TY - JOUR T1 - c-myc gene expression in human cells is controlled by glucose. AN - 79423209; 2558650 AB - The c-myc oncogene is implicated in normal growth and differentiation processes. Human cell lines IM9 and HepG2 stably cultured at "low" glucose concentrations (5.5 mM) show c-myc mRNA levels 3-4 times higher than cells cultured at "high" glucose concentrations (25 nM). D-fructose (a metabolizable exose) substitutes for D-glucose in reducing c-myc expression while 3-ortho-methylglucose (a non metabolizable exose) is uneffective. c-myc expression is up-regulated (by PMA) or down-regulated (by dexamethasone and long-term exposure to FCS) in human cells cultured at "low" glucose but not in cells cultured at "high" glucose. We previously demonstrated that insulin receptor gene expression in human cell lines in enhanced by glucose. Therefore, glucose controls in an opposite way the expression of two genes important in the regulation of eukaryotic cell growth and differentiation. JF - Biochemical and biophysical research communications AU - Briata, P AU - Laurino, C AU - Gherzi, R AD - Laboratory of Immunobiology, National Cancer Institute I.S.T. Genova, Italy. Y1 - 1989/12/29/ PY - 1989 DA - 1989 Dec 29 SP - 1123 EP - 1129 VL - 165 IS - 3 SN - 0006-291X, 0006-291X KW - Methylglucosides KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - RNA, Messenger KW - 3-O-Methylglucose KW - 146-72-5 KW - Fructose KW - 30237-26-4 KW - Dexamethasone KW - 7S5I7G3JQL KW - Glucose KW - IY9XDZ35W2 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Methylglucosides -- pharmacology KW - Carcinoma, Hepatocellular KW - Dexamethasone -- pharmacology KW - Humans KW - Lymphocytes KW - RNA, Messenger -- biosynthesis KW - Fructose -- pharmacology KW - Liver Neoplasms KW - Cattle KW - Tumor Cells, Cultured KW - Fetal Blood KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Glucose -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics KW - Glucose -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79423209?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-13 N1 - Date created - 1990-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. AN - 79368868; 2594037 AB - Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies. JF - The New England journal of medicine AU - Kaye, F J AU - Bunn, P A AU - Steinberg, S M AU - Stocker, J L AU - Ihde, D C AU - Fischmann, A B AU - Glatstein, E J AU - Schechter, G P AU - Phelps, R M AU - Foss, F M AD - National Cancer Institute-Navy Medical Oncology Branch, Bethesda, Md 20814. Y1 - 1989/12/28/ PY - 1989 DA - 1989 Dec 28 SP - 1784 EP - 1790 VL - 321 IS - 26 SN - 0028-4793, 0028-4793 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Electrons KW - Neoplasm Staging KW - Random Allocation KW - Humans KW - Vincristine -- administration & dosage KW - Combined Modality Therapy -- adverse effects KW - Doxorubicin -- administration & dosage KW - Etoposide -- administration & dosage KW - Radiotherapy Dosage KW - Middle Aged KW - Female KW - Male KW - Mycosis Fungoides -- therapy KW - Skin Neoplasms -- therapy KW - Skin Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Mycosis Fungoides -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79368868?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-17 N1 - Date created - 1990-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1990 May 17;322(20):1470-1 [2330018] N Engl J Med. 1989 Dec 28;321(26):1822-4 [2594040] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Hyperexpression and purification of Escherichia coli adenylate cyclase using a vector designed for expression of lethal gene products. AN - 19624978; 8730733 AB - We describe the construction of a new generation of vectors (pRE) for the hyperexpression of lethal gene products such as adenylate cyclase in Escherichia coli. The pRE vectors are based on the lambda PL promoter and lambda cII ribosome binding site described by Shimatake and Rosenberg (Nature, 292, 128-132, 1981). They have a unique NdeI restriction endonuclease site 3' of the lambda cII ribosome binding site that includes the ATG initiation codon, multilinker cloning sites 3' to the NdeI site, and two lambda transcription terminators 5' and 3' of the lambda PL promoter to eliminate nonspecific transcription and reduce leaky PL transcription, respectively. For hyperexpression of adenylate cyclase, tight control of transcription was necessary since elevation of cAMP levels above the physiological range is lethal to E. coli. Lethality associated with the overproduction of adenylate cyclase was shown to be mediated through the cAMP receptor protein. We used this expression system to overproduce adenylate cyclase 7500 fold, corresponding to 30% of the total cellular protein. Under these conditions the enzyme precipitated with significant loss of activity. Reducing the rate and amount of adenylate cyclase expression to 16% of the total cell protein produced one fourth of the enzyme in a soluble form with high specific activity. The soluble adenylate cyclase was purified to near homogeneity. Images JF - Nucleic Acids Research AU - Reddy, P AU - Peterkofsky, A AU - McKenney, K AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, Bethesda, MD 20892. Y1 - 1989/12/25/ PY - 1989 DA - 1989 Dec 25 SP - 10473 EP - 10488 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 17 IS - 24 SN - 0305-1048, 0305-1048 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Cyclic AMP KW - Transcription KW - Enzymes KW - Ribosomes KW - Expression vectors KW - Promoters KW - Lethality KW - Protein folding KW - Escherichia coli KW - Codons KW - Endonuclease KW - Adenylate cyclase KW - J 02310:Genetics & Taxonomy KW - N 14810:Methods KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19624978?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Expression vectors; Promoters; Lethality; Protein folding; Cyclic AMP; Codons; Enzymes; Transcription; Ribosomes; Endonuclease; Adenylate cyclase; Escherichia coli ER - TY - JOUR T1 - jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. AN - 79382552; 2513129 AB - We have cloned the human jun-B gene and determined its sequence and transforming and trans-activating activities. jun-B is less potent that c-jun in transforming and immortalizing primary rat embryo cells in cooperation with activated ras (effects enhanced by c-fos and TPA); unlike c-jun, jun-B does not transform Rat-1A cells alone. However, cotransfection of c-jun and jun-B into primary rat embryo cells with c-Ha-ras results in a significant decrease in transformation compared with c-jun alone, an event reversed by TPA. Cotransfection of c-jun and jun-B with or without c-fos into F9 teratocarcinoma cells results in decreased trans-activation of AP-1 compared with either gene alone. Introduction of jun-B into primary rat c-jun/ras transformants or c-jun into jun-B/ras transformants also results in a decrease in trans-activation. These findings demonstrate that, whereas jun-B and c-jun each participate in AP-1 trans-activation and malignant transformation, interactions between them involve negative regulation. JF - Cell AU - Schütte, J AU - Viallet, J AU - Nau, M AU - Segal, S AU - Fedorko, J AU - Minna, J AD - NCI-Navy Medical Oncology Branch, Bethesda, Maryland. Y1 - 1989/12/22/ PY - 1989 DA - 1989 Dec 22 SP - 987 EP - 997 VL - 59 IS - 6 SN - 0092-8674, 0092-8674 KW - DNA Probes KW - 0 KW - DNA-Binding Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - RNA Probes KW - Transcription Factors KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Animals KW - Protein-Tyrosine Kinases -- genetics KW - Base Sequence KW - Transfection KW - Humans KW - Restriction Mapping KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Genes, Regulator KW - Oncogenes KW - DNA-Binding Proteins -- genetics KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics KW - Transcription Factors -- genetics KW - Transcriptional Activation KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79382552?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-07 N1 - Date created - 1990-02-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M29039; GENBANK N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Structure of vaccinia virus late promoters. AN - 79441610; 2515287 AB - Functional elements of vaccinia virus late promoters were characterized by mutagenesis. Synthetic oligonucleotides were inserted into a plasmid vector containing the lacZ gene of Escherichia coli flanked by sequences from the thymidine kinase (TK) gene of vaccinia virus. The lacZ gene, under control of the synthetic promoter, was introduced into the vaccinia virus genome at the TK locus by homologous recombination, and each of the 122 recombinants thus obtained was assayed for beta-galactosidase expression. The relative amounts and 5' ends of lacZ mRNAs specified by a subset of the recombinants were determined by primer extension. The analysis indicated that late promoters may be considered in terms of three regions; an upstream sequence of about 20 base-pairs, rich in T and A residues, separated by a spacer region of about six base-pairs from a highly conserved (-1)TAAAT(+4) element within which transcription initiates. All single nucleotide substitutions within the three A residues of the TAAAT, as well as the addition of a fourth A residue, caused drastic reductions in promoter strength. All substitutions of the T residues at -1 and +4 were also detrimental to promoter activity, to an extent that depended on the strength of the promoter as determined by the upstream sequence. mRNA synthesis appeared to initiate within the three A residues regardless of promoter strength. The 5'-poly(A) leader, which is a unique feature of poxvirus late mRNAs, was diminished in length when either of the T residues at -1 and +4 was mutated, was absent or limited to a few nucleotides when any of the three A residues was substituted, but was unaffected by changes outside the TAAAT sequence. The data are consistent with a model for the generation of the normal 5'-poly(A) leader by an RNA polymerase slippage mechanism requiring three consecutive A residues. Single nucleotide substitutions within the six base-pairs upstream and three base-pairs downstream from the TAAAT sequence had modest effects on promoter strength. The most and least favourable changes led to a fourfold increase and an eightfold decrease in activity, respectively. Sequences further upstream were essential for late promoter function; tracts of T or A residues enhanced expression up to 20-fold, the former conferring much greater activity. Highest expression was obtained with a tract of 18 or 20 T residues.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Journal of molecular biology AU - Davison, A J AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/12/20/ PY - 1989 DA - 1989 Dec 20 SP - 771 EP - 784 VL - 210 IS - 4 SN - 0022-2836, 0022-2836 KW - DNA, Viral KW - 0 KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Base Sequence KW - Gene Expression Regulation, Viral KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - beta-Galactosidase -- genetics KW - Transcription, Genetic KW - DNA, Viral -- genetics KW - Structure-Activity Relationship KW - Vaccinia virus -- genetics KW - Regulatory Sequences, Nucleic Acid KW - Promoter Regions, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79441610?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-14 N1 - Date created - 1990-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Synergistic antitumor activity of etoposide and human interleukin-1 alpha against human melanoma cells. AN - 79371873; 2593167 AB - To investigate the possibility of increased activity of cytotoxic anticancer drugs combined with cytokines, we treated human melanoma cells with combinations of etoposide (VP-16) and human recombinant interleukin-1 alpha (rIL-1 alpha). We evaluated the combined cytotoxic effects of VP-16 and rIL-1 alpha using A375-C6 cells, which are sensitive to rIL-1 alpha, and A375-C5 cells, a clonal variant line resistant to rIL-1 alpha. We used the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium-bromid e) assay and the inhibition of [3H]thymidine incorporation into DNA. We analyzed data using the median effects principle of Chou and Talalay (Chou's analysis). The calculated combination index values, at a dose ratio of VP-16 to rIL-1 alpha of 12:1 in simultaneous exposure, indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. We observed more pronounced synergism with VP-16 and rIL-1 alpha toward the A375-C5 IL-1 alpha-resistant melanoma cells. These results suggest that rIL-1 alpha combined with cytotoxic antitumor drugs may provide increased benefit in the treatment of malignant melanoma. JF - Journal of the National Cancer Institute AU - Usui, N AU - Mimnaugh, E G AU - Sinha, B K AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/12/20/ PY - 1989 DA - 1989 Dec 20 SP - 1904 EP - 1909 VL - 81 IS - 24 SN - 0027-8874, 0027-8874 KW - Interleukin-1 KW - 0 KW - Recombinant Proteins KW - Etoposide KW - 6PLQ3CP4P3 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - DNA Damage KW - Humans KW - Drug Synergism KW - DNA -- biosynthesis KW - Etoposide -- pharmacology KW - Interleukin-1 -- pharmacology KW - Melanoma -- pathology KW - Interleukin-1 -- administration & dosage KW - Etoposide -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79371873?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-22 N1 - Date created - 1990-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Thirteen-week toxicity studies of 3,3'-dimethoxybenzidene and C.I. Direct Blue 15 in the Fischer 344 rat. AN - 79504206; 2631298 AB - The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination. JF - Toxicology AU - Morgan, D L AU - Jameson, C W AU - Mennear, J H AU - Ulland, B M AU - Lemen, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 297 EP - 309 VL - 59 IS - 3 SN - 0300-483X, 0300-483X KW - Azo Compounds KW - 0 KW - Benzidines KW - Coloring Agents KW - direct blue 15 KW - 5C44C6888V KW - Dianisidine KW - MJY508JZXV KW - Index Medicus KW - Weight Gain -- drug effects KW - Animals KW - Chemistry KW - Dose-Response Relationship, Drug KW - Kidney -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Thyroid Gland -- drug effects KW - Drinking -- drug effects KW - Liver -- drug effects KW - Chemical Phenomena KW - Female KW - Male KW - Organ Size -- drug effects KW - Coloring Agents -- toxicity KW - Azo Compounds -- toxicity KW - Dianisidine -- toxicity KW - Benzidines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79504206?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-05-08 N1 - Date created - 1990-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Transforming activity of nasopharyngeal carcinoma DNA detectable in mouse JB6 cells. AN - 79416747; 2558076 AB - A JB6 mouse epidermal recipient cell line has been used to detect nasopharyngeal carcinoma (NPC) DNA-associated transforming activity that is not detectable in the NIH 3T3 focus assay. NPC DNA showed both transforming activity and activity for transferring sensitivity to tumor-promoter-induced neoplastic transformation, assayed in 2 different variants of mouse JB6 cells. Comparison of DNAs from various NPC sources that did or did not harbor EBV DNA and that varied in degree of differentiation showed similar transforming activities and similar activities for transferring promotion sensitivity. Thus both a NPC DNA-associated promotion sensitivity and an oncogenic activity function independently of concurrent EBV gene expression. JF - International journal of cancer AU - Colburn, N H AU - Raab-Traub, N AU - Becker, D AU - Cao, Y AU - Winterstein, D AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 1012 EP - 1016 VL - 44 IS - 6 SN - 0020-7136, 0020-7136 KW - Carcinogens KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Neoplasm Transplantation KW - Carcinogens -- pharmacology KW - Animals KW - Humans KW - Mice, Nude KW - Mice KW - Herpesvirus 4, Human KW - Cell Line KW - Carcinoma -- pathology KW - DNA, Neoplasm -- genetics KW - Cell Transformation, Neoplastic -- drug effects KW - Nasopharyngeal Neoplasms -- genetics KW - Nasopharyngeal Neoplasms -- pathology KW - Cell Transformation, Neoplastic -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79416747?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-16 N1 - Date created - 1990-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Unique pathway of IL-3-driven hemopoietic differentiation. AN - 79368675; 2480385 AB - The results of this study support a proposed sequence of IL-3-induced hemopoietic cell proliferation and differentiation. Specifically, IL-3 uniquely induces the transient expression of Thy-1 Ag on Thy-1- bone marrow cells during a 2-wk culture period. Thy-1 Ag is expressed on immature myeloid cells that are undergoing lineage restrictions to granulocytes, macrophages, and mast cells. Flow microfluorimetry-separated Thy-1+ cells require the addition of IL-3 or granulocyte/macrophage-CSF to the culture medium for continued growth and, as these cells divide and undergo terminal differentiation they gradually lose Thy-1 Ag expression. The loss of Thy-1 expression is not strictly correlated with cellular proliferation since the expression of Thy-1 decreases on proliferating cells. Last, IL-3 does not maintain the Thy-1- stem cell population that can give rise to Thy-1+ cells in vitro. The relevance of this scheme of differentiation to normal hemopoiesis and to differentiation-arrested IL-3-dependent leukemic cell populations is discussed. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Keller, J R AU - Ihle, J N AD - Biological Carcinogenesis Development Program, NCI-Frederick Cancer Research Facility, MD 21701. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 4025 EP - 4033 VL - 143 IS - 12 SN - 0022-1767, 0022-1767 KW - Antigens, Surface KW - 0 KW - Antigens, Thy-1 KW - Epitopes KW - Interleukin-3 KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Abridged Index Medicus KW - Index Medicus KW - Phenotype KW - Animals KW - Kinetics KW - Mice KW - Flow Cytometry KW - Cell Separation KW - Antigens, Surface -- metabolism KW - Mice, Inbred BALB C KW - Epitopes -- immunology KW - Glucosephosphate Dehydrogenase -- metabolism KW - Epitopes -- metabolism KW - Hematopoietic Stem Cells -- immunology KW - Interleukin-3 -- physiology KW - Hematopoietic Stem Cells -- enzymology KW - Hematopoietic Stem Cells -- physiology KW - Cell Differentiation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79368675?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-19 N1 - Date created - 1990-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Sequence requirements for cytochrome P-450IIB1 catalytic activity. Alteration of the stereospecificity and regioselectivity of steroid hydroxylation by a simultaneous change of two hydrophobic amino acid residues to phenylalanine. AN - 79366292; 2574176 AB - The phenobarbital-inducible P-450 forms IIB1 and IIB2 are identical in sequence except for 14 amino acid differences within the carboxyl-terminal half of the molecule. IIB1 has about a 5-10-fold higher turnover number for most monooxygenase substrates examined although the substrate specificities of both enzymes are virtually identical. Both P-450s oxygenate testosterone to yield the 16 alpha-hydroxy, 16 beta-hydroxy, 17-keto, and 16 beta-hydroxy, 17-keto metabolites as major products. A variant IIB2 cDNA, isolated from an uninduced rat liver lambda gt11 library, and when expressed in Hep G2 cells using a vaccinia virus vector, was found to code for a protein that produced the 16 alpha-hydroxy and 17-keto metabolites of testosterone but no 16 beta-hydroxylated products. Although the published sequences of IIB1 and IIB2 are identical within the N-terminal halves of the proteins, sequence analysis of the variant cDNA revealed two amino acid substitutions in this region; Leu58----Phe and I1e114----Phe. When these two amino acid changes were incorporated into IIB1, via construction of a chimeric cDNA, the resultant expressed enzyme did not catalyze the 16 beta-hydroxylation of testosterone or androstenedione. Formation of the 16 alpha-hydroxy and 17-keto metabolites, however, was only slightly reduced compared with the parent IIB1. A IIB1 protein that possessed only the I1e114----Phe replacement catalyzed the production of all four testosterone metabolites with only slightly different product ratios compared with the parent enzyme. The substrate specificity of a IIB1 variant containing only the Leu58----Phe replacement could not be determined, since that protein did not accumulate in cells infected with the corresponding recombinant vaccinia virus. These data suggest that two distinct amino acid residues located within the amino-terminal fourth of IIB1 and IIB2 can affect substrate orientation at the active site. JF - The Journal of biological chemistry AU - Aoyama, T AU - Korzekwa, K AU - Nagata, K AU - Adesnik, M AU - Reiss, A AU - Lapenson, D P AU - Gillette, J AU - Gelboin, H V AU - Waxman, D J AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 21327 EP - 21333 VL - 264 IS - 35 SN - 0021-9258, 0021-9258 KW - RNA, Messenger KW - 0 KW - Isoleucine KW - 04Y7590D77 KW - Poly A KW - 24937-83-5 KW - Testosterone KW - 3XMK78S47O KW - Phenylalanine KW - 47E5O17Y3R KW - Steroid Hydroxylases KW - EC 1.14.- KW - Steroid 11-beta-Hydroxylase KW - EC 1.14.15.4 KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Vaccinia virus -- genetics KW - Animals KW - Liver -- enzymology KW - Testosterone -- isolation & purification KW - Testosterone -- metabolism KW - Cloning, Molecular -- methods KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Binding Sites KW - Rats, Inbred Strains KW - Rats KW - Base Sequence KW - Chimera KW - Genetic Vectors KW - Molecular Sequence Data KW - Poly A -- genetics KW - Steroid 11-beta-Hydroxylase -- metabolism KW - Steroid Hydroxylases -- genetics KW - Steroid 11-beta-Hydroxylase -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79366292?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-19 N1 - Date created - 1990-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A phase II study of mitoguazone and vinblastine in advanced transitional cell carcinoma of the urinary tract. AN - 79334619; 2684384 AB - This is a comparative study to evaluate response rate to mitoguazone (MGBG) and vinblastine (VLB) in 52 evaluable patients with advanced transitional cell carcinoma of the urinary tract. Of 38 patients with measurable disease, two of 18 (11%) on MGBG had partial remission (95% confidence interval: 0.01, 0.35), whereas four of 20 (20%) responded on the VLB arm (95% confidence level: 0.06-0.44). Both responses on the MGBG arm were seen in patients given prior chemotherapy. Side effects of both drugs were significant, with 46% of patients given VLB developing severe or life-threatening hematologic toxicity. Data indicate that both drugs, as single agents, are probably inferior to cisplatin for control of advanced transitional cell carcinoma of the urinary tract. JF - Cancer AU - Barrett, J T AU - Orofiamma, B AU - Khandekar, J D AU - Carbone, P P AU - Comis, R L AU - Davis, T E AD - National Cancer Institute, Bethesda, Maryland. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 2445 EP - 2447 VL - 64 IS - 12 SN - 0008-543X, 0008-543X KW - Vinblastine KW - 5V9KLZ54CY KW - Mitoguazone KW - OD5Q0L447W KW - Abridged Index Medicus KW - Index Medicus KW - Drug Evaluation KW - Randomized Controlled Trials as Topic KW - Drug Administration Schedule KW - Neoplasm Staging KW - Infusions, Intravenous KW - Humans KW - Male KW - Female KW - Vinblastine -- therapeutic use KW - Urologic Neoplasms -- pathology KW - Carcinoma, Transitional Cell -- pathology KW - Mitoguazone -- administration & dosage KW - Urologic Neoplasms -- drug therapy KW - Vinblastine -- administration & dosage KW - Mitoguazone -- therapeutic use KW - Mitoguazone -- adverse effects KW - Urologic Neoplasms -- mortality KW - Carcinoma, Transitional Cell -- mortality KW - Vinblastine -- adverse effects KW - Carcinoma, Transitional Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79334619?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-03 N1 - Date created - 1990-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. AN - 79334309; 2582450 AB - We have evaluated immunohistochemical characteristics of tumors and the infiltrating cells in patients treated with various immunotherapy regimens. Forty-eight patients with advanced malignancies were treated with high dose i.v. recombinant interleukin-2 alone or in combination with cyclophosphamide, recombinant tumor necrosis factor, recombinant interferon-alpha, antimelanoma antibody 9.2.27, adoptively transferred tumor infiltrating lymphocytes, or lymphokine-activated killer cells. Thirty-four patients with metastatic melanoma and two patients with breast carcinoma underwent excision of one or more s.c. metastases either before, during, or after treatment. Twelve patients with metastatic renal cell carcinoma underwent pretreatment nephrectomy and these tumors were also studied. Tumor cells were evaluated for class I (HLA-A,B,C) and II (HLA-DR) antigen expression and the mononuclear infiltrate was characterized using an avidin-biotin immunoperoxidase technique. All melanomas were class I antigen positive. Fifty-three % of biopsied metastatic melanoma lesions, 58% of primary renal cell carcinomas, and neither of the two breast carcinomas expressed class II antigen prior to therapy. The pretreatment expression of class II antigens by a tumor was not predictive of a clinical response to recombinant interleukin 2-based therapy. After treatment, however, seven of seven biopsied regressing individual metastases intensely expressed DR antigen on over fifty percent of the cells while only three of ten nonresponding lesions did so. Regressing lesions were permeated with macrophages and both CD4 and CD8 T-cell subsets. There were no CD1 or NKH-1 positive infiltrating cells detected in any lesion. The response to recombinant interleukin 2-based immunotherapy is associated with T-cell as well as macrophage infiltration. DR antigen expression by tumor cells and T-cell infiltrate appear in individual lesions to be associated with this response. JF - Cancer research AU - Rubin, J T AU - Elwood, L J AU - Rosenberg, S A AU - Lotze, M T AD - Surgery Branch, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1989/12/15/ PY - 1989 DA - 1989 Dec 15 SP - 7086 EP - 7092 VL - 49 IS - 24 Pt 1 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - HLA-D Antigens KW - Interleukin-2 KW - Recombinant Proteins KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- therapy KW - Macrophages -- immunology KW - Carcinoma, Renal Cell -- therapy KW - Humans KW - Breast Neoplasms -- therapy KW - Melanoma -- immunology KW - Breast Neoplasms -- immunology KW - Carcinoma -- therapy KW - Cyclophosphamide -- therapeutic use KW - Breast Neoplasms -- pathology KW - Neoplasm Metastasis KW - Carcinoma, Renal Cell -- immunology KW - T-Lymphocytes -- immunology KW - Recombinant Proteins -- therapeutic use KW - Combined Modality Therapy KW - Antigens, Neoplasm -- analysis KW - Carcinoma -- immunology KW - HLA-D Antigens -- analysis KW - Melanoma -- pathology KW - Carcinoma -- pathology KW - Melanoma -- therapy KW - Immunohistochemistry KW - Kidney Neoplasms -- immunology KW - Neoplasms -- pathology KW - Interleukin-2 -- therapeutic use KW - Neoplasms -- therapy KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79334309?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A transfected m1 muscarinic acetylcholine receptor stimulates adenylate cyclase via phosphatidylinositol hydrolysis. AN - 79334768; 2555356 AB - The m1 muscarinic acetylcholine receptor gene was transfected into and stably expressed in A9 L cells. The muscarinic receptor agonist, carbachol, stimulated inositol phosphate generation, arachidonic acid release, and cAMP accumulation in these cells. Carbachol stimulated arachidonic acid and inositol phosphate release with similar potencies, while cAMP generation required a higher concentration. Studies were performed to determine if the carbachol-stimulated cAMP accumulation was due to direct coupling of the m1 muscarinic receptor to adenylate cyclase via a GTP binding protein or mediated by other second messengers. Carbachol failed to stimulate adenylate cyclase activity in A9 L cell membranes, whereas prostaglandin E2 did, suggesting indirect stimulation. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated arachidonic acid release yet inhibited cAMP accumulation in response to carbachol. PMA also inhibited inositol phosphate release in response to carbachol, suggesting that activation of phospholipase C might be involved in cAMP accumulation. PMA did not inhibit prostaglandin E2-, cholera toxin-, or forskolin-stimulated cAMP accumulation. The phospholipase A2 inhibitor eicosatetraenoic acid and the cyclooxygenase inhibitors indomethacin and naproxen had no effect on carbachol-stimulated cAMP accumulation. Carbachol-stimulated cAMP accumulation was inhibited with TMB-8, an inhibitor of intracellular calcium release, and W7, a calmodulin antagonist. These observations suggest that carbachol-stimulated cAMP accumulation does not occur through direct m1 muscarinic receptor coupling or through the release of arachidonic acid and its metabolites, but is mediated through the activation of phospholipase C. The generation of cytosolic calcium via inositol 1,4,5-trisphosphate and subsequent activation of calmodulin by m1 muscarinic receptor stimulation of phospholipase C appears to generate the accumulation of cAMP. JF - The Journal of biological chemistry AU - Felder, C C AU - Kanterman, R Y AU - Ma, A L AU - Axelrod, J AD - Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1989/12/05/ PY - 1989 DA - 1989 Dec 05 SP - 20356 EP - 20362 VL - 264 IS - 34 SN - 0021-9258, 0021-9258 KW - Arachidonic Acids KW - 0 KW - Calcium Channel Blockers KW - Calmodulin KW - Inositol Phosphates KW - Phosphatidylinositols KW - Receptors, Muscarinic KW - Sulfonamides KW - Arachidonic Acid KW - 27YG812J1I KW - 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate KW - 57818-92-5 KW - Gallic Acid KW - 632XD903SP KW - W 7 KW - 65595-90-6 KW - Carbachol KW - 8Y164V895Y KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Calmodulin -- metabolism KW - Animals KW - Gallic Acid -- pharmacology KW - Cell Membrane -- enzymology KW - Inositol Phosphates -- metabolism KW - Cytosol -- enzymology KW - Calmodulin -- antagonists & inhibitors KW - Gene Expression KW - Mice KW - L Cells (Cell Line) -- enzymology KW - Models, Biological KW - Protein Kinase C -- metabolism KW - Genes KW - Calcium Channel Blockers -- pharmacology KW - Sulfonamides -- pharmacology KW - Kinetics KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Carbachol -- pharmacology KW - Receptors, Muscarinic -- genetics KW - Phosphatidylinositols -- metabolism KW - Transfection KW - Adenylyl Cyclases -- metabolism KW - Arachidonic Acids -- metabolism KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79334768?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-08 N1 - Date created - 1990-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Phosphorylation of phospholipase C-gamma by cAMP-dependent protein kinase. AN - 79334624; 2479646 AB - The mechanism by which cAMP modulates the activity of phosphoinositide-specific phospholipase C (PLC) was studied. Elevation of cAMP inhibited both basal and norepinephrine-stimulated phosphoinositide breakdown in C6Bu1 cells which contain at least three PLC isozymes, PLC-beta, PLC-gamma, and PLC-delta. Treatment of C6Bu1 cells with cAMP-elevating agents (cholera toxin, isobutylmethylxanthine, forskolin, and 8-bromo-cAMP) increased serine phosphate in PLC-gamma, but the phosphate contents in PLC-beta and PLC-delta were not changed. In addition, cAMP-dependent protein kinase selectively phosphorylated purified PLC-gamma among the three isozymes and added a single phosphate at serine. The serine phosphorylation, nevertheless, did not affect the activity of PLC-gamma in vitro. We propose, therefore, that the phosphorylation of PLC-gamma by cAMP-dependent protein kinase alters its interaction with putative modulatory proteins and leads to its inhibition. JF - The Journal of biological chemistry AU - Kim, U H AU - Kim, J W AU - Rhee, S G AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/12/05/ PY - 1989 DA - 1989 Dec 05 SP - 20167 EP - 20170 VL - 264 IS - 34 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Isoenzymes KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinases KW - EC 2.7.- KW - Type C Phospholipases KW - EC 3.1.4.- KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Animals KW - Amino Acids -- analysis KW - Cholera Toxin -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Tumor Cells, Cultured -- enzymology KW - Isoenzymes -- metabolism KW - Rats KW - Colforsin -- pharmacology KW - Phosphorylation KW - Kinetics KW - Cyclic AMP -- metabolism KW - Glioma KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Cell Line KW - Protein Kinases -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79334624?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-08 N1 - Date created - 1990-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Primary biliary cirrhosis: management of an unusual case with severe xanthomata by hepatic transplantation. AN - 85212143; pmid-2584673 AB - We report a patient with advanced primary biliary cirrhosis associated with Sjögren's syndrome, xanthelasma, and extensive, painful xanthomata involving cutaneous lipid deposits on her face, abdomen, hands, and buttocks and extensor surfaces over many joints. Despite conventional dietary and drug therapy, these lesions progressed rapidly over 3 years. There was symptomatic improvement of the xanthomata, but no objective amelioration of the xanthomatosis with the use of plasmapheresis over an 18-month period. Liver transplantation was undertaken for decompensated chronic liver disease and poor quality of life due to complications of xanthomatosis. Twelve months after transplantation, all xanthomata and xanthelasma and symptoms attributable to xanthomata had disappeared. Liver transplantation is a drastic but successful remedy for complications of abnormal lipid metabolism associated with primary biliary cirrhosis. JF - Journal of Clinical Gastroenterology AU - Peters, M G AU - Hoffnagle, J H AU - McGarvey, C AU - Fox, I AU - Gregg, R E AU - Jones, E A AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. PY - 1989 SP - 694 EP - 697 VL - 11 IS - 6 SN - 0192-0790, 0192-0790 KW - Xanthomatosis KW - Skin Diseases KW - Human KW - Adult KW - Hyperlipidemia KW - Sjogren's Syndrome KW - Case Report KW - Liver Cirrhosis, Biliary KW - Female KW - Liver Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85212143?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Treatment of polymyositis and dermatomyositis. AN - 79554043; 2702045 JF - Current opinion in rheumatology AU - Dalakas, M AD - National Institutes of Health, Bethesda, Maryland. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 443 EP - 449 VL - 1 IS - 4 SN - 1040-8711, 1040-8711 KW - Adrenal Cortex Hormones KW - 0 KW - Immunosuppressive Agents KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Adrenal Cortex Hormones -- therapeutic use KW - Muscular Diseases -- chemically induced KW - Prednisone -- therapeutic use KW - Humans KW - Immunosuppressive Agents -- therapeutic use KW - Adrenal Cortex Hormones -- adverse effects KW - Myositis -- drug therapy KW - Dermatomyositis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79554043?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-11-08 N1 - Date created - 1990-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The Callimico goeldii (Primates, Platyrrhini) genome: karyology and middle repetitive (LINE-1) DNA sequences. AN - 79493393; 2560695 AB - Callimico goeldii (Goeldi's marmoset) is a neotropical primate with 2n = 47,X1X2Y in the male, and 2n = 48,X1X1X2X2 in the female, due to a Y-autosome translocation. Karyological comparisons of Callimico, Callithrix jacchus and Cebus apella suggest that Callimico is a member of the Callitrichidae. Isozyme data and restriction mapping of LINE-1 repetitive elements in these species and in a variety of other neotropical primates confirm these findings and supply strong evidence for including Callimico in the Callitrichidae. JF - Chromosoma AU - Seuánez, H N AU - Forman, L AU - Matayoshi, T AU - Fanning, T G AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, MD 21701. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 389 EP - 395 VL - 98 IS - 6 SN - 0009-5915, 0009-5915 KW - DNA Transposable Elements KW - 0 KW - Isoenzymes KW - Index Medicus KW - Karyotyping KW - Isoenzymes -- analysis KW - Animals KW - X Chromosome KW - Chromosome Banding KW - DNA Transposable Elements -- genetics KW - Translocation, Genetic KW - Callitrichinae -- classification KW - Callitrichinae -- genetics KW - Genomic Library UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79493393?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-04-23 N1 - Date created - 1990-04-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Protein kinase C mediates the effect of vasopressin in pituitary corticotrophs. AN - 79489950; 2560804 AB - The role of protein kinase C (PKC) on vasopressin (VP) action was investigated by inhibition of endogenous PKC using prolonged incubation of the cells with phorbol ester, and by direct measurement of PKC activity in pituitary cells. Preincubation of the cells for 6 h with 100 nM TPA at 37 C resulted in a 90% decrease in total PKC activity. In the PKC-depleted cells, cAMP responses to stimulation with 100 nM CRF for 30 min were normal, but the potentiating effects of VP and PMA on CRF-stimulated cAMP production were abolished. The stimulation of ACTH secretion by VP and PMA alone was also abolished in PKC- depleted cells. PKC activity in cytosolic and detergent-solubilized membrane fractions from enriched pituitary corticotrophs obtained by centrifugal elutriation, was directly measured by enzymatic assays and by immunoblotting techniques. Basal PKC activity was higher in the cytosol than in the membranes (8.43 +/- 0.47 and 1.93 +/- 0.11 pmol 32P incorporated/10 min, respectively). After incubation of the cells with VP for 15 min or [3H] phorbol-12-myristate-13-acetate (PMA) for 30 min, PKC activity in cytosol was decreased by 40% and 89%, respectively, while the activity in the membrane was increased by 138% and 405%, respectively. Such VP- and PMA-induced translocation of PKC was also observed when the enzyme content in the cytosol and the membranes was measured by immunoblotting using a specific anti-PKC antibody and [125I]protein A. Autoradiographic analysis of immunoblots revealed an 80 kilodalton band characteristic of PKC, with OD higher in the cytosolic than in the membrane fractions.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Molecular endocrinology (Baltimore, Md.) AU - Carvallo, P AU - Aguilera, G AD - Section of Endocrine Physiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1935 EP - 1943 VL - 3 IS - 12 SN - 0888-8809, 0888-8809 KW - Phorbol Esters KW - 0 KW - Vasopressins KW - 11000-17-2 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Phorbol Esters -- pharmacology KW - Animals KW - Enzyme Activation KW - Cells, Cultured KW - Cyclic AMP -- metabolism KW - Female KW - Protein Kinase C -- antagonists & inhibitors KW - Pituitary Gland -- enzymology KW - Vasopressins -- pharmacology KW - Protein Kinase C -- physiology KW - Corticotropin-Releasing Hormone -- metabolism KW - Pituitary Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79489950?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-04-25 N1 - Date created - 1990-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Similar carcinogenic actions of nitrosoalkylureas of varying structure given to rats by gavage. AN - 79482145; 2626762 AB - To relate the tumorigenic effects of directly acting alkylating nitrosoalkylureas to their chemical structure, a series of these compounds was given to F344 rats by gavage at approximately equimolar doses. In some cases, more than one dose rate was used. Potency, as measured by time to death with tumors, was similar for nitrosomethylurea and nitrosoethylurea, although the tumor pattern was different between the two. Nitrosoallylurea was of similar potency, and induced a spectrum of tumors similar to nitroethylurea. Nitroso-n-butyl-, n-amyl- and n-hexyl-ureas were less potent than nitrosoethylurea, but induced a similar pattern of tumors. All of the nitrosoureas induced tumors of the forestomach, usually in high incidence, except nitroso-2-hydroxypropylurea, which caused death of the rats with thymic lymphoma within 6 months. Nitroso-3-hydroxypropylurea was much less potent than its 2-isomer, but induced no tumors of the thymus and was the only one of this group to induce tumors of the glandular stomach. Only nitrosomethylurea induced a high incidence of tumors of the nervous system, but no mammary carcinomas, which most of the other nitrosoureas induced in high incidence in females. Tumors of the lung, duodenum, colon and intestines were induced by several of the compounds, more commonly in males than in females, but a high incidence of liver tumors was found only in rats of both sexes given nitroso-2-phenylethylurea. JF - Toxicology and industrial health AU - Lijinsky, W AU - Kovatch, R M AD - NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, MD 21701. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 925 EP - 935 VL - 5 IS - 6 SN - 0748-2337, 0748-2337 KW - Nitrosourea Compounds KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Duodenal Neoplasms -- chemically induced KW - Chemistry KW - Chemical Phenomena KW - Thymus Neoplasms -- chemically induced KW - Lymphoma -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Colonic Neoplasms -- chemically induced KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79482145?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-04-12 N1 - Date created - 1990-04-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Etiology of retinoic acid-induced cleft palate varies with the embryonic stage. AN - 79476931; 2623642 AB - Retinoic acid (RA) has been shown to be teratogenic in many species, and 13-cis-RA is teratogenic in humans. Exposure to RA during embryonic morphogenesis produced a variety of malformations including limb defects and cleft palate. The type and severity of malformation depended on the stage of development exposed. The purpose of this study was to compare the effects of RA exposure in vivo on different stages of palate development. These results were compared to effects observed after exposure in organ culture. The vehicle used in RA dosing was also shown to be a major factor in the incidence of RA-induced cleft palate. For the in vivo studies, RA (100 mg/kg) in 10 ml corn oil/kg was given p.o. on gestation day (GD) 10 or 12, and the embryos were examined on GD 14 and 16. Exposure to RA in an oil:DMSO vehicle resulted in much higher incidences of cleft palate than were observed after dosing with RA in oil only. After exposure on GD 10, to RA, small palatal shelves formed which did not make contact and fuse on GD 14. The medial cells did not undergo programmed cell death. Instead, the medial cells differentiated into a stratified, squamous, oral-like epithelium. The RA-exposed medial cells did not incorporate 3H-TdR on GD 14 or 16, but the cells expressed EGF receptors and bound 125I-EGF. In contrast, RA-induced clefting after exposure on GD 12 did not involve growth inhibition. Shelves of normal size formed and made contact, but because of altered medial cell differentiation did not fuse. Medial cells differentiated into a pseudostratified, ciliated, nasal-like epithelium. This response was produced in vivo at exposure levels which produced cleft palate, and after exposure of palatal shelves to RA in vitro from GD 12-15. The medial cells exposed on GD 12 incorporated 3H-TdR on GD 14, expressed EGF receptors, and bound 125I-EGF. The responses to RA which lead to cleft palate differed after exposure on GD 10 or 12, and the pathways of differentiation which the medial cells followed depended on the developmental stage exposed. JF - Teratology AU - Abbott, B D AU - Harris, M W AU - Birnbaum, L S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 533 EP - 553 VL - 40 IS - 6 SN - 0040-3709, 0040-3709 KW - Pharmaceutical Vehicles KW - 0 KW - Tretinoin KW - 5688UTC01R KW - Epidermal Growth Factor KW - 62229-50-9 KW - Corn Oil KW - 8001-30-7 KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Animals KW - Gestational Age KW - Mice, Inbred C57BL KW - Microscopy, Electron KW - Mice KW - Organ Culture Techniques KW - Epidermal Growth Factor -- metabolism KW - Cleft Palate -- chemically induced KW - Palate -- drug effects KW - Tretinoin -- toxicity KW - Palate -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79476931?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-29 N1 - Date created - 1990-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Studies on covalent binding of (-)trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene metabolites to cytochromes P-450 LM2 and LM4 and NADPH-cytochrome P-450 reductase. AN - 79460693; 2515665 AB - 1. Metabolism of 14C-labelled benzo[a]pyrene (-)trans-7,8-dihydrodiol to protein- and DNA-binding products in a reconstituted enzyme system proceeds 5 to 10 times faster with rabbit cytochrome P-450 LM4 than with LM2. 2. Either cytochrome converts the substrate to ethyl acetate- and water-soluble metabolites, identified by h.p.l.c. Water-soluble metabolites comprise 78% of the total products with cytochrome P-450 LM2, but only 50% of those formed by LM4. The relative proportion of the two types of metabolites is differentially affected by certain modifiers such as 7,8-benzoflavone. 3. Half of the radioactivity in the aqueous phase of reaction mixtures containing cytochrome P-450 LM4 represents (-)trans-7,8-diol metabolites in complex primarily with NADPH and phosphate. The remaining water-soluble products are bound covalently to proteins in the reconstituted system. 4. Polyacrylamide gel electrophoresis, autoradiography, and measurement of the radioactivity in individual bands indicate that a larger fraction of metabolites is bound to cytochrome P-450 LM4 than to NADPH-cytochrome P-450 reductase, and only marginal binding to cytochrome P-450 LM2 is seen. Metabolite binding to added DNA is likewise substantially greater in magnitude when cytochrome P-450 LM4, as opposed to LM2, catalyses (-)trans-7,8-diol oxygenation. Thus, the degree of metabolite binding to monoxygenase proteins and to DNA correlates well with the catalytic activity of cytochrome P-450 LM4 and LM2 towards (-)trans-7,8-diol. 5. DNA causes a dramatic enhancement in the activity of cytochrome P-450 LM4 with (-)trans-7,8-diol, indicating that the cytochrome and/or the reductase may be functionally impaired by metabolites of this substrate. Such an effect may alter the balance between detoxication and activation of the carcinogenic benzo[a]pyrene. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Deutsch, J AU - Vatsis, K P AU - Leutz, J C AU - Coon, M J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1421 EP - 1435 VL - 19 IS - 12 SN - 0049-8254, 0049-8254 KW - Benzoflavones KW - 0 KW - Dihydroxydihydrobenzopyrenes KW - Deoxycholic Acid KW - 005990WHZZ KW - alpha-naphthoflavone KW - 604-59-1 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Deoxycholic Acid -- pharmacology KW - Biotransformation KW - DNA -- metabolism KW - In Vitro Techniques KW - Rabbits KW - Protein Binding KW - Chromatography, High Pressure Liquid KW - Catalysis KW - Benzoflavones -- pharmacology KW - Microsomes, Liver -- enzymology KW - Microsomes, Liver -- drug effects KW - NADPH-Ferrihemoprotein Reductase -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Dihydroxydihydrobenzopyrenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79460693?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-08 N1 - Date created - 1990-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A study of the interaction of the alkylating agent, NIH10236, with opioid receptors in vitro and in vivo. AN - 79452662; 2559348 AB - The series of experiments reported in this paper examined the spectrum of subtypes of opioid receptors alkylated in vitro by N-cyclopropylmethyl-7 alpha-methylfumaramido-6,14- endoethenotetrahydronororipavine (NIH10236) and four optical isomers of the methylfumaramidophenethyl derivatives of 3-methylfentanyl. Pretreatment of membranes with NIH10236 resulted in a wash-resistant inhibition of the binding of [3H]6 beta-fluoro-6-desoxyoxymorphone (mu binding sites), the binding of [3H][D-ala2,D-leu5]-enkephalin (both the higher and lower affinity delta binding sites) and was without effect on kappa binding sites labelled with [3H]bremazocine. All four potential alkylating derivatives of 3-methylfentanyl were inactive. Pretreatment of membranes with 1 microM of the reversible ligands, (+)-cis-3-methylfentanyl, but not its enantiomer, inhibited the binding of [3H]6 beta-fluoro-6-desoxyoxymorphone and the binding of [3H][D-ala2,D-leu5]enkephalin to the lower affinity binding sites by over 90%. This phenomenon is termed "pseudo-irreversible inhibition." Incubation of pretreated membranes for 60 min at 37 degrees C, in the presence of 200 mM NaCl and 50 microM GppNHp, only partially reversed the masking of opioid receptors by (+)-cis-3-methylfentanyl. For in vivo experiments, membranes were prepared 18-24 hr after the intracerebroventricular administration of 80 and 50 micrograms of NIH10236. This resulted in decreased labelling of mu binding sites, lower affinity [3H][D-ala2,D-leu5]enkephalin binding sites, as well as kappa binding sites, labelled by [3H]U69,593 and [3H]bremazocine. There was no apparent alteration in the higher affinity [3H][D-ala2,D-leu5]enkephalin binding site.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Neuropharmacology AU - Rothman, R B AU - Long, J B AU - Holaday, J W AU - Bykov, V AU - de Costa, B R AU - Kim, C H AU - Jacobson, A E AU - Rice, K C AD - Unit on Receptor Studies, LCS, NIMH, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1349 EP - 1356 VL - 28 IS - 12 SN - 0028-3908, 0028-3908 KW - Alkylating Agents KW - 0 KW - Ligands KW - Receptors, Opioid KW - Thebaine KW - 2P9MKG8GX7 KW - NIH 10236 KW - 88167-37-7 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - In Vitro Techniques KW - Membranes -- metabolism KW - Male KW - Receptors, Opioid -- metabolism KW - Alkylating Agents -- metabolism KW - Thebaine -- metabolism KW - Receptors, Opioid -- classification KW - Thebaine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79452662?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A note on approximating the cumulative distribution function of the time to tumor onset in multistage models. AN - 79432090; 2611323 AB - The general multistage theory of carcinogenesis is a very special type of interconnected birth and death process in which the final state is absorbing and all states except the first one are empty at time zero. An approximation proposed by Whittemore and Keller (1978, SIAM Review 20, 1-30) is assessed. It is shown that the adequacy of this approximation depends on the number of malignant cells resulting from a single normal cell. If more than one malignant cell is likely to occur, the approximation will fail. JF - Biometrics AU - Kopp, A AU - Portier, C J AD - Biomathematics Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1259 EP - 1263 VL - 45 IS - 4 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Animals KW - Biometry KW - Cocarcinogenesis KW - Time Factors KW - Neoplasms, Experimental -- etiology KW - Models, Statistical KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79432090?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-12 N1 - Date created - 1990-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China. AN - 79427393; 2611163 AB - The relation of mining and smelting exposure to arsenic and lung cancer was studied among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners who had lung cancer and an equal number of age matched controls from among tin miners without lung cancer to obtain information on risk factors for lung cancer including detailed history of employment and tobacco use. Occupational history was combined with industrial hygiene data to estimate cumulative arsenic exposure. Similar methods were also used to estimate radon exposure for simultaneous evaluation in this analysis. The results indicate that subjects in the highest quarter of cumulative arsenic exposure have a relative risk of 22.6 compared with subjects without exposure after adjusting for tobacco and radon exposure, and a positive dose response relation was observed. Simultaneous evaluation of arsenic and tobacco exposure indicates a greater risk for arsenic, whereas simultaneous assessment of arsenic and radon exposure suggests radon to be the greater risk. There is no evidence of synergism between arsenic and tobacco exposure. Among arsenic exposed individuals, cases of lung cancer have longer duration but lower average intensity of arsenic exposure than controls, indicating that duration of exposure to arsenic may be more important than intensity in the aetiology of lung cancer. Finally, risk of lung cancer among workers exposed to arsenic only in mining is only slightly less than for miners whose exposure to arsenic was limited to smelting, although risks are highest when workers were exposed to both mining and smelting. JF - British journal of industrial medicine AU - Taylor, P R AU - Qiao, Y L AU - Schatzkin, A AU - Yao, S X AU - Lubin, J AU - Mao, B L AU - Rao, J Y AU - McAdams, M AU - Xuan, X Z AU - Li, J Y AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 881 EP - 886 VL - 46 IS - 12 SN - 0007-1072, 0007-1072 KW - Tin KW - 7440-31-5 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Aged, 80 and over KW - Humans KW - China -- epidemiology KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Arsenic -- adverse effects KW - Lung Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Mining KW - Lung Neoplasms -- chemically induced KW - Occupational Diseases -- chemically induced KW - Metallurgy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79427393?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-26 N1 - Date created - 1990-02-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1977 Aug;19:127-30 [908288] S Afr Med J. 1969 Oct 25;43(43):1307-12 [4310754] J Natl Cancer Inst. 1969 Jun;42(6):1045-52 [5797547] J Occup Med. 1977 Nov;19(11):754-8 [915570] Yale J Biol Med. 1988 May-Jun;61(3):183-93 [3051699] Arch Environ Health. 1978 Nov-Dec;33(6):325-31 [736617] Scand J Work Environ Health. 1981 Dec;7(4):302-9 [7347915] Am J Epidemiol. 1987 Jun;125(6):929-38 [3578251] Br J Ind Med. 1978 Feb;35(1):8-15 [629894] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - 14-day and 90-day toxicity studies of C.I. Pigment Red 3 in Fischer 344 rats and B6C3F1 mice. AN - 79416934; 2606409 AB - Treatment of F344 rats and B6C3F1 mice with C.I. Pigment Red 3 in the diet (10, 5.0, 2.5, 1.25, 0.6 or 0.3%) for 14 and 90 days resulted in haematological alterations consistent with haemolytic anaemia. Rats appeared to be more sensitive than mice to the haematological effects. Histological lesions were observed in rats and mice after exposure for 90 days. Target organs in the rat were the spleen, bone marrow, liver and kidney. Lesions in the spleen consisted of a haematopoietic cell proliferation, iron-positive pigment and congestion of the red pulp, and inflammation of the splenic capsule. Changes in the livers of rats consisted of haematopoietic cell proliferation and iron-positive pigment in Kupffer cells. Haematopoietic cell proliferation also occurred in the bone marrow of treated rats. The presence of iron-positive pigment and a slightly increased incidence of protein casts were seen in the kidney. Target organs in mice were the spleen, liver and kidney. Histological lesions in mice after exposure for 90 days included increased haematopoietic cell proliferation in the liver and spleen, and iron-positive pigment in the spleen. Mild cytomegaly of the renal tubular epithelia was also observed in exposed mice. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Morgan, D L AU - Jameson, C W AU - Mennear, J H AU - Prejean, J D AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 793 EP - 800 VL - 27 IS - 12 SN - 0278-6915, 0278-6915 KW - Azo Compounds KW - 0 KW - Coloring Agents KW - toluidine red KW - 2425-85-6 KW - Index Medicus KW - Animals KW - Sex Factors KW - Anemia -- chemically induced KW - Kidney -- drug effects KW - Mice KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Spleen -- drug effects KW - Time Factors KW - Species Specificity KW - Bone Marrow -- drug effects KW - Female KW - Male KW - Organ Size -- drug effects KW - Coloring Agents -- toxicity KW - Azo Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79416934?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-14 N1 - Date created - 1990-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Morphologic characterization of alveolar macrophages from subjects with occupational exposure to inorganic particles. AN - 79411944; 2557785 AB - Alveolar macrophages recovered by bronchoalveolar lavage from 43 nonsmoking or greater than 5-yr ex-smoking subjects with occupational exposure to inorganic particles (asbestos, n 1/2 19; silica, n 1/2 10; coal, n 1/2 14) were evaluated by light microscopy and transmission and scanning electron microscopy to determine the morphologic changes resulting in these cells from chronic inorganic particulate inhalation. Alveolar macrophages from dust-exposed subjects, including those who had been free of exposure to particles for more than 1 yr, contained particles of higher proportion than did those of normal unexposed subjects. Most of these particles were located within phagolysosomes. The frequency of multinucleated alveolar macrophages was significantly higher in the dust-exposed groups. Ultrastructural studies showed alterations of the morphologic aspects of the surfaces of alveolar macrophages from the dust-exposed subjects, including increased numbers of rufflings, filopodia, pinocytotic vesicles, subplasmalemmal linear densities, and increased frequency of macrophage-macrophage and macrophage-lymphocyte interactions. Furthermore, the numbers of lysosomes were significantly increased in alveolar macrophages from the dust-exposed subjects. Together, these morphologic changes are consistent with the sequelae of phagocytosis, and they emphasize both the role of alveolar macrophages in eliminating inorganic particles from the alveolar spaces and the consequences this role has in alveolar macrophage activation. JF - The American review of respiratory disease AU - Takemura, T AU - Rom, W N AU - Ferrans, V J AU - Crystal, R G AD - Pathology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1674 EP - 1685 VL - 140 IS - 6 SN - 0003-0805, 0003-0805 KW - Air Pollutants, Occupational KW - 0 KW - Coal KW - Dust KW - Asbestos KW - 1332-21-4 KW - Silicon Dioxide KW - 7631-86-9 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Nucleus -- ultrastructure KW - Humans KW - Adult KW - Middle Aged KW - Bronchoalveolar Lavage Fluid -- cytology KW - Organelles -- ultrastructure KW - Dust -- analysis KW - Air Pollutants, Occupational -- adverse effects KW - Pulmonary Alveoli -- cytology KW - Macrophages -- ultrastructure KW - Dust -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79411944?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-29 N1 - Date created - 1990-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The use of chemotherapy in metastatic breast cancer. AN - 79410960; 2481671 AB - Recurrent breast cancer is incurable. Chemotherapeutic agents will be used in most patients with metastatic disease at some time during their course. There is little evidence that such agents prolong survival, and their toxicities are not inconsiderable. The focus of treatment should be on the palliation of symptoms. Single-agent regimens should not be assumed to be less effective than combinations, particularly as salvage therapies. Some new approaches to the management of metastatic disease are explored. JF - Hematology/oncology clinics of North America AU - Garber, J E AU - Henderson, I C AD - Clinical Epidemiology Branch, National Cancer Institute, Boston, Massachusetts. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 807 EP - 821 VL - 3 IS - 4 SN - 0889-8588, 0889-8588 KW - Antineoplastic Agents KW - 0 KW - Hormone Antagonists KW - Immunologic Factors KW - Index Medicus KW - Drug Evaluation KW - Randomized Controlled Trials as Topic KW - Combined Modality Therapy KW - Immunologic Factors -- therapeutic use KW - Humans KW - Hormone Antagonists -- therapeutic use KW - Neoplasm Metastasis KW - Quality of Life KW - Drug Resistance KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Remission Induction KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Palliative Care KW - Breast Neoplasms -- therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79410960?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-13 N1 - Date created - 1990-02-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The acute administration of vasodilators in primary pulmonary hypertension. Experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension. AN - 79410637; 2690706 AB - The hemodynamic responses to acute vasodilator administration were evaluated in 163 patients who were entered into the National Institutes of Health Registry on Primary Pulmonary Hypertension (PPH) between 1981 and 1985. Of a total of 491 drug administrations in these patients, 135 administrations in 104 patients were performed in a manner acceptable to the Registry. A single vasodilator was tried in 79 patients and more than one vasodilator in 25 patients. Two-thirds of the patients were in New York Heart Association Functional Classes III or IV. When the effects of all vasodilators were grouped together, there were significant decreases from baseline in mean pulmonary artery pressure (60 +/- 2 to 57 +/- 2 mm Hg, p less than 0.05) and total pulmonary resistance index (32.5 +/- 1.7 to 25.1 +/- 1.4 mm Hg/L/min/m2, p less than 0.0001), and increases in cardiac index (2.1 +/- 0.1 to 2.7 +/- 0.1 L/min/m2, p less than 0.0001). Mean systemic blood pressure fell (88 +/- 1 to 79 +/- 1 mm Hg, p less than 0.0001), whereas PaO2 was unchanged (70 +/- 3 to 71 +/- 3 mm Hg, p = NS). A fall in total pulmonary resistance greater than 20% was observed in 55% of the adequate drug trials. Adverse effects occurred in 32 of the total 491 patient-drug trials and were generally minor. Hypotension requiring treatment developed in six patients. There were two deaths attributable to vasodilator administration. Patients who died or had hypotension requiring treatment had higher right atrial pressures than did other treated patients (15 +/- 2 versus 9 +/- 1 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) JF - The American review of respiratory disease AU - Weir, E K AU - Rubin, L J AU - Ayres, S M AU - Bergofsky, E H AU - Brundage, B H AU - Detre, K M AU - Elliott, C G AU - Fishman, A P AU - Goldring, R M AU - Groves, B M AD - Division of Lung Diseases, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1623 EP - 1630 VL - 140 IS - 6 SN - 0003-0805, 0003-0805 KW - Vasodilator Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Multicenter Studies as Topic KW - Humans KW - Pulmonary Circulation -- drug effects KW - Vascular Resistance -- drug effects KW - Child KW - Blood Pressure -- drug effects KW - Cardiac Output -- drug effects KW - Adolescent KW - Hypertension, Pulmonary -- drug therapy KW - Hypertension, Pulmonary -- physiopathology KW - Vasodilator Agents -- adverse effects KW - Vasodilator Agents -- administration & dosage KW - Vasodilator Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79410637?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-29 N1 - Date created - 1990-01-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Toxicology of chemical mixtures: experimental approaches, underlying concepts, and some results. AN - 79404642; 2690403 AB - The toxicology of chemical mixtures will be the toxicology of the 1990s and beyond. While this branch of toxicology most closely reflects the actual human exposure situation, there is yet no standard protocol or consensus methodology for investigating the toxicology of mixtures. Thus, in this emerging science, experimentation is required just to develop a broadly applicable evaluation system. Several examples are discussed to illustrate the different experimental designs and the concepts behind each. These include the health effects studies of Love Canal soil samples, the Lake Ontario Coho salmon, the water samples repurified from secondary sewage in the city of Denver Potable Water Reuse Demonstration Plant, and the National Toxicology Program (NTP) effort on a mixture of 25 frequently detected groundwater contaminants derived from hazardous waste disposal sites. In the last instance, an extensive research program has been ongoing for the last 2 years at the NTP, encompassing general toxicology, immunotoxicology, developmental and reproductive toxicology, biochemical toxicology, myelotoxicology, genetic toxicology, neurobehavioral toxicology, and hepato- and renal toxicology. JF - Toxicology letters AU - Yang, R S AU - Hong, H L AU - Boorman, G A AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 183 EP - 197 VL - 49 IS - 2-3 SN - 0378-4274, 0378-4274 KW - Environmental Pollutants KW - 0 KW - Water Pollutants KW - Water Pollutants, Chemical KW - Index Medicus KW - Salmon KW - Rats KW - Animals KW - Public Health KW - Mice KW - Research Design KW - Water Pollutants -- toxicity KW - Environmental Pollutants -- toxicity KW - Water Pollutants, Chemical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79404642?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Site-directed mutagenesis of m1 muscarinic acetylcholine receptors: conserved aspartic acids play important roles in receptor function. AN - 79404152; 2557534 AB - Muscarinic acetylcholine receptors contain a region encompassing the second and third transmembrane domains that is rich in conserved aspartic acid residues. To investigate the role of four conserved aspartic acids at positions 71, 99, 105, and 122 in muscarinic receptor function, point mutations in the rat m1 muscarinic receptor gene were made that converted each Asp to Asn, and wild type or mutant genes were stably expressed in Chinese hamster ovary cells that normally lack muscarinic receptors. Substitution of Asp71 or Asp122 with Asn produced mutant receptors that displayed high affinity for carbachol but decreased efficacy and potency, respectively, in agonist-induced activation of phosphoinositide hydrolysis, suggesting that these residues may mediate receptor-GTP binding protein interactions. Substitution of Asp99 or Asp105 with Asn produced marked decreases in ligand binding affinities and/or covalent incorporation of [3H] propylbenzilylcholine mustard, suggesting that these residues may be involved in receptor-ligand interactions. JF - Molecular pharmacology AU - Fraser, C M AU - Wang, C D AU - Robinson, D A AU - Gocayne, J D AU - Venter, J C AD - Section of Receptor Biochemistry and Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 840 EP - 847 VL - 36 IS - 6 SN - 0026-895X, 0026-895X KW - Phosphatidylinositols KW - 0 KW - Receptors, Muscarinic KW - Aspartic Acid KW - 30KYC7MIAI KW - Propylbenzilylcholine Mustard KW - 36167-80-3 KW - Pirenzepine KW - 3G0285N20N KW - Quinuclidinyl Benzilate KW - 6581-06-2 KW - otenzepad KW - OM7J0XAL0S KW - Index Medicus KW - Rats KW - Phosphatidylinositols -- metabolism KW - Animals KW - Pirenzepine -- metabolism KW - Quinuclidinyl Benzilate -- metabolism KW - Pirenzepine -- analogs & derivatives KW - Propylbenzilylcholine Mustard -- metabolism KW - Mutation KW - Structure-Activity Relationship KW - Cricetinae KW - Aspartic Acid -- physiology KW - Receptors, Muscarinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79404152?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-31 N1 - Date created - 1990-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Selective inhibition of polymorphonuclear neutrophil activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 79403986; 2557688 AB - Although the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), via its interaction with the Ah receptor, is an extremely potent carcinogen and immunosuppressive agent in experimental animals, its possible actions on polymorphonuclear (PMN) function have not been determined. In addition to their importance against infectious organisms, PMNs have been implicated in antitumor resistance. The present studies examined the effects of in vivo exposure to TCDD on PMN function in B6C3F1 (TCDD sensitive, presence of high affinity Ah receptor) and DBA/2N (TCDD resistant at low doses, defective Ah receptor) mice. Animals received a single oral exposure of 5 or 10 micrograms/kg of TCDD and PMNs were obtained 5 days later from the peritoneal cavity following elicitation with sodium caseinate. TCDD reduced the cytolytic and cytostatic activity of PMA-activated PMNs in B6C3F1, but not in DBA/2N mice, suggesting that this response segregates with the Ah locus. Furthermore, TCDD was found to bind specifically to PMNs from Ah-responsive mice. Neither the production of superoxide and hydrogen peroxide nor degranulation, the latter measured by beta-glucuronidase release, was impaired. Supernatants recovered from PMN cell cultures of TCDD-sensitive mice, but not from resistant DBA/2N mice, showed reduced killing capacity for actinomycin D-treated L929 tumor cells, while their ability to bind to tumor cells was not altered. These data suggest that TCDD interferes with PMN-mediated tumor cell killing by altering the production or secretion of a cytolytic factor. Examination of bone marrow stem cells revealed that granulocytic but not monocytic colonies were reduced after TCDD exposure in vivo and in vitro. Although mature PMNs had detectable levels of Ah receptor, exposure in vitro of these cells to TCDD had no effect on antitumor activity. Thus, it is possible that TCDD may affect PMNs at the level of hematopoiesis, via a direct interaction with granulocyte precursor cells, or modulate PMNs at different stages of maturation. JF - Toxicology and applied pharmacology AU - Ackermann, M F AU - Gasiewicz, T A AU - Lamm, K R AU - Germolec, D R AU - Luster, M I AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences/NIH Research, Triangle Park, North Carolina 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 470 EP - 480 VL - 101 IS - 3 SN - 0041-008X, 0041-008X KW - Dioxins KW - 0 KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - Superoxides KW - 11062-77-4 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glucuronidase KW - EC 3.2.1.31 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Glucuronidase -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Hematopoietic Stem Cells -- cytology KW - Mice KW - Receptors, Drug -- physiology KW - Killer Cells, Natural -- drug effects KW - Mice, Inbred DBA KW - Binding Sites KW - Hematopoietic Stem Cells -- drug effects KW - Superoxides -- metabolism KW - Cell Survival -- drug effects KW - Receptors, Drug -- drug effects KW - Mice, Inbred C3H KW - Mice, Inbred C57BL KW - Colony-Forming Units Assay KW - Neutrophils -- drug effects KW - Neutrophils -- immunology KW - Polychlorinated Dibenzodioxins -- toxicity KW - Neutrophils -- physiology KW - Dioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79403986?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-08 N1 - Date created - 1990-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Spontaneous EEG changes during tobacco abstinence and nicotine substitution in human volunteers. AN - 79401160; 2600826 AB - Electroencephalographic correlates of tobacco abstinence and nicotine substitution were measured in adult male cigarette smokers in residence on a research ward in two experiments. After ad libitum smoking, seven subjects were deprived of nicotine for 10 days and then resumed smoking. During tobacco abstinence, there were significant decreases in alpha frequency and beta frequency and increases in theta power. These effects were observed as early as 29 hr and in some instances persisted for 7 days. In the second experiment, a group of eight heavy smokers chewed 12 pieces of either placebo or nicotine-containing polacrilex gum (2 or 4 mg) per day while deprived of cigarettes. In the placebo condition, electroencephalographic signs were similar to those accompanying tobacco deprivation in the first experiment. Administration of nicotine polacrilex prevented the appearance of these tobacco withdrawal signs. This study provides new information on the time course of certain electrophysiologic components of the tobacco withdrawal syndrome and confirms that the effects are specific to the deprivation of nicotine. The data also suggest that the 4-mg polacrilex was more effective than the 2-mg dose when the results across all measures were considered. JF - The Journal of pharmacology and experimental therapeutics AU - Pickworth, W B AU - Herning, R I AU - Henningfield, J E AD - National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 976 EP - 982 VL - 251 IS - 3 SN - 0022-3565, 0022-3565 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Humans KW - Adult KW - Male KW - Smoking -- physiopathology KW - Substance Withdrawal Syndrome -- physiopathology KW - Nicotine -- pharmacology KW - Electroencephalography UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79401160?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-30 N1 - Date created - 1990-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The sequential development of cancer: a morphological perspective. AN - 79400647; 2690406 AB - Cancer development proceeds through sequential or contemporaneous morphological changes from normal, preneoplastic, and premalignant lesions to highly malignant neoplasms. The morphological continuum that comprises cancer development is usually divided into diagnostic categories of hyperplasia (or dysplasia), benign neoplasia, and malignant neoplasia based on perceived biological behavior. Although a morphological continuum may be evident from the histological evaluation of preneoplastic and neoplastic lesions, it is not axiomatic that all preneoplastic or benign lesions progress. The probability of regression or progression from one category to another, or the rates at which these might occur, are seldom known for spontaneous or induced neoplasms. Host factors as well as exogenous stimuli may influence these events. The concept of neoplastic progression and the limitations of our knowledge of the biological behavior of preneoplastic lesions and benign neoplasms are important considerations in the interpretation of pathology data from carcinogenicity studies. JF - Toxicology letters AU - Eustis, S L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 267 EP - 281 VL - 49 IS - 2-3 SN - 0378-4274, 0378-4274 KW - Index Medicus KW - Rats KW - Animals KW - Carcinogenicity Tests KW - Hyperplasia -- pathology KW - Neoplasms, Experimental -- pathology KW - Precancerous Conditions -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79400647?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Triggers for higher-order toxicity testing. AN - 79400593; 2690402 AB - Strategies for selecting chemicals for definitive, higher-order toxicology tests are important because physical and personnel resources are limited and chemicals vary widely in the need for testing. The National Toxicology Program has developed strategies for selection of chemicals for definitive tests in several areas of toxicology. In addition to the number of people, the extent of human exposure, structure-activity considerations, and reports of observations in humans, specific triggers are sought from animal studies and short-term tests or in vitro screens which impact the chemical selection process and the design of definitive studies. Specific triggers in reproductive toxicology, for example, include observations in prechronic toxicology studies in rats and mice--weights and histopathologic examinations of reproductive organs, measurements of sperm production and function in males, and estrus cyclicity in females. Comparable tissue-specific triggers do not exist for developmental toxicity studies, and screening tests are not widely used for setting priorities for the conduct of definitive developmental toxicology studies. JF - Toxicology letters AU - Schwetz, B A AU - Morrissey, R E AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 171 EP - 179 VL - 49 IS - 2-3 SN - 0378-4274, 0378-4274 KW - Index Medicus KW - Rats KW - Animals KW - Mutagenicity Tests KW - Carcinogenicity Tests KW - Mice KW - Male KW - Female KW - Drug Evaluation, Preclinical KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79400593?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells. AN - 79398712; 2557616 AB - Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for approximately 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, we introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. BEAS-2B cells expressing both the transfected c-raf-1 and c-myc sequences formed large cell carcinomas in athymic nude mice with a latency of 4-21 weeks, whereas either pZip-raf- or pZip-myc-transfected cells were nontumorigenic after 12 months. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. A significant increase in the mRNA levels of neuron-specific enolase was detected in BEAS-2B cells containing both the c-raf-1 and c-myc genes and derived tumor cell lines. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Pfeifer, A M AU - Mark, G E AU - Malan-Shibley, L AU - Graziano, S AU - Amstad, P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 10075 EP - 10079 VL - 86 IS - 24 SN - 0027-8424, 0027-8424 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression KW - Mice KW - Mice, Nude KW - Molecular Weight KW - Neoplasm Transplantation KW - Chimera KW - Bronchi KW - Transfection KW - Blotting, Southern KW - Transplantation, Heterologous KW - Epithelium KW - Cell Line KW - Immunoassay KW - Protein-Tyrosine Kinases -- genetics KW - Simian virus 40 -- genetics KW - Proto-Oncogene Proteins -- isolation & purification KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics KW - Antigens, Polyomavirus Transforming -- genetics KW - Simian virus 40 -- immunology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79398712?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1980 Oct;36(1):62-78 [6160263] Mol Carcinog. 1988;1(3):151-60 [2855021] Mol Cell Biol. 1983 Feb;3(2):280-9 [6300662] Cancer Res. 1983 Jun;43(6):2806-11 [6303568] Nature. 1983 Jun 2-8;303(5916):401-6 [6304522] Nature. 1983 Aug 18-24;304(5927):596-602 [6308472] Science. 1983 Nov 18;222(4625):765-71 [6356357] Nature. 1983 Nov 10-16;306(5939):194-6 [6646201] Proc Natl Acad Sci U S A. 1984 Jan;81(1):71-5 [6320174] Cell. 1984 May;37(1):151-8 [6609772] Cell. 1984 Jun;37(2):521-8 [6327072] Biochem Biophys Res Commun. 1984 Jul 18;122(1):340-4 [6743336] Cell. 1984 Jul;37(3):1053-62 [6331674] J Natl Cancer Inst. 1984 Oct;73(4):801-7 [6148444] Cell. 1984 Oct;38(3):627-37 [6488314] Cancer Res. 1985 Jan;45(1):272-5 [2578097] Science. 1985 Mar 8;227(4691):1250-2 [2579430] Cancer Res. 1985 Jun;45(6):2913-23 [2985257] Cancer Res. 1985 Jun;45(6):2924-30 [2985258] Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] Virology. 1985 Oct 15;146(1):78-89 [2994296] Nature. 1985 Nov 7-13;318(6041):69-73 [2997622] Nature. 1985 Dec 19-1986 Jan 1;318(6047):667-70 [4079980] Cancer Res. 1986 Mar;46(3):1530-4 [3002619] Nucleic Acids Res. 1986 Jan 24;14(2):1009-15 [3003687] J Cell Biochem. 1986;30(3):195-218 [3084503] J Clin Invest. 1986 Aug;78(2):525-32 [3016030] Cancer Res. 1987 Apr 15;47(8):2148-55 [3030544] Mol Cell Biol. 1987 May;7(5):2031-4 [3037341] Science. 1987 Aug 28;237(4818):1036-9 [3616624] Science. 1987 Aug 28;237(4818):1039-41 [3616625] N Engl J Med. 1987 Oct 8;317(15):929-35 [3041218] Nature. 1987 Oct 1-7;329(6138):451-4 [2821400] Cancer. 1987 Dec 1;60(11):2669-74 [3677003] Cancer Res. 1987 Dec 1;47(23):6236-42 [2824028] Eur J Immunol. 1987 Oct;17(10):1491-8 [3119352] Cancer Res. 1988 Apr 1;48(7):1904-9 [2450641] Oncogene. 1988 Feb;2(2):187-93 [3285297] Am J Pathol. 1988 Jun;131(3):444-51 [3381877] Cell. 1988 Jun 17;53(6):857-67 [2454746] Science. 1988 Jul 15;241(4863):353-7 [2838909] Cell. 1988 Jul 15;54(2):275-83 [2839300] Am J Pathol. 1988 Jul;132(1):13-7 [2456019] Cancer Res. 1988 Aug 15;48(16):4689-94 [3293776] Adv Biochem Psychopharmacol. 1988;44:45-55 [3041752] Cancer Res. 1988 Sep 15;48(18):5163-6 [2842046] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6523-7 [2842776] Cancer Res. 1988 Oct 15;48(20):5738-41 [3048648] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8506-10 [2847163] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] Oncogene Res. 1988;3(1):99-103 [2905034] Mol Cell Biol. 1988 Aug;8(8):3373-81 [2850489] Oncogene Res. 1988;3(4):401-8 [3067190] Science. 1989 Mar 10;243(4896):1354-6 [2466340] Mol Cell Biol. 1989 Jan;9(1):67-73 [2784537] Cell. 1989 May 5;57(3):379-92 [2541911] Science. 1982 Jan 8;215(4529):181-2 [6274023] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Sensitization, kindling, and anticonvulsants in mania. AN - 79394790; 2689434 AB - Cocaine can induce manic syndromes ranging from mild hypomania to severe dysphoric and psychotic mania, in part depending on the number and duration of drug administrations. Repeated cocaine administration in animals results in increased motor (behavioral sensitization) and convulsive (pharmacologic kindling) responses. Study of these progressive syndromes in animals may provide insights into principles underlying the longitudinal evolution of manic syndromes in man, including the increased vulnerability to recurrence following successive episodes. Different phases in the evolution of behavioral sensitization are differentially responsive to neuroleptics while the same principle is evident for different anticonvulsants in kindling. The authors examine whether pharmaco-responsivity may also differ as a function of stage of progression of mania. Antimanic effects of lithium, neuroleptics, and the newer anticonvulsants, such as carbamazepine, valproic acid, and clonazepam, are discussed in this context. JF - The Journal of clinical psychiatry AU - Post, R M AU - Weiss, S R AD - Biological Psychiatric Branch, National Institute of Mental Health, Bethesda, Md. 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 23 EP - 30; discussion 45-7 VL - 50 Suppl SN - 0160-6689, 0160-6689 KW - Anticonvulsants KW - 0 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Disease Models, Animal KW - Stereotyped Behavior -- drug effects KW - Motor Activity -- drug effects KW - Mice KW - Cocaine -- pharmacology KW - Behavior, Animal -- drug effects KW - Anticonvulsants -- pharmacology KW - Kindling, Neurologic KW - Bipolar Disorder -- etiology KW - Bipolar Disorder -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79394790?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Chromatographic analysis of the aminoacyl-tRNAs which are required for translation of codons at and around the ribosomal frameshift sites of HIV, HTLV-1, and BLV. AN - 79388802; 2556852 AB - An examination of the frameshift signals or proposed signals within published sequences of retroviruses and other genetic elements from higher animals shows that each site utilizes a tRNA which normally contains Wybutoxine (Wye) base or Queuine (Q) base in the anticodon loop. We find experimentally that most of the Phe-tRNA present in HIV-1 infected cells lacks the highly modified Wye base in its anticodon loop and most of the Asn-tRNA in HTLV-1 and BLV infected cells lacks the highly modified Q base in its anticodon loop. Interestingly, Phe-tRNA translates a UUU codon within the ribosomal frameshift signal in HIV and Asn-tRNA translates a AAC codon within the proposed frameshift signals in HTLV-1 and BLV. Thus, the lack of a highly modified base in the anticodon loop of tRNAs in retroviral infected cells is correlated with the participation of these undermodified tRNAs in the corresponding frameshift event. This suggests that the "shifty" tRNAs proposed by Jacks et al. (Cell 55, 447-458, 1988) to carry out frameshifting may be hypomodified isoacceptors. JF - Virology AU - Hatfield, D AU - Feng, Y X AU - Lee, B J AU - Rein, A AU - Levin, J G AU - Oroszlan, S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 736 EP - 742 VL - 173 IS - 2 SN - 0042-6822, 0042-6822 KW - Codon KW - 0 KW - RNA, Messenger KW - RNA, Transfer, Amino Acyl KW - Index Medicus KW - AIDS/HIV KW - Protein Biosynthesis KW - Animals KW - Tumor Cells, Cultured KW - Chromatography KW - Ribosomes KW - Cell Line KW - Human T-lymphotropic virus 1 -- genetics KW - Codon -- genetics KW - Leukemia Virus, Bovine -- genetics KW - RNA, Transfer, Amino Acyl -- genetics KW - Retroviridae -- genetics KW - RNA, Transfer, Amino Acyl -- analysis KW - RNA, Messenger -- genetics KW - HIV -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79388802?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-24 N1 - Date created - 1990-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - CD4-Pseudomonas exotoxin hybrid protein blocks the spread of human immunodeficiency virus infection in vitro and is active against cells expressing the envelope glycoproteins from diverse primate immunodeficiency retroviruses. AN - 79371865; 2480605 AB - We previously described an unusual recombinant protein, designated CD4(178)-PE40, containing the gp120 binding region of human CD4 linked to active regions of Pseudomonas exotoxin A. The ability of this molecule to selectively inhibit protein synthesis in cells expressing the surface envelope glycoprotein of human immunodeficiency virus (HIV) suggested this molecule may be useful in treating infected individuals. To further evaluate its therapeutic potential, several in vitro properties of this hybrid toxin were examined. CD4(178)-PE40 was found to be an extremely potent cytotoxic agent, selectively killing HIV-infected cells with IC50 values around 100 pM. In a coculture system employing mixtures of HIV-infected and -uninfected cells, the hybrid toxin inhibited spread of the infection, as judged by a delay in HIV-induced cell killing and a dramatic suppression of free virus production. Experiments with control recombinant proteins indicated that this protective effect was primarily due to selective killing of the HIV-infected cells, rather than to a simple blocking effect of the CD4 moiety of the hybrid toxin. Using recombinant vaccinia viruses as expression vectors, we found the hybrid toxin to be active against cells expressing the envelope glycoproteins of divergent isolates of HIV-1, as well as HIV-2 and simian immunodeficiency virus. These results provide further support for the therapeutic potential of CD4(178)-PE40 in the treatment of HIV-infected individuals. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Berger, E A AU - Clouse, K A AU - Chaudhary, V K AU - Chakrabarti, S AU - FitzGerald, D J AU - Pastan, I AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20852. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 9539 EP - 9543 VL - 86 IS - 23 SN - 0027-8424, 0027-8424 KW - Antigens, CD4 KW - 0 KW - Antiviral Agents KW - Bacterial Proteins KW - CD4-Pseudomonas toxin KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Viral Envelope Proteins KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Cell Survival -- drug effects KW - Bacterial Proteins -- pharmacology KW - Humans KW - RNA-Directed DNA Polymerase -- metabolism KW - Cell Line KW - HIV -- drug effects KW - Exotoxins -- pharmacology KW - Recombinant Proteins -- pharmacology KW - Antiviral Agents -- pharmacology KW - Viral Envelope Proteins -- biosynthesis KW - Immunotoxins -- pharmacology KW - HIV -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79371865?