUTTY, G LONG, KO INOUYE, L GERY, I CHADER, GJ AGUIRRE, GD TI INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) IN PROGRESSIVE ROD CONE DEGENERATION (PRCD) - BIOCHEMICAL, IMMUNOCYTOCHEMICAL AND IMMUNOLOGICAL STUDIES SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE DOG; IMMUNOCYTOCHEMISTRY; IRBP; PROGRESSIVE ROD-CONE DEGENERATION; RETINA; RETINAL DEGENERATION; RETINITIS-PIGMENTOSA ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; VERTEBRATE RETINA; MESSENGER-RNA; VITAMIN-A; S-ANTIGEN; LOCALIZATION; PURIFICATION; ANTIBODIES; UVEITIS; RD C1 UNIV PENN,SCH VET MED,MED GENET SECT,3850 SPRUCE ST,PHILADELPHIA,PA 19104. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT OPHTHALMOL,SCHEIE EYE INST,PHILADELPHIA,PA 19104. FU NEI NIH HHS [EY-01244, EY-06855, EY-07035] NR 30 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1991 VL 53 IS 3 BP 389 EP 398 DI 10.1016/0014-4835(91)90245-A PG 10 WC Ophthalmology SC Ophthalmology GA GG008 UT WOS:A1991GG00800014 PM 1936175 ER PT J AU TOMBRANTINK, J CHADER, GG JOHNSON, LV AF TOMBRANTINK, J CHADER, GG JOHNSON, LV TI PEDF - A PIGMENT EPITHELIUM-DERIVED FACTOR WITH POTENT NEURONAL DIFFERENTIATIVE ACTIVITY SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID INTERPHOTORECEPTOR MATRIX; CELLS; INVITRO; GROWTH C1 NEI,BETHESDA,MD 20892. RP TOMBRANTINK, J (reprint author), UNIV SO CALIF,SCH MED,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90033, USA. NR 19 TC 446 Z9 476 U1 2 U2 9 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1991 VL 53 IS 3 BP 411 EP 414 DI 10.1016/0014-4835(91)90248-D PG 4 WC Ophthalmology SC Ophthalmology GA GG008 UT WOS:A1991GG00800017 PM 1936177 ER PT J AU LU, L SHEN, RN ZHOU, SZ WU, B KIM, YJ LIN, ZH RUSCETTI, S RALPH, P BROXMEYER, HE AF LU, L SHEN, RN ZHOU, SZ WU, B KIM, YJ LIN, ZH RUSCETTI, S RALPH, P BROXMEYER, HE TI EFFICACY OF RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR IN COMBINATION WITH WHOLE-BODY HYPERTHERMIA IN THE TREATMENT OF MICE INFECTED WITH THE POLYCYTHEMIA-INDUCING STRAIN OF THE FRIEND-VIRUS COMPLEX SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE MACROPHAGE COLONY-STIMULATING FACTOR (M-CSF); WHOLE-BODY HYPERTHERMIA (WBH); POLYCYTHEMIA-INDUCING FRIEND VIRUS COMPLEX (FVC-P); SPLEEN FOCUS-FORMING VIRUS (SFFV) ID FOCUS-FORMING VIRUS; NECROSIS FACTOR-ALPHA; NATURAL-KILLER CELLS; FACTOR CSF-1; HUMAN-MONOCYTES; MURINE INTERLEUKIN-3; MOLECULAR-CLONING; LEUKEMIA-CELLS; FACTOR-I; INVIVO AB Macrophage colony-stimulating factor (M-CSF, CSF-1) and whole-body hyperthermia (WBH) were evaluated, alone or in combination, for their capability to influence disease progression in mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). DBA/2 mice were injected i.v. with FVC-P and were treated with 20-mu-g/dose M-CSF s.c. twice a day for 5 days beginning 6 days after injection of FVC-P and/or with WBH (between 38.8-degrees-C and 40.2-degrees-C) given on days 5 and 12 after FVC-P injection. Fourteen days after viral inoculation, mice were sacrificed and spleen cells evaluated for: 1) spleen focus-forming virus (SFFV), by the spleen focus-forming unit assay (SFFU); 2) SFFV mRNA and genomic DNA using, respectively, Northern and Southern analysis with a B-E-SFFV DNA probe; and 3) natural killer (NK) cell activity, by Cr-51 release assay. Treatment with M-CSF or WBH alone had a small effect on SFFU numbers but little or no effect on SFFV mRNA expression and SFFV-specific DNA. However, dramatically decreased levels of SFFU and SFFV mRNA and specific DNA fragments were observed in mice treated with M-CSF in combination with WBH, and NK cell activity was restored to normal. These results suggest the possibility that M-CSF may have a therapeutic effect in combination with WBH in the in vivo treatment of certain hematologic malignancies and/or retroviral infections. C1 INDIANA UNIV,SCH MED,DEPT MED HEMATOL ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT RADIAT ONCOL,INDIANAPOLIS,IN 46202. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21701. CETUS CORP,DEPT CELL BIOL,EMERYVILLE,CA 94608. RP LU, L (reprint author), INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,MED RES & LIB BLDG,975 W WALNUT ST,ROOM 501,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [R37 CA-36464, R01 CA-36740] NR 56 TC 9 Z9 9 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 1991 VL 19 IS 8 BP 804 EP 809 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA GC099 UT WOS:A1991GC09900014 PM 1907925 ER PT J AU BACHRACH, CA BALDWIN, W AF BACHRACH, CA BALDWIN, W TI ABORTION UNDERREPORTING SO FAMILY PLANNING PERSPECTIVES LA English DT Letter RP BACHRACH, CA (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ALAN GUTTMACHER INST PI NEW YORK PA 120 WALL STREET, NEW YORK, NY 10005 SN 0014-7354 J9 FAM PLANN PERSPECT JI Fam. Plann. Perspect. PD SEP-OCT PY 1991 VL 23 IS 5 BP 233 EP 233 PG 1 WC Demography; Family Studies SC Demography; Family Studies GA GJ762 UT WOS:A1991GJ76200011 PM 1743278 ER PT J AU COUSINS, RJ BEERS, WH FITCH, FW LORDAN, JJ SMITH, MM HODSOLL, F HEALY, B AF COUSINS, RJ BEERS, WH FITCH, FW LORDAN, JJ SMITH, MM HODSOLL, F HEALY, B TI CONSENSUS CONFERENCE ON INDIRECT COSTS SO FASEB JOURNAL LA English DT Discussion C1 SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. UNIV CHICAGO,PATHOL,CHICAGO,IL 60637. JOHNS HOPKINS UNIV,BUSINESS AFFAIRS,BALTIMORE,MD 21218. DAVID M GRIFFITH ASSOCIATES,DIV HIGHER EDUC,CHICAGO,IL. NCI,BETHESDA,MD 20892. US OFF MANAGEMENT & BUDGET,WASHINGTON,DC. RP COUSINS, RJ (reprint author), UNIV FLORIDA,CTR NUTR & SCI,GAINESVILLE,FL 32611, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1991 VL 5 IS 12 BP 2624 EP 2637 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GE811 UT WOS:A1991GE81100002 ER PT J AU VENER, KJ CALKINS, BM AF VENER, KJ CALKINS, BM TI ANALYSIS OF SBIR PHASE-I AND PHASE-II REVIEW RESULTS AT THE NATIONAL-INSTITUTES-OF-HEALTH SO FASEB JOURNAL LA English DT Article DE COMMERCE; NATIONAL-INSTITUTES-OF-HEALTH; PROFESSIONAL COMPETENCE; RESEARCH DESIGN-STANDARDS; RESEARCH SUPPORT-ECONOMICS; UNITED-STATES AB A cohort of phase I and phase II summary statements for the SBIR grant applications was evaluated to determine the strengths and weaknesses in approved and disapproved applications. An analysis of outcome variables (disapproval or unfunded status) was examined with respect to exposure variables (strengths or shortcomings). Logistic regression models were developed for comparisons to measure the predictive value of shortcomings and strengths to the outcomes. Disapproved phase I results were compared with an earlier 1985 study. Although the magnitude of the frequencies of shortcomings was greater in the present study, the relative rankings within shortcomings class were more alike than different. Also, the frequencies of shortcomings were, with one exception, not significantly different in the two studies. Differences in the summary statement review may have accounted for some differences observed between the 1985 data and results of the present study. Comparisons of Approved/Disapproved and Approved-Unfunded/Funded yielded the following observations. For phase I applicants, a lack of a clearly stated, testable hypothesis, a poorly qualified or described investigative team, and inadequate methodological approaches contributed significantly (in that order) to a rating of disapproval. A critical flaw for phase II proposals was failure to accomplish objectives of the phase I study. Methodological issues also dominate the distinctions in both comparison groups. A clear result of the data presented here and that published previously is that SBIR applicants need continuing assistance to improve the chances of their success. These results should serve as a guide to assist NIH staff as they provide information to prospective applicants focusing on key elements of the application. A continuing review of the SBIR program would be helpful to evaluate the quality of the submitted science. C1 UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. RP VENER, KJ (reprint author), NIAMSD,BETHESDA,MD 20892, USA. FU PHS HHS [NIH 88-313] NR 6 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1991 VL 5 IS 12 BP 2640 EP 2644 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GE811 UT WOS:A1991GE81100003 PM 1916087 ER PT J AU STROBER, W HARRIMAN, GR AF STROBER, W HARRIMAN, GR TI THE REGULATION OF IGA B-CELL DIFFERENTIATION SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID STIMULATORY FACTOR-I; CONSTANT-REGION GENES; SUPPRESSOR T-CELLS; GROWTH FACTOR-BETA; HEAVY-CHAIN GENES; LYMPHOCYTES-B; PEYERS PATCH; ORAL TOLERANCE; SWITCH RECOMBINATION; ISOTYPE PRODUCTION C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NIAID,CLIN INVEST LAB,MUCOSAL IMMUNOL SECT,BETHESDA,MD 20892. NIAID,DIV INTRAMURAL RES,BETHESDA,MD 20892. NR 82 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 1991 VL 20 IS 3 BP 473 EP 494 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GD056 UT WOS:A1991GD05600004 PM 1917023 ER PT J AU WILLIAMS, SC CANTWELL, CA JOHNSON, PF AF WILLIAMS, SC CANTWELL, CA JOHNSON, PF TI A FAMILY OF C/EBP-RELATED PROTEINS CAPABLE OF FORMING COVALENTLY LINKED LEUCINE ZIPPER DIMERS INVITRO SO GENES & DEVELOPMENT LA English DT Article DE C/EBP-RELATED PROTEIN; GENE FAMILY; TISSUE-SPECIFIC TRANSCRIPTIONAL ACTIVATOR; DISULFIDE CROSS-LINKS ID ENHANCER-BINDING-PROTEIN; ENRICHED TRANSCRIPTIONAL ACTIVATOR; TISSUE-SPECIFIC EXPRESSION; LIVER NUCLEAR-PROTEIN; SERUM-ALBUMIN GENE; DNA-BINDING; EUKARYOTIC TRANSCRIPTION; DIMERIZATION SPECIFICITY; MOLECULAR-CLONING; CYCLIC-AMP AB Mouse and rat genomic DNA libraries were screened by reduced stringency hybridization with the DNA-binding domain of the c/ebp gene as a probe. Three genes were isolated that encode bZIP DNA-binding proteins (designated CRP1, CRP2, and CRP3) with strong amino acid sequence similarities to the C/EBP-binding domain. CRP2 is identical to the protein described recently by other groups as NF-IL6, LAP, IL-6DBP, and AGP/EBP, whereas CRP1 and CRP3 represent novel proteins. Several lines of evidence indicate that these three proteins, along with C/EBP, comprise a functional family. Each bacterially expressed polypeptide binds to DNA as a dimer with recognition properties that are virtually identical to those of C/EBP. Every member also bears a conserved cysteine residue at or near the carboxyl terminus, immediately following the leucine zipper, that at least in vitro allows efficient disulfide cross-linking between paired zipper helices. We developed a gel assay for covalent dimers to assess leucine zipper specificities among the family members. The results demonstrate that all pairwise combinations of dimer interactions are possible. To the extent that we have examined them, the same heterodimeric complexes can be detected intracellularly following cotransfection of the appropriate pair of genes into recipient cells. All members are also capable of activating in vivo transcription from promoters that contain a C/EBP-binding site. Our findings indicate that a set of potentially interacting C/EBP-like proteins exists, whose complexity is comparable to that of other bZIP protein subfamilies such as Jun, Fos, and ATF/CREB. RP WILLIAMS, SC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NCI NIH HHS [N01-CO-74101] NR 60 TC 526 Z9 532 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1991 VL 5 IS 9 BP 1553 EP 1567 DI 10.1101/gad.5.9.1553 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA GD966 UT WOS:A1991GD96600004 PM 1884998 ER PT J AU DOSTATNI, N LAMBERT, PF SOUSA, R HAM, J HOWLEY, PM YANIV, M AF DOSTATNI, N LAMBERT, PF SOUSA, R HAM, J HOWLEY, PM YANIV, M TI THE FUNCTIONAL BPV-1 E2 TRANS-ACTIVATING PROTEIN CAN ACT AS A REPRESSOR BY PREVENTING FORMATION OF THE INITIATION COMPLEX SO GENES & DEVELOPMENT LA English DT Article DE INVITRO TRANSCRIPTION; ACTIVATION; REPRESSION; DNA-BINDING INTERFERENCE; BPV-1 E2; TFIID ID BOVINE PAPILLOMAVIRUS TYPE-1; LONG CONTROL REGION; DNA RECOGNITION SEQUENCE; HPV18 REGULATORY REGION; CARBOXY-TERMINAL DOMAIN; GENE-PRODUCT; TRANSCRIPTIONAL REPRESSION; SACCHAROMYCES-CEREVISIAE; INVITRO TRANSCRIPTION; MUTATIONAL ANALYSIS AB The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters. To further understand the mechanisms by which the same transcription factor may act differentially, the full-length BPV-1 E2 protein was expressed and purified from yeast and assayed in vitro for its capacity to modulate transcription. E2 stimulated transcription of the HSV thymidine kinase (TK) promoter when E2-binding sites were positioned in an enhancer configuration approximately 100 bp upstream of the promoter start site. In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter. This repression was mediated through binding to the E2 DNA-binding site immediately upstream of the P105 promoter TATA box and could be abrogated by preincubation of the HPV-18 P105 promoter template with the nuclear extract allowing the formation of the preinitiation complex. In vitro DNA-binding experiments with purified E2 and TFIID showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site. In these respects, E2 is similar to the bacteriophage lambda-repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RP DOSTATNI, N (reprint author), INST PASTEUR,CNRS,UA 1149,DEPT BIOTECHNOL,UNITE VIRUS ONCOGENES,F-75724 PARIS,FRANCE. RI Ham, Jonathan/C-5164-2008 NR 64 TC 132 Z9 135 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP PY 1991 VL 5 IS 9 BP 1657 EP 1671 DI 10.1101/gad.5.9.1657 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA GD966 UT WOS:A1991GD96600013 PM 1653173 ER PT J AU DODGE, GR KOVALSZKY, I MCBRIDE, OW YI, HF CHU, ML SAITTA, B STOKES, DG IOZZO, RV AF DODGE, GR KOVALSZKY, I MCBRIDE, OW YI, HF CHU, ML SAITTA, B STOKES, DG IOZZO, RV TI HUMAN CLATHRIN HEAVY-CHAIN (CLTC) - PARTIAL MOLECULAR-CLONING, EXPRESSION, AND MAPPING OF THE GENE TO HUMAN-CHROMOSOME 17Q11-QTER SO GENOMICS LA English DT Article ID DNA C1 THOMAS JEFFERSON UNIV,DEPT PATHOL & CELL BIOL,JEFFERSON ALUMNI HALL,ROOM 249,PHILADELPHIA,PA 19107. NCI,BIOCHEM LAB,BETHESDA,MD 20205. THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA 19107. OI Iozzo, Renato/0000-0002-5908-5112 FU NCI NIH HHS [CA-39481, CA-47282] NR 16 TC 23 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1991 VL 11 IS 1 BP 174 EP 178 DI 10.1016/0888-7543(91)90115-U PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GA488 UT WOS:A1991GA48800021 PM 1765375 ER PT J AU MARES, A LEDBETTER, SA LEDBETTER, DH ROBERTS, R HEJTMANCIK, JF AF MARES, A LEDBETTER, SA LEDBETTER, DH ROBERTS, R HEJTMANCIK, JF TI ISOLATION OF A HUMAN-CHROMOSOME 14-ONLY SOMATIC-CELL HYBRID - ANALYSIS USING ALU AND LINE-BASED PCR SO GENOMICS LA English DT Note ID POLYMERASE CHAIN-REACTION; RAPID ISOLATION C1 BAYLOR COLL MED,INST MOLEC GENET,DEPT MED,HOUSTON,TX 77030. NEI,BETHESDA,MD 20892. RP MARES, A (reprint author), BAYLOR COLL MED,DEPT MED,MOLEC CARDIOL UNIT,ONE BAYLOR PLAZA,ROOM 506C,HOUSTON,TX 77030, USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1991 VL 11 IS 1 BP 215 EP 218 DI 10.1016/0888-7543(91)90122-U PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GA488 UT WOS:A1991GA48800028 PM 1765380 ER PT J AU WHITE, JJ LEDBETTER, DH EDDY, RL SHOWS, TB STEWART, DA NUELL, MJ FRIEDMAN, V WOOD, CM OWENS, GA MCCLUNG, JK DANNER, DB MORTON, CC AF WHITE, JJ LEDBETTER, DH EDDY, RL SHOWS, TB STEWART, DA NUELL, MJ FRIEDMAN, V WOOD, CM OWENS, GA MCCLUNG, JK DANNER, DB MORTON, CC TI ASSIGNMENT OF THE HUMAN PROHIBITION GENE (PHB) TO CHROMOSOME-17 AND IDENTIFICATION OF A DNA POLYMORPHISM SO GENOMICS LA English DT Note ID TUMOR SUPPRESSOR GENES; CANCER; LOCALIZATION; CARCINOMA; LOSSES C1 NIA,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT HUMAN GENET,BUFFALO,NY 14263. SR NOBLE FDN,DIV BIOMED,ARDMORE,OK 73402. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 18 TC 46 Z9 46 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1991 VL 11 IS 1 BP 228 EP 230 DI 10.1016/0888-7543(91)90126-Y PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GA488 UT WOS:A1991GA48800032 PM 1684951 ER PT J AU LIU, J CHEN, Y KOZAK, CA YU, L AF LIU, J CHEN, Y KOZAK, CA YU, L TI THE 5-HT2 SEROTONIN RECEPTOR GENE HTR-2 IS TIGHTLY LINKED TO ES-10 ON MOUSE CHROMOSOME-14 SO GENOMICS LA English DT Note ID SUBSTRATE-SPECIFICITY; SYNTHETIC PEPTIDES; FAMILY; DNA; RECOGNITION; PROTEINS; 5-HYDROXYTRYPTAMINE; REQUIREMENTS; PROBES; SITES C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP LIU, J (reprint author), INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202, USA. FU NINDS NIH HHS [NS28190] NR 31 TC 23 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 1991 VL 11 IS 1 BP 231 EP 234 DI 10.1016/0888-7543(91)90127-Z PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GA488 UT WOS:A1991GA48800033 PM 1765383 ER PT J AU MUTCHNICK, MG APPELMAN, HD CHUNG, HT ARAGONA, E GUPTA, TP CUMMINGS, GD WAGGONER, JG HOOFNAGLE, JH SHAFRITZ, DA AF MUTCHNICK, MG APPELMAN, HD CHUNG, HT ARAGONA, E GUPTA, TP CUMMINGS, GD WAGGONER, JG HOOFNAGLE, JH SHAFRITZ, DA TI THYMOSIN TREATMENT OF CHRONIC HEPATITIS-B - A PLACEBO-CONTROLLED PILOT TRIAL SO HEPATOLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; INTERLEUKIN-2 RECEPTOR EXPRESSION; CHRONIC ACTIVE HEPATITIS; ALPHA-INTERFERON; VIRUS-INFECTION; THYMIC HORMONES; PREDNISONE WITHDRAWAL; GAMMA-INTERFERON; CELL FUNCTION; LYMPHOCYTE-T AB Chronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin-alpha-1 in a prospective, placebo-controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin-alpha-1 and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin-treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p < 0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo-treated patients but in only one of seven thymosin-treated patients (p < 0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and in in vitro production of interferon-gamma over initial values. No significant side effects were observed in patients given thymosin or in placebo-treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 +/- 3 mo of follow-up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with chronic viral infection. C1 WAYNE STATE UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,DETROIT,MI 48201. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. YESHIVA UNIV ALBERT EINSTEIN COLL MED,LIVER RES CTR,BRONX,NY 10461. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. FU FDA HHS [FD-R-000096]; NCI NIH HHS [CA32605] NR 41 TC 118 Z9 122 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1991 VL 14 IS 3 BP 409 EP 415 DI 10.1016/0270-9139(91)90176-V PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GD077 UT WOS:A1991GD07700001 PM 1874487 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI MEDICAL MALPRACTICE IN 19TH-CENTURY AMERICA - ORIGINS AND LEGACY - DEVILLE,KA SO HISTORIAN LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PHI ALPHA THETA PI ALLENTOWN PA THE HISTORIAN 50 COLLEGE DR, ALLENTOWN, PA 18104-6100 SN 0018-2370 J9 HISTORIAN JI Historian PD FAL PY 1991 VL 54 IS 1 BP 149 EP 150 PG 2 WC History SC History GA GP745 UT WOS:A1991GP74500050 ER PT J AU RAMIREZ, M ARECHAGA, G SANCHEZ, B GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM AF RAMIREZ, M ARECHAGA, G SANCHEZ, B GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM TI DIURNAL-VARIATION OF LEUCYL AMINOPEPTIDASE ACTIVITY IN THE RAT HYPOTHALAMUS SO HORMONE AND METABOLIC RESEARCH LA English DT Note ID BRAIN C1 NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP RAMIREZ, M (reprint author), UNIV BASQUE COUNTRY,FAC MED,DEPT PHYSIOL,POB 699,BILBAO,SPAIN. RI Venzon, David/B-3078-2008 NR 10 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD SEP PY 1991 VL 23 IS 9 BP 452 EP 453 DI 10.1055/s-2007-1003725 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH354 UT WOS:A1991HH35400012 PM 1743618 ER PT J AU DILONARDO, JD KENDRICK, KA SEITZ, LA AF DILONARDO, JD KENDRICK, KA SEITZ, LA TI USE OF INPATIENT PSYCHIATRIC-CARE AT A VA MEDICAL-CENTER AFTER IMPLEMENTATION OF A PROSPECTIVE PAYMENT SYSTEM SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID 2-YEAR FOLLOW-UP; SCHIZOPHRENIC-PATIENTS; LONG HOSPITALIZATION; STAY; RECIDIVISM; SERVICES; RELAPSE; LENGTH AB A retrospective audit of patients' utilization of inpatient psychiatric care at a Department of Veterans Affairs medical center before and after implementation of a prospective payment system compared patterns of utilization by chronic and nonchronic patients. It also examined changes over time in the size of the two groups, total number of bed days used, mean number of admissions, mean length of stay, and mean cumulative two-year length of stay. Four years after implementation of the prospective payment system, chronic patients constituted 3 percent of the patient population but used 15.2 percent of all bed days. Both chronic and nonchronic patients had a similar decrease in mean length of stay over the period, but chronic patients' mean number of admissions rose by more than 70 percent. The mean cumulative two-year length of stay of chronic patients remained stable over the period while that of the nonchronic patients decreased by 33.2 percent. C1 GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20057. VET ADM MED CTR,WASHINGTON,DC 20422. DEPT VET AFFAIRS CENT OFF,WASHINGTON,DC. NIDA,ROCKVILLE,MD. RP DILONARDO, JD (reprint author), VET AFFAIRS MED CTR,WASHINGTON,DC, USA. NR 27 TC 6 Z9 6 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD SEP PY 1991 VL 42 IS 9 BP 939 EP 942 PG 4 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA GD075 UT WOS:A1991GD07500013 PM 1743666 ER PT J AU ANDERSON, WF AF ANDERSON, WF TI REFLECTIONS - OF HOPE AND OF CONCERN SO HUMAN GENE THERAPY LA English DT Editorial Material RP ANDERSON, WF (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,7D-18,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FAL PY 1991 VL 2 IS 3 BP 193 EP 194 DI 10.1089/hum.1991.2.3-193 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA GM005 UT WOS:A1991GM00500001 ER PT J AU CORNETTA, K MORGAN, RA GILLIO, A STURM, S BALTRUCKI, L OREILLY, R ANDERSON, WF AF CORNETTA, K MORGAN, RA GILLIO, A STURM, S BALTRUCKI, L OREILLY, R ANDERSON, WF TI NO RETROVIREMIA OR PATHOLOGY IN LONG-TERM FOLLOW-UP OF MONKEYS EXPOSED TO A MURINE AMPHOTROPIC RETROVIRUS SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; ENVELOPE GLYCOPROTEIN; ADENOSINE-DEAMINASE; PROTEINS; VIRUS AB Four monkeys were exposed to a retroviral vector and replication-competent murine amphotropic retrovirus in a bone marrow transplantation/gene transfer protocol (Kantoff et al., 1987). We have studied these animals 2 and 3 years post-transplantation and did not detect replicating virus in serum, peripheral blood mononuclear cells, or bone marrow cells. Amphotropic envelope sequences could not be detected in blood or bone marrow cells by Southern blotting or the polymerase chain reaction. Antibodies directed against the p30 and gp70 viral antigens were detected by Western blot and immunoprecipitation. The animals remain alive and well. Our findings suggest that primates can clear murine amphotropic retroviruses even when exposure occurs during a time of severe immunosuppression. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NR 14 TC 74 Z9 75 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FAL PY 1991 VL 2 IS 3 BP 215 EP 219 DI 10.1089/hum.1991.2.3-215 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA GM005 UT WOS:A1991GM00500004 PM 1661171 ER PT J AU ABASSI, ZA GOLOMB, E KEISER, HR AF ABASSI, ZA GOLOMB, E KEISER, HR TI EFFECTS OF URODILATIN IN RATS WITH HIGH-OUTPUT HEART-FAILURE SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1991 VL 18 IS 3 BP 394 EP 394 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF111 UT WOS:A1991GF11100091 ER PT J AU ABASSI, ZA KEISER, HR AF ABASSI, ZA KEISER, HR TI EFFECTS OF NEUTRAL ENDOPEPTIDASE INHIBITION ON THE EXCRETION OF ENDOTHELIN SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1991 VL 18 IS 3 BP 405 EP 405 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF111 UT WOS:A1991GF11100133 ER PT J AU GEIGER, H BAHNER, U KRAUS, I HOFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC AF GEIGER, H BAHNER, U KRAUS, I HOFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC TI ACE-INHIBITION AND ANF IN THE BRAINS OF 5/6 NPX RATS SO HYPERTENSION LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,W-8520 ERLANGEN,GERMANY. UNIV WURZBURG,W-8700 WURZBURG,GERMANY. NIMH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1991 VL 18 IS 3 BP 416 EP 416 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GF111 UT WOS:A1991GF11100176 ER PT J AU DAUBEWITHERSPOON, ME CARSON, RE AF DAUBEWITHERSPOON, ME CARSON, RE TI UNIFIED DEADTIME CORRECTION MODEL FOR PET SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article; Proceedings Paper CT SYMP AT THE 1990 MEDICAL IMAGING CONF : NUCLEAR SCIENCE CY OCT 22-27, 1990 CL CRYSTAL CITY, VA SP IEEE ID POSITRON EMISSION TOMOGRAPHY; COUNT RATE; TRANSMISSION; PILEUP AB A model of deadtime for emission and transmission scans in PET scanners with two-dimensional detectors has been developed. The model takes into account coincidence losses due to singles losses and multiple events, as well as mispositioning errors at higher count rates caused by pulse pile-up within a detector block. The model is applicable to emission distributions and to spatially varying singles distributions seen with a rotating pin transmission source. An automatic procedure to determine the parameters of this model based on decaying emission studies has also been developed. Different singles deadtime factors are required for emission and blank distributions due to differences in their energy spectra. The model was tested on emission and pin transmission data taken on the Scanditronix PC2048-15B scanner. RP DAUBEWITHERSPOON, ME (reprint author), NIH,DEPT NUCL MED,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 10 TC 25 Z9 25 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 1991 VL 10 IS 3 BP 267 EP 275 DI 10.1109/42.97575 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA GH744 UT WOS:A1991GH74400006 PM 18222827 ER PT J AU HASLOV, K PETERSEN, JW BAKER, PJ AF HASLOV, K PETERSEN, JW BAKER, PJ TI ADJUVANTICITY OF PERTUSSIS TOXIN IS MEDIATED BY DIFFERENTIAL-EFFECTS ON THE ACTIVITY OF T-SUPPRESSOR, T-AMPLIFIER AND T-HELPER CELLS SO IMMUNOBIOLOGY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; LYMPHOCYTOSIS-PROMOTING FACTOR; DELAYED-TYPE HYPERSENSITIVITY; HISTAMINE-SENSITIZING FACTOR; MONOPHOSPHORYL LIPID-A; LOW-DOSE PARALYSIS; ANTIBODY-RESPONSE; BORDETELLA-PERTUSSIS; CONCANAVALIN-A; ENHANCEMENT AB The immunomodulatory effects of pertussis toxin (Ptx) were studied in BALB/c mice immunized with type III pneumococcal polysaccharide (SSS-III). The antibody response to SSS-III is predominantly of the IgM class and is regulated by two opposing types of T cells, a T suppressor (T(S)) and a T amplifier (T(A)) cell. Treatment of mice with Ptx at the time of immunization with SSS-III results in an enhancement of the splenic antigen-specific IgM response, which was estimated by a plaque-forming cell assay. Numbers of non-antigen-specific IgM producing cells were not significantly affected. This adjuvant effect occurred in nu/+ but not in T cell deficient nu/nu mice. Such adjuvanticity appears to be due in part to the neutralization of T(S), since (a) Ptx-treatment was found to reverse T(S)-mediated low-dose immunological tolerance induced in mice previously exposed to a subimmunogenic dose of SSS-III, and (b) in vitro Ptx-treatment of a cell population enriched in SSS-III specific T(S), activity abolished the capacity of such cells to transfer suppression when given to recipients at the time of immunization with SSS-III. In another type of cell transfer experiment, it was shown that Ptx treatment resulted in an increased frequency of T(A) in mice immunized with SSS-III. We conclude that Ptx differentially affects at least two populations of regulatory T cells, and that these effects are not directly related to the mitogenicity of Ptx for T cells or to a direct effect upon B cells. C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2 RES FACIL,ROCKVILLE,MD. RP HASLOV, K (reprint author), STATENS SERUM INST,DEPT BACTERIOL VACCINE,DK-2300 COPENHAGEN,DENMARK. NR 38 TC 3 Z9 3 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD SEP PY 1991 VL 183 IS 1-2 BP 40 EP 54 PG 15 WC Immunology SC Immunology GA GF865 UT WOS:A1991GF86500004 PM 1834545 ER PT J AU ELKINS, KL BULLER, RML STASHAK, PW BAKER, PJ AF ELKINS, KL BULLER, RML STASHAK, PW BAKER, PJ TI CD4+ T-CELLS REGULATE THE MAGNITUDE OF THE ANTIBODY-RESPONSE TO SEVERAL HELPER T-CELL INDEPENDENT ANTIGENS SO IMMUNOBIOLOGY LA English DT Article ID BACTERIAL POLYSACCHARIDE ANTIGENS; B-CELLS; MONOCLONAL-ANTIBODY; LYMPHOCYTE-T; IMMUNOLOGICAL-UNRESPONSIVENESS; INVIVO; L3T4; LIPOPOLYSACCHARIDES; SUBPOPULATIONS; MODULATION AB The effect of prior depletion of CD4+ T cells on the magnitude of the primary antibody response to several antigens considered to be helper T cell independent (TI) was examined. Treatment of mice with the monoclonal antibody GK1.5 to remove CD4+ T cells had little effect on the magnitude of the specific antibody response to the lipopolysaccharide (LPS) of Escherichia coli 0113; however, such treatment reduced the magnitude of the splenic IgM antibody response to E. coli 055 LPS, Serratia marcescens LPS, TNP-Ficoll, and Type III pneumococcal polysaccharide (SSS-III), compared to control untreated or rat IgG treated mice. Thus, CD4+ T cells positively influence of magnitude of the antibody response to the majority of helper T cell independent antigens tested. C1 NIAID,IMMUNOGENET,TWINBROOK 2 RES FACIL,ROCKVILLE,MD. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP ELKINS, KL (reprint author), WALTER REED ARMY MED CTR,DEPT CELLULAR IMMUNOL,9260 MED CTR DR,ROCKVILLE,MD 20910, USA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD SEP PY 1991 VL 183 IS 1-2 BP 69 EP 78 PG 10 WC Immunology SC Immunology GA GF865 UT WOS:A1991GF86500006 PM 1682242 ER PT J AU DORON, DA JACOBOWITZ, DM HELDMAN, E FEUERSTEIN, G POLLARD, HB HALLENBECK, JM AF DORON, DA JACOBOWITZ, DM HELDMAN, E FEUERSTEIN, G POLLARD, HB HALLENBECK, JM TI EXTRACELLULAR-MATRIX PERMITS THE EXPRESSION OF VONWILLEBRAND-FACTOR, UPTAKE OF DI-I-ACETYLATED LOW-DENSITY-LIPOPROTEIN AND SECRETION OF PROSTACYCLIN IN CULTURES OF ENDOTHELIAL-CELLS FROM RAT-BRAIN MICROVESSELS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Article DE ENDOTHELIUM; PROSTAGLANDIN; DIFFERENTIATION; MATRIX ID CAPILLARY-LIKE STRUCTURES; VIII-RELATED ANTIGEN; LONG-TERM CULTURE; PLATELET-AGGREGATION; BASEMENT-MEMBRANE; GERBIL BRAIN; INVITRO; DIFFERENTIATION; LAMININ; TISSUE AB Microvascular endothelial cells from the adult rat brain were cultured on Matrigel and found to express many differentiated properties including secretion of prostacyclin (PGI2) and von Willebrand's factor (vWF). Brain microvascular endothelial cells (BMECs) were purified by dextran and percoll gradients after enzymatic treatment and cultured under various conditions. BMECs that were plated on Matrigel stained positively for factor VIII-related antigen and incorporated Di-I-acetylated low density lipoprotein, whereas BMEC plated on fibronectin, gelatin, or uncoated dishes did not express any of the above properties which are characteristic of endothelial cells. vWF was measured by a sensitive ELISA in the culture media of BMECs plated on different types of matrices. Specificity of the anti-human vWF antibodies for the rat vWF was verified by immunoabsorption on a solid phase, sodium dodecyl sulfate, and Western blot analysis. BMECs also secreted vWF into the culture media only when the cells were plated on Matrigel, and this secretion was augmented after a 6 h incubation with an interleukin-I tumor necrosis factor-alpha mixture, but not by lipopolysaccharide. From different matrices tested, only Matrigel permitted the secretion of PGI2 by BMECs. Cells also proved to be sensitive to mechanical stimulation and became refractory to secretagogue if the mechanical stimulation was serially repeated. Under the best conditions, stimulation of the cells with bradykinin (1-mu-M) substantially increased PGI2 secretion. These data indicate that growth of BMECs on Matrigel in vitro permits the expression of classical endothelial cell markers in a manner similar to the behavior of these cells in situ. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. SK&F LABS,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406. RP DORON, DA (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 405,BETHESDA,MD 20892, USA. NR 43 TC 12 Z9 12 U1 0 U2 1 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD SEP PY 1991 VL 27 IS 9 BP 689 EP 697 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GK634 UT WOS:A1991GK63400005 ER PT J AU YEH, CK MERTZ, PM OLIVER, C BAUM, BJ KOUSVELARI, EE AF YEH, CK MERTZ, PM OLIVER, C BAUM, BJ KOUSVELARI, EE TI CELLULAR CHARACTERISTICS OF LONG-TERM CULTURED RAT PAROTID ACINAR-CELLS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Article DE PAROTID GLAND; ACINAR CELL CULTURE; BASEMENT MEMBRANE ID GLAND; PROTEINS; LINE; ISOPROTERENOL AB We have successfully maintained and biochemically characterized differentiated rat parotid acinar cells cultured for long periods (6 mo.). The cells were cultured on a reconstituted basement membrane matrix in a medium containing a variety of agents that promote cellular proliferation and differentiation. The cultured cells retain the characteristics of the parental parotid acinar cells. They exhibit both secretory granules and abundant cellular organelles required for protein synthesis and secretion. In situ hybridization and immunocytochemistry demonstrate high levels of proline-rich protein mRNA and protein, and lower levels of amylase mRNA and protein, in their cytoplasm. These findings suggest that rat parotid acinar cells can be maintained in a differentiated state in vitro for long periods, and can serve as a useful model system for studying the regulation of exocrine secretory processes. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NR 25 TC 24 Z9 24 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD SEP PY 1991 VL 27 IS 9 BP 707 EP 712 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GK634 UT WOS:A1991GK63400007 PM 1717429 ER PT J AU LOBET, Y CLUFF, CW CIEPLAK, W AF LOBET, Y CLUFF, CW CIEPLAK, W TI EFFECT OF SITE-DIRECTED MUTAGENIC ALTERATIONS ON ADP-RIBOSYLTRANSFERASE ACTIVITY OF THE A-SUBUNIT OF ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXIN SO INFECTION AND IMMUNITY LA English DT Article ID AERUGINOSA EXOTOXIN-A; PERTUSSIS TOXIN; ADENYLATE-CYCLASE; CHOLERA-TOXIN; PSEUDOMONAS-AERUGINOSA; ENZYMATIC-ACTIVITIES; NUCLEOTIDE-SEQUENCE; DIPHTHERIA-TOXIN; FUNCTIONAL HOMOLOGY; VACCINE DEVELOPMENT AB Previous studies of the S1 subunit of pertussis toxin, an NAD+-dependent ADP-ribosyltransferase, suggested that a small amino-terminal region of amino acid sequence similarity to the active fragments of both cholera toxin and Escherichia coli heat-labile enterotoxin represents a region containing critical active-site residues that might be involved in the binding of the substrate NAD+. Other studies of two other bacterial toxins possessing ADP-ribosyltransferase activity, diphtheria toxin and Pseudomonas exotoxin A, have revealed the presence of essential glutamic acid residues vicinal to the active site. To help determine the relevance of these observations to activities of the enterotoxins, the A-subunit gene of the E. coli heat-labile enterotoxin was subjected to site-specific mutagenesis in the region encoding the amino-terminal region of similarity to the S1 subunit of pertussis toxin delineated by residues 6 through 17 and at two glutamic acid residues, 110 and 112, that are conserved in the active domains of all of the heat-labile enterotoxin variants and in cholera toxin. Mutant proteins in which arginine 7 was either deleted or replaced with lysine exhibited undetectable levels of ADP-ribosyltransferase activity. However, limited trypsinolysis of the arginine 7 mutants yielded fragmentation kinetics that were different from that yielded by the wild-type recombinant subunit or the authentic A subunit. In contrast, mutant proteins in which glutamic acid residues at either position 110 or 112 were replaced with aspartic acid responded like the wild-type subunit upon limited trypsinolysis, while exhibiting severely depressed, but detectable, ADP-ribosyltransferase activity. The latter results may indicate that either glutamic acid 110 or glutamic acid 112 of the A subunit of heat-labile enterotoxin is analogous to those active-site glutamic acids identified in several other ADP-ribosylating toxins. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. NR 59 TC 64 Z9 64 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1991 VL 59 IS 9 BP 2870 EP 2879 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GD020 UT WOS:A1991GD02000003 PM 1908825 ER PT J AU XU, YH MACEDONIA, J SHER, A PEARCE, E CHEEVER, AW AF XU, YH MACEDONIA, J SHER, A PEARCE, E CHEEVER, AW TI DYNAMIC ANALYSIS OF SPLENIC LYMPHOCYTE-TH1 AND LYMPHOCYTE-TH2 FUNCTIONS IN MICE INFECTED WITH SCHISTOSOMA-JAPONICUM SO INFECTION AND IMMUNITY LA English DT Article ID T-HELPER CELL; GRANULOMA-FORMATION; LYMPHOKINE PRODUCTION; CYTOKINE PRODUCTION; IMMUNE REGULATION; SECRETING CELLS; CLONES SECRETE; EGG GRANULOMA; TH1 CLONES; IFN-GAMMA AB Recent studies indicate that egg granuloma formation in murine Schistosoma mansoni infection is associated with Th2-mediated immune responses. The present study was designed to analyze dynamically the Th1 and Th2 responses in S. japonicum-infected animals and compare them with the results seen with S. mansoni. C3H mice were infected with 10 to 20 cercariae of S. japonicum and sacrificed 3 to 22 weeks later. Spleen cells were stimulated with parasite antigens (egg and adult worm) or the mitogen concanavalin A. Interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon (IFN-gamma) levels were measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA) or bioassays. Additionally, cytokine-producing cells were enumerated by ELISPOT. The results show that Th2 cytokine production, characterized by IL-4 and IL-5, represents the major response in the first month after egg laying begins, while the Th1 functions of IFN-gamma and IL-2 production are greatly depressed. However, by 22 weeks Th2 responses have diminished and IFN-gamma production in response to concanavalin A is apparent. IL-2 responses are minimal at all times. In vitro depletion of T-cell subsets indicates that CD4+ cells are the major subset responsible for production of IL-5 at 7 weeks of infection. These findings suggest that, as in the case of S. mansoni infection, S. japonicum-induced immunopathology is temporally associated with the host Th2 response, although other experiments indicate that IFN-gamma is also involved. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI02656] NR 39 TC 38 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1991 VL 59 IS 9 BP 2934 EP 2940 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GD020 UT WOS:A1991GD02000012 PM 1679041 ER PT J AU ESQUIVEL, F TAYLOR, CE BAKER, PJ AF ESQUIVEL, F TAYLOR, CE BAKER, PJ TI DIFFERENTIAL SENSITIVITY OF CD8+ SUPPRESSOR AND CYTOTOXIC LYMPHOCYTE-T ACTIVITY TO BACTERIAL MONOPHOSPHORYL LIPID-A SO INFECTION AND IMMUNITY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; ANTIBODY-PRODUCING CELLS; CELLULAR LEVEL; MICE; GENERATION; ANTIGEN; NUCLEOPROTEIN; INACTIVATION; EXPRESSION; ACTIVATION AB Treatment with a preparation of monophosphoryl lipid A, known to be capable of abolishing the expression of CD8+ suppressor T cell activity generated during the antibody response to type III pneumococcal polysaccharide (SSS-III), was found to have no adverse effect upon either induction or expression of CD8+ cytotoxic T lymphocyte activity specific for influenza A virus antigens. This suggests that suppressor T cells and cytotoxic T lymphocytes represent functionally distinct subsets of CD8+ T cells which can be differentiated on the basis of their sensitivities to inactivation by monophosphoryl lipid A. C1 NIAID,VIRAL DIS LAB,TWINBROOK RES FACIL 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852. NIAID,IMMUNOGENET LAB,TWINBROOK RES FACIL 2,ROCKVILLE,MD 20852. NR 32 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1991 VL 59 IS 9 BP 2994 EP 2998 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GD020 UT WOS:A1991GD02000020 PM 1831794 ER PT J AU MCCAUL, TF BANERJEEBHATNAGAR, N WILLIAMS, JC AF MCCAUL, TF BANERJEEBHATNAGAR, N WILLIAMS, JC TI ANTIGENIC DIFFERENCES BETWEEN COXIELLA-BURNETII CELLS REVEALED BY POSTEMBEDDING IMMUNOELECTRON MICROSCOPY AND IMMUNOBLOTTING SO INFECTION AND IMMUNITY LA English DT Article ID Q-FEVER ENDOCARDITIS; POLYACRYLAMIDE GELS; IMMUNOLOGICAL PROPERTIES; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; PHASE VARIANTS; PROTEINS; LIPOPOLYSACCHARIDES; NITROCELLULOSE; TRYPANOSOMES AB The aim of this study was to investigate the antigenic structures of the morphologically distinct cells of the Coxiella burnetii developmental cycle. Postembedding immunoelectron microscopy with polyclonal antibodies produced in rabbits to (i) phase I cells, (ii) a chloroform-methanol residue fraction of cells, (iii) the cell walls (CW) of large and small cells and small dense cells (SDC), and (iv) the peptidoglycan-protein complexes of small cells and SDC labelled the continuum of morphologically distinct cells. But these antibodies did not distinguish between the antigenic structures of the various cells. Monoclonal antibodies to the phase I lipopolysaccharide labelled the CW of a majority of the smaller cells, but there was diminished reactivity to the larger cells. Although monoclonal antibodies to a 29.5-kDa outer membrane protein labelled the CW of the large mother cells, the large cells, and the small cells, a minority of the SDC with compact CW were not labelled. The endogenous spore within the mother cell was not labelled by the polyclonal or monoclonal antibodies to cellular components. A selected population of SDC was prepared by osmotic lysis of large cells, differential centrifugation, Renografin step-gradient fractionation, and breakage of the small cells in a French press at 20,000 lb/in2. The pressure-resistant SDC collected as fraction CL did not contain the 29.5-kDa protein, as evidenced by the lack of (i) Coomassie brilliant blue staining of protein in the 29.5-kDa region of sodium dodecyl sulfate-polyacrylamide gels and (ii) reactivity of the 29.5-kDa protein antigenic epitopes in immunoblotting with monoclonal antibodies to the protein. In contrast, CW of the pressure-sensitive small cells contained the 29.5-kDa protein. Therefore, the observed ultrastructural differences between large and small cells and SDC reflect differences in sensitivity to breakage by pressure treatment and in cell-associated antigens. Although the process of differentiation in C. burnetii remains an enigma, we have taken steps toward identifying cellular antigens as markers of differentiation. The pressure-resistant SDC in fraction CL that are devoid of the 29.5-kDa protein may be useful for answering questions about the physiological events required for triggering outgrowth and sequential regulation of the Coxiella developmental cycle. C1 USA,MED RES INST INFECT DIS,DEPT INTRACELLULAR PATHOGENS,DIV BACTERIOL,FT DETRICK,FREDERICK,MD 21702. NIAID,OFF DIRECTOR INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. NR 39 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1991 VL 59 IS 9 BP 3243 EP 3253 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GD020 UT WOS:A1991GD02000055 PM 1715326 ER PT J AU MANGAN, DF TAICHMAN, NS LALLY, ET WAHL, SM AF MANGAN, DF TAICHMAN, NS LALLY, ET WAHL, SM TI LETHAL EFFECTS OF ACTINOBACILLUS-ACTINOMYCETEMCOMITANS LEUKOTOXIN ON HUMAN LYMPHOCYTES-T SO INFECTION AND IMMUNITY LA English DT Article ID CELL-DEATH; DNA FRAGMENTATION; CYTOLYSIS; APOPTOSIS; PERIODONTITIS; TRANSLATION; EXTRACTION; ACTIVATION; LYSIS AB The majority of strains of Actinobacillus actinomycetemcomitans isolated from patients with periodontal diseases secrete a leukotoxin that destroys human myeloid cells within minutes but has no effect on viability of peripheral blood lymphocytes in culture for 1.5 h. However, since this organism persists in the gingival crevice and thus may continuously release toxin over extended periods of time, we assessed the viability of T cells cultured with leukotoxin (0 to 250 ng/ml) for up to 2 days. Although the total numbers of cells recovered from cultures with or without leukotoxin were equivalent, leukotoxin killed up to 70% of the T cells in a time- and concentration-dependent manner. Cell death was associated with uptake of propidium iodide, release of Cr-51 from the cytoplasm, and morphological evidence of damage to the plasma membrane and apoptosis. Leukotoxin also induced increased cleavage of chromosomal DNA into nucleosome-sized fragments, suggesting activation of an endogenous nuclease in the T cells. These data suggest that leukotoxin kills T cells by pathways resembling necrosis and programmed cell death. Leukotoxin-induced lymphotoxicity may represent a critical mechanism by which A. actinomycetemcomitans suppresses the host local immune response and contributes to the pathogenesis of diseases involving this microorganism. C1 UNIV PENN,SCH DENT MED,DEPT PATHOL,PHILADELPHIA,PA 19104. RP MANGAN, DF (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [DE08239, DE09517, DE07118] NR 25 TC 97 Z9 99 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1991 VL 59 IS 9 BP 3267 EP 3272 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GD020 UT WOS:A1991GD02000058 PM 1879940 ER PT J AU HARINDRANATH, N GOLDFARB, IS IKEMATSU, H BURASTERO, SE WILDER, RL NOTKINS, AL CASALI, P AF HARINDRANATH, N GOLDFARB, IS IKEMATSU, H BURASTERO, SE WILDER, RL NOTKINS, AL CASALI, P TI COMPLETE SEQUENCE OF THE GENES ENCODING THE VH AND VL REGIONS OF LOW-AFFINITY AND HIGH-AFFINITY MONOCLONAL IGM AND IGA1 RHEUMATOID FACTORS PRODUCED BY CD5+ B-CELLS FROM A RHEUMATOID-ARTHRITIS PATIENT SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD5+ B-CELLS; IG V-GENES; RHEUMATOID FACTOR; RHEUMATOID ARTHRITIS ID IMMUNOGLOBULIN HEAVY-CHAIN; CHRONIC LYMPHOCYTIC-LEUKEMIA; COMPLEMENTARITY-DETERMINING REGION; ANTI-GAMMA-GLOBULINS; AMINO-ACID-SEQUENCE; LAMBDA-LIGHT CHAIN; VARIABLE REGIONS; SOMATIC MUTATION; NUCLEOTIDE-SEQUENCES; IMMUNE-COMPLEXES AB We have characterized the V(H) and V(L) genes of three low-affinity polyreactive and two high-affinity monoreactive IgM and IgA1 rheumatoid factor (RF) mAb generated using circulating CD5+ B cells from a single rheumatoid arthritis patient. We found that four and one RF mAb utilized genes of the V(H)IV and V(H)III families, respectively. The V(H)IV gene usage by these RF mAb differs from the preferential V(H)III, V(H)I, and, to a lesser extent, V(H)II gene usage by the IgM with RF activity found in patients with mixed cryoglobulinemia, Waldenstrom's macroglobulinemia, and other monoclonal gammopathies. In addition, in contrast to the preponderant kappa-L chain usage by the RF in these patients, a lambda-L chain was utilized by all RF mAb from our rheumatoid arthritis patient. Two RF mAbs utilized V-lambda-I, two V-lambda-IV, and one V-lambda-III L chains. The V(H) genes of the two low-affinity polyreactive IgM RF mAb were in germline configuration. When compared with the deduced amino acid sequence of the putatively corresponding genomic segment, the V(H) gene of the high-affinity monoreactive IgM RF mAb displayed five amino acid differences, all of which are in the complementarity determining regions (CDR), possibly the result of a process of somatic point mutation and clonal selection driven by Ag. The unavailability of the corresponding genomic V(H) segment sequences made it impossible to infer whether the V(H) genes utilized by the two IgA1 RF were in a germline or somatically mutated configuration. Sequencing of the genes encoding the H chain CDR3 (D segments) revealed that all three low-affinity polyreactive RF mAb displayed a much longer D segment (36 - 45 bases) than their high-affinity monoreactive counterparts (15-24 bases), raising the possibility that a long D segment may be one of the factors involved in antibody polyreactivity. C1 NYU,SCH MED,DEPT PATHOL,MSB-599,550 1ST AVE,NEW YORK,NY 10016. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. NYU,KAPLAN CANC CTR,SCH MED,NEW YORK,NY 10016. RI Casali, Paolo/F-6579-2010 FU NIAMS NIH HHS [R01 AR040908] NR 89 TC 122 Z9 122 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1991 VL 3 IS 9 BP 865 EP 875 DI 10.1093/intimm/3.9.865 PG 11 WC Immunology SC Immunology GA GE616 UT WOS:A1991GE61600003 PM 1718404 ER PT J AU KEHRL, JH AF KEHRL, JH TI TRANSFORMING GROWTH-FACTOR -BETA - AN IMPORTANT MEDIATOR OF IMMUNOREGULATION SO INTERNATIONAL JOURNAL OF CELL CLONING LA English DT Review DE TGF-BETA; IMMUNOSUPPRESSION; IMMUNOREGULATION; LYMPHOCYTES; MONOCYTES ID CELL SUPPRESSOR FACTOR; DEOXYRIBONUCLEIC-ACID CLONING; MESSENGER RIBONUCLEIC-ACID; LYMPHOCYTES-B; TGF-BETA; RETINOBLASTOMA PROTEIN; EMBRYO CHONDROCYTES; GENE-TRANSCRIPTION; COMPLEMENTARY-DNA; HUMAN-PLATELETS AB Transforming growth factor-beta (TGF-beta) is synthesized and secreted by a wide variety of cells, including cells of the immune system. Lymphocytes and monocytes possess high affinity TGF-beta-receptors and the addition of TGF-beta to in vitro cell cultures results in significant modulation of immune function. TGF-beta-inhibits the proliferation of thymocytes, T cells, B cells, and natural killer cells. Additionally, it inhibits certain differentiative functions of lymphocytes including a marked inhibition of immunoglobulin production by human B lymphocytes. TGF-beta has dichotomous actions on monocytes. It is a potent chemoattractant for monocytes and induces interleukin 1 mRNA expression while inhibiting generation of reactive oxygen intermediates and monocyte killing. Evidence is accumulating that TGF-beta-regulates immune function in vivo and that overproduction of TGF-beta may be associated with immunosuppression. RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 66 TC 95 Z9 97 U1 0 U2 0 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 0737-1454 J9 INT J CELL CLONING PD SEP PY 1991 VL 9 IS 5 BP 438 EP 450 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA GH260 UT WOS:A1991GH26000001 PM 1955735 ER PT J AU KUNIYASU, H YOSHIDA, K YOKOZAKI, H YASUI, W ITO, H TOGE, T CIARDIELLO, F PERSICO, MG SAEKI, T SALOMON, DS TAHARA, E AF KUNIYASU, H YOSHIDA, K YOKOZAKI, H YASUI, W ITO, H TOGE, T CIARDIELLO, F PERSICO, MG SAEKI, T SALOMON, DS TAHARA, E TI EXPRESSION OF CRIPTO, A NOVEL GENE OF THE EPIDERMAL GROWTH-FACTOR FAMILY, IN HUMAN GASTROINTESTINAL CARCINOMAS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Note DE CRIPTO; GASTROINTESTINAL CARCINOMA; GROWTH FACTOR ID HUMAN GASTRIC CARCINOMAS; AUTOCRINE GROWTH; RECEPTOR GENES; FACTOR-ALPHA; CELLS; EGF AB The expression of mRNA for cripto gene, a novel transforming gene of the epidermal growth factor family, was examined in 20 alimentary tract carcinoma cell lines, 60 surgically resected tumor tissues and their adjacent normal mucosas. Although the cripto mRNA was not detected in esophageal carcinomas or in normal mucosas, it was detected in gastric and colorectal carcinomas. In gastric carcinomas, 2.2 kb cripto mRNA was detected in one cell line, all the gastric carcinoma tissues and their adjacent normal mucosas. Of 23 gastric tumor tissues 8 (34.8%) exhibited a higher mRNA level than normal gastric mucosas. cripto mRNA was detected in 2 out of 6 colorectal carcinoma cell lines. Interestingly, 18 (81.8%) out of 22 colorectal carcinoma specimens expressed a higher level of cripto mRNA than that in normal mucosas. The level of the expression was higher than that in gastric carcinoma tissues. The expression was also correlated to tumor stage of colorectal carcinomas. C1 HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,1-2-3 KASUMI,MINAMI KU,HIROSHIMA 734,JAPAN. INT INST GENET & BIOPHYS,I-80125 NAPLES,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. HIROSHIMA UNIV,NUCL MED & BIOL RES INST,DEPT SURG,MINAMI KU,HIROSHIMA 734,JAPAN. OI Ciardiello, Fortunato/0000-0002-3369-4841; Yokozaki, Hiroshi/0000-0001-5276-3331 NR 13 TC 50 Z9 50 U1 0 U2 1 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD SEP PY 1991 VL 82 IS 9 BP 969 EP 973 PG 5 WC Oncology SC Oncology GA GF280 UT WOS:A1991GF28000003 PM 1938601 ER PT J AU LIJINSKY, W THOMAS, BJ KOVATCH, RM AF LIJINSKY, W THOMAS, BJ KOVATCH, RM TI LOCAL AND SYSTEMIC CARCINOGENIC EFFECTS OF ALKYLATING CARCINOGENS IN RATS TREATED BY INTRAVESICULAR ADMINISTRATION SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE NITROSAMINE; ALKYLATING AGENT; RAT; INTRAVESICULAR; TUMOR ID NUCLEIC-ACID ALKYLATION; BLADDER-TUMORS; F344 RATS; COMPARATIVE METABOLISM; GUINEA-PIGS; INDUCTION; HAMSTERS; NITROSAMINES; DNA; N-NITROSO-2,6-DIMETHYLMORPHOLINE AB Several nitrosamines and an azoxyalkane have been administered intravesically to groups of 12 female F344 rats, twice a week for 20 or 30 weeks. Many of the nitrosamines were as efficacious in giving rise to the same tumors of internal organs as when similar doses were administered orally, showing that absorption from the bladder was as rapid as from other sites. The tumors produced included lung and kidney tumors by nitrosodimethylamine, colon and Zymbal gland tumors by azoxymethane, liver tumors by methylnitrosoethylamine (but not by nitrosodimethylamine), liver and esophagus tumors by nitrosodiethylamine, liver and lung tumors by methylnitrosamino-3-pyridylbutanone, liver tumors by nitrosomorpholine, and tumors of the esophagus by methylnitroso-n-butylamine, 2,6-dimethylnitrosomorpholine and methylnitrosamino-N,N-dimethylethylamine. Bladder tumors were induced by intravesicular administration of only low doses of nitrosobis-(2-oxopropyl)amine and to a lesser extent by methylnitroso-n-hexylamine and nitroso-(2-hydroxypropyl)(2-oxopropyl)amine, which all induced tumors systemically in addition. The bladder mucosa seemed to lack enzymes necessary to activate most nitrosamines to locally acting proximate carcinogens, but was quite transparent to the passage of carcinogenic nitrosamines present in the urine into the body to induce tumors in distant organs. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 27 TC 17 Z9 17 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD SEP PY 1991 VL 82 IS 9 BP 980 EP 986 PG 7 WC Oncology SC Oncology GA GF280 UT WOS:A1991GF28000005 PM 1938603 ER PT J AU GOLDBERGER, BA CAPLAN, YH MAGUIRE, T CONE, EJ AF GOLDBERGER, BA CAPLAN, YH MAGUIRE, T CONE, EJ TI TESTING HUMAN HAIR FOR DRUGS OF ABUSE .3. IDENTIFICATION OF HEROIN AND 6-ACETYLMORPHINE AS INDICATORS OF HEROIN USE SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; POPPY-SEED; MORPHINE; URINE; CODEINE; CONSUMPTION; INGESTION; SPECTROSCOPY; URINALYSIS; OPIATES AB Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetyl-morphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing. C1 NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. NR 26 TC 126 Z9 129 U1 1 U2 5 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP-OCT PY 1991 VL 15 IS 5 BP 226 EP 231 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA GF917 UT WOS:A1991GF91700002 PM 1960970 ER PT J AU CONE, EJ YOUSEFNEJAD, D DARWIN, WD MAGUIRE, T AF CONE, EJ YOUSEFNEJAD, D DARWIN, WD MAGUIRE, T TI TESTING HUMAN HAIR FOR DRUGS OF ABUSE .2. IDENTIFICATION OF UNIQUE COCAINE METABOLITES IN HAIR OF DRUG-ABUSERS AND EVALUATION OF DECONTAMINATION PROCEDURES SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHROMATOGRAPHY; MORPHINE AB Two unique metabolites of cocaine, cocaethylene and norcocaine, were identified by GC/MS in the hair of cocaine users. Their presence cannot be explained by environmental contamination; thus, their presence together with cocaine provides convincing evidence that cocaine is excreted in hair after active cocaine administration. The amount of cocaine in hair predominated over all metabolites generally by a factor of 5-10. Two washing procedures were evaluated for their efficency in removal of cocaine from environmentally contaminated hair. Neither procedure completely removed cocaine, suggesting that false positives can result from environmental contamination. Analysis of the methanolic wash of the hair of cocaine users also revealed the presence of cocaine metabolites, indicating that washing removes cocaine from the interior as well as from the exterior surface of hair during decontamination procedures. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 16 TC 149 Z9 152 U1 2 U2 13 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP-OCT PY 1991 VL 15 IS 5 BP 250 EP 255 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA GF917 UT WOS:A1991GF91700007 PM 1960975 ER PT J AU SEDGWICK, SG HO, C WOODGATE, R AF SEDGWICK, SG HO, C WOODGATE, R TI MUTAGENIC DNA-REPAIR IN ENTEROBACTERIA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM LT2; ESCHERICHIA-COLI; RECA PROTEIN; ULTRAVIOLET-LIGHT; UMU OPERON; INDUCIBLE MUTAGENESIS; CHEMICAL MUTAGENESIS; INDUCED MUTABILITY; SEQUENCE-ANALYSIS; SOS MUTAGENESIS AB Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium umu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention. C1 NICHHD,VIRUSES & CELLULAR BIOL SECT,BLDG 6,ROOM 1A13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NATL INST MED RES,DIV GENET,LONDON NW7 1AA,ENGLAND. NR 52 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1991 VL 173 IS 18 BP 5604 EP 5611 PG 8 WC Microbiology SC Microbiology GA GF098 UT WOS:A1991GF09800002 PM 1885540 ER PT J AU ROSNER, JL CHAI, TJ FOULDS, J AF ROSNER, JL CHAI, TJ FOULDS, J TI REGULATION OF OMPF PORIN EXPRESSION BY SALICYLATE IN ESCHERICHIA-COLI SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEINS; INTEGRATION HOST FACTOR; RNA TRANSCRIPT MICRNA; GENE-EXPRESSION; MICF RNA; ENVIRONMENTAL SENSOR; K-12; MUTANTS; LOCUS; ENVZ AB The expression of ompF, the gene encoding a major outer membrane protein of Escherichia coli, is regulated by various environmental factors. The mechanism by which salicylate (SAL) drastically reduces ompF expression was studied here by means of lacZ fusions to ompF, ompC, and micF, by sodium dodecyl sulfate-gel electrophoresis of outer membrane proteins, and by measurements of outer membrane permeability. Growth of E. coli in LB broth containing SAL strongly reduced ompF-specific translation of an ompF-lacZ fusion. The extent of this reduction varied with the SAL concentration from 64% at 0.5 mM to 95% at 2 mM and > 99% at 10 mM. ompF-lacZ transcription was not affected by SAL, whereas ompC-lacZ transcription was elevated by 70%. Since the micF transcript is antisense to a portion of the ompF transcript and is capable of decreasing the translation of ompF, the effect of SAL on micF transcription was measured in a micF-lacZ fusion strain. SAL-grown cells contained three- to fourfold more micF transcript during the logarithmic phase of growth than did the control cultures. However, micF was not absolutely required for the response to SAL. In micF-deleted strains, the effects of SAL on ompF translation, on OmpF in the outer membrane, and on outer membrane permeability were diminished but still evident. The effect of SAL on ompF expression was independent of the osmolarity of the medium and was epistatic to certain ompB regulatory mutations: the high levels of ompF expression found in envZ3 and ompR472 strains were greatly reduced by growth in SAL. Unexpectedly, the OmpC- phenotypes of these mutants were suppressed by SAL. Thus, growth in SAL severely decreases the translation of ompF while enhancing the transcription of micF and ompC. In this respect, SAL-grown cells resemble certain marA and tolC mutants that have high levels of micF and ompC transcripts and low levels of OmpF. C1 NIDDKD,STRUCT BIOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,HORN POINT ENVIRONM LABS,CAMBRIDGE,MD 21613. RP ROSNER, JL (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 48 TC 55 Z9 57 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1991 VL 173 IS 18 BP 5631 EP 5638 PG 8 WC Microbiology SC Microbiology GA GF098 UT WOS:A1991GF09800006 PM 1715858 ER PT J AU BRANDAZZA, A LEE, E FERRERA, M TILLMAN, U SARMIENTOS, P WESTPHAL, H AF BRANDAZZA, A LEE, E FERRERA, M TILLMAN, U SARMIENTOS, P WESTPHAL, H TI USE OF THE UROKINASE-TYPE PLASMINOGEN-ACTIVATOR