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-19 N1 - Date created - 1990-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1984 May 4;224(4648):497-500 [6200935] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2433-7 [2648404] Science. 1986 Feb 7;231(4738):600-2 [3003906] Cell. 1986 Jul 4;46(1):1-4 [3013415] J Exp Med. 1986 Jul 1;164(1):280-90 [3014036] J Immunol Methods. 1986 Nov 6;93(2):157-65 [3490518] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] Mol Cell Biol. 1987 Jul;7(7):2538-44 [3112559] Nature. 1987 Aug 6-12;328(6130):539-43 [3497350] Cell. 1987 Sep 11;50(6):975-85 [2441877] Virology. 1987 Oct;160(2):323-9 [2444031] J Bacteriol. 1987 Nov;169(11):4967-71 [2889718] Science. 1987 Dec 18;238(4834):1704-7 [3500514] Nature. 1988 Jan 7;331(6151):76-8 [2829022] Nature. 1988 Jan 7;331(6151):78-81 [2829023] Nature. 1988 Jan 7;331(6151):82-4 [3257544] Nature. 1988 Jan 7;331(6151):84-6 [2829024] Cell. 1988 Mar 11;52(5):631-3 [2830988] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2357-61 [2451247] J Biol Chem. 1988 Jul 5;263(19):9470-5 [3132465] AIDS. 1988 Apr;2(2):101-5 [2454642] Nature. 1988 Sep 22;335(6188):369-72 [2843774] J Immunol. 1989 Jan 15;142(2):431-8 [2463307] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Prostaglandin hydroperoxidase-dependent activation of heterocyclic aromatic amines. AN - 79362298; 2512013 AB - Heterocyclic aromatic amines, derived from the pyrolysis of amino acids and proteins, are potent mutagens in the Ames Salmonella assay with rodent liver activation. Additionally, heterocyclic aromatic amines are multipotent carcinogens. We report evidence that these compounds are substrates for the hydroperoxidase activity of prostaglandin H synthase, as measured by alterations in UV/visible spectra, and are bioactivated to macromolecule-reactive species by this enzyme. Indirect electron paramagnetic resonance studies indicate that this activation may occur via a one-electron mechanism. 2-Amino-3-methylimidazo[4,5f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) are direct-acting mutagens in TA98. The mutagenicity of IQ and MeIQ, but not Trp-P-2, were enhanced by activation with ram seminal vesicle microsomes (a rich source of prostaglandin H synthase). Subsequent experiments utilized the newly constructed tester strain TA1538/1,8-DNP6 (pYG 121), which has enhanced arylamine N-acetyltransferase activity. In this strain IQ, MeIQ and 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1) were mutagenic with ram seminal vesicle microsome activation. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was a weak direct-acting mutagen, and was not activated by the ram seminal vesicles (RSV) system. The responses of IQ and MeIQ were markedly enhanced in TA1538/1.8-DNP6 (pYG 121), relative to TA98. These data are consistent with the involvement of prostaglandin H synthase-catalyzed activation in heterocyclic aromatic amine-induced extrahepatic neoplasia. JF - Carcinogenesis AU - Petry, T W AU - Josephy, P D AU - Pagano, D A AU - Zeiger, E AU - Knecht, K T AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 2201 EP - 2207 VL - 10 IS - 12 SN - 0143-3334, 0143-3334 KW - Amines KW - 0 KW - Heterocyclic Compounds KW - Proteins KW - prostaglandin hydroperoxidase KW - EC 1.11.- KW - Peroxidases KW - EC 1.11.1.- KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Index Medicus KW - Animals KW - Mutagenicity Tests KW - Biotransformation KW - Sheep KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Salmonella typhimurium -- drug effects KW - Microsomes -- enzymology KW - Proteins -- metabolism KW - Protein Binding KW - Seminal Vesicles -- enzymology KW - Male KW - Heterocyclic Compounds -- metabolism KW - Heterocyclic Compounds -- pharmacology KW - Amines -- pharmacology KW - Amines -- metabolism KW - Peroxidases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79362298?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-22 N1 - Date created - 1990-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cell specificity for the pulmonary metabolism of tobacco-specific nitrosamines in the Fischer rat. AN - 79358686; 2591016 AB - The activity and distribution of the metabolic pathways of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the structurally related nitrosamine, N'-nitrosonornicotine (NNN) were examined in pulmonary cells from F344 rats in order to investigate the mechanisms by which NNK and NNAL, but not NNN, cause lung tumors. The tritium labeled nitrosamines were incubated with Clara cells, alveolar macrophages, alveolar type II cells, or small cells and metabolites were analyzed by HPLC. O6-Methyl-guanine (O6MG) formation was also quantified in the cells incubated with NNK. Clara cells metabolized all compounds more extensively than the other cell types. Total alpha-hydroxylation, carbonyl reduction to NNAL, and pyridine N-oxidation in cells incubated with NNK, as well as concentrations of O6MG in DNA were higher in Clara cells than in other cell types. Carbonyl reduction of NNK predominated over the other metabolic pathways in all cell types. The high activity for alpha-hydroxylation of NNK in Clara cells is consistent with previous studies which proposed that the cell specificity for O6MG formation and the accumulation of this adduct during low-dose exposure to NNK may stem from the presence of a high affinity pathway in Clara cells for NNK activation. Metabolism of NNAL by alpha-hydroxylation, and by reconversion to NNK followed by alpha-hydroxylation were observed. Total alpha-hydroxylation of NNAL was less extensive than alpha-hydroxylation of NNK. NNN was metabolized by both the 2'- and 5'-alpha-hydroxylation pathways. 2'-Hydroxylation of NNN produces the same DNA pyridyloxobutylating agent as does methyl hydroxylation of NNK. However, NNN is not a methylating agent and does not induce lung tumors in rats. Metabolism of NNN by 2'-hydroxylation was, depending on cell type, 41-85% as extensive as total alpha-hydroxylation of NNK, indicating that the rates of formation of the DNA pyridyloxobutylating agent were similar from NNN and NNK. The results of this study demonstrate that Clara cells have a high capacity to metabolically activate NNK, NNAL and NNN and provide further support for the hypothesis that DNA methylation of pulmonary cells is important in NNK carcinogenesis. JF - Carcinogenesis AU - Belinsky, S A AU - White, C M AU - Trushin, N AU - Hecht, S S AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 2269 EP - 2274 VL - 10 IS - 12 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Mutagens KW - Nitrosamines KW - Tritium KW - 10028-17-8 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Biotransformation KW - Kinetics KW - DNA -- metabolism KW - Chromatography, High Pressure Liquid KW - Structure-Activity Relationship KW - Alkylation KW - Plants, Toxic KW - Nitrosamines -- metabolism KW - Tobacco KW - Lung -- metabolism KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358686?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-22 N1 - Date created - 1990-01-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Substance abuse education in residency training programs in emergency medicine. NIAAA Task Force of the American College of Emergency Physicians. AN - 79358660; 2589703 AB - The emergency department is the focal point for many social ills, not the least of which is substance abuse. We conducted a study to determine to what degree substance abuse education is taught in emergency medicine residency training programs. A set of educational objectives was developed by a task force composed of representatives of the American College of Emergency Physicians, the Society of Teachers of Emergency Medicine, and the University Association for Emergency Medicine. A questionnaire then was sent to the directors of all emergency medicine residency programs accredited by the Accreditation Council for Graduate Medical Education to determine the degree to which those objectives are covered in residency training. A 62% response rate was achieved. The data revealed that such topics as narcotic prescription law, patterns of risk, and issues pertaining to substance abuse by physicians were covered by fewer than half of the programs responding. Respondents were generally satisfied with the adequacy of training of residents and faculty in the area of substance abuse; however, they were dissatisfied with the adequacy of available training materials. Recommendations for changes in graduate curriculum as well as avenues for further research are provided. JF - Annals of emergency medicine AU - Taliaferro, E H AU - Rund, D A AU - Brown, C G AU - Goldfrank, L R AU - Jorden, R C AU - Ling, L J AU - Gallery, M E AD - NIAAA Task Force of the American College of Emergency Physicians, Dallas, Texas 75261-9911. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1344 EP - 1347 VL - 18 IS - 12 SN - 0196-0644, 0196-0644 KW - Abridged Index Medicus KW - Index Medicus KW - Attitude of Health Personnel KW - Humans KW - Curriculum KW - Surveys and Questionnaires KW - Emergency Medicine -- education KW - Substance-Related Disorders KW - Internship and Residency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358660?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents. A double-blind crossover comparison. AN - 79358323; 2686576 AB - Forty-eight children and adolescents with severe primary obsessive-compulsive disorder completed a 10-week double-blind crossover trial of clomipramine hydrochloride (mean dose [+/- SD], 150 +/- 53 mg/d) and desipramine hydrochloride (mean dose [+/- SD], 153 +/- 55 mg/d). Clomipramine was clearly superior to desipramine in significantly reducing obsessive-compulsive symptoms. Age at onset, duration and severity of illness, type of symptom, and plasma drug concentrations did not predict clinical response to clomipramine. Sixty-four percent of patients who received clomipramine as their first active treatment showed at least some sign of relapse during desipramine treatment. We further document the specificity of the antiobsessional effect of clomipramine and the need for maintenance treatment. JF - Archives of general psychiatry AU - Leonard, H L AU - Swedo, S E AU - Rapoport, J L AU - Koby, E V AU - Lenane, M C AU - Cheslow, D L AU - Hamburger, S D AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Md 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1088 EP - 1092 VL - 46 IS - 12 SN - 0003-990X, 0003-990X KW - Placebos KW - 0 KW - Clomipramine KW - NUV44L116D KW - Desipramine KW - TG537D343B KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Child KW - Adolescent KW - Recurrence KW - Male KW - Female KW - Obsessive-Compulsive Disorder -- diagnosis KW - Desipramine -- blood KW - Desipramine -- therapeutic use KW - Desipramine -- adverse effects KW - Obsessive-Compulsive Disorder -- psychology KW - Obsessive-Compulsive Disorder -- drug therapy KW - Clomipramine -- blood KW - Clomipramine -- adverse effects KW - Clomipramine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79358323?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-03 N1 - Date created - 1990-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. AN - 79356983; 2574001 AB - The debrisoquine-4-hydroxylase polymorphism is a genetic variation in oxidative drug metabolism characterized by two phenotypes, the extensive metabolizer (EM) and poor metabolizer (PM). Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize debrisoquine and numerous other drugs. The defect is caused by several mutant alleles of the CYP2D6 gene, two of which are detected in about 70% of PMs. We have constructed a genomic library from lymphocyte DNA of an EM positively identified by pedigree analysis to be homozygous for the normal CYP2D6 allele. The normal CYP2D6 gene was isolated; was completely sequenced, including 1,531 and 3,522 bp of 5' and 3' flanking DNA, respectively; and was found to contain nine exons within 4,378 bp. Two other genes, designated CYP2D7 and CYP2D8P, were also cloned and sequenced. CYP2D8P contains several gene-disrupting insertions, deletions, and termination codons within its exons, indicating that this is a pseudogene. CYP2D7, which is just downstream of CYP2D8P, is apparently normal, except for the presence, in the first exon, of an insertion that disrupts the reading frame. A hypothesis is presented that the presence of a pseudogene within the CYP2D subfamily transfers detrimental mutations via gene conversions into the CYP2D6 gene, thus accounting for the high frequency of mutations observed in the CYP2D6 gene in humans. JF - American journal of human genetics AU - Kimura, S AU - Umeno, M AU - Skoda, R C AU - Meyer, U A AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 889 EP - 904 VL - 45 IS - 6 SN - 0002-9297, 0002-9297 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Index Medicus KW - Phenotype KW - Base Sequence KW - Humans KW - Restriction Mapping KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Genomic Library KW - Male KW - Female KW - Pseudogenes KW - Polymorphism, Restriction Fragment Length KW - Cytochrome P-450 Enzyme System -- genetics KW - Multigene Family KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79356983?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genomics. 1988 Feb;2(2):174-9 [3410476] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5240-3 [2899325] Pharmacol Rev. 1988 Dec;40(4):243-88 [3072575] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Drug Metab Rev. 1979;9(2):301-17 [158499] Anal Biochem. 1983 Feb 15;129(1):216-23 [6305233] Biochemistry. 1984 Jun 5;23(12):2787-95 [6432035] J Biol Chem. 1985 Jul 25;260(15):9057-67 [4019462] Proc Natl Acad Sci U S A. 1986 Jan;83(1):130-4 [3001719] Prog Clin Biol Res. 1986;214:157-67 [3523506] J Biol Chem. 1986 Sep 5;261(25):11734-43 [3745165] DNA. 1987 Apr;6(2):149-61 [3582092] Am J Hum Genet. 1988 Jan;42(1):4-7 [3276177] Nature. 1988 Feb 4;331(6155):442-6 [3123997] Mol Biol Evol. 1987 Nov;4(6):572-93 [3484338] Mol Cell Biol. 1988 Feb;8(2):802-13 [2832737] DNA. 1989 Jan-Feb;8(1):1-13 [2651058] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Tyrosine kinase oncogenes abrogate interleukin-3 dependence of murine myeloid cells through signaling pathways involving c-myc: conditional regulation of c-myc transcription by temperature-sensitive v-abl. AN - 79342912; 2555703 AB - Retroviral expression vectors carrying the tyrosine kinase oncogenes abl, fms, src, and trk abrogate the requirements of murine myeloid FDC-P1 cells for interleukin-3 (IL-3). Factor-independent clones constitutively express c-myc in the absence of IL-3, whereas in parental cultures c-myc transcription requires the presence of the ligand. To directly test the effect of a tyrosine kinase oncogene on c-myc expression, retroviral constructs containing three different temperature-sensitive mutants of v-abl were introduced into myeloid IL-3-dependent FDC-P1 and 32D cells. At the permissive temperature, clones expressing temperature-sensitive abl behaved like wild-type abl-containing cells in their growth properties and expressed c-myc constitutively. Temperature shift experiments demonstrated that both IL-3 abrogation and the regulation of c-myc expression correlated with the presence of functional v-abl. Induction of c-myc expression by reactivation of temperature-sensitive v-abl mimicked c-myc induction by IL-3 in that it did not require protein synthesis and occurred at the level of transcription, with effects on both initiation and a transcription elongation block. However, v-abl-regulated FDC-P1 cell growth differed from IL-3-regulated growth in that c-fos and junB, which are normally induced by IL-3, were not induced by activation of v-abl. JF - Molecular and cellular biology AU - Cleveland, J L AU - Dean, M AU - Rosenberg, N AU - Wang, J Y AU - Rapp, U R AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 5685 EP - 5695 VL - 9 IS - 12 SN - 0270-7306, 0270-7306 KW - Interleukin-3 KW - 0 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Clone Cells KW - Animals KW - Promoter Regions, Genetic KW - Temperature KW - Moloney murine leukemia virus -- genetics KW - Cell Line KW - Gene Expression Regulation, Neoplastic KW - Protein-Tyrosine Kinases -- genetics KW - Leukemia Virus, Murine -- genetics KW - Oncogenes -- drug effects KW - Interleukin-3 -- pharmacology KW - Signal Transduction -- drug effects KW - Transcription, Genetic KW - Protein-Tyrosine Kinases -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Proto-Oncogenes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79342912?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1983 May;127(1):134-48 [6305011] J Immunol. 1983 Jul;131(1):282-7 [6190911] Nature. 1983 Aug 18-24;304(5927):596-602 [6308472] Cell. 1983 Dec;35(3 Pt 2):603-10 [6606489] Cell. 1984 Feb;36(2):241-7 [6692471] Biochem J. 1984 Aug 15;222(1):195-201 [6089758] Nature. 1984 Oct 4-10;311(5985):433-8 [6090941] Cell. 1985 Jul;41(3):677-83 [2988782] Cell. 1985 Jul;41(3):685-93 [2988783] Virology. 1985 Oct 15;146(1):78-89 [2994296] Recent Results Cancer Res. 1985;99:221-36 [4070776] J Cell Sci Suppl. 1985;3:187-98 [3011822] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1345-9 [2434953] Mol Cell Biol. 1986 Nov;6(11):4133-5 [3025637] Mol Cell Biol. 1986 Oct;6(10):3545-9 [3540594] Nucleic Acids Res. 1986 Nov 11;14(21):8331-46 [3537956] EMBO J. 1986 Nov;5(11):2859-65 [3024965] J Virol. 1983 Mar;45(3):1195-9 [6300457] J Exp Med. 1980 Oct 1;152(4):1036-47 [6968334] Oncogene. 1989 Sep;4(9):1129-35 [2674855] Proc Natl Acad Sci U S A. 1978 May;75(5):2488-92 [209468] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Oncogene. 1989 Apr;4(4):451-5 [2566144] J Immunol. 1987 May 15;138(10):3495-504 [3106484] J Immunol. 1987 Jun 1;138(11):3829-35 [2438328] J Immunol. 1987 Jul 1;139(1):123-9 [3495596] Mol Cell Biol. 1987 May;7(5):1673-80 [3037331] Cell. 1987 Sep 25;50(7):1021-9 [2441878] Proc Natl Acad Sci U S A. 1987 Nov;84(22):8021-5 [2825174] Oncogene. 1987 Mar;1(1):29-35 [2449644] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487-91 [3422745] Oncogene Res. 1987 Aug;1(3):279-96 [2453016] Oncogene Res. 1988 Feb;2(3):277-84 [3259302] Proc Natl Acad Sci U S A. 1988 May;85(10):3522-6 [3368463] Nature. 1988 Aug 11;334(6182):494-8 [2900470] Proc Natl Acad Sci U S A. 1988 Nov;85(21):7982-6 [2460860] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 [3057494] J Biol Chem. 1988 Dec 15;263(35):19203-9 [2461935] Proc Natl Acad Sci U S A. 1989 Jan;86(2):505-9 [2463629] Oncogene Res. 1988;3(4):357-75 [2976141] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Attenuation and cell culture adaptation of hepatitis A virus (HAV): a genetic analysis with HAV cDNA. AN - 79340308; 2555561 AB - RNA transcripts of hepatitis A virus (HAV) HM-175 cDNA from attenuated, cell culture-adapted HAV were infectious in cell culture. A full-length HAV cDNA from wild-type HAV (propagated in marmosets in vivo) was constructed. Chimeric cDNAs that contained portions of both wild-type and attenuated genomes were produced. Oligonucleotide-directed mutagenesis was used to engineer a point mutation into the VP1 gene of attenuated HAV cDNA, so that the sequence of this capsid protein would be identical to that of the wild-type virus. Transfection of monkey kidney cells with RNA transcripts from several of the chimeric cDNAs and from the mutagenized cDNA induced production of HAV. Comparison of the growth of attenuated, wild-type, chimeric, and mutant viruses in vitro indicated that the P2-P3 (nonstructural protein) region is important for cell culture adaptation of the virus; the 5' noncoding region may also contribute to adaptation, but to a lesser extent. Inoculation of marmosets with transfection-derived virus also suggested that the P2-P3 region plays an important role in attenuation of HAV HM-175. JF - Journal of virology AU - Cohen, J I AU - Rosenblum, B AU - Feinstone, S M AU - Ticehurst, J AU - Purcell, R H AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 5364 EP - 5370 VL - 63 IS - 12 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Viral Structural Proteins KW - Index Medicus KW - Animals KW - Chimera KW - Callitrichinae KW - Transfection KW - Capsid -- genetics KW - Restriction Mapping KW - Plasmids KW - Viral Structural Proteins -- genetics KW - Mutation KW - Cell Line KW - Cloning, Molecular KW - Hepatovirus -- physiology KW - Genes, Viral KW - DNA, Viral -- genetics KW - Hepatovirus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79340308?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-27 N1 - Date created - 1989-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 1977 Nov;18(2):524-30 [200565] Virology. 1988 Apr;163(2):299-307 [2833008] Science. 1981 Nov 20;214(4523):916-9 [6272391] Proc Natl Acad Sci U S A. 1982 Oct;79(19):5793-7 [6310545] Proc Natl Acad Sci U S A. 1983 Oct;80(19):5885-9 [6310601] Dev Biol Stand. 1983;54:429-32 [6317493] Proc Natl Acad Sci U S A. 1984 Mar;81(5):1539-43 [6324200] J Med Virol. 1984;14(4):373-86 [6096505] Nature. 1985 Apr 11-17;314(6011):548-50 [2986004] J Virol. 1986 May;58(2):348-58 [3009852] J Gen Virol. 1986 Aug;67 ( Pt 8):1741-4 [3016162] J Virol. 1986 Oct;60(1):124-30 [3018280] J Med Virol. 1986 Oct;20(2):165-75 [3021899] J Virol. 1987 Jan;61(1):50-9 [3023706] Proc Natl Acad Sci U S A. 1987 Apr;84(8):2497-501 [3031686] J Virol. 1987 Oct;61(10):3035-9 [3041024] J Virol Methods. 1987 Aug;17(1-2):183-9 [2822753] J Clin Microbiol. 1987 Oct;25(10):1822-9 [2822759] J Infect Dis. 1988 Feb;157(2):338-45 [2826614] Infect Immun. 1981 Apr;32(1):388-93 [6260685] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - trans activation of human immunodeficiency virus type 1 is sequence specific for both the single-stranded bulge and loop of the trans-acting-responsive hairpin: a quantitative analysis. AN - 79339173; 2479775 AB - We have used site-directed mutagenesis to delineate sequence specific domains within the human immunodeficiency virus type 1 (HIV-1) trans-acting-responsive (TAR) RNA element that are required for trans activation by the viral Tat protein. Our data in part corroborate a recent report [S. Feng and E. C. Holland, Nature (London) 334:165-167, 1988] that five nucleotides within the loop (+29 to +33) of the TAR hairpin are important for trans activation. We, however, found no absolute requirement for the CUGGG loop sequence. Mutants with substitutions within the loop retained between 9 and 50% activity compared with the wild type. A second sequence, important for trans activation, was found in the 3-base bulge loop (+22 to +24) of the TAR hairpin. Cross-trans-activation studies of mutant HIV-1 TAR elements with the HIV-2 Tat protein suggest that a similar recognition event(s) forms the basis for trans activation of HIV-1 and HIV-2. JF - Journal of virology AU - Berkhout, B AU - Jeang, K T AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 5501 EP - 5504 VL - 63 IS - 12 SN - 0022-538X, 0022-538X KW - RNA KW - 63231-63-0 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Mutation KW - HIV-1 -- genetics KW - Enhancer Elements, Genetic -- genetics KW - HIV-1 -- growth & development KW - Virus Activation KW - Transcriptional Activation KW - RNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79339173?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-27 N1 - Date created - 1989-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1987 Feb 27;48(4):691-701 [3643816] Nature. 1987 Apr 16-22;326(6114):662-9 [3031510] Cell. 1986 Mar 28;44(6):941-7 [2420471] Nature. 1986 Mar 27-Apr 2;320(6060):367-71 [3007995] Biochemistry. 1987 Mar 24;26(6):1563-8 [3297131] Nature. 1987 Aug 6-12;328(6130):548-50 [3039372] Genes Dev. 1989 Apr;3(4):547-58 [2470647] Nature. 1988 Jul 14;334(6178):165-7 [3386755] Mol Cell Biol. 1988 Jun;8(6):2555-61 [2841583] J Virol. 1988 Dec;62(12):4523-32 [2846868] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9753-7 [2849115] J Virol. 1989 Mar;63(3):1181-7 [2536828] EMBO J. 1989 Mar;8(3):765-78 [2721501] EMBO J. 1987 Dec 1;6(12):3755-60 [2828036] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Phosphorylation sites of the E2 transcriptional regulatory proteins of bovine papillomavirus type 1. AN - 79338026; 2555544 AB - The E2 open reading frame of bovine papillomavirus type 1 (BPV-1) encodes three transcriptional regulatory proteins. The full-length open reading frame encodes a protein of 410 amino acids which functions as a transcriptional transactivator. Two transcriptional repressor proteins, E2-TR and E8/E2, contain the C-terminal 249 and 204 amino acids, respectively. We have expressed both the full-length E2 protein and the E2-TR repressor protein in insect cells, by using recombinant baculoviruses, and in mammalian COS-1 cells, by using a chimeric simian virus 40/BPV-1 virus. Analysis of the E2 proteins revealed that both the transactivator and repressor forms are phosphorylated predominately on serine residues at similar sites in both expression systems. By a combination of peptide mapping and site-directed mutagenesis techniques, the serine residues at positions 298 and 301 were determined to be the major phosphorylation sites of the BPV-1 E2 proteins. JF - Journal of virology AU - McBride, A A AU - Bolen, J B AU - Howley, P M AD - Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 5076 EP - 5085 VL - 63 IS - 12 SN - 0022-538X, 0022-538X KW - Amino Acids KW - 0 KW - DNA, Viral KW - Repressor Proteins KW - Trans-Activators KW - Transcription Factors KW - Viral Structural Proteins KW - Index Medicus KW - Animals KW - Peptide Mapping KW - Insect Viruses -- genetics KW - Amino Acids -- analysis KW - Gene Expression KW - Amino Acid Sequence KW - Plasmids KW - Base Sequence KW - Phosphorylation KW - Genetic Vectors KW - Molecular Sequence Data KW - Genes, Viral KW - Viral Structural Proteins -- genetics KW - DNA, Viral -- genetics KW - Mutation KW - Cell Line KW - Bovine papillomavirus 1 -- metabolism KW - Trans-Activators -- metabolism KW - Transcription Factors -- metabolism KW - Trans-Activators -- genetics KW - Repressor Proteins -- metabolism KW - Papillomaviridae -- genetics KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics KW - Bovine papillomavirus 1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79338026?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-27 N1 - Date created - 1989-12-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1975 May 25;250(10):4007-21 [236308] EMBO J. 1988 Dec 1;7(12):3807-16 [2850174] Virology. 1982 May;119(1):22-34 [6280384] Mol Cell Biol. 1983 Dec;3(12):2156-65 [6318086] J Biol Chem. 1984 Oct 10;259(19):11686-94 [6434530] Cell. 1985 Aug;42(1):183-91 [2990724] Cell. 1985 Dec;43(2 Pt 1):393-404 [2416464] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8404-8 [3878519] Mol Cell Biol. 1985 Oct;5(10):2860-5 [3915537] Science. 1986 Oct 17;234(4774):364-8 [2876518] Nature. 1987 Jan 1-7;325(6099):70-3 [3025749] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1215-8 [3029771] EMBO J. 1987 Jan;6(1):145-52 [3034572] J Virol. 1987 Jul;61(7):2128-37 [3035214] Cell. 1987 Jul 3;50(1):69-78 [3036366] J Biol Chem. 1987 Jul 5;262(19):9136-40 [3474230] J Biol Chem. 1987 Oct 15;262(29):14042-8 [2820993] EMBO J. 1988 Feb;7(2):533-9 [2835232] J Virol. 1988 Jun;62(6):1925-31 [2835497] Oncogene Res. 1987 Sep-Oct;1(4):357-74 [2835736] Oncogene Res. 1988 May;2(4):385-401 [3041347] J Virol. 1988 Sep;62(9):3242-9 [2841476] Nature. 1988 Aug 11;334(6182):494-8 [2900470] Cell. 1988 Sep 9;54(6):855-64 [3044613] Proc Natl Acad Sci U S A. 1988 Aug;85(16):5864-8 [2842752] Biochim Biophys Acta. 1988 Sep 16;971(2):227-31 [2901861] FEBS Lett. 1988 Sep 12;237(1-2):225-8 [3169237] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7206-10 [2845402] EMBO J. 1988 Sep;7(9):2815-22 [2846284] EMBO J. 1988 Sep;7(9):2823-9 [2846285] Proc Natl Acad Sci U S A. 1989 Jan;86(2):510-4 [2536165] Cell. 1989 Feb 10;56(3):409-19 [2644045] Virology. 1989 Mar;169(1):236-8 [2538035] EMBO J. 1988 Dec 20;7(13):4245-53 [2854060] EMBO J. 1989 Jan;8(1):127-32 [2540954] J Virol. 1989 Jul;63(7):3151-4 [2542621] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4352-6 [2525256] Cell. 1989 Jun 16;57(6):891-3 [2544293] Nature. 1989 Jun 29;339(6227):679-84 [2662013] EMBO J. 1989 Apr;8(4):1111-9 [2663470] Genes Dev. 1989 May;3(5):620-7 [2545525] J Virol. 1989 Apr;63(4):1743-55 [2538655] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9007-11 [2848252] Proc Natl Acad Sci U S A. 1981 May;78(5):2727-31 [6265905] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. AN - 79337982; 2685181 AB - We performed an escalating dose study of the combined administration of interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) in 94 patients with metastatic cancer. Patients received alpha-IFN at a dose of 3 x 10(6) U/m2 in conjunction with IL-2 at doses of either 1 x 10(6) U/m2 (six patients), 3 x 10(6) U/m2 (32 patients), or 4.5 x 10(6) U/m2 (26 patients). Thirty patients received alpha-IFN at 6 x 10(6) U/m2 plus IL-2 at 4.5 x 10(6) U/m2. Patients each received cytokine as an intravenous bolus infusion every 8 hours for up to 5 consecutive days and after a 10-day rest received a second cycle of combination cytokines. Of the 91 patients evaluable for response, seven patients had a complete regression of cancer, and 18 had a partial regression. At the four increasing dose levels used in patients with renal cell cancer (35 patients) or melanoma (39 patients), objective responses were seen in 17% (of six patients), 24% (of 25 patients), 38% (of 16 patients), and 41% (of 27 patients), respectively. Of the 25 total responding patients, 16 are still responding 5 to 14 months after treatment. The toxicities associated with the combined administration of IL-2 and alpha-IFN were similar to those expected from each agent alone. There was one treatment-related death in the 94 patients treated in this study. Thus, using increasing doses of the combination of IL-2 and alpha-IFN, it appears that response rates may be related to the doses of the cytokines used, and that at the highest doses of these combination cytokines, response rates may be higher than those for either cytokine alone. A prospective randomized trial comparing the cytokine combinations with each cytokine administered alone is necessary as is the extension of this combination cytokine treatment to patients with other types of solid cancer. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Rosenberg, S A AU - Lotze, M T AU - Yang, J C AU - Linehan, W M AU - Seipp, C AU - Calabro, S AU - Karp, S E AU - Sherry, R M AU - Steinberg, S AU - White, D E AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1863 EP - 1874 VL - 7 IS - 12 SN - 0732-183X, 0732-183X KW - Interferon Type I KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - Index Medicus KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Clinical Trials as Topic KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Immunotherapy -- methods KW - Neoplasms -- drug therapy KW - Interferon Type I -- adverse effects KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interferon Type I -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79337982?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-10 N1 - Date created - 1990-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients. AN - 79337951; 2585024 AB - Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Fisher, B AU - Keenan, A M AU - Garra, B S AU - Steinberg, S M AU - White, D E AU - DiBisceglie, A M AU - Hoofnagle, J H AU - Yolles, P AU - Rosenberg, S A AU - Lotze, M T AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1852 EP - 1862 VL - 7 IS - 12 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Glycocholic Acid KW - G59NX3I3RT KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Regression Analysis KW - Neoplasms -- drug therapy KW - Glycocholic Acid -- blood KW - Prospective Studies KW - Humans KW - Retrospective Studies KW - Liver Diseases -- diagnostic imaging KW - Bilirubin -- blood KW - Liver Function Tests KW - Radionuclide Imaging KW - Cholestasis -- chemically induced KW - Interleukin-2 -- adverse effects KW - Chemical and Drug Induced Liver Injury UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79337951?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-10 N1 - Date created - 1990-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Dermatologic complications associated with administration of 2',3'-dideoxycytidine in patients with human immunodeficiency virus infection. AN - 79336836; 2555402 AB - We describe a distinctive mucocutaneous eruption that occurred in 14 of 20 (70%) patients with human immunodeficiency virus infection while they were being treated with a new therapeutic agent, 2'3'-dideoxycytidine. A maculopapular eruption developed in these patients on day 10 or 11 of treatment. Seven of 14 patients, especially those receiving higher-dose therapy, also had systemic symptoms. In addition, oral ulcers developed in 9 of 14 patients on days 4 to 6 of therapy. The occurrence of the cutaneous and oral lesions correlated with dose, route, and schedule of administration of 2'3'-dideoxycytidine. In most instances the mucocutaneous lesions resolved even with continuation of therapy. JF - Journal of the American Academy of Dermatology AU - McNeely, M C AU - Yarchoan, R AU - Broder, S AU - Lawley, T J AD - Dermatology Branch, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 1213 EP - 1217 VL - 21 IS - 6 SN - 0190-9622, 0190-9622 KW - HIV Antigens KW - 0 KW - Zalcitabine KW - 6L3XT8CB3I KW - 2',3'-dideoxycytidinene KW - CI9X00489L KW - Index Medicus KW - AIDS/HIV KW - Drug Evaluation KW - HIV Antigens -- analysis KW - Drug Administration Schedule KW - Humans KW - Adult KW - Middle Aged KW - Ulcer -- etiology KW - T-Lymphocytes, Helper-Inducer -- metabolism KW - Male KW - Drug Eruptions -- etiology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Drug Eruptions -- pathology KW - Zalcitabine -- analogs & derivatives KW - Zalcitabine -- adverse effects KW - Mouth Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79336836?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Selective immunosuppression of activated T cells with the chimeric toxin IL-2-PE40. Inhibition of experimental autoimmune uveoretinitis. AN - 79336615; 2511243 AB - A characteristic of activated T lymphocytes is the expression of high affinity IL-2R. We studied a new method of selective immunosuppression directed against activated T cells by using a chimeric recombinant protein (IL-2-PE40) composed of IL-2 fused to a modified Pseudomonas exotoxin lacking its cell recognition domain. As a model of T cell-mediated disease, we used experimental autoimmune uveoretinitis (EAU) produced in Lewis rats by active immunization with the retinal S-Ag. The treatment protocol consisted of i.p. injection of IL-2-PE40 at 0.25 micrograms/g every 12 h. Controls were PBS, PE40, or IL-2-PE40asp553 a mutant form of the molecule with reduced activity. Treatment with IL-2-PE40 resulted in a significant reduction of the incidence and severity of EAU over controls. The analysis of the effect of i.p. injection of IL-2-PE40 on the popliteal draining lymph nodes of immunized animals showed a marked reduction in the lymphocytes content. Transfer experiments demonstrated that IL-2-PE40 prevented the development of EAU effector T cells. Interestingly, although activated B cells were reported to express IL-2R, there was no significant reduction of antibody production against the immunizing Ag under IL-2-PE40 treatment, suggesting sparing of the B cells. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Roberge, F G AU - Lorberboum-Galski, H AU - Le Hoang, P AU - de Smet, M AU - Chan, C C AU - Fitzgerald, D AU - Pastan, I AD - Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892. Y1 - 1989/12/01/ PY - 1989 DA - 1989 Dec 01 SP - 3498 EP - 3502 VL - 143 IS - 11 SN - 0022-1767, 0022-1767 KW - Autoantibodies KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunosuppressive Agents KW - Immunotoxins KW - Interleukin-2 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred Lew KW - Pseudomonas aeruginosa -- immunology KW - Chimera KW - Humans KW - Lymphocyte Depletion KW - Recombinant Fusion Proteins -- pharmacology KW - Autoantibodies -- biosynthesis KW - Male KW - Cell Line KW - Lymphocyte Activation -- drug effects KW - Interleukin-2 -- pharmacology KW - Exotoxins -- pharmacology KW - Retinitis -- etiology KW - Retinitis -- immunology KW - Autoimmune Diseases -- etiology KW - Immunotoxins -- pharmacology KW - Immunosuppressive Agents -- pharmacology KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79336615?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-05 N1 - Date created - 1990-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Changes in estrogen receptor, DNA ploidy, and estrogen metabolism in rat hepatocytes during a two-stage model for hepatocarcinogenesis using 17 alpha-ethinylestradiol as the promoting agent. AN - 79332761; 2573415 AB - 17 alpha-Ethylestradiol (EE2) was administered chronically to diethylnitrosamine (DEN)-initiated (200/mg/kg, i.p.) adult ovariectomized Sprague-Dawley rats, by means of Silastic implants at an estimated dose of 90 micrograms/kg/day. Isolated hepatocytes from DEN/EE2-treated animals exhibited a 2- to 3-fold increase in nuclear estrogen receptor (ER) levels throughout the promotion period. Furthermore, approximately 30-40% of the receptor was occupied when quantified by an exchange assay. For all groups the ER had a sedimentation coefficient of approximately 8S for unoccupied ER and a binding affinity for 17 beta-estradiol of 0.25 nM. An ER of lower affinity for estradiol was present in animals initiated with DEN and/or promoted with EE2. The increase in hepatocyte ER was associated with a 5.2-fold increase in gamma-glutamyl transpeptidase and 2.5-fold decrease in glucose-6-phosphatase activity at 20 weeks. EE2 treatment caused a 50% increase in the maximal binding capacity (Bmax) of hepatic epidermal growth factor receptors, but the equilibrium binding constant (Kd) did not change. Modulation of mitotic activity of hepatocyte subpopulations by EE2 treatment was indicated by an increase in the proportion of diploid hepatocytes and an increase in the number of hepatocytes undergoing DNA synthesis. In general, effects on ER, epidermal growth factor receptor, gamma-glutamyl transpeptidase and glucose-6-phosphatase were greater in DEN/EE2-treated animals than in rats receiving only EE2. Modification of receptor pathways associated with hepatocyte growth control, ER and epidermal growth factor receptor, may be contributing factors in the clonal expansion of preneoplastic cells during EE2 promotion of hepatocarcinogenesis. JF - Cancer research AU - Vickers, A E AU - Nelson, K AU - McCoy, Z AU - Lucier, G W AD - Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/12/01/ PY - 1989 DA - 1989 Dec 01 SP - 6512 EP - 6520 VL - 49 IS - 23 SN - 0008-5472, 0008-5472 KW - Biomarkers, Tumor KW - 0 KW - Carcinogens KW - DNA, Neoplasm KW - Estrogens KW - Receptors, Estrogen KW - Ethinyl Estradiol KW - 423D2T571U KW - Epidermal Growth Factor KW - 62229-50-9 KW - gamma-Glutamyltransferase KW - EC 2.3.2.2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Biomarkers, Tumor -- metabolism KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - gamma-Glutamyltransferase -- metabolism KW - Ovariectomy KW - Epidermal Growth Factor -- metabolism KW - DNA, Neoplasm -- metabolism KW - Female KW - Ethinyl Estradiol -- pharmacology KW - Cell Division KW - Liver Neoplasms, Experimental -- genetics KW - Liver Neoplasms -- metabolism KW - Estrogens -- metabolism KW - Liver Neoplasms, Experimental -- metabolism KW - Liver Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- chemically induced KW - Receptors, Estrogen -- metabolism KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79332761?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-27 N1 - Date created - 1989-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Environmental cancer risks--real and unreal. AN - 79331431; 2583068 JF - Environmental research AU - Lijinsky, W AD - BRI Basic Research Program, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 207 EP - 209 VL - 50 IS - 2 SN - 0013-9351, 0013-9351 KW - Carcinogens, Environmental KW - 0 KW - Pesticides KW - Index Medicus KW - Risk Factors KW - Humans KW - Pesticides -- adverse effects KW - Carcinogens, Environmental -- adverse effects KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79331431?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-10 N1 - Date created - 1990-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Relationships among benzo(a)pyrene metabolism, benzo(a)pyrene-diol-epoxide:DNA adduct formation, and sister chromatid exchanges in human lymphocytes from smokers and nonsmokers. AN - 79330428; 2510927 AB - In the present study, benzo(a)pyrene (BP) metabolism, DNA adduct formation, ethoxyresorufin-O-deethylase activity, and sister chromatid exchange induction by BP were compared in human lymphocytes prepared from whole blood of smokers and nonsmokers following an in vitro incubation with BP. There was an approximate 7- to 10-fold variation in all parameters measured. To determine the source of this variation, participants were resampled, the assays were repeated, and all the data were analyzed to assess (a) smoking-related effects, (b) differences in multiple samples from the same individual, and (c) intraindividual, experimental, and interindividual variation. No smoking-related effects were observed except for baseline sister chromatid exchange frequency. The variation observed for BP-related DNA adducts and ethoxyresorufin-O-deethylase activity was primarily due to interindividual variation. For example, in vitro formation of DNA adducts did not change when samples were obtained at different times from the same individual and were not influenced significantly by culture conditions. No significant correlation existed between DNA adduct formation and BP metabolism [correlation coefficient (r) = 0.27] for either the total population or when segregated based on smoking status. Furthermore, no correlation was seen between DNA adducts and sister chromatid exchange induction by BP. Our studies have compared a number of commonly used lymphocyte markers and conclude that it is difficult to predict changes in one marker based on changes in another. However, in vitro formation, of PB-derived DNA adducts is consistent over time for individuals. JF - Cancer research AU - Thompson, C L AU - McCoy, Z AU - Lambert, J M AU - Andries, M J AU - Lucier, G W AD - National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, North Carolina 27709. Y1 - 1989/12/01/ PY - 1989 DA - 1989 Dec 01 SP - 6503 EP - 6511 VL - 49 IS - 23 SN - 0008-5472, 0008-5472 KW - Dihydroxydihydrobenzopyrenes KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Oxidoreductases -- metabolism KW - Cells, Cultured KW - Humans KW - Adult KW - Cytochrome P-450 Enzyme System -- metabolism KW - Male KW - Female KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - Sister Chromatid Exchange KW - DNA Damage KW - Smoking -- metabolism KW - Lymphocytes -- metabolism KW - Dihydroxydihydrobenzopyrenes -- metabolism KW - Benzo(a)pyrene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79330428?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-27 N1 - Date created - 1989-12-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Developmental pattern of estrogen receptor expression in female mouse genital tracts. AN - 79330313; 2583044 AB - The distribution of the estrogen receptor (ER) was investigated in neonatal female genital tracts (uterus, oviduct, cervix, and vagina) from days 1-22 after birth, using immunohistochemistry employing an anti-ER monoclonal antibody. In uteri, the ER in epithelial cells began to be observed by day 4. The number of positive epithelial cells and the staining intensity gradually increased until day 22 of age. On the other hand, uterine stroma cells gave a strong ER immunostaining even on day 1. The staining intensity reached a maximum by days 4-7 and then slightly decreased with age. In the oviduct, cervix, and vagina, epithelial cells showed positive ER immunostaining on day 1, and the intensity increased gradually until day 22. ER immunostaining in stroma cells was almost constant during the development period. The ER in both epithelial and stroma cells from these younger animals showed similar biochemical properties, i.e. an increased affinity for nuclei and resistance to extraction with PBS. Thus, during neonatal development of the female reproductive tract, ER is present not only in stroma cells but also in epithelial cells. This ER protein exhibits properties and characteristics similar to those of adult mice. The presence of ER suggests that some of the estrogen actions of cell proliferation, differentiation, and tissue abnormalities resulting from prenatal and postnatal estrogen administration may be mediated by receptor interactions. JF - Endocrinology AU - Yamashita, S AU - Newbold, R R AU - McLachlan, J A AU - Korach, K S AD - Receptor Biology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/12// PY - 1989 DA - December 1989 SP - 2888 EP - 2896 VL - 125 IS - 6 SN - 0013-7227, 0013-7227 KW - Receptors, Estrogen KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Abridged Index Medicus KW - Index Medicus KW - Uterus -- growth & development KW - Aging -- metabolism KW - Animals KW - Cell Nucleus -- metabolism KW - Cervix Uteri -- metabolism KW - Vagina -- growth & development KW - Mice KW - Tissue Distribution KW - Cervix Uteri -- growth & development KW - Endometrium -- metabolism KW - Uterus -- metabolism KW - Fallopian Tubes -- metabolism KW - Diethylstilbestrol -- pharmacology KW - Endometrium -- growth & development KW - Fallopian Tubes -- growth & development KW - Immunohistochemistry KW - Vagina -- metabolism KW - Female KW - Genitalia, Female -- drug effects KW - Genitalia, Female -- metabolism KW - Receptors, Estrogen -- analysis KW - Receptors, Estrogen -- metabolism KW - Animals, Newborn -- metabolism KW - Genitalia, Female -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79330313?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-09 N1 - Date created - 1990-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Duration of desensitization and ultrastructural changes in dorsal root ganglia in rats treated with resiniferatoxin, an ultrapotent capsaicin analog. AN - 79432629; 2611660 AB - We have previously demonstrated resiniferatoxin (RTX) to be an ultrapotent analog of capsaicin. Like capsaicin, RTX initially induces neurogenic inflammation, pain, and hypothermia and then causes desensitization of these responses. We examine here the duration of desensitization following acute treatment with the maximal tolerated dose of RTX. Desensitization to neurogenic inflammation began to diminish by 7 days, whereas desensitization to pain and to induction of hypothermia persisted for several weeks. Interestingly, a partial hypothermic response returned within 24 h if challenge was with RTX at 500-fold its ED50 for control animals; the animals, moreover, maintained their ability to thermoregulate in a hot environment. The time course of the morphological changes--ultrastructure and calcium staining--of dorsal root ganglion neurons was examined in parallel. The ultrastructural changes were evident by 4 h and persisted for the duration of the experiments. Limited calcium staining was visible at 12 and 24 h after treatment but then diminished. In comparison with capsaicin treatment, RTX caused more long-lasting desensitization as well as a distinct spectrum of response. JF - Brain research AU - Szallasi, A AU - Joo, F AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute Bethesda, MD 20892. Y1 - 1989/11/27/ PY - 1989 DA - 1989 Nov 27 SP - 68 EP - 72 VL - 503 IS - 1 SN - 0006-8993, 0006-8993 KW - Diterpenes KW - 0 KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats KW - Drug Tolerance KW - Animals KW - Mitochondria -- ultrastructure KW - Dose-Response Relationship, Drug KW - Mitochondria -- drug effects KW - Hypothermia -- chemically induced KW - Diterpenes -- pharmacology KW - Body Temperature Regulation -- drug effects KW - Diterpenes -- toxicity KW - Ganglia, Spinal -- ultrastructure KW - Ganglia, Spinal -- physiology KW - Neurons, Afferent -- ultrastructure KW - Capsaicin -- analogs & derivatives KW - Neurons, Afferent -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79432629?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-14 N1 - Date created - 1990-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Suppression of carrageenan-induced hyperalgesia, hyperthermia and edema by a bradykinin antagonist. AN - 79464764; 2482813 AB - Although bradykinin (BK) antagonists have antinociceptive effects, they have not been evaluated for anti-inflammatory activity. When administered with carrageenan into the rat hindpaw, NPC567 significantly blocked carrageenan-induced hyperalgesia, hyperthermia and edema. In addition, NPC567 did not alter the in vitro release of immunoreactive BK by plasma kallikrein. These results indicate that the antinociceptive activity of NPC567, a BK antagonist, may be related to its overall anti-inflammatory activity and that is mechanism of action does not include inhibition of plasma kallikrein. JF - European journal of pharmacology AU - Costello, A H AU - Hargreaves, K M AD - Neurobiology and Anesthesiology Branch, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/11/21/ PY - 1989 DA - 1989 Nov 21 SP - 259 EP - 263 VL - 171 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Analgesics KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Carrageenan KW - 9000-07-1 KW - Aprotinin KW - 9087-70-1 KW - NPC 567 KW - DV64B0PLEH KW - Kallikreins KW - EC 3.4.21.- KW - Bradykinin KW - S8TIM42R2W KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Kallikreins -- antagonists & inhibitors KW - Aprotinin -- pharmacology KW - Male KW - Fever -- chemically induced KW - Edema -- chemically induced KW - Pain -- prevention & control KW - Edema -- prevention & control KW - Bradykinin -- antagonists & inhibitors KW - Bradykinin -- analogs & derivatives KW - Pain -- chemically induced KW - Fever -- prevention & control KW - Analgesics -- pharmacology KW - Bradykinin -- pharmacology KW - Bradykinin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79464764?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-19 N1 - Date created - 1990-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Activation of the second promoter of the transforming growth factor-beta 1 gene by transforming growth factor-beta 1 and phorbol ester occurs through the same target sequences. AN - 79297070; 2808430 AB - Two distinct regions of the transforming growth factor-beta 1 (TGF-beta 1) promoter are responsive to autoregulation and activation by phorbol ester (12-O-tetradecanoylphorbol-13-acetate): sequences located between nucleotides -454 to -323 (first promoter) and between the two transcriptional start sites. We have now characterized in detail the induction of the second promoter (sequences between nucleotides + 1 to +271) of the TGF-beta 1 gene by both TGF-beta 1 and phorbol ester. By assaying progressively deleted mutations in the second promoter, we have found two regions responsible for the induction; each contains a phorbol ester-responsive element. In vitro transcription of the second promoter-chloramphenicol acetyltransferase chimeric genes using nuclear extracts of A-549 cells showed that deletion of the putative phorbol ester-responsive elements results in a 70-80% decrease in activity. DNase I footprinting and gel mobility shift assays showed that binding to an Sp1 site and the putative TRE elements are required for maximal expression of the second promoter region of the TGF-beta 1 gene. These results suggest that AP-1, which is capable of conferring phorbol ester or TGF-beta 1 responsiveness, is the major transcription factor involved in the second promoter-derived transcription of the TGF-beta 1 gene. JF - The Journal of biological chemistry AU - Kim, S J AU - Denhez, F AU - Kim, K Y AU - Holt, J T AU - Sporn, M B AU - Roberts, A B AD - Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/11/15/ PY - 1989 DA - 1989 Nov 15 SP - 19373 EP - 19378 VL - 264 IS - 32 SN - 0021-9258, 0021-9258 KW - Transforming Growth Factors KW - 76057-06-2 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Fibrosarcoma KW - Humans KW - Transcription, Genetic KW - Mice KW - Homeostasis KW - Plasmids KW - Base Sequence KW - Transfection KW - Cells, Cultured KW - Lung Neoplasms KW - Molecular Sequence Data KW - Mutation KW - Cell Line KW - Promoter Regions, Genetic -- drug effects KW - Genes -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Transforming Growth Factors -- pharmacology KW - Transforming Growth Factors -- biosynthesis KW - Transforming Growth Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79297070?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-15 N1 - Date created - 1989-12-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J05114; GENBANK; X02812 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Hepatic lesions in Danish epileptics after long-term exposure to anticonvulsant drugs including phenobarbitone. AN - 79291225; 2509719 JF - Journal of the National Cancer Institute AU - Ward, J M AU - Konishi, N AU - Ostergaard, K AD - Tumor Pathology and Pathogenesis Section, National Cancer Institute, Frederick, MD 21701. Y1 - 1989/11/15/ PY - 1989 DA - 1989 Nov 15 SP - 1753 EP - 1754 VL - 81 IS - 22 SN - 0027-8874, 0027-8874 KW - Anticonvulsants KW - 0 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Phenobarbital -- adverse effects KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Mice KW - Long-Term Care KW - Denmark KW - Male KW - Chemical and Drug Induced Liver Injury -- etiology KW - Anticonvulsants -- adverse effects KW - Epilepsy -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79291225?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-27 N1 - Date created - 1989-11-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: J Natl Cancer Inst. 1989 May 10;81(10):803-8 [2716074] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. AN - 79291176; 2810387 AB - Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL. JF - Journal of the National Cancer Institute AU - Griffith, K D AU - Read, E J AU - Carrasquillo, J A AU - Carter, C S AU - Yang, J C AU - Fisher, B AU - Aebersold, P AU - Packard, B S AU - Yu, M Y AU - Rosenberg, S A AD - Department of Transfusion Medicine, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/11/15/ PY - 1989 DA - 1989 Nov 15 SP - 1709 EP - 1717 VL - 81 IS - 22 SN - 0027-8874, 0027-8874 KW - Indium Radioisotopes KW - 0 KW - Interleukin-2 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Evaluation Studies as Topic KW - Drug Therapy, Combination KW - Infusions, Intravenous KW - Cells, Cultured KW - Immunotherapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Biopsy KW - Male KW - Female KW - Radionuclide Imaging KW - Cyclophosphamide -- administration & dosage KW - Interleukin-2 -- administration & dosage KW - Melanoma -- pathology KW - Melanoma -- diagnostic imaging KW - Lymphocytes -- diagnostic imaging KW - Indium Radioisotopes -- pharmacokinetics KW - Skin Neoplasms -- therapy KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- diagnostic imaging KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79291176?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-27 N1 - Date created - 1989-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modified Box-Cox transform for modulating the dynamic range of flow cytometry data. AN - 85266052; pmid-2582974 AB - We describe an algorithm, Vout = Integer ([2(12)-1/2(12 lambda)-1] V lambda in-1) + 1; lambda greater than 0 based upon Box-Cox transformations as an alternative to nonlinear electronic amplifiers to expand or compress high- or low-amplitude flow cytometer-derived signals. If the indexing parameter lambda less than 1, input channels in the high-amplitude input range are compressed in the output range as occurs when an electronic logarithmic amplifier is used. However, if lambda greater than 1, input channels in the low-amplitude input range are compressed in the output range as occurs when an electronic power amplifier is used. Our modified Box-Cox transform can be implemented either during data collection or off-line for the transformation of previously collected raw data. The transform is the equivalent of an infinite class of nonlinear amplifiers. As the transform is implemented in software, it does not suffer from many of the disadvantages of nonlinear electronic amplifiers. JF - Cytometry AU - Dvorak, J A AU - Banks, S M AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. PY - 1989 SP - 811 EP - 813 VL - 10 IS - 6 SN - 0196-4763, 0196-4763 KW - Software KW - Amplifiers KW - Automatic Data Processing KW - Flow Cytometry KW - Algorithms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85266052?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Primary lymphoma of the liver in a patient with acquired immune deficiency syndrome and chronic hepatitis B. AN - 85219545; pmid-2683745 AB - We describe the case of a homosexual man with asymptomatic infection with human immunodeficiency virus and hepatitis B virus who developed primary hepatic lymphoma. The lymphoma presented with rapid enlargement of the liver, and ultrasound examination revealed multiple hypoechoic lesions within the liver. Histological examination of the liver showed massive replacement by lymphomatous tissue, as well as changes of chronic active hepatitis B. Immunohistochemical stains for hepatitis B surface and core antigens were strongly positive in almost all hepatocytes, but not in tumor tissue. Whereas the occurrence of lymphoma probably is related to HIV infection, possible interactions between hepatitis B virus and HIV infection are discussed. Thus, the presence of mass lesions within the liver in a patient with HIV infection should raise the possibility of hepatic lymphoma even if there is no evidence of generalized lymphadenopathy. JF - The American Journal of Gastroenterology AU - Lisker-Melman, M AU - Pittaluga, S AU - Pluda, J M AU - Kleiner, D E AU - Thompson, P AU - Martin, P AU - Yarchoan, R AU - Di Bisceglie A M AD - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Cancer Institute, Bethesda, Maryland. PY - 1989 SP - 1445 EP - 1448 VL - 84 IS - 11 SN - 0002-9270, 0002-9270 KW - Human KW - Acquired Immunodeficiency Syndrome KW - Antigens, Viral KW - Hepatitis B Virus KW - Ultrasonography KW - HIV-1 KW - Liver Neoplasms KW - Antibodies, Viral KW - Adult KW - Hepatitis B KW - Case Report KW - Chronic Disease KW - Lymphoma KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85219545?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Immunocytochemical localization of neurofilament subunits in the spiral ganglion of normal and neomycin-treated guinea pigs. AN - 85144375; pmid-2606806 AB - Neurofilaments are a major component of the neuronal cytoskeleton and present in all neurons. The expression of subunits of neurofilaments has been shown to be altered by conditions such as development, aging, degeneration and regeneration of the neuron. In the present study, we determined 1) the distribution of neurofilament subunits in spiral ganglion cells of normal guinea pigs and 2) if this distribution is altered by hair cell degeneration. Immunocytochemical analyses were done with monoclonal antibodies to the 200,000 (NF 200), 160,000 (NF 160), and 68,000 (NF 68) daltons neurofilament subunits. In the normal guinea pig, type II spiral ganglion cells were intensely labeled with NF 200, NF 160, NF 68 antibodies, whereas type I cells were significantly labeled only with NF 200 antibody. Neurofilament subunit immunoreactivity was also localized in the auditory nerve and afferent and efferent fibers to the hair cells. To determine the effects of hair cell loss on neurofilament expression in spiral ganglion cells, guinea pigs were treated with neomycin at doses known to cause extensive hair cell damage. Type I and type II spiral ganglion cells responded differently to this treatment. Type II cells remained strongly immunoreactive after treatment although the number of such cells was reduced, especially in the longer surviving animals. NF 160 and NF 68 immunoreactivities increased gradually from base to apex in type I cells after neomycin treatment, while NF 200 immunoreactivity decreased in all turns. JF - Hearing Research AU - Dau, J AU - Wenthold, R J AD - Neurochemistry Section, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892. PY - 1989 SP - 253 EP - 263 VL - 42 IS - 2-3 SN - 0378-5955, 0378-5955 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85144375?accountid=14244 LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Differentiation and oncogenesis: phenotypically distinct lens tumors in transgenic mice. AN - 79577938; 2562221 AB - We report on two lines of transgenic mice that express a murine alpha A-crystallin/SV40 tumor antigen fusion gene in the eye lens. The alpha T1 line develops fast growing, poorly differentiated lens tumors, whereas the alpha T2 line produces lens tumors that are slow growing and well differentiated. There is a striking difference between these two lines in the temporal and spatial patterns of tumor antigen expression during initial lens development. In the alpha T1 line, the transgene is expressed very early in development in most lens cells, and no primary fiber differentiation takes place. In the alpha T2 line, transgene expression occurs after primary fiber formation has been initiated, and is restricted to differentiating fiber cells. The anterior epithelium from both alpha T lines undergoes normal development and remains morphologically normal until after birth, although in alpha T1 mice, these anterior cells produce considerable amounts of SV40 tumor antigens. This suggests that the state of differentiation of the lens cell plays an important role in its response to oncogene products. JF - The New biologist AU - Nakamura, T AU - Mahon, K A AU - Miskin, R AU - Dey, A AU - Kuwabara, T AU - Westphal, H AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 193 EP - 204 VL - 1 IS - 2 SN - 1043-4674, 1043-4674 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Crystallins KW - RNA, Messenger KW - RNA, Neoplasm KW - Recombinant Fusion Proteins KW - Index Medicus KW - Phenotype KW - Neoplasm Invasiveness KW - Animals KW - Mice, Transgenic -- embryology KW - Simian virus 40 -- genetics KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Mice KW - RNA, Neoplasm -- analysis KW - Epithelium -- pathology KW - Cell Transformation, Neoplastic -- genetics KW - Gene Expression Regulation, Neoplastic KW - Recombinant Fusion Proteins -- biosynthesis KW - Eye Neoplasms -- genetics KW - Lens, Crystalline -- pathology KW - Recombinant Fusion Proteins -- genetics KW - Lens, Crystalline -- embryology KW - Recombinant Fusion Proteins -- toxicity KW - Eye Neoplasms -- pathology KW - Crystallins -- genetics KW - Antigens, Polyomavirus Transforming -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79577938?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1991-05-16 N1 - Date created - 1991-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Context-dependent cocaine sensitization: differential effect of haloperidol on development versus expression. AN - 79479283; 2623021 AB - Repeated, intermittent administration of psychomotor stimulants has been shown to produce increasing effects (behavioral sensitization) in many species of animals. In a novel two-day sensitization paradigm, rats that received a single high dose of cocaine (40 mg/kg) compared with saline on day 1 showed an increased locomotor response to a challenge dose (10 mg/kg) on day 2. This effect is conditioned or context-dependent; i.e., it is only observed if the rats received cocaine in an environment similar to the test environment. If the cocaine-induced hyperactivity on day 1 is prevented with pharmacological agents such as haloperidol and diazepam, sensitization on day 2 does not occur. Furthermore, although moderate (0.2 mg/kg) and high doses (0.5 mg/kg) of haloperidol (day 1) prevented the development of sensitization to cocaine, they were ineffective when given prior to the day 2 challenge dose in preventing the expression of sensitization. Thus, this type of cocaine sensitization appears to involve conditioning, show stimulus generalization, and offer a possible model for clinical neuroleptic nonresponsiveness once stimulant-induced pathological behavior has been induced. JF - Pharmacology, biochemistry, and behavior AU - Weiss, S R AU - Post, R M AU - Pert, A AU - Woodward, R AU - Murman, D AD - Biological Psychiatry Branch, National Institute of Mental Health 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 655 EP - 661 VL - 34 IS - 3 SN - 0091-3057, 0091-3057 KW - Cocaine KW - I5Y540LHVR KW - Haloperidol KW - J6292F8L3D KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Motor Activity -- drug effects KW - Male KW - Behavior, Animal -- drug effects KW - Haloperidol -- pharmacology KW - Diazepam -- pharmacology KW - Homing Behavior KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79479283?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-26 N1 - Date created - 1990-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Acute toxicity of perfluorodecanoic acid in C57BL/6 mice differs from 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 79468819; 2620793 AB - Perfluorodecanoic acid (PFDA) is a 10-carbon straight-chain fatty acid. Its toxicity in rats has been reported to resemble that produced by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice which are "responsive" to TCDD toxicity carry the Ahb allele, while mice homozygous for the Ahd gene are less sensitive to TCDD toxicity. To characterize the toxicity of PFDA and determine if it is under the control of the Ah locus, female responsive C57BL/6N (Ahb/b) mice and congenic C57BL/6J mice, differing only at the Ah locus (responsive, Ahb/b; heterozygous responsive, Ahb/d and "nonresponsive," Ahd/d), were administered a single oral dose of PFDA, at levels from 0 to 320 mg/kg body weight, observed daily for overt signs of toxicity, and weighed three times weekly. In the wild-type congenic C57BL/6J (Ahb/b) subline, mice were killed at 2, 7, 14, and 30 days following exposure. All other mice were killed on Day 30. Serum was taken from the C57BL/6N mice for analysis of thyroid hormone levels. Selected organs from all mice were weighed and fixed for histopathological examination. Dose-related mortality was observed as early as 5 days postexposure and time-to-death was inversely related to dose. Dramatic decreases in body weight occurred shortly following treatment in all strains. Serum triiodothyronine (T3) and thyroxine (T4) levels increased with increasing dose. There was a marked increase (p less than 0.05) in absolute and relative liver weights and a significant decrease in thymus weights. Hepatocellular hypertrophy was observed in all treated mice other than controls. A marked increase in hepatocyte peroxisomes was observed in all treatment groups. Thus, in contrast to TCDD, the acute toxicity of PFDA in the female C57BL/6 mouse does not vary with the Ah allele and is distinct from that reported for TCDD. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Harris, M W AU - Uraih, L C AU - Birnbaum, L S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 723 EP - 736 VL - 13 IS - 4 SN - 0272-0590, 0272-0590 KW - Decanoic Acids KW - 0 KW - Dioxins KW - Fluorocarbons KW - Polychlorinated Dibenzodioxins KW - Thyroid Hormones KW - perfluorodecanoic acid KW - 335-76-2 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Mice KW - Thyroid Hormones -- blood KW - Species Specificity KW - Female KW - Organ Size -- drug effects KW - Mice, Inbred DBA KW - Polychlorinated Dibenzodioxins -- toxicity KW - Fluorocarbons -- toxicity KW - Dioxins -- toxicity KW - Decanoic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79468819?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-19 N1 - Date created - 1990-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The effect of ethanol on 35S-TBPS binding to mouse brain membranes in the presence of chloride. AN - 79468511; 2622867 AB - The effect of in vitro and in vivo administration of ethanol on the binding of 35S-t-butyl-bicyclophosphorothionate (35S-TBPS) to cortical brain membranes of C57Bl mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal 35S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on 35S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of 35S-TBPS binding produced by diazepam. 35S-TBPS binding to cortical brain membranes was inhibited by the putative Cl- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (greater than or equal to 100 mM ethanol). Chronic ethanol ingestion in vivo, which produced tolerance to and physical dependence on ethanol in the animals, did not alter the stimulatory and inhibitory effects of GABA and pentobarbital on 35S-TBPS binding. The enhancement of 35S-TBPS binding produced by diazepam was slightly, but significantly, enhanced in brain membranes from animals which had undergone 24 hours of ethanol withdrawal. Chronic ethanol treatment did not change the potency of picrotoxin and of the peripheral BDZ-receptor ligand RO 5-4864 to competitively inhibit 35S-TBPS binding. Our results suggest that in vitro addition of ethanol alters the activity of the GABA/benzodiazepine (BDZ) receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Pharmacology & toxicology AU - Liljequist, S AU - Culp, S AU - Tabakoff, B AD - Laboratory for Studies of Neuroadaptive Processes, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 362 EP - 367 VL - 65 IS - 5 SN - 0901-9928, 0901-9928 KW - Benzodiazepinones KW - 0 KW - Bridged Bicyclo Compounds KW - Bridged Bicyclo Compounds, Heterocyclic KW - Bridged-Ring Compounds KW - Chlorides KW - Sulfur Radioisotopes KW - 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid KW - 27816-59-7 KW - 4'-chlorodiazepam KW - 2QW0IK1742 KW - Ethanol KW - 3K9958V90M KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - tert-butylbicyclophosphorothionate KW - 70636-86-1 KW - Pentobarbital KW - I4744080IR KW - 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid KW - Q1O6DSW23R KW - Diazepam KW - Q3JTX2Q7TU KW - Index Medicus KW - Animals KW - gamma-Aminobutyric Acid -- pharmacology KW - Diazepam -- pharmacology KW - 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid -- pharmacology KW - Chlorides -- metabolism KW - Mice KW - 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid -- analogs & derivatives KW - Pentobarbital -- pharmacology KW - Drug Tolerance KW - Mice, Inbred C57BL KW - Substance-Related Disorders -- metabolism KW - Benzodiazepinones -- pharmacology KW - Male KW - Bridged Bicyclo Compounds -- pharmacology KW - Ethanol -- pharmacology KW - Brain -- drug effects KW - Bridged-Ring Compounds -- pharmacology KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79468511?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-23 N1 - Date created - 1990-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Allosteric binding of nickel(II) to calmodulin. AN - 79466678; 2620798 AB - The binding of Ni(II) to calmodulin (CAM) in the presence and in the absence of Ca(II) was investigated by equilibrium dialysis in order to test the physicochemistry of direct Ni(II)-CAM interactions that might be responsible for the effects of this metal on CAM observed in vivo. Samples containing 5 microM CAM, 5 mM Tris/HCl buffer (pH 7.4), and NaCl to maintain the ionic strength I = 3600 microM, with or without 200 microM CaCl2, were dialyzed at 37 degrees C against 1-300 microM 63NiCl2. In the presence of Ca(II), the CAM molecule has two binding sites for Ni(II) (K1 = 7.25 x 10(5) M-1; K2 = 3.79 x 10(5) M-1) (Hill coefficient = 1.20 +/- 0.03 SE). In the absence of Ca(II), a complicated Ni(II)-binding curve is obtained indicating formation of many mutually interacting complex species. Binding of Ni(II) to CAM in the presence of Ca(II) is inhibited slightly by added MnCl2 (50 microM) and very strongly by CuCl2 and ZnCl2 (10 microM). To elucidate the mechanism of this inhibition, binding of Zn(II) (0.5-50 microM 65ZnCl2) to CAM in the presence of Ca(II) (200 microM) was also studied. The maximum molecular ratio of Zn(II) to CAM in the Zn(II)/Ca(II)/CAM complex approached 0.5. Thus, the observed inhibition by Zn(II) of the Ni(II) binding to Ca(II)/CAM does not involve competition for the same binding sites but is rather caused by a conformational arrangement of CAM in its Ca(II)/Zn(II) complex that is different than the Ca(II) complex.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Raos, N AU - Kasprzak, K S AD - Inorganic Carcinogenesis Section, National Cancer Institute, FCRF, Frederick, Maryland 21701. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 816 EP - 822 VL - 13 IS - 4 SN - 0272-0590, 0272-0590 KW - Calmodulin KW - 0 KW - Copper KW - 789U1901C5 KW - Nickel KW - 7OV03QG267 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Calcium -- metabolism KW - Dialysis KW - Kinetics KW - Copper -- metabolism KW - Protein Binding KW - Calmodulin -- metabolism KW - Nickel -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79466678?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-19 N1 - Date created - 1990-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Results and evaluations of 48 continuous breeding reproduction studies conducted in mice. AN - 79463423; 2620795 AB - Results of 48 continuous breeding reproduction (RACB) studies are summarized and control data from these studies are used to determine the statistical sensitivity of each endpoint from different parts of these studies. Results of testing individual chemicals compared well with results of multigeneration studies reported in the literature. Continuous breeding studies were able to discriminate reproductive toxicants from nontoxicants, and provided valuable structure-activity information. When mice in continuous cohabitation produce multiple litters, the statistical sensitivity of fertility endpoints is quite high and is comparable to that associated with other sensitive indicators of reproductive function, such as testis weight and sperm parameter measures. The principal advantages of the RACB protocol in comparison to multigeneration studies are: (1) the increased sensitivity and statistical power, (2) the ability to monitor progression of toxicity and to detect subfertility, (3) use of a battery of endpoints including sperm measures, (4) the ability to determine the affected sex(es), and (5) slightly reduced testing time. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Morrissey, R E AU - Lamb, J C AU - Morris, R W AU - Chapin, R E AU - Gulati, D K AU - Heindel, J J AD - Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 747 EP - 777 VL - 13 IS - 4 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - Sexual Behavior, Animal -- drug effects KW - Evaluation Studies as Topic KW - Mice, Inbred Strains KW - Animals KW - Reference Values KW - Sex Factors KW - Mice KW - Birth Weight -- drug effects KW - Statistics as Topic KW - Male KW - Female KW - Pregnancy KW - Fertility -- drug effects KW - Reproduction -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79463423?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-19 N1 - Date created - 1990-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. AN - 79460117; 2620797 AB - This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Heindel, J J AU - Berkowitz, A S AU - Kyle, G AU - Luthra, R AU - Bruckner, J V AD - National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, North Carolina 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 804 EP - 815 VL - 13 IS - 4 SN - 0272-0590, 0272-0590 KW - Enzymes KW - 0 KW - Gonadal Steroid Hormones KW - Insecticides KW - 1,2-dibromo-3-chloropropane KW - 96K0FD4803 KW - Propane KW - T75W9911L6 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Enzymes -- blood KW - Drinking -- drug effects KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Gonadal Steroid Hormones -- blood KW - Male KW - Organ Size -- drug effects KW - Propane -- toxicity KW - Propane -- administration & dosage KW - Insecticides -- toxicity KW - Kidney Diseases -- physiopathology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Testis -- drug effects KW - Insecticides -- administration & dosage KW - Propane -- analogs & derivatives KW - Endocrine System Diseases -- chemically induced KW - Chemical and Drug Induced Liver Injury -- physiopathology KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79460117?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-19 N1 - Date created - 1990-03-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Metabolism, disposition, and mutagenicity of 2,6-diaminotoluene, a mutagenic noncarcinogen. AN - 79441275; 2575496 AB - 2,6-Diaminotoluene (2,6-DAT) is a major industrial chemical; approximately 100 million pounds are used annually in the synthesis of 2,6-toluene diisocyanate. 2,6-DAT is mutagenic in Salmonella typhimurium TA98 requiring metabolic activation, but has been previously shown to be a noncarcinogen in male and female F344 rats and male and female 86C3F1 mice dosed orally in 2-year bioassays. 2,6-DAT was rapidly and extensively absorbed following oral administration, indicating that its lack of carcinogenicity is not due to poor absorption from the gastrointestinal tract. 2,6-DAT was also rapidly excreted, with 85% of 2,6-DAT-associated radioactivity being recovered in the urine within 24 hr. Resolution of the urine by reverse phase HPLC demonstrated the presence of four metabolites, but none of the parent 2,6-DAT. Therefore, the lack of carcinogenicity of 2,6-DAT is not due to lack of biotransformation in vivo. Following separation by HPLC, the metabolites were analyzed by electron impact and fast atom bombardment mass spectroscopy and by NMR spectroscopy. The metabolites were identified as a) 3-hydroxy-2,6-DAT, b) 4-hydroxy-2-acetylamino-6-aminotoluene, c) 2-acetylamino-6-aminotoluene, and d) 2,6-di(acetylamino)-toluene. Metabolites b and d were found to be mutagenic in Salmonella typhimurium TA98 and then only in the presence of an activation system. Results of this study indicate that 2,6-DAT, which is a mutagen in in vitro tests, is also metabolized by the rat to compounds which are proximate mutagens.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Drug metabolism and disposition: the biological fate of chemicals AU - Cunningham, M L AU - Burka, L T AU - Matthews, H B AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1989 SP - 612 EP - 617 VL - 17 IS - 6 SN - 0090-9556, 0090-9556 KW - Mutagens KW - 0 KW - Phenylenediamines KW - 2,6-diaminotoluene KW - H838Q10551 KW - Index Medicus KW - Rats KW - Feces -- analysis KW - Animals KW - Rats, Inbred F344 KW - Mutagenicity Tests KW - Biotransformation KW - In Vitro Techniques KW - Salmonella typhimurium -- drug effects KW - Tissue Distribution KW - Salmonella typhimurium -- genetics KW - Male KW - Phenylenediamines -- toxicity KW - Phenylenediamines -- pharmacokinetics KW - Phenylenediamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79441275?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Thyroid peroxidase: rat cDNA sequence, chromosomal localization in mouse, and regulation of gene expression by comparison to thyroglobulin in rat FRTL-5 cells. AN - 79420285; 2691880 AB - A rat thyroid peroxidase cDNA has been isolated from a FRTL-5 thyroid cell library and sequenced. The cDNA is 2776 base pairs long with an open reading frame of 770 amino acids. By comparison to full-length human thyroid peroxidase cDNA and based on its identification of a 3.2 kilobase mRNA in rat thyroid FRTL-5 cell Northern blots, the rat peroxidase cDNA appears to lack 400-500 base pairs at the 5'-end of the mRNA. It exhibits only a 74% nucleotide and 77% amino acid sequence similarity to human thyroid peroxidase cDNA within the total aligned sequences, although the predicted active site regions are highly conserved (greater than 90-100%). The cDNA has been used to map the thyroid peroxidase gene in mice to chromosome 12 and to compare thyroid peroxidase and thyroglobulin gene expression in FRTL-5 rat thyroid cells. Despite the fact TSH action in both cases is duplicated, and presumably mediated, by cAMP, TSH-induced increases in thyroid peroxidase and thyroglobulin mRNA levels differ. Differences exist with respect to hormone concentration and time. The ability of TSH to increase thyroglobulin, but not thyroid peroxidase mRNA levels, requires insulin, 5% serum, or insulin-like growth factor-I. Insulin or insulin-like growth factor-I alone can increase thyroglobulin mRNA levels as well as or better than TSH but have only a small effect on thyroid peroxidase mRNA levels by comparison to TSH. The ability of TSH to increase thyroglobulin gene expression is readily detected in nuclear run-on assays but not the ability of TSH to increase thyroid peroxidase gene expression. Cycloheximide inhibits TSH-increased thyroglobulin but not peroxidase mRNA levels. Finally, methimazole and phorbol 12-myristate 13-acetate show different effects on TSH-induced increases in thyroglobulin and thyroid peroxidase mRNA levels. JF - Molecular endocrinology (Baltimore, Md.) AU - Isozaki, O AU - Kohn, L D AU - Kozak, C A AU - Kimura, S AD - Laboratory of Biochemistry and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 1681 EP - 1692 VL - 3 IS - 11 SN - 0888-8809, 0888-8809 KW - Actins KW - 0 KW - Amanitins KW - Insulin KW - Dactinomycin KW - 1CC1JFE158 KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Methimazole KW - 554Z48XN5E KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Thyrotropin KW - 9002-71-5 KW - DNA KW - 9007-49-2 KW - Thyroglobulin KW - 9010-34-8 KW - Cycloheximide KW - 98600C0908 KW - Iodide Peroxidase KW - EC 1.11.1.8 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Humans KW - Insulin -- pharmacology KW - Amino Acid Sequence KW - Methimazole -- pharmacology KW - Insulin-Like Growth Factor I -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Chromosome Mapping KW - Dactinomycin -- pharmacology KW - Rats, Inbred F344 KW - Base Sequence KW - Thyrotropin -- pharmacology KW - Genes KW - Amanitins -- pharmacology KW - Cycloheximide -- pharmacology KW - DNA -- genetics KW - Molecular Sequence Data KW - Thyroid Gland -- enzymology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Actins -- biosynthesis KW - Cell Line KW - Iodide Peroxidase -- biosynthesis KW - Thyroglobulin -- biosynthesis KW - Mice -- genetics KW - Iodide Peroxidase -- genetics KW - Rats -- genetics KW - Thyroglobulin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79420285?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-15 N1 - Date created - 1990-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vitro maturation and fertilization of domestic cat follicular oocytes. AN - 79390743; 2599509 AB - The time course and conditions necessary for oocyte maturation and subsequent fertilization in vitro were studied in the domestic cat. Darkly pigmented oocytes surrounded by cumulus cells and a tight corona radiata were collected from ovaries removed at ovariohysterectomy. After culture in Eagle's minimum essential medium, oocytes were evaluated for nuclear maturation by analyzing chromosomal spreads. Oocytes achieved metaphase II after intervals of 40-48 hr of in vitro incubation. The incidence of maturation was enhanced (P less than 0.05) when oocytes were recovered from inactive (54%) or follicular (56%) stage donors compared to those recovered from luteal phase (29%) or pregnant (35%) cats. The proportion of oocytes successfully maturing in vitro in medium containing no hormone supplementation (37%) was less (P less than 0.01) than counterparts cultured in follicle-stimulating hormone (FSH) only (48%) or FSH and luteinizing hormone (LH) (54%). The efficiency of maturation was not influenced (P greater than 0.05) by either maintenance/transport temperature (4 degrees C vs. 22 degrees C) or delaying recovery of oocytes from antral follicles (2-8 hr vs. 24-32 hr). Approximately 36% of the in vitro matured oocytes cocultured with spermatozoa demonstrated evidence of fertilization; however, there appeared to be a critical development period for maximizing the incidence of fertilization. These results demonstrate that domestic cat antral oocytes are capable of maturing in vitro, and maturation is influenced by the reproductive status of the donor and the presence of gonadotropins in the culture medium. These oocytes are capable of forming embryos and developing to at least the 16-cell stage in vitro. JF - Gamete research AU - Johnston, L A AU - O'Brien, S J AU - Wildt, D E AD - Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick, Maryland 21701. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 343 EP - 356 VL - 24 IS - 3 SN - 0148-7280, 0148-7280 KW - Gonadotropins KW - 0 KW - Index Medicus KW - Gonadotropins -- pharmacology KW - Animals KW - Embryonic and Fetal Development KW - Kinetics KW - Cats KW - Chromosomes -- ultrastructure KW - Female KW - Ovarian Follicle -- physiology KW - Fertilization in Vitro KW - Oogenesis KW - Ovarian Follicle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79390743?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-01 N1 - Date created - 1990-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Benzene risk assessments: review and update. AN - 79387267; 2688843 JF - Cell biology and toxicology AU - Bailer, A J AU - Hoel, D G AD - Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 287 EP - 295 VL - 5 IS - 3 SN - 0742-2091, 0742-2091 KW - Benzene KW - J64922108F KW - Index Medicus KW - Risk KW - Animals KW - Maximum Allowable Concentration KW - Humans KW - Benzene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79387267?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-30 N1 - Date created - 1990-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cycloleucine blocks NMDA responses in cultured hippocampal neurones under voltage clamp: antagonism at the strychnine-insensitive glycine receptor. AN - 79356683; 2556198 AB - 1. Radioligand binding studies have demonstrated that the neutral amino acid cycloleucine may act as a competitive antagonist at the glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor complex. In the present study, we examined the effects of cycloleucine on NMDA-evoked inward current responses in dissociated hippocampal neuronal cultures using the whole cell voltage-clamp technique. 2. In the presence of 1 microM glycine, cycloleucine caused a reversible, dose-dependent inhibition of NMDA responses with an IC50 of 24 microM. An increase in glycine to 100 microM resulted in a shift to the right of the cycloleucine concentration-effect curve (IC50, 1.4 mM). However, with cycloleucine concentrations less than or equal to 100 microM, a fraction of the block could not be overcome by glycine even at concentrations as high as 1 mM. 3. The cycloleucine block was unaffected by shifts in the holding potential (-60 to +60 mV), and there was no effect of cycloleucine on the reversal potential of the NMDA-evoked current. 4. Cycloleucine failed to effect kainic acid- and quisqualic acid-evoked currents at concentrations which inhibited NMDA responses. 5. We conclude that cycloleucine is a potent and selective antagonist of NMDA-receptor mediated responses. Although this effect occurs in part via competitive antagonism at the glycine modulatory site, the cycloleucine block cannot be completely reversed by glycine indicating an interaction with an additional site on the receptor-channel complex. JF - British journal of pharmacology AU - Hershkowitz, N AU - Rogawski, M A AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 1005 EP - 1013 VL - 98 IS - 3 SN - 0007-1188, 0007-1188 KW - Amino Acids KW - 0 KW - Receptors, Glycine KW - Receptors, Neurotransmitter KW - Cycloleucine KW - 0TQU7668EI KW - Aspartic Acid KW - 30KYC7MIAI KW - N-Methylaspartate KW - 6384-92-5 KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Cells, Cultured KW - Strychnine -- pharmacology KW - Membrane Potentials -- drug effects KW - Electrophysiology KW - Female KW - Pregnancy KW - Aspartic Acid -- analogs & derivatives KW - Hippocampus -- physiology KW - Receptors, Neurotransmitter -- metabolism KW - Cycloleucine -- pharmacology KW - Neurons -- drug effects KW - Hippocampus -- cytology KW - Amino Acids -- pharmacology KW - Aspartic Acid -- antagonists & inhibitors KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79356683?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-25 N1 - Date created - 1990-01-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1987 Nov 20;238(4830):1114-6 [2825347] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7744-8 [2823273] Eur J Pharmacol. 1987 Oct 27;142(3):489-90 [2448149] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1307-11 [2448800] J Physiol. 1987 Dec;394:501-27 [2451020] Neurosci Lett. 1988 Feb 3;84(3):351-5 [2451195] Neurosci Lett. 1988 Jun 7;88(3):325-30 [3386879] J Pharmacol Exp Ther. 1988 Jul;246(1):137-42 [2455788] Science. 1988 Aug 12;241(4867):835-7 [2841759] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6547-50 [2842779] Eur J Pharmacol. 1988 Jun 22;151(1):161-2 [2901361] Eur J Pharmacol. 1988 Jun 22;151(1):165-6 [2843389] J Neurophysiol. 1988 Aug;60(2):645-63 [2902200] Eur J Pharmacol. 1988 Sep 1;154(1):85-7 [2846328] J Neurosci. 1988 Oct;8(10):3733-41 [2848107] J Neurosci. 1988 Oct;8(10):3822-6 [2903914] Eur J Pharmacol. 1988 Jul 26;152(1-2):141-6 [3061829] Eur J Pharmacol. 1988 Oct 26;156(1):149-55 [3061832] Eur J Pharmacol. 1988 Oct 26;156(1):177-80 [2905271] Mol Pharmacol. 1989 Mar;35(3):360-8 [2564633] Nature. 1989 Mar 30;338(6214):425-7 [2538755] Science. 1989 Mar 24;243(4898):1611-3 [2467381] Eur J Pharmacol. 1989 Mar 7;172(1):9-17 [2541002] Neurosci Lett. 1989 Jan 30;96(3):323-8 [2541381] Eur J Pharmacol. 1989 Feb 28;161(2-3):281-2 [2542048] Neurosci Lett. 1989 Apr 10;98(3):333-8 [2657505] Biochim Biophys Acta. 1976 May 21;433(3):482-95 [179590] J Theor Biol. 1976 May 21;58(2):383-400 [181640] Am J Physiol. 1978 Aug;235(2):E97-102 [686171] J Neurophysiol. 1983 Dec;50(6):1249-64 [6663325] Nature. 1984 Feb 2-8;307(5950):462-5 [6320006] Nature. 1984 May 17-23;309(5965):261-3 [6325946] Neurosci Lett. 1985 Oct 24;61(1-2):135-9 [2417168] Nature. 1987 Feb 5-11;325(6104):529-31 [2433595] J Neurophysiol. 1987 Aug;58(2):251-66 [2443623] Eur J Pharmacol. 1987 Oct 27;142(3):487-8 [2828080] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Research on alcohol metabolism among Asians and its implications for understanding causes of alcoholism. AN - 79348648; 2511595 AB - Research into the causes of alcoholism is a relatively recent scientific endeavor. One area of study which could lead to better understanding of the disease is the possibility of a genetic predisposition to alcoholism. Recent work has demonstrated that people have varying complements of enzymes to metabolize alcohol. Current knowledge is examined about the influence of various ethanol metabolizing enzymes on alcohol consumption by Asians and members of other ethnic groups. The two principal enzymes involved in ethanol oxidative metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). ADH is responsible for the metabolism of ethanol to acetaldehyde. ALDH catalyzes the conversion of acetaldehyde to acetate. The different isozymes account for the diversity of alcohol metabolism among individuals. An isozyme of ADH (beta 2 beta 2) is found more frequently in Asians than in whites, and an ALDH isozyme (ALDH2), although present in Asians, often is in an inactive form. The presence of an inactive form of ALDH2 is thought to be responsible for an increase in acetaldehyde levels in the body. Acetaldehyde is considered responsible for the facial flushing reaction often observed among Asians who have consumed alcohol. A dysphoric reaction to alcohol, producing uncomfortable sensations, is believed to be a response to deter further consumption. Although the presence of an inactive ALDH2 isozyme may serve as a deterrent to alcohol consumption, its presence does not fully explain the levels of alcohol consumption by those with the inactive isozyme. Other conditions, such as social pressure, and yet undetermined biological factors, may play a significant role in alcohol consumption. JF - Public health reports (Washington, D.C. : 1974) AU - Suddendorf, R F AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857. PY - 1989 SP - 615 EP - 620 VL - 104 IS - 6 SN - 0033-3549, 0033-3549 KW - Isoenzymes KW - 0 KW - Ethanol KW - 3K9958V90M KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Aldehyde Dehydrogenase KW - EC 1.2.1.3 KW - Acetaldehyde KW - GO1N1ZPR3B KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Flushing KW - Acetaldehyde -- metabolism KW - Asia KW - Isoenzymes -- analysis KW - Aldehyde Dehydrogenase -- genetics KW - Alcoholism -- enzymology KW - Alcohol Dehydrogenase -- genetics KW - Aldehyde Dehydrogenase -- analysis KW - Alcohol Dehydrogenase -- metabolism KW - Ethanol -- metabolism KW - Aldehyde Dehydrogenase -- metabolism KW - Alcoholism -- genetics KW - Alcohol Dehydrogenase -- analysis KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79348648?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-02 N1 - Date created - 1990-01-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pharmacol Biochem Behav. 1983;18 Suppl 1:127-33 [6356156] Am J Hum Genet. 1983 Nov;35(6):1107-16 [6650498] Alcohol Clin Exp Res. 1983 Fall;7(4):372-7 [6362460] Biochem Genet. 1984 Feb;22(1-2):169-80 [6370230] Biochemistry. 1984 Aug 28;23(18):4082-7 [6487592] Biochemistry. 1984 Nov 20;23(24):5847-53 [6395883] Alcohol Clin Exp Res. 1985 May-Jun;9(3):263-71 [3893198] Alcohol. 1985 Jan-Feb;2(1):53-6 [3893465] Eur J Biochem. 1985 Nov 15;153(1):13-28 [4065146] Hepatology. 1986 May-Jun;6(3):502-10 [3519419] Ann Emerg Med. 1986 Sep;15(9):997-1004 [3526998] Contemp Issues Clin Biochem. 1984;1:135-48 [6400496] Ann N Y Acad Sci. 1987;492:11-24 [3474921] Ann N Y Acad Sci. 1987;492:25-34 [3474929] Clin Pharmacol Ther. 1967 Nov-Dec;8(6):824-9 [6059287] J Biol Chem. 1970 May 25;245(10):2505-12 [4315645] Ann Hum Genet. 1971 Feb;34(3):251-71 [5548434] Ann Hum Genet. 1973 Apr;36(4):401-14 [4748759] Ann Hum Genet. 1973 Jul;37(1):49-67 [4796765] Biochem Biophys Res Commun. 1975 Mar 3;63(1):202-8 [1125010] N Engl J Med. 1976 Jan 1;294(1):9-13 [1244489] Am J Hum Genet. 1975 Nov;27(6):789-96 [1200030] Biochim Biophys Acta. 1977 Jul 8;483(1):35-45 [18196] Adv Enzymol Relat Areas Mol Biol. 1977;45:427-83 [335822] Hum Genet. 1978 Jan 19;40(2):215-20 [624549] Alcohol Clin Exp Res. 1978 Jan;2(1):89-92 [345859] Hum Genet. 1978 Oct 31;44(2):181-5 [730161] Pharmacol Biochem Behav. 1979 Feb;10(2):303-11 [450943] Life Sci. 1980 May 26;26(21):1773-80 [6985464] Proc Natl Acad Sci U S A. 1980 Oct;77(10):5784-8 [7003596] Biochem Biophys Res Commun. 1981 Jan 15;98(1):122-30 [7011320] J Biol Chem. 1981 Dec 25;256(24):12968-73 [7031053] Semin Liver Dis. 1981 Aug;1(3):179-88 [7051301] Biochemistry. 1983 Apr 12;22(8):1852-7 [6342668] Am J Hum Genet. 1983 Jul;35(4):769-72 [6881146] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Rationale for continuous dopaminomimetic therapy of Parkinson's disease. AN - 79347784; 2685653 AB - Levodopa combined with carbidopa (Sinemet) remains the most effective approach to the symptomatic relief of Parkinson's disease. Over time, however, an increasing number of parkinsonian patients evidence motor response complications, notably abnormal involuntary movements and motor fluctuations. Clinical pharmacologic studies suggest that these phenomena may arise as a consequence of factors reflecting both natural disease progression and levodopa toxicity. Simple wearing-off responses appear primarily related to advancing degenerative changes afflicting the dopamine system. The appearance of peak-dose dyskinesias and complex, random motor fluctuations of the on-off type, on the other hand, may signal secondary postjunctional changes arising as a consequence of chronic intermittent excitation of postsynaptic dopamine receptors that are normally tonically stimulated. Therapeutically, prompt correction of wearing-off fluctuations can ordinarily be achieved by measures that deliver dopaminomimetics continuously to the central nervous system. In contrast, fluctuations of the on-off type initially persist despite stable circulating levodopa levels. With continuous levodopa treatment, however, the threshold for dyskinesias begins to rise and the dose-response relation shifts to the right; clinically, the severity of both dyskinesias and on-off fluctuations tends to diminish. It is thus tempting to speculate that the early and continuing treatment of Parkinson's disease with compounds providing a relatively constant level of central dopamine stimulation will preclude wearing-off phenomena and mitigate on-off fluctuations and severe dyskinesias. JF - Neurology AU - Chase, T N AU - Baronti, F AU - Fabbrini, G AU - Heuser, I J AU - Juncos, J L AU - Mouradian, M M AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 7 EP - 10; discussion 19 VL - 39 IS - 11 Suppl 2 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Drug Combinations KW - carbidopa, levodopa drug combination KW - Levodopa KW - 46627O600J KW - Carbidopa KW - MNX7R8C5VO KW - Abridged Index Medicus KW - Index Medicus KW - Drug Combinations -- pharmacokinetics KW - Humans KW - Drug Combinations -- therapeutic use KW - Levodopa -- pharmacokinetics KW - Parkinson Disease -- metabolism KW - Levodopa -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Carbidopa -- therapeutic use KW - Carbidopa -- pharmacokinetics KW - Parkinson Disease -- drug therapy KW - Antiparkinson Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79347784?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-04 N1 - Date created - 1990-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mechanism of inhibition of prostaglandin H synthase by eugenol and other phenolic peroxidase substrates. AN - 79344511; 2511429 AB - The mechanism of inhibition of prostaglandin H synthase (PHS) by eugenol was investigated using purified apoenzyme reconstituted with either manganese protoporphyrin IX (Mn-PHS) or hematin (Fe-PHS). Eugenol stimulated Fe-PHS activity at low concentrations and inhibited at higher concentrations, an activity typical of many phenolic compounds. Eugenol was also an excellent reducing cosubstrate for the peroxidase, being cooxidized to a reactive quinone methide in the process. Higher concentrations of eugenol were required to inhibit Fe-PHS than Mn-PHS (which retains cyclooxygenase activity but not peroxidase activity). Inhibition by eugenol was highly dependent on arachidonic acid concentration. In experiments using Mn-PHS, eugenol increased the time required for the initiation of O2 consumption after addition of arachidonic acid and also inhibited the rate of O2 uptake. Eugenol did not, however, affect the total amount of O2 consumed. The addition of 10 microM hydroperoxide (prostaglandin G2) to these incubations did not prevent the inhibitory effects of eugenol. Other phenolic compounds, including guaiacol, butylated hydroxyanisole, and acetaminophen inhibited Mn-PHS in a manner similar to eugenol. These results demonstrate that eugenol and other phenolic compounds specifically inhibit the cyclooxygenase component of PHS and that this inhibition occurs in addition to, or independent of, the effect of these compounds on peroxide tone or their peroxidative metabolism. We suggest that this inhibition is due to competition with arachidonic acid for the active site of PHS. JF - Molecular pharmacology AU - Thompson, D AU - Eling, T AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Biophysics, Research Triangle Park, North Carolina 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 809 EP - 817 VL - 36 IS - 5 SN - 0026-895X, 0026-895X KW - Apoenzymes KW - 0 KW - Arachidonic Acids KW - Cyclooxygenase Inhibitors KW - Phenols KW - Prostaglandins G KW - Butylated Hydroxyanisole KW - 25013-16-5 KW - Arachidonic Acid KW - 27YG812J1I KW - Eugenol KW - 3T8H1794QW KW - Manganese KW - 42Z2K6ZL8P KW - prostaglandin G2 KW - 51982-36-6 KW - Flufenamic Acid KW - 60GCX7Y6BH KW - Guaiacol KW - 6JKA7MAH9C KW - Iron KW - E1UOL152H7 KW - Peroxidases KW - EC 1.11.1.- KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Animals KW - Manganese -- metabolism KW - Phenols -- pharmacology KW - Sheep KW - Guaiacol -- pharmacology KW - Microsomes -- enzymology KW - Arachidonic Acids -- metabolism KW - Ascorbic Acid -- pharmacology KW - Seminal Vesicles -- enzymology KW - Iron -- metabolism KW - Oxidation-Reduction KW - Kinetics KW - Flufenamic Acid -- pharmacology KW - Prostaglandins G -- metabolism KW - Apoenzymes -- metabolism KW - Butylated Hydroxyanisole -- pharmacology KW - Male KW - Peroxidases -- metabolism KW - Eugenol -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79344511?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-02 N1 - Date created - 1990-01-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The human chromogranin A gene: chromosome assignment and RFLP analysis. AN - 79325070; 2573279 AB - Chromogranin A/secretory protein I (CgA) is a glycoprotein that is stored and released along with peptide hormones and neurotransmitters from several tissues, although its exact function is not known. A cDNA (gene symbol CHGA) clone was used as a probe in Southern blot analyses of human-rodent somatic cell hybrid DNAs. Discordancy analysis allowed confirmation of the assignment of the gene to chromosome 14. These results were extended using in situ chromosome hybridization, and a signal was found at 14q32. BglII digestion of genomic DNA from 28 unrelated Caucasian individuals probed with CHGA detected a two-allele RFLP with allelic frequencies of .34 and .66. JF - American journal of human genetics AU - Modi, W S AU - Levine, M A AU - Seuanez, H N AU - Dean, M AU - O'Brien, S J AD - Biological Carcinogenesis and Development Program, National Cancer Institute-Frederick Research Facility, MD 21701. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 814 EP - 818 VL - 45 IS - 5 SN - 0002-9297, 0002-9297 KW - CHGA protein, human KW - 0 KW - Chromogranin A KW - Chromogranins KW - Nerve Tissue Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Pedigree KW - Polymorphism, Restriction Fragment Length KW - Blotting, Southern KW - Humans KW - DNA -- genetics KW - Nucleic Acid Hybridization KW - Chromosome Mapping KW - Nerve Tissue Proteins -- genetics KW - Chromosomes, Human, Pair 14 KW - Chromogranins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79325070?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-08 N1 - Date created - 1989-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Histochem Cytochem. 1978 Aug;26(8):677-9 [99471] Neuroscience. 1976;1(2):65-80 [794758] J Biol Chem. 1982 Apr 10;257(7):3581-8 [7061498] Cytogenet Cell Genet. 1982;32(1-4):58-67 [6291862] Nature. 1983 Apr 28;302(5911):839-42 [6843651] Proc Natl Acad Sci U S A. 1982 Oct;79(19):6056-9 [6821132] Biochem Biophys Res Commun. 1984 Apr 30;120(2):493-9 [6547335] J Biol Chem. 1984 Sep 25;259(18):11597-600 [6147355] Nature. 1986 Sep 4-10;323(6083):82-6 [3018587] Biochem Biophys Res Commun. 1987 Jan 15;142(1):141-6 [3814131] Proc Natl Acad Sci U S A. 1987 Jul;84(14):5043-7 [3474638] J Pediatr. 1987 Oct;111(4):490-5 [2888841] J Biol Chem. 1988 Aug 15;263(23):11559-63 [3403545] Genomics. 1988 May;2(4):310-4 [3265409] Cytogenet Cell Genet. 1987;46(1-4):213-41 [3507275] Gene Anal Tech. 1987 Jul-Aug;4(4):75-85 [3507390] Mol Pharmacol. 1967 Jan;3(1):81-9 [6030895] Nature. 1967 Jul 1;215(5096):58-9 [6053402] Am J Hum Genet. 1980 May;32(3):314-31 [6247908] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Psychiatric disorders in the first-degree relatives of probands with bulimia nervosa. AN - 79322672; 2817120 AB - Data from a family study of psychiatric disorders showed higher rates of major affective disorders, eating disorders, and alcoholism in first-degree relatives of 40 bulimic probands than in first-degree relatives of 24 control subjects. More importantly, the data showed higher rates of major affective disorders in relatives of bulimic probands who themselves had no history of major affective disorders than in relatives of control subjects. This significant finding indicates a familial relationship between bulimia nervosa and major affective disorders, which suggests the possibility of a common diathesis. JF - The American journal of psychiatry AU - Kassett, J A AU - Gershon, E S AU - Maxwell, M E AU - Guroff, J J AU - Kazuba, D M AU - Smith, A L AU - Brandt, H A AU - Jimerson, D C AD - Laboratory of Clinical Science, NIMH, Bethesda, MD. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 1468 EP - 1471 VL - 146 IS - 11 SN - 0002-953X, 0002-953X KW - Abridged Index Medicus KW - Index Medicus KW - Feeding and Eating Disorders -- genetics KW - Humans KW - Adult KW - Antisocial Personality Disorder -- genetics KW - Alcoholism -- genetics KW - Substance-Related Disorders -- genetics KW - Mood Disorders -- genetics KW - Female KW - Mental Disorders -- genetics KW - Bulimia -- complications KW - Mental Disorders -- complications KW - Bulimia -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79322672?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-29 N1 - Date created - 1989-11-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 1990 Oct;147(10):1381-2 [2271032] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Role of a tumor-suppressor gene in the negative control of anchorage-independent growth of Syrian hamster cells. AN - 79312026; 2813423 AB - Tumor-suppressor genes control the neoplastic phenotype of tumor cells, but the function of these genes in normal cells is unknown. In this report we show that the loss of a tumor-suppressor gene function releases negative controls on the growth of cells in agar. This conclusion is based on observations of cell hybrids and studies of cell variants that have retained or lost a tumor-suppressor gene function. Nontumorigenic cell hybrids between normal Syrian hamster embryo cells and a benzo[a]pyrene-transformed tumor-cell line (BP6T) continued to secrete autocrine and/or paracrine growth factors produced by the tumor cells but failed to respond to these factors by growing in agar. Normal diploid cells also failed to grow in agar in response to the growth factors produced by the tumor cells. Clonal variants of nontumorigenic, immortal Syrian hamster cell lines were isolated that either retained (termed supB+) or had lost (termed supB-) the ability to suppress tumorigenicity of BP6T tumor cells after cell hybridization. Neither supB+ nor supB- variants grew in agar under conditions that allowed efficient growth of the tumor cells. However, supB- cells were reversibly induced to grow in agar with high colony-forming efficiencies in the presence of tumor cell-conditioned medium or by supplementation of the medium with a combination of growth factors. Under the same conditions, the supB+ cells failed to grow in agar. This enhanced growth-factor responsiveness in agar was used to select for supB- variants existing at a low frequency in the supB+ population. These two phenotypes, loss of tumor-suppressor function and enhanced growth-factor responsiveness in agar, were seen to cosegregate. These results indicate the tumor-suppressor gene function in these cells negatively regulates the growth response of cells in agar to mitogenic stimuli. This growth regulation may depend on cell shape or adhesion because supB+ and supB- cells grown attached to plastic responded similarly to growth factors. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Koi, M AU - Afshari, C A AU - Annab, L A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 8773 EP - 8777 VL - 86 IS - 22 SN - 0027-8424, 0027-8424 KW - Growth Substances KW - 0 KW - Index Medicus KW - Phenotype KW - Clone Cells KW - Animals KW - Growth Substances -- pharmacology KW - Mesocricetus KW - Hybrid Cells -- cytology KW - Tumor Stem Cell Assay KW - DNA Replication KW - Cell Line KW - Cricetinae KW - Cell Adhesion KW - Oncogenes KW - Cell Division -- drug effects KW - Suppression, Genetic KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79312026?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1986 Apr;46(4 Pt 1):1573-80 [2418950] Cancer Res. 1986 Mar;46(3):1015-29 [3002607] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5209-13 [3523486] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5992-6 [3461473] Mol Cell Biol. 1985 Dec;5(12):3386-96 [2427928] Science. 1986 Oct 10;234(4773):161-6 [3018928] Mol Cell Biol. 1986 Mar;6(3):870-7 [3022135] Nature. 1986 Oct 16-22;323(6089):643-6 [2877398] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8167-71 [3490663] Science. 1987 Mar 13;235(4794):1394-9 [3823889] Science. 1987 Apr 10;236(4798):175-80 [3031816] Cancer Res. 1987 May 1;47(9):2514-20 [3471327] Science. 1987 Jun 26;236(4809):1657-61 [2885916] Mol Cell Biol. 1987 Jul;7(7):2649-52 [3475570] Nature. 1987 Aug 13-19;328(6131):616-9 [2886919] Science. 1987 Dec 11;238(4833):1539-45 [3317834] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1590-4 [3125552] Cancer Res. 1988 Mar 15;48(6):1623-32 [2449958] Cancer Res. 1988 Jun 15;48(12):3302-6 [3370633] Cancer Res. 1988 Jul 1;48(13):3716-9 [3378214] Oncogene. 1987;1(3):271-6 [3330775] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5576-80 [2456572] Cell. 1989 Jan 13;56(1):77-84 [2642744] Mol Carcinog. 1988;1(3):180-8 [3074813] Proc Natl Acad Sci U S A. 1977 Sep;74(9):3845-9 [269435] Proc Natl Acad Sci U S A. 1977 Oct;74(10):4481-5 [270695] Nature. 1978 Jun 1;273(5661):345-9 [661946] Proc Natl Acad Sci U S A. 1978 Aug;75(8):3761-5 [278986] Science. 1982 Jan 15;215(4530):252-9 [7053574] Cancer Res. 1983 Apr;43(4):1581-6 [6299525] Cell. 1983 Jul;33(3):653-5 [6307524] Cell. 1983 Jul;33(3):931-8 [6307528] Nature. 1983 Oct 27-Nov 2;305(5937):779-84 [6633649] Science. 1984 Mar 9;223(4640):1028-33 [6320372] Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396-400 [6326125] Nature. 1984 Aug 23-29;310(5979):655-60 [6088986] Mol Cell Biol. 1984 Aug;4(8):1572-6 [6092919] Cancer Res. 1985 Feb;45(2):726-32 [2981612] Nature. 1985 Feb 28-Mar 6;313(6005):745-7 [3883191] Cancer Res. 1985 Apr;45(4):1437-43 [2983882] Proc Natl Acad Sci U S A. 1985 Apr;82(7):2062-6 [3856884] J Cell Biochem. 1985;27(2):143-56 [3886675] Nature. 1985 Aug 15-21;316(6029):636-9 [2993900] Mutat Res. 1986 Jul;168(1):3-14 [3012326] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Non-metallothionein-bound cadmium in the pathogenesis of cadmium nephrotoxicity in the rat. AN - 79309856; 2815080 AB - Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin figures in vacuoles in cytoplasm of proximal tubular lining cells reflecting degeneration of membranes. This change occurred after 4 weeks with 801 +/- 25 nmol/g (89.9 micrograms/g) total kidney cadmium or 390 nmol/g (43.7 micrograms/g) of cadmium not bound to metallothionein. Similar changes were observed after 6 weeks but after 8 weeks pathological changes consisted of focal cellular necrosis and interstitial fibrosis. Other ultrastructural changes included altered mitochondria and increased numbers of microbodies. Renal cadmium after 8 weeks exposure was 1827 +/- 48 nmol/g (215.3 +/- 5.8 micrograms/g) or 628 nmol/g (70.2 micrograms/g) of cadmium not bound to metallothionein. Total cadmium was higher in liver than in kidney but partitioning between bound and nonbound cadmium differed in the two organs. The fraction not bound to metallothionein increased with time of exposure in both liver and kidney. However, total cadmium in the liver did not exceed potentially available binding sites of metallothionein, whereas total cadmium did exceed potentially available binding sites of metallothionein in the kidney where pathologic changes occurred. The results indicated that degeneration of cellular membranes is an early cellular effect of cadmium exposure followed later by toxicity to organelles, cellular necrosis, and interstitial fibrosis. Cadmium-induced cellular toxicity is more directly related to the fraction of cadmium in the kidney that is not bound to metallothionein than is total cadmium per se. JF - Toxicology and applied pharmacology AU - Goyer, R A AU - Miller, C R AU - Zhu, S Y AU - Victery, W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27514. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 232 EP - 244 VL - 101 IS - 2 SN - 0041-008X, 0041-008X KW - Cadmium KW - 00BH33GNGH KW - Copper KW - 789U1901C5 KW - Metallothionein KW - 9038-94-2 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Kidney Tubules, Proximal -- ultrastructure KW - Liver -- analysis KW - Rats, Inbred Strains KW - Liver -- ultrastructure KW - Rats KW - Zinc -- analysis KW - Kidney Cortex -- drug effects KW - Kidney Cortex -- ultrastructure KW - Copper -- analysis KW - Kidney Tubules, Proximal -- drug effects KW - Microscopy, Electron KW - Male KW - Cadmium -- metabolism KW - Metallothionein -- analysis KW - Cadmium -- toxicity KW - Cadmium -- pharmacokinetics KW - Metallothionein -- metabolism KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79309856?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A comparison of three nucleoside analogs with anti-retroviral activity on immune and hematopoietic functions in mice: in vitro toxicity to precursor cells and microstromal environment. AN - 79308446; 2554533 AB - A number of 2'3'-dideoxynucleosides have been reported to markedly inhibit the in vitro growth of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that the continued therapeutic use of these nucleoside derivatives can be associated with adverse side effects. Since these side effects include myelotoxicity, as occurs in many patients treated with zidovudine (AZT; 3'-azido'3-deoxythymidine), and AIDS patients already represent an immunologically compromised population, we examined the immunological effects of three nucleoside inhibitors, including zidovudine, 2'3'-dideoxycytidine, and 2'3'-dideoxyadenosine (DDA) in a mouse model. Additional studies were conducted to further determine and characterize the potential toxic effects associated with these drugs on the hematopoietic system. Of the three dideoxynucleosides examined, only DDA altered immune functions following a 30-day subchronic exposure in mice. This was evidenced by a marked suppression of the antibody plaque-forming cell response and a slight alteration in macrophage function. None of the nucleoside derivatives affected bone marrow function following in vivo exposure, although AZT produced a mild macrocytic anemia in vivo and was myelotoxic when added in vitro to bone marrow cell cultures. In vitro studies indicated that AZT was capable of affecting both proliferating stem cells as well as the stromal cell microenvironment, both of which play a role in hematopoiesis. These data indicate that, although the mice may not develop the identical toxicities associated with nucleoside therapy in humans, certain adverse immunological and hematological effects were readily discerned which could have relevance to humans. JF - Toxicology and applied pharmacology AU - Luster, M I AU - Germolec, D R AU - White, K L AU - Fuchs, B A AU - Fort, M M AU - Tomaszewski, J E AU - Thompson, M AU - Blair, P C AU - McCay, J A AU - Munson, A E AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 328 EP - 339 VL - 101 IS - 2 SN - 0041-008X, 0041-008X KW - Antiviral Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Dideoxyadenosine KW - 4Q86AH641A KW - Zalcitabine KW - 6L3XT8CB3I KW - Index Medicus KW - AIDS/HIV KW - Stem Cells -- drug effects KW - HIV -- growth & development KW - Animals KW - HIV -- drug effects KW - Macrophages -- immunology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Mice KW - Macrophages -- drug effects KW - Virus Replication -- drug effects KW - Mice, Inbred C57BL KW - Immunity, Cellular -- drug effects KW - Spleen -- immunology KW - T-Lymphocytes -- drug effects KW - Spleen -- drug effects KW - Bone Marrow -- drug effects KW - T-Lymphocytes -- immunology KW - Bone Marrow -- immunology KW - Female KW - Antigen-Antibody Reactions -- drug effects KW - Zidovudine -- therapeutic use KW - Zidovudine -- toxicity KW - Hematopoiesis -- drug effects KW - Dideoxyadenosine -- therapeutic use KW - Zalcitabine -- toxicity KW - Zalcitabine -- therapeutic use KW - Dideoxyadenosine -- toxicity KW - Antiviral Agents -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79308446?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Combination of interleukins 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells. AN - 79307883; 2813429 AB - The effects of several hematopoietic growth factors on primitive murine bone marrow progenitor cells [colony-forming unit(s)-spleen (CFU-S)] have been investigated during culture for 2-6 days. Interleukin 3 (IL-3) was required for CFU-S survival in culture, and the combination of IL-3 and interleukin 6 (IL-6) increased the number of CFU-S in culture 10-fold over the number obtained with IL-3 alone. Stem cell function was measured by competitive repopulation; IL-3 was required, and IL-3 and IL-6 appear to act synergistically to enhance stem cell recovery from these cultures. These data appear to be relevant for retroviral-mediated gene transfer into stem and progenitor cells. Murine bone marrow cells were infected with a retrovirus containing the human beta-globin gene in the presence of various growth factors. Only 2 of 17 mice reconstituted with cells infected in the presence of IL-3 alone showed long-term expression of the human beta-globin gene (12 months), as opposed to 6 of 11 mice reconstituted with cells infected in the presence of IL-3 and IL-6. Medium conditioned by 5637 bladder carcinoma cells, a source of several hematopoietic growth factors, increased the frequency of infection of CFU-S but did not enhance stem cell infection or the repopulating potential of cultured bone marrow cells. Stem cells containing the human beta-globin provirus from these animals were shown to be capable of reconstituting secondary recipients in which the human beta-globin gene was expressed. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bodine, D M AU - Karlsson, S AU - Nienhuis, A W AD - Clinical Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 8897 EP - 8901 VL - 86 IS - 22 SN - 0027-8424, 0027-8424 KW - Interleukin-3 KW - 0 KW - Interleukin-6 KW - RNA, Messenger KW - Recombinant Proteins KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - RNA, Messenger -- analysis KW - Gene Expression KW - Mice KW - Mice, Inbred Strains KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Helper Viruses -- genetics KW - Retroviridae -- genetics KW - Colony-Forming Units Assay KW - Drug Synergism KW - Female KW - Transfection -- drug effects KW - Genes KW - Interleukin-3 -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Globins -- genetics KW - Interleukin-6 -- pharmacology KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79307883?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 1987 Dec 23;15(24):10159-77 [3480506] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8892-6 [2573068] Nature. 1988 Jan 7;331(6151):35-41 [2893284] J Immunol. 1988 May 1;140(9):3040-4 [3258892] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4360-4 [3288992] J Exp Med. 1988 Jun 1;167(6):1825-40 [3260264] Science. 1988 Jul 1;241(4861):58-62 [2898810] Proc Natl Acad Sci U S A. 1988 Aug;85(16):6062-6 [3413076] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099-103 [3262872] Blood. 1989 Feb;73(2):425-30 [2563662] Mol Cell Biol. 1988 Dec;8(12):5116-25 [3072474] Mol Cell Biol. 1989 Feb;9(2):798-808 [2565534] Blood. 1989 May 15;73(7):1828-35 [2469502] Nature. 1979 Oct 4;281(5730):381-2 [481601] Blood. 1980 Jan;55(1):77-81 [6985804] Virology. 1981 Apr 15;110(1):202-7 [7210505] Blood. 1983 May;61(5):823-9 [6338973] Proc Natl Acad Sci U S A. 1983 May;80(10):2931-5 [6574462] J Exp Med. 1984 Mar 1;159(3):679-90 [6699542] Mol Cell Biol. 1984 Jan;4(1):151-9 [6538258] Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070-4 [6322187] Nature. 1984 Aug 9-15;310(5977):476-80 [6087158] Science. 1984 Oct 26;226(4673):401-9 [6093246] Cell. 1985 Aug;42(1):71-9 [4016956] J Cell Physiol. 1985 Aug;124(2):182-90 [3930522] Nature. 1985 Nov 14-20;318(6042):149-54 [3903518] Science. 1985 Dec 20;230(4732):1395-8 [2999985] Exp Hematol. 1986 Mar;14(3):222-9 [3512279] Cell. 1986 Jun 20;45(6):917-27 [2871944] Science. 1986 Aug 1;233(4763):566-9 [3726549] Blood. 1989 May 15;73(7):1836-41 [2653465] Nature. 1989 May 4;339(6219):27-30 [2469962] EMBO J. 1989 Feb;8(2):441-8 [2542015] Genes Dev. 1989 Mar;3(3):314-23 [2721958] Mol Cell Biol. 1989 Apr;9(4):1426-34 [2657395] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035-9 [3501121] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Antitumor activity in mice of an immunotoxin made with anti-transferrin receptor and a recombinant form of Pseudomonas exotoxin. AN - 79300261; 2510169 AB - LysPE40 is a modified form of Pseudomonas exotoxin that lacks the cell-binding domain and has a chemically reactive lysine residue near the amino terminus. LysPE40 is made in Escherichia coli and secreted into the medium from which it is readily purified. Two immunotoxins were constructed by coupling LysPE40 to an antibody to the human transferrin receptor (TFR) or to an antibody to the human interleukin-2 receptor. These immunotoxins were selectively cytotoxic to receptor-bearing cells in tissue culture. Anti-TFR-LysPE40 given intraperitoneally to mice appeared rapidly in the blood and caused regression of A431 tumors growing as subcutaneous xenografts. These results show that it is possible to cause regression of a solid carcinoma by an immunotoxin if proper targeting can be achieved. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Batra, J K AU - Jinno, Y AU - Chaudhary, V K AU - Kondo, T AU - Willingham, M C AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 8545 EP - 8549 VL - 86 IS - 21 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Neoplasm Proteins KW - Protein Synthesis Inhibitors KW - Receptors, Interleukin-2 KW - Receptors, Transferrin KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Neoplasm Proteins -- biosynthesis KW - Recombinant Proteins -- pharmacology KW - Humans KW - Recombinant Proteins -- blood KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Antibodies, Monoclonal -- therapeutic use KW - Neoplasm Transplantation KW - Transplantation, Heterologous KW - Pseudomonas aeruginosa KW - Recombinant Proteins -- therapeutic use KW - Cell Line KW - Female KW - Exotoxins -- pharmacology KW - Exotoxins -- blood KW - Immunotoxins -- blood KW - Receptors, Interleukin-2 -- immunology KW - Carcinoma, Squamous Cell -- pathology KW - Immunotoxins -- therapeutic use KW - Receptors, Transferrin -- immunology KW - Exotoxins -- therapeutic use KW - Immunotoxins -- pharmacology KW - Carcinoma, Squamous Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79300261?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-08 N1 - Date created - 1989-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1986 Sep;83(17):6627-30 [3018739] Eur J Biochem. 1986 Feb 17;155(1):1-10 [3948873] Cell. 1987 Jan 16;48(1):129-36 [3098436] Cancer Res. 1987 Feb 15;47(4):947-52 [3492271] Proc Natl Acad Sci U S A. 1987 Apr;84(8):2474-8 [3104916] Proc Natl Acad Sci U S A. 1987 Jul;84(13):4538-42 [3299371] J Natl Cancer Inst. 1987 Nov;79(5):1163-72 [3500356] Science. 1987 Nov 20;238(4830):1098-104 [3317828] Cancer. 1988 May 1;61(9):1766-75 [2451555] Proc Natl Acad Sci U S A. 1988 May;85(9):2939-43 [3283735] J Biol Chem. 1988 Jul 5;263(19):9470-5 [3132465] Cancer Res. 1988 Nov 15;48(22):6396-403 [3263186] J Urol. 1989 Feb;141(2):428-31 [2643730] Proc Natl Acad Sci U S A. 1989 May;86(10):3778-81 [2786202] Cancer Res. 1989 Jul 1;49(13):3482-8 [2786451] J Immunol. 1981 Apr;126(4):1393-7 [6970774] J Immunol. 1981 Jul;127(1):347-51 [6787129] Proc Natl Acad Sci U S A. 1983 Jan;80(2):529-33 [6572905] Cancer Res. 1985 Feb;45(2):751-7 [2981613] Cell. 1986 Dec 5;47(5):641-8 [3536124] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Molecular analysis of O6-substituted guanine-induced mutagenesis of ras oncogenes. AN - 79299260; 2682655 AB - We have designed an Ha-ras/thymidine kinase (TK) cassette that permits the incorporation of chemically synthesized adducts within specific domains of the rat Ha-ras protooncogene. This cassette has been used to evaluate the mutagenicity of O6-substituted guanine residues, including O6-methylguanine and O6-benzylguanine, incorporated within the 12th codon of this locus. Mutations were monitored by the ability of these modified Ha-ras DNAs to transform Rat4 TK-cells. Our results indicate that both types of O6-substituted guanines are substantially mutagenic, although the methyl substituent induced a 2-fold higher percentage of transformed Rat4 TK+ colonies than its bulkier benzyl analogue. Interestingly, the mutagenicity of both O6-substituted guanines was found to be independent of their relative position within codon 12, therefore suggesting that the specific activation of Ha-ras oncogenes by GGA----GAA mutations in tumors induced by methylating carcinogens might be due to differences in the accessibility of these guanine residues to the carcinogen rather than to a differential rate of repair. Molecular analysis of the mutations induced by these O6-substituted guanines indicated that O6-methylguanine exclusively induced G----A transitions. In contrast, O6-benzylguanine produced G----C and G----T transversions in addition to G----A transitions. These results suggest that O6-methylguanine and its bulkier analogue O6-benzylguanine may induce mutagenesis by different mechanisms. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Mitra, G AU - Pauly, G T AU - Kumar, R AU - Pei, G K AU - Hughes, S H AU - Moschel, R C AU - Barbacid, M AD - Developmental Oncology, National Cancer Institute-Frederick Cancer Research Facility, MD 21701. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 8650 EP - 8654 VL - 86 IS - 22 SN - 0027-8424, 0027-8424 KW - Oligonucleotide Probes KW - 0 KW - Guanine KW - 5Z93L87A1R KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Transfection KW - Restriction Mapping KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Plasmids KW - Cell Line KW - Gene Amplification KW - Alkylation KW - Genes, ras KW - Guanine -- analysis KW - Guanine -- analogs & derivatives KW - Mutation KW - Guanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79299260?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Z Krebsforsch. 1967;69(2):103-201 [4230610] Oncogene. 1988 Dec;3(6):647-51 [2578002] J Natl Cancer Inst. 1975 Feb;54(2):401-14 [1113323] Nature. 1980 May 22;285(5762):207-10 [6246445] Virology. 1981 Aug;113(1):408-11 [7269249] Annu Rev Biochem. 1982;51:655-93 [7051963] Nature. 1983 Dec 15-21;306(5944):658-61 [6318112] Cancer Invest. 1984;2(3):223-31 [6733565] Proc Natl Acad Sci U S A. 1984 Jul;81(13):4008-12 [6330729] Nature. 1985 May 30-Jun 5;315(6018):382-5 [3923365] J Biol Chem. 1986 Jul 25;261(21):9879-85 [3525535] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5825-9 [3016723] Mol Cell Biol. 1987 Jan;7(1):379-87 [3031469] Annu Rev Biochem. 1987;56:779-827 [3304147] J Mol Biol. 1987 Apr 5;194(3):385-90 [3305959] Science. 1987 Sep 11;237(4820):1309-16 [3629242] Science. 1988 Jan 29;239(4839):487-91 [2448875] Carcinogenesis. 1988 May;9(5):691-6 [3284662] Carcinogenesis. 1988 Sep;9(9):1607-10 [3044637] Carcinogenesis. 1988 Nov;9(11):2139-43 [3180351] Mol Cell Biol. 1988 Aug;8(8):3565-9 [3062384] Adv Cancer Res. 1988;51:147-82 [3066145] Chem Res Toxicol. 1988 Jan-Feb;1(1):1-18 [2979705] Chem Res Toxicol. 1988 Nov-Dec;1(6):391-7 [2979756] Virology. 1973 Apr;52(2):456-67 [4705382] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Dietary restriction, tumors, and aging in rodents. AN - 79294054; 2681366 AB - A chronic 30-50% restriction of dietary energy intake (but without malnutrition) typically and strongly lowers the incidence of most spontaneous and induced tumors, delays their onsets, and extends maximum life span in rodents. When compared to normally fed controls, animals fed these dietary restriction (DR) regimens show decreased rates of change for most (but not all) age-sensitive biologic indexes studied to date. DR's impact on chemically induced tumors appears to depend more on energy than on fat restriction, and result from less promotion (and not less initiation). The molecular and cellular events underlying these various outcomes of DR are unclear. Viable explanations include less cellular oxidative damage, a retardation in the age-related changes in the immune system, hormonal changes, less exposure to dietary carcinogens and promoters, less energy for tumor growth, less carcinogen activation, and better DNA repair. New findings are consistent with the notion that DR reduces cellular damage mediated by active oxygen. A lower production or higher detoxification rate of active oxygen species, which damages molecules and promotes tumor growth, could explain DR's effects on aging and tumors. JF - Journal of gerontology AU - Weindruch, R AD - National Institute on Aging, Biomedical Research and Clinical Medicine Program, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 67 EP - 71 VL - 44 IS - 6 SN - 0022-1422, 0022-1422 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Animals KW - Mice KW - Longevity KW - Aging -- metabolism KW - Energy Intake KW - Neoplasms, Experimental -- metabolism KW - Neoplasms, Experimental -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79294054?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Anxiety and alcoholism. AN - 79287268; 2681171 AB - Patients with alcohol dependence commonly experience symptoms of anxiety, depression, and insomnia. It is essential that clinicians recognize and treat anxiety disorders in alcoholic patients. Panic attacks with and without agoraphobia are especially prevalent among alcoholics and their families. Treatments of choice for panic disorder are the monoamine oxidase inhibitors, as well as tricyclic antidepressants and the benzodiazepine alprazolam. Benzodiazepines seem to be effective in controlling two pathophysiologic characteristics of alcohol withdrawal--noradrenergic and hypothalamic-pituitary-adrenocortical overactivity. They also can be used to prevent and treat withdrawal seizures and delirium tremens. They are not indicated for the treatment of alcohol dependence per se. JF - The Journal of clinical psychiatry AU - Linnoila, M I AD - Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md. 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 26 EP - 29 VL - 50 Suppl SN - 0160-6689, 0160-6689 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Ethanol -- adverse effects KW - Substance Withdrawal Syndrome -- diagnosis KW - Humans KW - Substance Withdrawal Syndrome -- therapy KW - Anxiety Disorders -- etiology KW - Alcoholism -- therapy KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79287268?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-15 N1 - Date created - 1989-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Comments on the reanalysis of the National Cancer Institute study of workers exposed to formaldehyde. AN - 79286554; 2809794 JF - Journal of occupational medicine. : official publication of the Industrial Medical Association AU - Blair, A AU - Stewart, P A AD - National Cancer Institute, Division of Cancer Etiology, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 881 EP - 884 VL - 31 IS - 11 SN - 0096-1736, 0096-1736 KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Environmental Exposure KW - Middle Aged KW - Male KW - Formaldehyde -- adverse effects KW - Lung Neoplasms -- mortality KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79286554?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-08 N1 - Date created - 1989-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: J Occup Med. 1988 Nov;30(11):895-901 [3230440] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Alkyl and aryl carcinogen adducts detected in human peripheral lung. AN - 79284801; 2805234 AB - Human peripheral lung tissue samples were obtained at autopsy from 17 individuals of known occupational and smoking histories. A spectrum of different carcinogen-DNA adducts was detected using a variety of sensitive techniques. High-pressure liquid chromatography-linked synchronous fluorescent spectrophotometry and an ultrasensitive enzyme radioimmunoassay detected adducts derived from benzo[a]pyrene diol epoxide and other apparent polycyclic aromatic hydrocarbons. An amplified enzyme-linked immunosorbent assay demonstrated the presence of 4-aminobiphenyl-DNA adducts in many of these samples. A number of these specimens also contained O6-alkyldeoxyguanosine as measured by 32P-postlabeling techniques. Thus this pilot study indicates not only that human lung contains a spectrum of carcinogen-DNA adducts, but also that a full scale molecular dosimetry study of human exposure to both aryl and alkyl chemical carcinogens is warranted. JF - Carcinogenesis AU - Wilson, V L AU - Weston, A AU - Manchester, D K AU - Trivers, G E AU - Roberts, D W AU - Kadlubar, F F AU - Wild, C P AU - Montesano, R AU - Willey, J C AU - Mann, D L AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 2149 EP - 2153 VL - 10 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Smoking KW - DNA Damage KW - Humans KW - Adult KW - Environmental Exposure KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Alkylation KW - Lung -- analysis KW - DNA -- analysis KW - Carcinogens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79284801?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-18 N1 - Date created - 1989-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene via a hydroperoxide-dependent mechanism catalyzed by lipoxygenases. AN - 79284360; 2553290 AB - The lipoxygenase catalyzed epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) was examined. Epoxidation of the BP-7,8-diol was catalyzed by 5- and 15-lipoxygenase in the presence of either arachidonic acid, gamma-linolenic acid, or 15-hydroperoxyeicosatetraenoic acid (15-HPETE). The anti-9,10-epoxy-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene isomer was formed in greater quantities than the syn isomer, indicative of peroxyl radical mediated epoxidation. Epoxidation was dependent on time, enzyme and fatty acid concentration. There was no difference in the time course of epoxidation with either arachidonic acid or 15-HPETE, although the initial rate of oxygen consumption was approximately 55-fold greater with arachidonic acid. The lipoxygenase inhibitor and anti-oxidant nordihydroguaiaretic acid inhibited epoxidation in a dose-dependent manner in incubations initiated with either arachidonic acid or 15-HPETE. The anti-oxidant butylated hydroxyanisole also inhibited the epoxidation. Incubations conducted under anaerobic conditions with 15-lipoxygenase and either arachidonic acid or 15-HPETE significantly decreased epoxidation. This suggests that the oxygen inserted into BP-7,8-diol is derived from the atmosphere. The epoxidizing peroxyl radicals could not be detected but their precursors, carbon-centered radicals, were detected by using the ESR spin trapping technique in incubations of 15-lipoxygenase with 15-HPETE. This radical, formed by reduction and rearrangement of the hydroperoxide, may trap oxygen to form a peroxyl radical. We propose that the epoxidizing species is a peroxyl radical derived from 15-HPETE rather than from arachidonic acid. This proposal is based on the similar amounts of epoxidation, but dissimilar amount of oxygen consumed with both fatty acids. Since lipoxygenases are widely distributed in vivo, especially in areas where tumors arise such as the pulmonary epithelium, peroxyl radical formation by these enzymes may have an important role in chemical carcinogenesis. JF - Carcinogenesis AU - Hughes, M F AU - Chamulitrat, W AU - Mason, R P AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 2075 EP - 2080 VL - 10 IS - 11 SN - 0143-3334, 0143-3334 KW - Dihydroxydihydrobenzopyrenes KW - 0 KW - Epoxy Compounds KW - Leukotrienes KW - Lipid Peroxides KW - Peroxides KW - benzo(a)pyrene 7,8-dihydrodiol KW - 13345-25-0 KW - 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid KW - 67675-14-3 KW - Masoprocol KW - 7BO8G1BYQU KW - Lipoxygenase KW - EC 1.13.11.12 KW - Index Medicus KW - Peroxides -- metabolism KW - Oxygen Consumption KW - Electron Spin Resonance Spectroscopy KW - In Vitro Techniques KW - Lipid Peroxides -- metabolism KW - Leukotrienes -- metabolism KW - Masoprocol -- pharmacology KW - Lipoxygenase -- metabolism KW - Dihydroxydihydrobenzopyrenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79284360?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-18 N1 - Date created - 1989-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - N-nitrosocimetidine as an initiator of murine skin tumors with associated H-ras oncogene activation. AN - 79283760; 2680143 AB - N-Nitrosocimetidine (NCM) is a derivative of the drug cimetidine, a methylguanidine derivative used in the treatment of peptic ulcer, and is known to be inactive as a complete mouse skin carcinogen, even when given in repeated high doses for a long period. In the current experiment, NCM was tested for its ability to initiate skin tumors on Sencar mice. It was applied at doses of 1 or 0.3 mg, 5 times/week for 6 weeks, followed by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 microgram, 2 times/week for 50 weeks. Controls received acetone. The higher NCM dose had significant effects on TPA-promotable tumors, resulting in shortened time to first tumor, increased incidence of all tumors (2-fold) and of malignant tumors (4-fold), and greater tumor growth rate (2-fold), compared with the acetone/TPA-treated mice. The mice given the lower NCM dose did not exhibit increased tumor incidence, but their tumors had a significantly higher growth rate (3-fold) than those of the TPA controls. NCM without TPA treatment caused no tumors. Thus, NCM is a definitive, though weak initiator of TPA-promotable tumors. Nine tumors from the NCM-treatment groups were analyzed for activated oncogenes by the NIH 3T3 cell transfection assay. Five were positive and four of these were found by selective oligonucleotide hybridization analysis to have an A to T transversion in the second position of codon 61 of the H-ras oncogene. One of two tumors from the acetone/TPA group also contained transforming DNA and demonstrated this mutation. None of the tumors had a G----A transition mutation at the second position of codon 12 of this oncogene. Tumor initiation by NCM may then be associated with the same oncogene mutation reported for mouse skin tumors initiated by other types of carcinogens, although occurrence of the mutated oncogene in TPA controls precludes a definitive conclusion. JF - Carcinogenesis AU - Anderson, L M AU - Enomoto, T AU - Perantoni, A O AU - Riggs, C W AU - Kovatch, R M AU - Reed, C D AU - Giner-Sorolla, A AU - Rice, J M AD - Division of Cancer Etiology, NCI-Frederick Cancer Research Facility, MD 21701. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 2009 EP - 2013 VL - 10 IS - 11 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - nitrosocimetidine KW - 73785-40-7 KW - Cimetidine KW - 80061L1WGD KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Cocarcinogenesis KW - Dose-Response Relationship, Drug KW - Mice KW - Mutation KW - Survival Analysis KW - Skin Neoplasms -- genetics KW - Genes, ras KW - Skin Neoplasms -- chemically induced KW - Skin Neoplasms -- pathology KW - Cimetidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79283760?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-18 N1 - Date created - 1989-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Similar molecular requirements for antigen receptor-triggered secretion of interferon and granule enzymes by cytolytic T lymphocytes. AN - 79274653; 2478302 AB - At least two biologically significant responses are triggered by the crosslinking of the T-cell receptor (TcR) on the surface of cloned cytotoxic T lymphocytes (CTL): synthesis and secretion of macrophage-activating factor(s) (MAF) that can be attributed to interferon-gamma (IFN) and release of preformed cytolytic granules. We directly compared the molecular requirements for synthesis and secretion of IFN and secretion of granule enzymes triggered in the same cell by the same activating ligand (antigen or monoclonal antibody (mAb) to TcR). An increase in the surface density of activating ligand (immobilized anti-TcR mAb) enhanced both secretion of IFN and secretion of granules. Secretion of IFN occurred immediately after synthesis: only low (but detectable) levels of IFN were detected in cell cytosolic or particulate fractions isolated from Percoll gradients of lysed CTL, while very high levels of IFN were found in the stimulated CTL culture fluids. Inhibitors of RNA synthesis and protein synthesis blocked secretion of IFN, but did not inhibit release of preformed cytolytic granules. The requirement for TcR crosslinking in triggering both secretion of granules and secretion of IFN from CTL was pharmacologically reproduced by the synergistic action of PMA, a protein kinase C activator, and the Ca2+ ionophore A23187. Both secretion of IFN and secretion of granules were absolutely dependent upon extracellular Ca2+: EGTA completely blocked both TcR- and PMA/A23187-induced secretion of IFN and exocytosis of granules. These studies suggest that similar molecular mechanisms are involved in secretion of newly synthesized IFN and secretion of preformed cytolytic granules. One notable difference between the molecular requirements for the two secretory events was a much lower concentration requirement for PMA for IFN synthesis and secretion than for granule secretion in the synergistic interactions with A23187. Implications of these studies for the exocytosis model of cell-mediated cytotoxicity are discussed. JF - Cellular immunology AU - Fortier, A H AU - Nacy, C A AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 64 EP - 76 VL - 124 IS - 1 SN - 0008-8749, 0008-8749 KW - Receptors, Antigen, T-Cell KW - 0 KW - Interferons KW - 9008-11-1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Granzymes KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Serine Endopeptidases -- secretion KW - Calcium -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Protein Kinase C -- physiology KW - Mice, Inbred DBA KW - Cytoplasmic Granules -- enzymology KW - Interferons -- secretion KW - Receptors, Antigen, T-Cell -- physiology KW - T-Lymphocytes, Cytotoxic -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79274653?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-07 N1 - Date created - 1989-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Novel exogenous heme-dependent expression of mammalian cytochrome P450 using baculovirus. AN - 79271344; 2679389 AB - Rat P450 IIA1 is a membrane-bound hemoprotein that catalyzes the 7 alpha- and 6 alpha-hydroxylation of testosterone. A recombinant baculovirus, containing the cDNA encoding IIA1, was constructed and used to infect Spodoptera frugiperda cells. Infected cells contained up to 10% IIA1 protein as quantified by Western blot analysis; however, only a small percentage of this protein contained heme and was catalytically active. Addition of hemin to the culture medium during the course of viral infection resulted in a marked sixfold increase in both testosterone hydroxylase activity and heme-containing IIA1 protein. When the exogenously added protoheme was substituted with modified heme molecules containing hydrogen or ethyl groups at the 2 and 4 positions of the protoporphyrin IX, enzymes with only marginal changes in catalytic properties were produced. These data indicate that baculovirus can be used as a system to produce high levels of mammalian cytochrome P450s containing custom modified heme moieties. JF - Archives of biochemistry and biophysics AU - Asseffa, A AU - Smith, S J AU - Nagata, K AU - Gillette, J AU - Gelboin, H V AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/11/01/ PY - 1989 DA - 1989 Nov 01 SP - 481 EP - 490 VL - 274 IS - 2 SN - 0003-9861, 0003-9861 KW - Apoproteins KW - 0 KW - Heme KW - 42VZT0U6YR KW - Hemin KW - 743LRP9S7N KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - testosterone 7-alpha-hydroxylase, hamster KW - Index Medicus KW - Rats KW - Hemin -- pharmacology KW - Animals KW - Genetic Vectors KW - Recombination, Genetic KW - Steroid Hydroxylases -- metabolism KW - Spectrophotometry KW - Apoproteins -- metabolism KW - Insect Viruses -- genetics KW - Heme -- pharmacology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Heme -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79271344?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-03 N1 - Date created - 1989-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Interleukin 2, interleukin 2 receptor, and interferon-gamma synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T cells from elderly humans. AN - 79226848; 2507204 AB - The levels of interleukin 2 (IL-2), interleukin 2 receptor (IL-2R), and interferon-gamma (IFN-gamma) specific mRNA and their gene products were examined in phorbol myristate acetate (PMA) and calcium ionophore A23187-costimulated purified T cells from young and elderly humans. In addition, the number of high-affinity IL-2R per activated cell, the high-affinity IL-2R density, and the proliferative response of the cells were measured. Among PMA/A23187-stimulated T cells, there was no statistically significant age-related difference in IL-2 or IL-2R specific mRNA accumulation or in the amount of IL-2 or IL-2R synthesized. IFN-gamma specific mRNA was increased significantly in T cells from elderly individuals and the amount of IFN-gamma synthesized by PMA/A23187-activated T cells was nearly double that produced by cells from young individuals. Quantification of the number of high-affinity IL-2R by [125I]IL-2 binding demonstrated there was no decrease in either the mean number or the dissociation constant of the high-affinity IL-2R on activated T cells of the elderly. Despite producing large amounts of IL-2 and having comparable numbers of both low- and high-affinity IL-2R. PMA/A23187-stimulated T cells from elderly subjects still proliferated less vigorously than did T cells from young persons. The addition of exogenous IL-2 to the cultured cells did not fully correct this age difference. Our findings that the expression of the IL-2, IL-2R, and IFN-gamma genes are not constitutionally defective in the elderly support the hypothesis that the age-related decline in proliferation observed in mitogen-stimulated T cells of the elderly is most likely attributable to alterations in the transmission of signals from the cell membrane to the nucleus. JF - Clinical immunology and immunopathology AU - Chopra, R K AU - Holbrook, N J AU - Powers, D C AU - McCoy, M T AU - Adler, W H AU - Nagel, J E AD - Clinical Immunology Section, National Institute on Aging, Baltimore, Maryland 21224. Y1 - 1989/11// PY - 1989 DA - November 1989 SP - 297 EP - 308 VL - 53 IS - 2 Pt 1 SN - 0090-1229, 0090-1229 KW - Interleukin-2 KW - 0 KW - RNA, Messenger KW - Receptors, Interleukin-2 KW - Calcimycin KW - 37H9VM9WZL KW - Interferon-gamma KW - 82115-62-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Adult KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Aged KW - Gene Expression Regulation -- drug effects KW - Calcimycin -- pharmacology KW - RNA, Messenger -- genetics KW - Lymphocyte Activation -- drug effects KW - Receptors, Interleukin-2 -- physiology KW - Aging KW - Interferon-gamma -- biosynthesis KW - T-Lymphocytes -- physiology KW - Interleukin-2 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79226848?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-21 N1 - Date created - 1989-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Ultraviolet mutagenesis in a plasmid vector replicated in lymphoid cells from patient with the melanoma-prone disorder dysplastic nevus syndrome. AN - 79225097; 2790806 AB - The hereditary dysplastic nevus syndrome (DNS) is an autosomal dominant disorder in which affected individuals have increased numbers of dysplastic (premalignant) nevi and a greater than 100-fold increased risk of developing cutaneous melanoma. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS have been shown to be hypermutable to UV radiation (M.I.R. Perera et al., Cancer Res., 46: 1005-1009, 1986). To examine the mechanism involved in this UV hypermutability, we used a shuttle vector plasmid, pZ189, which carries a 160-base pair marker gene, supF, and can replicate in human cells. pZ189 was treated with UV radiation and transfected into DNS6BE, a lymphoblastoid cell line from a patient with hereditary DNS. Plasmid survival after UV was similar with the DNS6BE line and with a lymphoblastoid cell line from a normal donor. Plasmid mutation frequency was greater with the DNS line in accord with the DNS cellular hypermutability. Base sequence analysis was performed on 69 mutated plasmids recovered from the DNS line. There were significantly more plasmids with single base substitution mutations (P less than 0.01) in comparison to UV-treated plasmids passed through normal fibroblasts. pZ189 hypermutability and an increased frequency of single base substitutions was previously found with a cell line from a melanoma-prone xeroderma pigmentosum patient. These differences may be related to the increased melanoma susceptibility in both DNS and xeroderma pigmentosum. JF - Cancer research AU - Seetharam, S AU - Waters, H L AU - Seidman, M M AU - Kraemer, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/11/01/ PY - 1989 DA - 1989 Nov 01 SP - 5918 EP - 5921 VL - 49 IS - 21 SN - 0008-5472, 0008-5472 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - DNA, Neoplasm -- radiation effects KW - Base Sequence KW - Base Composition KW - Disease Susceptibility KW - Humans KW - Adult KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Lymphocytes -- cytology KW - Female KW - Cell Line KW - Ultraviolet Rays KW - DNA Replication -- radiation effects KW - Melanoma -- genetics KW - Genetic Vectors KW - Dysplastic Nevus Syndrome -- genetics KW - Plasmids -- radiation effects KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79225097?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-20 N1 - Date created - 1989-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Neurogenic component of phorbol ester-induced mouse skin inflammation. AN - 79221543; 2790819 AB - Tumor-promoting phorbol esters are potent inflammatory agents for mouse skin, and the potential mechanistic role of inflammation in tumor promotion is under active investigation. We have shown previously that resiniferatoxin, a uniquely irritant phorbol-related diterpene, acts as a capsaicin analogue to induce and then to block neurogenic inflammation. We report here that pretreatment of CD-1 mice with resiniferatoxin blocked the early (3 h) erythema and edema (6 h) in response to phorbol 12-myristate 13-acetate (PMA), whereas the edema at later times (12-24 h) was only partially blocked. Since the efficiency of resiniferatoxin pretreatment decreased as a function of time if PMA was applied 24, 48, or 96 h after resiniferatoxin administration, the late edema response to PMA may be a combination of increasing edema of nonneurogenic origin and the recovering neurogenic response due to the decreasing desensitization. For other phorbol esters, 12-deoxyphorbol mono- and diesters, and mezerein, differing kinetics of edema and differing degrees of blockade of edema following resiniferatoxin pretreatment were observed, as expected from the discrepancies between their inflammatory and tumor-promoting activities. PMA-induced skin hyperplasia, unlike edema, was not inhibited by resiniferatoxin pretreatment, suggesting that the early component of neurogenic inflammation was not essential for hyperplasia under our conditions. Distinction between inflammatory mechanisms may help to clarify the role of inflammation in tumor promotion. JF - Cancer research AU - Szallasi, A AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/11/01/ PY - 1989 DA - 1989 Nov 01 SP - 6052 EP - 6057 VL - 49 IS - 21 SN - 0008-5472, 0008-5472 KW - Diterpenes KW - 0 KW - Phorbol Esters KW - Terpenes KW - mezerein KW - 34807-41-5 KW - resiniferatoxin KW - A5O6P1UL4I KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Terpenes -- toxicity KW - Tetradecanoylphorbol Acetate -- toxicity KW - Mice, Inbred Strains KW - Animals KW - Hyperplasia KW - Dose-Response Relationship, Drug KW - Mice KW - Female KW - Administration, Topical KW - Inflammation KW - Erythema -- chemically induced KW - Diterpenes -- pharmacology KW - Skin -- drug effects KW - Diterpenes -- administration & dosage KW - Skin -- pathology KW - Skin -- innervation KW - Phorbol Esters -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79221543?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-20 N1 - Date created - 1989-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Enhancement of hydroxylation and deglycosylation of 2'-deoxyguanosine by carcinogenic nickel compounds. AN - 79220351; 2790811 AB - The effects of nickel subsulfide (Ni3S2) and nickel chloride [Ni(II)] on hydroxylation and deglycosylation of pure 2'-deoxyguanosine (dG) and on hydroxylation of guanine (Gu) residues in calf thymus DNA in the absence or presence of hydrogen peroxide (H2O2) and/or ascorbate (Ascb) were studied with the use of high-performance liquid chromatography. Incubation of 0.75 mM dG with 5 mg Ni3S2/ml (particle size less than 5 microns) at 37 degrees C in aerated 50 mM Tris/HCl buffer, pH 7.4, resulted in slow hydroxylation of dG to 8-hydroxy-2'-deoxyguanosine (8-OH-dG). This effect was greatly enhanced by 20 mM H2O2. Ni(II) alone at concentrations up to 10 mM was inactive but produced 8-OH-dG in the presence of 20 mM H2O2; the latter caused no dG hydroxylation by itself. Both Ni3S2 and Ni(II) increased the formation of 8-OH-dG from dG exposed to H2O2 + Ascb. At pH 7.4 and constant concentration of H2O2 and Ascb (20 and 8 mM, respectively), Ni(II) over the concentration range 1-10 mM raised the hydroxylation yield by up to five times that without Ni(II). Also, addition of 7.5 mM Ni(II) more than doubled the hydroxylation yield of Gu residues by the 20 mM H2O2 + 8 mM Ascb mixture (pH 7.4) in denatured DNA and doubled it in native DNA. Ni3S2 and Ni(II) alone had no effect on deglycosylation of dG and did not significantly influence the slow rate of Gu production from dG reacting with H2O2 or Ascb at pH 7.4. However, Ni(II), unlike Ni3S2, increased the extent of dG deglycosylation when added to the dG + H2O2 + Ascb system; 10 mM Ni(II) increased deglycosylation by a factor of 2.5 in 24 h. Thus, nickel carcinogens were shown for the first time to cause and/or enhance both hydroxylation and deglycosylation reactions of dG which may contribute to the observed genotoxic and carcinogenic effects of this metal. JF - Cancer research AU - Kasprzak, K S AU - Hernandez, L AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick, Maryland 21701-1013. Y1 - 1989/11/01/ PY - 1989 DA - 1989 Nov 01 SP - 5964 EP - 5968 VL - 49 IS - 21 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - nickel subsulfide KW - 12035-72-2 KW - nickel chloride KW - 696BNE976J KW - Nickel KW - 7OV03QG267 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Deoxyguanosine KW - G9481N71RO KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Chemistry KW - Kinetics KW - Hydrogen-Ion Concentration KW - Chemical Phenomena KW - Hydrolysis KW - Hydroxylation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79220351?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-20 N1 - Date created - 1989-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - FAB/MS/MS for the determination of biomolecules: A compendium AN - 21267212; 11793918 AB - First page of article. JF - Mass Spectrometry Reviews AU - Tomer, Kenneth B AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709 Y1 - 1989/11// PY - 1989 DA - Nov 1989 SP - 483 EP - 511 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 8 IS - 6 SN - 0277-7037, 0277-7037 KW - Biotechnology and Bioengineering Abstracts KW - Reviews KW - Mass spectroscopy KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21267212?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Reviews; Mass spectroscopy DO - http://dx.doi.org/10.1002/mas.1280080603 ER - TY - JOUR T1 - MPTP treatment combined with ethanol or acetaldehyde selectively destroys dopaminergic neurons in mouse substantia nigra. AN - 79271336; 2572305 AB - We have previously reported that ethanol and acetaldehyde potentiate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, enhancing dopamine (DA) depletion in the striatum. The present study was designed to determine whether such enhancement of neurotoxicity was specific for the nigro-striatal DA pathway. In 5-week-old mice acetaldehyde treatment did not enhance DA depletion seen 7 days after MPTP treatment. In 8-week-old animals, however, acetaldehyde or ethanol given with MPTP decreased striatal DA content to about 10% of controls, whereas the depletion was to 43% of controls when MPTP was given alone. In acetaldehyde or ethanol and MPTP-treated mice, changes in DA levels were observed only in the striatum. DA contents in the hypothalamus, olfactory bulb and frontal cortex were similar to that in controls. Contents of norepinephrine and serotonin in striatum, hypothalamus, olfactory bulb and cerebral cortex were not affected by any of the treatments. Three months after MPTP alone, striatal DA recovered to 74% of controls in 8-week-old mice, whereas no recovery occurred in acetaldehyde and MPTP-treated mice. Moreover, both tyrosine hydroxylase (TH) immunocytochemistry and Cresyl violet staining showed an extensive and selective cell loss in the pars compacta of the substantia nigra (SNc) of the mice treated with acetaldehyde or ethanol and MPTP, whereas MPTP alone caused only a limited cell degeneration. JF - Brain research AU - Zuddas, A AU - Corsini, G U AU - Schinelli, S AU - Johannessen, J N AU - di Porzio, U AU - Kopin, I J AD - Clinical Neuroscience Branch, NINDS, Bethesda, MD 20892. Y1 - 1989/10/30/ PY - 1989 DA - 1989 Oct 30 SP - 1 EP - 10 VL - 501 IS - 1 SN - 0006-8993, 0006-8993 KW - Serotonin KW - 333DO1RDJY KW - Ethanol KW - 3K9958V90M KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Acetaldehyde KW - GO1N1ZPR3B KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Drug Interactions KW - Norepinephrine -- metabolism KW - Mice, Inbred C57BL KW - Mice KW - Serotonin -- metabolism KW - Male KW - Substantia Nigra -- metabolism KW - Aging -- metabolism KW - Acetaldehyde -- pharmacology KW - Substantia Nigra -- pathology KW - Ethanol -- pharmacology KW - MPTP Poisoning KW - Substantia Nigra -- drug effects KW - Dopamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79271336?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-20 N1 - Date created - 1989-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Acetaldehyde directly enhances MPP+ neurotoxicity and delays its elimination from the striatum. AN - 79268665; 2804689 AB - We have previously shown that ethanol and acetaldehyde (ACE) potentiate MPTP toxicity in mice, selectively enhancing dopamine (DA) depletion in the striatum and markedly increasing loss of DA neurons in the substantia nigra. Several months after these combined treatments there is no evidence of any recovery. In the present study, we measured the accumulation of the MPTP toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) in both striatum and whole brain, after MPTP alone or after combined treatments with ethanol or acetaldehyde, in order to determine whether this enhancement of toxicity is caused by changes in the MPTP metabolism. We also investigated whether acetaldehyde interfered with the conversion of MPTP to MPP+ by glial cells in vitro and studied its effects on the MPP+ uptake and spontaneous release from mesencephalic DA neurons or striatal astrocytes in primary cell cultures from E13 mouse embryos. The results from the in vivo experiments indicated that relatively low doses of ethanol or acetaldehyde potentiate directly MPP+ toxicity, apparently without interfering with its pharmacokinetics. However when higher doses of these drugs were administered, they also decreased MPP+ clearance from the striatum. ACE also increased initial MPTP accumulation in the whole brain but failed to enhance MPP+ levels, thus indicating that ACE effect is not related to MPTP metabolism. In vitro studies confirmed that ACE does not modify MPTP metabolism in striatal or mesencephalic astrocytes in culture. In mesencephalic neuronal cultures ACE does not change the levels of MPP+ uptake (MPP+ is accumulated in putative DA neurons in vitro with a mechanism similar to that of the DA high affinity uptake) nor its spontaneous release. These results indicate that the slower MPP+ clearance from the stratum after ACE is not related to a direct effect of ACE on DA neurons or astrocytes. JF - Brain research AU - Zuddas, A AU - Corsini, G U AU - Schinelli, S AU - Barker, J L AU - Kopin, I J AU - di Porzio, U AD - Clinical Neuroscience Branch, NINDS, Bethesda, MD 20892. Y1 - 1989/10/30/ PY - 1989 DA - 1989 Oct 30 SP - 11 EP - 22 VL - 501 IS - 1 SN - 0006-8993, 0006-8993 KW - Ethanol KW - 3K9958V90M KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Acetaldehyde KW - GO1N1ZPR3B KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - Animals KW - Drug Interactions KW - Astrocytes -- cytology KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- metabolism KW - Astrocytes -- drug effects KW - Mice, Inbred C57BL KW - Ethanol -- toxicity KW - Mice KW - Male KW - Astrocytes -- metabolism KW - Corpus Striatum -- cytology KW - 1-Methyl-4-phenylpyridinium -- pharmacokinetics KW - Acetaldehyde -- pharmacology KW - 1-Methyl-4-phenylpyridinium -- toxicity KW - MPTP Poisoning KW - Corpus Striatum -- metabolism KW - Corpus Striatum -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79268665?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-20 N1 - Date created - 1989-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Phosphoroselenoate oligodeoxynucleotides: synthesis, physico-chemical characterization, anti-sense inhibitory properties and anti-HIV activity. AN - 79306829; 2682524 AB - Oligodeoxynucleotides with a phosphorus atom in which one of the non-bridging oxygen atoms is substituted by selenium were prepared and investigated with respect to their antisense properties. A general synthesis of phosphoroselenoate analogs of oligonucleotides is described using potassium selenocyanate as the selenium donor. The compounds, characterized by 31P NMR, were shown to decompose to phosphate with a half-life of ca. 30 days. Melting temperatures of duplexes between poly(rA) or poly(rI) with oligo(dT) and oligo(dC), respectively, indicate diminished hybridization capability of phosphoroselenoate oligomers relative to both the unmodified phosphodiester oligomers and the phosphorothioate congeners. A phosphoroselenoate 17-mer is a sequence specific inhibitor of rabbit beta-globin synthesis in wheat germ extract and in injected Xenopus oocytes. In contrast phosphoroselenoate analogs are potent non-sequence specific inhibitors in rabbit reticulocyte lysate. In vitro HIV assays were carried out on a phosphoroselenoate sequence and compared with a phosphorothioate analogue that has previously been shown to exhibit anti-HIV activity (Matsukura et al., Proc. Natl. Acad. Sci. (1987) 84, 7706-7710). The phosphoroselenoate was somewhat less active, and was much more toxic to the cells. JF - Nucleic acids research AU - Mori, K AU - Boiziau, C AU - Cazenave, C AU - Matsukura, M AU - Subasinghe, C AU - Cohen, J S AU - Broder, S AU - Toulmé, J J AU - Stein, C A AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/25/ PY - 1989 DA - 1989 Oct 25 SP - 8207 EP - 8219 VL - 17 IS - 20 SN - 0305-1048, 0305-1048 KW - Antiviral Agents KW - 0 KW - DNA, Antisense KW - Indicators and Reagents KW - Oligodeoxyribonucleotides KW - Organophosphorus Compounds KW - Polyribonucleotides KW - RNA, Messenger KW - Globins KW - 9004-22-2 KW - DNA KW - 9007-49-2 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Nucleic Acid Denaturation KW - Plants -- metabolism KW - Globins -- genetics KW - Rabbits KW - Magnetic Resonance Spectroscopy KW - Base Sequence KW - Oocytes -- metabolism KW - Reticulocytes -- metabolism KW - Molecular Sequence Data KW - Xenopus KW - Female KW - RNA, Messenger -- antagonists & inhibitors KW - Protein Biosynthesis -- drug effects KW - HIV -- drug effects KW - Antiviral Agents -- chemical synthesis KW - RNA, Messenger -- drug effects KW - Selenium -- pharmacology KW - Oligodeoxyribonucleotides -- pharmacology KW - Organophosphorus Compounds -- pharmacology KW - Organophosphorus Compounds -- chemical synthesis KW - Oligodeoxyribonucleotides -- chemical synthesis KW - RNA, Messenger -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79306829?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-04 N1 - Date created - 1989-12-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene. 1988 Dec 10;72(1-2):343-7 [3243433] Proc Natl Acad Sci U S A. 1988 Oct;85(19):7079-83 [3174622] Biochemistry. 1989 Feb 7;28(3):1340-6 [2469468] Pharm Res. 1988 Sep;5(9):539-49 [3073387] Nucleic Acids Res. 1989 Jun 12;17(11):4255-73 [2472605] Anal Biochem. 1978 Apr;85(2):506-18 [646104] Methods Enzymol. 1983;101:370-86 [6193395] Annu Rev Biochem. 1985;54:367-402 [2411211] J Chromatogr. 1985 Jun 19;326:263-80 [4030945] Biochemistry. 1985 Jul 2;24(14):3630-8 [4041432] Nucleic Acids Res. 1986 Aug 26;14(16):6433-51 [3018671] Nucleic Acids Res. 1987 May 11;15(9):3877-90 [3588311] Nucleic Acids Res. 1987 Jun 25;15(12):4717-36 [3037483] Nucleic Acids Res. 1987 Jul 24;15(14):5749-63 [3475677] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7706-10 [3499613] Cancer Res. 1988 May 15;48(10):2659-68 [3282648] EMBO J. 1988 Feb;7(2):427-34 [2452730] Nucleic Acids Res. 1988 Apr 25;16(8):3209-21 [2836790] Nucleic Acids Res. 1988 Jun 10;16(11):5137-51 [3387220] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5011-5 [2839827] Gene. 1988 Dec 10;72(1-2):51-8 [2468575] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents. AN - 79288511; 2572588 AB - Acquired resistance to multiple natural products in vitro is mediated by P-glycoprotein (Pgp). Expression of this protein has been demonstrated in some normal tissues and in tumor samples obtained from both untreated and treated patients. In situ hybridizations with RNA probes have demonstrated higher levels of expression of mdr-1/Pgp in well-differentiated tumors and in well-differentiated areas in tumors with mixed histologies. Expression of mdr-1/Pgp in human colon carcinoma cell lines was increased by the differentiating agents sodium butyrate, dimethyl sulfoxide, and dimethylformamide. In the SW-620 cell line addition of sodium butyrate resulted in a rapid induction of mdr-1/Pgp mRNA that was sustained for the duration of the exposure. The levels of P-glycoprotein were measured by immunoblotting and were also increased. Similar results were obtained in three other cell lines including the HCT-15 line. This induction occurred without alterations in nuclease sensitivity. Discontinuation of sodium butyrate was followed by a rapid fall in the levels of mRNA. The levels of P-glycoprotein returned to normal with a half-life of about 24 h. In spite of a 20-25-fold increase in the level of mdr-1/Pgp mRNA and P-glycoprotein, the SW-620 cell line did not demonstrate increased resistance to doxorubicin and vinblastine or decreased accumulation of vinblastine. In contrast, in the HCT-15 cell line, a 5-fold increase of mdr-1/Pgp was accompanied by a comparable fall in vinblastine accumulation which was reversed by verapamil. In the SW-620 cell line, the induced protein could be photolabeled using [3H]azidopine. Expression of mdr-1/Pgp appears to correlate with the degree of differentiation. However, its induction is not always accompanied by expression of the multidrug-resistance phenotype. JF - The Journal of biological chemistry AU - Mickley, L A AU - Bates, S E AU - Richert, N D AU - Currier, S AU - Tanaka, S AU - Foss, F AU - Rosen, N AU - Fojo, A T AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/25/ PY - 1989 DA - 1989 Oct 25 SP - 18031 EP - 18040 VL - 264 IS - 30 SN - 0021-9258, 0021-9258 KW - Blood Proteins KW - 0 KW - Butyrates KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA Probes KW - RNA, Messenger KW - Sulfuric Acid Esters KW - Sulfuric Acids KW - Butyric Acid KW - 107-92-6 KW - Dimethylformamide KW - 8696NH0Y2X KW - dimethyl sulfate KW - JW5CW40Z50 KW - Index Medicus KW - Transcription, Genetic -- drug effects KW - Humans KW - Cell Division -- drug effects KW - RNA, Messenger -- genetics KW - Cell Differentiation -- drug effects KW - Colonic Neoplasms KW - Cell Line KW - Blood Proteins -- genetics KW - Drug Resistance -- genetics KW - Dimethylformamide -- pharmacology KW - Genes, Neoplasm -- drug effects KW - Butyrates -- pharmacology KW - Sulfuric Acids -- pharmacology KW - Sulfuric Acid Esters -- pharmacology KW - Gene Expression KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79288511?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-27 N1 - Date created - 1989-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Synergy between a selective D1 antagonist and a selective D2 antagonist in the induction of catalepsy. AN - 79568903; 2485878 AB - The cataleptogenic effects of the selective D1 dopamine receptor antagonist, SCH 23390, and the selective D2 dopamine receptor antagonist, raclopride, when administered alone or in combination were studied in rats using the vertical grid and horizontal bar methods. In either model both agents, given alone, produced dose-dependent catalepsy. When administered together, there was a marked synergy between the two drugs. Thus, a low dose of SCH 23390 resulted in a 10-fold shift to the left of the raclopride dose-effect curve. When the same low dose of SCH 23390 was administered together with a subcataleptogenic dose of raclopride, marked catalepsy was produced. The finding of synergy between selective D1 and D2 dopamine antagonists in the induction of catalepsy suggests that mixed antagonists may possess greater antipsychotic activity than neuroleptics acting mainly on one receptor subtype. JF - Neuroscience letters AU - Parashos, S A AU - Marin, C AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/10/23/ PY - 1989 DA - 1989 Oct 23 SP - 169 EP - 173 VL - 105 IS - 1-2 SN - 0304-3940, 0304-3940 KW - Benzazepines KW - 0 KW - Dopamine Antagonists KW - Salicylamides KW - Raclopride KW - 430K3SOZ7G KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Benzazepines -- pharmacology KW - Dose-Response Relationship, Drug KW - Salicylamides -- pharmacology KW - Drug Synergism KW - Male KW - Catalepsy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79568903?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-12-06 N1 - Date created - 1990-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Alcohols selectively stimulate phospholipase D-mediated hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. AN - 79284746; 2806564 AB - Addition of alcohols to NIH 3T3 fibroblasts, prelabeled with [2-14C]ethanolamine, resulted in increased degradation of [14C]phosphatidylethanolamine (PtdEtn). Long-chain alcohols, like octanol or nonanol, were more potent than methanol or ethanol. The main water-soluble product of alcohol-stimulated [14C]PtdEtn hydrolysis was [14C]ethanolamine. Addition of ethanol to cells, specifically prelabeled with [32P]PtdEtn, enhanced the formation of [32P]phosphatidic acid (PtdOH), suggesting the involvement of a phospholipase D-type enzyme. At lower concentration (10-150 mM), ethanol acted through a protein kinase C (PKC)-independent mechanism. At higher concentrations (150-300 mM), the effect of ethanol was partially inhibited both by the PKC inhibitor H7 and by the down-regulation of PKC achieved by treatment of cells with 200 nM TPA for 24 h, suggesting that activation of PKC contributed to the ethanol effect. JF - FEBS letters AU - Kiss, Z AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/23/ PY - 1989 DA - 1989 Oct 23 SP - 45 EP - 48 VL - 257 IS - 1 SN - 0014-5793, 0014-5793 KW - Alcohols KW - 0 KW - Phosphatidylethanolamines KW - Ethanol KW - 3K9958V90M KW - Phospholipases KW - EC 3.1.- KW - Phospholipase D KW - EC 3.1.4.4 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Ethanol -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Hydrolysis KW - Phospholipase D -- metabolism KW - Phosphatidylethanolamines -- metabolism KW - Phospholipases -- metabolism KW - Alcohols -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79284746?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Tat trans-activates the human immunodeficiency virus through a nascent RNA target. AN - 79275812; 2478293 AB - Expression of the human immunodeficiency virus type 1 (HIV-1) genome is greatly dependent on the viral trans-activator protein Tat. Tat functions through the TAR element, which is represented in both viral DNA and RNA. At present, there is no definitive evidence that determines whether Tat acts through a DNA or RNA form of TAR. We have used an intramolecular mutagenesis approach to change selectively the RNA secondary structure of TAR without affecting its primary sequence. We show that a specific RNA secondary structure for TAR is needed for biological activity. Furthermore, transcripts that only transiently form a native TAR RNA hairpin, which is not maintained in the mature mRNA, are completely trans-activated by Tat, suggesting that TAR is recognized as a nascent RNA. JF - Cell AU - Berkhout, B AU - Silverman, R H AU - Jeang, K T AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/10/20/ PY - 1989 DA - 1989 Oct 20 SP - 273 EP - 282 VL - 59 IS - 2 SN - 0092-8674, 0092-8674 KW - Gene Products, tat KW - 0 KW - RNA, Antisense KW - RNA, Messenger KW - RNA, Viral KW - Trans-Activators KW - Viral Structural Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - RNA KW - 63231-63-0 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Gene Expression Regulation, Viral KW - Gene Expression KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Plasmids KW - RNA, Messenger -- antagonists & inhibitors KW - Base Sequence KW - Enhancer Elements, Genetic KW - Molecular Sequence Data KW - Mutation KW - Cell Line KW - RNA -- genetics KW - Trans-Activators -- metabolism KW - HIV-1 -- genetics KW - HIV-1 -- growth & development KW - Genes, Viral KW - RNA, Viral -- genetics KW - Virus Activation KW - Gene Products, tat -- metabolism KW - Viral Structural Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79275812?