GENE AS A GENERAL TOOL TO MONITOR EXPRESSION IN TRANSGENIC ANIMALS - STUDY OF THE TISSUE-SPECIFICITY OF THE MURINE WHEY ACIDIC PROTEIN (WAP) EXPRESSION SIGNALS SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE WHEY ACIDIC PROTEIN; TRANSGENIC MICE; TISSUE-SPECIFIC EXPRESSION; MILK; UROKINASE-TYPE PLASMINOGEN ACTIVATOR ID PRO-UROKINASE; HORMONAL-REGULATION; ESCHERICHIA-COLI; MAMMARY-GLAND; HUMAN-PLASMA; MOUSE; MICE; PROMOTER; MILK; FORM AB Urokinase-type plasminogen activator (uPA) is a proteolytic enzyme able to convert the zymogen plasminogen into the strong protease plasmin. The availability of very sensitive tests to measure the enzymatic activity of a plasminogen activator renders the corresponding gene an ideal candidate for the detection of promoter activity. In this paper we describe the utilization of the human uPA gene as detector of tissue-specificity of the murine whey acidic protein (WAP) expression signals in transgenic mice. The WAP promoter has been previously investigated for the production of foreign proteins in the milk of transgenic animals. In our genetic constructions, the human uPA cDNA was linked to the promoter region as well as to 3'-end distal sequences of the WAP gene. Five transgenic lines were obtained in which, however, expression levels of human uPA in the milk were still quite low. Surprisingly, four of these five positive transgenic mice show a consistent activity of the WAP promoter in brain extracts compared to other tissues. C1 NICHHD,MAMMALIAN GENET & DEV LAB,BETHESDA,MD. RP BRANDAZZA, A (reprint author), FARMITALIA CARLO ERBA SPA,DEPT BIOTECHNOL,VIALE BEZZI 24,I-20146 MILAN,ITALY. NR 26 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD SEP PY 1991 VL 20 IS 2 BP 201 EP 212 DI 10.1016/0168-1656(91)90228-N PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA GC674 UT WOS:A1991GC67400008 PM 1367547 ER PT J AU FU, YM SPIRITO, P YU, ZX BIRO, S SASSE, J LEI, J FERRANS, VJ EPSTEIN, SE CASSCELLS, W AF FU, YM SPIRITO, P YU, ZX BIRO, S SASSE, J LEI, J FERRANS, VJ EPSTEIN, SE CASSCELLS, W TI ACIDIC FIBROBLAST GROWTH-FACTOR IN THE DEVELOPING RAT EMBRYO SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOTHELIAL-CELL MITOGEN; EARLY XENOPUS EMBRYO; CHICK-EMBRYO; BRAIN; RETINA; FGF; EMBRYOGENESIS; LOCALIZATION; SEQUENCE; MESODERM AB Compared to basic fibroblast growth factor (bFGF), a widely distributed, broad spectrum mitogen and mesoderm inducer, acidic fibroblast growth factor (aFGF) is reported to have an essentially neural distribution and to be undetectable in the early embryo. In the present investigation, we used immunoblotting and immunochemistry to assess the cellular and tissue distributions of aFGF and bFGF in 11-20-d rat embryos. Immunoblotting of crude and heparin-bound embryo extracts revealed faint bands at the expected 17-18-kD and predominant bands at an apparent molecular mass of 26 to 28-kD (despite reducing conditions) using multiple specific antibodies for aFGF and bFGF. Pretreatment with 8 M urea yielded 18-20-kD aFGF and bFGF and some 24-26-kD bFGF. Immunoreactivity for both aFGF and bFGF was positive and similar in the cytoplasm, nuclei, and extracellular matrix of cells of neuroectodermal and mesodermal origin, while it was negative in endoderm-derived cells. The distribution of immunoreactive aFGF and bFGF also showed changes during development that were associated with the process of cellular and tissue differentiation. For example, intensity and extent of immunoreactivity for both peptides progressively increased in the middle layer of the spinal cord with increasing differentiation of the neural cells. The immunostaining patterns were very similar for aFGF and bFGF for each organ and at each stage. In conclusion, high molecular mass forms of immunoreactive aFGF and bFGF are present in the rat embryo. Acidic FGF and bFGF are both widely distributed in tissues of neuroectodermal and mesodermal origin, and their distribution was very similar. C1 SHRINERS HOSP CRIPPLED CHILDREN,TAMPA,FL 33612. NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BETHESDA,MD 20892. RP FU, YM (reprint author), NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 62 TC 114 Z9 115 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1991 VL 114 IS 6 BP 1261 EP 1273 DI 10.1083/jcb.114.6.1261 PG 13 WC Cell Biology SC Cell Biology GA GF096 UT WOS:A1991GF09600014 PM 1716635 ER PT J AU NAGAI, T YAMAKAWA, N AOTA, S YAMADA, SS AKIYAMA, SK OLDEN, K YAMADA, KM AF NAGAI, T YAMAKAWA, N AOTA, S YAMADA, SS AKIYAMA, SK OLDEN, K YAMADA, KM TI MONOCLONAL-ANTIBODY CHARACTERIZATION OF 2 DISTANT SITES REQUIRED FOR FUNCTION OF THE CENTRAL CELL-BINDING DOMAIN OF FIBRONECTIN IN CELL-ADHESION, CELL-MIGRATION, AND MATRIX ASSEMBLY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN-PLASMA FIBRONECTIN; ARG-GLY-ASP; HEPARIN-BINDING; CYTOSKELETAL ORGANIZATION; PROTEOLYTIC FRAGMENTS; SURFACE RECEPTORS; RECOGNITION; ATTACHMENT; INTEGRIN; PROTEINS AB Site-directed mutagenesis studies have suggested that additional peptide information in the central cell-binding domain of fibronectin besides the minimal Arg-Gly-Asp (RGD) sequence is required for its full adhesive activity. The nature of this second, synergistic site was analyzed further by protein chemical and immunological approaches using biological assays for adhesion, migration, and matrix assembly. Fragments derived from the cell-binding domain were coupled covalently to plates, and their specific molar activities in mediating BHK cell spreading were compared with that of intact fibronectin. A 37-kD fragment purified from chymotryptic digests of human plasma fibronectin had essentially the same specific molar activity as intact fibronectin. In contrast, other fragments such as an 11.5-kD fragment lacking NH2-terminal sequences of the 37-kD fragment had only poor spreading activity on a molar basis. Furthermore, in competitive inhibition assays of fibronectin-mediated cell spreading, the 37-kD fragment was approximately 325-fold more active than the GRGDS synthetic peptide on a molar basis. mAbs were produced using the 37-kD protein as an immunogen and their epitopes were characterized. Two separate mAbs, one binding close to the RGD site and the other to a site approximately 15 kD distant from the RGD site, individually inhibited BHK cell spreading on fibronectin by > 90%. In contrast, an antibody that bound between these two sites had minimal inhibitory activity. The antibodies found to be inhibitory in cell spreading assays for BHK cells also inhibited both fibronectin-mediated cell spreading and migration of human HT-1080 cells, functions which were also dependent on function of the alpha-5-beta-1 integrin (fibronectin receptor). Assembly of endogenously synthesized fibronectin into an extracellular matrix was not significantly inhibited by most of the anti-37-kD mAbs, but was strongly inhibited only by the antibodies binding close to the RGD site or the putative synergy site. These results indicate that a second site distant from the RGD site on fibronectin is crucial for its full biological activity in diverse functions dependent on the alpha-5-beta-1 fibronectin receptor. This site is mapped by mAbs closer to the RGD site than previously expected. C1 NIDR,DEV BIOL LAB,BLDG 30,ROOM 414,BETHESDA,MD 20892. HOWARD UNIV,CTR CANC,WASHINGTON,DC 20060. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-14718, CA-45290, CA-45515] NR 58 TC 134 Z9 135 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1991 VL 114 IS 6 BP 1295 EP 1305 DI 10.1083/jcb.114.6.1295 PG 11 WC Cell Biology SC Cell Biology GA GF096 UT WOS:A1991GF09600017 PM 1716636 ER PT J AU FURLONG, RA TAKEHARA, T TAYLOR, WG NAKAMURA, T RUBIN, JS AF FURLONG, RA TAKEHARA, T TAYLOR, WG NAKAMURA, T RUBIN, JS TI COMPARISON OF BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES INDICATES THAT SCATTER FACTOR AND HEPATOCYTE GROWTH-FACTOR ARE INDISTINGUISHABLE SO JOURNAL OF CELL SCIENCE LA English DT Article DE SCATTER FACTOR; HEPATOCYTE GROWTH FACTOR; BIOASSAYS; IMMUNOBLOTTING ID EPITHELIAL-CELLS; MOLECULAR-CLONING; RAT PLATELETS; PURIFICATION; FIBROBLASTS; EXPRESSION; CDNA AB Scatter factor, a stimulant of epithelial cell motility, and Hepatocyte Growth Factor (HGF) were compared by cross-biological studies using naturally occurring and recombinant proteins in four bioassays. Both scatter factor and HGF produced similar effects in cell motility and DNA synthesis assays. Antibodies to scatter factor or HGF neutralized the biological activities of each cytokine, and in immunoblotting reacted with species of the same M(r). These results, together with the available sequence data, suggest that scatter factor and HGF are the same protein. C1 IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 812,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP FURLONG, RA (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,TENNIS COURT RD,CAMBRIDGE CB2 1QP,ENGLAND. NR 26 TC 135 Z9 138 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1991 VL 100 BP 173 EP 177 PN 1 PG 5 WC Cell Biology SC Cell Biology GA GG030 UT WOS:A1991GG03000019 PM 1839027 ER PT J AU DOUDET, DJ MCLELLAN, CA CARSON, R ADAMS, HR MIYAKE, H AIGNER, TG FINN, RT COHEN, RM AF DOUDET, DJ MCLELLAN, CA CARSON, R ADAMS, HR MIYAKE, H AIGNER, TG FINN, RT COHEN, RM TI DISTRIBUTION AND KINETICS OF 3-O-METHYL-6-[F-18]FLUORO-L-DOPA IN THE RHESUS-MONKEY BRAIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE 3-O-METHYL-6[F-18]FLUORO-L-DOPA; POSITRON EMISSION TOMOGRAPHY; COMPARTMENT MODEL; [F-18]DOPA ID POSITRON EMISSION TOMOGRAPHY; DOPAMINE DISTRIBUTION; PARKINSONS-DISEASE; LIVING MONKEYS; HOODED RAT; METABOLISM; BLOOD; PLASMA; MPTP; 6-FLUORO-L-DOPA AB Most attempts to model accurately [F-18]DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[F-18]fluoro-L-DOPA ([F-18]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [F-18]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered F-18-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective F-18 regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [F-18]3-OM-DOPA. In conclusion, assumptions concerning [F-18]3-OM-DOPA's behavior in brain appear acceptable for [F-18]DOPA modeling purposes. C1 NIH,CC,DEPT NUCL MED,BETHESDA,MD 20892. NIMH,IRP,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP DOUDET, DJ (reprint author), NIMH,IRP,CLIN BRAIN IMAGING SECT,LCM,BLDG 10-4N317,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 28 TC 56 Z9 56 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1991 VL 11 IS 5 BP 726 EP 734 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA GD344 UT WOS:A1991GD34400003 PM 1874805 ER PT J AU JONES, TH BLUM, MS FALES, HM BRANDAO, CRF LATTKE, J AF JONES, TH BLUM, MS FALES, HM BRANDAO, CRF LATTKE, J TI CHEMISTRY OF VENOM ALKALOIDS IN THE ANT GENUS MEGALOMYRMEX SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE MEGALOMYRMEX; HYMENOPTERA; FORMICIDAE; VENOM; ALKALOIDS; ANTS; TRANS-2,5-DIALKYLPYRROLIDINE; 3,5-DIALKYLPYRROLIZIDINE; HOFMANN DEGRADATION ID THIEF ANT; MONOMORIUM; SOLENOPSIS AB Chemical analyses of three species in the Neotropical ant genus Megalomyrmex have identified this taxon as the third myrmicine genus to produce alkaloids as major venom products. Workers of M. leoninus and workers and ergatoids of M. goeldii produce one or more of four trans-2,5-dialkylpyrrolidines previously identified in other myrmicine genera. M. modestus, on the other hand, is distinctive in producing the novel alkaloid (5E,8E)-3-butyl-5-hexylpyrrolizidine (5d), whose structure was established using a micro-Hofmann degradation sequence. The relationship of Megalomyrmex to other alkaloid-producing ant genera is discussed along with the possible chemotaxonomic significance of the analyzed species when viewed in terms of the recognized species groups in this genus. C1 UNIV GEORGIA,DEPT ENTOMOL,ATHENS,GA 30602. UNIV SAO PAULO,MUSEU ZOOL,BR-01051 SAO PAULO,SP,BRAZIL. UNIV SIMON BOLIVAR,FDN TERRAMAR SC,CARACAS 1080,VENEZUELA. RP JONES, TH (reprint author), NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892, USA. RI Lattke, John/K-2934-2015; Museu de Zoologia da USP, MZ-USP/Q-2192-2016 OI Lattke, John/0000-0002-6793-3003; NR 20 TC 14 Z9 14 U1 1 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD SEP PY 1991 VL 17 IS 9 BP 1897 EP 1908 DI 10.1007/BF00993736 PG 12 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA GG642 UT WOS:A1991GG64200013 PM 24257928 ER PT J AU KUHAR, MJ LLOYD, DG APPEL, N LOATS, HL AF KUHAR, MJ LLOYD, DG APPEL, N LOATS, HL TI IMAGING RECEPTORS BY AUTORADIOGRAPHY - COMPUTER-ASSISTED APPROACHES SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE RECEPTOR; AUTORADIOGRAPHY; IMAGE ANALYSIS; QUANTIFICATION ID LOCALIZATION; BRAIN; DETECTOR; BINDING; RAT AB Receptor autoradiography is one of the first fields where 'desktop' computer-assisted image analysis has been applied. Less than 10 years ago, the first image analysis systems were commercially marketed. Improvements on these early systems have been substantial and there are currently a wide variety of systems available for investigators. These systems dramatically reduce the time required for analysis, improve accuracy and increase the willingness to work in these areas. New techniques allowing autoradiography without emulsion will further expand opportunities for image analysis. While great strides have been made, significant affordable improvements are likely in the near future. RP KUHAR, MJ (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 23 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD SEP-OCT PY 1991 VL 4 IS 5 BP 319 EP 327 DI 10.1016/0891-0618(91)90040-J PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GK803 UT WOS:A1991GK80300003 PM 1659833 ER PT J AU JONES, BP DUNCAN, CC BROUWERS, P MIRSKY, AF AF JONES, BP DUNCAN, CC BROUWERS, P MIRSKY, AF TI COGNITION IN EATING DISORDERS SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID ANOREXIA-NERVOSA; BULIMIC PATIENTS; METABOLISM; ABNORMALITIES; PERFORMANCE AB Cognitive functions were investigated in four groups of women: 30 underweight anorexics, 38 normal-weight bulimics, 20 long-term weight-restored anorexics, and 39 normal controls. A MANOVA was used to examine performance on five neuropsychological domains derived from prior principal components analyses of a comprehensive neuropsychological battery. Underweight anorexics performed more poorly than normal controls in four of five neuropsychological domains (focusing/execution, verbal, memory, and visuospatial), while normal-weight bulimics showed poorer performances only in focusing/execution. The absolute differences in scores between eating disorder groups and normal controls were for the most part small, suggesting subtle rather than frank cognitive difficulties. Poorer neuropsychological test performance was associated with anxiety but not depression as measured by the Tryon, Stein, and Chu Tension scale and scale 2 of the MMPI respectively. The findings support previous reports of attentional difficulties in eating disorders but do not support the hypothesis of differential right-hemisphere dysfunction in eating disorders. RP JONES, BP (reprint author), NIMH, PSYCHOL & PSYCHOPATHOL LAB, 9000 ROCKVILLE PIKE, BLDG 10, ROOM 4C-110, BETHESDA, MD 20892 USA. NR 54 TC 80 Z9 82 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD SEP PY 1991 VL 13 IS 5 BP 711 EP 728 DI 10.1080/01688639108401085 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA GK476 UT WOS:A1991GK47600007 PM 1955527 ER PT J AU WALTMAN, C BLACKMAN, MR CHROUSOS, GP RIEMANN, C HARMAN, SM AF WALTMAN, C BLACKMAN, MR CHROUSOS, GP RIEMANN, C HARMAN, SM TI SPONTANEOUS AND GLUCOCORTICOID-INHIBITED ADRENOCORTICOTROPIC HORMONE AND CORTISOL SECRETION ARE SIMILAR IN HEALTHY-YOUNG AND OLD MEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA-CORTISOL; CIRCADIAN-RHYTHM; AGE; ACTH; DEXAMETHASONE; RESPONSES AB We investigated the effects of age on pituitary-adrenocortical function in healthy young (21-38 yr, n = 11) vs. old (66-78 yr, n = 11) men by drawing frequent serial basal blood samples from 2000-0800 h for measurement of ACTH and cortisol, followed by an iv ovine CRH (oCRH) stimulation test. Subjects were readmitted at intervals and given increasing doses of oral dexamethasone (0.15, 0.3, 0.6, 1 mg) at midnight, followed by repeat blood sampling from 0400-0800 h and oCRH testing. We compared mean hormone levels for the entire 12-h and three component 4-h periods of the basal visit, and for each 4-h dexamethasone visit using the Mann-Whitney U test and repeated measures analysis of variance. Pulsatile secretion was characterized using the Pulsar computer program. Basal mean 12-h and 4-h ACTH and cortisol values did not differ with age (P > 0.1). Pulse analysis revealed no age change in the corresponding values for peak frequency, amplitude, or duration for either hormone examined. Increasing doses of dexamethasone produced progressive inhibition of mean ACTH and cortisol levels (P < 0.001) as well as decreased (P < 0.01) pulse frequency, amplitude, and duration with no age differences (P > 0.1). ACTH and cortisol responses to oCRH were progressively suppressed by increasing doses of dexamethasone (P < 0.02) and did not differ between age groups (P > 0.3) except for a slightly higher peak cortisol response (P = 0.05) in the older men at the 0.3 mg dexamethasone dose. We conclude that basal and oCRH-stimulated ACTH and cortisol secretion, as well as sensitivity of the ACTH-cortisol axis to glucocorticoid feedback suppression, are essentially unaltered with age in healthy men. C1 NIA, GERONTOL RES CTR,CLIN PHYSIOL LAB,ENDOCRINOL SECT, ROOM 2B15,4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FRANCIS SCOTT KEY MED CTR, DEPT MED, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [M01-RR-02719] NR 38 TC 112 Z9 114 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1991 VL 73 IS 3 BP 495 EP 502 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GC695 UT WOS:A1991GC69500008 PM 1651956 ER PT J AU BERZOFSKY, JA PENDLETON, CD CLERICI, M AHLERS, J LUCEY, DR PUTNEY, SD SHEARER, GM AF BERZOFSKY, JA PENDLETON, CD CLERICI, M AHLERS, J LUCEY, DR PUTNEY, SD SHEARER, GM TI CONSTRUCTION OF PEPTIDES ENCOMPASSING MULTIDETERMINANT CLUSTERS OF HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE TO INDUCE INVITRO T-CELL RESPONSES IN MICE AND HUMANS OF MULTIPLE MHC TYPES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LYMPHOCYTE-T; EPITOPES; VACCINE; AIDS; HLA; HIV ID MAJOR HISTOCOMPATIBILITY COMPLEX; MALARIA-CIRCUMSPOROZOITE PROTEIN; HIV-1 INFECTION INVITRO; MYELIN BASIC-PROTEIN; TOXIC LYMPHOCYTES-T; CLASS-II; ANTIGEN RECOGNITION; FINE SPECIFICITY; PROLIFERATIVE RESPONSE; EPITOPE AB To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,HUMAN IMMUNOVIRUS LAB,LACKLAND AFB,TX 78236. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP BERZOFSKY, JA (reprint author), NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BLDG 10,ROOM 6B-12,BETHESDA,MD 20892, USA. NR 56 TC 95 Z9 96 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1991 VL 88 IS 3 BP 876 EP 884 DI 10.1172/JCI115389 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GD669 UT WOS:A1991GD66900021 PM 1715888 ER PT J AU HUBBARD, RC FELLS, G GADEK, J PACHOLOK, S HUMES, J CRYSTAL, RG AF HUBBARD, RC FELLS, G GADEK, J PACHOLOK, S HUMES, J CRYSTAL, RG TI NEUTROPHIL ACCUMULATION IN THE LUNG IN ALPHA-1-ANTITRYPSIN DEFICIENCY - SPONTANEOUS RELEASE OF LEUKOTRIENE-B4 BY ALVEOLAR MACROPHAGES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EMPHYSEMA; INFLAMMATION; BRONCHOALVEOLAR LAVAGE; NEUTROPHIL ELASTASE ANTIPROTEASE ID IDIOPATHIC PULMONARY FIBROSIS; HUMAN-LEUKOCYTE ELASTASE; ALPHA-1-PROTEINASE INHIBITOR; CHEMOTACTIC ACTIVITY; ALPHA1-ANTITRYPSIN DEFICIENCY; POLYMORPHONUCLEAR LEUKOCYTES; BRONCHOALVEOLAR LAVAGE; PROTEINASE-INHIBITORS; POTENTIAL MECHANISM; CIGARETTE SMOKERS AB The emphysema of alpha-1-antitrypsin (alpha-1AT) deficiency is conceptualized to result from insufficient alpha-1AT allowing neutrophil elastase to destroy lung parenchyma. In addition to the deficiency of alpha-1AT in these individuals resulting from mutations in the alpha-1AT gene, it is recognized that, for unknown reasons, there are also increased numbers of neutrophils in their lungs compared with normal individuals. With the knowledge that alveolar macrophages have surface receptors for neutrophil elastase, we hypothesized that the neutrophil accumulation in the lower respiratory tract in alpha-1AT deficiency may result, in part, from release of neutrophil chemotactic activity by alveolar macrophages as they bind uninhibited neutrophil elastase. Consistent with this hypothesis, alpha-1AT-deficient alveolar macrophages spontaneously released nearly threefold more neutrophil chemotactic activity than normal alveolar macrophages. Analysis of alpha-1AT-deficient macrophage supernates by reverse-phase HPLC, molecular sieve chromatography, radioimmuno-assay, and absorption with anti-LTB4 antibody revealed that the majority of the chemotactic activity was leukotriene B4 (LTB4), a mediator absent from normal macrophage supernates. Consistent with this hypothesis, incubation of normal macrophages with human neutrophil elastase resulted in the release of the same neutrophil chemotactic mediator. Furthermore, purified human alpha-1AT was able to prevent the neutrophil elastase from stimulating the macrophages to release the chemotactic factor. Together, these findings suggest that the absence of a normal antineutrophil elastase screen in the lower respiratory tract permits free neutrophil elastase to bind to alveolar macrophages, resulting in the release of LTB4, a process which attracts neutrophils to the alveoli of alpha-1AT deficient individuals, thus accelerating the lung destruction that characterizes this disorder. C1 MERCK INST THERAPEUT RES,RAHWAY,NJ 07065. RP HUBBARD, RC (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 63 TC 125 Z9 127 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1991 VL 88 IS 3 BP 891 EP 897 DI 10.1172/JCI115391 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GD669 UT WOS:A1991GD66900023 PM 1653278 ER PT J AU SHIMADA, T FUJII, H MITSUYA, H NIENHUIS, AW AF SHIMADA, T FUJII, H MITSUYA, H NIENHUIS, AW TI TARGETED AND HIGHLY EFFICIENT GENE-TRANSFER INTO CD4+ CELLS BY A RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS RETROVIRAL VECTOR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE GENE TRANSFER; GENE THERAPY; AIDS; INTRACELLULAR IMMUNIZATION; COS CELLS ID NUCLEOTIDE-SEQUENCE; AIDS VIRUS; STEM-CELLS; HTLV-III; THERAPY; EXPRESSION; RECEPTOR; ENCODES; SAFE; LINE AB We have established a recombinant HIV gene transfer system based on transient expression of the HIV packaging functions and a recombinant vector genome in monkey kidney Cos cells. The recombinant HIV retroviral vector introduced the neo(R) gene into CD4+ cells with high efficiency, comparable to that achieved with the highest titer amphotropic murine recombinant retrovirus. Vector preparations were devoid of replication competent, infectious HIV. Gene transfer was dependent on CD4 expression, as shown by expression of the CD4 gene in HeLa cells, and could be inhibited by soluble CD4. This specific and efficient gene transfer system may be useful for development of gene therapy for which T cells are the desired targets. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP SHIMADA, T (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. NR 29 TC 84 Z9 84 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1991 VL 88 IS 3 BP 1043 EP 1047 DI 10.1172/JCI115365 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GD669 UT WOS:A1991GD66900041 PM 1885765 ER PT J AU FONG, TL SHINDO, M FEINSTONE, SM HOOFNAGLE, JH DIBISCEGLIE, AM AF FONG, TL SHINDO, M FEINSTONE, SM HOOFNAGLE, JH DIBISCEGLIE, AM TI DETECTION OF REPLICATIVE INTERMEDIATES OF HEPATITIS-C VIRAL-RNA IN LIVER AND SERUM OF PATIENTS WITH CHRONIC HEPATITIS-C SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE POLYMERASE CHAIN REACTION; HEPATITIS-C REPLICATION ID GENOME AB The hepatitis C virus is a positive stranded hepatotropic RNA virus. We describe a method of detecting positive and negative strands of hepatitis C viral RNA using the polymerase chain reaction. We tested serum and liver tissue from nine patients with chronic hepatitis C. The positive RNA strand of HCV was detected in the sera and livers of all nine, the negative strand was detected in the livers of eight (89%), and in the sera of five (55%). Titers of both strands of HCV RNA were determined by serial endpoint dilutions. The amount of the negative strand in the serum and liver was usually 10-100 times less than the positive strand. Predigestion of serum with ribonucleases did not alter the detection of the negative strand. This suggests that the negative strand found in the serum may be protected from digestion by being associated with virions. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,ROCKVILLE,MD 20893. RP FONG, TL (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 14 TC 187 Z9 195 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1991 VL 88 IS 3 BP 1058 EP 1060 DI 10.1172/JCI115368 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GD669 UT WOS:A1991GD66900044 PM 1653272 ER PT J AU SIMPSON, WJ SCHRUMPF, ME HAYES, SF SCHWAN, TG AF SIMPSON, WJ SCHRUMPF, ME HAYES, SF SCHWAN, TG TI MOLECULAR AND IMMUNOLOGICAL ANALYSIS OF A POLYMORPHIC PERIPLASMIC PROTEIN OF BORRELIA-BURGDORFERI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LYME-DISEASE; MONOCLONAL-ANTIBODY; IMMUNOBLOT ANALYSIS; SURFACE-PROTEINS; ANTIGEN; MANIFESTATIONS; SPIROCHETE; REACTIVITY; STRAINS; COMMON AB Borrelia burgdorferi is the causative agent of Lyme disease, a tick-borne spirochetosis with a worldwide prevalence. To assist the categorization and typing of fresh isolates from global foci, we have identified a unique species-specific periplasmic protein (P22-A) conserved among all North American and European isolates examined. The gene encoding this antigen was cloned, and the recombinant was used to screen serum collected from experimentally infected animals. Although antibodies were detected in all infected animals at 21 days after inoculation with live, low-passage spirochetes, the response was stronger in other animals that were inoculated with inactivated and lysed bacteria. This result, along with the immune electron microscopy data, suggests P22-A is concentrated in the periplasmic space. The P22-A antigens exhibited size heterogeneity among different isolates, ranging between 20 and 23 kDa, but as a group the P22-A antigens appeared to retain antigenic homogeneity. Thus, P22-A can serve as a structural marker for characterizing new isolates of B. burgdorferi and may prove useful in future serological assays with a mixture of B. burgdorferi-specific antigens. C1 NIAID,ARTHROPOD BORNE DIS SECT,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. NR 36 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1991 VL 29 IS 9 BP 1940 EP 1948 PG 9 WC Microbiology SC Microbiology GA GB716 UT WOS:A1991GB71600035 PM 1774319 ER PT J AU PUCCIO, CA MITTELMAN, A LICHTMAN, SM SILVER, RT BUDMAN, DR AHMED, T FELDMAN, EJ COLEMAN, M ARNOLD, PM ARLIN, ZA CHUN, HG AF PUCCIO, CA MITTELMAN, A LICHTMAN, SM SILVER, RT BUDMAN, DR AHMED, T FELDMAN, EJ COLEMAN, M ARNOLD, PM ARLIN, ZA CHUN, HG TI A LOADING DOSE CONTINUOUS INFUSION SCHEDULE OF FLUDARABINE PHOSPHATE IN CHRONIC LYMPHOCYTIC-LEUKEMIA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NERVOUS-SYSTEM TOXICITY; I CLINICAL-TRIAL; PHASE-I; DEOXYCYTIDINE KINASE; 9-BETA-D-ARABINOFURANOSYL-2-FLUOROADENINE 5'-MONOPHOSPHATE; PURINE ANTIMETABOLITE; BIOLOGIC ACTIVITY; DEOXYADENOSINE; 5'-PHOSPHATE; METABOLISM C1 NEW YORK MED COLL,DIV NEOPLAST DIS,VALHALLA,NY 10595. N SHORE UNIV HOSP,MANHASSET,NY 11030. NEW YORK HOSP,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,NEW YORK,NY 10021. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVESTIGAT DRUG BRANCH,BETHESDA,MD 20892. NR 34 TC 80 Z9 81 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1991 VL 9 IS 9 BP 1562 EP 1569 PG 8 WC Oncology SC Oncology GA GD398 UT WOS:A1991GD39800008 PM 1714949 ER PT J AU ROWINSKY, EK MCGUIRE, WP GUARNIERI, T FISHERMAN, JS CHRISTIAN, MC DONEHOWER, RC AF ROWINSKY, EK MCGUIRE, WP GUARNIERI, T FISHERMAN, JS CHRISTIAN, MC DONEHOWER, RC TI CARDIAC DISTURBANCES DURING THE ADMINISTRATION OF TAXOL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; HISTAMINE-RELEASE; CREMOPHOR-EL; HEART; CARDIOTOXICITY; DOXORUBICIN; VINBLASTINE; MEDIATION; DISEASE; SYSTEM C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,DIV MED ONCOL,BALTIMORE,MD 21205. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. RP ROWINSKY, EK (reprint author), JOHNS HOPKINS UNIV HOSP,CTR ONCOL,DIV PHARMACOL & EXPTL THERAPEUT,600 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [N01-CM-5 7738] NR 42 TC 214 Z9 219 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1991 VL 9 IS 9 BP 1704 EP 1712 PG 9 WC Oncology SC Oncology GA GD398 UT WOS:A1991GD39800026 PM 1678781 ER PT J AU PARKINSON, DR AF PARKINSON, DR TI LEVAMISOLE AND MELANOMA - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP PARKINSON, DR (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 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 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1991 VL 9 IS 9 BP 1715 EP 1715 PG 1 WC Oncology SC Oncology GA GD398 UT WOS:A1991GD39800030 ER PT J AU DOPPMAN, JL NIEMAN, LK TRAVIS, WD MILLER, DL CUTLER, GB CHROUSOS, GP NORTON, JA AF DOPPMAN, JL NIEMAN, LK TRAVIS, WD MILLER, DL CUTLER, GB CHROUSOS, GP NORTON, JA TI CT AND MR IMAGING OF MASSIVE MACRONODULAR ADRENOCORTICAL DISEASE - A RARE CAUSE OF AUTONOMOUS PRIMARY ADRENAL HYPERCORTISOLISM SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CUSHING SYNDROME; ADRENAL GLANDS, ABNORMALITIES; ADRENAL GLANDS, DISEASES; HYPERCORTISOLISM; MAGNETIC RESONANCE IMAGING; COMPUTED TOMOGRAPHY ID CUSHINGS-SYNDROME; HYPERPLASIA AB We studied four patients with adrenocorticotropic hormone (ACTH)-independent hypercortisolism due to bilateral massive enlargement of the adrenal glands. The combined weight of the adrenal glands ranged from 69 to 149 g and the adrenal cortex was replaced in three of four patients by multiple nodules ranging from microscopic to 4 cm in diameter. One patient had massive diffuse enlargement. All patients had low or undetectable levels of serum ACTH, absence of petrosal sinus to peripheral gradients of ACTH in bilateral samples from the inferior petrosal sinuses before and after stimulation by corticotropin releasing hormone, and absence of an adenoma on MR imaging of the pituitary gland. The marked degree of adrenocortical enlargement and absence of ACTH dependency separates this massive macronodular disease from the more common ACTH-dependent macronodular hyperplasia encountered in older patients with pituitary-dependent Cushing disease. All patients required bilateral adrenalectomy to control hypercortisolism. We present the spectrum of nodular adrenal disease associated with hypercortisolism and a differential diagnosis based on morphologic criteria. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,PATHOL LAB,DIV CANC BIOL & DIAG,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT RADIOL,WASHINGTON,DC 20057. RP DOPPMAN, JL (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,ROOM 1C660,BETHESDA,MD 20892, USA. NR 17 TC 32 Z9 34 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1991 VL 15 IS 5 BP 773 EP 779 DI 10.1097/00004728-199109000-00009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GF354 UT WOS:A1991GF35400009 PM 1653280 ER PT J AU ARMSTRONG, MR DOUEK, M SCHELLINGER, D PATRONAS, NJ AF ARMSTRONG, MR DOUEK, M SCHELLINGER, D PATRONAS, NJ TI REGRESSION OF PITUITARY MACROADENOMA AFTER PITUITARY APOPLEXY - CT AND MR STUDIES SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE PITUITARY GLAND, NEOPLASMS; ADENOMA; TREATMENT AND TREATMENT PLANNING; COMPUTED TOMOGRAPHY; MAGNETIC RESONANCE IMAGING ID CARDIAC-SURGERY; HEMORRHAGE; ADENOMAS AB We present a Case of a patient with apoplexy due to infarction of a large pituitary macroadenoma. Conservative treatment with steroids resulted in reversal of symptoms and the adenoma involuted. This suggests that medical management may be sufficient therapy in some patients with this complication. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT RADIOL,DIV NEURORADIOL,WASHINGTON,DC 20007. NR 19 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1991 VL 15 IS 5 BP 832 EP 834 DI 10.1097/00004728-199109000-00021 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GF354 UT WOS:A1991GF35400021 PM 1885805 ER PT J AU EIDELMAN, N BROWN, WE MEYER, JL AF EIDELMAN, N BROWN, WE MEYER, JL TI SELECTIVE-INHIBITION OF CRYSTAL-GROWTH ON OCTACALCIUM PHOSPHATE AND NONSTOICHIOMETRIC HYDROXYAPATITE BY PYROPHOSPHATE AT PHYSIOLOGICAL CONCENTRATION SO JOURNAL OF CRYSTAL GROWTH LA English DT Article ID INORGANIC PYROPHOSPHATE; BONE-FORMATION; CALCIUM; SERUM; TRANSFORMATION; CALCIFICATION; SOLUBILITY; CARTILAGE; TISSUES; APATITE AB Octacalcium phosphate, Ca8H2(PO4)6.5H2O (OCP), appears to be a precursor in biomineral formation. The formation of OCP as the precursor is supported by the observation that stoichiometric hydroxyapatite, Ca5(PO4)3OH (OHAp), cannot form directly because of the presence of its growth inhibitors in serum. Therefore, the effects of the physiological concentration of pyrophosphate (P2O74-), one of the most important calcium phosphate growth inhibitors in blood, on calcium phosphate growth rates on OCP and nonstoichiometric OHAp) (apatite) seeds were measured. The amounts of seed crystals used to initiate the growth were adjusted by trial and error so that the control growth rates (in the absence of P2O74-) were the same on both OCP and apatite seeds at a given supersaturation. The crystal growth on both kinds of seed crystals from supersaturated solutions in the presence of 1-mu-M P2O74- added once ("one-time" addition) at constant pH (7.4) and 25-degrees-C was determined by KOH titration and decreases in Ca and PO4 concentrations in the solutions. Crystal growth on OCP seed crystals in the presence of a constant concentration of 1-mu-M P2O74- was also measured. The growing phases were characterized by DELTA-Ca/DELTA-PO4 ratios, chemical potential plots, X-ray diffraction (XRD) and Fourier transform infrared (FTIR). The results of this study show that: (1) P2O74- ions inhibited the growth on the apatite seeds more than on the OCP seeds; (2) apparently OCP precipitated on both types of seeds, followed by its hydrolysis to a more apatite-like phase; (3) slower crystal growth was observed on OCP seeds in the presence of a constant physiological concentration of P2O74- (1-mu-M) than in the "one-time" addition of P2O74-. C1 NCI,BETHESDA,MD 20892. RP EIDELMAN, N (reprint author), NATL INST STAND & TECHNOL,PAFFENBARGER RES CTR,AMER DENT ASSOC HLTH FDN,GAITHERSBURG,MD 20899, USA. NR 36 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-0248 J9 J CRYST GROWTH JI J. Cryst. Growth PD SEP PY 1991 VL 113 IS 3-4 BP 643 EP 652 DI 10.1016/0022-0248(91)90100-J PG 10 WC Crystallography; Materials Science, Multidisciplinary; Physics, Applied SC Crystallography; Materials Science; Physics GA GM356 UT WOS:A1991GM35600034 ER PT J AU LEUKEFELD, CG BATTJES, RJ PICKENS, RW AF LEUKEFELD, CG BATTJES, RJ PICKENS, RW TI AIDS PREVENTION - CRIMINAL-JUSTICE INVOLVEMENT OF INTRAVENOUS DRUG-ABUSERS ENTERING METHADONE TREATMENT SO JOURNAL OF DRUG ISSUES LA English DT Article C1 NIDA,DIV CLIN RES,LEXINGTON,KY 40583. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RP LEUKEFELD, CG (reprint author), UNIV KENTUCKY,CTR DRUG & ALCOHOL ABUSE RES,LEXINGTON,KY 40506, USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU J DRUG ISSUES INC PI TALLAHASSEE PA PO BOX 4021, TALLAHASSEE, FL 32315 SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD FAL PY 1991 VL 21 IS 4 BP 673 EP 683 PG 11 WC Substance Abuse SC Substance Abuse GA GT122 UT WOS:A1991GT12200001 ER PT J AU LAL, RB RUDOLPH, DL PALKER, TJ COLIGAN, JE FOLKS, TM AF LAL, RB RUDOLPH, DL PALKER, TJ COLIGAN, JE FOLKS, TM TI A SYNTHETIC PEPTIDE ELICITS ANTIBODIES REACTIVE WITH THE EXTERNAL GLYCOPROTEIN OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; MONOCLONAL-ANTIBODY; ENVELOPE PROTEIN; HTLV-I; GENOME; IDENTIFICATION; EPITOPE; GP21 AB A synthetic peptide derived from the external glycoprotein of human T cell lymphotropic virus type I (HTLV-I) (Env-5; amino acids 242 to 256) reacted with IgG antibodies in serum specimens from HTLV-I-infected individuals. C-terminal residues of Env-5 were crucial for the antibody reactivity. Polyclonal rabbit antibodies to Env-5 did not inhibit syncytium formation but such antibodies reacted specifically with gp68env and gp46env glycoproteins of HTLV-I in an immunoblot analysis. Immunoprecipitation of the surface-labelled MT-2 (HTLV-I-infected) cell line with anti-Env-5 precipitated the gp68env precursor protein. It was concluded that peptide Env-5 mimics a surface-exposed epitope on the HTLV-I external glycoprotein. C1 NIA,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DIV RHEUMATOL & IMMUNOL,DURHAM,NC 27710. RP LAL, RB (reprint author), CTR DIS CONTROL,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333, USA. NR 21 TC 17 Z9 17 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1991 VL 72 BP 2321 EP 2324 DI 10.1099/0022-1317-72-9-2321 PN 9 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA GE992 UT WOS:A1991GE99200041 PM 1716657 ER PT J AU GILBERT, DA PACKER, C PUSEY, AE STEPHENS, JC OBRIEN, SJ AF GILBERT, DA PACKER, C PUSEY, AE STEPHENS, JC OBRIEN, SJ TI ANALYTICAL DNA FINGERPRINTING IN LIONS - PARENTAGE, GENETIC DIVERSITY, AND KINSHIP SO JOURNAL OF HEREDITY LA English DT Article ID HYPERVARIABLE MINISATELLITES; PANTHERA-LEO; SEQUENCE; POPULATION; AFRICAN; IDENTIFICATION; COOPERATION; PATERNITY; MUTATION; ALLELES AB The application of hypervariable minisatellite genomic families to the reconstruction of population genetic structure holds great promise in describing the demographic history and future prospects of free-ranging populations. This potential has not yet been realized due to unforeseen empirical constraints associated with the use of heterologous species probes, to theoretical limitations on the power of the procedure to track genic heterozygosity and kinship, and to the absence of extensive field studies to test genetic predictions. We combine here the technical development of feline-specific VNTR (variable number tandem repeat) families of genetic loci with the long-term demographic and behavioral observations of lion populations of the Serengeti ecosystem in East Africa. Minisatellite variation was used to quantify the extent of genetic variation in several populations that differed in their natural history and levels of inbreeding. Definitive parentage, both maternal and paternal, was assessed for 78 cubs born in 11 lion prides, permitting the assessment of precise genealogical relationships among some 200 lions. The extent of DNA restriction fragment sharing between lions was empirically calibrated with the coefficient of relatedness, r, in two different populations that had distinct demographic histories. The results suggest that reliable estimates of relative genetic diversity, of parentage, and of individual relatedness can be achieved in free-ranging populations, provided the minisatellite family is calibrated in established pedigrees for the species. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYN CORP,FREDERICK,MD 21701. UNIV MINNESOTA,DEPT ECOL & BEHAV BIOL,MINNEAPOLIS,MN 55455. FU NCI NIH HHS [N01-CO-74102] NR 54 TC 125 Z9 126 U1 4 U2 24 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 1991 VL 82 IS 5 BP 378 EP 386 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA GQ521 UT WOS:A1991GQ52100003 PM 1940281 ER PT J AU WELDON, PJ SAMPSON, HW WONG, L LLOYD, HA AF WELDON, PJ SAMPSON, HW WONG, L LLOYD, HA TI HISTOLOGY AND BIOCHEMISTRY OF THE SCENT GLANDS OF THE YELLOW-BELLIED SEA-SNAKE (PELAMIS-PLATURUS, HYDROPHIIDAE) SO JOURNAL OF HERPETOLOGY LA English DT Note C1 TEXAS A&M UNIV SYST,COLL MED,DEPT HUMAN ANAT & MED NEUROBIOL,COLLEGE STN,TX 77843. UNIV CALIF DAVIS,DEPT BIOCHEM,DAVIS,CA 95616. NHLBI,CHEM LAB,BETHESDA,MD 20892. RP WELDON, PJ (reprint author), TEXAS A&M UNIV SYST,COLL MED,DEPT BIOL,COLLEGE STN,TX 77843, USA. NR 11 TC 7 Z9 8 U1 1 U2 5 PU SOC STUD AMPHIBIANS REPTILES PI OXFORD PA DEPT OF ZOOLOGY MIAMI UNIV, OXFORD, OH 45056 SN 0022-1511 J9 J HERPETOL JI J. Herpetol. PD SEP PY 1991 VL 25 IS 3 BP 367 EP 370 DI 10.2307/1564602 PG 4 WC Zoology SC Zoology GA GD953 UT WOS:A1991GD95300021 ER PT J AU CHANG, K DING, I KERN, FG WILLINGHAM, MC AF CHANG, K DING, I KERN, FG WILLINGHAM, MC TI IMMUNOHISTOCHEMICAL ANALYSIS OF P53 AND HER-2/NEU PROTEINS IN HUMAN TUMORS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE P53; HER-2/NEU; IMMUNOHISTOCHEMISTRY; PEROXIDASE; HUMAN BREAST CANCER; COLON CANCER; OVARIAN CANCER ID MONOCLONAL-ANTIBODIES; BREAST-CANCER; LUNG-CANCER; ACTIVATING MUTATIONS; SUPPRESSOR GENE; MUTANT P53; CELL-LINES; EXPRESSION; ONCOGENE; TRANSFORMATION AB We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (115). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 of higher levels of mutant p53 in comparison with more normal cells. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RP CHANG, K (reprint author), NCI,MOLEC BIOL LAB,ULTRASTRUCT CYTOCHEM SECT,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA50376] NR 30 TC 81 Z9 88 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1991 VL 39 IS 9 BP 1281 EP 1287 PG 7 WC Cell Biology SC Cell Biology GA GB792 UT WOS:A1991GB79200015 PM 1680897 ER PT J AU DIXON, D MARSHALL, KLE GREENWELL, A SHIMIZU, T NETTESHEIM, P MARONPOT, RR AF DIXON, D MARSHALL, KLE GREENWELL, A SHIMIZU, T NETTESHEIM, P MARONPOT, RR TI COMPARISON OF AUTOMATED AND MANUAL STAINING TECHNIQUES FOR THE BINDING OF WHEAT-GERM-AGGLUTININ (WGA) IN MODIFIED B5-FIXED AND FORMALIN-FIXED PULMONARY TISSUE SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE AUTOMATED LECTIN STAINING; LUNG; MOUSE; WGA AB An automated method for lectin staining using the Fisher Code-On(TM) series, with a modification of its general program, "Immunocode," is described. The lectin wheat germ agglutinin (WGA) was used for staining procedures. Comparisons were made between the lectin staining quality of formalin- vs modified B5-fixed lung tissue, using manual and automated staining techniques. Although automated and manual methods for lectin staining were comparable, the results obtained by automated staining were highly reproducible and less subject to inconsistencies due to human error. Automated staining also decreased consumption of costly reagents and saved laboratory personnel time (approximately 3.0 hr, automated vs 4.8 hr, manually). The intensity and discreteness of WGA staining was superior in the modified B5-vs formalin-fixed lung tissues with both automated and manual staining methods. RP DIXON, D (reprint author), NIEHS,DIV TOXICOL RES & TESTING,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD SEP PY 1991 VL 14 IS 3 BP 149 EP 153 PG 5 WC Cell Biology SC Cell Biology GA GE887 UT WOS:A1991GE88700002 ER PT J AU BLAZAR, BR HIRSCH, R GRESS, RE CARROLL, SF VALLERA, DA AF BLAZAR, BR HIRSCH, R GRESS, RE CARROLL, SF VALLERA, DA TI INVIVO ADMINISTRATION OF ANTI-CD3 MONOCLONAL-ANTIBODIES OR IMMUNOTOXINS IN MURINE RECIPIENTS OF ALLOGENEIC T-CELL-DEPLETED MARROW FOR THE PROMOTION OF ENGRAFTMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; VERSUS-HOST-DISEASE; TUMOR-NECROSIS-FACTOR; GRAFT-REJECTION; HYBRID RESISTANCE; MICE; ALLOGRAFTS; ACTIVATION; ANTIGENS; OKT3 AB The role of host anti-donor cells in rejection of fully allogeneic donor T cell-depleted marrow was investigated by using mAb or immunotoxins directed against T cell or NK cell determinants. Immunotoxins consisting of mAb conjugated to a low oligosaccharide-containing fraction of purified ricin toxin A chain (RTA) facilitated in vivo-depletion of target cell populations. BALB/c and DBA/1 donors were selected based upon their expression (BALB/c) or lack of (DBA/1) hemopoietic histocompatibility (Hh1) Ag, which may serve as targets for donor rejection in C57BL/6 hosts. When studies directed toward eliminating CD3+ cells were performed in both systems, injections of intact anti-CD3 mAb or anti-CD3-RTA reproducibly produced the highest engraftment values. The fact that engraftment values obtained with anti-CD3 or anti-CD3-RTA therapy in allogeneic systems were substantially higher than in syngeneic controls suggested that engraftment stimulatory proteins were released upon TCR engagement. Elevated levels of cytokines and a high mortality rate in allogeneic recipients confirmed that this was the case. Nonstimulatory preparations of anti-CD3F(ab')2 fragments and anti-CD3F(ab')2-RTA promoted engraftment of both types of allogeneic marrow, as measured by short term I-125-IUdR assays, suggesting that stimulation was not a prerequisite for engraftment. Recipients of anti-CD3F(ab')2 or anti-CD3F(ab')2-RTA showed a marked reduction of host CD3+ cells as measured by immunofluorescence and flow cytometry. In long term chimerism studies, recipients of Hh1-disparate marrow and anti-CD3F(ab')2 had a dramatic increase in donor cell engraftment as compared to controls, indicating that positive effects on engraftment were long lived. Studies further showed that BALB/c donor cells exhibiting an Hh1 disparity were rejected by host cells expressing NK1.1 or Ly-1 (NK cells and T cells). In contrast, DBA/1 donor cells that were not Hh1-disparate were rejected by cells expressing Ly-1, but not NK1.1 (T cells only). These studies provide definitive data that CD3+ cells participate in the rejection of either Hh1+ or Hh1null T cell-depleted allografts and offer new strategies for alloengraftment using regimens containing nonmitogenic anti-CD3. C1 UNIV MINNESOTA HOSP & CLIN,DEPT THERAPEUT RADIOL,EXPTL CANC IMMUNOL SECT,MINNEAPOLIS,MN 55455. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. XOMA CORP,BERKELEY,CA 94710. RP BLAZAR, BR (reprint author), UNIV MINNESOTA HOSP & CLIN,DEPT PEDIAT,DIV BONE MARROW TRANSPLANTAT,BOX 109 UMHC,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [P01-CA-21737, R01-CA-31618, R01-CA-36725] NR 56 TC 62 Z9 62 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1991 VL 147 IS 5 BP 1492 EP 1503 PG 12 WC Immunology SC Immunology GA GC961 UT WOS:A1991GC96100005 PM 1831826 ER PT J AU BRANDES, ME MAI, UEH OHURA, K WAHL, SM AF BRANDES, ME MAI, UEH OHURA, K WAHL, SM TI TYPE-I TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS ON NEUTROPHILS MEDIATE CHEMOTAXIS TO TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD MONOCYTES; COLONY-STIMULATING FACTOR; TGF-BETA; POLYMORPHONUCLEAR NEUTROPHILS; INTERFERON-GAMMA; ACTIVATION; EXPRESSION; INVIVO; INTERLEUKIN-6 AB Participation of human polymorphonuclear neutrophils in the inflammatory response is mediated, in part, by soluble factors such as chemotactic peptides and cytokines. Although the cytokine, transforming growth factor beta (TGF-beta), has been shown to recruit monocytes and promote the inflammatory process, its effects on neutrophils are unknown. In this investigation, [I-125]TGF-beta-1 affinity binding studies were employed to show that neutrophils express TGF-beta receptors (350 +/- 20 receptors/cell), which exhibit high affinity for the ligand (dissociation constant, 50 pM). Affinity cross-linking studies identified the receptors to be primarily of the type I class. In contrast to the receptors on monocytes, neutrophil TGF-beta receptors were not down-regulated by exposure to specific inflammatory mediators. Additional studies examined whether exposure of neutrophils to TGF-beta could enhance specific functions, as occurs with monocytes. TGF-beta was shown to cause directed migration of neutrophils at femtomolar concentrations, thus it is the most potent neutrophil chemotactic factor yet identified. Neutrophil production of reactive oxygen intermediates was not stimulated by TGF-beta, nor did TGF-beta enhance or depress subsequent PMA- or FMLP-stimulated superoxide production. However, the stable expression of neutrophil TGF-beta receptors, and the capacity of this cytokine to stimulate neutrophil chemotaxis, suggest that the pro-inflammatory effects of TGF-beta are mediated by neutrophils in addition to monocytes. RP BRANDES, ME (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,ROOM 329,BETHESDA,MD 20892, USA. NR 46 TC 128 Z9 129 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1991 VL 147 IS 5 BP 1600 EP 1606 PG 7 WC Immunology SC Immunology GA GC961 UT WOS:A1991GC96100020 PM 1652608 ER PT J AU KABAT, EA WU, TT AF KABAT, EA WU, TT TI IDENTICAL V-REGION AMINO-ACID-SEQUENCES AND SEGMENTS OF SEQUENCES IN ANTIBODIES OF DIFFERENT SPECIFICITIES - RELATIVE CONTRIBUTIONS OF VH AND VL GENES, MINIGENES, AND COMPLEMENTARITY-DETERMINING REGIONS TO BINDING OF ANTIBODY-COMBINING SITES SO JOURNAL OF IMMUNOLOGY LA English DT Review ID CHAIN VARIABLE REGION; MOUSE HYBRIDOMA ANTIBODIES; GERM-LINE GENES; MURINE MONOCLONAL-ANTIBODIES; CROSS-IDIOTYPIC SPECIFICITY; BLOOD-CELL AUTOANTIBODIES; HEAVY-CHAIN; SOMATIC MUTATION; IMMUNE-RESPONSE; LIGHT-CHAINS AB By examining a large database of amino acid sequences of antibodies of various specificities, we have found that many antibodies of distinctly different specificities assemble identical V(L) domains with different V(H) domains. In contrast, rarely is the same V(H) domain found in sets of antibodies of different specificities. We identified additional sets of antibodies of different specificities and identical sequences covering amino acid residues V(H) 1 to 94 and V(L) 1 to 95. In addition, there were segments of additional antibodies for which complete sequences were not available, but identities were seen in V(L) CDR1, V(L) CDR2, and V(L) CDR3 up to the V(L)-J(L) junction. The finding that there are many identical V(L) 1 to 95 segments with different V(H) 1 to 94 sequences, and vice versa, raises important questions as to the role of V(H) in influencing the conformation of V(L) and, conversely, the role of V(L) in influencing the conformation of V(H). Evidence is also cited indicating that a single amino acid change may seriously disrupt site structure and in some instances abolish binding. Our findings suggest that it will be important in the future to investigate further conformational effects on antibody structure by using X-ray crystallography, nuclear magnetic resonance spectroscopy, or other methods, to obtain a better understanding of the functions and topography of antibody-combining sites. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. NIH,OFF DIRECTOR,BETHESDA,MD 20892. NORTHWESTERN UNIV,DEPT BIOCHEM,EVANSTON,IL 60208. NORTHWESTERN UNIV,DEPT MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NORTHWESTERN UNIV,DEPT BIOMED ENGN,EVANSTON,IL 60208. NORTHWESTERN UNIV,DEPT ENGN SCI & APPL MATH,EVANSTON,IL 60208. RP KABAT, EA (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032, USA. RI Wu, Tai/B-7638-2009 FU NIAID NIH HHS [3RO1-AI-27508, 5RO1-AI-125616] NR 136 TC 258 Z9 265 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1991 VL 147 IS 5 BP 1709 EP 1719 PG 11 WC Immunology SC Immunology GA GC961 UT WOS:A1991GC96100035 PM 1908882 ER PT J AU COLEBUNDERS, R RYDER, R FRANCIS, H NEKWEI, W BAHWE, Y LEBUGHE, I NDILU, M VERCAUTEREN, G NSEKA, K PERRIENS, J VANDERSTUYFT, P QUINN, TC PIOT, P AF COLEBUNDERS, R RYDER, R FRANCIS, H NEKWEI, W BAHWE, Y LEBUGHE, I NDILU, M VERCAUTEREN, G NSEKA, K PERRIENS, J VANDERSTUYFT, P QUINN, TC PIOT, P TI SEROCONVERSION RATE, MORTALITY, AND CLINICAL MANIFESTATIONS ASSOCIATED WITH THE RECEIPT OF A HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED BLOOD-TRANSFUSION IN KINSHASA, ZAIRE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PRIMARY HIV INFECTION; HTLV-III; AIDS; ANTIBODY; DONORS; RECIPIENTS; TRANSMISSION; PROGRESSION; COINCIDENT; RISK AB To evaluate the consequences of receiving human immunodeficiency virus type 1 (HIV-1)-seropositive blood, 90 HIV-1-seronegative recipients of HIV-1-seropositive blood (case patients) and 90 HIV-1-seronegative recipients of HIV-1-seronegative blood, matched forage, sex, number of transfusions, diagnosis, and severity of illness (controls), were followed for 12 months after transfusion at Mama Yemo Hospital in Kinshasa, Zaire. Of case patients and controls, 72% were children transfused for anemia caused by malaria. Of the 46 case patients alive 6 months after transfusion and for whom HIV-1 serologic results were obtained, 44 (96%) had seroconverted. Significantly more case patients (47%) than controls (16%) died within 1 year after transfusion (P < .001). In the first 3 months after transfusion, fatigue, diarrhea, fever, cough, pruritus, pallor, oral candidiasis, polyadenopathy, hepatosplenomegaly, and rhinorrhea were observed more often among seroconverters than controls (P < .04). Six percent of case patients and no controls had developed clinical AIDS after 12 months of follow-up. These findings underscore the urgent need for appropriate HIV screening facilities in transfusion centers worldwide. C1 DEPT PUBL HLTH,PROJECT SIDA,KINSHASA,ZAIRE. MAMA YEMO HOSP,KINSHASA,ZAIRE. CTR DIS CONTROL,CTR INFECT DIS,HIV AIDS PROGRAM,ATLANTA,GA 30333. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP COLEBUNDERS, R (reprint author), INST TROP MED,BELGIAN MED COOPERAT,NATL STR 155,B-2000 ANTWERP 1,BELGIUM. NR 37 TC 49 Z9 50 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1991 VL 164 IS 3 BP 450 EP 456 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GB383 UT WOS:A1991GB38300002 PM 1869835 ER PT J AU STEEL, C LUJANTRANGAY, A GONZALEZPERALTA, C ZEAFLORES, G NUTMAN, TB AF STEEL, C LUJANTRANGAY, A GONZALEZPERALTA, C ZEAFLORES, G NUTMAN, TB TI IMMUNOLOGICAL RESPONSES TO REPEATED IVERMECTIN TREATMENT IN PATIENTS WITH ONCHOCERCIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CIRCULATING IMMUNE-COMPLEXES; VOLVULUS INFECTION; MASS TREATMENT; BRUGIA-MALAYI; DIETHYLCARBAMAZINE; ANTIGEN; MICROFILARIAE; ANTIBODY; THERAPY; TRANSMISSION AB To assess the effect of ivermectin treatment on the immunologic status of individuals with onchocerciasis, 27 patients from Guatemala were studied before and at 6-month intervals during 2 years of repeated semiannual treatment with ivermectin. T cell proliferative responses to onchocercal antigen increased transiently by 6 months (mean stimulation index [SI] rising from 4.17 to 12.81) but returned to preivermectin levels thereafter. Changes in SI to nonparasite antigen paralleled those induced by parasite antigen. There were also significant decreases in levels of blood eosinophils, polyclonal IgG and IgE, parasite-specific IgG antibody, and IgG subclass antibodies by the end of the study. This study emphasizes the apparent long-term safety of ivermectin by demonstrating the absence of immunopathogenic responses induced by repeated ivermectin treatments. C1 SNEM MINIST PUBL HLTH,GUATEMALA CITY,GUATEMALA. UNIV ARIZONA,DEPT ENTOMOL,TUCSON,AZ 85721. RP STEEL, C (reprint author), NIH,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 51 TC 44 Z9 44 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1991 VL 164 IS 3 BP 581 EP 587 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GB383 UT WOS:A1991GB38300022 PM 1822959 ER PT J AU ROFFMAN, E FRENKEL, N AF ROFFMAN, E FRENKEL, N TI REPLICATION OF HUMAN HERPESVIRUS-6 IN THYMOCYTES ACTIVATED BY ANTI-CD3 ANTIBODY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID T-CELL ACTIVATION; HUMAN-LYMPHOCYTES; CD3 C1 NIAID,VIRAL DIS LAB,TWINBROOK 2,12441 PARKLAWN DR,BETHESDA,MD 20892. NR 10 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1991 VL 164 IS 3 BP 617 EP 618 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA GB383 UT WOS:A1991GB38300038 PM 1651362 ER PT J AU WARBURG, A AF WARBURG, A TI ENTOMOPATHOGENS OF PHLEBOTOMINE SAND FLIES - LABORATORY EXPERIMENTS AND NATURAL INFECTIONS SO JOURNAL OF INVERTEBRATE PATHOLOGY LA English DT Article DE ASCOGREGARINA; BEAUVARIA-BASSIANA; CYTOPLASMIC POLYHEDROSIS VIRUSES; DIPTERA; ENTOMOPATHOGENS; ENTOMOPHTHORALES; LEISHMANIASIS; LEPTOMONAS; NEMATODES; LUTZOMYIA-GOMEZI; LUTZOMYIA-LONGIPALPIS; LUTZOMYIA-LICHYI; LUTZOMYIA-PIA; LUTZOMYIA-SHANNONI; LUTZOMYIA-TOWNSENDI; LUTZOMYIA-TRAPIDOI; PHLEBOTOMUS-PAPATASI; PSYCHODIDAE; SERRATIA-MARCESCENS; SPIRURIDA; TRYPANOSOMATIDAE; TYLENCHIDA; YEAST ID DIPTERA; PSYCHODIDAE; LECUDINIDAE; SANDFLIES RP WARBURG, A (reprint author), NIH, MALARIA SECT, MED ENTOMOL UNIT, BETHESDA, MD 20892 USA. NR 33 TC 25 Z9 26 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-2011 EI 1096-0805 J9 J INVERTEBR PATHOL JI J. Invertebr. Pathol. PD SEP PY 1991 VL 58 IS 2 BP 189 EP 202 DI 10.1016/0022-2011(91)90063-V PG 14 WC Zoology SC Zoology GA GE051 UT WOS:A1991GE05100006 PM 1783777 ER PT J AU BERNSTEIN, EF HARISIADIS, L SALOMON, G NORTON, J SOLLBERG, S UITTO, J GLATSTEIN, E GLASS, J TALBOT, T RUSSO, A MITCHELL, JB AF BERNSTEIN, EF HARISIADIS, L SALOMON, G NORTON, J SOLLBERG, S UITTO, J GLATSTEIN, E GLASS, J TALBOT, T RUSSO, A MITCHELL, JB TI TRANSFORMING GROWTH-FACTOR-BETA IMPROVES HEALING OF RADIATION-IMPAIRED WOUNDS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; TYPE-1 NEUROFIBROMATOSIS; GENE-EXPRESSION; FIBROBLASTS; COLLAGEN; INVIVO; RATS; STIMULATION; MACROPHAGES; ADRIAMYCIN AB Exogenously applied TGF-beta-1 has been shown to increase wound strength in incisional wounds early in the healing process. An impaired wound healing model was first established in guinea pigs by isolating flaps of skin and irradiating the flaps to 15 Gray in one fraction using a 4-MeV linear accelerator. Incisions made 2 d after irradiation were excised 7 d later, and showed decreased linear wound bursting strength (WBS) as compared to non-irradiated control wounds on the contralateral side of each animal (p = 0.001). The effect of TGF-beta on healing of radiation-impaired wounds was studied using this model. Skin on both left and right sides of guinea pigs was irradiated as above. A linear incision was made in each side. Collagen with either 1, 5, or 20-mu-g of TGF-beta was applied to one side prior to closure with staples, whereas the contralateral side received saline in collagen. Wounds given either 1 or 5-mu-g of TGF-beta were found to be stronger than controls at 7 d (p < 0.05), whereas those receiving the higher 20-mu-g dose were weaker than controls (p < 0.05). Thus, TGF-beta in lower doses improved healing at 7 d but very large amounts of the growth factor actually impaired healing. In situ hybridization done on wound samples showed increased type I collagen gene expression by fibroblasts in wounds treated with 1-mu-g TGF-beta over control wounds. These results indicate that TGF-beta improved wound healing as demonstrated by increased WBS. This improvement is accompanied by an up-regulation of collagen gene expression by resident fibroblasts. C1 THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA 19107. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIH,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIH,SURG BRANCH,BETHESDA,MD 20892. NIH,BMEIB,BETHESDA,MD 20892. RP BERNSTEIN, EF (reprint author), HAHNEMANN UNIV,SCH MED,DIV DERMATOL,MS 401,PHILADELPHIA,PA 19102, USA. NR 30 TC 57 Z9 61 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1991 VL 97 IS 3 BP 430 EP 434 DI 10.1111/1523-1747.ep12481258 PG 5 WC Dermatology SC Dermatology GA GD668 UT WOS:A1991GD66800009 PM 1875042 ER PT J AU ZACHARIAE, COC THESTRUPPEDERSEN, K MATSUSHIMA, K AF ZACHARIAE, COC THESTRUPPEDERSEN, K MATSUSHIMA, K TI EXPRESSION AND SECRETION OF LEUKOCYTE CHEMOTACTIC CYTOKINES BY NORMAL HUMAN MELANOCYTES AND MELANOMA-CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATING FACTOR MCAF; HUMAN KERATINOCYTES CONTAIN; GROWTH-STIMULATORY ACTIVITY; HUMAN DERMAL FIBROBLASTS; FACTOR-ALPHA; INTERFERON-GAMMA; GENE-EXPRESSION; MESSENGER-RNA; INTERLEUKIN-1 AB The capacity of human melanocytes and melanoma cells to produce IL-8 and monocyte chemotactic and activating factor (MCAF) was investigated. Melanocytes expressed mRNA for IL-8 and MCAF, when stimulated with either IL-1-alpha or TNF-alpha, but not when stimulated with IL-6, IFN-gamma, or LPS alone. IL-8 and MCAF could be induced in a dose-dependent fashion with doses as low as 0.1 ng/ml TNF-alpha and 0.5 ng/ml IL-1-alpha. IL-8 and MCAF mRNA were rapidly expressed and peaked between 2 and 4 h for IL-8 and between 4 and 8 h for MCAF. This correlated well with the accumulation of IL-8 antigen as measured by a radioimmunoassay. Supernatants from melanocyte cultures stimulated with either IL-1-alpha or TNF-alpha and separated on a heparin-Sepharose column became positive for neutrophil and monocyte chemotactic activity in a dose- and time-dependent fashion. When IFN-gamma was added to melanocyte cultures stimulated with suboptimal doses of TNF-alpha there was a synergistic increase in secreted IL-8 protein and monocyte chemotactic activity. These data provide further evidence for the possible role of melanocytes in the initiation of an inflammatory reaction. Three different malignant melanoma cell lines stimulated with either TNF-alpha or IL-1-alpha expressed IL-8 mRNA, but not mRNA for MCAF. The IL-8 mRNA signal corresponded well with the amount of secreted IL-8 protein. These data suggest that IL-8 and MCAF may play a role in growth regulation and spreading of melanomas. C1 NCI,DIV CANC TREATMENT,MOLEC IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. RP ZACHARIAE, COC (reprint author), MARSELISBORG HOSP,DEPT DERMATOL,DK-8000 AARHUS C,DENMARK. NR 48 TC 77 Z9 79 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1991 VL 97 IS 3 BP 593 EP 599 DI 10.1111/1523-1747.ep12481934 PG 7 WC Dermatology SC Dermatology GA GD668 UT WOS:A1991GD66800036 PM 1875058 ER PT J AU HORNE, MK CHAO, ES WILSON, OJ SCIALLA, SJ LYNCH, MA KRAGEL, PJ AF HORNE, MK CHAO, ES WILSON, OJ SCIALLA, SJ LYNCH, MA KRAGEL, PJ TI A HEPARIN-LIKE ANTICOAGULANT AS PART OF GLOBAL ABNORMALITIES OF PLASMA GLYCOSAMINOGLYCANS IN A PATIENT WITH TRANSITIONAL CELL-CARCINOMA SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID SULFATE; PROTEOGLYCANS; PLATELETS; DISORDER; BLOOD AB A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples. C1 MOSES TAYLOR HOSP,WAINWRIGHT SPECIAL HEMATOL LAB,SCRANTON TEMPLE RESIDENCY PROGRAM,SCRANTON,PA. RP HORNE, MK (reprint author), NCI,DIV CANC BIOL & DIAG,PATHOL LAB,ROOM 2C390,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 11 Z9 11 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD SEP PY 1991 VL 118 IS 3 BP 250 EP 260 PG 11 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA GF667 UT WOS:A1991GF66700008 PM 1919298 ER PT J AU RADZIOCH, D HUDSON, T BOULE, M BARRERA, L URBANCE, JW VARESIO, L SKAMENE, E AF RADZIOCH, D HUDSON, T BOULE, M BARRERA, L URBANCE, JW VARESIO, L SKAMENE, E TI GENETIC-RESISTANCE SUSCEPTIBILITY TO MYCOBACTERIA - PHENOTYPIC-EXPRESSION IN BONE-MARROW DERIVED MACROPHAGE LINES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE BCG GENE; MYCOBACTERIUM-SMEGMATIS; MACROPHAGES; BACTERICIDAL ACTIVITY; TUMORICIDAL ACTIVITY ID PROTO-ONCOGENE PRODUCT; INBRED MOUSE STRAINS; FACTOR-I RECEPTOR; C-FMS; NATURAL-RESISTANCE; BOVIS BCG; SALMONELLA-TYPHIMURIUM; LIVER MACROPHAGES; MESSENGER-RNA; GROWTH-FACTOR AB Congenic strains of mice susceptible (B10A.Bcg(s)) or resistant (B10A.Bcg(r)) to BCG were established. Here we describe the model system which has been established to analyze the functional activities of macrophages in the two strains. We have immortalized bone marrow macrophages from B10A.Bcg(s) and B10A.Bcg(r) congenic strains of mice and derived cloned macrophage lines designated B10S and B10R, respectively. B10R and B10S cell lines exhibited surface markers and morphology typical of macrophages. B10S and B10R were similar in their phagocytic activity, in their level of c-fms, in their transforming growth factor-beta (TGF-beta) mRNAs expression, and in their expression of tumoricidal activity in response to interferon-gamma (IFN-gamma) plus lipopolysaccharides (LPS). However, B10R macrophages expressed a higher level of Ia mRNA when activated with IFN-gamma compared with B10S macrophages. Analysis of the bacteriostatic activity of the two cell lines revealed that B10R macrophages were much more active in inhibiting Mycobacterium smegmatis replication than B10S. To measure the intracellular destruction of bacilli, a bactericidal assay based on hybridization with an oligonucleotide probe specific for mycobacterial ribosomal RNA was designed. The results demonstrated that B10R macrophages were endowed with enhanced constitutive bactericidal activity as compared with B10S. In conclusion we have obtained macrophage lines from bone marrow of B10A.Bcg(s) and B10A.Bcg(r) mice that express to a similar extent functional and phenotypic characteristics of macrophages. However, we demonstrate that relative to B10S macrophages, the B10R macrophages have higher expression of Ia mRNA and that they are constitutively more active in expressing mycobactericidal activity. C1 MONTREAL GEN HOSP,RES INST,DEPT MED,MONTREAL H3G 1A4,QUEBEC,CANADA. UNIV ILLINOIS,DEPT VET MED,URBANA,IL 61801. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. RI varesio, luigi/J-8261-2016; OI varesio, luigi/0000-0001-5659-2218; Barrera, Luis/0000-0002-6108-6747 NR 40 TC 83 Z9 83 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1991 VL 50 IS 3 BP 263 EP 272 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA GA274 UT WOS:A1991GA27400006 PM 1856597 ER PT J AU CARROLL, FI GAO, YG RAHMAN, MA ABRAHAM, P PARHAM, K LEWIN, AH BOJA, JW KUHAR, MJ AF CARROLL, FI GAO, YG RAHMAN, MA ABRAHAM, P PARHAM, K LEWIN, AH BOJA, JW KUHAR, MJ TI SYNTHESIS, LIGAND-BINDING, QSAR, AND COMFA STUDY OF 3-BETA-(PARA-SUBSTITUTED PHENYL)TROPANE-2-BETA-CARBOXYLIC ACID METHYL-ESTERS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECEPTORS; ANALOGS AB A series of 3-beta-(p-substituted phenyl)tropane-2-beta-carboxylic acid methyl esters (2) were synthesized and found to possess high affinity for the cocaine binding site in rat striatum. The p-chloro (2c) and p-iodo (2n) compounds, which were the most potent analogues prepared, were found to be 85 and 78 times more potent than (-)-cocaine. The p-bromo (2m) and p-methyl (2d) were also 56 and 60 times more potent than cocaine. QSAR and CoMFA studies were conducted to correlate binding affinity of the cocaine analogues with their structural features. Whereas the QSAR study gave relatively low correlations, the CoMFA study gave a correlation with high predictive value. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP CARROLL, FI (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIDA NIH HHS [DA05477] NR 17 TC 190 Z9 191 U1 4 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP PY 1991 VL 34 IS 9 BP 2719 EP 2725 DI 10.1021/jm00113a008 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GF103 UT WOS:A1991GF10300008 PM 1895292 ER PT J AU THOMPSON, RD SECUNDA, S DALY, JW OLSSON, RA AF THOMPSON, RD SECUNDA, S DALY, JW OLSSON, RA TI N6,9-DISUBSTITUTED ADENINES - POTENT, SELECTIVE ANTAGONISTS AT THE ADENOSINE-A1-RECEPTOR SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ADENOSINE RECEPTOR; ADENYLATE-CYCLASE; HUMAN-FIBROBLASTS; AGONISTS; 1,3-DIPROPYL-8-PHENYLXANTHINE; INHIBITION; ANALOGS; DOG AB N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors. The present study assessed the effect of N6 and N-9 substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine-5'-uronamide. The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl > phenyl > tetrahydrofuryl > methyl > 2-hydroxyethyl. The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor. An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold. The N6-cyclophenyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent. A 2-chloro substituent did not alter the potency of an N6-substituted 9-methyladenine. C1 UNIV S FLORIDA,DEPT INTERNAL MED,TAMPA,FL 33612. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV S FLORIDA,DEPT BIOCHEM & MOLEC BIOL,TAMPA,FL 33612. FU NHLBI NIH HHS [HL-30391] NR 29 TC 60 Z9 61 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP PY 1991 VL 34 IS 9 BP 2877 EP 2882 DI 10.1021/jm00113a029 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GF103 UT WOS:A1991GF10300029 PM 1895305 ER PT J AU FURLONG, TJ MORIYAMA, T SPRING, KR AF FURLONG, TJ MORIYAMA, T SPRING, KR TI ACTIVATION OF OSMOLYTE EFFLUX FROM CULTURED RENAL PAPILLARY EPITHELIAL-CELLS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE SORBITOL; OSMOLYTES; ARACHIDONIC ACID; CYTOCHROME-P-450 ID ARACHIDONIC-ACID METABOLISM; LEUKOTRIENE BIOSYNTHESIS; 5,8,11,14-EICOSATETRAYNOIC ACID; IRREVERSIBLE INHIBITION; ALDOSE REDUCTASE; ORGANIC SOLUTES; MEDULLARY CELLS; RAT-LIVER; SORBITOL; OSMOREGULATION AB The rabbit renal papillary epithelial cell line PAP-HT25 accumulates sorbitol and other organic osmolytes when cultured in hypertonic media. When returned to isotonic media, PAP-HT25 cells swell because of water influx and then shrink to their normal volume because of rapid osmolyte and water efflux (volume regulatory decrease, VRD). Sorbitol efflux from PAP-HT25 cells during VRD was reduced to 18% of control by incubation of the cells with 100-mu-M eicosatetraynoic acid (ETYA), indicating that an enzyme that metabolizes arachidonic acid (AA) is a key component of the efflux process. Sorbitol efflux was unaffected by incubation with cyclooxygenase and lipoxygenase inhibitors but was reduced to 9% by incubation with 100-mu-M ketoconazole and to 37% by incubation with 100-mu-M SKF-525A, indicating that the cytochrome P-450 limb of the AA cascade is involved in the efflux process. The efflux of other organic osmolytes betaine and myoinositol, but not glycerolphosphorylcholine, was also inhibited by incubation with ETYA and ketoconazole. RP FURLONG, TJ (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 51 TC 44 Z9 44 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1991 VL 123 IS 3 BP 269 EP 277 DI 10.1007/BF01870410 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA GE656 UT WOS:A1991GE65600008 PM 1744906 ER PT J AU NUSSINOV, R AF NUSSINOV, R TI DISTINCT PATTERNS IN THE DINUCLEOTIDE NEAREST NEIGHBORS TO G/C-OLIGOMER AND A/T-OLIGOMER IN EUKARYOTIC SEQUENCES SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE DNA SEQUENCE ANALYSIS; FREQUENCIES; SEQUENCE PATTERNS; DNA STRUCTURE ID ALTERED DNA CONFORMATION; MARKOV-CHAIN ANALYSIS; PROTEIN; TRACTS; RULES AB The eukaryotic and prokaryotic databases are scanned for potential nearest-neighbor doublet preferences at the 5' and 3' flanks of some oligomers. Here we focus on oligomers containing alternating nucleotides, i.e., UV, UVUV, and UUVV where U not-equal V. Strong, consistent trends are observed in eukaryotic sequences. A/T alternation oligomers are preferentially flanked by A/T. G/C flanks are disfavored. G/C alternation oligomers are preferentially flanked by G/C. A/T flanks are disfavored. These trends are consistent with those observed previously for homooligomer tracts (Nussinov et al. 1989a,b). G/C tracts are preferentially flanked by G/C. A/T nearest neighbors are disfavored. The reverse holds for A/T tracts. Additional patterns are described here as well. The possible origin of these DNA composition and sequence trends is discussed. These trends are suggested to stem from protein-DNA interaction constraints. C1 TEL AVIV UNIV,SACKLER FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RP NUSSINOV, R (reprint author), NCI,MATH BIOL LAB,BLDG 10,ROOM 4B-56,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD SEP PY 1991 VL 33 IS 3 BP 259 EP 266 DI 10.1007/BF02100677 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA GC291 UT WOS:A1991GC29100011 PM 1757996 ER PT J AU SCHAUFELBERGER, DE KOLECK, MP BEUTLER, JA VATAKIS, AM ALVARADO, AB ANDREWS, P MARZO, LV MUSCHIK, GM ROACH, J ROSS, JT LEBHERZ, WB REEVES, MP EBERWEIN, RM RODGERS, LL TESTERMAN, RP SNADER, KM FORENZA, S AF SCHAUFELBERGER, DE KOLECK, MP BEUTLER, JA VATAKIS, AM ALVARADO, AB ANDREWS, P MARZO, LV MUSCHIK, GM ROACH, J ROSS, JT LEBHERZ, WB REEVES, MP EBERWEIN, RM RODGERS, LL TESTERMAN, RP SNADER, KM FORENZA, S TI THE LARGE-SCALE ISOLATION OF BRYOSTATIN-1 FROM BUGULA-NERITINA FOLLOWING CURRENT GOOD MANUFACTURING PRACTICES SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PROTEIN-KINASE-C; HEMATOPOIETIC PROGENITOR CELLS; PHORBOL ESTER RECEPTOR; ACTIVATORS; INVITRO; AGENTS; GROWTH AB A novel process was designed for the large-scale isolation of bryostatin 1 {1} from the bryozoan Bugula neritina L. in order to obtain multigram quantities of highly pure material for formulation studies, preclinical toxicology, and clinical trials in cancer patients. Multigram quantities of bryostatin 1 were obtained from a collection of approximately 10,000 gallons of wet animal. A phorbol dibutyrate (PDBu) receptor binding assay and hplc with photodiode array detection were used for the design, validation, and control of the isolation process. C1 NCI,PRI DYNCORP,FERMENTAT PROD FACIL,CHEM SYNTH & ANAL LAB,FREDERICK CANC RES & DEV CTR,POB B,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DTP,NAT PROD BRANCH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES & DEV,WALLINGFORD,CT 06492. RI vatakis, argiro/A-1180-2008; Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NCI NIH HHS [N01-CO-74102] NR 16 TC 83 Z9 85 U1 0 U2 7 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP-OCT PY 1991 VL 54 IS 5 BP 1265 EP 1270 DI 10.1021/np50077a004 PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA GM639 UT WOS:A1991GM63900004 PM 1800630 ER PT J AU MOORE, SA GIORDANO, MJ KIM, HY SALEM, N SPECTOR, AA AF MOORE, SA GIORDANO, MJ KIM, HY SALEM, N SPECTOR, AA TI BRAIN MICROVESSEL 12-HYDROXYEICOSATETRAENOIC ACID IS THE (S) ENANTIOMER AND IS LIPOXYGENASE DERIVED SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BRAIN MICROVESSELS; CEREBRAL ENDOTHELIUM; ARACHIDONIC ACID; EICOSAPENTAENOIC ACID; 12-HYDROXYEICOSATETRAENOIC ACID; 12-HYDROXYEICOSAPENTAENOIC ACID; LIPOXYGENASE ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ARACHIDONIC-ACID; CYTOCHROME-P-450 METABOLITES; FATTY-ACIDS; RAT-BRAIN; LEUKOTRIENE; ISCHEMIA; BIOSYNTHESIS; INHIBITION; INJURY AB 12-Hydroxyeicosatetraenoic acid (12-HETE) production from arachidonic acid by cerebral microvessels isolated from perfused adult murine brain was reduced by the lipoxygenase inhibitors baicalein, esculetin, gossypol, nordihydroguaiaretic acid, and quercetin. Except for quercetin and gossypol, the IC50 did not exceed 10-mu-M. Each inhibitor, except baicalein, also decreased microvessel prostaglandin production when present in concentrations above their IC50 value for 12-HETE. In contrast, inhibitors of the cytochrome P450 monooxygenase system, clotrimazole, metyrapone, and proadifen (SKF-525A), had little effect on mirovessel 12-HETE production. Chiral phase HPLC analysis revealed that only the (S) enantiomer of 12-HETE was formed. The major microvessel metabolite of eicosapentaenoic acid co-eluted with 12-hydroxyeicosapentaenoic acid (12-HEPE) on reversephase HPLC and the (S) enantiomer of 12-HEPE on chiral phase HPLC. Furthermore, like 12-HETE, 12-HEPE production was blocked by lipoxygenase inhibitors. These studies demonstrate that brain microvessels produce only the (S) enantiomeric 12-hydroxy derivatives of both arachidonic acid and eicosapentaenoic acid by the action of a lipoxygenase that can be selectively inhibited by baicalein. Since arachidonic acid and eicosapentaenoic acid are available to cerebral blood vessels in certain pathological settings, these 12-hydroxy acid lipoxygenase products may mediate some of the cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures. C1 UNIV IOWA, DEPT BIOCHEM, IOWA CITY, IA 52242 USA. NIAAA, CLIN STUDIES LAB, BETHESDA, MD USA. RP UNIV IOWA, DEPT PATHOL, DIV NEUROPATHOL, ROOM 119 MED LABS, IOWA CITY, IA 52242 USA. FU NHLBI NIH HHS [HL-14230]; NINDS NIH HHS [NS-01096, NS-24621] NR 55 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1991 VL 57 IS 3 BP 922 EP 929 DI 10.1111/j.1471-4159.1991.tb08239.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GA379 UT WOS:A1991GA37900027 PM 1907312 ER PT J AU MURPHY, VA WADHWANI, KC SMITH, QR RAPOPORT, SI AF MURPHY, VA WADHWANI, KC SMITH, QR RAPOPORT, SI TI SATURABLE TRANSPORT OF MANGANESE(II) ACROSS THE RAT-BLOOD BRAIN BARRIER SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MANGANESE; BRAIN; CHOROID PLEXUS; CSF; BLOOD BRAIN BARRIER; SATURABLE TRANSPORT ID CEREBROVASCULAR PERMEABILITY; MAMMALIAN BRAIN; ADULT-RATS; METABOLISM; CHLORIDE; NEUROTRANSMITTERS; TRANSFERRIN; RECEPTOR; PLASMA; IRON AB Unanesthetized adult male rats were infused intravenously with solutions containing Mn-54 (II) and one of six concentrations of stable Mn(II). The infusion was timed to produce a near constant [Mn] in plasma for up to 20 min. Plasma was collected serially and on termination of the experiment, samples of CSF, eight brain regions, and choroid plexus (CP) were obtained. Influx of Mn (J(Mn)) was calculated from uptake of Mn-54 into tissues and CSF at two different times. Plasma [Mn] was varied 1,000-fold (0.076-78 nmol/ml). Over this plasma concentration range, J(Mn) increased 123 times into CP, 18-120 times into brain, and 706 times into CSF. CP and brain J(Mn) values fit saturation kinetics with K(m) (nmol/ml) equal to 15 for CP and 0.7-2.1 for brain, and V(max) (10(-2) nmol . g-1 . s-1) of 27 for CP and 0.025-0.054 for brain. Brain J(Mn) except at cerebral cortex had a nonsaturable component. CSF J(Mn) varied linearly with plasma [Mn]. These findings suggest that Mn transport into brain and CP is saturable, but transport into CSF is nonsaturable. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892. NR 41 TC 114 Z9 118 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1991 VL 57 IS 3 BP 948 EP 954 DI 10.1111/j.1471-4159.1991.tb08242.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GA379 UT WOS:A1991GA37900030 PM 1861159 ER PT J AU JOHANNESSEN, JN SOBOTKA, TJ WEISE, VK MARKEY, SP AF JOHANNESSEN, JN SOBOTKA, TJ WEISE, VK MARKEY, SP TI PROLONGED ALTERATIONS IN CANINE STRIATAL DOPAMINE METABOLISM FOLLOWING SUBTOXIC DOSES OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) AND 4'-AMINO-MPTP ARE LINKED TO THE PERSISTENCE OF PYRIDINIUM METABOLITES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM; PARKINSONISM; DOPAMINE; DOG; DOSE RESPONSE ID BRAIN MONOAMINE-OXIDASE; PARKINSONS-DISEASE; NEUROTOXIC METABOLITE; TYROSINE-HYDROXYLASE; 1-METHYL-4-PHENYLPYRIDINIUM; INHIBITION; ANALOGS; N-METHYL-4-PHENYLPYRIDINIUM; TETRAHYDROISOQUINOLINE; MITOCHONDRIA AB Single toxic doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).HCl (2.5 mg/kg i.v.) and 4'-amino-MPTP.2HCl (22.5 mg/kg) induce loss of striatal dopamine (DA) and tyrosine hydroxylase (TH) activity and of nigral DA neurons in the dog. To examine the subacute neurochemical changes induced by low doses of MPTP and 4'-amino-MPTP, dose-response studies of these compounds were carried out in the dog, using 6- and 3-week survival times for these two compounds, respectively. Low single doses of MPTP (1.0, 0.5, and 0.1 mg/kg i.v.) and 4'-amino-MPTP (15, 7.5, and 3.75 mg/kg i.v.) did not cause depletion of canine striatal DA or TH or a loss of nigral neurons. However, levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DO-PAC) and homovanillic acid (HVA) were decreased in a dose-related fashion, with significant loss of DOPAC being evident 6 weeks after the lowest administered dose of MPTP and 3 weeks after 4'-amino-MPTP. This selective loss of DA metabolites following nontoxic doses of MPTP and 4'-amino-MPTP led to a shift in the ratio of DA to DOPAC or HVA, which was characteristic for each compound. The measurement of striatal 1-methyl-4-phenylpyridinium (MPP+) and 4'-amino-MPP+ levels revealed that high concentrations (up to 150-mu-M) persist in the striatum for weeks following administration of a single nontoxic dose of MPTP or 4'-amino-MPTP. A causal relationship between the striatal concentration of MPP+ or 4'-amino-MPP+ and the change in DA metabolism as relected in the DA/DOPAC ratio is suggested by a significant correlation between these measures. It is suggested that presynaptic sequestration and retention of MPP+ and 4'-amino-MPP+ by striatal DA terminals result in the inhibition of the monoamine oxidase contained within these terminals. C1 NINCDS,NEURAL REGENERAT LAB,BETHESDA,MD 20892. US EPA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20460. RP JOHANNESSEN, JN (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-40,BETHESDA,MD 20892, USA. NR 37 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1991 VL 57 IS 3 BP 981 EP 990 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GA379 UT WOS:A1991GA37900035 PM 1677682 ER PT J AU ATACK, JR LITVAN, I THAL, LJ MAY, C RAPOPORT, SI CHASE, TN AF ATACK, JR LITVAN, I THAL, LJ MAY, C RAPOPORT, SI CHASE, TN TI CEREBROSPINAL-FLUID ACETYLCHOLINESTERASE IN PROGRESSIVE SUPRANUCLEAR PALSY - REDUCED ACTIVITY RELATIVE TO NORMAL SUBJECTS AND LACK OF INHIBITION BY ORAL PHYSOSTIGMINE SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Note ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; NEURONAL LOSS; NEOSTRIATUM; DEMENTIA; DISEASE; RAT AB Acetylcholinesterase (AChE) activity was measured in lumbar cerebrospinal fluid (CSF) of 11 patients with progressive supranuclear palsy (PSP) and 18 age-matched healthy control subjects. Mean CSF AChE activity in PSP subjects was significantly reduced by 31% relative to control subjects (p < 0.002). In the light of evidence of a central cholinergic deficit, physostigmine was administered orally (0.5-2.0 mg every two hours, six times a day for 10 days) to eight of the 11 PSP patients. CSF was sampled when the patients were on placebo and when receiving physostigmine and CSF AChE and butyrylcholinesterase (BChE) activities were measured. There was no significant change in either CSF AChE or BChE activities following physostigmine treatment. These data suggest that the doses of physostigmine used were insufficient to produce marked inhibition of AChE within the central nervous system. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,NEUROL SERV,SAN DIEGO,CA 92161. OI Litvan, Irene/0000-0002-3485-3445 NR 23 TC 17 Z9 17 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 1991 VL 54 IS 9 BP 832 EP 835 DI 10.1136/jnnp.54.9.832 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA GE993 UT WOS:A1991GE99300017 PM 1955905 ER PT J AU YAMASAKI, DS WURTZ, RH AF YAMASAKI, DS WURTZ, RH TI RECOVERY OF FUNCTION AFTER LESIONS IN THE SUPERIOR TEMPORAL SULCUS IN THE MONKEY SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PURSUIT EYE-MOVEMENTS; DORSOLATERAL PONTINE NUCLEUS; VISUAL RESPONSE PROPERTIES; CORTICAL AREAS MT; CHEMICAL LESIONS; MACAQUE MONKEY; STRIATE CORTEX; AFFERENT BASIS; RHESUS-MONKEY; ALERT MONKEY AB 1. Ibotenic acid lesions in the monkey's middle temporal area (MT) and the medial superior temporal area (MST) in the superior temporal sulcus (STS) have previously been shown to produce a deficit in initiation of smooth-pursuit eye movements to moving visual targets. The deficits, however, recover within a few days. In the present experiments we investigated the factors that influence that recovery. 2. We tested two aspects of the monkey's ability to use motion information to acquire moving targets. We used eye-position error as a measure of the monkey's ability to make accurate initial saccades to the moving target. We measured eye speed within the first 100 ms after the saccade to evaluate the monkey's initial smooth pursuit. 3. We determined that pursuit recovery was not dependent specifically on the use of neurotoxic lesions. Although the rate of recovery was slightly altered by replacing the usual neurotoxin (ibotenic acid) with another neurotoxin [alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] or with an electrolytic lesion, pursuit recovery still occurred within a period of days to weeks. 4. There was a relationship between the size and location of the lesion and the recovery time. The time to recovery for eye-position error and initial eye speed increased with the fraction of MT removed. Whether the rate of recovery and size of lesions within regions on the anterior bank were related was unresolved. 5. We found that a large AMPA lesion within the STS that removed all of MT and nearly all of MST drastically altered the rate of recovery. Recovery was incomplete more than 7 mo after the lesion. Even with this lesion, however, the monkey's ability to use motion information for pursuit was not completely eliminated. 6. The large lesion also included parts of areas V1, V2, V3, and V4, but analysis of the visual fields associated with this lesion indicated that these areas probably did not have a substantial effect on recovery. 7. We tested whether visual motion experience of the monkey after a lesion was necessary for recovery by limiting the monkey's experience either by using a mask or by using 4-Hz stroboscopic illumination. In one monkey the eye-position error component of pursuit was prolonged to > 2 wk, but recovery of eye speed was not. Reduced motion experience had little effect on recovery in the other two monkeys. These results suggest that such visual motion experience is not necessary for the recovery of pursuit. 8. We conclude that recovery of function after MT lesions consists of at least two processes: a rapid phase that depends on the surviving portions of MT and possibly MST and a slower phase that is dependent on areas outside of the STS. We think that the persistence of the deficit after the near total ablation of MT and MST strengthens the argument that these areas are critical for visual motion processing in the normal monkey. But the presence of some motion sensitivity even after such massive lesions suggests that areas outside of the STS also contribute to that processing. C1 NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,BETHESDA,MD 20892. NR 56 TC 64 Z9 64 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1991 VL 66 IS 3 BP 651 EP 672 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GE056 UT WOS:A1991GE05600001 PM 1753278 ER PT J AU MCCLURKIN, JW GAWNE, TJ RICHMOND, BJ OPTICAN, LM ROBINSON, DL AF MCCLURKIN, JW GAWNE, TJ RICHMOND, BJ OPTICAN, LM ROBINSON, DL TI LATERAL GENICULATE NEURONS IN BEHAVING PRIMATES .1. RESPONSES TO 2-DIMENSIONAL STIMULI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RETINAL GANGLION-CELLS; TWO-DIMENSIONAL PATTERNS; INFERIOR TEMPORAL CORTEX; RECEPTIVE-FIELD ORGANIZATION; PRIMARY VISUAL-CORTEX; SINGLE UNITS; SPATIAL SUMMATION; X-CELLS; Y-CELL; CONDUCTION VELOCITIES AB 1. Using behaving monkeys, we studied the visual responses of single neurons in the parvocellular layers of the lateral geniculate nucleus (LGN) to a set of two-dimensional black and white patterns. We found that monkeys could be trained to make sufficiently reliable and stable fixations to enable us to plot and characterize the receptive fields of individual neurons. A qualitative examination of rasters and a statistical analysis of the data revealed that the responses of neurons were related to the stimuli. 2. The data from 5 of the 13 "X-like" neurons in our sample indicated the presence of antagonistic center and surround mechanisms and linear summation of luminance within center and surround mechanisms. We attribute the lack of evidence for surround antagonism in the eight neurons that failed to exhibit center-surround antagonism either to a mismatch between the size of the pixels in the stimuli and the size of the receptive field or to the lack of a surround mechanism (i.e., the type II neurons of Wiesel and Hubel). 3. The data from five other neurons confirm and extend previous reports indicating that the surround regions of X-like neurons can have nonlinearities. The responses of these neurons were not modulated when a contrast-reversing, bipartite stimulus was centered on the receptive field, which suggests a linear summation within the center and surround mechanisms. However, it was frequently the case for these neurons that stimuli of identical pattern but opposite contrast elicited responses of similar polarity, which indicates nonlinear behavior. 4. We found a wide variety of temporal patterns in the responses of individual LGN neurons, which included differences in the magnitude, width, and number of peaks of the initial on-transient and in the magnitude of the later sustained component. These different temporal patterns were repeatable and clearly different for different visual patterns. These results suggest that visual information may be carried in the shape as well as in the amplitude of the response waveform. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP MCCLURKIN, JW (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 66 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1991 VL 66 IS 3 BP 777 EP 793 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GE056 UT WOS:A1991GE05600011 PM 1753287 ER PT J AU MCCLURKIN, JW GAWNE, TJ OPTICAN, LM RICHMOND, BJ AF MCCLURKIN, JW GAWNE, TJ OPTICAN, LM RICHMOND, BJ TI LATERAL GENICULATE NEURONS IN BEHAVING PRIMATES .2. ENCODING OF VISUAL INFORMATION IN THE TEMPORAL SHAPE OF THE RESPONSE SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; RETINAL GANGLION-CELLS; SINGLE UNITS; SPATIAL SUMMATION; CONDUCTION VELOCITIES; X-CELLS; Y-CELLS; NUCLEUS; CORTEX; MACAQUE AB 1. We used the Karhunen-Loeve (K-L) transform to quantify the temporal distribution of spikes in the responses of lateral geniculate (LGN) neurons. The basis functions of the K-L transform are a set of waveforms called principal components, which are extracted from the data set. The coefficients of the principal components are uncorrelated with each other and can be used to quantify individual responses. The shapes of each of the first three principal components were very similar across neurons. 2. The coefficient of the first principal component was highly correlated with the spike count, but the other coefficients were not. Thus the coefficient of the first principal component reflects the strength of the response, whereas the coefficients of the other principal components reflect aspects of the temporal distribution of spikes in the response that are uncorrelated with the strength of the response. Statistical analysis revealed that the coefficients of up to 10 principal components were driven by the stimuli. Therefore stimuli govern the temporal distribution as well as the number of spikes in the response. 3. Through the application of information theory, we were able to compare the amount of stimulus-related information carried by LGN neurons when two codes were assumed: first, a univariate code based on response strength alone; and second, a multivariate temporal code based on the coefficients of the first three principal components. We found that LGN neurons were able to transmit an average of 1.5 times as much information using the three-component temporal code as they could using the strength code. 4. The stimulus set we used allowed us to calculate the amount of information each neuron could transmit about stimulus luminance, pattern, and contrast. All neurons transmitted the greatest amount of information about stimulus luminance, but they also transmitted significant amounts of information about stimulus pattern. This pattern information was not a reflection of the luminance or contrast of the pixel centered on the receptive field. 5. In addition to measuring the average amount of information each neuron transmitted about all stimuli, we also measured the amount of information each neuron transmitted about the individual stimuli with both the univariate spike count code and the multivariate temporal code. We then compared the amount of information transmitted per stimulus with the magnitudes of the responses to the individual stimuli. We found that the magnitudes of both the univariate and the multivariate responses to individual stimuli were poorly correlated with the information transmitted about the individual stimuli. That is, neurons were able to transmit large amounts of information in either small, medium, or large responses. 6. We conclude from these findings the following. 1) The responses of LGN neurons can be viewed as different combinations of a few stereotypic waveforms, with the amount of each waveform determined by the stimulus that was presented. 2) LGN neurons can transmit more stimulus-related information if they use a multivariate temporal code to transmit several independent messages about stimuli. 3) The function of LGN neurons is better described as encoding rich descriptions of stimuli than as encoding of individual parameters of stimuli. 4) The receptive fields of X-like LGN neurons must be functionally more complex than the center-surround models that have been presented previously. Our results suggest that representing the receptive fields of X-like LGN neurons as a set of three independent spatiotemporal filters provides a more complete description of their function than does the representation of their receptive fields as a center and a surround mechanism. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP MCCLURKIN, JW (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 46 Z9 47 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1991 VL 66 IS 3 BP 794 EP 808 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GE056 UT WOS:A1991GE05600012 PM 1753288 ER PT J AU GAWNE, TJ MCCLURKIN, JW RICHMOND, BJ OPTICAN, LM AF GAWNE, TJ MCCLURKIN, JW RICHMOND, BJ OPTICAN, LM TI LATERAL GENICULATE NEURONS IN BEHAVING PRIMATES .3. RESPONSE PREDICTIONS OF A CHANNEL MODEL WITH MULTIPLE SPATIAL-TO-TEMPORAL FILTERS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; RETINAL GANGLION-CELLS; PRIMARY VISUAL-CORTEX; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; X-CELLS; CAT; NUCLEUS; INFORMATION; TRANSMISSION AB 1. For the experiments reported in these papers, we recorded the responses of lateral geniculate (LGN) neurons to a large set of two-dimensional, black and white patterns based on Walsh functions and to a set of test stimuli. In the first two papers we reported that these neurons encode stimulus-related information in both the strength and the shape of the response waveforms and that there are more than two independent components in the response. These results cannot be explained by existing models. This paper provides a model of LGN neurons that not only accounts for the foregoing observations, but also yields predictions confirmed by direct tests. 2. The model represents a neuron as a set of three parallel channels. The input to each channel is an array of pixel luminances. Each channel consists of an input nonlinearity cascaded into a linear spatial-to-temporal filter. The output of each channel is a basic waveform, a principal component. The response of the neuron is the sum of the outputs of the three channels. 3. The model accounted for much of the variance in the coefficients of the first three principal components of the neuronal responses to the set of Walsh stimuli. Using parameters derived from the responses of neurons to the Walsh stimuli only, the model also predicted the responses to "center-surround" annuli of different contrasts and mean luminances, as well as to superpositions of pairs of Walsh patterns. The model made statistically significant predictions of the coefficients of two of the principal components of these responses. 4. After the parameters of the model had been fit to reproduce the responses of neurons to the Walsh stimuli, we found that the input nonlinearity of the model was compressed al both the high and low luminance levels. This compression produced response saturation that closely resembled the response saturation of neurons reported in the first paper in this series. Although not absolutely smooth, the spatial filter for the first channel had a dominant excitatory or inhibitory center and an antagonistic surround. Thus this spatial filter accounted for both the center and the surround structures of previous models of LGN receptive fields. There was greater variety in the structures of the spatial filters for the second and third channels, but none had a center-surround organization. Many of the spatial filters for these higher channels contained oriented ridges or valleys. Other spatial filters were dominated by a bipolar pair of pixels. 5. The model of LGN neurons that we present in this paper represents an extension over previous models in four ways. First, the model is capable of explaining the responses of neurons to a wider range of luminances than previous models. Second, the model is capable of explaining the shapes of the response waveforms as well as their magnitudes. Third, the concept of a single receptive field is extended to a series of spatial-to-temporal filters. Fourth, the model suggests that LGN neurons provide a description of both the brightness and the form of a stimulus in their response waveforms. C1 NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 30 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1991 VL 66 IS 3 BP 809 EP 823 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GE056 UT WOS:A1991GE05600013 PM 1753289 ER PT J AU WANG, XJ RINZEL, J ROGAWSKI, MA AF WANG, XJ RINZEL, J ROGAWSKI, MA TI A MODEL OF THE T-TYPE CALCIUM CURRENT AND THE LOW-THRESHOLD SPIKE IN THALAMIC NEURONS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RAT SENSORY NEURONS; LATERAL GENICULATE-NUCLEUS; ELECTROPHYSIOLOGICAL PROPERTIES; RETICULARIS THALAMI; RELAY NEURONS; HIPPOCAMPAL-NEURONS; PYRAMIDAL NEURONS; WAVE DISCHARGES; CA-2+ CHANNELS; CELLS AB 1. A model of the transient, low-threshold voltage-dependent (T-type) Ca2+ current is constructed using recent whole-cell voltage-clamp data from enzymatically isolated rat thalamocortical relay neurons. The T-type Ca2+ current is described according to the Hodgkin-Huxley scheme, using the m3h format, with rate constants determined from the experimental data (22-24-degrees-C; extracellular Ca2+ concentration [Ca2+]o = 3 mM). 2. The T-type Ca2+ current inactivates rapidly during maintained depolarization (time constant, tau-h almost-equal-to 20 ms at -20 mV), yet recovery from inactivation is slow (time constant, tau-r almost-equal-to 270 ms at -80 mV). To reconcile these observations, a two-step kinetic scheme is proposed for the inactivation gate. Each of the time constants in this scheme is voltage dependent, with a maximum at about -85 mV (45 ms for one and 275 ms for the other). 3. Numerical simulations of recovery in a two-pulse, voltage-clamp protocol compare favorably with experimental results obtained by Coulter et al. as well as those obtained in an independent series of experiments with guinea pig thalamic neurons ([Ca2+]o = 10 mM). 4. For current-clamp simulations, a leakage current g(L)(V - V(L)) is included; with V(L) = -65 mV, the calculated resting membrane potential is -63 mV. 5. It is shown that the T-type Ca2+ current together with the leakage current suffices to describe the low-threshold spike (LTS), a slow, triangular-shaped depolarizing event that can be evoked only from relatively hyperpolarized membrane potentials and that underlies the burst firing of Na+-dependent action potentials in thalamic neurons. Outward currents are not required to reproduce the basic shape of the LTS. 6. The LTS can be activated with either a depolarizing current step from a sufficiently hyperpolarized level or on termination of a hyperpolarizing current step. In either case, the amplitude of the LTS is a monotonically increasing, sigmoid-shaped function of the hyperpolarizing current step intensity. 7. Because of the slower kinetic step of the channel's inactivation gate, our model predicts that recovery of the LTS to greater than one-half amplitude would require a prolonged hyperpolarization of > 100 ms (at body temperature). This imposes an upper limit (almost-equal-to 10 Hz) on the frequency of repetitive hyperpolarizations that can elicit a train of LTSs and hence on the frequency of any rhythm that requires LTS-mediated bursting of thalamic neurons. This finding is consistent with the views that the T-type Ca2+ current in thalamic neurons is critical to the generation of the 10-Hz spindle oscillations and that it may also play a role in the epileptic discharge during absence seizures. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. RP WANG, XJ (reprint author), NIDDK,MATH RES BRANCH,BLDG 31,RM 4B-54,BETHESDA,MD 20892, USA. RI Rogawski, Michael/B-6353-2009; Wang, Xiao-Jing/D-2722-2009 OI Rogawski, Michael/0000-0002-3296-8193; NR 51 TC 88 Z9 91 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1991 VL 66 IS 3 BP 839 EP 850 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA GE056 UT WOS:A1991GE05600015 PM 1661326 ER EF