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-04 N1 - Date created - 1989-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Evaluation of the effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA) on HIV-1 production in vitro. AN - 79272428; 2478129 AB - Effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of the common Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4.), on HIV-1 production was evaluated in vitro. Reverse transcriptase (RT) activity in the supernatant was inhibited by nearly 50% in EHNA-treated HIV-1 infected H9 cells, when compared with untreated but infected H9 cells. There was also a significant decrease in cell viability, but this was reversed following the addition of deoxycytidine (dC) to these cultures. The combined treatment was also effective in suppressing HIV-1 release from HIV-1-infected U937 cells. This combined EHNA plus dC treatment had no effect on RT activity in the cell lysates, suggesting that the inhibition of HIV-1 production may be due to the disturbance of virus release from infected cells. JF - Biochemical and biophysical research communications AU - Sei, Y AU - Inoue, M AU - Tsuboi, I AU - Yokoyama, M M AU - Arora, P K AD - Laboratory of Neuroscience, NIDDK, Bethesda, MD 20892. Y1 - 1989/10/16/ PY - 1989 DA - 1989 Oct 16 SP - 345 EP - 350 VL - 164 IS - 1 SN - 0006-291X, 0006-291X KW - Adenosine Deaminase Inhibitors KW - 0 KW - Antiviral Agents KW - HIV Envelope Protein gp120 KW - Deoxycytidine KW - 0W860991D6 KW - 9-(2-hydroxy-3-nonyl)adenine KW - 59262-86-1 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - Adenine KW - JAC85A2161 KW - Index Medicus KW - AIDS/HIV KW - HIV Envelope Protein gp120 -- metabolism KW - Flow Cytometry KW - RNA-Directed DNA Polymerase -- metabolism KW - Drug Synergism KW - Deoxycytidine -- pharmacology KW - Cell Line KW - Virus Replication -- drug effects KW - Antiviral Agents -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects KW - Adenine -- analogs & derivatives KW - Adenine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79272428?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-20 N1 - Date created - 1989-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Excitatory amino acid neurotoxicity at the N-methyl-D-aspartate receptor in cultured neurons: role of the voltage-dependent magnesium block. AN - 79270458; 2572299 AB - Results of the present report show that cerebellar neurons in primary culture are resistant to glutamate concentrations as high as 5 mM in the presence of glucose and Mg2+, but sensitive to glutamate concentrations lower than 35 microM when the neurons are deprived of glucose. Glutamate toxicity is also potentiated when Mg2+ is removed but glucose and EDTA are present; in this case, higher concentrations of glutamate (1 mM) are required for full toxicity. Glucose concentrations as low as 50 microM are fully protective against the toxicity of 100 microM glutamate; pyruvate and, to a lesser extent, lactate are also protective. Significantly, increasing concentrations of extracellular Mg2+ are fully protective against the toxicity of 100 microM glutamate in the absence of glucose and against the toxicity of 1 mM glutamate in the presence of glucose and EDTA. We interpret these results as support for our hypothesis that the pivotal event in glutamate's transition to neurotoxin is relief of the Mg2+ block of the N-methyl-D-aspartate (NMDA) receptor channel, which is known to be voltage-dependent. Partial depolarization in response to depletion of high-energy phosphates relieves the voltage-dependent block enabling glutamate to stimulate an excessive ion influx which results in the death of the neuron by a mechanism which is not yet understood. We propose that this mechanism may be operative in the neuronal damage associated with a variety of neurodegenerative disorders. JF - Brain research AU - Cox, J A AU - Lysko, P G AU - Henneberry, R C AD - Molecular Neurobiology Section, NINDS, Bethesda, MD 20892. Y1 - 1989/10/16/ PY - 1989 DA - 1989 Oct 16 SP - 267 EP - 272 VL - 499 IS - 2 SN - 0006-8993, 0006-8993 KW - Glutamates KW - 0 KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, Neurotransmitter KW - Glutamic Acid KW - 3KX376GY7L KW - Magnesium KW - I38ZP9992A KW - Index Medicus KW - Receptors, Neurotransmitter -- physiology KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Cells, Cultured KW - Cerebellum -- cytology KW - Cerebellum -- drug effects KW - Magnesium -- pharmacology KW - Neurotoxins -- pharmacology KW - Glutamates -- toxicity KW - Cerebellum -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79270458?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-01 N1 - Date created - 1989-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Excitatory amino acid neurotoxicity at the N-methyl-D-aspartate receptor in cultured neurons: pharmacological characterization. AN - 79268503; 2572298 AB - L-Glutamate neurotoxicity at the N-methyl-D-aspartate (NMDA) receptor was characterized in cultured cerebellar granule cells. When deprived of glucose for 40 min, these cells were killed by 20-60 microM L-glutamate. However, the neurons were resistant to glutamate at concentrations as high as 5 mM when glucose and Mg2+ were present throughout. Both competitive and non-competitive NMDA receptor antagonists completely blocked neurotoxicity due to glutamate and other NMDA receptor agonists. CPP [+/-)-3-(2-carboxypiperazin-4-yl)-prophyl-1-phosphonic acid) was the most effective competitive antagonist with full protection at 100 microM while MK-801 [+/-)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]-cyclohepten-5,10-imin e) was the most effective non-competitive antagonist with full protection at 20 nM. Other antagonists with higher selectivity for other subtypes of glutamate receptors were ineffective. We conclude that glutamate toxicity in energy-deprived cerebellar granule cells is mediated by NMDA receptors. Results are discussed in terms of an hypothesis offering an explanation for the transition of glutamate from neurotransmitter to neurotoxin which emphasizes the responsiveness of the receptor to agonists rather than focusing on the presence of high concentrations of agonist. JF - Brain research AU - Lysko, P G AU - Cox, J A AU - Vigano, M A AU - Henneberry, R C AD - Molecular Neurobiology Section, NINDS, Bethesda, MD 20892. Y1 - 1989/10/16/ PY - 1989 DA - 1989 Oct 16 SP - 258 EP - 266 VL - 499 IS - 2 SN - 0006-8993, 0006-8993 KW - Dibenzocycloheptenes KW - 0 KW - Glutamates KW - Neurotoxins KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, Neurotransmitter KW - Glutamic Acid KW - 3KX376GY7L KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Cell Survival -- drug effects KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Cells, Cultured KW - Receptors, Neurotransmitter -- antagonists & inhibitors KW - Dibenzocycloheptenes -- pharmacology KW - Cerebellum -- cytology KW - Cerebellum -- drug effects KW - Neurotoxins -- pharmacology KW - Glutamates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79268503?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-01 N1 - Date created - 1989-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Digital necrosis and disseminated Pneumocystis carinii infection after aerosolized pentamidine prophylaxis. AN - 79262753; 2802423 JF - Annals of internal medicine AU - Davey, R T AU - Margolis, D AU - Kleiner, D AU - Deyton, L AU - Travis, W AD - National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 681 EP - 682 VL - 111 IS - 8 SN - 0003-4819, 0003-4819 KW - Aerosols KW - 0 KW - Pentamidine KW - 673LC5J4LQ KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Pneumonia, Pneumocystis -- prevention & control KW - Acquired Immunodeficiency Syndrome -- complications KW - Necrosis -- chemically induced KW - Humans KW - Adult KW - Pneumonia, Pneumocystis -- etiology KW - Recurrence KW - Male KW - Pentamidine -- administration & dosage KW - Toes -- pathology KW - Pneumocystis KW - Pentamidine -- adverse effects KW - Mycoses -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79262753?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-30 N1 - Date created - 1989-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modes of death and types of cardiac diseases in opiate addicts: analysis of 168 necropsy cases. AN - 79259085; 2801561 AB - One hundred sixty-eight opiate addicts, whose hearts were submitted for necropsy study, were examined with prime focus on modes of death and types of cardiac abnormalities. Twenty various modes of death were identified: active infective endocarditis or its consequences in 67 (40%), drug overdose in 39 (24%), coronary artery disease in 14 (8%), pulmonary granulomatosis in 7 (4%) and 15 various diseases (7 cardiac and 8 noncardiac) in the remaining 41 (24%) patients. Of the 168 hearts examined, only 7 (4%) were normal. Although infective endocarditis (active, healed or both) was most common (80 [48%] patients), there was a broad range of other cardiac abnormalities present: cardiomegaly in 114 (68%) (including 22 patients without another cardiac abnormality), coronary artery disease in 35 (21%), acquired valvular heart disease in 16 (10%), myocardial heart disease in 14 (8%) and a congenital cardiac anomaly in 19 (11%). Of the 35 hearts with various coronary artery diseases, 28 had significant (greater than 75%) narrowing of the cross-sectional area of 1 or more of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries by atherosclerotic plaque. Of 112 coronary arteries in these 28 hearts, 52 (46%) were significantly narrowed (a mean of 1.9 of the 4 major coronary arteries/patient). In 27 of these 28 cases, each 5-mm segment of the 4 major coronary arteries was examined histologically. Of the 1,435 five-mm segments examined, 189 (13%) were narrowed 76 to 100% in cross-sectional area by plaque; 347 (24%), 51 to 75%; 336 (23%), 26 to 50%; and 563 segments (39%) were narrowed 0 to 25% in cross-sectional area by plaque. The percents of 5-mm segments narrowed 76 to 100% in cross-sectional area were greater in those patients with (128 of 793 [16%]) than without (61 of 642 [9%]) clinical evidence of myocardial ischemia (p = 0.001). In this study a very high frequency of cardiac abnormalities (161 [96%]) was found at necropsy and most deaths (97 [58%]) were related to cardiac disease. Although death was most often due to diseases whose association to opiate addiction is well recognized (such as infective endocarditis, drug overdose and pulmonary granulomatosis from the venous injection of talc), several other modes of death were present. Most prominent among these was coronary artery disease (14 patients [8%]). JF - The American journal of cardiology AU - Dressler, F A AU - Roberts, W C AD - Pathology Branch, National Institutes of Health, Bethesda, Maryland. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 909 EP - 920 VL - 64 IS - 14 SN - 0002-9149, 0002-9149 KW - Narcotics KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Kidney Diseases -- pathology KW - Calcinosis -- pathology KW - Myocardium -- pathology KW - Humans KW - Aged KW - Organ Size KW - Kidney Diseases -- mortality KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Cardiomyopathies -- pathology KW - Coronary Disease -- pathology KW - Adult KW - Middle Aged KW - Chronic Disease KW - Adolescent KW - Male KW - Female KW - Substance-Related Disorders -- blood KW - Narcotics -- blood KW - Substance-Related Disorders -- mortality KW - Heart Diseases -- mortality KW - Substance-Related Disorders -- complications KW - Heart Diseases -- etiology KW - Heart Diseases -- pathology KW - Cause of Death UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79259085?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The rise in concentration of free Ca2+ and of pH provides sequential, synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells. AN - 79237327; 2794509 AB - Ag stimulation of rat basophilic leukemia (RBL-2H3) cells results in hydrolysis of inositol phospholipids, a transient increase in concentration of cytosol Ca2+ [( Ca2+]i), a gradual increase in cytosolic pH (pHi) and the activation of protein kinase C. To determine whether all these changes serve as signals for secretion, studies were conducted with cells permeabilized with streptolysin O in which pHi and [Ca2+]i could be varied independently of each other and enzyme activities could be manipulated. At resting pHi (approximately 7.0) and [Ca2+]i (0.1 microM), the permeabilized cells showed little secretory response to Ag. At resting pHi, elevated levels of Ca2+ (0.33 microM) were required for maximal secretory response to Ag. At a pHi of 7.4, however, 0.1 microM [Ca2+]i was sufficient to sustain near maximal responses to Ag. Therefore, a small increase of [Ca2+]i to 0.33 microM was required to initiate secretion, but once the pHi was elevated secretion could be sustained at near basal levels of [Ca2+]i. Since elevating the [Ca2+]i and pHi, by themselves promoted little secretion, another potentiating signal must have been generated by antigen stimulation. This signal was possibly transduced via hydrolysis of inositol phospholipids and protein kinase C. Even with an elevated [Ca2+]i (0.33 microM) the hydrolysis of the phospholipids and secretion stimulated by Ag were inhibited by guanosine 5'(2-O-thio)diphosphate and neomycin. Furthermore, both protein-kinase C and the secretory response to Ag were lost after permeabilized cells were washed but both were retained if cells were exposed to PMA before permeabilization. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ali, H AU - Collado-Escobar, D M AU - Beaven, M A AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 2626 EP - 2633 VL - 143 IS - 8 SN - 0022-1767, 0022-1767 KW - Antigens KW - 0 KW - Dinitrophenols KW - Inositol Phosphates KW - Serum Albumin, Bovine KW - Immunoglobulin E KW - 37341-29-0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Inositol Phosphates -- metabolism KW - Leukemia -- immunology KW - Hydrogen-Ion Concentration KW - Dinitrophenols -- immunology KW - Hydrolysis KW - Leukemia -- enzymology KW - Rats KW - Immunoglobulin E -- immunology KW - Leukemia -- metabolism KW - Serum Albumin, Bovine -- immunology KW - Cell Membrane Permeability KW - Protein Kinase C -- physiology KW - Drug Synergism KW - Cell Line KW - Cell-Free System KW - Calcium -- metabolism KW - Basophils -- enzymology KW - Basophils -- metabolism KW - Antigens -- immunology KW - Signal Transduction KW - Basophils -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79237327?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Studies of protein kinase C in the rat basophilic leukemia (RBL-2H3) cell reveal that antigen-induced signals are not mimicked by the actions of phorbol myristate acetate and Ca2+ ionophore. AN - 79235936; 2551964 AB - Exogenous activators of protein kinase C such as PMA in combination with a Ca2+ ionophore (A23187), cause secretion in rat basophilic (RBL-2H3) cells,but they do so through stimulatory signals that are not the same as those generated by Ag or oligomers of IgE. On the one hand, the synergy between PMA and A23187 and the suppression of Ag-mediated signals (hydrolysis of inositol phospholipids and rise in concentration of cytosolic Ca2+) by PMA were totally dependent on protein kinase C. The loss of synergistic and inhibitory actions of PMA, for example, correlated with the loss of protein kinase C (as determined by immunoblotting techniques) when cells were continuously exposed to PMA. Furthermore, the permeabilization of RBL-2H3 cells resulted in the loss of both protein kinase C and the inhibitory action of PMA, but both were retained if cells were exposed to PMA before permeabilization Ag-induced secretion, on the other hand, was not as dependent on the presence of protein kinase C. The potent inhibitor of this enzyme, staurosporine, which blocked completely the secretory response to the combination of PMA and A23187, did not inhibit Ag-induced secretion except at concentrations (greater than 10 nM) that inhibited Ag-stimulated hydrolysis of inositol phospholipids as well. Also RBL-2H3 cells still showed some secretory-response (approximately 25% of normal) to Ag when cells were depleted (greater than 98%) of protein kinase C by prolonged treatment with PMA. Previous studies have indicated that the secretory response to PMA and A23187 is much lower than that elicited by Ag when the concentrations of stimulants were matched to give the same increase in concentrations of cytosolic Ca2+. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cunha-Melo, J R AU - Gonzaga, H M AU - Ali, H AU - Huang, F L AU - Huang, K P AU - Beaven, M A AD - Laboratory of Chemical Pharmacology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 2617 EP - 2625 VL - 143 IS - 8 SN - 0022-1767, 0022-1767 KW - Alkaloids KW - 0 KW - Antigens KW - Phosphatidylinositols KW - Calcimycin KW - 37H9VM9WZL KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Phosphatidylinositols -- metabolism KW - Animals KW - Leukemia -- metabolism KW - Leukemia -- immunology KW - Kinetics KW - Enzyme Activation -- drug effects KW - Alkaloids -- pharmacology KW - Leukemia -- enzymology KW - Cell Line KW - Protein Kinase C -- metabolism KW - Basophils -- physiology KW - Basophils -- enzymology KW - Protein Kinase C -- antagonists & inhibitors KW - Signal Transduction -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Protein Kinase C -- physiology KW - Calcimycin -- pharmacology KW - Basophils -- metabolism KW - Antigens -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79235936?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab')2, and Fab in tumors. AN - 79226846; 2790783 AB - In order to understand the pharmacology of monoclonal antibodies and their conjugates, one must consider both global and microscopic aspects of antibody distribution. Here we present an analysis of antibody distribution in tumors based on the following factors: (a) molecular weight and valence of the antibody; (b) global pharmacokinetic profile following i.v. bolus injection; (c) penetration through the vascular wall; (d) diffusive and convective transport through interstitial space in the tumor; (e) antigen-antibody interaction; (f) antibody metabolism. Partial differential equations were developed to incorporate these factors and then solved numerically using parameter values from animal experiments, from clinical protocols at our institution, from studies of antibody binding characteristics in vitro, and from the literature. Salient findings from this model are that (a) antigen-antibody interaction in the tumor can retard antibody percolation away from blood capillaries, thus constituting a "binding site barrier"; (b) high antibody affinity tends to decrease antibody penetration and result in a more heterogeneous distribution; (c) high molecular weight [IgG greater than F(ab')2 greater than Fab] slows percolation and results in less uniform spatial distribution; (d) the average antibody concentration in the tumor does not increase linearly with antibody dose; (e) raising the rate of antibody metabolism results in low concentration and poor percolation; (f) perhaps most interesting, there is predicted to be a range of antibody dose and affinity within which the specificity ratio and average concentration could be kept high while limiting the heterogeneity of distribution. PERC, the computer program package developed for these analyses, provides a convenient and flexible way to assess the impact of global and microscopic parameters on the distribution of immunoglobulin in tumors. For calculations presented here, the input data were obtained from experimental sources, and qualitative features of the output proved consistent with the few interpretable observations available. However, detailed validation would require much more data than are currently at hand. The mathematical findings should therefore be considered as aids to concept development and as a set of null hypotheses with which to guide experimentation. Experiments and simulations will continue in tandem. It should be noted that the PERC package (and also the general principles delineated here) can be applied as well to biological ligands other than antibodies. JF - Cancer research AU - Fujimori, K AU - Covell, D G AU - Fletcher, J E AU - Weinstein, J N AD - Laboratory of Mathematical Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 5656 EP - 5663 VL - 49 IS - 20 SN - 0008-5472, 0008-5472 KW - Immunoglobulin Fab Fragments KW - 0 KW - Immunoglobulin G KW - Immunotoxins KW - Index Medicus KW - Software KW - Neoplasms -- blood supply KW - Antibody Affinity KW - Neoplasms -- therapy KW - Molecular Weight KW - Structure-Activity Relationship KW - Models, Theoretical KW - Immunotoxins -- pharmacokinetics KW - Immunoglobulin G -- pharmacokinetics KW - Immunoglobulin Fab Fragments -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79226846?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-15 N1 - Date created - 1989-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Sister chromatid exchange and chromosome fragility in the nevoid basal cell carcinoma syndrome. AN - 79223006; 2507127 AB - Previous studies of chromosome stability in the nevoid basal cell carcinoma syndrome have yielded inconsistent results and suffered from small sample sizes and less than optimal controls. We investigated chromosome fragility and sister chromatid exchange in 20 affected individuals from five multiplex pedigrees, and 15 first- or second-degree unaffected relatives. The percentage of case and control cells showing breaks or rearrangements was compared using a test of proportions. A similar procedure was used to compare site-specific sister chromatid exchanges in baseline cultures from affected persons and controls. No significant differences were noted for either chromosome fragility or sister chromatid exchange between the two groups. These results suggest that cancer susceptibility in the nevoid basal cell carcinoma syndrome is not caused by or manifested as chromosome instability. JF - Cancer genetics and cytogenetics AU - Bale, A E AU - Bale, S J AU - Murli, H AU - Ivett, J AU - Mulvihill, J J AU - Parry, D M AD - Clinical Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 273 EP - 279 VL - 42 IS - 2 SN - 0165-4608, 0165-4608 KW - Mitomycins KW - 0 KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Mitomycin KW - 50SG953SK6 KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - Index Medicus KW - Humans KW - 4-Nitroquinoline-1-oxide -- pharmacology KW - Cells, Cultured KW - Adult KW - Chromosome Fragility KW - Methylnitronitrosoguanidine -- pharmacology KW - Lymphocytes -- cytology KW - Middle Aged KW - Mitomycins -- pharmacology KW - Lymphocytes -- drug effects KW - Female KW - Male KW - Carcinoma, Basal Cell -- genetics KW - Sister Chromatid Exchange KW - Basal Cell Nevus Syndrome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79223006?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-21 N1 - Date created - 1989-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Preferential sites for viral integration on mammalian genome. AN - 79221488; 2551486 AB - Chromosomal localization of human papillomavirus (HPV) 16 and 18 on human cervical carcinomas and epithelial cell lines obtained after HPV transfection has uncovered a nonrandom association of viral integration and specific genome sites. Fragile sites appear to be preferential targets for viral integration because of their structural and functional characteristics through which chromosomal anomalies, alterations in protooncogene activity, and gene amplification can occur. Individually or in association, such changes lead to the acquisition of an unlimited cell growth potential but not tumorigenicity. Genetic instability and uncontrolled cell division resulting from HPV integration increase the cell's susceptibility to other exogenous carcinogenic factors that may complete the process of neoplastic development. JF - Cancer genetics and cytogenetics AU - Popescu, N C AU - DiPaolo, J A AD - Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/15/ PY - 1989 DA - 1989 Oct 15 SP - 157 EP - 171 VL - 42 IS - 2 SN - 0165-4608, 0165-4608 KW - Index Medicus KW - Karyotyping KW - Chromosome Banding KW - Humans KW - Proto-Oncogenes KW - Chromosome Mapping KW - Female KW - Papillomaviridae -- isolation & purification KW - Uterine Cervical Neoplasms -- microbiology KW - Uterine Cervical Neoplasms -- genetics KW - Papillomaviridae -- genetics KW - Genes, Viral KW - Genomic Library UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79221488?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-21 N1 - Date created - 1989-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors. AN - 79222716; 2551505 AB - The bovine papillomavirus E5 transforming gene encodes a 44 amino acid protein product that is localized to cytoplasmic membranes, including the plasma membrane. We now report that E5 can cooperate with human EGF receptors and with human CSF-1 receptors to induce cellular transformation of NIH 3T3 cells. Cooperation occurred in the absence of receptor stimulation by ligand, and it was further augmented by treatment with ligand. Cooperation was not seen between E5 and either c-fes or c-src. The cooperation between E5 and high levels of EGF receptors was associated with inhibition of receptor degradation and persistence of activated receptors on the cell surface. We conclude that E5 may enhance the receptor activity via inhibition of receptor down-modulation. JF - Cell AU - Martin, P AU - Vass, W C AU - Schiller, J T AU - Lowy, D R AU - Velu, T J AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/06/ PY - 1989 DA - 1989 Oct 06 SP - 21 EP - 32 VL - 59 IS - 1 SN - 0092-8674, 0092-8674 KW - Colony-Stimulating Factors KW - 0 KW - Oncogene Proteins, Viral KW - Proto-Oncogene Proteins KW - Receptors, Cell Surface KW - Receptors, Colony-Stimulating Factor KW - oncogene protein E5, Bovine papillomavirus type 1 KW - Transforming Growth Factors KW - 76057-06-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Humans KW - Mice KW - Drug Synergism KW - Transforming Growth Factors -- biosynthesis KW - Proto-Oncogene Proteins -- physiology KW - Cell Line KW - Receptors, Cell Surface -- metabolism KW - Colony-Stimulating Factors -- metabolism KW - Receptor, Epidermal Growth Factor -- metabolism KW - Papillomaviridae -- physiology KW - Receptor, Epidermal Growth Factor -- physiology KW - Oncogene Proteins, Viral -- physiology KW - Bovine papillomavirus 1 -- physiology KW - Receptors, Cell Surface -- physiology KW - Cell Transformation, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79222716?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-08 N1 - Date created - 1989-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Targeted toxin therapy for the treatment of cancer. AN - 79203774; 2550658 AB - Protein toxins such as Pseudomonas exotoxin, diphtheria toxin, and ricin may be useful in cancer therapy because they are among the most potent cell-killing agents. One molecule of a toxin delivered to the cytoplasm of a cancer cell will be lethal for that cell. However, to be therapeutically useful, these toxins need to be targeted to specific sites on the surface of cancer cells, then be internalized and ultimately reach the cell cytoplasm. This process is accomplished by eliminating binding to toxin receptors and redirecting the cell-killing activity of the toxin to receptors or antigens present on cancer cells. Typically, toxins are conjugated to cell-binding proteins such as monoclonal antibodies or growth factors. These conjugates bind and kill cancer cells selectively while normal cells, which don't bind the conjugates, are spared. Because the genes for many protein toxins have been cloned, it is possible to make genetic modifications to their structure. By deleting the DNA that codes for the toxin binding region and replacing it with various complementary DNA encoding other cell-binding proteins, it has been possible to make chimeric toxins that kill cells on the basis of the newly acquired binding activity. The ability to make these chimeras may be useful in designing future toxin-based anticancer therapies. JF - Journal of the National Cancer Institute AU - FitzGerald, D AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/04/ PY - 1989 DA - 1989 Oct 04 SP - 1455 EP - 1463 VL - 81 IS - 19 SN - 0027-8874, 0027-8874 KW - Antibodies, Monoclonal KW - 0 KW - Diphtheria Toxin KW - Exotoxins KW - Immunotoxins KW - Receptors, Cell Surface KW - Ricin KW - 9009-86-3 KW - Index Medicus KW - Animals KW - Humans KW - Receptors, Cell Surface -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Ricin -- therapeutic use KW - Immunotoxins -- therapeutic use KW - Diphtheria Toxin -- therapeutic use KW - Pseudomonas KW - Exotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79203774?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Occupational risks of bladder cancer in the United States: II Nonwhite men. AN - 79199802; 2778835 AB - Occupational risks of bladder cancer among nonwhite men were assessed based on interviews with 126 cases and 383 controls conducted during the National Bladder Cancer Study, a population-based, case-control study conducted in 10 areas of the United States. Our findings indicated that nonwhite men who were ever employed as auto workers have an elevated risk of bladder cancer [relative risk (RR) = 2.3; 95% confidence intervals (CI) = 0.8-6.4] with a significant positive trend in RR with increasing duration of employment (P = .017) and with the RR rising to 4.7 for those employed at least 10 years. Dry cleaners, ironers, and pressers also experienced increased bladder cancer risk (RR = 2.8, CI = 1.1-7.4). Nonsignificant excesses of similar magnitude to those seen among white men were found for nonwhite men employed in several other occupations. Overall, our findings suggest that the risk of occupational bladder cancer among white and nonwhite men is similar. When inconsistencies between whites and nonwhites did occur, they appeared either due to chance or possibly racial differences in exposure among men within the same industry and occupation. In all, we estimate that the population attribute risk for occupation among nonwhite U.S. men is 27% (CI = 9% to 56%), which is slightly higher than the estimate of 21% to 25% previously reported for white U.S. men, although this difference was not statistically significant. JF - Journal of the National Cancer Institute AU - Silverman, D T AU - Levin, L I AU - Hoover, R N AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/04/ PY - 1989 DA - 1989 Oct 04 SP - 1480 EP - 1483 VL - 81 IS - 19 SN - 0027-8874, 0027-8874 KW - Index Medicus KW - United States KW - Age Factors KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Aged KW - Middle Aged KW - Textile Industry KW - Time Factors KW - Male KW - Urinary Bladder Neoplasms -- epidemiology KW - African Americans KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79199802?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Identification of a new P450 expressed in human lung: complete cDNA sequence, cDNA-directed expression, and chromosome mapping. AN - 79405439; 2574990 AB - A cDNA coding for a P450 expressed in human lung was isolated from a lambda gt11 library constructed from human lung mRNA using a cDNA probe to rat P450 IVA1. The cDNA-deduced amino acid sequence of this P450, designated IVB1, consisted of 511 amino acids and had a calculated molecular weight of 59,558. The IVB1 amino acid sequence bore 51%, 53%, and 52% similarities to rat IVA1, IVA2, and rabbit P450p-2, respectively. Comparison of the primary amino acid sequence of human IVB1 with rat IVA and rabbit p-2 P450 sequences revealed a region of absolute sequence identity of 17 amino acids between residues 304 and 320. However, the functional significance of this conserved sequence is unknown. Human IVB1 also appears to be related to P450 isozyme 5 that has been extensively characterized in rabbits. The IVB1 cDNA was inserted into a vaccinia virus expression vector and the enzyme expressed in human cell lines. The expressed enzyme had an absorption spectrum with a lambda max at 450 nm when reduced and complexed with carbon monoxide, typical of other cytochrome P450s. Unlike rabbit P450 isozyme 5, however, human IVB1 was unable to activate the promutagen 2-aminofluorene. Human lung microsomal P450s were also unable to metabolize this compound despite the presence of IVB1 mRNA in three out of four human lungs analyzed. In contrast to its expression in lung, IVB1 mRNA was undetectable in livers from 14 individuals, including those from which the lungs were derived. IVB1-related mRNA was also expressed in rat lung and was undetectable in untreated rat liver.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Nhamburo, P T AU - Gonzalez, F J AU - McBride, O W AU - Gelboin, H V AU - Kimura, S AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/03/ PY - 1989 DA - 1989 Oct 03 SP - 8060 EP - 8066 VL - 28 IS - 20 SN - 0006-2960, 0006-2960 KW - Mutagens KW - 0 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Vaccinia virus -- genetics KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mutagens -- pharmacokinetics KW - Rabbits KW - Chromosome Mapping KW - Cloning, Molecular KW - Rats KW - Chromosomes, Human, Pair 1 KW - Base Sequence KW - Biotransformation KW - Polymorphism, Restriction Fragment Length KW - Molecular Sequence Data KW - Gene Expression Regulation, Enzymologic KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Lung -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79405439?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-15 N1 - Date created - 1990-02-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02871; GENBANK N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Computer-assisted evaluation of polydisperse two-dimensional gel patterns of polysaccharide-protein conjugate preparations with regard to size and net charge. AN - 85269075; pmid-2612463 AB - Native Hemophilus influenzae polysaccharide-protein conjugate particles were analyzed by a two-dimensional agarose electrophoresis procedure. In view of their preparation by random chemical crosslinking, the conjugates necessarily exhibit a polydisperse two-dimensional gel pattern which varies depending on the conditions of the particular preparation. The polydisperse patterns were interpreted with regard to the size and surface net charge density of the conjugate on the basis of the extended Ogston model. Data processing was performed by a new program, designated ZWEIDI.DO, written in the language of M-LAB (modeling laboratory). The program computes particle and gel fiber specific parameters from the positions of standards and unknown(s) on the two-dimensional gel using a simultaneous linear least-square curve fitting routine. Based on these calculations, the program serves to compute a nomogram of iso-size and iso-free-mobility profiles. Superimposing these profiles on the gel patterns, the size and free mobility range of the polydisperse conjugate mixtures is obtained. Potentially, the procedure could serve as a tool for quality control in the production of conjugates as vaccines and for the physical characterization of polydisperse subcellular particles and vesicles. JF - Electrophoresis AU - Tietz, D AU - Chrambach, A AD - Section on Macromolecular Analysis, National Institute of Child Health and Human Development, Bethesda, MD 20892. PY - 1989 SP - 667 EP - 680 VL - 10 IS - 10 SN - 0173-0835, 0173-0835 KW - Software KW - Bacterial Proteins KW - Haemophilus influenzae KW - Electrophoresis, Gel, Two-Dimensional KW - Electrophoresis, Agar Gel KW - Densitometry KW - Models, Theoretical KW - Computer Simulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269075?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - EEG and brainstem auditory evoked response potentials in adult male drug abusers with self-reported histories of aggressive behavior. AN - 85257717; pmid-2790098 AB - Auditory brainstem evoked response (BAER) and spontaneous electroencephalogram (EEG) were measured in 124 adult male drug abusers. We examined the relationships among psychiatric diagnoses, paper and pencil measures of aggression and hostility, and electrophysiological features. Subjects meeting criteria for antisocial personality disorder (ASP), as defined by DSM-III, were not significantly different from non-ASP subjects for either BAER or spontaneous EEG measures. The more overtly aggressive subjects had significant delays in BAER latency. Aggressive subjects also had more delta activity and less alpha activity in the spontaneous EEG, as have been observed in "psychopaths" and "criminals." Although ASP and aggression are related, these data indicate that aggressiveness may be a separate, albeit overlapping, trait. As both early aggression and a diagnosis of ASP are predictors of later drug use, the findings that only aggression was associated with EEG slowing and brainstem delays may indicate that ASP and aggression make independent contributions to vulnerability to the development of drug abuse. JF - Biological Psychiatry AU - Fishbein, D H AU - Herning, R I AU - Pickworth, W B AU - Haertzen, C A AU - Hickey, J E AU - Jaffe, J H AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. PY - 1989 SP - 595 EP - 611 VL - 26 IS - 6 SN - 0006-3223, 0006-3223 KW - Arousal KW - Human KW - MMPI KW - Alcoholism KW - Adult KW - Evoked Potentials, Auditory KW - Brain Stem KW - Substance-Related Disorders KW - Antisocial Personality Disorder KW - Aggression KW - Male KW - Reaction Time KW - Electroencephalography KW - Psychotropic Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85257717?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells. AN - 79579007; 2518795 AB - Pretreatment of mammalian cell with DNA-damaging agents, such as UV light or mitomycin C, but not the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), results in the enhanced repair of subsequently transfected UV-damaged expression vectors. To determine the cellular factors that are responsible for this enhancement, we have used a modified gel retardation assay to detect the proteins that interact with damaged DNA. We have identified a constitutive DNA binding protein in extracts from primate cells that has a high affinity for UV-irradiated double-stranded DNA. Cells pretreated with UV light, mitomycin C, or aphidicolin, but not TPA or serum starvation, have higher levels of this damage-specific DNA binding (DDB) protein. These results suggest that the signal for induction of DDB protein can either be damage to the DNA or interference with cellular DNA replication. The induction of DDB protein varies among primate cells with different phenotypes: (1) virus-transformed repair-proficient cells have partially or fully lost the ability to induce DDB protein above constitutive levels; (2) primary cells from repair-deficient xeroderma pigmentosum (XP) group C, and transformed XP groups A and D, show constitutive DDB protein, but do not show induced levels of this protein 48 h after UV; and (3) primary and transformed repair-deficient cells from one XP E patient are lacking both the constitutive and the induced DDB activity. The correlation between the induction of the DDB protein and the enhanced repair of UV-damaged expression vectors implies the involvement of the DDB protein in this inducible cellular response. JF - Molecular toxicology AU - Protić, M AU - Hirschfeld, S AU - Tsang, A P AU - Wagner, M AU - Dixon, K AU - Levine, A S AD - Section on Viruses and Cellular Biology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. PY - 1989 SP - 255 EP - 270 VL - 2 IS - 4 SN - 0883-9492, 0883-9492 KW - Culture Media KW - 0 KW - DNA-Binding Proteins KW - Diterpenes KW - Mitomycins KW - Aphidicolin KW - 38966-21-1 KW - Mitomycin KW - 50SG953SK6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Diterpenes -- pharmacology KW - Animals KW - Ultraviolet Rays KW - Humans KW - Plasmids -- radiation effects KW - Haplorhini KW - Phenotype KW - Blood KW - Base Sequence KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Plasmids -- drug effects KW - Mitomycins -- pharmacology KW - Cell Line KW - DNA Repair -- radiation effects KW - DNA-Binding Proteins -- drug effects KW - DNA-Binding Proteins -- biosynthesis KW - DNA Damage -- radiation effects KW - DNA-Binding Proteins -- radiation effects KW - DNA Repair -- drug effects KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79579007?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1991-09-19 N1 - Date created - 1991-09-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The acidic amino-terminal region of the HIV-1 Tat protein constitutes an essential activating domain. AN - 79572463; 2562188 AB - The Tat protein encoded by the human immunodeficiency virus (HIV) is an efficient activator of HIV gene expression. Many eukaryotic transcriptional activators contain a nucleic acid binding domain and a separate activating domain. These activating regions are acidic and often amphipathic. The amino terminus of the HIV-1 Tat protein is acidic with a periodicity of acidic, polar, and hydrophobic residues consistent with that of an amphipathic alpha helix. This region appears to be important for Tat function. We have analyzed the functional significance of acidic residues within the amino-terminal region of Tat by means of site-directed mutagenesis and by testing the capacity of mutant proteins to trans-activate the viral long terminal repeat (LTR) Conservative changes (acidic to acidic) were well tolerated, whereas acidic to neutral and acidic to basic changes markedly reduced Tat activity. The relative importance of each of the three acidic residues correlated with proximity to the amino terminus. Substitution of the entire domain with heterologous sequences that might form an acidic, amphipathic alpha helix partially restored activity when compared with an amino-terminal truncation mutant. In contrast to the observed importance of acidic residues, hydroxylated residues between amino acids 40 and 47 were dispensable for Tat function. These data suggest that the acidity of the amino terminal region is important for Tat function and that Tat-mediated trans-activation may be similar to that of other known activator proteins. JF - The New biologist AU - Rappaport, J AU - Lee, S J AU - Khalili, K AU - Wong-Staal, F AD - Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 101 EP - 110 VL - 1 IS - 1 SN - 1043-4674, 1043-4674 KW - Gene Products, tat KW - 0 KW - Recombinant Fusion Proteins KW - tat Gene Products, Human Immunodeficiency Virus KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - DNA -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Gene Products, tat -- physiology KW - HIV-1 -- genetics KW - Gene Expression Regulation, Viral KW - Gene Products, tat -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79572463?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1991-04-29 N1 - Date created - 1991-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Anxiolytic properties of 1-aminocyclopropanecarboxylic acid, a ligand at strychnine-insensitive glycine receptors. AN - 79474881; 2576136 AB - The effects of 1-aminocyclopropanecarboxylic acid were investigated on performance in an elevated plus-maze. This compound is a high-affinity, partial agonist ligand at strychnine-insensitive glycine receptors of the N-methyl-D-aspartate receptor complex. Like chlordiazepoxide, 1-aminocyclopropanecarboxylic acid increased in a dose-dependent manner both the percent entries into and the percent time spent in the open arms of the plus-maze. However, 1-aminocyclopropanecarboxylic acid was significantly less efficacious than chlordiazepoxide in these measures and increased, while chlordiazepoxide decreased, the time spent in the middle platform of the plus-maze. These findings indicate that ligands acting through strychnine-insensitive glycine receptors on the N-methyl-D-aspartate receptor complex may represent a new class of anxiolytic agents with a profile which differs from the benzodiazepines. JF - Pharmacology, biochemistry, and behavior AU - Trullas, R AU - Jackson, B AU - Skolnick, P AD - Laboratory of Neuroscience, NIDDK, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 313 EP - 316 VL - 34 IS - 2 SN - 0091-3057, 0091-3057 KW - Amino Acids KW - 0 KW - Amino Acids, Cyclic KW - Anti-Anxiety Agents KW - Receptors, Glycine KW - Receptors, Neurotransmitter KW - 1-aminocyclopropane-1-carboxylic acid KW - 3K9EJ633GL KW - Strychnine KW - H9Y79VD43J KW - Index Medicus KW - Animals KW - Conflict (Psychology) KW - Task Performance and Analysis KW - Mice KW - Male KW - Anti-Anxiety Agents -- pharmacology KW - Receptors, Neurotransmitter -- metabolism KW - Strychnine -- pharmacology KW - Amino Acids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79474881?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-27 N1 - Date created - 1990-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Toxicology studies of a chemical mixture of 25 groundwater contaminants. I. Chemistry development. AN - 79444509; 2612771 AB - As part of an effort to evaluate the toxicology of a chemically defined mixture of 25 frequently detected groundwater contaminants, we report here the formulation and analytical chemistry of this mixture. Many problems were anticipated, including limitation of solubility, chemical interactions, and extreme volatility in the aqueous solution of 25 chemicals. The final technically achievable stock solution was prepared based on EPA survey concentrations of these chemicals in groundwater around hazardous waste disposal sites, their toxicity information, and solubility of the individual compounds in the matrix of the aqueous solution of these 25 chemicals. Because the anticipated animal studies were to be conducted at various laboratories, for ease of handling and maximum stability, the stock solution was stored or shipped as two substock solutions: an organic substock with 18 neat organic chemicals in a glass vial sealed with minimum headspace and an aqueous substock solution with 6 metals of various salt forms and phenol. The concentrations of the solutions were such that direct mixing of the organic and aqueous substocks produced the desired high dose level for the animal experiments. Analyses of all 25 chemicals in the drinking water mixture required six different chromatographic and spectroscopic methods. Some loss of organic volatiles during mixing of the substocks and during the first 24 hr following preparation did occur. However, the concentrations of acetone, phenol, and all the metals remained constant during preparation. Solutions held under simulated animal cage conditions for 96 hr showed losses of the organic volatiles; the majority of which occurred within the first 24 hr. This study shows that it is possible to conduct animal experiments on an aqueous mixture containing 25 groundwater contaminants. Furthermore, a reasonable estimate of intake of individual chemicals can be achieved provided that dosing solutions are prepared fresh at frequent intervals (e.g., 48 to 72 hr) and that comprehensive analyses are carried out. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Yang, R S AU - Goehl, T J AU - Brown, R D AU - Chatham, A T AU - Arneson, D W AU - Buchanan, R C AU - Harris, R K AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 366 EP - 376 VL - 13 IS - 3 SN - 0272-0590, 0272-0590 KW - Aroclors KW - 0 KW - Hydrocarbons KW - Indicators and Reagents KW - Metals KW - Phenols KW - Water Pollutants KW - Water Pollutants, Chemical KW - aroclor 1260 KW - 11096-82-5 KW - Acetone KW - 1364PS73AF KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Index Medicus KW - Hydrocarbons -- analysis KW - Drug Stability KW - Chemistry KW - Chromatography, Gas KW - Diethylhexyl Phthalate -- analysis KW - Chemical Phenomena KW - Acetone -- analysis KW - Aroclors -- analysis KW - Phenols -- analysis KW - Metals -- analysis KW - Water Pollutants -- toxicity KW - Water Supply -- analysis KW - Water Pollutants, Chemical -- analysis KW - Water Pollutants, Chemical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79444509?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Variability of safe dose estimates when using complicated models of the carcinogenic process. A case study: methylene chloride. AN - 79441108; 2612786 AB - Advances in understanding carcinogenesis have led to the development of mathematical models that have biologically interpretable parameters. These models utilize more of the available scientific data than the empirical models routinely employed for quantifying carcinogenic risk. They also require consideration of sources of uncertainty in risk estimates that were previously ignored, such as animal-to-animal variability of physiological and pharmacological constants. A numerical technique is proposed for studying the consequences of incorporating the intrapopulation variability of biologically interpretable parameters into the risk assessment process. To demonstrate the technique, the variability of safe dose estimates for exposure to methylene chloride is considered. The results suggest that intrapopulation variability of the model parameters can increase the variability of safe dose estimates an appreciable amount. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Portier, C J AU - Kaplan, N L AD - Statistics and Biomathematics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 533 EP - 544 VL - 13 IS - 3 SN - 0272-0590, 0272-0590 KW - Carcinogens KW - 0 KW - Hydrocarbons, Chlorinated KW - Methylene Chloride KW - 588X2YUY0A KW - Index Medicus KW - United States KW - Mice, Inbred Strains KW - Animals KW - United States Environmental Protection Agency KW - Kinetics KW - Humans KW - Body Weight -- drug effects KW - Mice KW - Monte Carlo Method KW - Models, Biological KW - Male KW - Hydrocarbons, Chlorinated -- toxicity KW - Methylene Chloride -- toxicity KW - Carcinogenicity Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79441108?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Toxicology studies of a chemical mixture of 25 groundwater contaminants. III. Male reproduction study in B6C3F1 mice. AN - 79435860; 2612772 AB - A mixture of chemicals has been developed that models contaminated groundwater around hazardous waste sites. We investigated the effects of this mixture on spermatogenesis in B6C3F1 mice. The animals consumed three different concentrations of this mixture for 90 days, after which time they were euthanatized. Although there was a concentration-related decrease in the amount of fluid consumed at the higher two concentrations, there were no differences in body weight among the groups. Similarly, there was no effect of mixture consumption upon the histology of liver, kidney, testis, epididymis, or seminal vesicles or upon the absolute organ weights of these organs. Kidney weight relative to body weight was increased in the high dose group. Epididymal sperm number and testicular spermatid count were not affected by treatment. These studies show that, at exposure levels that decrease fluid intake and increase adjusted kidney weight, there were no effects of this mixture on gametogenesis in male mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Chapin, R E AU - Phelps, J L AU - Schwetz, B A AU - Yang, R S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 388 EP - 398 VL - 13 IS - 3 SN - 0272-0590, 0272-0590 KW - Water Pollutants KW - 0 KW - Water Pollutants, Chemical KW - Index Medicus KW - Spermatids -- drug effects KW - Mice, Inbred Strains KW - Animals KW - Spermatids -- cytology KW - Sperm Count KW - Drinking -- drug effects KW - Body Weight -- drug effects KW - Mice KW - Male KW - Organ Size -- drug effects KW - Gametogenesis -- drug effects KW - Water Pollutants -- toxicity KW - Water Supply -- analysis KW - Reproduction -- drug effects KW - Water Pollutants, Chemical -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79435860?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mechanism of action of GnRH: the participation of calcium mobilization and activation of protein kinase C in gonadotropin secretion. AN - 79402774; 2689778 AB - The role of protein kinase C in luteinizing hormone (LH) release was analyzed in studies on the secretory responses to gonadotropin releasing hormone (GnRH) and phorbol esters in pituitary cell cultures. 12-O-tetradecanoyl-phorbol 13-acetate (TPA), 4 beta-phorbol 12,13-bibenzoate, and 4 beta-phorbol 12,13-diacetate stimulated LH release with ED50s of 5, 10 and 1000 nM, respectively, and with about 70% of the efficacy of GnRH. Phorbol ester-stimulated LH secretion was decreased but not abolished by progressive reduction of [Ca2+] in the incubation medium, and the residual response was identical with that of GnRH in Ca2+-deficient medium. TPA increased [Ca2+]i to a peak after 30 s in normal medium but not in the absence of extracellular Ca2+, indicating that protein kinase C promotes calcium entry but can also mediate secretory responses without changes in calcium influx and [Ca2+]i. The extracellular Ca2+-dependent action of TPA on LH release was blocked by CoCl2 but not by nifedipine. The secretory actions of TPA and GnRH were additive at low doses and converged to a common maximum LH response at high concentrations of the agonists. TPA caused rapid translocation of cytosolic protein kinase C to the particulate fraction, followed by a progressive decrease in total enzyme activity to less than 10% after 6 h. Partial recovery of the cytosolic enzyme (to 20%) occurred after washing and reincubation for 15 h. Such kinase C-depleted cells showed prominent dose-dependent reductions in the actions of both GnRH and TPA on LH release in normal and Ca2+-deficient media. These observations show that the actions of kinase C on LH release include extracellular Ca2+-dependent and independent components, and support the hypothesis that protein kinase C participates in the LH secretory response to GnRH in pituitary gonadotrophs. JF - Journal of steroid biochemistry AU - Stojilković, S S AU - Chang, J P AU - Ngo, D AU - Tasaka, K AU - Izumi, S AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 693 EP - 703 VL - 33 IS - 4B SN - 0022-4731, 0022-4731 KW - Phorbol Esters KW - 0 KW - Pituitary Hormone-Releasing Hormones KW - Luteinizing Hormone KW - 9002-67-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Phorbol Esters -- pharmacology KW - Animals KW - Enzyme Activation KW - Cells, Cultured KW - Female KW - Protein Kinase C -- metabolism KW - Luteinizing Hormone -- secretion KW - Calcium -- metabolism KW - Pituitary Gland, Anterior -- drug effects KW - Pituitary Gland, Anterior -- secretion KW - Pituitary Hormone-Releasing Hormones -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79402774?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-06 N1 - Date created - 1990-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Current carcinogen perspectives: De minimis, Delaney and decisions. AN - 79401377; 2690341 AB - Advances in analytical chemistry, as applied to foods, as well as further investigations of the role of essential trace elements, constituents of natural products, and metabolic processes, have all shown that the Delaney clause of the 1958 Food Additives Amendment is an anachronism. Although the limitations of this clause are now known, prospects for its deletion are not very promising. JF - The Science of the total environment AU - Weisburger, E K AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/01/ PY - 1989 DA - 1989 Oct 01 SP - 5 EP - 13 VL - 86 IS - 1-2 SN - 0048-9697, 0048-9697 KW - Carcinogens KW - 0 KW - Food Additives KW - Index Medicus KW - United States KW - United States Food and Drug Administration KW - Humans KW - Legislation, Food UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79401377?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-02 N1 - Date created - 1990-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. AN - 79344010; 2573827 AB - More than 20 different cDNA clones encoding DNA-damage-inducible transcripts in rodent cells have recently been isolated by hybridization subtraction (A. J. Fornace, Jr., I. Alamo, Jr., and M. C. Hollander, Proc. Natl. Acad. Sci. USA 85:8800-8804, 1988). In most cells, one effect of DNA damage is the transient inhibition of DNA synthesis and cell growth. We now show that five of our clones encode transcripts that are increased by other growth cessation signals: growth arrest by serum reduction, medium depletion, contact inhibition, or a 24-h exposure to hydroxyurea. The genes coding for these transcripts have been designated gadd (growth arrest and DNA damage inducible). Two of the gadd cDNA clones were found to hybridize at high stringency to transcripts from human cells that were induced after growth cessation signals or treatment with DNA-damaging agents, which indicates that these responses have been conserved during mammalian evolution. In contrast to results with growth-arrested cells that still had the capacity to grow after removal of the growth arrest conditions, no induction occurred in HL60 cells when growth arrest was produced by terminal differentiation, indicating that only certain kinds of growth cessation signals induce these genes. All of our experiments suggest that the gadd genes are coordinately regulated: the kinetics of induction for all five transcripts were similar; in addition, overexpression of gadd genes was found in homozygous deletion c14CoS/c14CoS mice that are missing a small portion of chromosome 7, suggesting that a trans-acting factor encoded by a gene in this deleted portion is a negative effector of the gadd genes. The gadd genes may represent part of a novel regulatory pathway involved in the negative control of mammalian cell growth. JF - Molecular and cellular biology AU - Fornace, A J AU - Nebert, D W AU - Hollander, M C AU - Luethy, J D AU - Papathanasiou, M AU - Fargnoli, J AU - Holbrook, N J AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 4196 EP - 4203 VL - 9 IS - 10 SN - 0270-7306, 0270-7306 KW - Culture Media KW - 0 KW - Growth Inhibitors KW - RNA, Messenger KW - Poly A KW - 24937-83-5 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Humans KW - Poly A -- biosynthesis KW - Gene Expression KW - Cell Differentiation -- genetics KW - Mice KW - Amino Acid Sequence KW - Hydroxyurea -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Methyl Methanesulfonate -- pharmacology KW - Culture Media -- metabolism KW - Rats KW - Base Sequence KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Kinetics KW - Molecular Sequence Data KW - Male KW - Female KW - DNA Damage KW - Growth Inhibitors -- pharmacology KW - Cell Division -- genetics KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79344010?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-29 N1 - Date created - 1989-12-29 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M29238; GENBANK N1 - SuppNotes - Cited By: Nature. 1983 Oct 27-Nov 2;305(5937):779-84 [6633649] Exp Cell Res. 1989 May;182(1):61-74 [2541007] Nucleic Acids Res. 1986 Jul 25;14(14):5793-811 [2426659] Cell. 1979 Feb;16(2):225-37 [36985] Nature. 1981 Apr 30;290(5809):797-9 [7012641] Nature. 1983 Aug 11-17;304(5926):552-4 [6877378] Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Mol Cell Biol. 1986 May;6(5):1760-6 [3785178] Mol Cell Biol. 1987 Apr;7(4):1450-8 [3037320] Mol Cell Biol. 1987 May;7(5):1894-9 [3600649] Mol Cell Biol. 1987 Jul;7(7):2644-8 [3039354] J Cell Physiol. 1987 Oct;133(1):151-7 [3312241] Mutat Res. 1988 May;193(3):193-206 [2966294] Nature. 1988 Jun 16;333(6174):676-9 [3287181] Science. 1988 Jul 15;241(4863):317-22 [3291120] Cell. 1988 Sep 9;54(6):787-93 [3409319] Science. 1988 Oct 14;242(4876):229-37 [3051381] Nucleic Acids Res. 1988 Oct 25;16(20):9587-96 [2460824] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8800-4 [3194391] Nucleic Acids Res. 1989 Feb 11;17(3):1215-30 [2537950] Cancer Res. 1989 Apr 1;49(7):1687-92 [2466559] Mol Cell Biol. 1989 Feb;9(2):851-3 [2710127] Nature. 1984 Apr 12-18;308(5960):613-7 [6546784] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation. AN - 79343095; 2573830 AB - Expression of a multidrug resistance gene (mdr1) and its protein product, P-glycoprotein (Pgp), has been correlated with the onset of multidrug resistance in vitro in human cell lines selected for resistance to chemotherapeutic agents derived from natural products. Expression of this gene has also been observed in normal tissues and human tumors, including neuroblastoma. We therefore examined total RNA prepared from human neuroblastoma cell lines before and after differentiation with retinoic acid or sodium butyrate. An increase in the level of mdr1 mRNA was observed after retinoic acid treatment of four neuroblastoma cell lines, including the SK-N-SH cell line. Western blot (immunoblot) analysis demonstrated concomitant increases in Pgp. However, studies of 3H-vinblastine uptake failed to show a concomitant Pgp-mediated decrease in cytotoxic drug accumulation. To provide evidence that Pgp was localized on the cell surface, an immunotoxin conjugate directed against Pgp was added to cells before and after treatment with retinoic acid. Incorporation of [3H]leucine was decreased by the immunotoxin in the retinoic acid-treated cells compared with the undifferentiated cells. These results demonstrate that whereas expression of the mdr1 gene can be modulated by differentiating agents, increased levels of expression are not necessarily associated with increased cytotoxic drug accumulation. JF - Molecular and cellular biology AU - Bates, S E AU - Mickley, L A AU - Chen, Y N AU - Richert, N AU - Rudick, J AU - Biedler, J L AU - Fojo, A T AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 4337 EP - 4344 VL - 9 IS - 10 SN - 0270-7306, 0270-7306 KW - Bacterial Toxins KW - 0 KW - Butyrates KW - Exotoxins KW - Immunotoxins KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA, Messenger KW - RNA, Neoplasm KW - Virulence Factors KW - Butyric Acid KW - 107-92-6 KW - Tretinoin KW - 5688UTC01R KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Clone Cells KW - Butyrates -- pharmacology KW - Humans KW - Gene Expression KW - Pseudomonas KW - Cell Membrane -- analysis KW - RNA, Messenger -- biosynthesis KW - Blotting, Western KW - Tumor Cells, Cultured KW - Cell Differentiation -- drug effects KW - Time Factors KW - Tretinoin -- pharmacology KW - Neuroblastoma -- genetics KW - Drug Resistance -- genetics KW - Membrane Glycoproteins -- biosynthesis KW - Neuroblastoma -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79343095?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-29 N1 - Date created - 1989-12-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Physiol. 1974 Feb;83(1):103-16 [4855907] Prog Clin Biol Res. 1988;271:509-24 [3406015] Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 [990323] Cancer Res. 1970 Apr;30(4):1174-84 [5533992] Cancer Res. 1973 Nov;33(11):2643-52 [4748425] Cancer Res. 1977 May;37(5):1364-71 [856461] Natl Cancer Inst Monogr. 1976 Nov;44:49-54 [1030781] Cancer Res. 1978 Nov;38(11 Pt 1):3751-7 [29704] Cancer Res. 1979 Jun;39(6 Pt 1):2070-6 [571759] J Biol Chem. 1979 Dec 25;254(24):12701-5 [500733] World J Surg. 1980 Jan;4(1):29-37 [7385901] J Natl Cancer Inst. 1982 Apr;68(4):589-96 [7040765] Mol Cell Biol. 1982 Aug;2(8):881-9 [6127625] J Pediatr Surg. 1982 Dec;17(6):821-25 [6298396] J Natl Cancer Inst. 1983 Oct;71(4):741-7 [6137586] Exp Cell Res. 1983 Oct;148(1):21-30 [6313408] J Clin Oncol. 1984 Jul;2(7):719-32 [6737018] J Clin Oncol. 1984 Jul;2(7):742-7 [6539811] J Natl Cancer Inst. 1984 Aug;73(2):405-16 [6589432] Cell Differ. 1984 Jun;14(2):135-44 [6467378] J Natl Cancer Inst. 1984 Sep;73(3):649-54 [6590911] Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 [6091052] Nature. 1985 Jan 31-Feb 6;313(6001):404-6 [3855502] Somat Cell Mol Genet. 1985 Mar;11(2):117-26 [3856953] Cancer Res. 1989 Jan 1;49(1):219-25 [2535691] Prog Clin Biol Res. 1985;175:55-68 [2986175] Cancer Res. 1985 Jul;45(7):3002-7 [4005839] Pharmacol Ther. 1985;28(1):51-75 [2865753] J Natl Cancer Inst. 1986 Mar;76(3):375-87 [3456456] J Biol Chem. 1986 Jun 15;261(17):7762-70 [3711108] Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9 [2432605] Exp Cell Biol. 1986;54(5-6):287-300 [3026862] J Biol Chem. 1987 Jan 15;262(2):505-8 [3027054] J Biol Chem. 1987 Feb 15;262(5):2166-70 [2434476] J Biol Chem. 1987 Jun 5;262(16):7884-8 [3034908] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7735-8 [2444983] J Biol Chem. 1988 Jan 25;263(3):1454-8 [2891711] Oncology. 1988;45(3):148-52 [3368191] Cell. 1988 May 20;53(4):519-29 [2897240] Prog Clin Biol Res. 1988;271:31-9 [3406005] J Natl Cancer Inst. 1976 Sep;57(3):727-9 [185404] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. AN - 79341462; 2573831 AB - The human multidrug resistance gene (MDR1) encodes a drug efflux pump glycoprotein (P-glycoprotein) responsible for resistance to multiple cytotoxic drugs. A plasmid carrying a human MDR1 cDNA under the control of a chicken beta-actin promoter was used to generate transgenic mice in which the transgene was mainly expressed in bone marrow and spleen. Immunofluorescence localization studies showed that P-glycoprotein was present on bone marrow cells. Furthermore, leukocyte counts of the transgenic mice treated with daunomycin did not fall, indicating that their bone marrow was resistant to the cytotoxic effect of the drug. Since bone marrow suppression is a major limitation to chemotherapy, these transgenic mice should serve as a model to determine whether higher doses of drugs can cure previously unresponsive cancers. JF - Molecular and cellular biology AU - Galski, H AU - Sullivan, M AU - Willingham, M C AU - Chin, K V AU - Gottesman, M M AU - Pastan, I AU - Merlino, G T AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 4357 EP - 4363 VL - 9 IS - 10 SN - 0270-7306, 0270-7306 KW - Actins KW - 0 KW - Membrane Glycoproteins KW - P-Glycoprotein KW - RNA, Messenger KW - Recombinant Fusion Proteins KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Promoter Regions, Genetic -- physiology KW - Daunorubicin -- toxicity KW - Humans KW - Bone Marrow -- metabolism KW - Mice KW - Mice, Transgenic KW - Plasmids KW - RNA, Messenger -- biosynthesis KW - Bone Marrow Cells KW - Actins -- genetics KW - Transfection KW - Fluorescent Antibody Technique KW - Drug Resistance -- genetics KW - Leukopenia -- chemically induced KW - Membrane Glycoproteins -- analysis KW - Leukopenia -- prevention & control KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79341462?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-29 N1 - Date created - 1989-12-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1970 Apr;30(4):1174-84 [5533992] J Biol Chem. 1987 Jan 15;262(2):505-8 [3027054] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Proc Natl Acad Sci U S A. 1976 Aug;73(8):2634-8 [8777] Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 [990323] J Mol Biol. 1977 Jun 15;113(1):237-51 [881736] Cancer Res. 1979 Jun;39(6 Pt 1):2070-6 [571759] Cancer Treat Rep. 1981;65 Suppl 4:9-18 [6809317] Somat Cell Mol Genet. 1985 Mar;11(2):117-26 [3856953] Nature. 1985 Aug 29-Sep 4;316(6031):817-9 [2863759] Annu Rev Genet. 1986;20:465-99 [3545063] Biochem Biophys Res Commun. 1986 Dec 30;141(3):956-62 [2880583] Proc Natl Acad Sci U S A. 1987 May;84(9):3004-8 [3472246] Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831-5 [2440031] Anal Biochem. 1987 Apr;162(1):156-9 [2440339] FASEB J. 1987 Jul;1(1):51-4 [2886389] J Histochem Cytochem. 1987 Dec;35(12):1451-6 [2890686] J Clin Oncol. 1987 Dec;5(12):1922-7 [3681376] Mol Cell Biol. 1988 Jan;8(1):480-5 [3422100] Proc Natl Acad Sci U S A. 1988 Feb;85(3):836-40 [3422466] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1389-93 [3422740] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1595-9 [3422751] Proc Natl Acad Sci U S A. 1988 May;85(10):3580-4 [3368466] Science. 1988 Jun 10;240(4858):1468-74 [3287623] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4486-90 [2898143] J Biol Chem. 1988 Sep 5;263(25):12163-6 [2900833] J Natl Cancer Inst. 1989 Jan 18;81(2):116-24 [2562856] J Biol Chem. 1989 Jun 5;264(16):9539-46 [2722849] Science. 1986 May 2;232(4750):643-5 [3457471] Science. 1986 May 9;232(4751):751-5 [2421411] J Biol Chem. 1986 Jun 15;261(17):7762-70 [3711108] Proc Natl Acad Sci U S A. 1986 Jun;83(11):3847-50 [3459160] J Natl Cancer Inst. 1986 Aug;77(2):459-69 [3461207] Mol Cell Biol. 1985 Oct;5(10):2720-32 [3837182] Annu Rev Biochem. 1986;55:987-1035 [3527055] Cancer Res. 1986 Nov;46(11):5941-6 [3756931] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785-9 [2429319] Cell. 1986 Nov 7;47(3):371-80 [3768958] Cell. 1986 Nov 7;47(3):381-9 [2876781] Nature. 1986 Oct 23-29;323(6090):728-31 [3022150] Mol Cell Biol. 1986 May;6(5):1671-8 [2431283] Mol Cell Biol. 1986 Nov;6(11):4039-45 [3796599] Proc Natl Acad Sci U S A. 1987 Jan;84(1):265-9 [2432605] Biochim Biophys Acta. 1973 Oct 25;323(3):466-83 [4796512] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cytochrome P-450-dependent formation of alkylating metabolites of the 2-chloroethylnitrosoureas MeCCNU and CCNU. AN - 79330507; 2818619 AB - Rat liver microsomes catalyzed the biotransformation of the clinically important nitrosourea anticancer agents 1-(2-chloroethyl)-3-(trans-4-methyl-cyclohexyl)-1-nitrosourea (MeCCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) to alkylating metabolites that bound covalently to microsomal protein and to DNA. The enzyme-mediated microsomal alkylation required NADPH and oxygen and was inhibited by carbon monoxide, indicating the participation of a cytochrome P-450-dependent monooxygenase. Additional studies with inhibitors such as piperonyl butoxide and with the inducers 3-methylcholanthrene and phenobarbital were consistent with this view. In contrast to these observations on the formation of alkylating metabolites, carbamylation reactions were not affected significantly by microsomal metabolism. Reduced glutathione, cysteine or N-acetylcysteine decreased the microsomal alkylation by MeCCNU and produced a corresponding increase in the formation of polar metabolites that was resolved by HPLC as three distinct N-acetylcysteine-MeCCNU adducts. The addition of semicarbazide to the reaction decreased microsomal alkylation by 30%, indicating that the formation of the alkylating species may proceed via an aldehyde intermediate. Renal microsomes were not found to catalyze the alkylation reaction. Moreover, MeCCNU inhibited the renal slice accumulation of p-aminohippuric acid only in the presence of liver microsomes and NADPH, suggesting that a liver metabolite may be responsible for the renal toxicity of the parent nitrosourea. JF - Biochemical pharmacology AU - Kramer, R A AD - Developmental Therapeutics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10/01/ PY - 1989 DA - 1989 Oct 01 SP - 3185 EP - 3192 VL - 38 IS - 19 SN - 0006-2952, 0006-2952 KW - Alkylating Agents KW - 0 KW - Semustine KW - 13909-09-6 KW - NADP KW - 53-59-8 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Glutathione KW - GAN16C9B8O KW - Acetylcysteine KW - WYQ7N0BPYC KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Phenobarbital -- pharmacology KW - Biotransformation KW - DNA -- metabolism KW - Microsomes, Liver -- enzymology KW - Acetylcysteine -- metabolism KW - NADP -- pharmacology KW - Glutathione -- pharmacology KW - Male KW - Alkylation KW - Alkylating Agents -- metabolism KW - Cytochrome P-450 Enzyme System -- physiology KW - Semustine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79330507?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-28 N1 - Date created - 1989-11-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Evolution of the cytochrome P450 genes. AN - 79320542; 2683414 AB - 1. The P450 gene superfamily is presently known to contain more than 78 members, divided into 14 families. 2. The superfamily has undergone divergent evolution, and the ancestral gene is probably more than 2 billion years old. 3. The recent 'burst' in new P450 genes, particularly in the II family during the past 800 million years, appears to be the result of 'animal-plant warfare'. 4. Due to the presence or absence of a particular P450 gene in one species but not the other, it may not be correct to extrapolate toxicity or cancer data from rodent to human. 5. Increases in the P450 gene product (enzyme induction) almost always reflect an elevated rate in gene transcription, although there are several exceptions. 6. The mechanisms of P450 gene regulation (induction) by classes of inducers might become better understood through the comparison of different phyla that differ in response to a particular class of inducers. 7. Amongst several carefully selected phyla, delineation between which electron donor (presence of Fe2S2 protein or NADPH-P450 oxidoreductase, or both) interacts with P450 may provide valuable information about the evolution of eukaryotes from prokaryotes. JF - Xenobiotica; the fate of foreign compounds in biological systems AU - Nebert, D W AU - Nelson, D R AU - Feyereisen, R AD - Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 1149 EP - 1160 VL - 19 IS - 10 SN - 0049-8254, 0049-8254 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Space life sciences KW - Animals KW - Gene Expression Regulation, Enzymologic KW - Multigene Family KW - Plants -- genetics KW - Genes KW - Cytochrome P-450 Enzyme System -- genetics KW - Biological Evolution KW - Cytochrome P-450 Enzyme System -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79320542?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. AN - 79264434; 2679456 AB - We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant setting. IL-2 was administered either alone (155 patients) or in conjunction with activated immune cells such as lymphokine activated killer (LAK) cells (214 patients) or tumor infiltrating lymphocytes (TIL) (66 patients), with other cytokines such as alpha interferon (a-IFN)(128 patients) or tumor necrosis factor (TNF)(38 patients), with monoclonal antibodies (32 patients), or with the chemotherapeutic agent cyclophosphamide (19 patients). Initial results with the treatment of high-dose IL-2 alone or in conjunction with LAK cells have indicated that objective regressions of cancer can be achieved in 20% to 35% of patients with selected advanced metastatic cancers. Although most responses have been seen in patients with metastatic renal cell cancer, melanoma, colorectal cancer, and non-Hodgkin's lymphoma, many histologic types of cancer have not been treated in significant numbers. These regressions can be durable; of 18 patients achieving a complete response, ten have not experienced recurrence at intervals from 18 to 52 months. Although combinations of IL-2 with TNF do not appear to result in increased responses, there is a suggestion in our initial phase I studies that the combination of a-IFN and IL-2 is more effective than the administration of cytokine alone and this combination deserves further study. Similarly the adoptive transfer of TIL in conjunction with IL-2 also appears to be more effective than the use of IL-2 alone. The toxic side effects in patients treated with high-dose IL-2 are presented and include malaise, nausea and vomiting, hypotension, fluid retention, and organ dysfunction. Treatment-related deaths were seen in 1% of all treatment courses and in 1.5% of patients. These studies demonstrate that a purely immunologic manipulation can mediate the regression of advanced cancers in selected patients and may provide a base for the development of practical, effective biologic treatments for some cancer patients. JF - Annals of surgery AU - Rosenberg, S A AU - Lotze, M T AU - Yang, J C AU - Aebersold, P M AU - Linehan, W M AU - Seipp, C A AU - White, D E AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 474 EP - 84; discussion 484-5 VL - 210 IS - 4 SN - 0003-4932, 0003-4932 KW - Antibodies, Monoclonal KW - 0 KW - Biological Factors KW - Cytokines KW - Interferon Type I KW - Interleukin-2 KW - Tumor Necrosis Factor-alpha KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Animals KW - Killer Cells, Natural -- transplantation KW - Interferon Type I -- administration & dosage KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Aged KW - Mice KW - Biological Factors -- administration & dosage KW - Antibodies, Monoclonal -- administration & dosage KW - Drug Evaluation KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Interleukin-2 -- therapeutic use KW - Immunization, Passive KW - Neoplasms -- therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79264434?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-28 N1 - Date created - 1989-10-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1984 Mar 30;223(4643):1412-4 [6367046] J Clin Oncol. 1989 Mar;7(3):291-4 [2645383] J Immunol. 1985 Oct;135(4):2865-75 [2993418] J Natl Cancer Inst. 1985 Oct;75(4):595-603 [3876465] N Engl J Med. 1985 Dec 5;313(23):1485-92 [3903508] J Immunol. 1985 Dec;135(6):4273-80 [3877766] J Immunol. 1986 Sep 1;137(5):1735-42 [3528289] Science. 1986 Sep 19;233(4770):1318-21 [3489291] Cancer Res. 1986 Oct;46(10):4973-8 [3489517] JAMA. 1986 Dec 12;256(22):3117-24 [3491225] Ann Intern Med. 1987 Feb;106(2):257-74 [2432815] J Immunol. 1987 Feb 1;138(3):989-95 [3100623] N Engl J Med. 1987 Apr 9;316(15):889-97 [3493432] N Engl J Med. 1987 Apr 9;316(15):898-905 [3493433] J Immunol Methods. 1987 Aug 3;101(2):171-81 [3611795] J Immunol Methods. 1987 Aug 24;102(1):127-41 [3305708] Cancer Res. 1988 Jan 1;48(1):122-9 [3257159] Science. 1988 May 27;240(4856):1169-76 [3131876] Important Adv Oncol. 1986;:55-91 [3330541] Cancer Res. 1988 Jul 15;48(14):4011-7 [3260130] Ann Surg. 1988 Aug;208(2):121-35 [3041925] Cancer Res. 1988 Sep 1;48(17):5007-10 [3261630] Cancer Res. 1988 Oct 15;48(20):5810-7 [3262413] Cancer Res. 1988 Oct 15;48(20):5864-7 [3139285] Cancer Res. 1988 Dec 15;48(24 Pt 1):7140-5 [3263900] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] J Clin Oncol. 1989 Feb;7(2):250-61 [2644399] J Immunol. 1985 Aug;135(2):1488-97 [3891854] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium. AN - 79260978; 2619815 AB - Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of [14C]adenine nucleotides from hepatocytes prelabeled with [14C]-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, [14C]adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the [14C]adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death. JF - Toxicology and applied pharmacology AU - Kutty, R K AU - Singh, Y AU - Santostasi, G AU - Krishna, G AD - Section on Drug-Tissue Interaction, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 1 EP - 10 VL - 101 IS - 1 SN - 0041-008X, 0041-008X KW - Calcium Radioisotopes KW - 0 KW - Marine Toxins KW - Oxocins KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - maitotoxin KW - 9P59GES78D KW - Verapamil KW - CJ0O37KU29 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Verapamil -- pharmacology KW - L-Lactate Dehydrogenase -- metabolism KW - Calcium -- metabolism KW - Liver -- cytology KW - Liver -- drug effects KW - Adenosine Triphosphate -- metabolism KW - Calcium -- physiology KW - Liver -- metabolism KW - Marine Toxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79260978?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-14 N1 - Date created - 1989-11-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Toxicol Appl Pharmacol 1990 Jan;102(1):195 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Apparent deficiency of metallothionein in the Wistar rat prostate. AN - 79257043; 2799820 AB - The high affinity metal-binding protein metallothionein (MT) is thought to detoxify cadmium (Cd) but appears to be deficient in several known targets of Cd carcinogenesis. The rat ventral prostate (VP) was recently identified as one of these target tissues. The nature of the Cd-binding proteins in the prostate has not been well defined, and thus this study attempted to define the nature of these proteins in the Wistar rat. A Zn-, Cd-binding protein fraction in the low-molecular-weight range was seen by gel filtration in cytosol from either dorsal prostate (DP) or VP. These prostatic proteins eluted with a relative elution volume similar to that of authentic MT, and were extractable by heat treatment and sequential acetone precipitation, a technique originally developed for purification of MT. Preparations of such partially purified prostatic protein were further purified using a reverse-phase HPLC technique developed for MT isoform isolation. One form was detected from the VP while the DP displayed five separate forms, eluting in a range like that of the two isoforms of rat MT. However, on the basis of amino acid content, none of these prostatic forms were classifiable as MTs, due to the absence of cysteine, a very common amino acid in MT. Unlike MT which is devoid of aromatic amino acids, the prostatic proteins also contained significant amounts of tyrosine and phenylalanine. The prostatic proteins also contained much more glutamate than MT. Cadmium treatment, which is known to cause a marked induction of MT, did not alter levels of this protein in the prostate, while markedly increasing hepatic MT. The present results indicate that these low-molecular-weight Cd-, Zn-binding proteins present in the rat prostate are not MTs and provide a further correlation between MT deficiency and sensitivity to the carcinogenic effects of Cd. JF - Toxicology and applied pharmacology AU - Waalkes, M P AU - Perantoni, A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 83 EP - 94 VL - 101 IS - 1 SN - 0041-008X, 0041-008X KW - Amino Acids KW - 0 KW - Carrier Proteins KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Animals KW - Cytosol -- analysis KW - Amino Acids -- analysis KW - Zinc -- metabolism KW - Tissue Distribution KW - Liver -- analysis KW - Molecular Weight KW - Rats KW - Rats, Inbred Strains KW - Chromatography, Gel KW - Chromatography, High Pressure Liquid -- methods KW - Carrier Proteins -- analysis KW - Male KW - Cadmium -- metabolism KW - Metallothionein -- deficiency KW - Prostate -- analysis KW - Cadmium -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79257043?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-14 N1 - Date created - 1989-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Specific inhibition of FSH-stimulated cAMP accumulation by delta 9-tetrahydrocannabinol in cultures of rat Sertoli cells. AN - 79256995; 2552614 AB - delta 9-Tetrahydrocannabinol (THC), the major psychoactive component in marihuana, is a reproductive toxicant in both man and animals. THC acts at both the level of the pituitary-hypothalamic axis and the testis, specifically the Leydig cell; an effect on the Sertoli cell has not been shown. Since THC inhibits cAMP accumulation in several cell types, we have examined the effect of THC on Sertoli cell function using altered cAMP accumulation as a marker of toxicity. THC reduced the FSH-induced accumulation of cAMP at concentrations which were neither cytotoxic nor affected cellular ATP levels. This inhibition was evident after 3 hr and did not affect the dose of FSH which gave half-maximal stimulation, suggesting that THC does not compete with FSH for binding to its receptor. The ability of THC to inhibit cAMP accumulation was not affected by incubation in the presence of phosphodiesterase inhibitors, making it unlikely that it acts via stimulation of phosphodiesterase activity. This THC-induced inhibition of Sertoli cell cAMP is specific for FSH; it does not affect the ability of forskolin, cholera toxin, isoproterenol, or prostaglandin E1 to stimulate Sertoli cell cAMP. Furthermore, inhibition occurs in the presence of pertussis toxin, suggesting that this effect of THC is independent of the inhibitory adenylate cyclase pathway. Inhibition of Sertoli cell cAMP also occurs with other cannabinoids which are present in marihuana, but which are not psychoactive. These data indicate that a part of the testicular toxicity of THC may be due to a specific alteration of the hormonal control of Sertoli cell function via an inhibition of FSH-stimulated cAMP accumulation. JF - Toxicology and applied pharmacology AU - Heindel, J J AU - Keith, W B AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 124 EP - 134 VL - 101 IS - 1 SN - 0041-008X, 0041-008X KW - Adenylyl Cyclase Inhibitors KW - 0 KW - Cannabinoids KW - Dronabinol KW - 7J8897W37S KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Follicle Stimulating Hormone KW - 9002-68-0 KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cells, Cultured KW - Adenosine Triphosphate -- metabolism KW - Cannabinoids -- pharmacology KW - Male KW - Microscopy, Electron, Scanning KW - Sertoli Cells -- drug effects KW - Follicle Stimulating Hormone -- antagonists & inhibitors KW - Sertoli Cells -- metabolism KW - Dronabinol -- pharmacology KW - Second Messenger Systems -- drug effects KW - Cyclic AMP -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79256995?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-14 N1 - Date created - 1989-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Differential expression of an 80-kDa protein kinase C substrate in preneoplastic and neoplastic mouse JB6 cells. AN - 79255724; 2798414 AB - An 80-kDa protein (p80), previously reported to be a major protein kinase C substrate in preneoplastic JB6 mouse epidermal cells, has been shown to be transiently phosphorylated by phorbol 12-O-tetradecanoate 13-acetate. Phosphorylation was maximal at 2 hr of phorbol 12-O-tetradecanoate 13-acetate treatment and returned to basal levels by 24 hr. In contrast, using a p80-specific antibody, we found that phorbol 12-O-tetradecanoate 13-acetate treatment produced no increase in p80 concentration. p80 showed a progressive decrease in JB6 cells during progression from a preneoplastic to neoplastic phenotype. The lack of p80 expression in neoplastic cells was not attributable to lack of protein kinase C; the protein kinase activity and protein concentration were similar in cells of all three phenotypes. When p80 mRNA was analyzed by hybridization to a putative p80 cDNA clone, its relative concentration paralleled that of p80 protein, with high levels present in preneoplastic JB6 cells, and little or no evidence for p80-hybridizing RNA in transformed cells. Thus, p80 appears to be regulated pretranslationally at the level of mRNA concentration during preneoplastic progression in mouse epidermal JB6 cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Simek, S L AU - Kligman, D AU - Patel, J AU - Colburn, N H AD - Cell Biology Section, National Cancer Institute-Frederick Cancer Research Facility, MD 21701-1013. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 7410 EP - 7414 VL - 86 IS - 19 SN - 0027-8424, 0027-8424 KW - Neoplasm Proteins KW - 0 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Mice KW - Substrate Specificity KW - Mice, Inbred BALB C KW - Cell Line KW - Protein Kinase C -- metabolism KW - Neoplasm Proteins -- isolation & purification KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Neoplasms, Experimental -- metabolism KW - Precancerous Conditions -- metabolism KW - Neoplasm Proteins -- metabolism KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79255724?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1979 Oct 18;281(5732):589-91 [492322] J Biol Chem. 1988 May 5;263(13):6424-31 [3360787] Science. 1965 Oct 8;150(3693):178-85 [5319951] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Mol Biol. 1977 Jun 15;113(1):237-51 [881736] J Biol Chem. 1977 Nov 25;252(22):8310-9 [914873] Cell. 1980 Jan;19(1):245-54 [6153576] Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201-5 [6159641] Proc Natl Acad Sci U S A. 1981 Nov;78(11):6912-6 [6947266] Teratog Carcinog Mutagen. 1980;1(1):87-96 [6119803] J Cell Biochem. 1982;18(3):261-70 [7068782] Carcinogenesis. 1983;4(4):489-90 [6301704] Proc Natl Acad Sci U S A. 1983 Dec;80(23):7244-8 [6316349] J Cell Physiol. 1984 Feb;118(2):133-42 [6319436] Biochem Biophys Res Commun. 1984 May 16;120(3):1053-9 [6233972] Carcinogenesis. 1984 Sep;5(9):1115-21 [6467502] Mol Cell Biol. 1985 Apr;5(4):890-3 [2985973] J Biol Chem. 1985 Dec 5;260(28):15194-9 [3905792] Int J Cancer. 1986 Feb 15;37(2):293-302 [3002990] EMBO J. 1986 Jan;5(1):77-83 [3956481] Cancer Res. 1986 Jun;46(6):3040-5 [3698022] Proc Natl Acad Sci U S A. 1986 May;83(9):2822-6 [3458242] Mol Cell Biol. 1985 Sep;5(9):2231-7 [3016523] Carcinogenesis. 1986 Dec;7(12):1949-56 [3096584] J Cell Physiol. 1987 Jan;130(1):111-7 [3543027] J Biol Chem. 1987 Dec 5;262(34):16686-91 [3680270] J Cell Physiol. 1987 Nov;133(2):377-82 [3680394] Cancer Res. 1988 Mar 1;48(5):1195-200 [3342399] Oncogene. 1987 Mar;1(1):37-46 [2830575] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cell-specific induction of mouse Cyp1a1 mRNA during development. AN - 79254327; 2477842 AB - The dioxin-inducible cytochrome P(1)450 (Cyp1a1 gene) and P(3)450 (Cyp1a2 gene) enzymes have been implicated in the metabolism of numerous polycyclic hydrocarbons and arylamines, respectively. The prototypic inducer 3-methylcholanthrene was given to the pregnant mouse, and the intrauterine response was examined with the use of in situ hybridization. During the early postimplantation stage, inducible Cyp1a1 mRNA is detected in specific cell types in the extraembryonic tissues only. This selective expression along with the lack of detectable constitutive Cyp1a1 and constitutive or inducible Cyp1a2 gene transcripts between 5.3 and 14.5 days of gestation suggest that (i) these two genes appear to play no endogenous role during differentiation and (ii) the metabolic activity of the inducible Cyp1a1 enzyme may be important to the embryo and fetus from the standpoint of protection against toxic foodstuff and other environmental chemicals. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Dey, A AU - Westphal, H AU - Nebert, D W AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 7446 EP - 7450 VL - 86 IS - 19 SN - 0027-8424, 0027-8424 KW - Isoenzymes KW - 0 KW - RNA, Antisense KW - RNA, Messenger KW - Methylcholanthrene KW - 56-49-5 KW - RNA KW - 63231-63-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Embryonic and Fetal Development KW - Mice, Inbred C57BL KW - Mice KW - Plasmids KW - Female KW - RNA -- genetics KW - Pregnancy KW - Cloning, Molecular KW - RNA, Messenger -- antagonists & inhibitors KW - Yolk Sac -- metabolism KW - Methylcholanthrene -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Isoenzymes -- biosynthesis KW - Decidua -- metabolism KW - Lung -- embryology KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Lung -- metabolism KW - Isoenzymes -- genetics KW - RNA, Messenger -- biosynthesis KW - Liver -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79254327?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anat Rec. 1987 Feb;217(2):203-19 [3578838] Mol Cell Biol. 1986 May;6(5):1471-7 [3785172] Methods Enzymol. 1987;152:649-61 [3657592] J Exp Pathol. 1987 Winter;3(1):61-74 [3681488] Science. 1968 May 3;160(3827):541-2 [5644060] J Biol Chem. 1968 Dec 10;243(23):6242-9 [4387094] Cancer Res. 1969 Oct;29(10):1763-9 [5823944] Arch Biochem Biophys. 1969 Oct;134(1):76-89 [4981257] Toxicol Appl Pharmacol. 1972 Nov;23(3):399-407 [5085454] Adv Reprod Physiol. 1971;5:1-26 [4949999] Proc Natl Acad Sci U S A. 1976 Oct;73(10):3381-5 [1068451] Mol Pharmacol. 1977 Mar;13(2):259-68 [854023] J Biol Chem. 1979 Nov 10;254(21):11015-23 [500620] Proc Natl Acad Sci U S A. 1980 Jun;77(6):3524-8 [6932035] Environ Health Perspect. 1981 Jun;39:11-22 [7016519] Proc Natl Acad Sci U S A. 1981 Nov;78(11):6991-5 [6273901] Pharmacol Rev. 1982 Jun;34(2):189-222 [6287505] Cancer Res. 1982 Dec;42(12):4875-917 [6814745] Cancer Res. 1982 Dec;42(12):5030-7 [6291746] Methods Enzymol. 1978;52:226-40 [672631] CRC Crit Rev Biochem. 1979;6(4):401-37 [378536] Mol Pharmacol. 1983 Jul;24(1):146-55 [6408394] Dev Biol. 1984 Feb;101(2):485-502 [6692991] Mol Pharmacol. 1984 Jul;26(1):117-21 [6749129] J Biol Chem. 1984 Sep 10;259(17):10705-13 [6547952] EMBO J. 1984 Aug;3(8):1881-5 [6479150] Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 [6091052] Proc Natl Acad Sci U S A. 1985 May;82(10):3311-5 [3858824] Biochem Biophys Res Commun. 1985 Jul 16;130(1):396-406 [4040754] Dev Biol. 1985 Nov;112(1):177-84 [4054433] Placenta. 1986 May-Jun;7(3):263-81 [3737578] Annu Rev Biochem. 1987;56:945-93 [3304150] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Long-term follow-up of children exposed in utero to antineoplastic agents. AN - 79253198; 2678492 JF - Seminars in oncology AU - Garber, J E AD - Clinical Studies Section, National Cancer Institute, Boston, MA. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 437 EP - 444 VL - 16 IS - 5 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Follow-Up Studies KW - Child KW - Adolescent KW - Male KW - Female KW - Pregnancy KW - Abnormalities, Drug-Induced -- epidemiology KW - Prenatal Exposure Delayed Effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79253198?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-17 N1 - Date created - 1989-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Comparison of arachidonic acid metabolism by pulmonary intravascular and alveolar macrophages exposed to particulate and soluble stimuli. AN - 79242173; 2552225 AB - Pulmonary intravascular macrophages, as prominent components of the pulmonary mononuclear phagocyte system, could be significant mediators of lung inflammation. We have shown that intravascular and alveolar macrophages metabolize exogenous arachidonic acid to its inflammatory metabolites via the lipoxygenase and cyclooxygenase pathways after exposure to the calcium ionophore A23187. In this study, we compare the metabolism of endogenous arachidonic acid by porcine intravascular and alveolar macrophages after exposure to soluble and particulate stimuli. Since intravascular and alveolar macrophages are exposed to various stimuli in vivo, it is essential to know the range of inflammatory mediators that these cells can generate. Alveolar macrophages attached to plastic and exposed to the various stimuli produced prostaglandin F2 alpha, 12-hydroxyheptade-catrienoic acid (HHT), hydroxyeicosatetraenoic acids (HETE), and leukotriene B4. In contrast, adherent and stimulated intravascular macrophages produced several cyclooxygenase products and lipoxygenase products including 5-HETE, 12-HETE, and leukotriene B4. Both macrophages released large amounts of arachidonic acid upon exposure to each stimulant. Intravascular macrophages that were adherent to plastic or were stimulated with glass, asbestos, or A23187 released significantly (p less than 0.05) more metabolized arachidonic acid than similarly treated alveolar macrophages. The major cyclooxygenase metabolite released by alveolar macrophages was prostaglandin 2 alpha, whereas HHT was the primary metabolite of intravascular macrophages. The major lipoxygenase metabolite released by both macrophage types was 5-HETE, but intravascular macrophages also released substantial amounts of 12-HETE and leukotriene B4. In both macrophage preparations, lipoxygenase products composed most released metabolites. After exposure to iron, asbestos, and A23187 intravascular macrophages released significantly more (p less than 0.05) lipoxygenase metabolites than alveolar macrophages. However, in alveolar macrophages, chrysotile asbestos induced greater activity by the cyclooxygenase pathway than by the lipoxygenase pathway. Both asbestos and iron spheres induced release of arachidonic acid and its metabolites, but the most potent stimulants in both macrophage preparations were A23187, zymosan, and lipopolysaccharide. We conclude that stimulated intravascular macrophages use both cyclooxygenase and lipoxygenase pathways to metabolize endogenous arachidonic acid, that these macrophages are metabolically more active than alveolar macrophages, and that both macrophage types are induced to metabolize arachidonic acid by various particulate and soluble stimuli. Furthermore, we have shown that intravascular macrophages predominantly utilize the lipoxygenase rather than cyclooxygenase pathways to metabolize endogenous arachidonic acid. JF - Laboratory investigation; a journal of technical methods and pathology AU - Bertram, T A AU - Overby, L H AU - Brody, A R AU - Eling, T E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 457 EP - 466 VL - 61 IS - 4 SN - 0023-6837, 0023-6837 KW - Arachidonic Acids KW - 0 KW - Lipopolysaccharides KW - Asbestos KW - 1332-21-4 KW - Calcimycin KW - 37H9VM9WZL KW - Zymosan KW - 9010-72-4 KW - Iron KW - E1UOL152H7 KW - Microbial Collagenase KW - EC 3.4.24.3 KW - Index Medicus KW - Swine KW - Microbial Collagenase -- pharmacology KW - Animals KW - Phagocytosis KW - Macrophages -- cytology KW - Zymosan -- pharmacology KW - Iron -- pharmacology KW - Lipopolysaccharides -- pharmacology KW - Asbestos -- pharmacology KW - Macrophages -- physiology KW - Arachidonic Acids -- metabolism KW - Calcimycin -- pharmacology KW - Glass KW - Pulmonary Alveoli -- physiology KW - Pulmonary Alveoli -- metabolism KW - Pulmonary Alveoli -- cytology KW - Macrophages -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79242173?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-13 N1 - Date created - 1989-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Comparison of octahydromezerein and mezerein as protein kinase C activators and as mouse skin tumor promoters. AN - 79221513; 2507191 AB - Although mezerein resembles 12-O-tetradecanoylphorbol-13-acetate (TPA) in being a potent ligand for protein kinase C in vitro, its properties as a tumor promoter on mouse skin differ from those of TPA. Mezerein is a good second-stage promoter of papillomas, an inefficient complete promoter of papillomas, and an effective promoter of carcinomas. The mechanism and structural features responsible for the anomalous tumor promoting activity of mezerein are unknown. We have examined here the in vitro and in vivo activities of octahydromezerein (OHM) and compared them to those of TPA and mezerein. OHM was of interest because if it acted like mezerein it would afford a convenient route for radioactive labeling. Alternatively, if it functioned as a complete tumor promoter, it would implicate unsaturation as the critical structural feature of mezerein responsible for its altered promoting activity. Consistent with this latter possibility, we find that OHM was an effective complete tumor promoter for SENCAR mice. Moreover, the pattern and magnitude of papilloma induction, yielding a peak at 16-20 weeks followed by a decline by 30-32 weeks, resembled that for TPA; mezerein, in contrast, induced a gradual but steady increase in the number of papillomas which did not reach the OHM level by 32 weeks. The dosage of OHM for inducing a comparable degree of acute and chronic hyperplasia to that induced by mezerein was 3- to 10-fold higher. This difference agrees with the relative binding affinities to protein kinase C; the Ki for OHM was 2.7 nM, compared to 0.58 nM for mezerein. JF - Carcinogenesis AU - Sharkey, N A AU - Hennings, H AU - Yuspa, S H AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 1937 EP - 1941 VL - 10 IS - 10 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Diterpenes KW - Terpenes KW - octahydromezerein KW - 124392-15-0 KW - mezerein KW - 34807-41-5 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tetradecanoylphorbol Acetate -- toxicity KW - Mice, Inbred Strains KW - Animals KW - Hyperplasia KW - Enzyme Activation KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Mice KW - Female KW - Terpenes -- toxicity KW - Protein Kinase C -- metabolism KW - Carcinogens -- pharmacology KW - Skin -- drug effects KW - Papilloma -- pathology KW - Skin Neoplasms -- chemically induced KW - Skin -- pathology KW - Skin Neoplasms -- pathology KW - Terpenes -- pharmacology KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79221513?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-13 N1 - Date created - 1989-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Deficient G2 phase repair of radiation-induced chromatin damage in the SENCAR mouse. AN - 79220682; 2791207 AB - The SENCAR mouse, selectively bred for sensitivity to skin tumor induction by two-stage chemical carcinogenesis, is also genetically hypersensitive to skin carcinogenesis by high doses of UV. Skin fibroblasts from the SENCAR mouse exposed during G2 phase to radiation associated with intracellular hydroxyl radical formation, i.e. X-rays or near UV/visible light, showed a higher frequency of chromatid breaks at 2 h post-irradiation than skin fibroblasts from six other inbred strains of mice including C3H/HeN. However the level was similar to that reported previously for the BALB/cAn mouse known to be resistant to chemical carcinogenesis of skin. When exposed for 2 h to visible light (8 W/m2), chromatid breaks persisted in fibroblasts from the SENCAR mouse during the 4 h post-irradiation period, but showed an abrupt decline in C3H/HeN fibroblasts within 1 h after irradiation. Skin fibroblasts from the tumor-sensitive SENCAR mouse differed from those of the resistant BALB/cAn in response to beta-cytosine arabinoside (ara-C) an inhibitor of the repair polymerase. Ara-C added to cultures of SENCAR and BALB/cAn cells after G2 X-irradiation (68R) increased chromatid gaps 18-fold and breaks 2-fold in BALB/cAn cells but had no effect on SENCAR cells even though incorporated into DNA to the same extent. The present results suggest that the SENCAR mouse is deficient in at least two aspects of DNA repair: (i) ligation or a prior step in the repair process leading to ligation and (ii) repair endonucleolytic incision at DNA lesions induced by irradiation. JF - Carcinogenesis AU - Sanford, K K AU - Parshad, R AU - Price, F M AU - Gantt, R AU - Jones, G M AU - Tarone, R E AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 1911 EP - 1916 VL - 10 IS - 10 SN - 0143-3334, 0143-3334 KW - Chromatin KW - 0 KW - Index Medicus KW - Mice, Inbred Strains KW - Fibroblasts -- drug effects KW - Animals KW - X-Rays KW - Cells, Cultured KW - Chromatids -- radiation effects KW - Mice KW - Light KW - Fibroblasts -- cytology KW - Mice, Inbred BALB C KW - Species Specificity KW - Ultraviolet Rays KW - Skin -- radiation effects KW - DNA Repair KW - Chromatin -- radiation effects KW - Skin -- cytology KW - Interphase -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79220682?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-13 N1 - Date created - 1989-11-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A case-control study of soft-tissue sarcoma. AN - 79201355; 2773915 AB - The roles of nonagricultural occupations, tobacco use, beverage consumption, medical history, and other factors in the development of soft-tissue sarcoma were examined in a population-based case-control study in Kansas. Based on 133 cases diagnosed between 1976-1982 and 948 controls, there were significant excesses associated with use of the drug chloramphenicol (odds ratio (OR) = 5.4, 95% confidence interval (Cl) 1.2-23.9) and chewing tobacco or snuff (OR = 1.8, 95% Cl 1.1-2.9). The risk associated with smokeless tobacco varied with the location of the tumors; greater risks were observed for tumors of the upper gastrointestinal tract (OR = 3.3), the lung, pleura, and thorax (OR = 3.1), and the head, neck, and face region (OR = 2.4) than other regions of the body (OR = 1.4). A nonsignificant excess was seen with the use of cholesterol-lowering drugs, such as clofibrate (OR = 1.7). Four cases reported histories of prior radiation treatment to the same area of their bodies as their tumors. Soft-tissue sarcoma was also associated with employment in woodworking occupations (OR = 1.7, 95% Cl 0.9-3.2) and risk increased with increasing duration of employment. Persons with first-degree blood relatives with a history of Hodgkin's disease, lymphoma, or cancers of the pancreas, prostate, brain, or skin were at increased risk. Many of the associations observed in this study, notably the risk of soft-tissue sarcoma with smokeless tobacco and medications such as chloramphenicol, deserve further evaluation. JF - American journal of epidemiology AU - Zahm, S H AU - Blair, A AU - Holmes, F F AU - Boysen, C D AU - Robel, R J AU - Fraumeni, J F AD - Epidemiology and Biostatistics Program, National Cancer Institute, Rockville, MD 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 665 EP - 674 VL - 130 IS - 4 SN - 0002-9262, 0002-9262 KW - Chloramphenicol KW - 66974FR9Q1 KW - Index Medicus KW - Beverages KW - Chloramphenicol -- adverse effects KW - Humans KW - Wood KW - Aged KW - Tobacco, Smokeless KW - Plants, Toxic KW - Demography KW - Kansas KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - Cohort Studies KW - Middle Aged KW - Occupations KW - Male KW - Soft Tissue Neoplasms -- epidemiology KW - Soft Tissue Neoplasms -- etiology KW - Sarcoma -- etiology KW - Sarcoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79201355?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. AN - 79195497; 2777040 AB - To determine the long-term efficacy, safety, and toxicity of omeprazole, we studied 40 patients with Zollinger-Ellison syndrome given omeprazole for 6-51 mo (median 29). The mean daily dose of omeprazole required to control gastric acid secretion was 82 +/- 31 mg. Thirty-one patients required omeprazole once per day. In 9 patients acid output was not controlled by 120 mg once per day, but was controlled by 60 mg every 12 h. The daily dose of omeprazole correlated with the previous dose of histamine H2-receptor antagonist (r = 0.89, p less than 0.001), basal acid output (r = 0.43, p less than 0.01), and maximal acid output (r = 0.39, p less than 0.02) but not with serum concentration of gastrin (r = -0.32). Increases in the dose of omeprazole were required in 9 patients. Twenty-nine patients had mild peptic symptoms with acid outputs less than 10 mEq/h while taking histamine H2-receptor antagonists. Symptoms resolved completely in 23 patients and partially in 3 when taking omeprazole. Omeprazole prevented mucosal disease in all patients including 17 in whom histamine H2-receptor antagonists had produced only partial resolution despite acid output being less than 10 mEq/h and in those with symptoms during omeprazole therapy. Omeprazole therapy was not associated with any significant side effects, nor with any evidence of hematologic or biochemical toxicity. Serum concentrations of gastrin did not change significantly during therapy. In 6 patients treated with omeprazole for 1 yr there was no change in basal or maximal acid output. In all patients, gastric morphology and histopathology demonstrated no evidence of gastric carcinoid formation. These results demonstrate that with long-term treatment of up to 4 yr, omeprazole is safe, with no evidence of hematologic, biochemical, or gastric toxicity. Furthermore, omeprazole remained effective, with only 23% of patients requiring an increase in dose, and continued to control symptoms in patients who had not been entirely symptom-free despite high doses of histamine H2-receptor antagonists. Omeprazole is now the drug of choice in patients with Zollinger-Ellison syndrome. JF - Gastroenterology AU - Maton, P N AU - Vinayek, R AU - Frucht, H AU - McArthur, K A AU - Miller, L S AU - Saeed, Z A AU - Gardner, J D AU - Jensen, R T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 827 EP - 836 VL - 97 IS - 4 SN - 0016-5085, 0016-5085 KW - Omeprazole KW - KG60484QX9 KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Prospective Studies KW - Humans KW - Adult KW - Intestinal Mucosa -- pathology KW - Aged KW - Middle Aged KW - Time Factors KW - Gastric Mucosa -- pathology KW - Male KW - Female KW - Gastric Acid -- secretion KW - Zollinger-Ellison Syndrome -- metabolism KW - Zollinger-Ellison Syndrome -- drug therapy KW - Omeprazole -- adverse effects KW - Omeprazole -- therapeutic use KW - Omeprazole -- administration & dosage KW - Zollinger-Ellison Syndrome -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79195497?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-17 N1 - Date created - 1989-10-17 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - GABAA receptor complex in an experimental model of hepatic encephalopathy: evidence for elevated levels of an endogenous benzodiazepine receptor ligand. AN - 79178196; 2549194 AB - The involvement of the gamma-aminobutyric acidA (GABAA) receptor complex in the pathogenesis of hepatic encephalopathy was examined in thioacetamide-treated rats with fulminant hepatic failure. Partially purified extracts from encephalopathic rat brain were approximately three times more potent in inhibiting [3H]Ro 15-1788 binding to benzodiazepine receptors than identically prepared extracts from control rats. High levels of inhibitory activity were also found in extracts of plasma, heart, and liver from thioacetamide-treated rats. The inhibition of [3H]Ro 15-1788 binding by brain extracts appeared to be competitive and reversible and was unaffected by treatment with either proteolytic enzymes or boiling. Further, GABA significantly enhanced the potency of these extracts in inhibiting [3H]flunitrazepam binding. In contrast, no differences were found in radioligand binding to the constituent recognition sites of the GABAA receptor complex in well-washed brain membranes prepared from control and encephalopathic animals. These findings suggest that the recognition-site qualities of the constituent proteins of the GABAA receptor complex are unchanged in an experimental model of hepatic encephalopathy. However, significant elevations in the level of a substance or substances with neurochemical properties characteristic of a benzodiazepine receptor agonist may contribute to the electrophysiological and behavioral manifestations of hepatic encephalopathy. JF - Journal of neurochemistry AU - Basile, A S AU - Gammal, S H AU - Jones, E A AU - Skolnick, P AD - Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 1057 EP - 1063 VL - 53 IS - 4 SN - 0022-3042, 0022-3042 KW - Receptors, GABA-A KW - 0 KW - Thioacetamide KW - 075T165X8M KW - Flumazenil KW - 40P7XK9392 KW - Index Medicus KW - Animals KW - Reference Values KW - Flumazenil -- metabolism KW - Cerebral Cortex -- metabolism KW - Disease Models, Animal KW - Cerebellum -- metabolism KW - Rats KW - Rats, Inbred Strains KW - Kinetics KW - Binding, Competitive KW - Cell Membrane -- metabolism KW - Male KW - Receptors, GABA-A -- metabolism KW - Brain -- metabolism KW - Hepatic Encephalopathy -- metabolism KW - Hepatic Encephalopathy -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79178196?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Inhibition of initiator-promoter-induced skin tumorigenesis in female SENCAR mice fed a vitamin A-deficient diet and reappearance of tumors in mice fed a diet adequate in retinoid or beta-carotene. AN - 79165900; 2504490 AB - Retinoids have chemopreventive activity for epithelial tumors in a variety of systems, including the two-stage tumorigenesis system of mouse skin in which only the promotion stage is inhibited. We asked whether dietary vitamin A deficiency could affect the skin tumorigenic response, prior to major changes in body weight or general health of the animals. Two regimens were tested to induce vitamin A deficiency. SENCAR mice were either (a) fed a vitamin A-deficient diet from 4 or 9 weeks of age or (b) their mothers were fed the diet from the time of birth of the experimental animals which were then weaned on the same diet. The latter regimen produced typical symptoms of vitamin A deficiency in the offspring by Weeks 12-14 and all the mice died by Week 19; the former regimen permitted sufficient accumulation of retinol and its esters to sustain life for up to 45 and 75 weeks, respectively, in the majority of mice. For our experiments, vitamin A depletion was produced by placing the mothers on the deficient diet at birth of the experimental animals. A single topical dose of 20 micrograms of 7,12-dimethylbenz(a)anthracene (DMBA) was used as the initiator at 3 weeks of age and 1 to 2 micrograms of 12-O-tetradecanoylphorbol-13-acetate (TPA) once weekly as the tumor promoter for 10 weeks (from Week 4 through 13 of the experiment). Fifty-five % of mice (n = 40) on Purina laboratory chow (mean body weight, 31.4 g) developed skin tumors (2.58 per mouse) at 12 weeks, versus 2.5% (0.05 papillomas per mouse) of mice (n = 40) kept on the purified vitamin A-deficient diet (mean body weight, 30.3 g), a 98% decrease in tumor/mouse. Retinoic acid (RA) (1-3 micrograms/g diet) supplementation after Week 12 caused a rapid tumorigenic response in 95% of the mice by week 22. This tumor response occurred to a reduced extent in the absence of continued TPA treatment up to Week 13. Even though tumor incidence increased within 1 week of RA and 95% of the mice showed the tumorigenic response, the number of tumors per mouse was about 50% of that observed in mice maintained on standard Purina diet. This was confirmed in an experiment in which the mice were maintained for life either on Purina or on the RA (3 micrograms/g) containing purified diet, the latter being the control group for the effect of vitamin A deficiency on skin tumorigenesis.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - De Luca, L M AU - Shores, R L AU - Spangler, E F AU - Wenk, M L AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/01/ PY - 1989 DA - 1989 Oct 01 SP - 5400 EP - 5406 VL - 49 IS - 19 SN - 0008-5472, 0008-5472 KW - beta Carotene KW - 01YAE03M7J KW - Carotenoids KW - 36-88-4 KW - Tretinoin KW - 5688UTC01R KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cocarcinogenesis KW - Mice KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms, Experimental -- pathology KW - Liver -- analysis KW - Neoplasms, Experimental -- chemically induced KW - Weight Loss KW - Diet KW - Female KW - Male KW - Vitamin A Deficiency -- physiopathology KW - Vitamin A Deficiency -- mortality KW - Skin Neoplasms -- chemically induced KW - Carotenoids -- analysis KW - Tretinoin -- administration & dosage KW - Skin Neoplasms -- pathology KW - Carotenoids -- administration & dosage KW - Skin Neoplasms -- prevention & control KW - Tretinoin -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79165900?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-05 N1 - Date created - 1989-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Pharmacokinetics of buthionine sulfoximine (NSC 326231) and its effect on melphalan-induced toxicity in mice. AN - 79165855; 2766304 AB - Intravenous doses of buthionine sulfoximine (BSO, NSC 326231), an inhibitor of glutathione synthesis, were eliminated rapidly from mouse plasma in a biexponential manner. The initial phase of the plasma concentration versus time curve had a half-life of 4.9 min and accounted for 94% of the total area under the curve. The half-life of the terminal phase of the curve was 36.7 min and the area accounted for only 6% of the total area under the curve. Plasma clearance of BSO was 28.1 ml/min/kg and the steady state volume of distribution was 280 ml/kg. The oral bioavailability of BSO, based on plasma BSO levels, was extremely low. However, comparable glutathione depletion was apparent after i.v. and p.o. doses of BSO, suggesting a rapid tissue uptake and/or metabolism of BSO. Therefore, due to the rapid elimination of BSO from mouse plasma, plasma drug levels do not directly correlate with BSO-induced tissue glutathione depletion. Administration of multiple i.v. doses of BSO to male and female mice resulted in a marked 88% depletion of liver glutathione at doses of 400-1600 mg/kg/dose. Toxicity of i.v. administered BSO was limited to a transient depression of peripheral WBC levels in female mice given six doses of 1600 mg/kg. Multiple i.v. doses of BSO of up to 800 mg/kg/dose (every 4 h for a total of six doses) did not alter the toxicity of i.v. administered melphalan. However, multiple doses of 1600 mg/kg/dose of BSO did potentiate histopathological evidence of melphalan-induced bone marrow toxicity in 30% of the mice and, additionally, the combination of BSO and melphalan produced renal tubular necrosis in 80% of the male mice. The potentiation of melphalan induced toxicity did not appear to be related to GSH depletion, since: quantitatively similar amount of GSH depletion occurred at lower dose of BSO without any increase in melphalan toxicity. JF - Cancer research AU - Smith, A C AU - Liao, J T AU - Page, J G AU - Wientjes, M G AU - Grieshaber, C K AD - Toxicology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/10/01/ PY - 1989 DA - 1989 Oct 01 SP - 5385 EP - 5391 VL - 49 IS - 19 SN - 0008-5472, 0008-5472 KW - Methionine Sulfoximine KW - 1982-67-8 KW - Buthionine Sulfoximine KW - 5072-26-4 KW - Glutathione KW - GAN16C9B8O KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Administration, Oral KW - Animals KW - Drug Administration Schedule KW - Drug Interactions KW - Injections, Intravenous KW - Liver -- metabolism KW - Glutathione -- blood KW - Mice KW - Mice, Inbred BALB C KW - Mice, Inbred DBA KW - Half-Life KW - Premedication KW - Drug Evaluation, Preclinical KW - Methionine Sulfoximine -- blood KW - Methionine Sulfoximine -- administration & dosage KW - Methionine Sulfoximine -- toxicity KW - Melphalan -- administration & dosage KW - Methionine Sulfoximine -- pharmacology KW - Methionine Sulfoximine -- analogs & derivatives KW - Methionine Sulfoximine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79165855?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-05 N1 - Date created - 1989-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Relationship between the formation of promutagenic adducts and the activation of the K-ras protooncogene in lung tumors from A/J mice treated with nitrosamines. AN - 79159208; 2670201 AB - Lung and liver tumors were induced in female A/J mice after treatment for 7 weeks (3 times/week, i.p.) with either 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) (50 mg/kg) or nitrosodimethylamine (NDMA) (3 mg/kg). Both compounds can be activated via alpha-hydroxylation to methylating agents, while NNK may also undergo hydroxylation at the N-methyl carbon to form a pyridyloxobutylated adduct. The purpose of these studies was to identify and characterize the activated oncogenes present in tumors induced by NDMA and NNK. Following transfection of high molecular weight DNA onto NIH/3T3 mouse fibroblasts, transforming genes were detected in 90% of both NNK- (10 of 11) and NDMA- (9 of 10) induced lung tumors. In contrast, transformation of NIH/3T3 fibroblasts was observed only in 40% (2 of 5) and 13% (1 of 8) of the liver tumors from NNK- and NDMA-treated mice, respectively. Southern blot analysis indicated that the transforming gene present in all lung tumors was an activated K-ras oncogene. Both rearranged bands and amplified signals were detected in the transfectants. The one transformant from the NDMA-induced liver tumor contained an activated K-ras gene. In contrast, the two liver transformants from NNK-induced tumors did not contain an activated ras or raf gene. Hybridization with oligonucleotide probes that were centered around either codon 12 or 61 of the K-ras gene were utilized to localize the mutations. Activation of this gene appeared to occur largely via a mutation in codon 12 (15 of 20 transformants) and was observed with a similar frequency in pulmonary tumors induced by either compound. The remaining mutations were found in codon 61. The specific mutation within these two codons was determined by amplifying the exon containing the base change, followed by direct sequencing. With one exception the mutation observed in codon 12 was a GC to AT transition (GGT to GAT). One transformant contained a GC to TA transversion. The activating mutation detected in codon 61 was always an AT to GC transition of the middle A (CAA to CGA). The GC to AT mutation observed in codon 12 is consistent with the formation of the O6-methylguanine adduct. Similar concentrations (23 to 32 pmol/mumol deoxyguanosine) of this promutagenic adduct were detected in lungs during treatment with either NNK or NDMA.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Belinsky, S A AU - Devereux, T R AU - Maronpot, R R AU - Stoner, G D AU - Anderson, M W AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/10/01/ PY - 1989 DA - 1989 Oct 01 SP - 5305 EP - 5311 VL - 49 IS - 19 SN - 0008-5472, 0008-5472 KW - Codon KW - 0 KW - Nitrosamines KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Neoplasms, Experimental -- chemically induced KW - Blotting, Southern KW - Neoplasms, Experimental -- analysis KW - DNA Mutational Analysis KW - Mice KW - Female KW - Genes, ras KW - Adenocarcinoma -- chemically induced KW - Transfection KW - Lung Neoplasms -- genetics KW - Gene Expression Regulation KW - Adenocarcinoma -- genetics KW - Lung Neoplasms -- chemically induced KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79159208?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-05 N1 - Date created - 1989-10-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The Structure of Attitude Strength AN - 61256476; 91X6186 AB - While many studies support the claim that strong attitudes have greater impact on cognition & behavior than do weak ones, the claim is called into question by the diversity of indicators commonly used for testing attitude strength with respect to a target object: attributed importance, intensity, extremity, or certainty of attribution, ego involvement, frequency of verbal reference, attention to relevant information, attitude accessibility, knowledge about & direct experience with target object, & affective-cognitive consistency. The interaction between these indicators is explored here through surveys of 288 Ohio State U students on abortion, capital punishment, & defense spending. Multitrait-multimethod confirmatory factor analysis of results suggests that while individual indicators can be grouped in various ways, no consistent, univocal scale of attitude strength emerges. 6 Tables, 51 References. Adapted from the source document. JF - Chung Yang Yen Chiu Yuan Min Tsu Hsueh Yen Chiu So Chi K'an/Bulletin of the Institute of Ethnology Academia Sinica AU - Chuang, Yao-chia AD - F3 No 28 Alley 122 Lane 411 Nei Hu Rd Section 1, Taipei Taiwan Y1 - 1989/10// PY - 1989 DA - October 1989 SP - 227 EP - 256 IS - 68 SN - 0001-3935, 0001-3935 KW - attitude strength, cognitive impacts, measurement problems KW - surveys KW - university students, Ohio KW - Social Attitudes KW - Cognition KW - Methodological Problems KW - Ohio KW - article KW - 0312: social psychology; personality & culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61256476?accountid=14244 LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - CYMHAZ N1 - SubjectsTermNotLitGenreText - Ohio; Cognition; Social Attitudes; Methodological Problems ER - TY - JOUR T1 - Behavioral evaluation of the anti-excitotoxic properties of MK-801: comparison with neurochemical measurements. AN - 79293235; 2530473 AB - The ability of MK-801 to protect striatal neurons from the excitotoxic action of quinolinic acid was evaluated by means of apomorphine-induced rotational behavior and by measurement of striatal choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activity, neurochemical markers for cholinergic and GABAergic neurons, respectively. Animals with a unilateral quinolinic acid lesion of the striatum exhibited a vigorous rotational response when challenged with apomorphine (0.5 mg/kg, s.c.) 6 days later and were found to have an 88 90% depletion of striatal ChAT and GAD activity. Treatment with a high dose of MK-801 (10 mg/kg, i.p.) prior to intrastriatal injection of quinolinic acid eliminated the subsequent rotational response to apomorphine and resulted in complete protection of striatal ChAT and GAD activity. Lower doses of MK-801 (1, 3 and 5 mg/kg, i.p.) failed to significantly reduce the rotational response to apomorphine but provided partial, dose-dependent protection of both ChAT and GAD activity. The rotational response to apomorphine correlated with the percent reduction in both ChAT activity (r = 0.57, P less than 0.0005) and GAD activity (r = 0.49, P less than 0.0005). Rotational behavior may thus provide a means to evaluate the functional integrity of the striatum. JF - Neuroscience letters AU - Susel, Z AU - Engber, T M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/09/25/ PY - 1989 DA - 1989 Sep 25 SP - 125 EP - 129 VL - 104 IS - 1-2 SN - 0304-3940, 0304-3940 KW - Anticonvulsants KW - 0 KW - Dibenzocycloheptenes KW - Pyridines KW - Quinolinic Acids KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Glutamate Decarboxylase KW - EC 4.1.1.15 KW - Quinolinic Acid KW - F6F0HK1URN KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Apomorphine -- pharmacology KW - Choline O-Acetyltransferase -- metabolism KW - Male KW - Glutamate Decarboxylase -- metabolism KW - Corpus Striatum -- physiopathology KW - Dibenzocycloheptenes -- pharmacology KW - Corpus Striatum -- drug effects KW - Stereotyped Behavior -- drug effects KW - Pyridines -- antagonists & inhibitors KW - Nervous System Diseases -- physiopathology KW - Nervous System Diseases -- chemically induced KW - Dibenzocycloheptenes -- therapeutic use KW - Nervous System Diseases -- prevention & control KW - Quinolinic Acids -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79293235?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-20 N1 - Date created - 1989-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A single glutamic acid residue plays a key role in the transcriptional activation function of lambda repressor. AN - 79189261; 2570642 AB - Previous experiments have suggested that negative charge is an important aspect of the activating region of lambda repressor as it is for at least one class of eukaryotic transcriptional activators. Here we randomize amino acids in the activating region of repressor and assay the function of over 100 variants. We find that acidic residues at the four solvent-exposed positions on the surface of an alpha helix (helix 2 in the structure) together comprise a strong activating region. Only one of these acidic residues, however, is critical for activation, and at this position glutamate is strongly preferred to aspartate. At the three remaining positions, certain uncharged residues (different ones at each position) function as well as or better than the acidic residues. Basic residues, however, are highly detrimental to function at all four positions. Our mutagenesis studies also suggest limitations on amino acid substitutions that allow formation of the helix-turn-helix DNA binding motif found in repressor and in many other DNA binding regulatory proteins. JF - Cell AU - Bushman, F D AU - Shang, C AU - Ptashne, M AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1989/09/22/ PY - 1989 DA - 1989 Sep 22 SP - 1163 EP - 1171 VL - 58 IS - 6 SN - 0092-8674, 0092-8674 KW - DNA-Binding Proteins KW - 0 KW - Glutamates KW - Repressor Proteins KW - Transcription Factors KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - phage repressor proteins KW - Glutamic Acid KW - 3KX376GY7L KW - Index Medicus KW - Base Sequence KW - Models, Molecular KW - Operon KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Plasmids KW - Nucleic Acid Conformation KW - Protein Conformation KW - Genes KW - Bacteriophage lambda -- genetics KW - Repressor Proteins -- physiology KW - Escherichia coli -- genetics KW - Transcription, Genetic KW - Gene Expression Regulation KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79189261?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-24 N1 - Date created - 1989-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Toxicity of levamisole and 5-fluorouracil in human colon carcinoma cells. AN - 79200100; 2778828 AB - The combination of 5-fluorouracil (5-FU) with the immunomodulator levamisole (Lev) has been clinically tested in patients with metastatic colorectal carcinoma and as adjuvant therapy following primary tumor surgery. In some studies in advanced disease, the addition of Lev to 5-FU improved the median duration of response; in the adjuvant setting, the combination was associated with improvement in the disease-free survival. We studied whether Lev was directly toxic to three human colorectal carcinoma cell lines (HCT 116, SNU-C4, and NCI-H630). We also evaluated the toxicity of Lev in combination with 5-FU in these three cell lines. Lev inhibited the growth of all three colorectal cell lines, but only at concentrations two logs above that achieved with a standard 150-mg oral dose of Lev. In cell growth studies, 500 and 1,000 microM Lev increased the toxicity of 5-FU in HCT 116 cells in an additive fashion. In clonogenic assays, continuous exposure to 10 or 100 microM Lev was minimally toxic and did not enhance the lethality associated with a 24-hour exposure to 5-FU in any of the cell lines. Lev alone at 1,000 microM decreased colony formation by 45% in HCT 116 cells. A combination of 1,000 microM Lev with 10 microM 5-FU resulted in a decrease in HCT 116 colony formation from 54% to 6% of control levels. Continuous exposure of NCI-H630 cells to 500 microM Lev decreased colony formation to 76.5% of control levels; when Lev was combined with 50 microM 5-FU, colony formation was decreased from 59.5% to 27.5% of control levels. We conclude that at concentrations achievable with conventional doses of Lev, there was no evidence of direct toxicity in these colorectal cell lines. Furthermore, an additive interaction with 5-FU was evident only at suprapharmacologic doses of Lev. JF - Journal of the National Cancer Institute AU - Grem, J L AU - Allegra, C J AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09/20/ PY - 1989 DA - 1989 Sep 20 SP - 1413 EP - 1417 VL - 81 IS - 18 SN - 0027-8874, 0027-8874 KW - Levamisole KW - 2880D3468G KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Clone Cells KW - Drug Administration Schedule KW - Tumor Cells, Cultured KW - Humans KW - Drug Synergism KW - Levamisole -- pharmacology KW - Colonic Neoplasms -- drug therapy KW - Fluorouracil -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79200100?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-13 N1 - Date created - 1989-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Activation of immobilized, biotinylated choleragen AI protein by a 19-kilodalton guanine nucleotide-binding protein. AN - 79428308; 2514798 AB - Cholera toxin catalyzes the ADP-ribosylation that results in activation of the stimulatory guanine nucleotide-binding protein of the adenylyl cyclase system, known as Gs. The toxin also ADP-ribosylates other proteins and simple guanidino compounds and auto-ADP-ribosylates its AI protein (CTA1). All of the ADP-ribosyltransferase activities of CTAI are enhanced by 19-21-kDa guanine nucleotide-binding proteins known as ADP-ribosylation factors, or ARFs. CTAI contains a single cysteine located near the carboxy terminus. CTAI was immobilized through this cysteine by reaction with iodoacetyl-N-biotinyl-hexylenediamine and binding of the resulting biotinylated protein to avidin-agarose. Immobilized CTAI catalyzed the ARF-stimulated ADP-ribosylation of agmatine. The reaction was enhanced by detergents and phospholipid, but the fold stimulation by purified sARF-II from bovine brain was considerably less than that observed with free CTA. ADP-ribosylation of Gsa by immobilized CTAI, which was somewhat enhanced by sARF-II, was much less than predicted on the basis of the NAD:agmatine ADP-ribosyltransferase activity. Immobilized CTAI catalyzed its own auto-ADP-ribosylation as well as the ADP-ribosylation of the immobilized avidin and CTA2, with relatively little stimulation by sARF-II. ADP-ribosylation of CTA2 by free CTAI is minimal. These observations are consistent with the conclusion that the cysteine near the carboxy terminus of the toxin is not critical for ADP-ribosyltransferase activity or for its regulation by sARF-II. Biotinylation and immobilization of the toxin through this cysteine may, however, limit accessibility to Gsa or SARF-II, or perhaps otherwise reduce interaction with these proteins whether as substrates or activator. JF - Biochemistry AU - Noda, M AU - Tsai, S C AU - Adamik, R AU - Bobak, D A AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/09/19/ PY - 1989 DA - 1989 Sep 19 SP - 7936 EP - 7940 VL - 28 IS - 19 SN - 0006-2960, 0006-2960 KW - NAD KW - 0U46U6E8UK KW - Biotin KW - 6SO6U10H04 KW - Cholera Toxin KW - 9012-63-9 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Enzyme Activation KW - Molecular Weight UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79428308?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Synthetic non-peptide inhibitors of HIV protease. AN - 79227790; 2675834 AB - We have studied the inhibition of HIV protease by the antifungal antibiotic cerulenin, as well as by several related synthetic, structurally simpler analogs. The effect of these compounds on HIV protease was conveniently studied by monitoring the cleavage of an authentic single peptide bond in a synthetic nonapeptide corresponding to a natural cleavage site in HIV-1 gag precursor polyprotein. The relative inhibitory effects of these compounds have afforded an insight into the structural characteristics which impart antiprotease activity. JF - Biochemical and biophysical research communications AU - Blumenstein, J J AU - Copeland, T D AU - Oroszlan, S AU - Michejda, C J AD - Laboratory of Chemical and Physical Carcinogenesis, NCI-Frederick Cancer Research Facility MD 21701. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 980 EP - 987 VL - 163 IS - 2 SN - 0006-291X, 0006-291X KW - Antifungal Agents KW - 0 KW - Protease Inhibitors KW - Cerulenin KW - 17397-89-6 KW - Endopeptidases KW - EC 3.4.- KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Endopeptidases -- metabolism KW - Hydrolysis KW - Structure-Activity Relationship KW - Protease Inhibitors -- pharmacology KW - Antifungal Agents -- pharmacology KW - Cerulenin -- pharmacology KW - Protease Inhibitors -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79227790?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Monoclonal antibodies to rat liver cytochrome P-450 2c/RLM5 that regiospecifically inhibit steroid metabolism. AN - 79215913; 2783161 AB - Hybridomas were formed from myeloma cells and spleen cells derived from BALB/c female mice immunized with purified liver microsomal cytochrome P-450 2c/RLM5 (P-450 gene IIC11) isolated from untreated adult male rats. Six hybridoma clones produced monoclonal antibodies (MAbs) of the IgM(kappa) type. All the MAbs bound strongly to P-450 2c/RLM5 when measured by radioimmunoassay, and four of the six specifically immunoprecipitated P-450 2c/RLM5 in an Ouchterlony double-immunodiffusion test. These four MAbs also bound but did not immunoprecipitate P-450 RLM3. The MAbs that precipitated P-450 2c/RLM5 neither bound nor precipitated P-450 PB-B (gene IIB1) and P-450 BNF-B (gene IA1) of rats or P-450 LM2 and P-450 LM4 of rabbits. In contrast, mouse polyclonal anti-P-450 2c/RLM5 antibody strongly immunoprecipitated P-450 RLM3 as well as P-450 2c/RLM5 and to a lesser extent P-450 PB-B and P-450 LM2. The MAbs that precipitated P-450 2c/RLM5 also inhibited by more than 90% androstenedione 16 alpha-hydroxylase activity of untreated rat microsomes, but did not inhibit microsomal 6 beta- or 7 alpha-hydroxylation. In addition, complete inhibition of both androstenedione 16 alpha-hydroxylation and testosterone 16 alpha-hydroxylation was observed in a reconstituted system with P-450 2c/RLM5. Androstenedione 6 beta-hydroxylation catalyzed by P-450 2c/RLM5 was also inhibited, whereas P-450 3-catalyzed 7 alpha-hydroxylation was not inhibited by the MAbs. P-450 2c/RLM5 catalyzed 2 alpha-, 16 alpha- and 6 beta-hydroxylation of progesterone in a reconstituted system were also inhibited by the MAb by 60-80%. These MAbs should prove useful for "reaction phenotyping," i.e. for defining the contribution of microsomal P-450 2c/RLM5 to the oxidative metabolism of endogenous steroids and other P-450 substrates in animal and human tissues. JF - Biochemical pharmacology AU - Park, S S AU - Waxman, D J AU - Lapenson, D P AU - Schenkman, J B AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 3067 EP - 3074 VL - 38 IS - 18 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - Steroids KW - Androstenedione KW - 409J2J96VR KW - Progesterone KW - 4G7DS2Q64Y KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - CYP2C9 protein, human KW - EC 1.14.13.- KW - Cytochrome P-450 CYP2C9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C11 protein, rat KW - CYP2C8 protein, human KW - Cytochrome P-450 CYP2C8 KW - Cytochrome P450 Family 2 KW - Steroid 16-alpha-Hydroxylase KW - Index Medicus KW - Rats KW - Antibody Specificity KW - Animals KW - Progesterone -- metabolism KW - Mice KW - Mice, Inbred BALB C KW - Androstenedione -- metabolism KW - Male KW - Female KW - Hydroxylation KW - Microsomes, Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- immunology KW - Steroids -- metabolism KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79215913?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-16 N1 - Date created - 1989-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Induction of rat liver microsomal and nuclear cytochrome P-450 by dietary 2-acetylaminofluorene and butylated hydroxytoluene. AN - 79215756; 2783162 AB - The influence of dietary 2-acetylaminofluorene (AAF) on the cytochrome P-450 content of rat liver microsomal and nuclear fractions was immunochemically probed with monoclonal and polyclonal antibodies to cytochromes P-450c and P-450d. Cytochrome P-450d but not P-450c was immunodetected in microsomes, nuclear envelopes, and nuclei from untreated rats. The levels of both cytochromes P-450c and P-450d were elevated after a diet of either 0.1% AAF for 1 week or 0.05% AAF for 3 weeks. However, the level of cytochrome P-450c relative to P-450d was lower after the more prolonged AAF feeding. Supplementation of AAF-containing diets with 0.3% butylated hydroxytoluene (BHT), which affords protection against AAF hepatocarcinogenesis in high-fat fed rats, protected and/or induced total (spectral) nuclear envelope cytochrome P-450 content. Immunochemical studies of liver fractions showed that BHT enhanced the AAF-dependent induction of cytochrome P-450c, but not of P-450d. This was a concerted effect of AAF + BHT since dietary BHT by itself did not affect the levels of cytochrome P-450c or P-450d as compared to control rats. Since 1- to 3-week dietary AAF had little effect on total (spectral analyses) microsomal cytochrome P-450 but markedly reduced total P-450 in nuclear envelopes, the coordinated induction of specific cytochrome P-450s in the different fractions suggests selective induction and depression of different forms of cytochrome P-450 and provides additional evidence for independent regulation of the drug-metabolizing system in nuclear envelope and microsomes. In addition, these results suggest that regulation of cytochrome P-450 may play a crucial role in the nutritional modulation of AAF hepatocarcinogenesis. JF - Biochemical pharmacology AU - Friedman, F K AU - Miller, H AU - Park, S S AU - Graham, S A AU - Gelboin, H V AU - Carubelli, R AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 3075 EP - 3081 VL - 38 IS - 18 SN - 0006-2952, 0006-2952 KW - Antibodies, Monoclonal KW - 0 KW - Butylated Hydroxytoluene KW - 1P9D0Z171K KW - Methylcholanthrene KW - 56-49-5 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Immunoblotting KW - Animals KW - Enzyme Induction -- drug effects KW - Methylcholanthrene -- pharmacology KW - Diet KW - Male KW - Cell Nucleus -- enzymology KW - 2-Acetylaminofluorene -- pharmacology KW - Microsomes, Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- immunology KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Butylated Hydroxytoluene -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79215756?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-16 N1 - Date created - 1989-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Free-radical formation by mitomycin C and its novel analogs in cardiac microsomes and the perfused rat heart. AN - 79204433; 2550081 AB - Using a spin-trapping technique, we have examined free-radical formation by mitomycin C and its analogs, BMY 25282 and BMY 25067, in rat cardiac microsomes and isolated perfused rat hearts. All three drugs stimulated 2--4-fold OH radical formation in cardiac microsomes which was inhibited by SOD and catalase. Superoxide anion radical was also detected in the presence of diethylenetetraaminopentaacetic acid. Addition of DMSO yielded methyl radicals, thus indicating the production of free OH under these conditions. Similar stimulation of OH formation (2--3-fold) in the perfusates from rat hearts was detected with all three drugs. Perfusion with catalase (550 U/ml) completely suppressed the OH signal both in the presence and absence of the drugs, thus suggesting the intermediacy of hydrogen peroxide. However, BMY 25067-induced OH formation was more sensitive to inhibition by superoxide dismutase (SOD) and the iron chelator ICRF-187. Perfusion with DMSO produced methyl radicals at the expense of OH in the presence of all three drugs. SOD and catalase inhibited DMPO-OH signals, indicating that most of the OH formation was extracellular in this setting. While mitomycin C and BMY 25067 (up to 10 microM) did not affect the heart rate, perfusion with 10 microM BMY 25282 caused acute arrhythmia and cardiac standstill within 20 min. An initial surge in OH formation (2-fold) accompanied this cardiotoxic effect. Both the arrhythmia and the free radical signal were partially blocked by SOD, catalase and ICRF-187, indicating that iron-dependent oxygen radical formation from BMY-25282 (and possibly other compounds) is involved, in part, in inducing toxic manifestations in the rat heart and possibly in clinic. JF - Biochimica et biophysica acta AU - Politi, P M AU - Rajagopalan, S AU - Sinha, B K AD - Clinical Pharmacology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 341 EP - 348 VL - 992 IS - 3 SN - 0006-3002, 0006-3002 KW - Free Radicals KW - 0 KW - Hydroxides KW - Mitomycins KW - Superoxides KW - 11062-77-4 KW - Hydroxyl Radical KW - 3352-57-6 KW - Mitomycin KW - 50SG953SK6 KW - N(6)-((dimethylamino)methylene)mitomycin C KW - 88949-01-3 KW - N-7-(2-(nitrophenyldithio)ethyl)mitomycin C KW - 95056-36-3 KW - Catalase KW - EC 1.11.1.6 KW - Index Medicus KW - Animals KW - Perfusion KW - Catalase -- pharmacology KW - Rats, Inbred Strains KW - Rats KW - Superoxides -- metabolism KW - Heart Rate -- drug effects KW - Electron Spin Resonance Spectroscopy KW - Kinetics KW - In Vitro Techniques KW - Hydroxides -- metabolism KW - Male KW - Microsomes -- metabolism KW - Heart -- drug effects KW - Mitomycins -- pharmacology KW - Myocardium -- metabolism KW - Microsomes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79204433?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-25 N1 - Date created - 1989-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Phase I trial and pharmacokinetic evaluation of fazarabine in children. AN - 79166768; 2475244 AB - A phase I trial of fazarabine (1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 16 children with refractory malignancies. Dose-limiting toxicity consisting of reversible granulocytopenia and thrombocytopenia was observed in 4 of 4 solid tumor patients treated at the starting dose of 20 mg/m2/h. Subsequent patients were treated at a dose of 15 mg/m2/h which was determined to be the maximum tolerated dose. Moderate nausea and vomiting were the only other toxicities observed. Plasma steady-state concentrations of fazarabine were attained by 2-4 h in all patients and were 1.8 and 2.5 microM at the 15- and 20-mg/m2/h doses, respectively. The total body clearance of fazarabine was 571 and 550 ml/min/m2 at the 15- and 20-mg/m2/h doses, respectively. In three of four patients evaluated, fazarabine was detectable in the cerebrospinal fluid (CSF). Steady-state CSF concentrations ranged from 0.29 to 0.74 microM in these three individuals and the steady-state CSF:plasma ratios ranged from 0.22-0.25. Both the plasma and CSF steady-state concentrations were within the 0.1 to 1 microM range reported to be cytotoxic in vitro against the Molt-4 human T-lymphoblastic leukemia cell line. Based on the above, the optimal dose for phase II trials of fazarabine administered as a 24-h infusion is 15 mg/m2/h (360 mg/m2/day). JF - Cancer research AU - Heideman, R L AU - Gillespie, A AU - Ford, H AU - Reaman, G H AU - Balis, F M AU - Tan, C AU - Sato, J AU - Ettinger, L J AU - Packer, R J AU - Poplack, D G AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 5213 EP - 5216 VL - 49 IS - 18 SN - 0008-5472, 0008-5472 KW - Antimetabolites, Antineoplastic KW - 0 KW - fazarabine KW - 5V71D8JOKK KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Neoplasms -- drug therapy KW - Drug Evaluation KW - Infusions, Intravenous KW - Humans KW - Metabolic Clearance Rate KW - Child KW - Male KW - Female KW - Azacitidine -- therapeutic use KW - Azacitidine -- pharmacokinetics KW - Azacitidine -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166768?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Enhanced therapeutic efficacy of an immunotoxin in combination with chemotherapy against an intraperitoneal human tumor xenograft in athymic mice. AN - 79165765; 2504482 AB - A mouse IgG2b anti-pan carcinoma monoclonal antibody, NR-LU-10, was shown to bind homogeneously to ascites xenografts of both ovarian and colon carcinoma. Following linkage to a highly potent holotoxin, Pseudomonas exotoxin A (PE), NR-LU-10 demonstrated high potency and selectivity in vitro (ID50 = 100 pg/ml; elimination of greater than or equal to 4.5 logs of cells). The conjugate was evaluated for therapeutic efficacy against a human colon tumor (HT-29) transplantable in the peritoneal cavity of nude mice. Beginning 3 days after HT-29 injection, mice received either three or six i.p. injections of 0.5 micrograms of unconjugated NR-LU-10 or immunotoxin conjugate (NR-LU-10/PE) every other day. Mice that received three or six treatments of NR-LU-10 alone had median survival times (MSTs) of 39 and 40 days, respectively, which did not differ significantly from the MST observed for the untreated control groups (MST = 35 days). In contrast, treatment with three or six injections of 0.5 micrograms NR-LU-10/PE exhibited significantly increased MSTs (P = 0.002) of 50 and 60 days, respectively. Coinjection of unconjugated NR-LU-10 (20 micrograms) and 0.5 micrograms of NR-LU-10/PE blocked the therapeutic effect of the immunotoxin (MST = 33 days). The therapeutic efficacy of NR-LU-10/PE was further enhanced against HT-29 when administered i.p. during and after cytoreductive chemotherapy. The i.p. administration of 300 mg/lg of cyclophosphamide plus 100 mg/kg of the chemoprotective drug, WR-2721, 10 and 17 days posttumor cell inoculation induced a significant increase in MST from 36 days to 59 days (P = 0.002). Interestingly, groups of mice that received either two, four, or seven treatments of NR-LU-10/PE following cytoreductive therapy exhibited a further significant increase (P = 0.001) in MSTs of 89, 97, and 105 days, respectively. Therefore, the use of immunotoxin therapy following cytoreductive chemotherapy significantly prolonged survival time of mice bearing the HT-29 colon tumor over that observed with chemotherapy or NR-LU-10/PE alone. JF - Cancer research AU - Pearson, J W AU - Sivam, G AU - Manger, R AU - Wiltrout, R H AU - Morgan, A C AU - Longo, D L AD - Laboratory of Experimental Immunology, NCI-Frederick Cancer Research Facility, Maryland 21701. Y1 - 1989/09/15/ PY - 1989 DA - 1989 Sep 15 SP - 4990 EP - 4995 VL - 49 IS - 18 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Humans KW - Antigens, Neoplasm -- analysis KW - Transplantation, Heterologous KW - Mice, Nude KW - Mice KW - Flow Cytometry KW - Pseudomonas aeruginosa KW - Tumor Stem Cell Assay KW - Male KW - Cell Line KW - Antibodies, Monoclonal -- therapeutic use KW - Colonic Neoplasms -- therapy KW - Immunotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79165765?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine. AN - 79219926; 2790457 AB - The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated. JF - Brain research AU - Weiss, S R AU - Post, R M AU - Szele, F AU - Woodward, R AU - Nierenberg, J AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/09/11/ PY - 1989 DA - 1989 Sep 11 SP - 72 EP - 79 VL - 497 IS - 1 SN - 0006-8993, 0006-8993 KW - Anesthetics KW - 0 KW - Anticonvulsants KW - Carbamazepine KW - 33CM23913M KW - Lidocaine KW - 98PI200987 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Dose-Response Relationship, Drug KW - Male KW - Anticonvulsants -- pharmacology KW - Kindling, Neurologic -- drug effects KW - Anesthetics -- pharmacology KW - Carbamazepine -- pharmacology KW - Lidocaine -- pharmacology KW - Cocaine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79219926?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-14 N1 - Date created - 1989-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The CYP2D gene subfamily: analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats. AN - 79334117; 2819073 AB - The DA rat has been proposed as an animal model for the human debrisoquine 4-hydroxylase/bufuralol 1'-hydroxylase genetic deficiency. To determine the mechanism of this deficiency, we isolated and sequenced five cDNAs in the CYP2D gene subfamily including a new IID1 allele and two cDNAs of novel P450s, designated IID3 and IID5. IID3 and IID5 cDNA-deduced amino acid sequences contained 500 and 504 residues with calculated molecular weights of 56,683 and 57,081, respectively. IID5 displayed 20 amino acid differences with the IID1, yet bore only 72% and 76% similarity to IID2 and IID3. Despite an overall nucleotide similarity of 80-98% between the 4 cDNAs, a region of 134 nucleotides of sequence exists that contains only 1 base difference. This region is probably the result of gene conversion events between the P450 IID genes. Although all IID cDNAs were expressed into immunodetectable proteins using the COS cell SV40-based expression system, only IID1 could effectively catalyze the oxidation of the prototype substrate bufuralol. Expression of a cDNA isolated in an earlier study [Gonzalez, F. J., Matsunaga, T., Nagata, K., Meyer, U. A., Nebert, D. W., Pastewka, J., Kozak, C. A., Gillette, J., Gelboin, H. V., & Hardwick, J. P. (1987) DNA 6, 149-161], previously called db1 and now designated IID1v, produced a protein with a drastically reduced activity as compared to cDNA-expressed IID1 despite only four amino acid differences between the two cDNA-deduced protein sequences.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Matsunaga, E AU - Zanger, U M AU - Hardwick, J P AU - Gelboin, H V AU - Meyer, U A AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/05/ PY - 1989 DA - 1989 Sep 05 SP - 7349 EP - 7355 VL - 28 IS - 18 SN - 0006-2960, 0006-2960 KW - RNA, Messenger KW - 0 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Gene Conversion KW - Blotting, Northern KW - Sequence Homology, Nucleic Acid KW - Biological Evolution KW - Multigene Family KW - Disease Models, Animal KW - Amino Acid Sequence KW - Rats, Inbred Strains KW - Rats KW - Alleles KW - Base Sequence KW - Blotting, Western KW - Gene Expression Regulation, Enzymologic KW - DNA -- genetics KW - Molecular Sequence Data KW - Male KW - Aging -- genetics KW - Female KW - Cytochrome P-450 Enzyme System -- genetics KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79334117?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J02869; GENBANK; J02868; J02867 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. AN - 79332559; 2573390 AB - A cDNA designated hIIB1, representing the entire coding sequence of a P450 in the IIB gene family, was isolated from a human liver lambda gt11 library by using the rat IIB1 cDNA as a probe. The hIIB1 protein, deduced from the cDNA sequence, contained 491 amino acids, had a calculated molecular weight of 56,286, and displayed 76% amino acid similarity with the rat IIB1 protein. Expression of this cDNA, using the vaccinia virus system, yielded a P450 that had a reduced CO-binding spectrum with an absorption maximum of 452 nm. The expressed human enzyme was able to catalyze the deethylation of 7-ethoxy-coumarin. Total RNA from 13 livers was probed for levels of hIIB mRNA. Two livers had high levels, four contained moderate levels, and eight contained very low, or no detectable, mRNA. These data suggest either that defective hIIB1 genes exist in humans or that the hIIB1 gene is regulated and variably induced in our liver specimens. To search for mutant mRNA transcripts, libraries were constructed from livers expressing low levels of hIIB1 mRNA. A cDNA, designated hIIB2, was isolated that was identical with the hIIB1 cDNA except for the presence of an unusual alteration of the DNA near its 5' end corresponding to the putative exon 4. This alteration was caused by a deletion of 29 bp and an insertion of 44 bp of nonhomologous DNA. This sequence replacement occurs at the junction of the third and fourth exons as predicted from the structure of the rat IIB1 gene, suggesting that a faulty splice might have given rise to the variant hIIb2 transcript.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biochemistry AU - Yamano, S AU - Nhamburo, P T AU - Aoyama, T AU - Meyer, U A AU - Inaba, T AU - Kalow, W AU - Gelboin, H V AU - McBride, O W AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/05/ PY - 1989 DA - 1989 Sep 05 SP - 7340 EP - 7348 VL - 28 IS - 18 SN - 0006-2960, 0006-2960 KW - RNA, Messenger KW - 0 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Chromosome Deletion KW - Sequence Homology, Nucleic Acid KW - Exons KW - Multigene Family KW - Humans KW - Amino Acid Sequence KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - Adult KW - Molecular Sequence Data KW - Middle Aged KW - Repetitive Sequences, Nucleic Acid KW - Mutation KW - Female KW - Male KW - Gene Expression Regulation, Enzymologic KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA -- genetics KW - Chromosomes, Human, Pair 19 KW - Liver -- metabolism KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - RNA, Messenger -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79332559?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-11 N1 - Date created - 1990-01-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M29873; GENBANK; M29874; J02864 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Enhancement of immunotoxin efficacy by acid-cleavable cross-linking agents utilizing diphtheria toxin and toxin mutants. AN - 79176480; 2475487 AB - We have utilized a new class of acid-cleavable protein cross-linking reagents in the construction of antibody-diphtheria toxin conjugates (Srinivaschar, K., and Neville, D. M., Jr. (1989) Biochemistry 28, 2501-2509). The potency of anti-CD5 conjugates assayed by inhibition of protein synthesis on CD5 bearing cells (Jurkat) is correlated with cross-linker hydrolytic rates. The maximum increase in potency of the cleavable conjugates over non-cleavable conventional conjugates is 50-fold and is specific for the CD5 uptake route as judged by competition with excess anti-CD5. The potency of conjugates made from diphtheria toxin and the anti-high molecular weight melanoma-associated antigen (HMW-MAA) is enhanced 3-10-fold by a cleavable cross-linker. However the potency of transferrin or anti-CD3 diphtheria toxin conjugates is only minimally enhanced (2-3-fold). Mutant diphtheria toxins, CRM103 and CRM9, previously shown to express less than 1/100 of the wild type in binding affinity were substituted into these conjugates as probes for possible intracellular toxin receptor interactions. Both mutants were equally as toxic to Jurkat target cells exhibiting 1/700 the wild-type potency. CRM9 non-cleavable conjugates were equally as potent as wild-type conjugates for transferrin and anti-CD3-mediated uptake but not for anti-CD5-mediated uptake where toxicity was reduced 60-fold over the wild-type analog. The cleavable cross-linker enhanced the toxicity of anti-CD5-CRM103 and anti-CD5-CRM9 conjugates, but potency was only 1/10 that of the analogous wild-type cleavable conjugate. These data are consistent with a model in which potentiation of toxicity of the anti-CD5 and anti-high molecular weight melanoma-associated antigen conjugates by the cleavable cross-linker occurs from an enhanced intracellular toxin-toxin receptor interaction that ultimately results in increased toxin translocation to the cytosol compartment. In contrast, these data indicate that the anti-CD3 and transferrin uptake systems do not require this interaction in agreement with previous work (Johnson, V.G., Wilson, D., Greenfield, L., and Youle, R. J. (1988) J. Biol. Chem. 263, 1295-1300). JF - The Journal of biological chemistry AU - Neville, D M AU - Srinivasachar, K AU - Stone, R AU - Scharff, J AD - Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1989/09/05/ PY - 1989 DA - 1989 Sep 05 SP - 14653 EP - 14661 VL - 264 IS - 25 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD5 KW - Antigens, Differentiation KW - Antigens, Neoplasm KW - Cross-Linking Reagents KW - Diphtheria Toxin KW - Immunotoxins KW - Melanoma-Specific Antigens KW - Neoplasm Proteins KW - Protein Synthesis Inhibitors KW - Transferrin KW - Index Medicus KW - Animals KW - Antigens, Differentiation -- immunology KW - Humans KW - Hydrogen-Ion Concentration KW - Melanoma -- immunology KW - Hydrolysis KW - Molecular Weight KW - Transferrin -- metabolism KW - Protein Synthesis Inhibitors -- toxicity KW - Antibodies, Monoclonal -- toxicity KW - Transferrin -- toxicity KW - Neoplasm Proteins -- metabolism KW - Catalysis KW - Immunotoxins -- toxicity KW - Diphtheria Toxin -- toxicity KW - Diphtheria Toxin -- metabolism KW - Immunotoxins -- metabolism KW - Diphtheria Toxin -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79176480?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-11 N1 - Date created - 1989-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cerebral glucose utilization in rat brain during phenobarbital withdrawal. AN - 79270961; 2804629 AB - The phenobarbital withdrawal syndrome in rats is characterized by tremors, arched back, weight loss and hyperactivity. This syndrome is shown to be associated with both general and localized increases in cerebral glucose utilization. An increase in glucose utilization (significant at the P less than or equal to 0.001 level) was observed in 72% of the 57 structures examined. Increases in glucose utilization of greater than or equal to 180% of control values were noted in structures associated with the motor system (columns in the frontal sensorimotor cortex, globus pallidus, dentate nucleus of the cerebellum and ovoid areas in the cerebellar vermis), thalamic nuclei (lateral and posterior), dorsal lateral geniculate, mammillary body, cingulate cortex, locus ceruleus, and cerebellar flocculus and paraflocculus. The structures showing the greatest increase in glucose utilization were cerebellar paraflocculus (257% of control), columns in the frontal sensorimotor cortex (247% of control) and ovoid areas in the cerebellar vermis (223% of control). Areas of the brain that have been described as cell body areas for serotonergic (raphe), noradrenergic (locus ceruleus), dopaminergic (substantia nigra, zona compacta) and GABAergic (globus pallidus) neurons also showed increases in glucose utilization. The pattern of cerebral glucose utilization accompanying the phenobarbital withdrawal syndrome in rats contrasts with that for morphine withdrawal and exhibits both similarities and differences with respect to ethanol withdrawal. JF - Brain research AU - Marietta, C A AU - Wixon, H N AU - Weight, F F AU - Eckardt, M J AD - Laboratory of Physiologic and Pharmacologic Studies, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852. Y1 - 1989/09/04/ PY - 1989 DA - 1989 Sep 04 SP - 173 EP - 179 VL - 496 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Deoxyglucose KW - 9G2MP84A8W KW - Glucose KW - IY9XDZ35W2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Female KW - Deoxyglucose -- metabolism KW - Brain -- physiopathology KW - Substance Withdrawal Syndrome -- metabolism KW - Glucose -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79270961?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Xenobiotic metabolism in human brain--presence of cytochrome P-450 and associated mono-oxygenases. AN - 79270923; 2804643 AB - The cytochromes P-450, a family of heme proteins, play an important role in the oxidation of drugs and carcinogens, as well as endogenous substrates. We report the presence of cytochrome P-450 and associated mono-oxygenase activity in human brain regions and their selective enrichment in the brainstem. Immunocytochemical studies on human medulla with antibodies raised to phenobarbital-inducible rat liver cytochrome P-450 indicate that the enzyme is primarily localized in the neuronal cell bodies and to a lesser extent in the axons. These observations indicate that the human brain could be involved in metabolism of xenobiotics and endogenous compounds, mediated through cytochrome P-450. JF - Brain research AU - Ravindranath, V AU - Anandatheerthavarada, H K AU - Shankar, S K AD - Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bangalore, India. Y1 - 1989/09/04/ PY - 1989 DA - 1989 Sep 04 SP - 331 EP - 335 VL - 496 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Enzyme Inhibitors KW - 0 KW - Xenobiotics KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Index Medicus KW - Humans KW - In Vitro Techniques KW - Adult KW - Enzyme Inhibitors -- pharmacology KW - Aged KW - Middle Aged KW - Brain Stem -- enzymology KW - Brain -- enzymology KW - Mixed Function Oxygenases -- metabolism KW - Brain Stem -- metabolism KW - Xenobiotics -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79270923?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-21 N1 - Date created - 1989-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide. AN - 79587672; 2519824 AB - The characterization of eight benzo[a]pyrene-deoxyribonucleoside adducts derived from reaction of the anti-dihydrodiol epoxide and deoxyguanylic and deoxyadenylic acids is described. It is reported that the epoxide ring is opened by the purine amino groups to yield similar amounts of both cis and trans products. NMR data show that the 7- and 8-hydroxyl groups are pseudodiaxial in the cis products and pseudodiequatorial in the trans products, and we suggest that these products arise from reaction with the diaxial and diequatorial conformers of the dihydrodiol epoxides, respectively. The chiral nature of the interactions of these metabolites with DNA restricts the range of products formed with this macromolecule, and a trans product with deoxyguanosine is the major product formed with either enantiomer of the anti-dihydrodiol epoxide. JF - Chemical research in toxicology AU - Cheng, S C AU - Hilton, B D AU - Roman, J M AU - Dipple, A AD - BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, Maryland 21701. PY - 1989 SP - 334 EP - 340 VL - 2 IS - 5 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Deoxyadenosines KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Stereoisomerism KW - Circular Dichroism KW - Deoxyadenosines -- chemistry KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - DNA Damage KW - Carcinogens -- chemistry KW - DNA -- chemistry KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79587672?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1992-03-09 N1 - Date created - 1992-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Botulinum toxin therapy in hemifacial spasm: clinical and electrophysiologic studies. AN - 79500193; 2630907 AB - Three patients with idiopathic hemifacial spasm were studied clinically and electrophysiologically before and after injections of botulinum toxin into the involved periocular and facial muscles. The spasms were improved for approximately 3 months, and the effect was repeatable on reinjection. The spasms diminished only as long as the muscles were clinically weak, and spasms were observed electromyographically even though therapy eliminated the clinical spasms. Uninjected muscles continued to have spasms. Transmission of excitation from the zygomatic branch to the marginal mandibular branch of the facial nerve and vice versa in all patients was unaltered after therapy, but the amplitude of the response was decreased. The efficacy of botulinum toxin in hemifacial spasm appears to be related to the production of muscle weakness; there is no demonstrable effect on phenomena believed to be ectopic excitation or ephaptic transmission in the facial nerve. JF - Muscle & nerve AU - Geller, B D AU - Hallett, M AU - Ravits, J AD - Division of Intramural Research, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 716 EP - 722 VL - 12 IS - 9 SN - 0148-639X, 0148-639X KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Index Medicus KW - Neuromuscular Junction -- drug effects KW - Humans KW - Injections, Intramuscular KW - Adult KW - Electromyography KW - Middle Aged KW - Female KW - Facial Muscles -- drug effects KW - Botulinum Toxins -- therapeutic use KW - Spasm -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79500193?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-05-08 N1 - Date created - 1990-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Chemoprevention and modern cancer prevention. AN - 79447395; 2694155 AB - Chemoprevention is a new area of research emphasis in cancer control. The rationale is based on the accumulation of laboratory and epidemiological data indicating that various agents may halt or reverse cancer progression in animals and may reduce risks in humans. For planning purposes, research leads are submitted to a strategic system of staging with defined criteria and decision points. A research lead that enters an intervention stage must evolve through a series of phases of testing and evaluation. Human intervention clinical trials have begun to test the hypothesis that certain agents can lower cancer incidence. JF - Preventive medicine AU - Malone, W F AU - Kelloff, G J AU - Boone, C AU - Nixon, D W AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland 20852-4200. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 553 EP - 561 VL - 18 IS - 5 SN - 0091-7435, 0091-7435 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Drug Evaluation, Preclinical KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- toxicity KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79447395?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-05 N1 - Date created - 1990-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Some statistical considerations for design of cancer prevention trials. AN - 79447264; 2694163 AB - Carcinogenesis is believed to occur in at least two stages, initiation and promotion, followed by a preneoplastic lesion which develops into cancer. Cancer prevention trials can be classified as primary if the intervention precedes initiation, secondary if it occurs during promotion, and tertiary if it is applied to a preneoplastic lesion. Tertiary prevention trials resemble treatment trials, but primary and secondary prevention trials may be very different in size, duration, and cost. After reviewing some basic questions which must be addressed in designing any cancer prevention trial, some special design considerations appropriate for primary and secondary prevention trials are discussed. These include the use of factorial designs, group or cluster randomization, special sample size calculations needed for large-scale trials of long duration with cancer incidence as the endpoint, and the idea of the case-cohort approach for monitoring and for subsequent exploratory analysis of trial data. JF - Preventive medicine AU - Byar, D P AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 688 EP - 699 VL - 18 IS - 5 SN - 0091-7435, 0091-7435 KW - Index Medicus KW - Animals KW - Factor Analysis, Statistical KW - Random Allocation KW - Humans KW - Clinical Trials as Topic KW - Case-Control Studies KW - Cluster Analysis KW - Research Design -- statistics & numerical data KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79447264?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-05 N1 - Date created - 1990-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. AN - 79416501; 2575218 AB - We have sequenced the human CYP1A2 (cytochrome P(3)450) gene, 1,906 basepairs (bp) of the 5' flanking region, and 113 bp of the 3' flanking region. The gene spans almost 7.8 kilobases, comprising seven exons and six introns. The transcriptional start site was determined by both primer extension and S1 mapping. Including the first noncoding exon of 55 bp, the entire mRNA is 3,121 bp in length, and the open reading frame, starting with nucleotide 10 of exon 2, encodes 515 amino acids (mol wt = 58,294). Between the human CYP1A2 and CYP1A1 (cytochrome P(1)450) genes, exons 2, 4, 6, and especially 5 are strikingly conserved in both nucleotide similarity and total number of bases. Alignment of the upstream sequences and exon 1 of human CYP1A2 with that of mouse or rat CYP1A2 revealed two possibly significant regions of similarity: 1) 68% in the approximately 150 bases immediately 5' from the mRNA cap site and 2) 80% identify between the human -841 to -758 segment and the mouse -1,529 to -1,439 segment. The canonical 5-bp box (CACGC), found upstream of all mammalian CYP1A1 genes to date and believed to interact with the inducer.aromatic hydrocarbon receptor complex, was not found on either strand in the 1,906 bp of the 5' flanking region of human CYP1A2. In contrast, alignment of the upstream sequences, exon 1, and intron 1 of human CYP1A1 with that of mouse or rat CYP1A1 revealed large, highly conserved regions. Conserved regions were found in intron 1 of the human, mouse, and rat CYP1A2 gene. These data suggest that the regulatory elements controlling the CYP1A2 gene might differ in location from those controlling the CYP1A1 gene. Among 12 human liver samples, striking differences (greater than 15-fold) in the 3.3-kilobase 1A2 mRNA levels were seen. This result may reflect significant genetic differences in constitutive and/or inducible CYP1A2 gene expression that could play an important role in individual risk of environmental toxicity or cancer. JF - Molecular endocrinology (Baltimore, Md.) AU - Ikeya, K AU - Jaiswal, A K AU - Owens, R A AU - Jones, J E AU - Nebert, D W AU - Kimura, S AD - Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1399 EP - 1408 VL - 3 IS - 9 SN - 0888-8809, 0888-8809 KW - RNA, Messenger KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Sequence Homology, Nucleic Acid KW - Exons KW - Humans KW - RNA, Messenger -- analysis KW - Mice KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - Restriction Mapping KW - In Vitro Techniques KW - Introns KW - Molecular Sequence Data KW - Cytochrome P-450 Enzyme System -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79416501?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-15 N1 - Date created - 1990-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Neoplastic transformation of human epithelial cells in vitro. AN - 79359004; 2686534 AB - Efforts to investigate the progression of events that lead human cells of epithelial origin to become neoplastic in response to carcinogenic agents have been aided by the development of tissue culture systems for propagation of epithelial cells. We have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. Primary human epidermal keratinocytes acquired indefinite lifespan in culture but did not undergo malignant conversion in response to infection with Adl2-SV40 virus. Subsequent addition of Ki-MSV, which contains a K-ras oncogene, to these cells induced morphological alterations and the acquisition of neoplastic properties. Nontumorigenic human epidermal keratinocytes immortalized by Adl2-SV40 virus (RHEK-1) were also transformed by treatment with chemical carcinogens (MNNG or 4NQO) and by X-ray irradiation. Such transformants showed morphological alterations and induced carcinomas when transplanted into nude mice. This in vitro system may be useful in assessing environmental carcinogens for human epithelial cells and in detecting new human oncogenes since ras oncogenes were not activated in these chemical--or X-ray--transformed RHEK-1 lines. Subsequently, it was found that this line could be transformed neoplastically by a variety of retroviruses containing H-ras, bas, fes, fms, erbB and src oncogenes. In addition, our recent results indicate that nontumorigenic RHEK-1 cells can be transformed following transfection with an activated human oncogene. Thus, this in vitro system may be useful in studying the interaction of a variety of carcinogenic agents and human epithelial cells. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of tumor viruses and chemical carcinogens or X-ray irradiation and support a multistep process for neoplastic conversion. Further, evidence for the multistep nature of neoplastic transformation of human epithelial cells in vitro using other model systems is presented. JF - Anticancer research AU - Rhim, J S AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. PY - 1989 SP - 1345 EP - 1365 VL - 9 IS - 5 SN - 0250-7005, 0250-7005 KW - Index Medicus KW - Epithelial Cells KW - Cells, Cultured KW - Humans KW - Keratinocytes -- cytology KW - Retroviridae -- genetics KW - Cell Line KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79359004?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-03 N1 - Date created - 1990-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Time course of verapamil interaction with morphine effects on physiological parameters in rats. AN - 79344040; 2573706 AB - The effects of subcutaneous doses of morphine and verapamil on respiratory and cardiovascular parameters have been assessed in conscious rats. Verapamil (10 mg kg-1) was injected simultaneously with morphine (16 mg kg-1) or at 10, 30, or 60 min before morphine administration. Morphine induced respiratory depression, as indicated by marked hypercapnia, hypoxia and acidosis, and caused marked tachycardia. Although morphine produced only a minor and inconsistent (but statistically significant, P less than 0.01) reduction of mean arterial blood pressure, morphine potentiated verapamil-induced hypotension. Verapamil suppressed morphine-induced hypercapnia only when injected simultaneously with morphine. Verapamil alone did not affect arterial blood gases or pH, but decreased heart rate and mean arterial blood pressure. Verapamil attenuated and delayed the maximum positive chronotropic effects of morphine at all times tested. Antagonism by verapamil of respiratory depression and tachycardia produced by morphine was unrelated to morphine levels in plasma. Thus, the explanation of verapamil-morphine interactions on respiration and cardiovascular function is not pharmacokinetic. JF - The Journal of pharmacy and pharmacology AU - Della Puppa, A AU - Ford-Rice, F AU - Snyder, F R AU - Cone, E AU - London, E D AD - Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 617 EP - 623 VL - 41 IS - 9 SN - 0022-3573, 0022-3573 KW - Carbon Dioxide KW - 142M471B3J KW - Morphine KW - 76I7G6D29C KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Oxygen Consumption -- drug effects KW - Heart Rate -- drug effects KW - Drug Interactions KW - Blood Pressure -- drug effects KW - Time Factors KW - Carbon Dioxide -- blood KW - Male KW - Morphine -- pharmacokinetics KW - Verapamil -- pharmacokinetics KW - Verapamil -- pharmacology KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79344040?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-08 N1 - Date created - 1990-01-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Magnetic resonance imaging studies of the brains of anesthetized rats treated with manganese chloride. AN - 79331668; 2819480 AB - An understanding of the distribution of manganese ions in the brain is of interest in connection with the development of an understanding of the neurotoxicity of this element. Information about the time dependent biodistribution of manganese ions in the brains of intact rats subsequent to single IP injections of MnCl2 has been obtained from magnetic resonance imaging (MRI) studies. The enhanced MRI contrast is based on the reduction in the spin lattice relaxation time (T1) of water protons which exchange into the coordination sphere of the manganese ions. These studies indicate rapid and significant accumulations of water accessible manganese in the ventricles, the pineal gland, and the pituitary gland. The rapid appearance of high levels of manganese in the ventricular cerebrospinal fluid indicates that manganese readily crosses the filtration barrier of the choroid plexus and is thereafter apparently absorbed by the ependymal surfaces of the ventricles and transported to the subarachnoid space. JF - Brain research bulletin AU - London, R E AU - Toney, G AU - Gabel, S A AU - Funk, A AD - National Institute of Environmental Health Sciences, NIH, Res. Triangle Park, NC 27709. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 229 EP - 235 VL - 23 IS - 3 SN - 0361-9230, 0361-9230 KW - Chlorides KW - 0 KW - Manganese Compounds KW - Manganese KW - 42Z2K6ZL8P KW - manganese chloride KW - QQE170PANO KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Magnetic Resonance Imaging KW - Animals KW - Pineal Gland -- metabolism KW - Anesthesia KW - Cerebral Ventricles -- metabolism KW - Pituitary Gland -- metabolism KW - Male KW - Blood-Brain Barrier KW - Brain -- metabolism KW - Manganese -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79331668?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-03 N1 - Date created - 1990-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Purification, toxicity, and antiendotoxin activity of polymyxin B nonapeptide. AN - 79330340; 2554795 AB - Polymyxin B, a relatively toxic antibiotic, has potent endotoxin-neutralizing properties that may be beneficial as adjunctive therapy in gram-negative sepsis. Polymyxin B nonapeptide (deacylated polymyxin B) is devoid of antibiotic activity but retains the capacity to disorganize the outer membrane of gram-negative bacteria. To evaluate the potential therapeutic usefulness of this derivative, we produced purified polymyxin B nonapeptide, tested its in vivo toxicity in animals, and evaluated its in vitro antiendotoxin activity. Effectiveness as an antiendotoxin agent was assessed by examining the ability of polymyxin B nonapeptide to block the enhanced release of toxic oxygen radicals induced by lipopolysaccharide in human neutrophils (priming). In vivo, at doses of 1.5 and 3.0 mg/kg, polymyxin B nonapeptide did not exhibit the neuromuscular blocking, neurotoxic, or nephrotoxic effects that were observed with polymyxin B sulfate. Both polymyxin B and polymyxin B nonapeptide inhibited lipopolysaccharide-induced neutrophil priming in a concentration-dependent manner, but the parent compound, polymyxin B, was 63 times more effective on a weight basis. The inhibitory activity of both compounds, however, diminished rapidly when they were added after the start of the lipopolysaccharide-neutrophil incubation. We conclude that polymyxin B nonapeptide is less toxic than polymyxin B and, at the doses tested, lacks the neurotoxicity and nephrotoxicity of the parent compound. Polymyxin B nonapeptide retains the antiendotoxin activity of polymyxin B but is much less potent. The findings suggest that these compounds block an early step in the neutrophil priming process, possibly lipopolysaccharide attachment to or insertion into the neutrophil membrane. JF - Antimicrobial agents and chemotherapy AU - Danner, R L AU - Joiner, K A AU - Rubin, M AU - Patterson, W H AU - Johnson, N AU - Ayers, K M AU - Parrillo, J E AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1428 EP - 1434 VL - 33 IS - 9 SN - 0066-4804, 0066-4804 KW - Indicators and Reagents KW - 0 KW - Lipopolysaccharides KW - Polymyxins KW - Superoxides KW - 11062-77-4 KW - Polymyxin B KW - 1404-26-8 KW - polymyxin B nonapeptide KW - 86408-36-8 KW - Index Medicus KW - Animals KW - Humans KW - Lipopolysaccharides -- metabolism KW - Spectrophotometry, Ultraviolet KW - Chromatography, High Pressure Liquid KW - Rats, Inbred Strains KW - Neutrophils -- drug effects KW - Neutrophils -- metabolism KW - Rats KW - Superoxides -- metabolism KW - In Vitro Techniques KW - Dogs KW - Chromatography, Thin Layer KW - Polymyxins -- isolation & purification KW - Polymyxins -- toxicity KW - Polymyxins -- metabolism KW - Polymyxins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79330340?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-12 N1 - Date created - 1989-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 1977 Oct;136(4):469-74 [198485] J Exp Med. 1965 Aug 1;122:207-35 [14316942] Infect Immun. 1979 Mar;23(3):660-4 [222676] Am J Med. 1980 Mar;68(3):332-43 [6987870] Infect Immun. 1981 Jul;33(1):315-8 [6266967] Br J Pharmacol. 1981 Nov;74(3):701-7 [6170378] Infect Immun. 1982 May;36(2):548-57 [6282752] J Immunol Methods. 1982 Aug 13;52(3):333-40 [6290568] N Engl J Med. 1982 Nov 11;307(20):1225-30 [6752708] Biochem Biophys Res Commun. 1982 Dec 31;109(4):1129-33 [6301427] Nature. 1983 Jun 9-15;303(5917):526-8 [6406904] Rev Infect Dis. 1983 Jul-Aug;5(4):629-38 [6353525] Antimicrob Agents Chemother. 1983 Jul;24(1):107-13 [6414364] Antimicrob Agents Chemother. 1983 Jul;24(1):114-22 [6194743] J Immunol. 1984 May;132(5):2582-9 [6325539] Antimicrob Agents Chemother. 1984 Jun;25(6):701-5 [6331296] J Infect Dis. 1984 Sep;150(3):380-8 [6384378] J Exp Med. 1984 Dec 1;160(6):1656-71 [6096475] J Infect Dis. 1985 Jun;151(6):1012-8 [3889171] Antimicrob Agents Chemother. 1985 Apr;27(4):548-54 [2988430] Invest Urol. 1969 Mar;6(5):505-19 [4304849] Ann Intern Med. 1970 Jun;72(6):857-68 [5448745] J Lab Clin Med. 1971 May;77(5):802-10 [4326749] Biochem Biophys Res Commun. 1985 May 16;128(3):1364-72 [2988537] Antimicrob Agents Chemother. 1985 Jul;28(1):107-12 [2412488] FEBS Lett. 1985 Dec 2;193(2):227-30 [2998882] Infect Immun. 1971 Nov;4(5):563-6 [4343409] J Clin Invest. 1973 Mar;52(3):741-4 [4346473] J Pharmacol Exp Ther. 1973 Mar;184(3):757-65 [4347051] JAMA. 1974 Mar 4;227(9):1023-8 [4405926] Surg Gynecol Obstet. 1974 May;138(5):755-9 [4362912] N Engl J Med. 1974 Oct 3;291(14):733-4 [4851512] J Clin Invest. 1975 Jun;55(6):1357-72 [166094] J Infect Dis. 1975 Sep;132(3):316-35 [1159333] Immunochemistry. 1976 Oct;13(10):813-8 [187544] Antimicrob Agents Chemother. 1986 Mar;29(3):496-500 [3013085] Antimicrob Agents Chemother. 1986 Aug;30(2):340-1 [3021053] J Clin Invest. 1987 Sep;80(3):605-12 [3624479] J Infect Dis. 1987 Nov;156(5):706-12 [2821123] J Infect Dis. 1988 Mar;157(3):565-8 [3343526] Biochim Biophys Acta. 1959 Jul;34:255-6 [14422133] Pediatr Res. 1979 Jan;13(1):48-51 [219410] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The role of neuronal energy in the neurotoxicity of excitatory amino acids. AN - 79303906; 2572985 AB - Excitatory amino acids, acting at receptors such as the N-methyl-D-aspartate (NMDA) subtype, are good candidates for a major role in the neuronal death characteristic of Alzheimer's disease. Recent evidence from studies with cultured neurons suggests that perturbations in the energy metabolism of the neuron may be involved in the transition of NMDA agonists from neurotransmitters to neurotoxins via a mechanism that involves relief of the voltage-dependent Mg++ block of the NMDA channel. JF - Neurobiology of aging AU - Henneberry, R C AD - Laboratory of Molecular Biology, NINDS, Bethesda, MD 20892. PY - 1989 SP - 611 EP - 3; discussion 618-20 VL - 10 IS - 5 SN - 0197-4580, 0197-4580 KW - Glutamates KW - 0 KW - Receptors, N-Methyl-D-Aspartate KW - Receptors, Neurotransmitter KW - Glutamic Acid KW - 3KX376GY7L KW - Index Medicus KW - Animals KW - Humans KW - Receptors, Neurotransmitter -- metabolism KW - Glutamates -- metabolism KW - Alzheimer Disease -- metabolism KW - Glutamates -- toxicity KW - Energy Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79303906?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-18 N1 - Date created - 1989-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Differentiation of PC12 cells with v-src: comparison with nerve growth factor. AN - 79293162; 2810396 AB - The PC12 rat pheochromocytoma cell line is used extensively as a model to study neuronal differentiation. These cells resemble adrenal chromaffin cells, differentiating both morphologically and biochemically when cultured in the presence of dexamethasone, but develop a sympathetic neuron-like phenotype when cultured in the presence of nerve growth factor. Expression of the protein product of the v-src oncogene in PC12 cells also induces neurite outgrowth similar to that resulting from nerve growth factor treatment (Alema et al: Nature 316:557-559, 1985). It is thus possible that c-src or a src-like tyrosine kinase participates in the signal transduction pathway by which nerve growth factor acts on PC12 cells. In this study a temperature-sensitive v-src gene has been introduced into PC12 cells. When cultures of these src-transformed cells are switched from the nonpermissive (40 degrees C) to the permissive (37 degrees C) temperature they elaborate neurites. The differentiation induced by src has been compared with that induced by nerve growth factor by determining whether src-transformed PC12 cells at 37 degrees C exhibit the same biochemical alterations as those induced in PC12 cells treated with nerve growth factor. Neurite extension at 37 degrees C in v-src-transformed cells, like NGF-induced differentiation, is accompanied by an increase in the nerve growth factor-inducible large external (NILE) protein. However, neurite extension in v-src-transformed cells is not blocked by the protein kinase inhibitor K-252a, which completely blocks NGF-induced neurite extension. Likewise, EGF receptor down-regulation and the development of saxitoxin and tetanus toxin binding sites are either much reduced or completely absent in src-differentiated compared with NGF-differentiated PC12 cells. JF - Journal of neuroscience research AU - Rausch, D M AU - Dickens, G AU - Doll, S AU - Fujita, K AU - Koizumi, S AU - Rudkin, B B AU - Tocco, M AU - Eiden, L E AU - Guroff, G AD - Unit on Molecular and Cellular Neurobiology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 49 EP - 58 VL - 24 IS - 1 SN - 0360-4012, 0360-4012 KW - Amphibian Proteins KW - 0 KW - Carbazoles KW - Carrier Proteins KW - Indole Alkaloids KW - Membrane Glycoproteins KW - Nerve Growth Factors KW - Neural Cell Adhesion Molecule L1 KW - Tetanus Toxin KW - saxitoxin-binding protein, Rana catesbeiana KW - Saxitoxin KW - 35523-89-8 KW - staurosporine aglycone KW - 97161-97-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Carrier Proteins -- metabolism KW - Cell Differentiation KW - Saxitoxin -- metabolism KW - Pheochromocytoma KW - Rats KW - Phenotype KW - Adrenal Gland Neoplasms KW - Membrane Glycoproteins -- biosynthesis KW - Binding, Competitive KW - Tetanus Toxin -- metabolism KW - Carbazoles -- pharmacology KW - Retroviridae -- genetics KW - Tumor Cells, Cultured -- cytology KW - Neurons -- cytology KW - Oncogenes -- physiology KW - Nerve Growth Factors -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79293162?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-18 N1 - Date created - 1989-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Influence of viral infections on body weight, survival, and tumor prevalence in Fischer 344/NCr rats on two-year studies. AN - 79293019; 2554057 AB - Sendai virus (SV), pneumonia virus of mice (PVM), and rat coronavirus/sialodacryoadenitis virus (RCV/SDAV) were common viral infections of rats in the National Cancer Institute-National Toxicology Program (NCI-NTP) studies from 1977 to 1983. Influence of these viral infections on body weight, survival, and prevalences of spontaneous tumors in the F344/NCr rats of 28 diet control groups at five different laboratories were evaluated. Tumor prevalences evaluated in this investigation included the following: leukemia and tumors of the anterior pituitary, lungs, salivary glands and Harderian glands in both sexes; adrenal pheochromocytomas in male rats; and mammary tumors in female rats. SV and PVM but not RCV/SDAV infections were associated with significant (P less than 0.05) decreases in body weights of male and female rats. Male rat groups with PVM infection had a lower prevalence of leukemia and male rat groups with RCV/SDAV infection had a higher prevalence of anterior pituitary tumors than the corresponding uninfected groups. Female rat groups with SV infection had greater survival and a higher prevalence of lung tumors than groups without SV infection. However, none of the tumor prevalence and survival differences were statistically significant when interlaboratory variability and time-related effects were taken into account. JF - Laboratory animal science AU - Rao, G N AU - Haseman, J K AU - Edmondson, J AD - Division of Toxicology Research and Testing, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 389 EP - 393 VL - 39 IS - 5 SN - 0023-6764, 0023-6764 KW - Index Medicus KW - Rats KW - Body Weight KW - Animals KW - Rats, Inbred F344 KW - Parainfluenza Virus 1, Human KW - Male KW - Female KW - Neoplasms -- veterinary KW - Respirovirus Infections -- physiopathology KW - Coronaviridae Infections -- epidemiology KW - Respirovirus Infections -- veterinary KW - Coronaviridae Infections -- physiopathology KW - Rodent Diseases -- epidemiology KW - Paramyxoviridae Infections -- veterinary KW - Neoplasms -- epidemiology KW - Coronaviridae Infections -- veterinary KW - Rodent Diseases -- physiopathology KW - Paramyxoviridae Infections -- epidemiology KW - Respirovirus Infections -- epidemiology KW - Paramyxoviridae Infections -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79293019?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-27 N1 - Date created - 1989-11-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The failure of intravenous cyclophosphamide therapy in refractory idiopathic inflammatory myopathy. AN - 79292383; 2681763 AB - Eleven patients with idiopathic inflammatory myopathy refractory to treatment with corticosteroids and other immunosuppressive agents were treated with monthly intravenous cyclophosphamide (0.75-1.357 g/m2). Six patients completed a full course of 7 infusions at which point only one patient met predefined criteria for improvement in both strength and function. Five had modest improvement in strength but did not meet the criteria for improvement. All patients have subsequently required treatment with other medications. Major complications observed during therapy included serious infections in 2 patients (streptococcal endocarditis and disseminated Mycobacterium avium intracellulare) and death in one patient in which the contribution of cyclophosphamide cannot be excluded. We conclude that intravenous cyclophosphamide as used in our study cannot be recommended for the treatment of patients with refractory inflammatory myopathy. JF - The Journal of rheumatology AU - Cronin, M E AU - Miller, F W AU - Hicks, J E AU - Dalakas, M AU - Plotz, P H AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1225 EP - 1228 VL - 16 IS - 9 SN - 0315-162X, 0315-162X KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Infection -- etiology KW - Infusions, Intravenous KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Aged KW - Middle Aged KW - Cardiomyopathies -- chemically induced KW - Male KW - Female KW - Cyclophosphamide -- administration & dosage KW - Myositis -- drug therapy KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79292383?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-07 N1 - Date created - 1989-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Human selenite metabolism: a kinetic model. AN - 79214090; 2551194 AB - A model is developed to describe the kinetics of sodium selenite metabolism in humans, based on plasma, urine, and fecal samples obtained from six subjects over a 4-wk period after a single oral 200-micrograms dose of the enriched stable isotope tracer 74Se. The model describes absorption, distributed along the gastrointestinal tract, and enterohepatic recirculation. The model includes four kinetically distinct plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. For the six subjects, the ranges of mean residence times for the four plasma components are, respectively, 0.2-1.1 h, 3-8 h, 9-42 h, and 200-285 h; for the hepatopancreatic subsystem 4-41 days; and for the tissue pool 115-285 days. Approximately 84% of the administered dose was absorbed, and after 12 days approximately 65% remained in the body. The model predicts that after 90 days approximately 35% of this Se would be retained, primarily in the tissues. Separating Se metabolism into several distinct kinetic components is a first step in identifying the efficacious, nutritious, and toxic forms of the element. JF - The American journal of physiology AU - Patterson, B H AU - Levander, O A AU - Helzlsouer, K AU - McAdam, P A AU - Lewis, S A AU - Taylor, P R AU - Veillon, C AU - Zech, L A AD - Biometry Branch, National Institutes of Health, Bethesda 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - R556 EP - R567 VL - 257 IS - 3 Pt 2 SN - 0002-9513, 0002-9513 KW - Selenium KW - H6241UJ22B KW - Sodium Selenite KW - HIW548RQ3W KW - Index Medicus KW - Feces -- metabolism KW - Kinetics KW - Humans KW - Male KW - Female KW - Selenium -- blood KW - Selenium -- pharmacokinetics KW - Selenium -- urine KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79214090?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-17 N1 - Date created - 1989-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Impaired production of nerve growth factor in the submandibular gland of diabetic mice. AN - 79213747; 2528912 AB - The production of nerve growth factor (NGF) in submandibular glands was examined in two kinds of diabetic mice. In genetically diabetic (C57BL/KsJ db/db) mice, which manifest marked insulin resistance and hyperglycemia, the concentration of NGF in the submandibular gland was less than one-tenth that of the nondiabetic controls. In streptozotocin-induced diabetic C57BL/KsJ mice, which show pancreatic insulitis leading to insulin deficiency and hyperglycemia, the glandular NGF concentration fell in a time-dependent manner to 26% of control level at 5 wk after the streptozotocin injection. A daily administration of insulin to the streptozotocin-induced diabetic mice restored the NGF concentration to almost the control level. The molecular size of NGF (13 kDa) in the glandular extracts of the genetically diabetic (db/db) mice in Western blots was indistinguishable from that of the control mice, but its level was reduced in the glands of the diabetic (db/db) animals. Although plasma NGF concentrations were normally below the sensitivity of the assay (less than 0.80 ng/ml) in both the control and the diabetic (db/db) mice, administration of cyclocytidine, which stimulates NGF release from the submandibular gland into the blood circulation, increased the plasma NGF level to 5.95 ng/ml in the control mice, but it failed to do so in the diabetic (db/db) mice. These findings suggest that, in diabetic mice, NGF production in the submandibular gland and its capacity to release NGF into the circulation are decreased. JF - The American journal of physiology AU - Kasayama, S AU - Oka, T AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - E400 EP - E404 VL - 257 IS - 3 Pt 1 SN - 0002-9513, 0002-9513 KW - Insulin KW - 0 KW - Nerve Growth Factors KW - Streptozocin KW - 5W494URQ81 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Insulin -- deficiency KW - Hyperglycemia -- metabolism KW - Mice KW - Insulin -- pharmacology KW - Islets of Langerhans -- pathology KW - Male KW - Cell Survival KW - Nerve Growth Factors -- metabolism KW - Diabetes Mellitus, Experimental -- genetics KW - Submandibular Gland -- metabolism KW - Diabetes Mellitus, Experimental -- metabolism KW - Diabetes Mellitus, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79213747?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-18 N1 - Date created - 1989-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Use of buprenorphine in the treatment of opiate addiction. I. Physiologic and behavioral effects during a rapid dose induction. AN - 79213440; 2776393 AB - A new, rapid dose-induction procedure was used in the evaluation of buprenorphine hydrochloride (buprenorphine) as a treatment for opiate dependence. Nineteen heroin-dependent men were given buprenorphine sublingually in ascending daily doses of 2, 4, and 8 mg and then maintained on 8 mg daily. The observations of the transition from heroin to buprenorphine for the first 4 days are described. During this period, subjects reported significantly elevated ratings of "good effects" and feelings of "overall well-being" and decreased ratings of "overall sickness." Data from subscales of the Addiction Research Center Inventory indicated increasing euphoria and decreasing dysphoria and sedation after buprenorphine administration. Subjects and observers consistently identified buprenorphine as an opiate and not as an opiate antagonist. These findings indicate that a rapid dose induction with buprenorphine is acceptable to heroin-dependent persons and that it causes minimal withdrawal symptoms. JF - Clinical pharmacology and therapeutics AU - Johnson, R E AU - Cone, E J AU - Henningfield, J E AU - Fudala, P J AD - National Institute on Drug Abuse, Addiction Research Center, Francis Scott Key Medical Center, Baltimore, MD 21224. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 335 EP - 343 VL - 46 IS - 3 SN - 0009-9236, 0009-9236 KW - Buprenorphine KW - 40D3SCR4GZ KW - Abridged Index Medicus KW - Index Medicus KW - Pupil -- drug effects KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Blood Pressure -- drug effects KW - Pulse -- drug effects KW - Time Factors KW - Administration, Sublingual KW - Male KW - Buprenorphine -- therapeutic use KW - Heroin Dependence -- physiopathology KW - Buprenorphine -- administration & dosage KW - Heroin Dependence -- rehabilitation KW - Heroin Dependence -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79213440?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - T-type calcium channels mediate the transition between tonic and phasic firing in thalamic neurons. AN - 79212547; 2550936 AB - Thalamic neurons undergo a shift from tonic to phasic (burst) firing upon hyperpolarization. This state transition results from deinactivation of a regenerative depolarizing event referred to as the low-threshold spike. Isolated adult guinea pig thalamic (dorsal lateral geniculate) neurons exhibited low-threshold spikes that could be blocked by low concentrations of nickel but were unaffected by the dihydropyridine nimodipine. Whole-cell voltage-clamp recordings from these cells demonstrated a low-threshold, rapidly inactivating (T) Ca2+ current that manifested similar voltage dependency and time course as the low-threshold spike. Like low-threshold spikes, the T-type Ca2+ current was eliminated by nickel but was unaffected by nimodipine. In thalamic neurons, T-type Ca2+ channels underlie the low-threshold spike and, therefore, play a critical role in regulating the firing pattern of these cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Suzuki, S AU - Rogawski, M A AD - Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 7228 EP - 7232 VL - 86 IS - 18 SN - 0027-8424, 0027-8424 KW - Calcium Channels KW - 0 KW - Tetrodotoxin KW - 4368-28-9 KW - Nimodipine KW - 57WA9QZ5WH KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Animals KW - Electric Conductivity KW - Nickel -- pharmacology KW - Guinea Pigs KW - Nimodipine -- pharmacology KW - In Vitro Techniques KW - Membrane Potentials KW - Tetrodotoxin -- pharmacology KW - Calcium Channels -- physiology KW - Calcium Channels -- drug effects KW - Neurons -- physiology KW - Geniculate Bodies -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79212547?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-24 N1 - Date created - 1989-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Circ Res. 1986 Aug;59(2):229-35 [2427250] J Physiol. 1989 Apr;411:161-77 [2482353] Science. 1987 Feb 6;235(4789):680-2 [2433765] Soc Gen Physiol Ser. 1987;41:167-87 [2436308] Proc Natl Acad Sci U S A. 1987 Jun;84(12):4327-31 [2438698] J Physiol. 1987 Feb;383:231-49 [2443646] J Physiol. 1987 May;386:547-70 [2445968] J Physiol. 1987 May;386:571-601 [2445969] Neurosci Lett. 1987 Oct 16;81(1-2):117-22 [3696461] J Physiol. 1987 Dec;394:149-72 [2451016] J Comp Neurol. 1975 Jan 1;159(1):45-67 [45862] Nature. 1980 Jul 24;286(5771):391-3 [7402320] J Physiol. 1981 Jun;315:569-84 [7310722] J Physiol. 1983 Apr;337:303-20 [6875932] Nature. 1984 Mar 15-21;308(5956):282-4 [6608056] J Neurophysiol. 1984 Jun;51(6):1196-219 [6737028] J Physiol. 1984 Apr;349:205-26 [6737292] J Physiol. 1984 Apr;349:227-47 [6737293] Circ Res. 1984 Sep;55(3):336-48 [6088117] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6388-92 [6093100] Brain Res. 1984 Nov;320(1):1-63 [6440659] J Physiol. 1985 Feb;359:431-46 [2582115] Pflugers Arch. 1985 Apr;403(4):360-8 [2409515] Nature. 1985 Aug 1-7;316(6027):440-3 [2410796] Nature. 1985 Aug 1-7;316(6027):443-6 [2410797] J Gen Physiol. 1985 Jul;86(1):1-30 [2411846] Pflugers Arch. 1985 Jul;404(3):259-65 [2412202] J Gen Physiol. 1986 Jan;87(1):161-82 [2419479] J Neurophysiol. 1986 Mar;55(3):527-39 [2420945] Brain Res. 1986 Feb 26;366(1-2):262-71 [2421822] J Neurosci Methods. 1986 May;16(3):227-38 [3523050] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5340-4 [2425366] Exp Brain Res. 1986;63(1):1-20 [3015651] J Physiol. 1987 Dec;394:173-200 [2451017] J Mol Biol. 1988 Feb 5;199(3):491-502 [2965250] Science. 1988 Apr 8;240(4849):213-5 [2451291] J Physiol. 1987 Nov;392:603-16 [2451732] Ann N Y Acad Sci. 1988;522:16-24 [2454050] Physiol Rev. 1988 Jul;68(3):649-742 [2839857] Neuroscience. 1988 May;25(2):503-12 [3399056] J Neurophysiol. 1988 Jun;59(6):1854-70 [3404208] Science. 1988 Dec 23;242(4886):1654-64 [3059497] Annu Rev Physiol. 1989;51:367-84 [2540697] J Neurophysiol. 1989 Jun;61(6):1270-83 [2501459] J Physiol. 1989 Jul;414:587-604 [2607443] Science. 1987 Jan 2;235(4784):46-52 [2432656] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mono-2-ethylhexyl phthalate, a metabolite of di-(2-ethylhexyl) phthalate, causally linked to testicular atrophy in rats. AN - 79210471; 2781553 AB - Acute testicular atrophy results when appropriate dosages of di-(2-ethylhexyl) phthalate (DEHP) or its hydrolysis product mono-2-ethylhexyl phthalate (MEHP) are given to male rats. Events thought to be involved in this pathological effect also occur in cultures of testicular cells in vitro, but require MEHP rather than DEHP. Primary cultures of hepatocytes, Sertoli cells, and Leydig cells were incubated with 14C-labeled MEHP [8 microM] for up to 24 hr. No significant reduction in viability was produced under these conditions. In contrast to the hepatocytes, which extensively metabolized MEHP to a variety of products in 1 hr, the testicular cell cultures were apparently unable to metabolize MEHP (beyond a slight hydrolysis to phthalic acid by Sertoli cells) in 18-24 hr. MEHP was efficiently taken up by hepatocytes, but much less so by testicular cells. These results, combined with related observations from the literature, support the hypothesis that MEHP itself is the metabolite of DEHP responsible for testicular atrophy in rats. JF - Toxicology and applied pharmacology AU - Albro, P W AU - Chapin, R E AU - Corbett, J T AU - Schroeder, J AU - Phelps, J L AD - National Institute of Environmental Health Sciences, Laboratory of Molecular Biophysics, Research Triangle Park, North Carolina. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 193 EP - 200 VL - 100 IS - 2 SN - 0041-008X, 0041-008X KW - Phthalic Acids KW - 0 KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - mono-(2-ethylhexyl)phthalate KW - FU2EWB60RT KW - Index Medicus KW - Sertoli Cells -- drug effects KW - Rats KW - Atrophy -- chemically induced KW - Animals KW - Leydig Cells -- metabolism KW - Sertoli Cells -- metabolism KW - Liver -- drug effects KW - Cells, Cultured KW - Liver -- metabolism KW - Leydig Cells -- drug effects KW - Hydrolysis KW - Atrophy -- metabolism KW - Male KW - Diethylhexyl Phthalate -- metabolism KW - Testis -- metabolism KW - Testis -- drug effects KW - Testis -- pathology KW - Diethylhexyl Phthalate -- toxicity KW - Phthalic Acids -- metabolism KW - Diethylhexyl Phthalate -- analogs & derivatives KW - Phthalic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79210471?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Methylphenidate and pemoline do not cause depletion of rat brain monoamine markers similar to that observed with methamphetamine. AN - 79209688; 2551071 AB - Methylphenidate (Ritalin) and pemoline (Cylert) are central nervous system stimulants which are widely prescribed for attention deficit and other psychiatric disorders. Several other related stimulants, including amphetamine and methamphetamine, have been shown to cause long lasting decreases in monoamine markers in rat brain, characteristic of axonal degeneration. To assess the neurotoxic potential of methylphenidate and pemoline, we compared the effects of multiple injections (sc, bid for up to 4 days) of methylphenidate (21 and 50 mg/kg) and pemoline (20 and 70 mg/kg) with methamphetamine (5 and 15 mg/kg) on rat brain norepinephrine, dopamine, and serotonin levels and transport sites. While decreases were observed in all brain monoamine markers measured in rats treated with methamphetamine, no changes were observed in animals treated with methylphenidate as compared to saline-treated controls. Pemoline failed to induce significant changes in the level of monoamine transport sites; however, a wide array of changes were observed in the levels of 5-hydroxyindoleacetic acid, dopamine, and norepinephrine in various brain areas after a 3-day treatment regimen with a high dose (70 mg/kg) of pemoline. The lack of changes in monoamine transport sites following the repeated administration of high doses of methylphenidate and pemoline suggests that these drugs do not affect axonal integrity. However, the pattern of changes observed in the levels of monoamines after pemoline treatment may have relevance to the self-injurious behavior seen in these animals. JF - Toxicology and applied pharmacology AU - Zaczek, R AU - Battaglia, G AU - Contrera, J F AU - Culp, S AU - De Souza, E B AD - Neuroscience Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 227 EP - 233 VL - 100 IS - 2 SN - 0041-008X, 0041-008X KW - Biogenic Monoamines KW - 0 KW - Biomarkers KW - Methylphenidate KW - 207ZZ9QZ49 KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - Pemoline KW - 7GAQ2332NK KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Synaptic Transmission -- drug effects KW - Norepinephrine -- metabolism KW - Dopamine -- metabolism KW - Biomarkers -- metabolism KW - Serotonin -- metabolism KW - Male KW - Self Mutilation -- chemically induced KW - Brain -- drug effects KW - Pemoline -- toxicity KW - Brain -- metabolism KW - Methylphenidate -- toxicity KW - Biogenic Monoamines -- metabolism KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79209688?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Organic anion and cation transport in crab urinary bladder. AN - 79209555; 2675639 AB - Crab urinary bladder, a simple, flat-sheet epithelium, is structurally and functionally analogous to vertebrate renal proximal tubule. Like proximal tubule, crab bladder plays an important role in the excretion of potentially toxic, charged metabolites and xenobiotics. Bladders from Cancer borealis secrete monovalent, organic anions and cations in vivo and in vitro. For organic cations, secretion is a two-step process, with mediated and energetically downhill uptake into cells at the serosal membrane and uphill exit at the luminal membrane. The uptake step may be driven by the electrical potential difference across the serosal membrane, the luminal step by organic cation-proton exchange. Monovalent organic anions are also secreted by a separate two-step process. Recent experiments with intact bladder tissue and isolated membrane vesicles show that (as in mammalian proximal tubule) uphill serosal uptake can be coupled indirectly to the Na+ gradient. Organic anion (p-aminohippurate; PAH) uptake is driven by exchange for certain divalent organic anions, e.g., glutarate and alpha-ketoglutarate. The divalent anion gradient (in greater than out) is in turn maintained by Na+-coupled divalent uptake. The PAH exist step at the luminal membrane is mediated and downhill; it may involve anion exchange. JF - The American journal of physiology AU - Miller, D S AU - Smith, P M AU - Pritchard, J B AD - Laboratory of Cellular and Molecular Pharmacology, National Institutes of Health, Research Triangle Park, North Carolina 27709. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - R501 EP - R505 VL - 257 IS - 3 Pt 2 SN - 0002-9513, 0002-9513 KW - Anions KW - 0 KW - Cations KW - Index Medicus KW - Animals KW - Kidney -- metabolism KW - Biomechanical Phenomena KW - Biological Transport KW - Urinary Bladder -- metabolism KW - Brachyura -- metabolism KW - Anions -- metabolism KW - Cations -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79209555?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-17 N1 - Date created - 1989-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effect of nickel(II)acetate on distribution of calmodulin in the rat kidney. AN - 79209162; 2781596 AB - The effect of subcutaneous injection of a single dose of nickel(II)acetate (95 mumol/kg body wt.) on the distribution of calmodulin in the membrane and cytosolic fractions of kidneys of F344/NCr rats was studied with the use of radioimmunoassay. Over the first 8 h post-injection, the membrane-bound calmodulin concentration increased by 20% versus the control value of 3.84 +/- 0.54 SE micrograms/g wet tissue. That increase was then followed by a gradual decrease to the control value in 7 d. At the same time intervals, the cytosolic calmodulin concentration first decreased by 13% from the control value of 8.81 +/- 2.1 SE micrograms/g wet tissue and then slowly increased, reaching a level of 12% above the control at day 7 post-injection. Statistical analysis of the results after 8 h revealed a downward trend in the membrane-bound (P less than 0.0014) and upward trend in the cytosolic (P less than 0.0207) calmodulin concentrations until day 7. However, the total renal calmodulin calculated from the membrane/cytosolic distribution data did not show any statistically significant treatment-related differences among the mean values (13.39 micrograms/g for the nickel(II)acetate-treated rats vs. 12.56 micrograms/g wet tissue for the controls between days 1 and 7). Therefore, the observed effect of nickel(II)acetate must be attributed only to temporary transfer of calmodulin from the soluble cytosolic form into an insoluble, membrane-bound form, without any detectable influence on its degradation or synthesis rate. JF - Toxicology letters AU - Raos, N AU - Kasprzak, K S AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick, MD 21701. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 275 EP - 282 VL - 48 IS - 3 SN - 0378-4274, 0378-4274 KW - Acetates KW - 0 KW - Calmodulin KW - Acetic Acid KW - Q40Q9N063P KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Cytosol -- analysis KW - Cell Communication -- drug effects KW - Tissue Distribution KW - Cell Membrane -- analysis KW - Male KW - Calmodulin -- metabolism KW - Calmodulin -- analysis KW - Kidney -- analysis KW - Kidney -- drug effects KW - Acetates -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79209162?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-23 N1 - Date created - 1989-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Induction of hepatic metallothionein in male B6C3F1 mice exposed to hepatic tumor promoters: effects of phenobarbital, acetaminophen, sodium barbital, and di(2-ethylhexyl) phthalate. AN - 79208485; 2781555 AB - The effects of various compounds known to be hepatic tumor promoters and toxins in the male B6C3F1 mouse liver, including di(2-ethylhexyl)phthalate (DEHP), acetaminophen (ACT), barbital (BB), and phenobarbital (PB) on hepatic metallothionein (MT) concentrations were assessed after chronic exposure. From 6 weeks of age, male mice were maintained on diets containing DEHP at 12,000 or 6000 ppm, ACT at 10,000 or 5000 ppm, BB at 1,000 ppm, or drinking water with PB at 500 ppm for up to 24 weeks. MT was measured in hepatic cytosol at 0, 2, 8, and 24 weeks of exposure. DEHP proved a very effective inducer, producing elevations of MT as high as 11-fold. The increases in hepatic MT with DEHP were both dose- and time-related. ACT was likewise effective in producing hepatic MT elevations (maximum 6.7-fold) in a dose- and time-related fashion. BB and PB, however, had no effect on hepatic MT levels at any time point. While DEHP, BB, and PB treatments produced hepatomegaly, histopathological analysis at 24 weeks revealed that in both DEHP- and ACT-treated livers hepatocellular proliferation was prominent while livers exposed to BB or PB showed predominantly hepatocellular hypertrophy. Gel-filtration of DEHP-treated liver cytosol revealed that zinc was associated with the MT peak. This peak also bound cadmium in vitro and could be extracted by heat treatment and selective acetone precipitation, both typical characteristics of MT. Further confirmation of the presence of MT after DEHP treatment was obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (10 to 20% acrylamide). Results indicate that some, but not all, tumor promoters can induce target organ MT and that such an induction appears associated with those promoters inducing persistent cellular hyperplasia but not those inducing cellular hypertrophy. JF - Toxicology and applied pharmacology AU - Waalkes, M P AU - Ward, J M AD - Division of Cancer Etiology, National Cancer Institute, Frederick, Maryland 21701-1013. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 217 EP - 226 VL - 100 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Phthalic Acids KW - Cadmium KW - 00BH33GNGH KW - Acetaminophen KW - 362O9ITL9D KW - Barbital KW - 5WZ53ENE2P KW - Metallothionein KW - 9038-94-2 KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Zinc KW - J41CSQ7QDS KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Zinc -- analysis KW - Phenobarbital -- pharmacology KW - Cytosol -- analysis KW - Chromatography, Gel KW - Electrophoresis, Polyacrylamide Gel KW - Dose-Response Relationship, Drug KW - Cadmium -- analysis KW - Mice KW - Male KW - Barbital -- pharmacology KW - Liver -- ultrastructure KW - Carcinogens -- pharmacology KW - Metallothionein -- biosynthesis KW - Liver -- drug effects KW - Phthalic Acids -- pharmacology KW - Liver -- metabolism KW - Diethylhexyl Phthalate -- pharmacology KW - Acetaminophen -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79208485?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Amiodarone-induced complications after cardiac operation for obstructive hypertrophic cardiomyopathy. AN - 79202911; 2774719 AB - The occurrence of unanticipated and seemingly unexplicable major complications of hepatic, pulmonary, and cardiac dysfunction after palliative operation for obstructive hypertrophic cardiomyopathy prompted a review of 71 sequential patients. Fifty-five patients had been treated preoperatively with beta-blockers, calcium-channel inhibitors, or both, and 16 had received amiodarone for six to 566 days (mean time, 210 days) at total doses ranging from 8 to 175 g (mean dose, 82 g) and had drug-free intervals prior to operation of zero to 457 days (mean time, 91 days). Comparisons were made between the two treatment groups and between those with and without major complications within the amiodarone-treated group. Preoperative cardiac studies, sex, age, functional class, and type of operation were not related to outcome for the entire patient cohort. In amiodarone-treated patients, the major findings were as follows: a 50% incidence of hepatic dysfunction with a tenfold increase in concentrations of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase; a 25% incidence of pulmonary dysfunction necessitating a fourfold increase in the number of days of ventilator support; and a 19% incidence of low cardiac output syndrome with two deaths. Only 44% of the amiodarone-treated group had no serious complications. The incidence of major complications of the liver, lungs, and heart was 2%, 0%, and 2%, respectively, in patients not treated with amiodarone. Abnormal preoperative pulmonary function studies were predictive of prolonged postoperative ventilatory support. Discontinuation of amiodarone for several months prior to operation appeared to reduce the incidence of major complications. The necessary drug-free interval required preoperatively could not be determined from this retrospective experience.(ABSTRACT TRUNCATED AT 250 WORDS) JF - The Annals of thoracic surgery AU - Kupferschmid, J P AU - Rosengart, T K AU - McIntosh, C L AU - Leon, M B AU - Clark, R E AD - Surgery Branch, NHLBI, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 359 EP - 364 VL - 48 IS - 3 SN - 0003-4975, 0003-4975 KW - Amiodarone KW - N3RQ532IUT KW - Abridged Index Medicus KW - Index Medicus KW - Lung Diseases -- chemically induced KW - Arrhythmias, Cardiac -- etiology KW - Postoperative Complications KW - Humans KW - Chemical and Drug Induced Liver Injury KW - Adult KW - Retrospective Studies KW - Arrhythmias, Cardiac -- drug therapy KW - Cardiac Output, Low -- chemically induced KW - Male KW - Female KW - Cardiomyopathy, Hypertrophic -- surgery KW - Amiodarone -- therapeutic use KW - Cardiomyopathy, Hypertrophic -- complications KW - Amiodarone -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79202911?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The addition of lithium to carbamazepine. Antidepressant efficacy in treatment-resistant depression. AN - 79202083; 2505730 AB - The addition of lithium carbonate to various antidepressant agents, including heterocyclics and monoamine oxidase inhibitors, has been reported to rapidly effect an antidepressant response in otherwise treatment-unresponsive depressed patients. Fifteen depressed patients diagnosed by DSM-III criteria who had not responded to double-blind treatment with carbamazepine were treated with the blind addition of lithium to carbamazepine. Eight patients (53%) responded with a moderate to marked improvement. The time to onset of substantial clinical improvement was rapid; ie, the mean (+/- SD) was 4.1 +/- 2.4 days for lithium potentiation compared with 9.7 +/- 4.1 days in a separate group of depressed patients responding to lithium alone. Side effects during carbamazepine-lithium combination therapy were minimal. The mechanisms by which lithium appears to rapidly potentiate the effects of carbamazepine in treatment-resistant depression are discussed. JF - Archives of general psychiatry AU - Kramlinger, K G AU - Post, R M AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 794 EP - 800 VL - 46 IS - 9 SN - 0003-990X, 0003-990X KW - Antidepressive Agents KW - 0 KW - Lithium Carbonate KW - 2BMD2GNA4V KW - Carbamazepine KW - 33CM23913M KW - Lithium KW - 9FN79X2M3F KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Antidepressive Agents -- therapeutic use KW - Middle Aged KW - Drug Synergism KW - Male KW - Female KW - Depressive Disorder -- psychology KW - Lithium -- therapeutic use KW - Depressive Disorder -- drug therapy KW - Carbamazepine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79202083?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-27 N1 - Date created - 1989-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Quantitative approaches for assessing chromosome loss in Saccharomyces cerevisiae: general methods for analyzing downturns in dose response. AN - 79193929; 2671711 AB - Statistical methods are considered for analysis of data arising from a mitotic chromosome loss assay in Saccharomyces cerevisiae strain D61.M. The methods make use of reproducibility trial data from the assay (presented herein) and previous data, which suggest a unimodal, 'umbrella-patterned' dose response. Computer simulations are employed to illustrate the operating characteristics of the umbrella response methods. These methods are generally applicable to any toxicity assay that exhibits a downturn in dose response. Experimental design considerations are also discussed. These include applications of 2-stage sampling rules to first gauge the dose window of peak response, then test if the response deviates significantly from untreated levels. JF - Mutation research AU - Piegorsch, W W AU - Zimmermann, F K AU - Fogel, S AU - Whittaker, S G AU - Resnick, M A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 11 EP - 29 VL - 224 IS - 1 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - Alleles KW - Computer Simulation KW - Aneuploidy KW - Dose-Response Relationship, Drug KW - Mutation KW - Mathematics KW - Saccharomyces cerevisiae -- genetics KW - Chromosome Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79193929?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-06 N1 - Date created - 1989-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Treatment of localized aggressive lymphomas with combination chemotherapy followed by involved-field radiation therapy. AN - 79192604; 2788716 AB - Localized lymphomas of diffuse and aggressive histology sometimes undergo early hematogenous dissemination such that local therapies (surgery alone or followed by radiation therapy) are not curative in 100% of cases. We have treated 47 clinical stage I or IE patients with aggressive lymphoma histologies (diffuse large-cell, diffuse mixed, diffuse immunoblastic, follicular large-cell, diffuse small-non-cleaved cell) with four monthly cycles of an eight-drug combination chemotherapy program consisting of cyclophosphamide, etoposide, doxorubicin, nitrogen mustard (mechlorethamine), procarbazine, high-dose methotrexate with leucovorin rescue, and prednisone (Pro-MACE-MOPP) administered systemically followed by 40 Gy involved-field radiation therapy. Forty-five (96%) patients achieved a complete remission and no patient has relapsed with a median follow-up time of 42 months (range, 8 to 90). Both patients failing to achieve a complete remission died of lymphoma, and one patient died free of lymphoma 45 months after diagnosis during coronary artery bypass surgery unrelated to lymphoma or its treatment. Hospital admissions were necessary to manage complications on nine of 188 (5%) cycles of treatment. There were no treatment-related deaths. ProMACE-MOPP plus involved-field radiation therapy is safe and effective treatment for localized aggressive lymphoma. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Longo, D L AU - Glatstein, E AU - Duffey, P L AU - Ihde, D C AU - Hubbard, S M AU - Fisher, R I AU - Jaffe, E S AU - Gilliom, M AU - Young, R C AU - DeVita, V T AD - Medicine Branch, National Cancer Institute, Bethesda, MD. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1295 EP - 1302 VL - 7 IS - 9 SN - 0732-183X, 0732-183X KW - Procarbazine KW - 35S93Y190K KW - Mechlorethamine KW - 50D9XSG0VR KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Mechlorethamine -- administration & dosage KW - Drug Administration Schedule KW - Combined Modality Therapy KW - Humans KW - Leucovorin -- administration & dosage KW - Vincristine -- administration & dosage KW - Aged KW - Doxorubicin -- administration & dosage KW - Procarbazine -- administration & dosage KW - Etoposide -- administration & dosage KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Methotrexate -- administration & dosage KW - Prednisone -- administration & dosage KW - Female KW - Male KW - Remission Induction KW - Lymphoma -- drug therapy KW - Lymphoma -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79192604?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-27 N1 - Date created - 1989-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Estimating Rn-induced lung cancer in the United States. AN - 79187539; 2777548 AB - The proportion of lung cancer deaths attributable to Rn among residents of single-family homes in the U.S. (approximately 70% of the housing stock) is estimated using the log-normal distribution of Rn concentrations proposed by Nero et al. (1986) and the risk model developed by the National Academy of Sciences' BEIR IV Committee. The risk model, together with the exposure distribution, predicts that approximately 14% of lung cancer deaths among such residents (about 13,300 deaths per year, or 10% of all U.S. lung cancer deaths) may be due to indoor Rn exposure. The 95% confidence interval is 7%-25%, or approximately 6600 to 24,000 lung cancer deaths. These estimated attributable risks due to Rn are similar for males and females and for smokers and nonsmokers, but higher baseline risks of lung cancer result in much larger absolute numbers of Rn-attributable cancers among males (approximately 9000) and among smokers (approximately 11,000). Because of the apparent skewness of the exposure distribution, most of the contribution to the attributable risks arises from exposure rates below 148 Bq m-3 (4 pCi L-1), i.e., below the EPA "action level." As a result, if all exposure rates that exceed 148 Bq m-3 (approximately 8% of homes) were eliminated, the models predict that the total annual lung cancer burden in the U.S. would drop by 4-5%, or by about 3800 lung cancer deaths, in contrast to a maximum reduction of 14% if all indoor Rn exposure above the 1st percentile were eliminated. JF - Health physics AU - Lubin, J H AU - Boice, J D AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 417 EP - 427 VL - 57 IS - 3 SN - 0017-9078, 0017-9078 KW - Air Pollutants KW - 0 KW - Air Pollutants, Radioactive KW - Radon KW - Q74S4N8N1G KW - Index Medicus KW - United States KW - Smoking KW - Risk KW - Humans KW - Male KW - Female KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Housing KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- mortality KW - Lung Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79187539?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-19 N1 - Date created - 1989-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vitro photodynamic therapy of human lung cancer. AN - 79183194; 2528031 AB - Photodynamic therapy (PDT) using a dihematoporphyrin ether (DHE) sensitizes malignant cells to damage by 630-nm light. This study investigated in vitro PDT sensitivity of human lung cancer cells (A549) and those factors which influence cell survival as determined by the colony formation assay. After incubation for 2, 4, or 6 hr with [DHE] of 2.5, 25, or 50 micrograms/ml, A549 received red light at dose rates of 0.27 or 0.09 mW/cm2 and energies of 0-250 mJ/cm2. Neither 630-nm light alone nor DHE alone affected cell survival. A dose rate of 0.27 mW/cm2 required less energy than 0.09 mW/cm2 for 90% cytotoxicity (180 mJ/cm2 vs 250 mJ/cm2, P less than 0.05). The energy required for 90% cytotoxicity with 25 micrograms/ml [DHE] was dependent on DHE incubation time (2 hr, 90% cytotoxicity not reached; 4 hr, 116 mJ/cm2; 6 hr, 69 mJ/cm2; P less than 0.05). In contrast, cellular [DHE] as measured by fluorescence, plateaued after 2 hr of incubation. Fluorescence microscopy revealed a time-dependent redistribution of fluorescence from the cell membrane to perinuclear and intracytoplasmic organelles. A 99% cytotoxicity required significantly less energy as [DHE] was increased (2.5 micrograms/ml, no cytotoxicity; 25 micrograms/ml, 243 mJ/cm2; 50 micrograms/ml, 111 mJ/cm2; P less than 0.05). Intracellular [DHE] was directly dependent on the incubating media [DHE] (2.5 micrograms/ml, 0.09 +/- 0.01 micrograms/10(6) cells; 25 micrograms/ml, 0.80 +/- 0.07 micrograms/10(6) cells; 50 micrograms/ml, 1.31 +/- 0.11 micrograms/10(6) cells; P less than 0.05). PDT cytotoxicity was inversely proportional to concentration of serum in the DHE media. These data illustrate that lung cancer in vitro is sensitive to PDT and is influenced by dose rate, energy input, and DHE environmental manipulations. These factors may be important in increasing the efficiency of PDT of thoracic malignancies in vivo. JF - The Journal of surgical research AU - Matthews, W AU - Rizzoni, W AU - Mitchell, J AU - Russo, A AU - Pass, H AD - Thoracic Oncology Section, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 276 EP - 281 VL - 47 IS - 3 SN - 0022-4804, 0022-4804 KW - Hematoporphyrins KW - 0 KW - Proteins KW - Radiation-Sensitizing Agents KW - Dihematoporphyrin Ether KW - 97067-70-4 KW - Index Medicus KW - Proteins -- pharmacology KW - Osmolar Concentration KW - Microscopy, Fluorescence KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Humans KW - Hematoporphyrins -- metabolism KW - Hematoporphyrins -- therapeutic use KW - Environmental Exposure KW - Time Factors KW - Radiation-Sensitizing Agents -- therapeutic use KW - Carcinoma -- pathology KW - Carcinoma -- drug therapy KW - Photochemotherapy KW - Lung Neoplasms -- drug therapy KW - Carcinoma -- metabolism KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79183194?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-25 N1 - Date created - 1989-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Passive immunization against tumor necrosis factor partially abrogates interleukin 2 toxicity. AN - 79178921; 2788701 AB - Passive immunization against TNF allowed non-tumor-bearing C3H/HEN mice and tumor-bearing C57BL/6 mice to tolerate significantly more doses of IL-2 before death (p less than 0.005 and p less than 0.001, respectively). The antitumor effect of IL-2 against both 3-d and 10-d pulmonary metastases was maintained in mice treated concurrently with neutralizing antibodies to TNF. In one experiment with 10-d pulmonary metastases, increased administration of IL-2 made possible by passive immunization against TNF significantly improved the antitumor response compared to equitoxic doses of IL-2 and control antibody. The results indicate that TNF is a mediator of IL-2 toxicity but contributes minimally to the antitumor effects of IL-2. Strategies to inhibit TNF may improve the therapeutic index of IL-2 as a neoplastic agent. JF - The Journal of experimental medicine AU - Fraker, D L AU - Langstein, H N AU - Norton, J A AD - Surgical Metabolism Section, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 1015 EP - 1020 VL - 170 IS - 3 SN - 0022-1007, 0022-1007 KW - Interleukin-2 KW - 0 KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Neoplasm Metastasis KW - Mice, Inbred C57BL KW - Mice KW - Female KW - Interleukin-2 -- therapeutic use KW - Tumor Necrosis Factor-alpha -- immunology KW - Immunization, Passive KW - Tumor Necrosis Factor-alpha -- physiology KW - Interleukin-2 -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79178921?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1984 Sep 28;225(4669):1487-9 [6332379] Science. 1985 Aug 30;229(4716):869-71 [3895437] J Immunol. 1985 Oct;135(4):2492-7 [3928750] J Immunol. 1985 Oct;135(4):2865-75 [2993418] J Immunol. 1986 Sep 1;137(5):1735-42 [3528289] Science. 1986 Oct 24;234(4775):470-4 [3764421] J Clin Immunol. 1988 Nov;8(6):426-36 [3265420] Ann Intern Med. 1987 Jun;106(6):817-22 [3495213] Cancer Res. 1988 Oct 15;48(20):5864-7 [3139285] Ann Intern Med. 1988 Dec 15;109(12):953-8 [3264128] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] J Clin Oncol. 1989 Jan;7(1):1-4 [2783337] J Clin Oncol. 1989 Jan;7(1):7-20 [2783338] N Engl J Med. 1987 Apr 9;316(15):889-97 [3493432] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Methadone treatment and acquired immunodeficiency syndrome. AN - 79177290; 2491420 AB - In light of the recent growth in public financial support for the rapid expansion of drug abuse treatment capacity, the unique effectiveness of methadone hydrochloride treatment in reducing intravenous opioid abuse and the associated sharing of injection equipment is reviewed and discussed, and its potential effect on preventing the spread of acquired immunodeficiency syndrome is examined. In addition to methadone, treatment variables that clinical research suggests are integral to effective treatment are identified. Methadone treatment is one of the most helpful means of reducing the risk of acquired immunodeficiency syndrome available, provided that programs of quality are expanded. The medical profession and universities are urged to take steps to ensure quality effort in prevention and treatment. JF - JAMA AU - Cooper, J R AD - Office of Medical and International Affairs, National Institute on Drug Abuse, Rockville, Md 20857. PY - 1989 SP - 1664 EP - 1668 VL - 262 IS - 12 SN - 0098-7484, 0098-7484 KW - Methadone KW - UC6VBE7V1Z KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Methadone -- therapeutic use KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79177290?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-05 N1 - Date created - 1989-10-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1989 Sep 22-29;262(12):1681-2 [2769924] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Induction of target cell DNA release by the cytotoxic T lymphocyte granule protease granzyme A. AN - 79176884; 2788710 AB - The rapid breakdown of target cell DNA during CTL-mediated lysis has been difficult to explain by the granule exocytosis model of cytotoxicity. The involvement of CTL granule proteases in this process was strongly suggested by experiments in which CTL were pretreated with the serine protease inhibitor PMSF, in combination with agents that raise the pH of acidic intracellular compartments. While PMSF pretreatment alone had little effect on target lysis or DNA breakdown, the combination of PMSF and NH4Cl or monensin profoundly reduced target cell DNA release, while little effect was observed on target lysis, as measured by 51Cr release. CTL granule extracts cause release of 125I-DNA from detergent-permeabilized cells. This nuclear DNA-releasing (NDR) activity is inhibited by serine esterase inhibitors that also inhibit the granule BLT-esterase activity, and is specifically immunoabsorbed by antibodies to the CTL granule protease granzyme A. The NDR activity comigrates with BLT-esterase activity during subcellular fractionation, solubilization, gel filtration, and aprotinin-Sepharose affinity chromatography. SDS-PAGE analysis of the affinity-purified product indicates a molecular mass of 60,000 daltons under non-reducing conditions, which moves to 30,000 daltons upon reduction, consistent with previously reported behavior of granzyme A. When the purified material was reduced and alkylated, both esterase and NDR activities comigrated at 30,000 daltons upon gel filtration. Although fully lytic concentrations of purified LGL granule cytolysin alone failed to induce target cell DNA release, a combination of purified granzyme A and the cytolysin induces substantial DNA release. JF - The Journal of experimental medicine AU - Hayes, M P AU - Berrebi, G A AU - Henkart, P A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 933 EP - 946 VL - 170 IS - 3 SN - 0022-1007, 0022-1007 KW - Cytotoxins KW - 0 KW - Serine Proteinase Inhibitors KW - Ammonium Chloride KW - 01Q9PC255D KW - Phenylmethylsulfonyl Fluoride KW - 57KD15003I KW - DNA KW - 9007-49-2 KW - Monensin KW - 906O0YJ6ZP KW - Granzymes KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Index Medicus KW - Animals KW - Monensin -- pharmacology KW - Mice KW - Cytotoxins -- pharmacology KW - Ammonium Chloride -- pharmacology KW - Phenylmethylsulfonyl Fluoride -- pharmacology KW - Molecular Weight KW - Cell Line KW - Serine Endopeptidases -- physiology KW - Cytoplasmic Granules -- enzymology KW - Serine Endopeptidases -- isolation & purification KW - T-Lymphocytes, Cytotoxic -- enzymology KW - DNA -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79176884?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1988 Feb 1;167(2):514-27 [2450162] J Immunol. 1987 Oct 1;139(7):2398-405 [3498759] J Immunol. 1988 Aug 1;141(3):774-8 [3260910] Biochemistry. 1988 Apr 19;27(8):2641-6 [3042021] J Immunol. 1988 Oct 1;141(7):2191-4 [2844898] Nature. 1989 Jan 12;337(6203):181-4 [2521375] J Exp Med. 1989 Mar 1;169(3):765-77 [2538546] FEBS Lett. 1976 Dec 31;72(2):271-4 [16386038] Immunology. 1972 Oct;23(4):577-90 [4628464] J Immunol. 1980 Feb;124(2):870-8 [6965393] J Immunol. 1980 Mar;124(3):1028-33 [6987305] Nature. 1980 Apr 10;284(5756):555-6 [6245367] J Immunol. 1980 Sep;125(3):1256-61 [7410838] J Biol Chem. 1982 Dec 10;257(23):14300-5 [6815193] Immunol Rev. 1983;72:97-118 [6347870] Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361-5 [6312454] J Immunol. 1983 Nov;131(5):2477-83 [6415172] J Immunol. 1984 Jan;132(1):38-42 [6317746] J Immunol. 1984 Jun;132(6):3197-204 [6373925] J Exp Med. 1984 Jul 1;160(1):75-93 [6736872] Nature. 1985 Apr 25-May 1;314(6013):743-5 [3873011] Adv Exp Med Biol. 1985;184:493-508 [2994413] Annu Rev Immunol. 1985;3:31-58 [3904772] J Cell Biochem. 1986;30(2):133-70 [2422185] EMBO J. 1986 Jul;5(7):1595-600 [3488903] Nature. 1986 Aug 21-27;322(6081):740-3 [3489187] Cell. 1986 Oct 24;47(2):183-94 [3094960] J Cell Biochem. 1986;32(2):151-67 [3023406] EMBO J. 1986 Dec 1;5(12):3267-74 [3545816] Nature. 1987 May 7-13;327(6117):12 [3494952] Cell. 1987 Jun 5;49(5):679-85 [3555842] Immunol Rev. 1988 Mar;103:99-109 [3292399] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Inflammatory properties of human C5a and C5a des Arg/ in mast cell-depleted human skin. AN - 79176044; 2527912 AB - C5a and its degradation product, C5a des Arg, elicit immediate cutaneous inflammatory reactions after intradermal injection. Histologically, these reactions are characterized by neutrophil-rich leukocytic infiltrates, leukocytoclasis, edema, and dermal mast cell degranulation. It has not been possible to assess in vivo the relative contributions of resident mast cells and circulating leukocytes to this reaction because the accumulation of leukocytes and degranulation of mast cells occur simultaneously after injection of these anaphylatoxins. To assess the role of mast cells in these inflammatory reactions, we have examined the reactivity of human skin selectively depleted of dermal mast cells by local corticosteroid treatment. Corticosteroid-treated skin became virtually devoid of dermal mast cells within 4-6 wk as assessed by light microscopy, immunofluorescence with fluorescein-conjugated avidin, or electron microscopy. Mast cell-depleted skin demonstrated normal vasopermeability and vasodilatory responsiveness to intradermal injection of histamine, but the reactivity of these sites to the mast cell secretagogue, morphine, was absent. Moreover, no clinical reactions were detectable in mast cell-depleted human skin after intradermal challenge with 50 ng of either C5a or C5a des Arg, despite the fact that biopsies of these sites revealed substantial, neutrophil-rich infiltrates. These infiltrates were qualitatively and quantitatively identical to C5a or C5a des Arg-induced infiltrates in mast cell replete skin. This experimental approach in vivo has allowed the independent analysis of the anaphylactogenic and chemoattractant activities of human C5a and C5a des Arg in human skin, demonstrated the importance of dermal mast cells in these clinical responses, and shown that leukocytes can accumulate at these injection sites directly in response to these mediators. JF - The Journal of investigative dermatology AU - Swerlick, R A AU - Yancey, K B AU - Lawley, T J AD - Dermatology Branch, National Cancer Institute, Bethesda, Maryland. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 417 EP - 422 VL - 93 IS - 3 SN - 0022-202X, 0022-202X KW - Adrenal Cortex Hormones KW - 0 KW - Complement C5 KW - Complement C5a, des-Arginine KW - Morphine KW - 76I7G6D29C KW - Complement C5a KW - 80295-54-1 KW - Histamine KW - 820484N8I3 KW - Index Medicus KW - Drug Eruptions -- immunology KW - Adrenal Cortex Hormones -- pharmacology KW - Cell Count -- drug effects KW - Skin Tests KW - Humans KW - Biopsy KW - Drug Eruptions -- pathology KW - Mast Cells -- immunology KW - Complement C5 -- immunology KW - Skin -- immunology KW - Skin -- cytology KW - Mast Cells -- cytology KW - Complement C5 -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79176044?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-11 N1 - Date created - 1989-10-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Invest Dermatol. 1990 Apr;94(4):499 [2313120] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. AN - 79172641; 2475508 AB - Epidermal differentiation is characterized by a series of coordinated morphological and biochemical changes which result in a highly specialized, highly organized, stratified squamous epithelium. Among the specific markers expressed in differentiating epidermis are (a) two early spinous cell proteins, keratins 1 and 10 (K1 and K10); and (b) two later granular cell proteins, filaggrin and a cornified envelope precursor (CE). In vitro, epidermal basal cells are selectively cultured in 0.05 mM Ca2+ medium, and terminal differentiation is induced when the Ca2+ concentration is increased to 1 mM. However, only a small fraction of the cells express the markers K1, K10, CE, or filaggrin in the higher Ca2+ medium. To explore the factors required for marker expression, cultured epidermal cells were exposed to intermediate Ca2+ concentrations and extracts were analyzed using specific antibody and nucleic acid probes for the four markers of interest. These studies revealed that marker expression was enhanced at a restricted concentration of Ca2+ in the medium of 0.10-0.16 mM. At this Ca2+ concentration, both protein and mRNA levels for each marker were substantially increased, whereas at higher or lower Ca2+ concentrations they were diminished or undetected. The percentage of cells expressing each marker was increased two- to threefold in the permissive Ca2+ medium as determined by immunofluorescence analysis. This optimal level of Ca2+ was required both to initiate and sustain marker expression. At the permissive Ca2+ concentration, expression of the markers was sequential and similar to the order of appearance in vivo. K1 was expressed within 8-12 h and K10 was expressed in the ensuing 12-24-h period. CE and filaggrin were expressed in the subsequent 24 h. Inhibition of K1 expression by cycloheximide suggested that an inducible protein was involved. Other investigators have determined that a shallow Ca2+ gradient exists in epidermis, where the basal cells and spinous cells are in a Ca2+ environment substantially below serum Ca2+ levels. These in vitro results suggest that the Ca2+ environment is a fundamental regulator of expression of epidermal differentiation markers and provide an explanation for the existence of the Ca2+ gradient in vivo. JF - The Journal of cell biology AU - Yuspa, S H AU - Kilkenny, A E AU - Steinert, P M AU - Roop, D R AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1207 EP - 1217 VL - 109 IS - 3 SN - 0021-9525, 0021-9525 KW - Cytoskeletal Proteins KW - 0 KW - Intermediate Filament Proteins KW - Sulfur Radioisotopes KW - filaggrin KW - Keratins KW - 68238-35-7 KW - Methionine KW - AE28F7PNPL KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Electrophoresis, Polyacrylamide Gel KW - Methionine -- metabolism KW - Cell Differentiation KW - Transcription, Genetic KW - Mice KW - Mice, Inbred BALB C KW - Molecular Weight KW - Animals, Newborn KW - Cells, Cultured KW - Fluorescent Antibody Technique KW - Keratins -- genetics KW - Intermediate Filament Proteins -- isolation & purification KW - Intermediate Filament Proteins -- genetics KW - Cytoskeletal Proteins -- biosynthesis KW - Epidermis -- drug effects KW - Intermediate Filament Proteins -- biosynthesis KW - Epidermis -- cytology KW - Cytoskeletal Proteins -- isolation & purification KW - Epidermis -- metabolism KW - Calcium -- pharmacology KW - Keratins -- isolation & purification KW - Keratins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79172641?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-04 N1 - Date created - 1989-10-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1985 Nov;45(11 Pt 2):5845-50 [2414001] Carcinogenesis. 1989 Apr;10(4):777-80 [2702726] Cell. 1986 Aug 15;46(4):583-9 [2873896] Differentiation. 1986;31(2):141-53 [2427382] J Invest Dermatol. 1986 Oct;87(4):472-6 [2428884] J Biol Chem. 1987 Apr 15;262(11):5188-96 [3558389] J Invest Dermatol. 1987 Jul;89(1):44-50 [3298447] J Invest Dermatol. 1987 Jul;89(1):51-8 [2885378] Cell. 1980 Apr;19(4):1033-42 [6155214] Proc Natl Acad Sci U S A. 1981 Jul;78(7):4097-101 [6170061] Cancer Res. 1982 Jun;42(6):2344-9 [6122503] In Vitro. 1982 Jul;18(7):633-42 [7141447] Proc Natl Acad Sci U S A. 1983 Feb;80(3):716-20 [6187003] Cell. 1983 Jul;33(3):915-24 [6191871] J Biol Chem. 1983 Oct 25;258(20):12118-21 [6688806] J Biol Chem. 1983 Nov 10;258(21):13268-72 [6195160] J Mol Biol. 1983 Nov 5;170(3):651-73 [6195345] Carcinogenesis. 1983 Nov;4(11):1413-8 [6139180] Proc Natl Acad Sci U S A. 1984 Jan;81(1):238-42 [6141559] Cell. 1984 Apr;36(4):827-34 [6200236] Biochemistry. 1984 Mar 13;23(6):1239-45 [6712945] J Cell Biol. 1984 Apr;98(4):1388-96 [6201491] Cell. 1984 May;37(1):159-70 [6202418] Differentiation. 1984;26(2):154-69 [6203803] J Biol Chem. 1984 Jul 10;259(13):8037-40 [6203901] Eur J Biochem. 1984 Jul 2;142(1):29-36 [6204871] In Vitro. 1984 Aug;20(8):652-62 [6500605] Anal Biochem. 1969 Oct 1;31(1):146-8 [5380692] Exp Cell Res. 1974 May;86(1):95-105 [4857507] Biochem Biophys Res Commun. 1976 Nov 22;73(2):470-8 [11802] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5350-4 [414220] Nature. 1978 Dec 14;276(5689):729-31 [732879] Cell. 1979 Jul;17(3):573-82 [383305] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Cell. 1979 Nov;18(3):681-94 [42494] Cell. 1980 Jan;19(1):245-54 [6153576] Cell. 1985 Mar;40(3):685-95 [2578891] J Invest Dermatol. 1985 Jun;84(6):508-12 [3998499] Proc Natl Acad Sci U S A. 1985 Jun;82(12):4270-3 [3858880] Exp Cell Res. 1985 Aug;159(2):536-9 [2411581] J Cell Biol. 1987 Jul;105(1):427-40 [2440897] J Invest Dermatol. 1987 Oct;89(4):349-52 [3668277] J Biol Chem. 1987 Nov 15;262(32):15643-8 [3680218] Cancer Res. 1988 Jan 1;48(1):74-81 [2891434] J Invest Dermatol. 1988 Jan;90(1):37-43 [2447194] J Invest Dermatol. 1988 Mar;90(3):382-6 [2450145] Philos Trans R Soc Lond B Biol Sci. 1987 Dec 15;317(1187):525-36 [2894687] Differentiation. 1987;35(2):143-50 [2450799] Am J Pathol. 1988 Apr;131(1):171-81 [2451428] Arch Dermatol. 1988 May;124(5):709-12 [3284469] Cancer Res. 1988 Jun 1;48(11):3245-52 [2452688] Carcinogenesis. 1988 Jun;9(6):1033-8 [2453303] Lab Invest. 1988 Jun;58(6):660-6 [2454348] Cell. 1988 Aug 12;54(4):491-6 [3401924] J Biol Chem. 1988 Sep 15;263(26):13333-9 [2458346] Annu Rev Biochem. 1988;57:593-625 [3052284] J Cell Biol. 1986 May;102(5):1767-77 [2422179] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Beta-adrenergic receptor binding in brain of alcoholics. AN - 79172304; 2548890 AB - The binding of agonists and antagonists to beta-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral cortical and cerebellar membrane preparations was not different in alcoholics compared to that in controls, suggesting that the number of beta-adrenergic receptors was not affected by chronic ethanol ingestion. Agonist binding data, however, indicated the loss of the high-affinity agonist binding state of the beta-adrenergic receptor, representing the receptor-guanine nucleotide binding protein (Gs) complex. Such changes were observed in cerebral cortex but not in cerebellum of intoxicated alcoholics. These data suggest that cerebral cortical beta-adrenergic receptors are uncoupled from adenylate cyclase in these subjects. In cerebral cortical and cerebellar membranes of sober alcoholics both the high- and low-affinity agonist binding sites were observed. These findings are similar to those seen in animal studies and suggest that the effect of chronic ethanol ingestion on beta-adrenergic receptor-adenylate cyclase coupling is brain region specific and reversible with abstinence. Ethanol-induced changes in the coupling of receptors to adenylate cyclase may contribute to the physiological and behavioral manifestations of alcohol abuse. JF - Experimental neurology AU - Valverius, P AU - Borg, S AU - Valverius, M R AU - Hoffman, P L AU - Tabakoff, B AD - Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 280 EP - 286 VL - 105 IS - 3 SN - 0014-4886, 0014-4886 KW - Receptors, Adrenergic, beta KW - 0 KW - Isoproterenol KW - L628TT009W KW - Index Medicus KW - Reference Values KW - Cerebral Cortex -- metabolism KW - Kinetics KW - Humans KW - Cell Membrane -- metabolism KW - Male KW - Isoproterenol -- pharmacology KW - Cerebellum -- metabolism KW - Receptors, Adrenergic, beta -- metabolism KW - Alcoholism -- metabolism KW - Receptors, Adrenergic, beta -- drug effects KW - Brain -- metabolism KW - Alcoholic Intoxication -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79172304?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-10 N1 - Date created - 1989-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Lack of promoting effect of clonazepam on the development of N-nitrosodiethylamine-initiated hepatocellular tumors in mice is correlated with its inability to inhibit cell-to-cell communication in mouse hepatocytes. AN - 79169310; 2766464 AB - The tumor-promoting ability of clonazepam (CZP), a widely used benzodiazepine anticonvulsant, was investigated in an in vivo mouse liver tumor promotion assay and an in vitro mouse hepatocyte intercellular communication assay. The development of preneoplastic hepatocellular foci of cellular alteration and hepatocellular neoplasms was studied in male B6C3F1 mice initiated, at 5 weeks of age, with a single i.p. injection of N-nitrosodiethylamine (NDEA; 90 mg/kg body weight) in tricaprylin, followed by administration of either phenobarbital (PB; 0.05%) or CZP (0.068% or 0.136%) in diet beginning 2 weeks after carcinogen injection and continuing to 60 weeks of age. Several mice from each group were killed after 9, 21, 33 or 53 weeks on test diet, and portions of liver and other organs were fixed in formalin and examined histologically. Unlike PB, CZP did not promote the development of preneoplastic hepatocellular foci or neoplasms (adenomas and carcinomas) in NDEA-initiated mice. Following limited (2 weeks) dietary exposure at 0.15%, CZP was a potent inducer of hepatic P450IIB1-mediated alkoxyresorufin O-dealkylase activities. In contrast, the degree of induction in hepatic tissue from mice fed 0.136% CZP for 53 weeks was markedly lower than that in mice fed 0.05% PB for 53 weeks. In the in vitro assay, diazepam, a strong tumor promoter in mouse liver, significantly inhibited mouse hepatocyte gap junctional intercellular communication, while CZP had no significant effect on this parameter. Thus, CZP, a drug structurally related to diazepam, is inactive as a liver tumor promoter in mice. JF - Carcinogenesis AU - Diwan, B A AU - Lubet, R A AU - Nims, R W AU - Klaunig, J E AU - Weghorst, C M AU - Henneman, J R AU - Ward, J M AU - Rice, J M AD - Biological Carcinogenesis and Development Program Resources, Inc., National Cancer Institute, Frederick, MD 21701-1013. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1719 EP - 1724 VL - 10 IS - 9 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Clonazepam KW - 5PE9FDE8GB KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP2B1 KW - EC 1.14.14.1 KW - Aminopyrine N-Demethylase KW - EC 1.5.3.- KW - Diazepam KW - Q3JTX2Q7TU KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Diazepam -- pharmacology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mice KW - Mice, Inbred Strains KW - Phenobarbital -- pharmacology KW - Oxidoreductases -- metabolism KW - Aminopyrine N-Demethylase -- metabolism KW - Carcinoma -- pathology KW - Adenoma -- chemically induced KW - Adenoma -- pathology KW - Male KW - Carcinoma -- chemically induced KW - Diethylnitrosamine -- toxicity KW - Liver Neoplasms -- pathology KW - Liver -- pathology KW - Liver Neoplasms, Experimental -- pathology KW - Liver -- drug effects KW - Cell Communication -- drug effects KW - Liver Neoplasms -- chemically induced KW - Liver -- physiology KW - Clonazepam -- pharmacology KW - Clonazepam -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79169310?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The rat clofibrate-inducible CYP4A gene subfamily. I. Complete intron and exon sequence of the CYP4A1 and CYP4A2 genes, unique exon organization, and identification of a conserved 19-bp upstream element. AN - 79166744; 2766932 AB - The P450 CYP4A1 and CYP4A2 genes were isolated from a rat genomic library constructed in the vector lambda EMBL3 and their complete sequences were determined. The CYP4A1 and CYP4A2 genes spanned 14,144 and 10,576 bp and contained 13 and 12 exons, respectively. The CYP4A1 gene contained an additional intron that splits the exon corresponding to exon 12 of the CYP4A2 gene, resulting in a noncoding 13th exon in CYP4A1. The exon numbers of these genes were distinct among known P450 genes, and yet several intron-exon junctions along the P450 amino acid coding region were conserved with P450 genes in the CYP2, CYP11, and CYP21 gene families. On the basis of these data, the number of exons in the putative ancestral P450 gene was estimated. The evolutionary implications of this finding are discussed. No consensus TATA sequence was found upstream of either gene's transcription start site. Comparison of the CYP4A1 and CYP4A2 promoters with other genes that lack TATA boxes did not reveal any strong consensus sequence in their immediate upstream regions. However, a conserved 19-bp sequence was located at the positions of 42 and 48 bp upstream from the CYP4A1 and CYP4A2 genes' start sites, respectively. The CYP4A2 gene also contained two 378-bp direct repeats upstream from the start site; these repeats are derived from portions of the long interspersed middle repetitive element present in high copy numbers in the rat genome. JF - DNA (Mary Ann Liebert, Inc.) AU - Kimura, S AU - Hanioka, N AU - Matsunaga, E AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 30892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 503 EP - 516 VL - 8 IS - 7 SN - 0198-0238, 0198-0238 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Genetic Vectors KW - Restriction Mapping KW - Molecular Sequence Data KW - Transcription, Genetic KW - Amino Acid Sequence KW - Repetitive Sequences, Nucleic Acid KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Exons KW - Cytochrome P-450 Enzyme System -- genetics KW - Genes -- drug effects KW - Introns KW - Multigene Family -- drug effects KW - Clofibrate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166744?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Interindividual variation among humans in carcinogen metabolism, DNA adduct formation and DNA repair. AN - 79166450; 2670300 AB - Chemical carcinogens are generally activated enzymatically to electrophiles that form covalently bound carcinogen-DNA adducts. Detoxifying enzymes are competing with the activating enzymes for these procarcinogenic chemical substrates. Wide person-to-person variations in these two types of enzymatic activities are found. Repair rates of DNA damage caused by carcinogens also vary among individuals. These interindividual differences in the metabolism of chemical carcinogens and repair rates of carcinogen-induced DNA damage reflect acquired and inherited host factors that may influence an individual's risk for development of cancer. JF - Carcinogenesis AU - Harris, C C AD - Laboratory of Human Carcinogenesis, NCI, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1563 EP - 1566 VL - 10 IS - 9 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Neoplasms -- pathology KW - Humans KW - Models, Biological KW - Neoplasms -- etiology KW - Cell Transformation, Neoplastic KW - DNA Repair KW - Carcinogens -- metabolism KW - DNA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166450?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The rat clofibrate-inducible CYP4A subfamily. II. cDNA sequence of IVA3, mapping of the Cyp4a locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CYP4A genes. AN - 79166082; 2766933 AB - A novel P450 cDNA, designated IVA3, was isolated from a lambda gt11 cDNA library from clofibrate-treated rat liver by screening with the lauric acid omega-hydroxylase, IVA1, cDNA probe. This cDNA encoded a protein with 507 amino acids and a calculated Mr of 58,239. The IVA3 cDNA shared 65% and 97% nucleotide and 72% and 96% DNA-deduced amino acid sequence similarities with IVA1 and IVA2, respectively. The CYP4A gene family, designated the Cyp4a locus, was mapped to mouse chromosome 4 using a panel of mouse-hamster somatic cell hybrids. Levels of the IVA mRNAs were analyzed in rat tissues and cell cultures after treatment with the hypolipidemic drug clofibrate. The IVA1, IVA2, and IVA3 mRNAs were present at very low levels in the livers of untreated rats and markedly induced in rats treated with clofibrate. Dose-response and time-course studies revealed that all three genes were regulated coordinately in liver. In contrast to the coordinate induction in liver, only the CYP4A3 gene was induced in the rat hepatoma cell line McA-RH7777. In the kidney, IVA1 and IVA3 mRNAs were present at low levels and were induced by clofibrate in a manner similar to that in liver. In contrast, the IVA2 mRNA was expressed in the kidney of untreated rats at a level similar to that of the maximally induced IVA2 mRNA in liver. These data indicate that the CYP4A1, CYP4A2, and CYP4A3 genes are regulated coordinately in liver while only CYP4A2 is activated constitutively in kidney. JF - DNA (Mary Ann Liebert, Inc.) AU - Kimura, S AU - Hardwick, J P AU - Kozak, C A AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 517 EP - 525 VL - 8 IS - 7 SN - 0198-0238, 0198-0238 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Clofibrate KW - HPN91K7FU3 KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - Liver -- metabolism KW - Amino Acid Sequence KW - Mice KW - DNA -- drug effects KW - Rats KW - Rats, Inbred Strains KW - Base Sequence KW - Liver -- drug effects KW - DNA -- genetics KW - Molecular Sequence Data KW - Male KW - Cytochrome P-450 Enzyme System -- genetics KW - Genes -- drug effects KW - Gene Expression Regulation KW - Multigene Family -- drug effects KW - Chromosome Mapping KW - Clofibrate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79166082?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Panic response to lactate administration in alcoholic and nonalcoholic patients with panic disorder. AN - 79163634; 2764173 AB - The authors administered lactate to 12 abstinent alcoholics with panic disorder, 10 nonalcoholic patients with panic disorder, and eight control subjects. They found that the alcoholic patients had fewer panic attacks in response to lactate infusion than the nonalcoholic patients. This finding was not attributable to differences in baseline anxiety or the change in plasma chemical values brought about by sodium lactate administration. The authors suggest that there may be subgroups of patients with panic disorder who need further characterization to meaningfully elucidate the pathophysiology of the disorder. JF - The American journal of psychiatry AU - George, D T AU - Nutt, D J AU - Waxman, R P AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1161 EP - 1165 VL - 146 IS - 9 SN - 0002-953X, 0002-953X KW - Blood Glucose KW - 0 KW - Chlorides KW - Lactates KW - Lactic Acid KW - 33X04XA5AT KW - Sodium KW - 9NEZ333N27 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Blood Pressure KW - Calcium -- blood KW - Humans KW - Hydrogen-Ion Concentration KW - Chlorides -- blood KW - Blood Glucose -- analysis KW - Adult KW - Pulse KW - Sodium -- blood KW - Female KW - Male KW - Psychological Tests KW - Lactates -- blood KW - Fear KW - Lactates -- administration & dosage KW - Anxiety Disorders -- chemically induced KW - Alcoholism -- physiopathology KW - Panic KW - Anxiety Disorders -- physiopathology KW - Alcoholism -- psychology KW - Alcoholism -- complications KW - Anxiety Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79163634?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-19 N1 - Date created - 1989-09-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 1990 Jun;147(6):819-20 [2343939] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Sleep panic attacks: new clinical findings and theoretical implications. AN - 79161786; 2764179 AB - Forty-five panic disorder patients and 26 normal control subjects were surveyed regarding their histories of sleep panic attacks, insomnia, and vulnerability to exogenous panic stimuli. Sixty-nine percent (N = 31) of the patients reported having experienced sleep panic at some time in their lives, and 33% (N = 15) of the patients experienced recurrent sleep panic. The implications of these findings for the management of panic disorder are discussed. JF - The American journal of psychiatry AU - Mellman, T A AU - Uhde, T W AD - Section on Anxiety and Affective Disorders, NIMH, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 1204 EP - 1207 VL - 146 IS - 9 SN - 0002-953X, 0002-953X KW - Caffeine KW - 3G6A5W338E KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Sleep Initiation and Maintenance Disorders -- complications KW - Adult KW - Caffeine -- adverse effects KW - Sleep Initiation and Maintenance Disorders -- diagnosis KW - Middle Aged KW - Sleep Initiation and Maintenance Disorders -- psychology KW - Male KW - Female KW - Sleep Wake Disorders -- diagnosis KW - Fear KW - Anxiety Disorders -- psychology KW - Anxiety Disorders -- diagnosis KW - Sleep Wake Disorders -- complications KW - Sleep Wake Disorders -- psychology KW - Panic KW - Anxiety Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79161786?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-19 N1 - Date created - 1989-09-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 1990 Aug;147(8):1091-2 [2115749] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Parity as a risk factor for cervical cancer. AN - 79152660; 2763994 AB - In a case-control study of 759 invasive cervical cancer patients and 1,430 controls in Colombia, Costa Rica, Mexico, and Panama conducted during 1986-1987, an association with number of pregnancies persisted after adjustment for sexual and socioeconomic variables. Risks rose steadily to 5.1 (95% confidence interval 2.7-9.7) for those with 14 or more pregnancies and a relation of risk to multiparity was observed in all four study countries. Pregnancy associations appeared to relate to the number of live births rather than to miscarriages or abortions, with multiparity relations most pronounced among premenopausal women and oral contraceptive users. Human papillomaviruses types 16 and 18, as measured by filter in situ hybridization, were not significantly associated with number of births and did not explain the strong relation of parity to risk. Our results indicate the need for further consideration of reproductive factors on cervical cancer risk, with attention given to possible mechanisms of action, including hormonal factors and cervical trauma. JF - American journal of epidemiology AU - Brinton, L A AU - Reeves, W C AU - Brenes, M M AU - Herrero, R AU - de Britton, R C AU - Gaitan, E AU - Tenorio, F AU - Garcia, M AU - Rawls, W E AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 486 EP - 496 VL - 130 IS - 3 SN - 0002-9262, 0002-9262 KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Adult KW - Menarche KW - Middle Aged KW - Cesarean Section KW - Menopause KW - Female KW - Uterine Cervical Neoplasms -- etiology KW - Parity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79152660?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-20 N1 - Date created - 1989-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effects of magainins and cecropins on the sporogonic development of malaria parasites in mosquitoes. AN - 79141860; 2759705 AB - Magainins and cecropins are families of peptides with broad antimicrobial and antiparasitic activities derived respectively from the skin of frogs or from giant silk moths. In insects, cecropins function as part of an inducible immune system against a number of bacterial infections. When injected into anopheline mosquitoes previously infected with a variety of Plasmodium species, both magainins and cecropins disrupt sporogonic development by aborting the normal development of oocysts; sporozoites are not formed and the vector cannot transmit the parasite to another host. It may be possible to induce effective transmission-blocking immunity in the mosquito vector by the introduction and expression of genes coding for magainins, cecropins, or similarly acting parasiticidal peptides into the mosquito genome. JF - Infection and immunity AU - Gwadz, R W AU - Kaslow, D AU - Lee, J Y AU - Maloy, W L AU - Zasloff, M AU - Miller, L H AD - Malaria Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 2628 EP - 2633 VL - 57 IS - 9 SN - 0019-9567, 0019-9567 KW - Antimalarials KW - 0 KW - Antimicrobial Cationic Peptides KW - Insect Hormones KW - Peptides KW - Xenopus Proteins KW - magainin 1 peptide, Xenopus KW - 108433-99-4 KW - cecropin A KW - 80451-04-3 KW - Index Medicus KW - Insect Vectors -- parasitology KW - Animals KW - Dose-Response Relationship, Drug KW - Zygote -- growth & development KW - Lethal Dose 50 KW - Zygote -- drug effects KW - Microinjections KW - Plasmodium -- drug effects KW - Antimalarials -- pharmacology KW - Antimalarials -- administration & dosage KW - Plasmodium -- growth & development KW - Peptides -- administration & dosage KW - Insect Hormones -- administration & dosage KW - Insect Hormones -- pharmacology KW - Peptides -- pharmacology KW - Anopheles -- parasitology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79141860?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-15 N1 - Date created - 1989-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trans R Soc Trop Med Hyg. 1968;62(6):731-65 [4389153] Annu Rev Biochem. 1970;39:841-66 [4920831] Nature. 1981 Jul 16;292(5820):246-8 [7019715] Proc Natl Acad Sci U S A. 1985 Apr;82(8):2240-3 [3857578] Eur J Biochem. 1985 Jun 18;149(3):531-5 [3839186] Science. 1986 Oct 31;234(4776):607-10 [3532325] FASEB J. 1988 Oct;2(13):2878-83 [3049204] Science. 1987 Aug 14;237(4816):779-81 [3039658] Annu Rev Microbiol. 1987;41:103-26 [3318666] Proc Natl Acad Sci U S A. 1988 Feb;85(3):910-3 [3277183] FEBS Lett. 1988 Feb 15;228(2):337-40 [3125066] Proc Natl Acad Sci U S A. 1988 Jul;85(14):5072-6 [2455891] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449-53 [3299384] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Target cell lysis by cytotoxic T lymphocytes redirected by antibody-coated polystyrene beads. AN - 79134867; 2668408 AB - Cytotoxic T lymphocytes were found to mediate rapid lysis of target cells not normally recognized in the presence of small polystyrene beads coated with a combination of anti-T3 and antitarget cell antibodies. Lysis was not seen with beads bearing one of these antibodies alone, nor with a mixture of two types of beads each coated with a single antibody. The effector cells mediating this lysis include long term allospecific human CTL, and both human and mouse CTL clones recognizing mouse class I MHC Kb Ag. TNP-modified mouse tumor cells, a human lymphoblastoid line, and human red cells were found to be good targets for this cytotoxicity. Polystyrene beads with diameters of 3 to 15 mu caused target lysis, with a dose-response curve which typically went through a maximum and declined at high bead numbers. Maximal bead-redirected lysis by CTL was less efficient than that mediated by soluble antibody heteroconjugates of the same two antibodies. Bead-redirected target lysis was calcium dependent. These results are interpreted as a form of bystander lysis induced by the beads, since the target cell membrane is not directly crosslinked to the region of CTL activation. These observations thus favor a mechanism of lysis involving the polarized secretion of a locally acting lytic agent by CTL. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kolber, M A AU - Quinones, R R AU - Henkart, P A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 1461 EP - 1466 VL - 143 IS - 5 SN - 0022-1767, 0022-1767 KW - Antibodies KW - 0 KW - Antibodies, Monoclonal KW - Antigens, Differentiation, T-Lymphocyte KW - Polystyrenes KW - Trinitrobenzenes KW - Abridged Index Medicus KW - Index Medicus KW - Trinitrobenzenes -- immunology KW - Cytotoxicity Tests, Immunologic -- methods KW - Particle Size KW - Humans KW - Immunosorbent Techniques KW - Antigens, Differentiation, T-Lymphocyte -- immunology KW - Antibodies, Monoclonal -- physiology KW - Microspheres KW - Cell Line KW - Cytotoxicity, Immunologic KW - Antibodies -- physiology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79134867?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-13 N1 - Date created - 1989-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Current approaches to the chemotherapy of B-cell chronic lymphocytic leukemia: a review. AN - 79132052; 2667343 AB - Standard therapy has not substantially improved the outcome of patients with chronic lymphocytic leukemia (CLL). However, an increased understanding of the biology and immunology of CLL, and the availability of several new and active chemotherapy agents (eg, fludarabine, 2'-deoxycoformycin [DCF], 2-chlorodeoxyadenosine [CDA]) has stimulated enthusiasm for clinical trials. DCF induces CRs or PRs in 25% of heavily treated patients. Fludarabine has been associated with a response rate of greater than 50% in previously treated patients, and greater than 70% in untreated patients, with almost a third of these achieving a CR. Currently, phase I and II clinical trials are evaluating combinations of these drugs with each other or with conventional agents (eg, fludarabine/chlorambucil [CLB]/prednisone [P]; DCF/CLB/P; fludarabine/DCF; fludarabine/P) in previously treated patients. To facilitate comparison of these regimens, each study is adhering to the NCl-Working Group guidelines for eligibility and response criteria, and toxicity assessment. A collaborative phase III trial will then compare the most promising of these regimens with "standard" chemotherapy in previously untreated patients. The widespread availability of these clinical trials will allow clinicians ready access to the new treatments. JF - American journal of hematology AU - Cheson, B D AD - Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/09// PY - 1989 DA - September 1989 SP - 72 EP - 77 VL - 32 IS - 1 SN - 0361-8609, 0361-8609 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Prognosis KW - Clinical Trials as Topic KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Leukemia, Lymphocytic, Chronic, B-Cell -- pathology KW - Antineoplastic Agents -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79132052?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-01 N1 - Date created - 1989-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Enhancement of the activity of immunotoxins by analogues of verapamil. AN - 79130092; 2788030 AB - Verapamil has been shown to enhance immunotoxin activity but only at concentrations that are too high for in vivo use. Therefore, four structural analogues of verapamil (D792, D595, D528, and Sz45) were evaluated for their ability to enhance the in vitro activity of immunotoxins made with either ricin A chain or Pseudomonas exotoxin. The following immunotoxins were used: HB21-PE and 454A12-rRTA which recognize the human transferrin receptor; and 260F9-rRTA which reacts with human ovarian carcinoma and breast carcinoma cells. The activities of the immunotoxins were determined in ovarian carcinoma cells and in KB cells using inhibition of either protein synthesis or colony formation as a measure for the cytotoxicity of the immunotoxins. Each of the four analogues enhanced the activity of ricin A-immunotoxins in a dose-dependent manner. D792 and D595 also increased the activity of IIB21-PE. Low concentrations of either Sz45 or D528 enhanced the activity of HB21-PE, but high concentrations of these two analogues either had less enhancing potency than low concentrations or even decreased the activity of HB21-PE. Specificity of enhancement by the analogues was shown by competition of the activity of the immunotoxins by the corresponding antibody and by inactivity of an irrelevant immunotoxin. The amount of enhancement ranged from 2-fold to greater than 60-fold and was dependent on the cell line and on the experimental conditions. The enhancing ability of the drugs did not correlate with their calcium-antagonistic activity. When compared with verapamil, D792 and D595 had greater enhancing potency with regard to both ricin A-immunotoxins and Pseudomonas exotoxin-immunotoxins. Greater enhancing potency and less in vivo toxicity makes D792 a candidate for use in the enhancement of immunotoxins in vivo. JF - Cancer research AU - Pirker, R AU - FitzGerald, D J AU - Raschack, M AU - Frank, Z AU - Willingham, M C AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/09/01/ PY - 1989 DA - 1989 Sep 01 SP - 4791 EP - 4795 VL - 49 IS - 17 SN - 0008-5472, 0008-5472 KW - Bacterial Toxins KW - 0 KW - Calcium Channel Blockers KW - Exotoxins KW - Immunotoxins KW - Protein Synthesis Inhibitors KW - Virulence Factors KW - Ricin KW - 9009-86-3 KW - Verapamil KW - CJ0O37KU29 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Exotoxins -- pharmacology KW - Humans KW - Lethal Dose 50 KW - Mice KW - Drug Synergism KW - Tumor Stem Cell Assay KW - Ricin -- pharmacology KW - Female KW - Verapamil -- analogs & derivatives KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Tumor Cells, Cultured -- pathology KW - Verapamil -- pharmacology KW - Immunotoxins -- pharmacology KW - Verapamil -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79130092?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-15 N1 - Date created - 1989-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Res 1990 Apr 15;50(8):2546 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Functional analysis of domains II, Ib, and III of Pseudomonas exotoxin. AN - 79140177; 2503515 AB - Pseudomonas exotoxin is composed of three structural domains that are responsible for cell recognition, membrane translocation, and ADP-ribosylation. The substitution of the cell recognition domain (domain Ia) with a growth factor such as transforming growth factor alpha (TGF alpha), creates a cell-specific cytotoxic agent, TGF alpha-PE40, which kills cells bearing epidermal growth factor (EGF) receptors. We have used TGF alpha-PE40 to define the role of sequences in domains II, Ib, and III. Various mutations were made in these domains and mutant forms of TGF alpha-PE40 expressed in Escherichia coli. Mutant proteins were then tested for their ADP-ribosylation, EGF receptor-binding, and cell-killing activities. Additionally, the amino boundary of domain III, which contains the ADP-ribosylation activity, was determined by deletion analysis. Data indicate that (i) the functional amino terminus of domain III is near amino acid 400; (ii) deletion of various regions in domain II or conversion of cysteines 265 and 268 to serines results in a loss of cytotoxicity which ranged from 10-fold to more than 150-fold, indicating that domain II is essential for full expression of cytotoxicity; (iii) deletion of the amino terminus of domain Ib results in a molecule with somewhat increased cytotoxic activity, indicating that domain Ib is not essential for the cytotoxic effect of TGF alpha-PE40; and (iv) TGF alpha-PE40, produced by denaturing and refolding of insoluble material from inclusion bodies, binds better to EGF receptors and is about 10-fold more cytotoxic to cells bearing EGF receptors than is the secreted form of soluble TGF alpha-PE40. JF - The Journal of biological chemistry AU - Siegall, C B AU - Chaudhary, V K AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/08/25/ PY - 1989 DA - 1989 Aug 25 SP - 14256 EP - 14261 VL - 264 IS - 24 SN - 0021-9258, 0021-9258 KW - Exotoxins KW - 0 KW - Iodine Radioisotopes KW - Protein Synthesis Inhibitors KW - Recombinant Fusion Proteins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Protein Synthesis Inhibitors -- toxicity KW - Receptor, Epidermal Growth Factor -- metabolism KW - Tumor Cells, Cultured -- metabolism KW - Humans KW - Carcinoma, Squamous Cell -- metabolism KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- toxicity KW - Adenosine Diphosphate Ribose -- metabolism KW - Mutation KW - Epidermal Growth Factor -- metabolism KW - Pseudomonas aeruginosa -- metabolism KW - Exotoxins -- genetics KW - Genes, Bacterial KW - Pseudomonas aeruginosa -- genetics KW - Exotoxins -- metabolism KW - Exotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79140177?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-13 N1 - Date created - 1989-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A functional protein kinase C is required for induction of 2-5A synthetase by recombinant interferon-alpha A in Daudi cells. AN - 79131899; 2474543 AB - Treatment of Daudi B lymphoblastoid cells with interferon (IFN)-alpha or -beta has been reported (Yap, W. H., Teo, T. S., and Tan, Y. H. (1986) Science 234, 355-358) to cause a transient increase in the level of diacylglycerol, which is the endogenous activator of protein kinase C (PK-C). To assess the role for PK-C in the induction of 2-5A synthetase mRNA and activity by IFN-alpha in Daudi cells, we have examined the effects of PK-C inhibitors and activators. We have found that the PK-C inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), strongly inhibits the induction of 2-5A synthetase mRNA and activity by recombinant IFN-alpha A (rIFN-alpha A) and that this inhibition appears to be at a post-transcriptional level. The inhibition by H7 could not be attributed to a generalized decrease in macromolecular synthesis or to inhibition of the binding or internalization of rIFN-alpha A. Moreover, pretreatment of Daudi cells for 24 h with phorbol esters to down-regulate or desensitize PK-C substantially inhibited the subsequent induction of 2-5A synthetase mRNA and activity by rIFN-alpha A. These data suggest that PK-C activity is required for the induction of 2-5A synthetase by rIFN-alpha A. However, phorbol esters, which are potent PK-C activators, did not induce 2-5A synthetase. Taken together, our data indicate that a functional PK-C is required for 2-5A synthetase induction by rIFN-alpha A at a post-transcriptional level in Daudi cells but that activation of PK-C is not sufficient for induction of this enzyme. JF - The Journal of biological chemistry AU - Faltynek, C R AU - Princler, G L AU - Gusella, G L AU - Varesio, L AU - Radzioch, D AD - Biological Carcinogenesis and Development Program, National Cancer Institute, Frederick, Maryland 21701. Y1 - 1989/08/25/ PY - 1989 DA - 1989 Aug 25 SP - 14305 EP - 14311 VL - 264 IS - 24 SN - 0021-9258, 0021-9258 KW - Interferon Type I KW - 0 KW - Isoquinolines KW - Phorbol Esters KW - Piperazines KW - RNA, Messenger KW - Recombinant Proteins KW - Sulfonamides KW - RNA KW - 63231-63-0 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - N-(2-guanidinoethyl)-5-isoquinolinesulfonamide KW - 91742-10-8 KW - Protein Kinase C KW - EC 2.7.11.13 KW - 2',5'-Oligoadenylate Synthetase KW - EC 2.7.7.84 KW - Index Medicus KW - Protein Biosynthesis KW - Phorbol Esters -- pharmacology KW - Isoquinolines -- pharmacology KW - Humans KW - Endocytosis -- drug effects KW - Transcription, Genetic KW - Piperazines -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Cell Line KW - RNA -- biosynthesis KW - Protein Kinase C -- antagonists & inhibitors KW - 2',5'-Oligoadenylate Synthetase -- genetics KW - Tumor Cells, Cultured -- drug effects KW - Interferon Type I -- pharmacology KW - Interferon Type I -- metabolism KW - Protein Kinase C -- physiology KW - 2',5'-Oligoadenylate Synthetase -- biosynthesis KW - Tumor Cells, Cultured -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79131899?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-13 N1 - Date created - 1989-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Combined zidovudine and interferon-alpha therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS) AN - 79144463; 2757312 AB - To evaluate the toxicity and potential clinical efficacy of combined therapy with zidovudine and interferon-alpha for patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). Nonrandomized, open trial study. Outpatient clinic of a government referral-based research hospital. Volunteer sample of 39 patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. Patients received zidovudine, 250, 100, or 50 mg orally every 4 hours; 6 weeks after interferon-alpha was begun at a dose of 5 million U/d, and the dose was increased every 2 weeks until a maximum tolerated dose was determined. Patients then received the maximum tolerated dose of the combination for a minimum of 12 weeks before formal efficacy evaluations. In the dose-escalation phase, the ability to tolerate interferon-alpha was clearly related to the zidovudine dose. Of the 13 patients receiving 250 mg of zidovudine, only 1 patient was able to tolerate at least 10 million U/d of interferon-alpha. Of the 12 patients receiving 100 mg of zidovudine, 8 tolerated 10 million U/d, 5 tolerated 15 million U/d, and none tolerated higher doses. Of the 12 patients receiving 50 mg of zidovudine, 8 tolerated 10 million U/d, 7 tolerated 15 million U/d, and 6 tolerated 20 million U/d or more. Dose-limiting toxicities included neutropenia (57%), fatigue (16%), thrombocytopenia (14%), and hepatic dysfunction (10%). Of the 22 patients who received a stable dose of both drugs for 12 weeks, 11 patients had a complete or partial tumor response and 8 showed an anti-HIV effect. Peak serum levels of interferon-alpha (32 to 250 U/mL) and zidovudine (0.40 to 3.85 microM) were in the ranges previously shown to be synergistic against HIV. Combination therapy with zidovudine and interferon-alpha can be administered to patients with HIV infection and Kaposi sarcoma in doses that effect antiviral and antitumor responses; it appears to have a potential role in managing such patients. JF - Annals of internal medicine AU - Kovacs, J A AU - Deyton, L AU - Davey, R AU - Falloon, J AU - Zunich, K AU - Lee, D AU - Metcalf, J A AU - Bigley, J W AU - Sawyer, L A AU - Zoon, K C AD - National Institute of Allergy and Infectious Diseases, Bethesda, Maryland. Y1 - 1989/08/15/ PY - 1989 DA - 1989 Aug 15 SP - 280 EP - 287 VL - 111 IS - 4 SN - 0003-4819, 0003-4819 KW - Interferon Type I KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Dose-Response Relationship, Drug KW - Combined Modality Therapy KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Leukocyte Count KW - Zidovudine -- therapeutic use KW - Interferon Type I -- adverse effects KW - Acquired Immunodeficiency Syndrome -- therapy KW - Acquired Immunodeficiency Syndrome -- complications KW - Zidovudine -- pharmacokinetics KW - Interferon Type I -- administration & dosage KW - Zidovudine -- adverse effects KW - Interferon Type I -- pharmacokinetics KW - Interferon Type I -- therapeutic use KW - Zidovudine -- administration & dosage KW - Sarcoma, Kaposi -- therapy KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79144463?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-01 N1 - Date created - 1989-09-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Intern Med. 1990 Feb 15;112(4):306-7 [2334482] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The male factor in the etiology of cervical cancer among sexually monogamous women. AN - 79130020; 2547727 AB - To address the hypothesis that male sexual behavior may affect the etiology of invasive cervical cancer, a case-control study was undertaken in Panama, Costa Rica, Colombia and Mexico. The study enrolled husbands of those women with invasive cervical cancer and of those age-matched controls who reported only one lifetime sexual partner. A total of 204 case and 485 control husbands (78% and 72%, respectively, of identified husbands) were interviewed, clinically examined, and had penile swabs taken for papillomavirus assays. Risk increased significantly (p = 0.005) with the number of sexual partners reported by the husband (RR = 2.0 for 26+ vs. less than 6 partners). Low educational status of the husband was also an important predictor of risk, possibly indicating the role of unmeasured aspects of sexual behavior. Visits to prostitutes, circumcision status and sexually transmitted disease histories were not important predictors of risk, but evidence from clinical examination indicated that poor genital hygiene may be involved. Human papillomavirus (HPV) expression as defined by filter in situ hybridization was detected in 20-23% of subjects and, except in the small group with both HPV types 6/11 and 16/18, was not related to risk. This may reflect sampling problems in the male or the importance of host factors which enhance viral carcinogenicity in the female. JF - International journal of cancer AU - Brinton, L A AU - Reeves, W C AU - Brenes, M M AU - Herrero, R AU - Gaitan, E AU - Tenorio, F AU - de Britton, R C AU - Garcia, M AU - Rawls, W E AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08/15/ PY - 1989 DA - 1989 Aug 15 SP - 199 EP - 203 VL - 44 IS - 2 SN - 0020-7136, 0020-7136 KW - DNA, Viral KW - 0 KW - Index Medicus KW - Educational Status KW - DNA, Viral -- analysis KW - Risk Factors KW - Humans KW - Papillomaviridae -- genetics KW - Circumcision, Male KW - Male KW - Female KW - Uterine Cervical Neoplasms -- etiology KW - Sexual Behavior UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79130020?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-20 N1 - Date created - 1989-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vitro neoplastic progression of rat tracheal epithelial cells transformed by diverse carcinogens. AN - 79081162; 2472879 AB - Preneoplastic transformants were isolated from primary rat tracheal epithelial cells after treatment with (a) mutagenic concentrations of the alkylating agent N-methyl-N-nitro-N'-nitrosoguanidine, (b) nonmutagenic concentrations of the DNA hypomethylating agent 5-azacytidine, or (c) after arising spontaneously. We have addressed the question of whether preneoplastic transformants induced by different carcinogens differ in their ability to progress to the immortal stage and to become neoplastic. Spontaneous transformants occurred with a very low frequency, and 5-azacytidine induced preneoplastic transformants half as efficiently as N-methyl-N-nitro-N'-nitrosoguanidine. However, no phenotypic differences could be detected between the 70 preneoplastic colonies isolated from the 3 groups; colony size, cell density, and clonogenicity were not statistically different. Clones from all 3 groups became immortal and further progressed to become neoplastic with similar frequencies. The level of expression of the oncogenes H-ras, K-ras, and raf was also similar in all 3 groups. These experiments indicated that there was no difference in the ability of spontaneous transformants or those induced by N-methyl-N-nitro-N'-nitrosoguanidine or 5-azacytidine to progress to become immortal or neoplastic. This suggests that whereas the nature of the carcinogen influenced the frequency of the initial transforming event, progression to the neoplastic stage was independent of the nature of the transforming insult. JF - Cancer research AU - Walker, C AU - Nettesheim, P AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/08/15/ PY - 1989 DA - 1989 Aug 15 SP - 4427 EP - 4430 VL - 49 IS - 16 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Rats KW - Animals KW - Precancerous Conditions -- genetics KW - Precancerous Conditions -- chemically induced KW - Epithelium -- pathology KW - Precancerous Conditions -- pathology KW - Epithelium -- drug effects KW - Cell Transformation, Neoplastic -- pathology KW - Tracheal Neoplasms -- chemically induced KW - Trachea -- pathology KW - Cell Transformation, Neoplastic -- chemically induced KW - Tracheal Neoplasms -- pathology KW - Trachea -- drug effects KW - Tracheal Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79081162?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-23 N1 - Date created - 1989-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Evidence of alpha 1-adrenergic----protein kinase C----Na+/H+ antiporter-dependent increase in pinealocyte intracellular pH. Role in the adrenergic stimulation of cGMP accumulation. AN - 79121370; 2568991 AB - The regulation of intracellular pH (pHi) in isolated rat pinealocytes was studied using the fluorescent pH indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Resting pHi was 7.09 when the extracellular pH (pHe) was 7.2. Treatment of pinealocytes with the physiological regulator of pineal function, norepinephrine, resulted in a concentration-dependent increase in pHi. Further analysis indicated that norepinephrine is probably acting via an alpha 1-adrenergic----[Ca2+]i----Ca2+/phospholipid- dependent protein kinase (protein kinase C) mechanism to activate the Na+/H+ antiporter, thereby causing cytoplasmic alkalization. A potential influence of cytosolic alkalization on the responsiveness of cyclic nucleotides to adrenergic agonists was also studied. Five analogs of the antiporter inhibitor amiloride reduced norepinephrine stimulation of cGMP accumulation with the same relative potency as they act on the antiporter. In contrast, although inhibitory effects of these compounds on cAMP accumulation were detectable, they occurred at 10-100-fold higher concentrations, and the relative potency of these inhibitors did not indicate they were acting via the antiporter. These findings provide evidence that 1) alpha 1-adrenergic receptor activation increases pinealocyte pHi through Ca2+----protein kinase C-dependent activation of the Na+/H+ antiporter; and 2) norepinephrine stimulation of cGMP accumulation is pHi-dependent. It would appear that alpha 1-adrenergic regulation of pHi via the Na+/H+ antiporter may be of general importance in the control of cGMP accumulation. JF - The Journal of biological chemistry AU - Ho, A K AU - Chik, C L AU - Weller, J L AU - Cragoe, E J AU - Klein, D C AD - Section on Neuroendocrinology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1989/08/05/ PY - 1989 DA - 1989 Aug 05 SP - 12983 EP - 12988 VL - 264 IS - 22 SN - 0021-9258, 0021-9258 KW - Adrenergic alpha-Agonists KW - 0 KW - Adrenergic alpha-Antagonists KW - Carrier Proteins KW - Receptors, Adrenergic, alpha KW - Sodium-Hydrogen Antiporter KW - 5H-amiloride KW - 1203-87-8 KW - Phenylephrine KW - 1WS297W6MV KW - Amiloride KW - 7DZO8EB0Z3 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Cyclic GMP KW - H2D2X058MU KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Cytosol -- physiology KW - Animals KW - Adrenergic alpha-Agonists -- pharmacology KW - Enzyme Activation KW - Norepinephrine -- pharmacology KW - Hydrogen-Ion Concentration KW - Amiloride -- pharmacology KW - Amiloride -- analogs & derivatives KW - Rats KW - Calcium -- metabolism KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Potassium -- pharmacology KW - Adrenergic alpha-Antagonists -- pharmacology KW - Phenylephrine -- pharmacology KW - Protein Kinase C -- metabolism KW - Cyclic GMP -- metabolism KW - Carrier Proteins -- antagonists & inhibitors KW - Carrier Proteins -- physiology KW - Protein Kinase C -- physiology KW - Pineal Gland -- physiology KW - Receptors, Adrenergic, alpha -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79121370?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-07 N1 - Date created - 1989-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The cardiovascular response of normal humans to the administration of endotoxin. AN - 79091176; 2664516 AB - Marked abnormalities in cardiovascular function accompany septic shock, and bacterial endotoxin is believed to be one of the principal mediators of these abnormalities. To evaluate the cardiovascular effects of endotoxemia in humans, we measured hemodynamic variables in nine normal subjects given an intravenous bolus dose of endotoxin (Escherichia coli, 4 ng per kilogram of body weight) and in six normal subjects given a bolus dose of saline, before and three hours after administration. All the subjects then underwent volume loading with normal saline (mean, 2217 ml) during the fourth and fifth hours after administration of the bolus, and the measurements were repeated. Three hours after the administration of endotoxin and before volume loading, the cardiac index had increased by 53 percent and the heart rate by 36 percent (both changes were significant; P less than or equal to 0.008), and the systemic vascular-resistance index had decreased by 46 percent (P = 0.004). After volume loading (five hours after the administration of endotoxin), the left ventricular ejection fraction decreased by 1 percent of the base-line value in the subjects given endotoxin, but increased by 14 percent in the controls (P = 0.008). The left ventricular end-diastolic and end-systolic volume indexes increased by 18 percent (P = 0.07) and 24 percent (P = 0.042), respectively. Left ventricular performance, as measured by the ratio of the peak systolic pressure to the end-systolic volume index, was depressed (a decrease of 0.90 in the subjects given endotoxin vs. an increase of 0.76 in the controls; P = 0.024). We conclude that the administration of endotoxin to normal subjects causes a depression of left ventricular function that is independent of changes in left ventricular volume or vascular resistance. The changes in function are similar to those observed in septic shock and suggest that endotoxin is a major mediator of the cardiovascular dysfunction in this condition. JF - The New England journal of medicine AU - Suffredini, A F AU - Fromm, R E AU - Parker, M M AU - Brenner, M AU - Kovacs, J A AU - Wesley, R A AU - Parrillo, J E AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/08/03/ PY - 1989 DA - 1989 Aug 03 SP - 280 EP - 287 VL - 321 IS - 5 SN - 0028-4793, 0028-4793 KW - Endotoxins KW - 0 KW - Tumor Necrosis Factor-alpha KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Calcium -- blood KW - Humans KW - Vascular Resistance -- drug effects KW - Heart Rate -- drug effects KW - Adult KW - Escherichia coli KW - Tumor Necrosis Factor-alpha -- analysis KW - Shock, Septic -- physiopathology KW - Blood Pressure -- drug effects KW - Toxemia -- physiopathology KW - Stroke Volume -- drug effects KW - Female KW - Male KW - Hemodynamics -- drug effects KW - Heart -- drug effects KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79091176?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-15 N1 - Date created - 1989-08-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1989 Dec 28;321(26):1828-30 [2594042] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Pathologic anatomy of the dilated cardiomyopathies. AN - 79119785; 2756900 AB - Dilated cardiomyopathies are characterized by systolic pump failure and by dilatation of the ventricular cavity. Thus, they differ from the other 2 main types of cardiomyopathies, namely, hypertrophic cardiomyopathy and restrictive/obliterative cardiomyopathy. The term dilated cardiomyopathy designates a number of heterogeneous syndromes: idiopathic dilated cardiomyopathy, alcoholic cardiomyopathy, postpartal cardiomyopathy, infantile cardiomyopathy with histiocytoid change in cardiac muscle cells, anthracycline cardiomyopathy, Keshan disease, and several ultrastructurally distinct abnormalities, some of which maybe familial. The pathologic features of these syndromes are reviewed in detail. JF - The American journal of cardiology AU - Ferrans, V J AD - National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/08/02/ PY - 1989 DA - 1989 Aug 02 SP - 9C EP - 11C VL - 64 IS - 6 SN - 0002-9149, 0002-9149 KW - Antibiotics, Antineoplastic KW - 0 KW - Selenium KW - H6241UJ22B KW - Abridged Index Medicus KW - Index Medicus KW - Selenium -- deficiency KW - Infant KW - Cardiomyopathy, Alcoholic -- pathology KW - Puerperal Disorders -- pathology KW - Myocardium -- pathology KW - Humans KW - Female KW - Antibiotics, Antineoplastic -- adverse effects KW - Pregnancy KW - Cardiomyopathy, Dilated -- etiology KW - Cardiomyopathy, Dilated -- chemically induced KW - Cardiomyopathy, Dilated -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79119785?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-30 N1 - Date created - 1989-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - 4-Ipomeanol: a novel investigational new drug for lung cancer. AN - 79089842; 2664191 AB - 4-Ipomeanol (IPO) is the first agent to undergo preclinical development at the National Cancer Institute (NCI) based principally on a specific biochemical-biological rationale for clinical investigation as an antineoplastic agent targeted against lung cancer. This disease-specific development of IPO was initially stimulated by observations that the compound was activated by metabolism, preferentially within the mammalian lung, specifically within bronchiolar Clara cells, and that its predominant toxicity was to the lung in most species. IPO is inactive or only minimally active against most conventional antitumor test systems. However, some human lung cancer cell lines, as well as a variety of fresh human lung tumor biopsy specimens, have been shown to be capable of mediating the in situ biotransformation of IPO to a potentially cytotoxic intermediate. In this report, the biochemistry, metabolism, preclinical pharmacology, and toxicology of IPO are reviewed and the clinical development plans for this unique and challenging new agent are presented. JF - Journal of the National Cancer Institute AU - Christian, M C AU - Wittes, R E AU - Leyland-Jones, B AU - McLemore, T L AU - Smith, A C AU - Grieshaber, C K AU - Chabner, B A AU - Boyd, M R AD - Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08/02/ PY - 1989 DA - 1989 Aug 02 SP - 1133 EP - 1143 VL - 81 IS - 15 SN - 0027-8874, 0027-8874 KW - Antineoplastic Agents KW - 0 KW - Terpenes KW - 4-ipomeanol KW - 32954-58-8 KW - Index Medicus KW - Drug Evaluation KW - Animals KW - Humans KW - Drug Evaluation, Preclinical KW - Terpenes -- toxicity KW - Lung Neoplasms -- drug therapy KW - Terpenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79089842?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-22 N1 - Date created - 1989-08-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Natl Cancer Inst 1990 Sep 5;82(17):1434 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modulation of excitatory amino acid receptors by group IIB metal cations in cultured mouse hippocampal neurones. AN - 79547738; 2561788 AB - 1. Responses to the excitatory amino acids kainate, quisqualate, N-methyl-D-aspartate (NMDA), L-glutamate and L-aspartate were recorded in mouse hippocampal neurones in cell culture, using the whole-cell configuration of the patch clamp technique. Agonists were applied rapidly from an array of flow pipes each of 250 microns diameter, positioned within 100 microns of the nerve cell body. 2. Responses to NMDA, L-aspartate and to low concentrations of L-glutamate, recorded with glycine in the extracellular fluid, were strongly antagonized by 50 microM-zinc. Responses to kainate, quisqualate, and in glycine-free solution, responses to L-glutamate, were potentiated by 50 microM-zinc, but partially antagonized by 1 mM-zinc. On average, with 50 microM-zinc, responses to NMDA were reduced to 0.19 times control, while responses to kainate and quisqualate were increased to 1.09 and 1.14 times control. With 1 mM-zinc responses to kainate and quisqualate were reduced to 0.54 and 0.42 times control. 3. Cadmium had a similar, though less potent action, and at 50 microM antagonized responses to NMDA but potentiated responses to kainate and quisqualate. On average, with 50 microM-cadmium, responses to NMDA were reduced to 0.39 times control, while responses to kainate and quisqualate were increased to 1.08 and 1.15 times control. With 1 mM-cadmium responses to NMDA were reduced to 0.04 times control while responses to kainate and quisqualate were reduced to 0.79 and 0.60 times control. Mercury was neurotoxic and increased the leakage current; however, no reduction of the response to NMDA was produced by 5 microM-mercury. 4. The equilibrium dissociation constant (Kd) for zinc antagonism of responses to NMDA, estimated from fit of a single binding site adsorption isotherm, was 13 microM; cadmium was about 4 times less potent than zinc. These effects of zinc and cadmium were nearly voltage independent. In contrast the antagonism of responses to NMDA by 150 microM-magnesium was highly voltage dependent, such that the Kd for magnesium increased e-fold per 17.6 mV depolarization. 5. The potency of zinc as an NMDA antagonist did not vary with the concentration of NMDA, and was not greatly influenced by a 1000-fold variation in the concentration of the NMDA-modulator glycine. This suggests that zinc acts as a non-competitive antagonist, and does not directly interfere with the binding of NMDA to the agonist recognition site nor with the binding of glycine to an allosteric site on the NMDA receptor complex.(ABSTRACT TRUNCATED AT 400 WORDS) JF - The Journal of physiology AU - Mayer, M L AU - Vyklicky, L AU - Westbrook, G L AD - Laboratory of Developmental Neurobiology, NICHD, National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 329 EP - 350 VL - 415 SN - 0022-3751, 0022-3751 KW - Amino Acids KW - 0 KW - Cations, Divalent KW - Glutamates KW - Receptors, Amino Acid KW - Receptors, Cell Surface KW - Receptors, Glutamate KW - Receptors, Neurotransmitter KW - Mercury KW - FXS1BY2PGL KW - Zinc KW - J41CSQ7QDS KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Drug Interactions KW - Mercury -- pharmacology KW - Receptors, Neurotransmitter -- drug effects KW - Mice KW - Zinc -- pharmacology KW - Glutamates -- physiology KW - Cells, Cultured KW - Glycine -- pharmacology KW - Mice, Inbred C57BL KW - Membrane Potentials -- drug effects KW - Hippocampus -- physiology KW - Neurons -- physiology KW - Amino Acids -- physiology KW - Receptors, Cell Surface -- drug effects KW - Cations, Divalent -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79547738?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-09-04 N1 - Date created - 1990-09-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1987 Sep 15;420(2):313-23 [3676764] Nature. 1987 Aug 13-19;328(6131):640-3 [3039375] J Physiol. 1988 May;399:227-45 [2457088] J Physiol. 1988 May;399:247-66 [2457089] Proc Natl Acad Sci U S A. 1988 Sep;85(17):6547-50 [2842779] Eur J Pharmacol. 1988 Jun 22;151(1):103-12 [2843387] Neurosci Lett. 1988 Jul 8;89(3):313-8 [2458553] J Neurophysiol. 1988 Aug;60(2):645-63 [2902200] Proc Natl Acad Sci U S A. 1989 Feb;86(4):1411-5 [2537497] J Physiol. 1989 Aug;415:351-65 [2561789] J Physiol. 1979 Oct;295:139-70 [42780] Neuroscience. 1980;5(12):2325-7 [6970348] Annu Rev Pharmacol Toxicol. 1981;21:165-204 [6112965] J Membr Biol. 1982;64(1-2):55-66 [6276548] Nature. 1982 Mar 25;296(5855):357-9 [6278324] J Physiol. 1982 Oct;331:577-97 [6296371] Nature. 1984 Feb 2-8;307(5950):462-5 [6320006] J Physiol. 1984 Sep;354:29-53 [6148411] Exp Brain Res. 1984;57(1):158-66 [6151515] J Physiol. 1985 Apr;361:65-90 [2580984] Brain Res. 1985 May 20;334(2):281-6 [2859913] Biophys J. 1986 Mar;49(3):607-18 [2421791] Neurosci Lett. 1986 May 23;66(3):305-10 [2425291] Nature. 1987 Feb 5-11;325(6104):529-31 [2433595] J Neurochem. 1987 Jun;48(6):1699-708 [2883254] Prog Neurobiol. 1987;28(3):197-276 [2883706] Science. 1987 May 1;236(4801):589-93 [2883728] J Physiol. 1987 Dec;394:501-27 [2451020] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Captopril and capsaicin modify opioid withdrawal in the morphine-dependent rat. AN - 79453267; 2482512 AB - The involvement of neurokinins, especially substance P, in the opiate withdrawal syndrome was studied by treating rats with drugs that have been reported to increase (captopril) or decrease (capsaicin) tissue levels of substance P. Preliminary experiments with captopril (0.1, 0.3, 1 or 3 mg/kg, SC) showed that the 0.3 mg/kg dose enhanced some of the naloxone-precipitated withdrawal signs. Captopril alone had no effect in the morphine-dependent rat. On experimental days, either saline or captopril (0.3 mg/kg) was injected (SC) immediately before naloxone in morphine-dependent rats that were pretreated (4 to 10 days before the morphine pellet implantation) with either capsaicin (125 mg/kg, SC) or the capsaicin vehicle (N = 8 for each of 4 groups). Capsaicin treatment inhibited the following withdrawal signs: rhinorrhea, lacrimation and salivation. Captopril increased the occurrence of these secretory responses in vehicle-treated but not in capsaicin-treated animals. Other withdrawal signs were not altered by either captopril or capsaicin treatment. The results support the conclusion that substance P and related neurokinins may be involved in the expression of some signs of opioid withdrawal. JF - Pharmacology, biochemistry, and behavior AU - Sharpe, L G AU - Jaffe, J H AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 899 EP - 902 VL - 33 IS - 4 SN - 0091-3057, 0091-3057 KW - Substance P KW - 33507-63-0 KW - Naloxone KW - 36B82AMQ7N KW - Morphine KW - 76I7G6D29C KW - Captopril KW - 9G64RSX1XD KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Naloxone -- pharmacology KW - Animals KW - Dose-Response Relationship, Drug KW - Male KW - Substance Withdrawal Syndrome -- physiopathology KW - Substance P -- physiology KW - Captopril -- pharmacology KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79453267?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-03-06 N1 - Date created - 1990-03-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Specific polypeptide differences in normal versus malignant breast tissue by two-dimensional electrophoresis. AN - 79279255; 2806203 AB - High resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with computer-assisted densitometry was used to analyze 800-1000 silver stained postmitochrondrial and 600-800 cytosolic polypeptides extracted from malignant and nonmalignant human breast tissues. The 2D-PAGE patterns of polypeptides from malignant and normal tissues were similar, although both qualitative and quantitative polypeptide differences were noted. Six cytosolic polypeptides (pI/molecular mass x 10(-3), 5.20/80, 5.75/43, 6.20/40, 5.43/35, 5.46/34.5, and 5.50/34 were detected exclusively in malignant tissues. One constitutive polypeptide, p52 (7.25/52), was not detected in tumor samples. Marked quantitative differences in spot density were noted in polypeptides localized mainly in the molecular weight ranges of 22-40 kDa and pI of 5.65-7.00. An overall increase in polypeptide expression was noted in this region of 2D-PAGE gels of malignant tissues as compared to normal. Twenty-two acidic and 19 polypeptides separated under nonequilibrium isoelectric focusing conditions were significantly increased in tumor samples while one polypeptide was decreased. One polypeptide, p24 (6.15/24), was expressed in greatest concentrations in tumors which also expressed the greatest estrogen receptor content. Expression of p24 was markedly reduced in normal tissue and in malignant tissues expressing low levels of estrogen and progesterone receptors. No significant differences in the expression of the Yb and Ya subunits of glutathione-S-transferases (GST)-A, -B and ligandin were observed between normal and malignant breast tissue. None of the Yp subunits of the placental isoform of GST were detected in either normal or malignant breast tissues. JF - Electrophoresis AU - Wirth, P J AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. PY - 1989 SP - 543 EP - 554 VL - 10 IS - 8-9 SN - 0173-0835, 0173-0835 KW - Antibodies, Monoclonal KW - 0 KW - Neoplasm Proteins KW - Peptides KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Humans KW - Biopsy KW - Receptors, Estrogen -- analysis KW - Glutathione Transferase -- analysis KW - Receptors, Progesterone -- analysis KW - Rats KW - Blotting, Western KW - Automatic Data Processing KW - Mitochondria -- analysis KW - Densitometry KW - Electrophoresis, Gel, Two-Dimensional -- methods KW - Peptides -- analysis KW - Breast Neoplasms -- analysis KW - Neoplasm Proteins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79279255?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-04 N1 - Date created - 1989-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Ethanol: an enhancer of transplantation antigen expression. AN - 79259507; 2478042 AB - Major histocompatibility antigens (MHC) play a pivotal role in the immune response. Abnormal expression of MHC antigens has been correlated with aberrant regulation of the immune response. Studies on the effect of ethanol on class I MHC antigens demonstrate that ethanol significantly enhances their cell surface expression in a variety of cell lines in vitro. These changes in cell surface levels reflect increased intracellular protein synthesis and increased steady state mRNA levels. The effective ethanol concentrations (0.1-1.0%) are physiologically attainable. Measurement of class I MHC antigens on peripheral blood lymphocytes in a population of acutely ethanol-intoxicated patients showed a highly significant increase relative to controls. The possibility that the elevated levels of MHC antigens induced by ethanol may play a role in the evolution of ethanol-related disease is discussed. JF - Alcoholism, clinical and experimental research AU - Singer, D S AU - Parent, L J AU - Kolber, M A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 480 EP - 484 VL - 13 IS - 4 SN - 0145-6008, 0145-6008 KW - Histocompatibility Antigens Class I KW - 0 KW - Histocompatibility Antigens Class II KW - Ethanol KW - 3K9958V90M KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Teratoma -- genetics KW - Animals KW - Histocompatibility Antigens Class II -- genetics KW - Ovarian Neoplasms -- genetics KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Mice KW - Adult KW - Mice, Inbred C3H KW - Middle Aged KW - Lymphocytes -- drug effects KW - Cell Line KW - Female KW - Male KW - RNA -- genetics KW - Major Histocompatibility Complex -- drug effects KW - Ethanol -- pharmacokinetics KW - Ethanol -- pharmacology KW - Alcoholic Intoxication -- immunology KW - Histocompatibility Antigens Class I -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79259507?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-09 N1 - Date created - 1989-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Reproductive toxicity of 2,2-bis(bromomethyl)-1,3-propanediol in a continuous breeding protocol in Swiss (CD-1) mice. AN - 79231768; 2792593 AB - The effect of 2,2-bis(bromomethyl)-1,3-propanediol (BMP) on reproduction in Swiss CD-1 mice was evaluated by use of a continuous breeding protocol. BMP was administered in the feed at 0.1, 0.2, and 0.4% concentrations. Both male and female F0 mice (20 pairs per treatment group, 40 pairs of control animals) were dosed 7 days prior to and during a 98-day cohabitation period. Although the fertility index was unchanged in the high-dose group, BMP exposure significantly decreased the numbers of litters per pair, pups born alive per litter, and pup weight when adjusted for litter size. Crossover mating between treated and control F0 animals indicated a specific effect only on female reproductive capacity. At the highest dose, BMP caused a body weight decrease in the F0 animals of both sexes with no effect on relative organ weights. Sperm concentration, motility, morphology, and estrual cyclicity were unaffected by BMP exposure. Histopathology in the F0 animals revealed specific kidney lesions in both sexes; males were more sensitive than females. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated to nonsiblings of the same treatment group. The effect of high-dose BMP exposure on F1 fertility, body and organ weights, sperm parameters, and estrual cyclicity was the same as that for the F0 animals, with the exception of the lack of renal lesions seen in the F1 females. These data show that BMP impaired fertility in female mice in both generations in the absence of an effect on reproductive organ weights and estrual cyclicity. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Treinen, K A AU - Chapin, R E AU - Gulati, D K AU - Mounce, R AU - Morris, L Z AU - Lamb, J C AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 245 EP - 255 VL - 13 IS - 2 SN - 0272-0590, 0272-0590 KW - Flame Retardants KW - 0 KW - Propylene Glycols KW - 2,2-bis(bromomethyl)-1,3-propanediol KW - 3296-90-0 KW - Index Medicus KW - Eating -- drug effects KW - Animals KW - Kidney Diseases -- pathology KW - Mice, Inbred ICR KW - Kidney -- pathology KW - Mice KW - Estrus -- drug effects KW - Spermatozoa -- drug effects KW - Body Weight -- drug effects KW - Female KW - Male KW - Kidney Diseases -- chemically induced KW - Organ Size -- drug effects KW - Propylene Glycols -- toxicity KW - Flame Retardants -- toxicity KW - Fertility -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79231768?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-28 N1 - Date created - 1989-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Commentary on "Are there location/cage/systematic nontreatment effects in long-term rodent studies? A question revisited". AN - 79229558; 2792589 JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 189 EP - 192 VL - 13 IS - 2 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - Animals KW - Research Design KW - Toxicology -- standards KW - Animals, Laboratory -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79229558?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-28 N1 - Date created - 1989-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Barbital sodium, a tumor promoter for kidney tubules, urinary bladder, and liver of the F344 rat, induces persistent increases in levels of DNA synthesis in renal tubules but not in urinary bladder epithelium or hepatocytes. AN - 79227657; 2792600 AB - The nephrotoxicity of barbital sodium (NaBB), a renal and urinary bladder tumor promoter, was investigated in male F344/NCr rats. In an 8-week toxicity study, NaBB was administered to 6-week-old male rats for 8 weeks at dietary levels of 16,000, 8000, 4000, 2000, 1000, or 0 ppm. Rats tolerated NaBB at levels of 4000 ppm and below with no weight depression or mortality. Liver-to-body weight ratios, however, were significantly increased at 4000 ppm, and toxic renal lesions were observed histologically. Light microscopic studies of male rats fed 1000 ppm NaBB for 2-52 weeks or 4000 or 8000 ppm for 8 weeks revealed elevated levels of DNA synthesis in renal tubular cells as measured with tritiated thymidine autoradiography or 5-bromo-2'-deoxyuridine immunohistochemistry that were associated with degenerative and regenerative nephrotoxic lesions. Increased labeling indices of urothelium and hepatocytes were not seen in rats exposed to 1000 ppm NaBB which is effective as a bladder and liver tumor promoter at these doses. These studies provide evidence for the chronic nephrotoxicity and renal tubular hyperplasia induced by NaBB in F344 rats, which are associated with the tumor-promoting activity of NaBB at the doses studied. Hyperplasia in the urinary bladder or liver was not found, however, for this bladder and liver tumor promoter. The conflicting findings in liver, bladder, and kidney are discussed. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Hagiwara, A AU - Diwan, B A AU - Ward, J M AD - Division of Cancer Etiology, National Cancer Institute, Frederick, Maryland. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 332 EP - 340 VL - 13 IS - 2 SN - 0272-0590, 0272-0590 KW - Barbiturates KW - 0 KW - Barbital KW - 5WZ53ENE2P KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Urinary Bladder -- pathology KW - Animals KW - Liver -- pathology KW - Kidney Tubules -- pathology KW - Cell Nucleus -- ultrastructure KW - Cell Nucleus -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Epithelial Cells KW - Immunohistochemistry KW - Time Factors KW - Male KW - Organ Size -- drug effects KW - Kidney Neoplasms -- chemically induced KW - Liver Neoplasms, Experimental -- physiopathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Barbiturates -- toxicity KW - DNA -- biosynthesis KW - Barbital -- toxicity KW - Urinary Bladder Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79227657?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-28 N1 - Date created - 1989-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Nerve growth factor and phorbol esters increase the number of choline acetyltransferase-positive cells in two morphologically distinct classes of basal forebrain neurons in primary cultures. AN - 79213722; 2776295 AB - Nerve growth factor (NGF) has been shown to be active in the CNS as a neurotrophic agent. Cholinergic neurons of the basal forebrain are one cell type in the CNS which have been identified as a target for NGF. When dissociated cell cultures from the basal forebrain were treated for 7 days with NGF (20 ng/100 microliters), the number of choline acetyltransferase (ChAT)-immunopositive cells was increased from 30 +/- 6 to 58 +/- 3. Cholinergic cells taken from the basal forebrain exhibit 3 different morphologies: stellate, pyramidal, and bipolar. The NGF treatment was found to increase the number of stellate cells from 7 +/- 2 to 23 +/- 2 and the number of pyramidal cells from 14 +/- 2 to 26 +/- 2, but had no effect on the number of bipolar cells. The activation of protein kinase C by phorbol 12-myristate, 13-acetate (TPA) also increased the number of ChAT-positive cells in a dose-dependent manner. A maximal increase was observed with 10 ng/ml of TPA which increased the number of positive cells from a basal level of 21 +/- 4 to 42 +/- 4. As was the case with NGF, only the stellate and pyramidal cells were affected by the phorbol ester treatment. In co-addition experiments, the cultures were treated with 10 ng/100 of NGF and 10 ng/ml of TPA, with the result that there was no further increase in the number of immunopositive cells over the NGF controls. These results suggest that the mechanisms by which NGF and TPA increase the number of ChAT-positive cells are interactive at some point. The effect of TPA at the higher doses of NGF was distinctly different. When cells were treated with 20 ng/100 microliters of NGF and 0.05-50 ng/ml of TPA, the NGF response was down-regulated to the level of the vehicle-treated controls. JF - Brain research. Developmental brain research AU - Alderson, R F AU - Hua, Z W AU - Hersh, L B AD - Laboratory of Developmental Neurobiology, NICHD, Bethesda, MD 20892. Y1 - 1989/08/01/ PY - 1989 DA - 1989 Aug 01 SP - 229 EP - 241 VL - 48 IS - 2 SN - 0165-3806, 0165-3806 KW - Nerve Growth Factors KW - 0 KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Mice KW - Immunohistochemistry KW - Male KW - Female KW - Frontal Lobe -- cytology KW - Nerve Growth Factors -- pharmacology KW - Frontal Lobe -- drug effects KW - Cholinergic Fibers -- cytology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cholinergic Fibers -- drug effects KW - Choline O-Acetyltransferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79213722?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-19 N1 - Date created - 1989-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cancer and other mortality patterns among United States furniture workers. AN - 79204269; 2775670 AB - Cause specific mortality was investigated among 36,622 members of a national furniture workers' union who were first employed in unionised shops between 1946 and 1962. Overall mortality for each race and sex group was less than expected when compared with United States death rates (white men SMR = 0.8, black men SMR = 0.7, white women SMR = 0.8, black women SMR = 0.5); however, raised risks were observed among white men employed in specific types of furniture industries and followed up for 20 or more years after first employment. Lymphatic and haematopoietic cancers were significantly raised (SMR = 1.8) among wood furniture workers followed up for at least 20 years due to excess deaths from leukaemia (SMR = 2.0) and non-Hodgkin's lymphoma (SMR = 2.0). Mortality from acute myeloid leukaemia was particularly high in this group (SMR = 4.7) based on six observed cases. Metal furniture workers followed up for at least 20 years experienced a significant excess of all cancers combined (SMR = 1.6), with non-significant increases in cancers of the lung, stomach, and colorectum. This group also had non-significant excesses of liver cirrhosis, arteriosclerotic heart disease, and cerebrovascular disease. Nasal cancer was not found to be significantly raised in this cohort, though the average follow up period may not have been sufficient to detect an excess risk for this uncommon tumour. JF - British journal of industrial medicine AU - Miller, B A AU - Blair, A E AU - Raynor, H L AU - Stewart, P A AU - Zahm, S H AU - Fraumeni, J F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 508 EP - 515 VL - 46 IS - 8 SN - 0007-1072, 0007-1072 KW - Index Medicus KW - United States KW - Humans KW - Cohort Studies KW - Residence Characteristics KW - Male KW - Female KW - Cause of Death KW - Interior Design and Furnishings KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Facility Design and Construction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79204269?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-23 N1 - Date created - 1989-10-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Occup Med. 1986 Jun;28(6):425-33 [3723215] Am J Epidemiol. 1986 Oct;124(4):569-77 [3752051] J Occup Med. 1987 Sep;29(9):734-40 [3316543] Am J Ind Med. 1988;13(1):5-41 [3344755] Int J Cancer. 1988 Mar 15;41(3):354-8 [3346099] Cancer Res. 1988 Apr 1;48(7):1960-4 [3349470] Lancet. 1967 Jul 15;2(7507):136-7 [4165646] Lancet. 1967 Nov 4;2(7523):988-9 [4167528] Comput Biomed Res. 1974 Aug;7(4):325-32 [4850570] Am J Epidemiol. 1976 Feb;103(2):226-35 [1251836] J Occup Med. 1976 Mar;18(3):165-8 [1255276] Cancer. 1976 Oct;38(4):1591-601 [991080] J Occup Med. 1976 Dec;18(12):797-801 [993873] J Natl Cancer Inst. 1976 Nov;57(5):1193-5 [1003549] Br J Prev Soc Med. 1976 Dec;30(4):225-30 [1009272] Cancer Res. 1977 Oct;37(10):3473-4 [908001] J Natl Cancer Inst. 1977 Oct;59(4):1147-85 [903993] Z Gesamte Hyg. 1978 Mar;24(3):174-7 [654358] Lancet. 1978 Sep 16;2(8090):626-7 [80546] Lancet. 1979 Jan 6;1(8106):1-4 [83461] Arch Environ Health. 1978 Nov-Dec;33(6):300-7 [736613] J Occup Med. 1980 Jan;22(1):25-9 [7354410] Am J Epidemiol. 1980 Feb;111(2):183-93 [7355881] Int J Epidemiol. 1979 Dec;8(4):375-82 [541161] J Toxicol Environ Health. 1980 Sep-Nov;6(5-6):1267-73 [7463519] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] Scand J Work Environ Health. 1980 Sep;6(3):201-5 [6937825] Occup Health Saf. 1981 Jul;50(7):23-5, 28, 30 passim [7243152] Am J Ind Med. 1980;1(2):159-65 [7342763] Am J Ind Med. 1984;6(3):185-205 [6475965] Am J Ind Med. 1984;6(3):207-30 [6475966] Scand J Work Environ Health. 1984 Aug;10(4):211-7 [6494840] Am Ind Hyg Assoc J. 1984 Dec;45(12):809-11 [6549104] Br J Ind Med. 1985 Jun;42(6):403-5 [4005193] Am J Epidemiol. 1986 Feb;123(2):235-49 [3946373] Br J Ind Med. 1986 Feb;43(2):84-90 [3947573] Cancer. 1982 Jul 15;50(2):364-71 [7083144] Am J Ind Med. 1983;4(4):565-75 [6869381] Br J Cancer. 1983 Aug;48(2):217-25 [6882662] Am J Ind Med. 1984;5(5):343-57 [6720695] Am J Epidemiol. 1984 Jun;119(6):896-906 [6731431] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Colchicine administered into the area of the nucleus basalis decreases cortical nicotinic cholinergic receptors labelled by [3H]-acetylcholine. AN - 79201180; 2779754 AB - Lesions in the nucleus basalis in the rat are known to decrease presynaptic markers for acetylcholine, including levels of cholineacetyltransferase (CHAT), high affinity uptake of choline and levels of acetylcholinesterase. Effects of lesions of the nucleus basalis on populations of nicotinic and muscarinic receptors are less well understood. After bilateral injection of the neurotoxic agent, colchicine into the nucleus basalis in the rat, levels of CHAT in the cerebral cortex were reduced 44%. Muscarinic cholinergic [( 3H]QNB) and dopaminergic [( 3H]spiroperidol) binding was not changed in the cortex, hippocampus or striatum. However, significant decreases in nicotinic binding sites, labelled by [( 3H]acetylcholine), were observed in the frontal cortex of nucleus basalis treated animals; scatchard plot analysis indicated a significant decrease in the number, but not affinity, of nicotinic binding sites. Colchicine injected into the nucleus basalis had no effect on the binding of [3H]acetylcholine in the hippocampus, but decreased binding of [3H]acetylcholine in the striatum. Subsequent experiments, in which colchicine was administered into the striatum at a site above the nucleus basalis had no significant effect on nicotinic binding in the striatum or frontal cortex. These results support the hypothesis that degeneration of the nucleus-basalis-cortical cholinergic pathway results in a loss of presynaptic nicotinic binding sites in the cortex as well as in the striatum (through transsynaptic degeneration of the cortico-striatal pathway). JF - Neuropharmacology AU - Tilson, H A AU - Schwartz, R D AU - Ali, S F AU - McLamb, R L AD - Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 855 EP - 861 VL - 28 IS - 8 SN - 0028-3908, 0028-3908 KW - Receptors, Cholinergic KW - 0 KW - Receptors, Muscarinic KW - Spiperone KW - 4X6E73CJ0Q KW - Quinuclidinyl Benzilate KW - 6581-06-2 KW - Choline O-Acetyltransferase KW - EC 2.3.1.6 KW - Acetylcholine KW - N9YNS0M02X KW - Colchicine KW - SML2Y3J35T KW - Index Medicus KW - Animals KW - Membranes -- metabolism KW - Choline O-Acetyltransferase -- metabolism KW - Corpus Striatum -- enzymology KW - Hippocampus -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Corpus Striatum -- drug effects KW - Hippocampus -- enzymology KW - Male KW - Receptors, Muscarinic -- metabolism KW - Cerebral Cortex -- drug effects KW - Colchicine -- pharmacology KW - Receptors, Cholinergic -- drug effects KW - Cerebral Cortex -- metabolism KW - Cerebral Cortex -- enzymology KW - Acetylcholine -- pharmacology KW - Colchicine -- administration & dosage KW - Olivary Nucleus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79201180?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-20 N1 - Date created - 1989-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Degradation and disposal of some antineoplastic drugs. AN - 79201124; 2550609 AB - Bulk quantities and pharmaceutical preparations of the antineoplastic drugs carmustine (BCNU), lomustine (CCNU), chlorozotocin, N-[2-chloroethyl]-N'-[2,6-dioxo-3-piperidinyl]-N-nitrosourea (PCNU), methyl CCNU, mechlorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide, uracil mustard, and spiromustine may be degraded using nickel-aluminum alloy in KOH solution. The drugs are completely destroyed and only nonmutagenic reaction mixtures are produced. Destruction of cyclophosphamide in tablets requires refluxing in HCl before the nickel-aluminum alloy reduction. Streptozotocin, chlorambucil, and mechlorethamine may be degraded using an excess of saturated sodium bicarbonate solution. The nitrosourea drugs BCNU, CCNU, chlorozotocin, PCNU, methyl CCNU, and streptozotocin were also degraded using hydrogen bromide in glacial acetic acid. The drugs were completely destroyed but some of the reaction mixtures were mutagenic and the products were found to be, in some instances, the corresponding mutagenic, denitrosated compounds. JF - Journal of pharmaceutical sciences AU - Lunn, G AU - Sansone, E B AU - Andrews, A W AU - Hellwig, L C AD - Environmental Control and Research Program, Program Resources, Inc., NCI-Frederick Cancer Research Facility, MD 21701. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 652 EP - 659 VL - 78 IS - 8 SN - 0022-3549, 0022-3549 KW - Acetates KW - 0 KW - Antineoplastic Agents KW - Bicarbonates KW - Mutagens KW - Nitrosourea Compounds KW - Thiosulfates KW - Mechlorethamine KW - 50D9XSG0VR KW - Nickel KW - 7OV03QG267 KW - Sodium Bicarbonate KW - 8MDF5V39QO KW - Sodium KW - 9NEZ333N27 KW - Aluminum KW - CPD4NFA903 KW - Index Medicus KW - Animals KW - Salmonella -- genetics KW - Chemistry KW - Nitrosourea Compounds -- analysis KW - Nitrosourea Compounds -- toxicity KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Rats KW - Oxidation-Reduction KW - Mutagenicity Tests KW - Mechlorethamine -- analysis KW - Chemical Phenomena KW - In Vitro Techniques KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79201124?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-25 N1 - Date created - 1989-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome. AN - 79196059; 2528321 AB - Dementia and brain atrophy are established features of a large proportion of patients with acquired immune deficiency syndrome (AIDS). To investigate a potential mechanism for atrophy in AIDS, we measured the concentration of the endogenous neurotoxin quinolinic acid in the cerebrospinal fluid of 10 patients with AIDS and found that they had 3-fold higher quinolinic acid concentrations than 9 age-matched control subjects: 53.8 +/- 10.7 pmol/ml versus 18.4 +/- 3.4 pmol/ml, respectively (p less than 0.005). It remains to be determined whether increased brain quinolinic acid concentrations are involved in the pathogenesis of the neuropathology of AIDS. JF - Annals of neurology AU - Heyes, M P AU - Rubinow, D AU - Lane, C AU - Markey, S P AD - Laboratory of Neurophysiology, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 275 EP - 277 VL - 26 IS - 2 SN - 0364-5134, 0364-5134 KW - Pyridines KW - 0 KW - Quinolinic Acids KW - Tryptophan KW - 8DUH1N11BX KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Male KW - Female KW - Pyridines -- cerebrospinal fluid KW - Quinolinic Acids -- cerebrospinal fluid KW - Tryptophan -- metabolism KW - Acquired Immunodeficiency Syndrome -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79196059?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-03 N1 - Date created - 1989-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Bendectin and human congenital malformations. AN - 79194076; 2772850 AB - The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal. JF - Teratology AU - Shiono, P H AU - Klebanoff, M A AD - National Institute of Child Health and Human Development, Prevention Research Program, Bethesda, Maryland 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 151 EP - 155 VL - 40 IS - 2 SN - 0040-3709, 0040-3709 KW - Drug Combinations KW - 0 KW - Pyridines KW - dicyclomine, doxylamine, pyridoxine drug combination KW - Dicyclomine KW - 4KV4X8IF6V KW - Doxylamine KW - 95QB77JKPL KW - Pyridoxine KW - KV2JZ1BI6Z KW - Index Medicus KW - Vomiting KW - Humans KW - Pregnancy KW - Urogenital Abnormalities KW - Digestive System Abnormalities KW - Pregnancy Trimester, First KW - Prospective Studies KW - Central Nervous System -- abnormalities KW - Drug Combinations -- adverse effects KW - Lung -- abnormalities KW - Female KW - Head -- abnormalities KW - Heart Defects, Congenital -- chemically induced KW - Pyridoxine -- adverse effects KW - Abnormalities, Drug-Induced -- etiology KW - Pyridines -- adverse effects KW - Doxylamine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79194076?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-04 N1 - Date created - 1989-10-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Teratology 1990 Feb;41(2):250-1 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Transmembrane signals mediating adrenocorticotropin release from mouse anterior pituitary cells. AN - 79189587; 2550296 AB - The effect of arginine vasopressin (AVP) and corticotropin releasing factor (CRF) an adrenocorticotropin (ACTH) secretion, phosphatidylinositol breakdown and cAMP accumulation was examined in primary cultures of mouse anterior pituitary cells. AVP and CRF added alone stimulated ACTH secretion in a dose-dependent manner. At 10(-8) M concentration of peptide, AVP and CRF stimulated ACTH secretion 2.8- and 4.6-fold, respectively. AVP and CRF added in combination at equal doses gave an additive effect. CRF enhanced cAMP accumulation, but AVP had no effect on basal or CRF-induced cAMP accumulation. Both forskolin (10(-5) M) and 8-bromo-cAMP (10(-3) M) increased ACTH secretion in these cells by 2.8- and 1.7-fold, respectively. AVP induced the breakdown of phosphoinositides, and CRF alone, or in combination with AVP did not modify this effect. Phorbol 12-myristate 13-acetate (10(-7) M), dioctanoylglycerol (10(-4) M) and phospholipase C (100 mU/ml) also stimulated ACTH secretion in these cells by 4.2-, 2.4-, and 3.7-fold, respectively. Depletion of intracellular and extracellular Ca2+ decreased ACTH secretion, but had no significant effect on CRF-induced cAMP accumulation. However, AVP-induced phosphoinositide breakdown was dependent on extracellular Ca2+. These results indicate that CRF stimulates ACTH secretion via the cAMP-dependent pathway and AVP via the phosphoinositide breakdown-phospholipase C pathway. In the presence of AVP and CRF, both pathways appear to operate independently to produce an additive effect on ACTH secretion. JF - Molecular and cellular endocrinology AU - Castro, M G AU - Gusovsky, F AU - Loh, Y P AD - Section on Cellular Neurobiology, Laboratory of Neurochemistry and Neuroimmunology, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 165 EP - 173 VL - 65 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Diglycerides KW - 0 KW - Phosphatidylinositols KW - 1,2-dioctanoylglycerol KW - 1069-87-0 KW - Arginine Vasopressin KW - 113-79-1 KW - Colforsin KW - 1F7A44V6OU KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Egtazic Acid KW - 526U7A2651 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Cyclic AMP KW - E0399OZS9N KW - Type C Phospholipases KW - EC 3.1.4.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Mice KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Corticotropin-Releasing Hormone -- pharmacology KW - Arginine Vasopressin -- pharmacology KW - Colforsin -- pharmacology KW - Diglycerides -- pharmacology KW - Cells, Cultured KW - Calcium -- physiology KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Type C Phospholipases -- pharmacology KW - Egtazic Acid -- pharmacology KW - Male KW - Adrenocorticotropic Hormone -- metabolism KW - Pituitary Gland, Anterior -- metabolism KW - Pituitary Gland, Anterior -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79189587?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-23 N1 - Date created - 1989-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Molindone hydrochloride: a review of laboratory and clinical findings. AN - 79172263; 2671060 AB - Molindone hydrochloride, a dihydroindolone neuroleptic, is structurally distinct from other classes of neuroleptics. Molindone exhibits many similarities to other neuroleptics, including dopamine receptor blockade, antipsychotic efficacy, and extrapyramidal side effects. Despite these similarities, molindone also has atypical properties and inhibits the enzyme monoamine oxidase in vitro and in vivo. Several studies have shown that molindone causes less dopamine receptor supersensitivity than other neuroleptics and thus may be less likely to cause tardive dyskinesia. It also appears to have a greater effect on mesolimbic and mesocortical dopamine neurons than on those in the nigrostriatal dopamine system. Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents. The authors review the laboratory and clinical data on molindone and discuss the relevance of atypical research findings to the clinical characteristics of this antipsychotic agent. JF - Journal of clinical psychopharmacology AU - Owen, R R AU - Cole, J O AD - Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 268 EP - 276 VL - 9 IS - 4 SN - 0271-0749, 0271-0749 KW - Indoles KW - 0 KW - Receptors, Dopamine KW - Molindone KW - RT3Y3QMF8N KW - Index Medicus KW - Receptors, Dopamine -- drug effects KW - Behavior, Animal -- drug effects KW - Animals KW - Humans KW - Adult KW - Substantia Nigra -- drug effects KW - Corpus Striatum -- drug effects KW - Schizophrenia -- drug therapy KW - Child KW - Indoles -- therapeutic use KW - Molindone -- therapeutic use KW - Molindone -- adverse effects KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79172263?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-27 N1 - Date created - 1989-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Prevention and treatment of endotoxin and sepsis lethality with recombinant human tumor necrosis factor. AN - 79158659; 2669193 AB - Tumor necrosis factor (TNF) is a macrophage product released in response to endotoxin that has been implicated as a cause of the toxicity and lethality seen in septic shock. Previous work suggests that tolerance to nutritional and lethal effects of TNF occur after repeated exposure to recombinant tumor necrosis factor (rTNF). In this study pretreatment of rats with a single low intravenous dose of rTNF prevented subsequent death when a lethal dose of rTNF was administered 24 hours later (tolerance or tachyphylaxis). Pretreatment with rTNF also afforded protection against the lethal effects of either endotoxin or cecal ligation and puncture when rats were challenged 24 hours later. Recombinant TNF injected 6 hours after cecal ligation and puncture initially resulted in a significant survival advantage for treated animals. When this experiment was repeated with a different lot of rTNF, however, the therapeutic benefit of rTNF was not obtained until the dose was decreased by a factor of 10. Protection against the lethal effects of cecal ligation and puncture did not occur when rTNF was given 24 hours after the insult. A single low dose of rTNF can result in tolerance or tachyphylaxis to the lethal effects of TNF. The results suggest that the early administration of low-dose rTNF may be useful in the prevention and treatment of the lethality of sepsis. JF - Surgery AU - Sheppard, B C AU - Fraker, D L AU - Norton, J A AD - Surgical Metabolism Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 156 EP - 61; discussion 161-2 VL - 106 IS - 2 SN - 0039-6060, 0039-6060 KW - Endotoxins KW - 0 KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Drug Tolerance KW - Animals KW - Rats, Inbred F344 KW - Tachyphylaxis KW - Male KW - Bacterial Infections -- therapy KW - Escherichia coli KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Endotoxins -- pharmacology KW - Bacterial Infections -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79158659?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-08 N1 - Date created - 1989-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Interleukin 7 is a T-cell growth factor. AN - 79158585; 2788279 AB - Interleukin 7 (IL-7) is a 25-kDa cytokine which was purified and its corresponding cDNA was cloned based upon its ability to stimulate the proliferation of pre-B cells. It has been shown that IL-7 can also function as a costimulator with Con A for the proliferation of T lymphocytes by inducing the production of interleukin 2 (IL-2). We demonstrate here that IL-7 in combination with phorbol 12-myristate 13-acetate can directly drive the proliferation of purified T cells and that this response is not inhibited by cyclosporine A or by antibodies to IL-2 and IL-4. Stimulation of T cells with phorbol myristate acetate and IL-2, IL-4, or IL-7 prepared T cells to respond to any of the three lymphokines. Although T cells activated in vitro by anti-CD3 or allogeneic cells failed to proliferate when challenged with IL-7, T cells primed in vivo to the same stimuli demonstrated a significant proliferative response when restimulated in vitro with IL-7. IL-7 can, therefore, function both as a growth factor for T cells in an IL-2-independent manner and as a competence factor for the induction of lymphokine responsiveness. The ability to induce IL-7 responsiveness via stimulation of the T-cell receptor complex in vivo, but not in vitro, raises the possibility that IL-7 may play a role in T-cell growth and differentiation in vivo. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chazen, G D AU - Pereira, G M AU - LeGros, G AU - Gillis, S AU - Shevach, E M AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 5923 EP - 5927 VL - 86 IS - 15 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Interleukin-7 KW - Interleukins KW - Recombinant Proteins KW - Concanavalin A KW - 11028-71-0 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - DNA Replication -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lymph Nodes -- drug effects KW - Concanavalin A -- pharmacology KW - Female KW - Lymph Nodes -- immunology KW - Lymphocyte Activation -- drug effects KW - T-Lymphocytes -- cytology KW - Interleukins -- pharmacology KW - T-Lymphocytes -- drug effects KW - Interleukins -- immunology KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79158585?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-12 N1 - Date created - 1989-09-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1979 Jun;122(6):2491-7 [87465] J Exp Med. 1989 Mar 1;169(3):707-16 [2522498] J Immunol. 1981 Dec;127(6):2488-95 [6170707] J Exp Med. 1982 Mar 1;155(3):914-23 [6977612] Immunol Rev. 1983;74:29-56 [6195085] Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214-8 [6332315] Hybridoma. 1982;1(2):125-31 [6821397] Nature. 1985 May 23-29;315(6017):333-6 [2582266] Annu Rev Immunol. 1985;3:133-57 [3933529] Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654-8 [3090545] J Exp Med. 1986 Sep 1;164(3):709-22 [3489060] J Exp Med. 1987 Jan 1;165(1):157-72 [3098893] J Immunol. 1987 Feb 15;138(4):1121-9 [3543122] Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8 [2950524] Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629-33 [3499611] J Exp Med. 1988 Mar 1;167(3):988-1002 [3258354] J Exp Med. 1988 Apr 1;167(4):1417-27 [2965738] Nature. 1988 Jun 9;333(6173):571-3 [3259677] J Immunol. 1988 Jul 15;141(2):369-76 [2838547] J Immunol. 1988 Jul 15;141(2):504-11 [3133410] Transplantation. 1988 Aug;46(2 Suppl):53S-60S [3136567] J Immunol. 1988 Dec 1;141(11):3868-74 [3263438] Proc Natl Acad Sci U S A. 1989 Jan;86(1):302-6 [2643102] Immunol Rev. 1979;47:63-90 [398327] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Structural requirements for anthracycline-induced cardiotoxicity and antitumor effects. AN - 79155940; 2763305 AB - By employing rat cardiac myocytes in culture and mouse L-1210 leukemia cells, we have compared different anthracycline analogs with respect to their ability to kill cardiac myocytes and tumor cells. Anthracyclines induced a decrease in cellular ATP and glutathione from both cardiac myocytes and L-1210 cells in a time- and concentration-dependent fashion. Moreover, the decrease in ATP in cardiac myocytes was followed by release of the cytoplasmic enzyme lactic acid dehydrogenase and of adenine nucleotides after anthracycline treatment. At very low concentrations of anthracyclines, at which ATP and glutathione were not affected, the drugs induced complete cessation of the growth of L-1210 cells. Some structural alterations in the anthracycline molecule resulted in parallel changes in antitumor activity and in cardiotoxicity. But other structural alterations resulted in dissimilar changes in antitumor activity and cardiotoxicity. Although the results indicate that the structural requirements for inducing cardiotoxicity and antitumor activity may be different, they also indicate that the mechanisms by which anthracycline causes cell death in tumor cells and cardiac myocytes may be the same. JF - Toxicology and applied pharmacology AU - Singh, Y AU - Ulrich, L AU - Katz, D AU - Bowen, P AU - Krishna, G AD - Section on Drug Tissue Interaction, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 9 EP - 23 VL - 100 IS - 1 SN - 0041-008X, 0041-008X KW - Doxorubicin KW - 80168379AG KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Cells, Cultured KW - Lethal Dose 50 KW - Cell Division -- drug effects KW - Mice KW - Leukemia L1210 -- drug therapy KW - Structure-Activity Relationship KW - Daunorubicin -- pharmacology KW - Doxorubicin -- analogs & derivatives KW - Doxorubicin -- pharmacology KW - Daunorubicin -- toxicity KW - Heart -- drug effects KW - Doxorubicin -- toxicity KW - Daunorubicin -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79155940?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-13 N1 - Date created - 1989-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mapping and insertional mutagenesis of a vaccinia virus gene encoding a 13,800-Da secreted protein. AN - 79154992; 2763467 AB - The objective of this study was to identify and characterize the gene encoding a protein of approximately 12 kDa that is secreted from cells infected with the vaccinia virus. The absence of this protein from the medium of cells infected with a spontaneous deletion mutant (6/2) suggested that the open reading frame (ORF) was located within a 12,800-base pair segment near the left end of the genome (G. Kotwal and B. Moss, Nature (London) 335, 176-178, 1988). Antibody to the 12-kDa protein immunoprecipitated an appropriate size in vitro translation product of mRNA that hybridized to a DNA segment containing an ORF (N1L) that could encode a 13.8-kDa polypeptide. The similarity in the sizes of the in vitro translation product and the secreted protein was consistent with the absence of processing. Transcriptional analysis revealed major and minor early RNA start sites preceding the N1L ORF as well as a late RNA start site with an atypical TAAAAT sequence. The N1L gene was interrupted by replacing a segment of the ORF with the Escherichia coli beta-galactosidase gene. When two-dimensional polyacrylamide gel electrophoretic patterns of [35S]methionine-labeled proteins secreted from cells infected with parental and recombinant viruses were compared, a spot missing from the latter corresponded in molecular weigh and isoelectric point with that predicted from the N1L ORF. The latter analysis revealed the presence of other secreted proteins of similar molecular weight but different isoelectric points that also appear to map within the left end of the vaccinia genome. The recombinant virus was attenuated as judged by the increased intracranial LD50 for mice but nevertheless induced antibody and cytotoxic responses after intradermal and intraperitoneal injections. Relative to the parental virus, the recombinant was also more attenuated for immunodeficient nude mice, based on their survival time after infection. JF - Virology AU - Kotwal, G J AU - Hügin, A W AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 579 EP - 587 VL - 171 IS - 2 SN - 0042-6822, 0042-6822 KW - N1L protein, Vaccinia virus KW - 0 KW - RNA, Messenger KW - Viral Proteins KW - Index Medicus KW - Base Sequence KW - DNA Mutational Analysis KW - Restriction Mapping KW - Isoelectric Point KW - Molecular Sequence Data KW - Transcription, Genetic KW - Amino Acid Sequence KW - RNA, Messenger -- genetics KW - Molecular Weight KW - Viral Proteins -- genetics KW - Vaccinia virus -- genetics KW - Genes, Viral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79154992?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-12 N1 - Date created - 1989-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Molecular cloning, characterization, and expression of human ADP-ribosylation factors: two guanine nucleotide-dependent activators of cholera toxin. AN - 79147644; 2474826 AB - ADP-ribosylation factors (ARFs) are small guanine nucleotide-binding proteins that enhance the enzymatic activities of cholera toxin. Two ARF cDNAs, ARF1 and ARF3, were cloned from a human cerebellum library. Based on deduced amino acid sequences and patterns of hybridization of cDNA and oligonucleotide probes with mammalian brain poly(A)+ RNA, human ARF1 is the homologue of bovine ARF1. Human ARF3, which differs from bovine ARF1 and bovine ARF2, appears to represent a newly identified third type of ARF. Hybridization patterns of human ARF cDNA and clone-specific oligonucleotides with poly(A)+ RNA are consistent with the presence of at least two, and perhaps four, separate ARF messages in human brain. In vitro translation of ARF1, ARF2, and ARF3 produced proteins that behaved, by SDS/PAGE, similar to a purified soluble brain ARF. Deduced amino acid sequences of human ARF1 and ARF3 contain regions, similar to those in other G proteins, that are believed to be involved in GTP binding and hydrolysis. ARFs also exhibit a modest degree of homology with a bovine phospholipase C. The observations reported here support the conclusion that the ARFs are members of a multigene family of small guanine nucleotide-binding proteins. Definition of the regulation of ARF mRNAs and of function(s) of recombinant ARF proteins will aid in the elucidation of the physiologic role(s) of ARFs. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bobak, D A AU - Nightingale, M S AU - Murtagh, J J AU - Price, S R AU - Moss, J AU - Vaughan, M AD - Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 6101 EP - 6105 VL - 86 IS - 16 SN - 0027-8424, 0027-8424 KW - RNA, Messenger KW - 0 KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - ARF4 protein, human KW - Index Medicus KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Poly A -- genetics KW - Molecular Sequence Data KW - Brain -- metabolism KW - Amino Acid Sequence KW - Nucleic Acid Hybridization KW - Adenosine Diphosphate Ribose -- metabolism KW - RNA -- genetics KW - GTP-Binding Proteins -- metabolism KW - DNA -- metabolism KW - DNA -- genetics KW - GTP-Binding Proteins -- genetics KW - Cloning, Molecular KW - Cholera Toxin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79147644?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-19 N1 - Date created - 1989-09-19 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M25204; GENBANK; M25203 N1 - SuppNotes - Cited By: Anal Biochem. 1983 Jul 1;132(1):6-13 [6312838] Proc Natl Acad Sci U S A. 1988 Oct;85(20):7652-6 [3174659] J Cyclic Nucleotide Protein Phosphor Res. 1983-1984;9(6):435-48 [6396323] J Biol Chem. 1986 Jun 15;261(17):7906-11 [3086320] Proc Natl Acad Sci U S A. 1987 May;84(10):3107-11 [3106961] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5139-42 [3110784] Annu Rev Biochem. 1987;56:779-827 [3304147] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194-8 [6219389] Methods Enzymol. 1987;152:337-42 [3309564] J Biol Chem. 1988 Feb 5;263(4):1768-72 [3123477] Science. 1988 Jan 29;239(4839):487-91 [2448875] J Biol Chem. 1988 Feb 25;263(6):2577-80 [2830256] Nature. 1988 Mar 17;332(6161):269-72 [2831461] Adv Enzymol Relat Areas Mol Biol. 1988;61:303-79 [3128060] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 [3162770] FASEB J. 1988 May;2(8):2356-67 [2452111] Cell. 1988 Jun 3;53(5):669-71 [2836065] J Biol Chem. 1988 Jun 15;263(17):8282-7 [3131341] J Biol Chem. 1988 Jul 15;263(20):9926-32 [3133371] J Biol Chem. 1988 Nov 25;263(33):17255-7 [3141419] J Biol Chem. 1988 Dec 15;263(35):18965-71 [3143720] Anal Biochem. 1989 May 1;178(2):239-42 [2751085] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4620-4 [3133654] Proc Natl Acad Sci U S A. 1988 Aug;85(15):5488-91 [3135549] Oncogene. 1988 Aug;3(2):201-4 [3045729] Nucleic Acids Res. 1988 Aug 11;16(15):7583-600 [2970625] J Biol Chem. 1984 May 25;259(10):6228-34 [6327671] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mutagenesis of phi X174 am3 cs70 incorporated into the genome of mouse L-cells. AN - 79139944; 2761552 AB - The objective of our work with phi X174 has been to develop a shuttle vector that can be used comparatively in bacterial cells, different types of mammalian cells, and possibly in the various tissues of transgenic mice, with a constant mechanism for detection and analysis of mutations independent of any host-cell type. Toward that end, we have efficiently rescued phi X174 am3 cs70 that is host-silent and stably integrated into the genome of mouse L-cells. The particular mouse L-cell line contains tandem arrays, single copies, and fragments of phi X that, upon restriction enzyme excision, can result in 5 potentially active copies per diploid genome. The excised phi X DNA is recovered by column chromatography, ligated, and transfected into highly competent spheroplasts. The Rescue Efficiency, defined as the number of viable phages produced out of the total number of potentially recoverable copies, is approx. 10(-3). The Recovery Ratio, defined as the Rescue Efficiency for chromosomally-integrated phage DNA divided by the Rescue Efficiency for phi X am3 cs70, is close to one. Mouse L-cells containing the integrated phi X174 am3 cs70 were treated with 20 mM ethyl methanesulfonate. The reversion frequency of am3 among progeny phages rescued from treated cells was 1.4 X 10(-5) (193 revertants in 1.4 X 10(7) phages). This is significantly higher than the 5.8 X 10(-7) reversion frequency of am3 (7 revertants in 1.2 X 10(7) phages) among progeny phages rescued from untreated cells. JF - Mutation research AU - Burkhart, J G AU - Malling, H V AD - Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 125 EP - 134 VL - 213 IS - 2 SN - 0027-5107, 0027-5107 KW - DNA, Viral KW - 0 KW - Index Medicus KW - L Cells (Cell Line) KW - Animals KW - Mutagenicity Tests KW - Electrophoresis, Agar Gel KW - Chromatography, Liquid KW - Mice KW - DNA, Viral -- isolation & purification KW - Genetic Vectors KW - Bacteriophages -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79139944?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-13 N1 - Date created - 1989-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Prophylactic zidovudine after occupational exposure to the human immunodeficiency virus: an interim analysis. AN - 79126680; 2760486 AB - Note from Dr. Merle A. Sande--Health care workers are at risk of acquiring human immunodeficiency virus (HIV) infection subsequent to accidental sticks with needles contaminated with blood from infected patients. The risk is small but real. Postexposure management is critically important, but few solid data are available. Can zidovudine (AZT, azidothymidine) prevent infection? How soon after exposure must the drug be given? At what dosage? For how long? Two leading authorities were asked to discuss this problem and to offer recommendations. Both have developed programs in their institutions, Dr. David K. Henderson at the Warren Grant Magnuson Clinical Center at the National Institutes of Health and Dr. Julie L. Gerberding at the University of California, San Francisco. JF - The Journal of infectious diseases AU - Henderson, D K AU - Gerberding, J L AD - Hospital Epidemiology Service, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 321 EP - 327 VL - 160 IS - 2 SN - 0022-1899, 0022-1899 KW - Zidovudine KW - 4B9XT59T7S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Zidovudine -- therapeutic use KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Zidovudine -- adverse effects KW - Occupational Diseases -- prevention & control KW - Health Manpower UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79126680?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-08 N1 - Date created - 1989-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Systemic therapy for small-cell lung cancer: old themes replayed, new ones awaited. AN - 79123363; 2547029 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Viallet, J AU - Ihde, D C AD - National Cancer Institute Bethesda, MD. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 985 EP - 987 VL - 7 IS - 8 SN - 0732-183X, 0732-183X KW - Mitomycins KW - 0 KW - Mitomycin KW - 50SG953SK6 KW - Etoposide KW - 6PLQ3CP4P3 KW - Lomustine KW - 7BRF0Z81KG KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Cisplatin KW - Q20Q21Q62J KW - Altretamine KW - Q8BIH59O7H KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Etoposide -- administration & dosage KW - Humans KW - Mitomycins -- administration & dosage KW - Altretamine -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Lomustine -- administration & dosage KW - Methotrexate -- administration & dosage KW - Cisplatin -- administration & dosage KW - Lung Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Small Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79123363?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-29 N1 - Date created - 1989-08-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 1990 Jul;8(7):1282-3 [2162913] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Comparative tumorigenicity of N-nitroso-2-hydroxymorpholine, N-nitrosodiethanolamine and N-nitrosomorpholine in A/J mice and F344 rats. AN - 79120487; 2752522 AB - N-Nitroso-2-hydroxymorpholine (NHMOR), a genotoxic metabolite of the environmental carcinogens N-nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA), was assayed for tumorigenicity in A/J mice and F344 rats. Groups of female mice were given NHMOR, NMOR or NDELA in the drinking water over a 10-week period; total doses were 53-55 mumol/mouse. The experiment was terminated after 30 weeks. Whereas NMOR was a potent tumorigen, inducing 20.3 lung tumors/mouse, NHMOR and NDELA were only weakly tumorigenic, giving 1.2 and 1.4 lung tumors/mouse respectively. Groups of female F344 rats were also given these three nitrosamines in drinking water for 50 weeks, as follows: NHMOR, total dose 0.6 mmol/rat; NHMOR, 1.2 mmol; NMOR, 1.1 mmol and NDELA, 5.6 mmol. The experiment was terminated after 120 weeks. NMOR was a potent carcinogen, inducing liver tumors in 100% of the rats. NDELA gave hepatocellular tumors in 70% of the rats. NHMOR was inactive even at the higher dose. The results of this study do not support the hypothesis that NHMOR is a proximate carcinogen of NDELA or NMOR. JF - Carcinogenesis AU - Hecht, S S AU - Lijinsky, W AU - Kovatch, R M AU - Chung, F L AU - Saavedra, J E AD - NCI-Frederick Cancer Research Facility, MD 21701. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 1475 EP - 1477 VL - 10 IS - 8 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Nitrosamines KW - N-nitrosodiethanolamine KW - 30YI1289VY KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - N-nitrosomorpholine KW - 3L25FO7FN7 KW - N-nitroso-2-hydroxymorpholine KW - 67587-52-4 KW - Index Medicus KW - Thyroid Neoplasms -- chemically induced KW - Animals KW - Adenocarcinoma -- chemically induced KW - Liver Neoplasms -- chemically induced KW - Hemangiosarcoma -- chemically induced KW - Mice KW - Structure-Activity Relationship KW - Adenocarcinoma -- pathology KW - Rats KW - Mice, Inbred A KW - Rats, Inbred F344 KW - Liver Neoplasms -- pathology KW - Liver Neoplasms, Experimental -- pathology KW - Hemangiosarcoma -- pathology KW - Thyroid Neoplasms -- pathology KW - Lung Neoplasms -- chemically induced KW - Species Specificity KW - Female KW - Lung Neoplasms -- pathology KW - Diethylnitrosamine -- toxicity KW - Diethylnitrosamine -- analogs & derivatives KW - Nitrosamines -- toxicity KW - Carcinogens -- toxicity KW - Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79120487?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-31 N1 - Date created - 1989-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vitro processing of dengue virus structural proteins: cleavage of the pre-membrane protein. AN - 79118137; 2501515 AB - Processing of dengue virus structural proteins was assessed in vitro. RNA transcripts for cell-free translation were prepared from cloned DNA (dengue virus type 4, strain 814669 genome) encoding capsid, pre-membrane (prM), and the first 23 amino acids of envelope (E). Processing of a 33-kilodalton precursor polypeptide encoded by wild-type RNA transcripts occurred only in the presence of added microsomal membranes. Under these conditions, cleavage at the capsid-prM and prM-E sites and glycosylation of prM occurred in association with translocation. Amino acid sequence analysis confirmed that translation initiated at the predicted N terminus of the capsid and that capsid-prM cleavage occurred at the predicted site for the action of signal peptidase following a candidate signal sequence (hydrophobic residues 100 to 113) in the dengue virus precursor. Mutations were introduced into the dengue virus DNA template by site-directed mutagenesis, altering nucleotide sequences encoding the capsid and the candidate signal for prM. The phenotypes of the mutants were deduced by analysis of the products of cell-free translation of the respective RNA transcripts. The resulting observations confirmed that cleavage at the capsid-prM and prM-E sites is effected entirely by signal peptidase and that the candidate signal is required for translocation. JF - Journal of virology AU - Markoff, L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 3345 EP - 3352 VL - 63 IS - 8 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Glycoproteins KW - Protein Precursors KW - Protein Sorting Signals KW - RNA, Viral KW - Viral Proteins KW - Viral Structural Proteins KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase KW - EC 3.2.1.96 KW - Index Medicus KW - Protein Biosynthesis KW - Protein Precursors -- metabolism KW - Protein Sorting Signals -- genetics KW - Glycoside Hydrolases -- metabolism KW - Capsid -- genetics KW - Transcription, Genetic KW - Amino Acid Sequence KW - Precipitin Tests KW - Glycoproteins -- metabolism KW - Restriction Mapping KW - RNA, Viral -- genetics KW - DNA, Viral -- genetics KW - Mutation KW - Viral Proteins -- genetics KW - Protein Processing, Post-Translational KW - Viral Proteins -- metabolism KW - Dengue Virus -- genetics KW - Dengue Virus -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79118137?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-18 N1 - Date created - 1989-08-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1972 Jul;49(1):283-9 [4625020] J Immunol. 1967 Aug;99(2):291-6 [4961907] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Virology. 1978 Sep;89(2):423-37 [568848] Virology. 1981 Mar;109(2):418-27 [6259820] Virology. 1981 Apr 15;110(1):26-34 [7210510] Biochem J. 1981 Jun 1;195(3):639-44 [7316978] J Biol Chem. 1982 Oct 25;257(20):12180-90 [6896877] J Mol Biol. 1983 Jun 5;166(4):477-535 [6864790] Methods Enzymol. 1983;100:468-500 [6225933] Proc Natl Acad Sci U S A. 1985 Jul;82(14):4648-52 [3895223] Science. 1985 Aug 23;229(4715):726-33 [4023707] Virology. 1985 Sep;145(2):227-36 [2992152] Virology. 1985 May;143(1):224-9 [2998002] Cell. 1986 Jan 31;44(2):283-92 [3943125] J Mol Biol. 1986 Feb 5;187(3):309-23 [3009829] FEBS Lett. 1986 May 12;200(2):314-6 [3635477] Nucleic Acids Res. 1986 Jun 11;14(11):4683-90 [3714490] Virology. 1986 Nov;155(1):77-88 [3022479] Virology. 1986 Dec;155(2):365-77 [3024394] Virology. 1987 Feb;156(2):293-304 [3027980] Arch Virol. 1987;92(3-4):273-91 [3813888] Virology. 1987 Jun;158(2):348-60 [3035787] Adv Virus Res. 1987;33:45-90 [3035906] Virology. 1987 Aug;159(2):217-28 [3039728] Virology. 1987 Aug;159(2):237-43 [2441520] J Mol Biol. 1987 Jun 5;195(3):621-36 [2821280] Virology. 1987 Nov;161(1):262-7 [3672932] J Virol. 1987 Dec;61(12):4019-22 [3316711] J Gen Virol. 1988 Jan;69 ( Pt 1):1-21 [2826659] J Gen Virol. 1988 Jan;69 ( Pt 1):23-34 [2826667] Virology. 1988 Jan;162(1):167-80 [2827375] Virology. 1973 Feb;51(2):454-65 [4632654] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mechanisms of hypertension in the elderly. AN - 79110123; 2666486 AB - It has long been recognized that, with advancing age, basal systolic blood pressure increases within the clinically "normal" range in many individuals. Likewise, the prevalence of clinical hypertension, either systolic plus diastolic or isolated systolic, also increases with age. This report reviews the purported mechanisms underlying these types of hypertension and discusses age-associated changes in the cardiovascular system of normotensive individuals that could plausibly interact with these pathophysiologic mechanisms of hypertension. JF - Journal of the American Geriatrics Society AU - Lakatta, E G AD - Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland 21224. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 780 EP - 790 VL - 37 IS - 8 SN - 0002-8614, 0002-8614 KW - Sodium, Dietary KW - 0 KW - Index Medicus KW - Animals KW - Sodium, Dietary -- adverse effects KW - Humans KW - Hemodynamics KW - Autonomic Nervous System -- physiopathology KW - Aging -- physiology KW - Hypertension -- physiopathology KW - Hypertension -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79110123?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-06 N1 - Date created - 1989-09-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The effect of intravenous interleukin-2 on brain water content. AN - 79107071; 2787395 AB - Parenteral treatment with interleukin-2 (IL-2) is effective against certain advanced cancers outside the central nervous system. Prior to commencement of Phase II trials in patients with brain tumors, the neurological and neuroradiological features of 10 patients treated with intravenous administration of repeated doses of IL-2 were studied. Three patients had malignant gliomas, and seven patients had extracranial cancer without evidence of intracranial metastasis. All were treated with intravenous doses of 10(5) U/kg three times daily for up to 5 days. The patients with gliomas received cranial computerized axial tomography (CT) scans before IL-2 therapy was initiated and during the later stages of treatment. The patients with extracranial cancer underwent T2-weighted magnetic resonance (MR) imaging before and later during therapy. After two to 11 doses of IL-2, the patients with gliomas had marked neurological deterioration that was associated with a mild to marked increase in peritumoral edema and mass effect visible on CT scans. With cessation of treatment and appropriate supportive care, all returned to their pretreatment state. The patients with extracranial cancer were either neurologically unchanged or underwent minor transient changes in mental status (lethargy and confusion). In these patients, the MR signal intensity was quantified and compared in eight anatomic regions of interest. In six of the seven patients, there were increases in gray and white matter signal intensity consistent with increased cerebral water content. The percentage changes (means +/- standard error of the means) were 12.6% +/- 7.3% in the gray matter and 17.0% +/- 6.2% in the white matter. This study demonstrates that treatment with a high parenteral dose of IL-2 is not tolerated by patients with gliomas due to increased cerebral edema. In patients with extracranial cancer but no brain disease, parenteral IL-2 induces an increase in the cerebral water content of both gray and white matter. JF - Journal of neurosurgery AU - Saris, S C AU - Patronas, N J AU - Rosenberg, S A AU - Alexander, J T AU - Frank, J AU - Schwartzentruber, D J AU - Rubin, J T AU - Barba, D AU - Oldfield, E H AD - Clinical Neurosurgery Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 169 EP - 174 VL - 71 IS - 2 SN - 0022-3085, 0022-3085 KW - Interleukin-2 KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intravenous KW - Humans KW - Brain Chemistry -- drug effects KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Interleukin-2 -- therapeutic use KW - Brain Edema -- chemically induced KW - Brain Neoplasms -- metabolism KW - Glioma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79107071?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-23 N1 - Date created - 1989-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment. AN - 79104408; 2568405 AB - Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals. JF - Journal of neurochemistry AU - Johannessen, J N AU - Chiueh, C C AU - Bacon, J P AU - Garrick, N A AU - Burns, R S AU - Weise, V K AU - Kopin, I J AU - Parisi, J E AU - Markey, S P AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/08// PY - 1989 DA - August 1989 SP - 582 EP - 589 VL - 53 IS - 2 SN - 0022-3042, 0022-3042 KW - Pyridines KW - 0 KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Pargyline KW - 9MV14S8G3E KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Monoamine Oxidase KW - EC 1.4.3.4 KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Brain -- drug effects KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Tissue Distribution KW - Behavior, Animal -- drug effects KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Norepinephrine -- metabolism KW - Brain -- pathology KW - Dogs KW - Monoamine Oxidase -- metabolism KW - Female KW - Male KW - Pargyline -- pharmacology KW - Pyridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79104408?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-25 N1 - Date created - 1989-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Human peripheral lymphocyte growth regulation and response to phorbol esters is linked to synthesis and phosphorylation of the cytosolic protein, prosolin. AN - 79080235; 2745978 AB - Prosolin is a major cytosolic protein (Mr 18400, isoelectric point 5.9) first reported in HL-60 promyelocytic leukemia cells. It is rapidly phosphorylated (15 to 30 min) in response to TPA treatment as an early event in a sequence that leads to cessation of cell proliferation and to differentiation of promyelocytes into monocytes. In our study we examined the expression of prosolin in human peripheral lymphocytes and investigated the effects of TPA treatment on prosolin phosphorylation and on lymphocyte proliferation. Prosolin was not expressed in resting PBL but was induced after 24 to 36 h of PHA stimulation, simultaneously with induction of DNA synthesis. In rapidly proliferating (IL-2 dependent) PBL prosolin was a major cytosolic component, comprising 0.5% of total cytosolic protein, of which approximately 28% was phosphorylated. Expression of prosolin decreased again when either mitogen-induced or IL-2-dependent proliferation diminished during extended periods in culture. Thus, expression of prosolin is correlated with periods when PBL are cycling through S-phase. TPA treatment of IL-2-dependent PBL at the peak of their growth caused phosphorylation of about two-thirds of preexisting unphosphorylated prosolin within 1 h. This was accompanied by cessation of cell proliferation, as indicated by measurements of TdR incorporation. Although TPA has well known mitogenic effects in lymphocytes during initial activation, this result shows that it exerts an antiproliferative effect in rapidly dividing PBL. It is suggested that increased phosphorylation of prosolin may be an initiating event in the antiproliferative response to TPA, which would occur only in proliferating lymphocytes expressing prosolin. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cooper, H L AU - McDuffie, E AU - Braverman, R AD - Cell and Molecular Physiology Section, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/08/01/ PY - 1989 DA - 1989 Aug 01 SP - 956 EP - 963 VL - 143 IS - 3 SN - 0022-1767, 0022-1767 KW - Neoplasm Proteins KW - 0 KW - Phosphoproteins KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Phosphorylation KW - Humans KW - Cell Division -- drug effects KW - Cell Differentiation -- drug effects KW - Lymphocyte Activation -- drug effects KW - Cytosol -- physiology KW - Neoplasm Proteins -- biosynthesis KW - Lymphocytes -- immunology KW - Phosphoproteins -- biosynthesis KW - Neoplasm Proteins -- isolation & purification KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lymphocytes -- metabolism KW - Lymphocytes -- physiology KW - Phosphoproteins -- isolation & purification KW - Neoplasm Proteins -- metabolism KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79080235?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-18 N1 - Date created - 1989-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site. AN - 79066342; 2743314 AB - The ability of zinc acetate to modify the carcinogenic effects of CdCl2 in male Wistar [Crl:(WI)BR] rats was studied over a 2-year period. Groups of rats received a single s.c. injection of Cd (30.0 mumol/kg) in the dorsal thoracic midline or i.m. in the right thigh at time 0. Zinc was given in three separate s.c. doses of 0.1, 0.3, or 1.0 mmol/kg (at -6, 0, and +18 h relative to cadmium) in the lumbosacral area or p.o. at 100 ppm in the drinking water (-2 to +100 weeks). Cadmium treatments (s.c.) resulted in the appearance of tumors at the injection site and in the testes. The incidence of s.c. injection site tumors (mostly mixed sarcomas) was markedly reduced by high dose (1.0 mmol/kg) s.c. zinc (50% reduction) and was almost abolished by p.o. zinc (92% reduction). Testicular tumors (mostly Leydig cell adenomas) induced by s.c. cadmium were reduced in a dose-related fashion by zinc and were found to be highly dependent on the ability of zinc to prevent the chronic degenerative effects of cadmium in the testes. Oral zinc had no effect on s.c. cadmium-induced testicular tumors, while i.m. cadmium alone did not induce these tumors. In rats in which s.c. cadmium-induced testicular tumors and chronic degenerative effects were prevented by zinc (1.0 mmol/kg, s.c.), a marked elevation in prostatic tumors (exclusively adenomas) occurred (control, 9.6%; cadmium plus high zinc 29.6%). Cadmium given i.m., which did not result in testicular tumors or degeneration, also induced an elevated incidence (42.3%) of prostatic tumors, again indicating a dependence on testicular function. Prostatic tumor incidence was also significantly elevated (25.0%) in rats receiving 1.0 mmol/kg zinc, s.c., in combination with i.m. cadmium. These results indicate that zinc inhibition of cadmium carcinogenesis is a complex phenomenon, depending not only on dose and route but also on the target site in question. JF - Cancer research AU - Waalkes, M P AU - Rehm, S AU - Riggs, C W AU - Bare, R M AU - Devor, D E AU - Poirier, L A AU - Wenk, M L AU - Henneman, J R AD - Inorganic Carcinogenesis Section, National Cancer Institute, Frederick, Maryland. Y1 - 1989/08/01/ PY - 1989 DA - 1989 Aug 01 SP - 4282 EP - 4288 VL - 49 IS - 15 SN - 0008-5472, 0008-5472 KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Metallothionein -- biosynthesis KW - Dose-Response Relationship, Drug KW - Injections, Subcutaneous KW - Male KW - Zinc -- pharmacology KW - Sarcoma, Experimental -- prevention & control KW - Sarcoma, Experimental -- chemically induced KW - Skin Neoplasms -- chemically induced KW - Testicular Neoplasms -- prevention & control KW - Prostatic Neoplasms -- chemically induced KW - Cadmium -- toxicity KW - Prostatic Neoplasms -- prevention & control KW - Testicular Neoplasms -- chemically induced KW - Skin Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79066342?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-25 N1 - Date created - 1989-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - In vivo activity against HIV and favorable toxicity profile of 2',3'-dideoxyinosine. AN - 79123347; 2502840 AB - The purine analog 2',3'-dideoxyinosine (ddI), which has anti-retroviral activity in vitro was administered for up to 42 weeks to 26 patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex (ARC). Ten of these individuals were AZT-intolerant. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid (CSF). Comparatively little evidence of an effect against human immunodeficiency virus (HIV) was seen at the lowest four doses. However, patients in the four highest dose groups (ddI at 1.6 milligrams per kilogram intravenously and then greater than or equal to 3.2 milligrams per kilogram orally at least every 12 hours or higher) had increases in their circulating CD4+ T cells (P less than 0.0005), increased CD4/CD8 T cell ratios (P less than 0.01), and, where evaluable, more than an 80% decrease in serum HIV p24 antigen (P less than 0.05). The patients also had evidence of improved immunologic function, had reduced viremic symptomatology, and gained a mean of 1.6 kilogram with these comparatively infrequent dosing schedules (every 8 or 12 hours). The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release) and mild headaches and insomnia. These results suggest that serious short-term toxicity at therapeutic doses is not an inherent feature in the profile of agents with clinical anti-HIV activity. Further controlled studies to define the safety and efficacy of this agent may be worth considering. JF - Science (New York, N.Y.) AU - Yarchoan, R AU - Mitsuya, H AU - Thomas, R V AU - Pluda, J M AU - Hartman, N R AU - Perno, C F AU - Marczyk, K S AU - Allain, J P AU - Johns, D G AU - Broder, S AD - Clinical Oncology Program, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07/28/ PY - 1989 DA - 1989 Jul 28 SP - 412 EP - 415 VL - 245 IS - 4916 SN - 0036-8075, 0036-8075 KW - Antiviral Agents KW - 0 KW - Dideoxynucleosides KW - HIV Antigens KW - HIV Core Protein p24 KW - Retroviridae Proteins KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - Molecular Structure KW - Retroviridae Proteins -- analysis KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials as Topic KW - Leukocyte Count KW - Biological Availability KW - HIV Antigens -- analysis KW - Hypersensitivity, Delayed KW - Immunity, Cellular KW - Adult KW - Middle Aged KW - T-Lymphocytes -- immunology KW - Male KW - Female KW - Antiviral Agents -- therapeutic use KW - HIV -- drug effects KW - AIDS-Related Complex -- immunology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Dideoxynucleosides -- therapeutic use KW - Antiviral Agents -- cerebrospinal fluid KW - Dideoxynucleosides -- pharmacology KW - AIDS-Related Complex -- drug therapy KW - Antiviral Agents -- pharmacology KW - Acquired Immunodeficiency Syndrome -- immunology KW - Dideoxynucleosides -- adverse effects KW - Antiviral Agents -- adverse effects KW - Dideoxynucleosides -- cerebrospinal fluid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79123347?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-30 N1 - Date created - 1989-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane. AN - 79092643; 2663854 AB - The depletion of an inositol 1, 4,5-trisphosphate-sensitive intracellular Ca2+ pool has been proposed to be the signal for Ca2+ entry in agonist-activated cells. Consistent with this idea, thapsigargin, which releases intracellular Ca2+ without inositol phosphate formation, has been reported to activate Ca2+ entry in certain cells. We now report the effects of thapsigargin on Ca2+ entry in parotid acinar cells. In fura-2-loaded parotid acinar cells, thapsigargin caused a sustained elevation of [Ca2+], but did not increase inositol phosphate formation. In the absence of extracellular Ca2+, the increase in [Ca2+], was transient, suggesting that thapsigargin activates both the release of Ca2+ from intracellular stores and the entry of Ca2+ from the extracellular space. In the absence of extracellular Ca2+, pretreatment with methacholine, an agonist believed to mobilize Ca2+ through the production of inositol 1,4,5-trisphosphate, inhibited but did not completely block the response to thapsigargin; likewise, pretreatment with thapsigargin inhibited the response to methacholine. In permeabilized cells, thapsigargin gradually released Ca2+, whereas inositol 1,4,5-trisphosphate caused a rapid and transient discharge of Ca2+. The simultaneous addition of thapsigargin with inositol 1,4,5-trisphosphate evoked a maximum Ca2+ release similar to that for inositol 1,4,5-trisphosphate alone, but the reuptake seen with inositol 1,4,5-trisphosphate alone was abolished. In intact cells, methacholine and thapsigargin together produced a greater initial release of Ca2+ than either alone, but they were not additive in the sustained phase of Ca2+ mobilization. These results demonstrate that the mechanisms for activation of Ca2+ entry by thapsigargin and methacholine are the same and are consistent with the idea that entry is initiated by the depletion of the intracellular inositol 1,4,5-trisphosphate-sensitive Ca2+ pool. The results also indicate that, in contrast to previously proposed models, Ca2+ entry into agonist-activated cells occurs directly across the plasma membrane to the cytoplasm rather than through a cycle of uptake and release by the intracellular Ca2+ pool. JF - The Journal of biological chemistry AU - Takemura, H AU - Hughes, A R AU - Thastrup, O AU - Putney, J W AD - Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07/25/ PY - 1989 DA - 1989 Jul 25 SP - 12266 EP - 12271 VL - 264 IS - 21 SN - 0021-9258, 0021-9258 KW - Carcinogens KW - 0 KW - Ethers KW - Inositol Phosphates KW - Methacholine Compounds KW - Plant Extracts KW - Sugar Phosphates KW - Methacholine Chloride KW - 0W5ETF9M2K KW - Inositol KW - 4L6452S749 KW - Ionomycin KW - 56092-81-0 KW - Thapsigargin KW - 67526-95-8 KW - Inositol 1,4,5-Trisphosphate KW - 85166-31-0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Ethers -- pharmacology KW - Cell Membrane -- drug effects KW - Methacholine Compounds -- pharmacology KW - Inositol -- metabolism KW - Models, Biological KW - Biological Transport -- drug effects KW - Rats KW - Cells, Cultured KW - Kinetics KW - Cell Membrane Permeability KW - Cell Membrane -- metabolism KW - Signal Transduction KW - Calcium -- metabolism KW - Plant Extracts -- pharmacology KW - Carcinogens -- pharmacology KW - Sugar Phosphates -- metabolism KW - Parotid Gland -- drug effects KW - Inositol Phosphates -- metabolism KW - Sugar Phosphates -- pharmacology KW - Parotid Gland -- metabolism KW - Parotid Gland -- cytology KW - Inositol Phosphates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79092643?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-18 N1 - Date created - 1989-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Thirteen-week toxicity study of n-hexane in B6C3F1 mice after inhalation exposure. AN - 79107275; 2749745 AB - B6C3F1 mice were exposed to n-hexane 6 h/day, 5 days/week for 13 weeks at concentrations of 0, 500, 1000, 4000, and 10,000 ppm and at 1000 ppm 22 h/day, 5 days/week for 13 weeks (1000C group). Toxicological endpoints assessed included clinical signs, body and organ weight changes, gross and histopathology, neuropathology, and a battery of neurobehavioral tests. All mice survived the treatment. Exposure-related effects of n-hexane included sneezing at 10,000 ppm and body weight gain depression at 1000C and 10,000 ppm. Histopathologic changes included mild inflammatory, erosive and regenerative lesions in the olfactory and respiratory epithelium of the nasal cavity at 1000C, 4000, and 10,000 ppm. The only neurobehavioral parameter affected was a decrease in locomotor activity in female mice at 1000C and 10,000 ppm. In teased fiber preparations of tibial nerve, paranodal axonal swellings were observed at 1000C or at 10,000 ppm, but not in the control groups. The severity of the peripheral nerve lesion was mild. These studies show that n-hexane has minimal toxicity to the nervous system and respiratory system of mice. JF - Toxicology AU - Dunnick, J K AU - Graham, D G AU - Yang, R S AU - Haber, S B AU - Brown, H R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07/17/ PY - 1989 DA - 1989 Jul 17 SP - 163 EP - 172 VL - 57 IS - 2 SN - 0300-483X, 0300-483X KW - Hexanes KW - 0 KW - n-hexane KW - 2DDG612ED8 KW - Index Medicus KW - Mice, Inbred Strains KW - Animals KW - Reference Values KW - Turbinates -- pathology KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Turbinates -- drug effects KW - Mice KW - Administration, Inhalation KW - Male KW - Female KW - Hexanes -- administration & dosage KW - Hexanes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79107275?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-23 N1 - Date created - 1989-08-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Pyrethroids: involvement of sodium channels in effects on inositol phosphate formation in guinea pig synaptoneurosomes. AN - 79099299; 2546657 AB - The effects of pyrethroids were studied on phosphoinositide breakdown in guinea pig synaptoneurosomes. Similar to other agents that activate voltage-dependent sodium channels, type I and type II pyrethroids stimulated phosphoinositide breakdown. Type II pyrethroids, like deltamethrin and fenvalerate, were more potent and, at least for deltamethrin, more efficacious than type I pyrethroids, like allethrin, resmethrin and permethrin. The effects of type II pyrethroids could be partially inhibited by the sodium channel blocker tetrodotoxin. The effects of allethrin and resmethrin were not affected by 5 microM tetrodotoxin. Stimulation of phosphoinositide breakdown by fenvalerate was additive to the stimulation elicited by the receptor agonists carbamylcholine and norepinephrine, but not to the stimulation elicited by sodium channel agents (batrachotoxin, scorpion venom and pumiliotoxin B). Stimulation by allethrin was not additive to the stimulation elicited either by receptor agonists or sodium channel agents. A submaximal concentration of allethrin, a type I pyrethroid, did not greatly affect the dose-dependent stimulation elicited by a type II pyrethroid, deltamethrin, while a higher concentration of allethrin prevented further stimulation by type II pyrethroids. A local anesthetic, dibucaine, which inhibits sodium channel activation, inhibited phosphoinositide breakdown induced by type II, but not by type I pyrethroids, except at higher concentrations. Thus, type II pyrethroids appear to stimulate phosphoinositide breakdown in synaptoneurosomes in a manner analogous to other sodium channel agents, while type I pyrethroids elicit phosphoinositide breakdown by a different mechanism, probably not involving sodium channels. JF - Brain research AU - Gusovsky, F AU - Secunda, S I AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, NIDDK, Bethesda, MD 20892. Y1 - 1989/07/17/ PY - 1989 DA - 1989 Jul 17 SP - 72 EP - 78 VL - 492 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Inositol Phosphates KW - 0 KW - Insecticides KW - Nitriles KW - Pyrethrins KW - Sodium Channels KW - Sugar Phosphates KW - decamethrin KW - 2JTS8R821G KW - fenvalerate KW - Z6MXZ39302 KW - Index Medicus KW - Animals KW - Synaptosomes -- drug effects KW - Guinea Pigs KW - Insecticides -- pharmacology KW - Synaptosomes -- metabolism KW - Sugar Phosphates -- metabolism KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Inositol Phosphates -- metabolism KW - Sodium Channels -- metabolism KW - Pyrethrins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79099299?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-31 N1 - Date created - 1989-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Radiation dose and breast cancer risk in patients treated for cancer of the cervix. AN - 79091660; 2744900 AB - The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses. JF - International journal of cancer AU - Boice, J D AU - Blettner, M AU - Kleinerman, R A AU - Engholm, G AU - Stovall, M AU - Lisco, H AU - Austin, D F AU - Bosch, A AU - Harlan, L AU - Krementz, E T AU - Latouret, H B AU - Merril, J A AU - Petters, L J AU - Schulz, M D AU - Wactawski, J AU - Storm, H H AU - Björkholm, E AU - Pettersson, F AU - Bell, C M AU - Coleman, M P AU - Fraser, P AU - Neal, F E AU - Prior, P AU - Choi, N W AU - Hislop, T G AU - Koch, M AU - Kreiger, N AU - Robb, D AU - Robson, D AU - Thomson, D H AU - Lochmüller, H AU - von Fournier, D AU - Frischkorn, R AU - Kjørstad, K E AU - Rimpela, A AU - Pejovic, M H AU - Kirn, V P AU - Stankusova, H AU - Pisani, P AU - Sigurdsson, K AU - Hutchison, G B AU - MacMahon, B AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 7 EP - 16 VL - 44 IS - 1 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Ovary -- radiation effects KW - Age Factors KW - Risk Factors KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Female KW - Neoplasms, Radiation-Induced -- etiology KW - Breast Neoplasms -- etiology KW - Uterine Cervical Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79091660?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-16 N1 - Date created - 1989-08-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Int J Cancer 1991 Jul;127(1):118 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A single amino acid substitution in HLA-A2 can alter the selection of the cytotoxic T lymphocyte repertoire that responds to influenza virus matrix peptide 55-73. AN - 79066477; 2472444 AB - Previous studies have demonstrated that certain amino acid substitutions in the alpha two domain at positions 152 and 156 in the alpha two helix of the HLA-A2 molecule can affect presentation of the influenza virus matrix peptide M1 55-73 without abolishing binding of the M1 peptide. HLA-A2.1-restricted M1 55-73 peptide-specific CTL lines obtained from almost all HLA-A2.1+ individuals fail to recognize the M1 peptide presented by site-directed mutants of HLA-A2 that have either a Val----Ala or Val----Gln substitution at position 152 or a Leu----Trp substitution at position 156. Only one HLA-A2+ individual (donor Q66, HLA-A2,-B53,-B63) has been found who is able to generate a unique repertoire of HLA-A2-restricted M1 peptide-specific CTL that can recognize peptide presented by HLA-A2 mutants with either an Ala or Gln substitution at position 152 or a Trp substitution at position 156. These Q66 M1 peptide-specific CTL could be selected by stimulation with M1 peptide-pulsed transfectants that express the mutant HLA-A2 gene with the Trp substitution at 156. To determine if the presence of the unique CTL repertoire could be attributed to a variant HLA-A2 molecule in Q66, sequences were determined from polymerase chain reaction-amplified segments of the HLA-A2 RNA. Two different HLA-A2 genes were found expressed in Q66 cells: one is identical to HLA-A2.1 and the other is identical to HLA-A2.2F (Gln----Arg at position 43, Val----Leu at position 95, and Leu----Trp at position 156). These results demonstrate that a different CTL repertoire specific for HLA-A2 plus the M1 55-73 peptide is generated in an individual that expresses both HLA-A2.1 and HLA-A2.2F compared to individuals who express HLA-A2.1 alone, and that the unique repertoire can be selected by the presence of an HLA-A2 molecule with a single amino acid substitution at position 156. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Shimojo, N AU - Cowan, E P AU - Engelhard, V H AU - Maloy, W L AU - Coligan, J E AU - Biddison, W E AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 558 EP - 564 VL - 143 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Viral KW - 0 KW - Epitopes KW - HLA-A Antigens KW - HLA-A2 Antigen KW - Peptide Fragments KW - Viral Matrix Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Base Sequence KW - Humans KW - Antigens, Viral -- immunology KW - Adult KW - Molecular Sequence Data KW - Cytotoxicity Tests, Immunologic KW - Amino Acid Sequence KW - Antigen-Presenting Cells -- immunology KW - Epitopes -- immunology KW - Mutation KW - Cell Line KW - T-Lymphocytes, Cytotoxic -- classification KW - Influenza A virus -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - HLA-A Antigens -- immunology KW - Peptide Fragments -- immunology KW - Viral Matrix Proteins -- immunology KW - HLA-A Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79066477?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-31 N1 - Date created - 1989-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Induction of endogenous cytokine-mRNA in circulating peripheral blood mononuclear cells by IL-2 administration to cancer patients. AN - 79064984; 2661690 AB - The lymphokine IL-2 plays a central role in immune regulation. Recent clinical trials have shown that when administered systemically either alone, or in combination with lymphokine-activated killer cells, IL-2 can cause regression of metastatic tumors in some patients with a variety of otherwise refractory cancers. To evaluate the mechanism of in vivo action of IL-2, as well as the toxicity associated with its administration, we have studied the in vivo cytokine-mRNA expression of circulating PBMC in cancer patients undergoing treatment with high dose IL-2. Before IL-2 administration, we found low level or no evidence of cytokine-mRNA expression in PBMC. After IL-2 infusion, circulating PBMC showed enhanced proliferative activity and contained significant levels of mRNA for TNF-alpha and IL-6 as well as mRNA for the p55 IL-2R, Tac, but no mRNA coding for granulocyte-monocyte-CSF and TNF-beta (lymphotoxin). IL-1 beta mRNA was expressed at very low levels in circulating PBMC after IL-2 infusion. Each of these cytokine -mRNA was, however, inducible in vitro by stimulation of PBMC with IL-2 alone. The results of these in vivo studies suggest that IL-2 may be a physiologic inducer of TNF and IL-6 which, because of their pleiotropic effects, may be important endogenous signals in the body's immune response and account for some of the physiologic changes seen in patients receiving high dose IL-2. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kasid, A AU - Director, E P AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 736 EP - 739 VL - 143 IS - 2 SN - 0022-1767, 0022-1767 KW - Biological Factors KW - 0 KW - Cytokines KW - Interleukin-2 KW - Interleukin-6 KW - Interleukins KW - RNA, Messenger KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Interleukin-2 -- blood KW - Lymphocyte Activation KW - Drug Administration Schedule KW - Interleukins -- blood KW - Humans KW - Tumor Necrosis Factor-alpha -- blood KW - Recombinant Proteins -- administration & dosage KW - Interleukin-2 -- blood KW - Interleukin-2 -- administration & dosage KW - Leukocytes, Mononuclear -- metabolism KW - Biological Factors -- metabolism KW - RNA, Messenger -- isolation & purification KW - RNA, Messenger -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79064984?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-31 N1 - Date created - 1989-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. AN - 79061530; 2662848 AB - Idiopathic inflammatory myopathy, a category encompassing polymyositis, dermatomyositis, and a number of other disorders, is very uncommon, but has been the focus of intense study in the Arthritis and Rheumatism Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the past several years. We describe the clinical picture, stressing the need for biopsy to ensure correct diagnosis. It is especially important to recognize the treatment-resistant variant, inclusion body myositis. The extraskeletal manifestations, particularly the cardiopulmonary, oropharyngeal, gastrointestinal, and endocrine involvement, are described. The cardiopulmonary involvement, especially interstitial lung disease, arrhythmias, and cardiac failure, may dominate the clinical picture. The known causes are varied, and include drugs, toxins, and some infectious agents, however, in most cases a cause cannot yet be identified. Circumstantial evidence suggests that picornaviruses may initiate some cases in humans, and a very similar disease in mice caused by a picornavirus is actively under study. Studies of autoantibodies and cellular immune function support a central role for disordered immunity in the pathogenesis. The myositis-specific autoantibodies, especially those directed at certain enzymes important in protein synthesis (the aminoacyl-transfer RNA synthetases), are found in a clinically distinct subset of patients. Although most patients respond initially to corticosteroids, cytotoxic drugs are sometimes added when steroid toxicity or refractoriness develops. We describe several newer therapies under study for such cases and outline future directions in research. JF - Annals of internal medicine AU - Plotz, P H AU - Dalakas, M AU - Leff, R L AU - Love, L A AU - Miller, F W AU - Cronin, M E AD - National Institutes of Health, Bethesda, MD 20892. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 143 EP - 157 VL - 111 IS - 2 SN - 0003-4819, 0003-4819 KW - Autoantibodies KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Cell Movement KW - Animals KW - Neoplasms -- complications KW - Autoantibodies -- metabolism KW - Humans KW - Disease Models, Animal KW - Antibody Formation KW - Lymphocytes -- physiology KW - Dermatomyositis -- pathology KW - Myositis -- immunology KW - Myositis -- therapy KW - Dermatomyositis -- etiology KW - Myositis -- physiopathology KW - Myositis -- pathology KW - Myositis -- etiology KW - Dermatomyositis -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79061530?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-04 N1 - Date created - 1989-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effects of bryostatins and retinoic acid on phorbol ester- and diacylglycerol-induced squamous differentiation in human tracheobronchial epithelial cells. AN - 79033509; 2567623 AB - Previous studies have shown that normal human tracheobronchial epithelial (HBE) cells undergo squamous differentiation upon treatment with phorbol 12-myristate 13-acetate (PMA). In this study, we report that induction of this differentiation program is accompanied by an increase in the accumulation of cholesterol sulfate and in transglutaminase type I activity, two markers of squamous differentiation. Several carcinoma cell lines did not exhibit an increase in these differentiation markers after PMA-treatment and appear to have acquired a defect in the mechanism that triggers differentiation. The diacylglycerol analogue, didecanoylglycerol (diC10), was also able to induce squamous differentiation. Bryostatin 1, another activator of protein kinase C, did not induce terminal cell division or increase cholesterol sulfate accumulation or transglutaminase type I activity. Bryostatin 1 not only failed to inhibit cell proliferation and to induce differentiation but antagonized the PMA- and diC10-induced commitment to terminal differentiation. The bryostatin blocked both the PMA-induced terminal cell division as well as the expression of the two differentiation markers. Retinoids were found not to affect the PMA-induced commitment to terminal cell division but did inhibit the expression of the differentiated phenotype. Our results indicate that the bryostatins and retinoids affect the multistep process of squamous differentiation in tracheobronchial epithelial cells at two different stages. JF - Cancer research AU - Jetten, A M AU - George, M A AU - Pettit, G R AU - Rearick, J I AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 22709. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 3990 EP - 3995 VL - 49 IS - 14 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Diglycerides KW - Glycerides KW - Lactones KW - Macrolides KW - Sulfates KW - bryostatin 1 KW - 37O2X55Y9E KW - Tretinoin KW - 5688UTC01R KW - bryostatin 2 KW - 87745-28-6 KW - Transglutaminases KW - EC 2.3.2.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Sulfates -- metabolism KW - Transglutaminases -- metabolism KW - Epithelial Cells KW - Cells, Cultured KW - Kinetics KW - Humans KW - Organ Culture Techniques KW - Epithelium -- drug effects KW - Tretinoin -- pharmacology KW - Diglycerides -- pharmacology KW - Bronchi -- cytology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Trachea -- cytology KW - Bronchi -- drug effects KW - Trachea -- drug effects KW - Cell Differentiation -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Glycerides -- pharmacology KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79033509?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-03 N1 - Date created - 1989-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Augmentation of antitumor efficacy by the combination of recombinant tumor necrosis factor and chemotherapeutic agents in vivo. AN - 79033146; 2736513 AB - We evaluated the in vivo antitumor effects of the combination of recombinant human tumor necrosis factor (rhTNF) and three chemotherapeutic agents in an established murine tumor model. C57BL/6 mice bearing a subdermal weakly immunogenic 3-methylcholanthrene-induced sarcoma (MCA-106) received one i.v. dose of cyclophosphamide (Cy) (100 mg/kg), doxorubicin (5 mg/kg), or 5-fluorouracil (75 mg/kg) on either Day 8, 10, or 12. All animals received one i.v. dose of rhTNF (4 or 6 micrograms/mouse) on Day 10. The most effective time for administration of the chemotherapeutic agent was determined to be 48 h following rhTNF administration of all agents tested. The combined results of four separate experiments evaluating tumor size on Day 28 following tumor inoculation revealed that the groups treated with 4 or 6 micrograms of rhTNF and Cy (on Day 12) had tumor size reductions of 70 and 94%, respectively, compared to untreated controls (P2 less than 0.005). Mice treated with Cy alone, or with 4 or 6 micrograms of rhTNF alone had tumor size reductions of 30, 35, and 41%, respectively, compared to untreated controls (P2 less than 0.02). Analysis of cure rates demonstrates that the combination of Cy with 4 or 6 micrograms tumor necrosis factor cured 35 and 48% of the animals, respectively (P2 less than 0.01), compared to 10, 0, and 14% of mice treated with single agent Cy, 4 micrograms rhTNF, or 6 micrograms rhTNF, respectively. The timing of Cy and TNF administration was critical since administration of Cy prior to or concurrent with rhTNF was not effective in reducing tumor area or increasing cure rates over those achieved with either agent alone. Mice treated with doxorubicin alone had an increase in tumor size of 139 +/- 29% over untreated controls (P2 less than 0.05) on Day 28 following tumor inoculation and none were cured. In contrast, mice treated with doxorubicin plus 4 or 6 micrograms rhTNF exhibited early reductions in tumor size such that on Day 28 the average tumor areas were decreased by 66 +/- 34% (P2 less than 0.05) and 73 +/- 1% (P2 less than 0.02) of untreated controls with cure rates of 29% and 43% (P2 less than 0.02), respectively. However, the combination of 6 micrograms rhTNF plus doxorubicin led to substantial lethal toxicity with only 29% of mice surviving treatment. 5-Fluorouracil alone resulted in an increase in tumor area of 164% (P2 less than 0.05) over that of untreated controls on Day 28 following tumor inoculation.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Krosnick, J A AU - Mulé, J J AU - McIntosh, J K AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 3729 EP - 3733 VL - 49 IS - 14 SN - 0008-5472, 0008-5472 KW - Recombinant Proteins KW - 0 KW - Tumor Necrosis Factor-alpha KW - Methylcholanthrene KW - 56-49-5 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Drug Evaluation, Preclinical KW - Recombinant Proteins -- therapeutic use KW - Recombinant Proteins -- administration & dosage KW - Female KW - Sarcoma, Experimental -- drug therapy KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Cyclophosphamide -- therapeutic use KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Sarcoma, Experimental -- chemically induced KW - Sarcoma, Experimental -- pathology KW - Doxorubicin -- therapeutic use KW - Doxorubicin -- administration & dosage KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79033146?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-03 N1 - Date created - 1989-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Evaluation of the transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice. AN - 79032291; 2736518 AB - The transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was assessed in three strains of mice: A/J; C3H/He x C57BL/6 F1 (hereafter called C3B6F1); and Swiss outbred [Cr:NIH(S)]. NNK (100 mg/kg) was administered i.p. on Days 14, 16, and 18 of gestation to A/J and C3H/He mice and on Days 15, 17 and 19 of gestation to the Swiss mice. The effects of postnatal treatment with tumor-promoting agents, including 0.05% sodium barbital in the drinking water until death or a single dose of Aroclor 1254 (a mixture of polychlorinated biphenyls, PCB) given on Postnatal Day 8 or 56, were also examined. Progeny were sacrificed at age 24 wk (A/J) or 72 wk (C3B6F1 and Swiss). Significant incidences of tumors occurred in the lungs of strain A/J progeny and in the livers of male C3B6F1 and Swiss progeny. Lung tumor incidence was 8 of 34 (24%) in the female offspring of the A/J mice treated with NNK, compared with 1 of 39 (3%) in controls (P less than 0.05). A 2-fold difference in lung tumor incidence in male offspring of NNK-treated (4 of 23, 13%) versus control (3 of 48, 6%) A/J mice was not of statistical significance. However, the incidence of lung tumors in NNK-exposed progeny A/J mice in both sexes combined (12 of 66, 18%) was also significantly greater than in controls (4 of 87, 5%). The incidence of liver tumors in the male C3B6F1 mice exposed transplacentally to NNK was 12 of 30 (40%) compared to 8 of 46 (17%) in controls (P less than 0.05). No effects of postnatal sodium barbital or PCB were observed on transplacental NNK tumorigenicity in C3B6F1 mice. The combined incidence of liver carcinoma in male mice in all NNK-treated groups (13 of 141, 9%) was significantly greater (P less than 0.05) than in controls (5 of 144, 3%). In male Swiss mice exposed transplacentally to NNK, the incidence of liver tumors was 3 of 57 (5%) compared to 0 of 35 controls, and postnatal treatment with PCB on Day 56 caused a significant increase (5 of 26, 19%) (P less than 0.05) in the incidence of NNK-induced liver tumors. The combined incidence of liver tumors in the male offspring of the Swiss mice treated with NNK, with or without PCB, was 8 of 83 (10%) which was significantly greater (P less than 0.05) than in controls (0 of 66).(ABSTRACT TRUNCATED AT 400 WORDS) JF - Cancer research AU - Anderson, L M AU - Hecht, S S AU - Dixon, D E AU - Dove, L F AU - Kovatch, R M AU - Amin, S AU - Hoffmann, D AU - Rice, J M AD - Division of Cancer Etiology, National Cancer Institute, Frederick, Maryland 21701. Y1 - 1989/07/15/ PY - 1989 DA - 1989 Jul 15 SP - 3770 EP - 3775 VL - 49 IS - 14 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Nitrosamines KW - 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone KW - 7S395EDO61 KW - Index Medicus KW - Animals KW - Fetus -- drug effects KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Placenta -- physiology KW - Neoplasms, Experimental -- pathology KW - Male KW - Female KW - Pregnancy KW - Plants, Toxic KW - Nitrosamines -- toxicity KW - Maternal-Fetal Exchange KW - Liver Neoplasms, Experimental -- pathology KW - Tobacco KW - Carcinogens -- toxicity KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79032291?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-03 N1 - Date created - 1989-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The use of native T7 DNA polymerase for site-directed mutagenesis. AN - 79150903; 2668888 JF - Nucleic acids research AU - Bebenek, K AU - Kunkel, T A AD - Laboratory of Molecular Genetics, NIEHS, Research Triangle Park, NC 27709. Y1 - 1989/07/11/ PY - 1989 DA - 1989 Jul 11 SP - 5408 VL - 17 IS - 13 SN - 0305-1048, 0305-1048 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - T-Phages -- enzymology KW - Escherichia coli -- enzymology KW - DNA Replication KW - DNA -- chemical synthesis KW - Mutation KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79150903?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-11 N1 - Date created - 1989-09-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1971 Apr 25;246(8):2692-701 [4928650] J Biol Chem. 1974 Sep 10;249(17):5668-76 [4606459] J Biol Chem. 1987 Nov 25;262(33):16212-23 [3316214] J Biol Chem. 1983 Sep 25;258(18):11174-84 [6309835] Science. 1985 Apr 19;228(4697):291-7 [3838593] J Biol Chem. 1981 Apr 25;256(8):4087-94 [6971292] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Recognition properties of peptides hydropathically complementary to residues 356-375 of the c-raf protein. AN - 79064060; 2472393 AB - Two peptides with hydropathic complementarity to residues 356-375 of the c-raf protein were synthesized to determine if they recognize the raf-(356-375) peptide as well as the entire protein. One peptide was deduced from the complementary mRNA for the raf protein corresponding to residues 356-375, whereas the other was deduced solely from the amino acid sequence of the 20-mer segment using a computer program able to generate peptide sequences with hydropathic complementarity to a given sequence. Specific binding of both peptides to the raf 20-mer segment was demonstrated when either the raf 20-mer peptide or the complementary peptides were immobilized on a column. Binding affinities were in the millimolar-micromolar range. Identical binding properties were observed with peptides synthesized with either all D- or all L-amino acids, suggesting a lack of conformational dependence. Binding was also unaffected by the presence of 8 M urea or detergents, was dependent on solvent characteristics of pH and ionic strength, and was abolished by the presence of competing peptides in the eluting buffer. Recognition between raf complementary peptides was accompanied by spectral changes in the far and near UV region, as monitored by circular dichroism. Proteolytic degradation was retarded by the binding of these peptides. Once immobilized on a column, these peptides proved useful for the isolation by affinity chromatography of a recombinant c-raf protein from an Escherichia coli crude cell extract. JF - The Journal of biological chemistry AU - Fassina, G AU - Roller, P P AU - Olson, A D AU - Thorgeirsson, S S AU - Omichinski, J G AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07/05/ PY - 1989 DA - 1989 Jul 05 SP - 11252 EP - 11257 VL - 264 IS - 19 SN - 0021-9258, 0021-9258 KW - Peptide Fragments KW - 0 KW - Proto-Oncogene Proteins KW - RNA, Complementary KW - RNA, Messenger KW - RNA KW - 63231-63-0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Software KW - Sequence Homology, Nucleic Acid KW - Circular Dichroism KW - Amino Acid Sequence KW - Chromatography, High Pressure Liquid KW - Binding Sites KW - Chromatography, Affinity KW - Adenosine Triphosphate -- metabolism KW - Binding, Competitive KW - Molecular Sequence Data KW - Trypsin -- metabolism KW - Protein Conformation KW - Peptide Fragments -- metabolism KW - Proto-Oncogene Proteins -- isolation & purification KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Escherichia coli -- analysis KW - Peptide Fragments -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79064060?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-02 N1 - Date created - 1989-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mammalian topoisomerase II activity is modulated by the DNA minor groove binder distamycin in simian virus 40 DNA. AN - 79045841; 2544590 AB - DNA topoisomerases II are nuclear enzymes that have been identified recently as targets for some of the most active anticancer drugs. Antitumor topoisomerase II inhibitors such as teniposide (VM-26) produce enzyme-induced DNA cleavage and inhibition of enzyme activity. By adding to such reactions distamycin, a compound whose effects on DNA have been extensively characterized, we investigated the effects of drug binding upon topoisomerase II-mediated DNA cleavage induced by VM-26. We have found a correspondence between distamycin binding (determined by footprinting analysis) and topoisomerase II-mediated cleavage of SV40 DNA (determined by sequencing gel analysis). Distamycin binding potentiated the cleavage of specific sites in the near proximity of distamycin-binding sites (within at least 25 base pairs), which indicates that DNA secondary structure is involved in topoisomerase II-DNA interactions. That distamycin potentiated cleavage only at sites that were recognized in the absence of distamycin and suppressed cleavage directly at distamycin-binding sites indicates that topoisomerase II recognizes DNA on the basis of primary sequence. In addition, distamycin stimulated topoisomerase II-mediated DNA relaxation and antagonized the inhibitory effect of VM-26. These results show that the DNA sequence-specific binding of distamycin produces local and propagated effects in the DNA which markedly affect topoisomerase II activity. JF - The Journal of biological chemistry AU - Fesen, M AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07/05/ PY - 1989 DA - 1989 Jul 05 SP - 11354 EP - 11359 VL - 264 IS - 19 SN - 0021-9258, 0021-9258 KW - DNA, Viral KW - 0 KW - Distamycins KW - Pyrroles KW - Teniposide KW - 957E6438QA KW - DNA Restriction Enzymes KW - EC 3.1.21.- KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Base Sequence KW - Electrophoresis KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - Leukemia L1210 -- enzymology KW - Mice KW - Repetitive Sequences, Nucleic Acid KW - Nucleic Acid Conformation -- drug effects KW - Teniposide -- pharmacology KW - Binding Sites KW - Distamycins -- metabolism KW - Simian virus 40 -- genetics KW - DNA Topoisomerases, Type II -- metabolism KW - Pyrroles -- pharmacology KW - Distamycins -- pharmacology KW - DNA, Viral -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79045841?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-02 N1 - Date created - 1989-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effects of MPP+ on the release of serotonin and 5-hydroxyindoleacetic acid from rat striatum in vivo. AN - 79280488; 2478372 AB - A procedure utilizing brain dialysis was employed to investigate the effects of 1-methyl-4-phenylpyridinium ion (MPP+), the major metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on the in vivo release of 5-hydroxytryptamine (5-HT) from the rat striatum. MPP+ (10(-5)-10(-2) M) was administered through the microdialysis probe and dialysates were collected and assayed for monoamines and their metabolites by a high performance liquid chromatography coupled with an electrochemical detector (HPLC-EC). In addition to a dopamine (DA) releasing action, MPP+ caused a cumulatively dose-dependent increase in the release of 5-HT while concomitantly producing a decrease in the efflux of 5-hydroxyindoleacetic acid (5-HIAA). This MPP+-induced increase in the 5-HT release, may play an important role in the acute 5-HT syndrome seen in animals after MPTP. JF - European journal of pharmacology AU - Miyake, H AU - Chiueh, C C AD - Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892. Y1 - 1989/07/04/ PY - 1989 DA - 1989 Jul 04 SP - 49 EP - 55 VL - 166 IS - 1 SN - 0014-2999, 0014-2999 KW - Biogenic Monoamines KW - 0 KW - Neurotoxins KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Anesthesia KW - Dose-Response Relationship, Drug KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Homovanillic Acid -- metabolism KW - Biogenic Monoamines -- metabolism KW - Male KW - Hydroxyindoleacetic Acid -- metabolism KW - Corpus Striatum -- metabolism KW - Neurotoxins -- pharmacology KW - Corpus Striatum -- drug effects KW - Serotonin -- metabolism KW - 1-Methyl-4-phenylpyridinium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79280488?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-01 N1 - Date created - 1989-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - cDNA-directed expression of human thyroid peroxidase. AN - 79121013; 2753139 AB - A human thyroid peroxidase cDNA, hTPO-1 [(1987) Proc. Natl. Acad. Sci. USA 84, 5555-5559], was expressed in human Hep G2 cells using a vaccinia virus cDNA-expression system. When examined by immunoblot analysis, the level of hTPO-1 protein expression reached a maximum approx. 24 h after infection and remained at a similar level up to 72 h post-infection. The expressed protein was enzymatically active as measured by guaiacol oxidation. Monoclonal antibody-assisted immunoaffinity column chromatography was used for partial purification of vaccinia-expressed hTPO-1, resulting in more than 300-fold higher specific activity and a measurable difference spectrum of the hTPO-1 (Fe3+)-CN complex. JF - FEBS letters AU - Kimura, S AU - Kotani, T AU - Ohtaki, S AU - Aoyama, T AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07/03/ PY - 1989 DA - 1989 Jul 03 SP - 377 EP - 380 VL - 250 IS - 2 SN - 0014-5793, 0014-5793 KW - Guaiacol KW - 6JKA7MAH9C KW - DNA KW - 9007-49-2 KW - Peroxidases KW - EC 1.11.1.- KW - Index Medicus KW - Oxidation-Reduction KW - Blotting, Western KW - Humans KW - Guaiacol -- pharmacology KW - DNA -- metabolism KW - Peroxidases -- genetics KW - Thyroid Gland -- enzymology KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79121013?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-07 N1 - Date created - 1989-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Perineurial permeability and endoneurial edema during Wallerian degeneration of the frog peripheral nerve. AN - 85251153; pmid-2475214 AB - Perineurial permeabilities to [3H]sucrose and [14C]dextran (MW = 70,000), and water content, conduction velocity (CV) and maximum amplitude (MAP) of the compound action potential, were determined in Wallerian degenerated nerves (sciatic or tibial) of the frog and compared with values in the contralateral uncut nerves. Three days after transection of the lumbosacral plexuses, about 2 cm proximal to the sciatic nerve, mean water content of the sciatic nerve was significantly higher than in the contralateral uncut nerve. After 10 days, the degenerating sciatic nerve showed significant increases in the mean perineurial permeabilities to [3H]sucrose and [14C]dextran when compared to values in the contralateral nerve. Means MAP's and CV's were significantly decreased. At 21 days and after, no compound action potential was detected and perineurial permeability and nerve water content had increased further. Decreases in mean MAP's and CV's and permeability increases of the perineurium were less in degenerating tibial nerves than in degenerating sciatic nerves. It is concluded that following transection, (1) Wallerian degeneration produces an irreversible increase in perineurial permeability, (2) the increase of perineurial permeability follows a proximodistal gradient, and (3) the frog peripheral nerve develops endoneurial edema during Wallerian degeneration as do degenerated nerves of mammals. JF - Brain Research AU - Wadhwani, K C AU - Latker, C H AU - Balbo, A AU - Rapoport, S I AD - Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892. PY - 1989 SP - 231 EP - 239 VL - 493 IS - 2 SN - 0006-8993, 0006-8993 KW - Peripheral Nerves KW - Rana pipiens KW - Sucrose KW - Animal KW - Action Potentials KW - Time Factors KW - Female KW - Dextrans KW - Nerve Degeneration KW - Wallerian Degeneration KW - Cell Membrane Permeability UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85251153?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A study of proteins in the auditory system of rabbits using two-dimensional gels: identification of glial fibrillary acidic protein and vitamin D-dependent calcium binding protein. AN - 85246732; pmid-2776001 AB - Two-dimensional gel electrophoresis and computerized optical densitometry were employed to compare the relative content of proteins across major auditory brain regions in rabbits. Areas examined included the dorsal and ventral cochlear nuclei which receive the primary afferents from the organ of Corti, the lateral superior olivary nucleus which has strong reciprocal relationships with the cochlear nucleus, and the successively more rostral projections of the auditory pathways to inferior colliculus, medial geniculate and auditory cortex. Twelve proteins demonstrated significant decreases and 5 proteins significant increases in content at successively more rostral levels of the auditory system, including 2 proteins which were highly localized to the cochlear nuclei and 2 proteins greatest in amounts in the auditory cortex. One protein which was localized to the cochlear nuclei and lateral superior olive (molecular weight (MW) = 50.3, isoelectric point (pI) = 5.7) was identified as the glial fibrillary acidic protein by reaction of specific antisera on blots. Antisera to the vitamin D-dependent calcium binding protein reacted specifically with one protein (MW = 27.2, pI = 4.8) which was greatest in amount in the lateral superior olive (LSO) versus other auditory regions examined. The significance of these findings rests in the potential for identifying specific markers for cellular elements that are important in auditory function and which might be lost as a consequence of developmental abnormalities or other traumas. JF - Brain Research AU - Winsky, L AU - Harvey, J A AU - McMaster, S E AU - Jacobowitz, D M AD - Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892. PY - 1989 SP - 136 EP - 146 VL - 493 IS - 1 SN - 0006-8993, 0006-8993 KW - Auditory Cortex KW - Calcium-Binding Protein, Vitamin D-Dependent KW - Immunoblotting KW - Inferior Colliculus KW - Support, U.S. Gov't, P.H.S. KW - Auditory Pathways KW - Animal KW - Rabbits KW - Glial Fibrillary Acidic Protein KW - Geniculate Bodies KW - Electrophoresis, Gel, Two-Dimensional KW - Cochlear Nerve KW - Olivary Nucleus KW - Male KW - Brain Chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85246732?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Fast in vitro movement of outer hair cells in an external electric field: effect of digitonin, a membrane permeabilizing agent. AN - 85142361; pmid-2793606 AB - Isolated outer hair cells from the organ of Corti show elongation and contraction in response to an externally applied ac electric field as well as to a direct current injection into these cells. This is thought to be the basis of the positive feedback mechanism for fine tuning of the mammalian hearing organ. To test whether the mechanical response depends on the intracellular electric field or on the membrane potential, we used digitonin to shunt the membrane resistance. We observed that the application of digitonin abolished the cellular response of the outer hair cells to an ac external electric field (5-30 Hz). Coinciding with the abolition of the cellular response, the nuclear matrix started to oscillate synchronous to the external field, indicating an appreciable increase of the intracellular electric field. If the intracellular electric field was the regulating factor of the motile response, the initiation of the movement of the nuclear matrix would have been accompanied by an enhancement of the cellular movement. Our observation is therefore consistent with the interpretation that the (local) membrane potential, and not the intracellular electric field, regulates the hair cell movement. JF - Hearing Research AU - Iwasa, Kuni H AU - Kachar, B AD - National Institute on Deafness and Other Communication Disorders PY - 1989 SP - 247 EP - 254 VL - 40 IS - 3 SN - 0378-5955, 0378-5955 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85142361?accountid=14244 LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The Fenton degradation as a nonenzymatic model for microsomal denitrosation of N-nitrosodimethylamine. AN - 79587036; 2519780 AB - The microsomal metabolism of the carcinogen N-nitrosodimethylamine (NDMA) was suggested to be initiated by hydrogen atom abstraction to form an alpha-nitrosamino radical, which either oxidizes further to an alpha-hydroxy nitrosamine as the initial product of the activating dealkylation pathway or fragments to the nitric oxide radical and N-methylformaldimine as the first step of the presumably inactivating denitrosation route. To examine the chemistry of the alpha-nitrosamino radical in a nonenzymatic setting, we exposed NDMA to the Fenton reagent, which is known to be capable of abstracting hydrogen atoms from organic species. The products observed were those expected of a denitrosation model. Solutions containing 13 mM [14C]NDMA, 15 mM FeSO4, 15 mM H2O2, and 7.5 mM H2SO4 were kept at 4-10 degrees C for 1 h and then basified to yield methylamine (3.2 +/- 0.5 mM, mean +/- SD, n = 8), formaldehyde (3.1 +/- 0.9 mM), and unreacted nitrosamine (10.2 +/- 0.7 mM) as the only radioactive species detected, with total nitrate/nitrite also being found at a level of 2.8 +/- 0.5 mM. N-Methylformaldiminium ion was identified as an intermediate. The parallels between these results and those seen in the microsomal reaction support the hypothesis that the alpha-nitrosamino radical is a common intermediate in enzymatic denitrosation versus dealkylation of NDMA.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Chemical research in toxicology AU - Heur, Y H AU - Streeter, A J AU - Nims, R W AU - Keefer, L K AD - Chemistry Section, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701. PY - 1989 SP - 247 EP - 253 VL - 2 IS - 4 SN - 0893-228X, 0893-228X KW - Imines KW - 0 KW - Nitroso Compounds KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Dimethylnitrosamine KW - M43H21IO8R KW - Index Medicus KW - Mass Spectrometry KW - Cytochrome P-450 Enzyme System -- metabolism KW - Models, Biological KW - Imines -- metabolism KW - Chromatography, High Pressure Liquid KW - Magnetic Resonance Spectroscopy KW - Catalysis KW - Nitroso Compounds -- metabolism KW - Microsomes -- metabolism KW - Dimethylnitrosamine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79587036?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1992-03-02 N1 - Date created - 1992-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Medication effect on lymphocyte morphology in schizophrenia. AN - 79571913; 2577275 AB - Past studies on the occurrence of atypical lymphocytes in the blood of individuals with schizophrenia are contradictory; some researchers have argued that such cells are a genetic marker of the disease while others have explained the cells simply as an effect of antipsychotic drugs. The present study blindly measured atypical lymphocytes in 14 schizophrenics on medication for at least 6 weeks and off medication for at least 4 weeks, ten Huntington's disease patients on antipsychotic medication, and ten normal controls. The patients with schizophrenia (P less than 0.05) and those with Huntington's disease (P less than 0.02) both had significantly more atypical lymphocytes than the normal controls. However no difference was found in the percentage of atypical lymphocytes in patients with schizophrenia on and off medication. The authors cite the need for studies of first-admission, never-tested patients to definitively settle this question. JF - Schizophrenia research AU - Torrey, E F AU - Upshaw, Y D AU - Suddath, R AD - Twin Study Unit, NIMH Neurosciences Center, St. Elizabeths Hospital, Washington, DC 20032. PY - 1989 SP - 385 EP - 390 VL - 2 IS - 4-5 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Huntington Disease -- blood KW - Humans KW - Adult KW - Huntington Disease -- drug therapy KW - Cell Nucleus -- drug effects KW - Huntington Disease -- psychology KW - Male KW - Female KW - Antipsychotic Agents -- administration & dosage KW - Schizophrenia -- blood KW - Schizophrenic Psychology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Lymphocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79571913?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1991-03-08 N1 - Date created - 1991-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mechanisms of arsenic-induced cell transformation. AN - 79565723; 2484623 AB - Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Studies with cells in culture have provided some possible mechanisms by which arsenic and arsenical compounds may exert a carcinogenic activity. Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. The trivalent sodium arsenite was greater than tenfold more potent than the pentavalent sodium arsenate. The compounds also exhibited toxicity; however, transformation was observed at nontoxic as well as toxic doses. At low doses, enhanced colony forming efficiency of the cells was observed. To understand the mechanism of arsenic-induced transformation, the genetic effects of the two arsenicals were examined over the same doses that induced transformation. No arsenic-induced gene mutations were detected at two genetic loci. However, cell transformation and cytogenetic effects, including endoreduplication, chromosome aberrations, and sister chromatid exchanges, were induced by the arsenicals with similar dose responses. These results support a possible role for chromosomal changes in arsenic-induced transformation. The two arsenic salts also induced another form of mutation-gene amplification. Both sodium arsenite and sodium arsenate induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene.(ABSTRACT TRUNCATED AT 250 WORDS) JF - Biological trace element research AU - Barrett, J C AU - Lamb, P W AU - Wang, T C AU - Lee, T C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1989 SP - 421 EP - 429 VL - 21 SN - 0163-4984, 0163-4984 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Humans KW - Arsenic -- toxicity KW - Cell Transformation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79565723?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-11-02 N1 - Date created - 1990-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Neoplastic transformation of BALB/3T3 cells by metals and the quest for induction of a metastatic phenotype. AN - 79565032; 2484630 AB - In the mouse embryo cell line BALB/3T3 Clone A31-1-1, dose-dependent morphologic neoplastic transformation was obtained with NaAsO2, Na2HAsO4, CdCl2, and K2CrO4. Cellular uptake was four fold higher for As3+ than for As5+, and As5- was metabolized to As3+ in cytosol. Cytotoxicity and transformation rates were four fold higher for As3+ than As5+, but when correlated to cellular As burden they were equivalent. As3+ appears responsible for the transforming activity. The foci transformed by metals (or by other carcinogens) gave rise to tumorigenic cell lines (sc sarcomas in nude mice), none of which, however, induced metastases when tested by sc or by iv injection in nude mice. Thus carcinogens change this aneuploid cell line from a preneoplastic stage to the expression of malignant growth but not of metastatic activity. Metastatic and type IV collagenolytic activities can be induced by transfection of the c-Ha-ras oncogene and inhibited by the Ad2-E1a gene (so far shown in other cell types). It remains to be seen whether metal or other carcinogens can induce the nonmetastatic phenotype to become metastatic. The molecular mechanisms of metal carcinogenesis, studied in cell culture systems, in combination with other factors or oncogenes, may reveal the effect of individual metal carcinogens on discrete steps of the complex process of carcinogenesis. JF - Biological trace element research AU - Saffiotti, U AU - Bertolero, F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. PY - 1989 SP - 475 EP - 482 VL - 21 SN - 0163-4984, 0163-4984 KW - Arsenates KW - 0 KW - Arsenites KW - Chromates KW - Metals KW - Potassium Compounds KW - Sodium Compounds KW - Cadmium KW - 00BH33GNGH KW - sodium arsenite KW - 48OVY2OC72 KW - potassium chromate(VI) KW - 5P0R38CN2X KW - sodium arsenate KW - 7631-89-2 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Phenotype KW - Animals KW - Arsenic -- toxicity KW - Cell Survival -- drug effects KW - Chromates -- toxicity KW - Cadmium -- toxicity KW - Arsenates -- toxicity KW - Mice KW - Mice, Inbred BALB C KW - Cell Transformation, Neoplastic -- pathology KW - Neoplasm Metastasis KW - Cell Transformation, Neoplastic -- drug effects KW - Metals -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79565032?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-11-02 N1 - Date created - 1990-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Tissue susceptibility factors in cadmium carcinogenesis. Correlation between cadmium-induction of prostatic tumors in rats and an apparent deficiency of metallothionein. AN - 79550489; 2484631 AB - Recently, in two separate studies we have observed cadmium (Cd)-induction of prostatic tumors (PT) in rats. Cd (sc or im) at doses nontoxic to the testes markedly increased PT formation (2.5 mumols/kg, sc, 8 PT/29 exposed, 28%; 30 mumols/kg, im, 11/26, 42%; control 14/127, 11%). The administration of zinc (Zn; 1 mmol/kg, sc, at -6, 0 and +18 h) to prevent testicular toxicity and tumors from Cd (30 mumols/kg, sc, 0 h) also resulted in an elevated incidence of PT (8/27, 30%). The nature of the metal-binding proteins in the prostate has not been defined, although metallothionein (MT), a low Mr Cd-binding protein that confers tolerance to Cd, is deficient in other target tissues of Cd carcinogenesis, such as the rat testes. Using a technique that extracts MT from liver, a low-Mr Cd-binding protein was extracted from both ventral (VP) and dorsal prostate (DP) and isolated by gel filtration. In contrast to the two forms of rat MT, reverse phase HPLC of VP and DP extract eluted 1 and 5 forms, respectively. The amino acid compositions of the VP and DP proteins were quite distinct from MT, with much less cys than MT and the presence of residues not found in MT (leu, tyr, phe). Thus Cd-induction of PT appears to be dependent on functional testes and, as is the case with Cd-induced testicular formation, appears to be associated with a deficiency of MT. JF - Biological trace element research AU - Waalkes, M P AU - Perantoni, A AU - Rehm, S AD - Division of Cancer Etiology, National Cancer Institute, Frederick, MD 21701-1013. PY - 1989 SP - 483 EP - 490 VL - 21 SN - 0163-4984, 0163-4984 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Metallothionein KW - 9038-94-2 KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Testis -- metabolism KW - Chromatography, Gel KW - Testicular Neoplasms -- chemically induced KW - Male KW - Chromatography, High Pressure Liquid KW - Testicular Neoplasms -- metabolism KW - Prostatic Neoplasms -- metabolism KW - Metallothionein -- deficiency KW - Prostatic Neoplasms -- chemically induced KW - Cadmium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79550489?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-11-02 N1 - Date created - 1990-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Subchronic toxicology studies of hexachloro-1,3-butadiene (HCBD) in B6C3F1 mice by dietary incorporation. AN - 79506498; 2632770 AB - Two-week repeated-dose and 13-week subchronic studies of HCBD were conducted in B6C3F1 mice. Groups of five mice/sex received 0, 30, 100, 300, 1,000, or 3,000 ppm HCBD in feed for 15 days. Toxic responses, primarily in the higher dose groups, included abnormal clinical signs (lethargy, hunched posture, rough coat, sensitivity to light, and/or incoordination), mortality (all mice in the top two dose groups died by day 7), body and organ weight depression, and gross and histopathological changes. The most prevalent microscopic lesion, seen in all HCBD-treated mice of both sexes, was renal tubular cell necrosis and/or regeneration. Regeneration was seen only in the lower dose groups. Thirteen-week studies were conducted in which groups of 10 mice/sex received 0, 1, 3, 10, 30, or 100 ppm HCBD in feed. No treatment-related clinical signs or mortality were observed. Body weight gain was reduced in the 30- and 100-ppm males (-49 and -56, respectively), and the 100-ppm females (-47). Significant reduction in kidney weights was seen in the 30- and 100-ppm males and 100-ppm females. A treatment-related increase in tubular cell regeneration in the renal cortex occurred in both male and female mice. This lesion was characterized by an increase both in number and basophilic staining intensity of the tubular epithelial cells. Regeneration was seen in the outer stripe of the outer medulla and extended into the medullary rays (pars recta); severity increased with dose. Female mice were more susceptible to the toxicity of HCBD than male mice. Although no adverse effects were observed at the 10-ppm level for male mice in the subchronic study, the regenerative lesion was present in female mice at 1 ppm, the lowest dose administered. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Yang, R S AU - Abdo, K M AU - Elwell, M R AU - Levy, A C AU - Brennecke, L H AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. PY - 1989 SP - 323 EP - 332 VL - 9 IS - 4 SN - 0731-8898, 0731-8898 KW - Butadienes KW - 0 KW - Environmental Pollutants KW - hexachlorobutadiene KW - CQ8AAO9MO1 KW - Index Medicus KW - Animals KW - Kidney Diseases -- pathology KW - Kidney Diseases -- physiopathology KW - Environmental Pollutants -- toxicity KW - Kidney -- pathology KW - Kidney Tubules -- pathology KW - Sex Characteristics KW - Kidney Tubules -- physiopathology KW - Mice KW - Organ Size KW - Necrosis KW - Regeneration KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Epithelium -- pathology KW - Female KW - Male KW - Kidney Diseases -- chemically induced KW - Butadienes -- toxicity KW - Butadienes -- administration & dosage KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79506498?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-05-17 N1 - Date created - 1990-05-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The Lexington addicts, 1971-1972: demographic characteristics, drug use patterns, and selected infectious disease experience. AN - 79387769; 2599682 AB - The demographics, drug habits, and medical complications of a cohort of 1,129 addicts treated at Lexington in the period 1971-1972 were studied. These patients, admitted from 41 different states, had a mean period of addiction of 5.4 years. Over one-third of the sample had engaged in pimping or prostitution, and there were no differences by gender in terms of involvement. Eight-eight percent had shared injection equipment, and surprisingly, 78% admitted to some effort at sterilizing their "works." Hepatitis was the most common associated medical condition: 87% had serologic markers of hepatitis B virus (HBV) infection, 60% had evidence of hepatitis A virus (HAV) exposure, and 47% had abnormal liver function parameters. Gynecomastia was evident in 2% of male subjects. Thirteen percent of the sample had a reactive VDRL assay, but 64% of these were biologically false positive. Subtle abnormalities of immune function were also observed; 18% of the patients had recent unexplained weight loss, 6% had lymphadenopathy, 8% had leukopenia, and 2% had lymphocytopenia. We conclude that both HBV and HAV were important infectious disease risks in these addicts, and that many evidenced deficiencies in immune function well before AIDS became a major public health concern. JF - The International journal of the addictions AU - Lange, W R AU - Ball, J C AU - Pfeiffer, M B AU - Snyder, F R AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 609 EP - 626 VL - 24 IS - 7 SN - 0020-773X, 0020-773X KW - Street Drugs KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Age Factors KW - Sex Factors KW - Humans KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Cohort Studies KW - Incidence KW - Kentucky KW - Middle Aged KW - Adolescent KW - Heroin Dependence -- complications KW - Female KW - Male KW - Opioid-Related Disorders -- epidemiology KW - Communicable Diseases -- epidemiology KW - Substance Abuse, Intravenous -- epidemiology KW - Substance Abuse, Intravenous -- complications KW - Communicable Diseases -- transmission KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79387769?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-02-06 N1 - Date created - 1990-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Tripelennamine interactions with the psychotomimetic sigma agonist N-allylnormetazocine. AN - 79348876; 2555824 AB - The pharmacological effects of individual and combined intravenous doses of the antihistamine tripelennamine and the psychotomimetic sigma benzomorphan opioid derivative, N-allylnormetazocine (NANM), on nociceptive reflexes, autonomic parameters and behavior were assessed in the chronic spinal dog. NANM (1.65 mg/kg, IV) produced antinociception, mydriasis, tachycardia, hyperthermia and behavioral signs of canine delirium. Tripelennamine (1.25 mg/kg, IV) produced antinociception, mydriasis and tachycardia without affecting behavior. The combined effects of the two drugs were additive except for heart rate. However, tripelennamine did not antagonize any of the physiological effects or the signs of canine delirium produced by NANM. The findings are inconsistent with the hypothesis that tripelennamine antagonizes the psychotomimetic NANM-like effects of pentazocine to make pentazocine-tripelennamine combinations (T's and Blues) more desirable as a heroin substitute. JF - Pharmacology, biochemistry, and behavior AU - Vaupel, D B AD - Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 717 EP - 720 VL - 33 IS - 3 SN - 0091-3057, 0091-3057 KW - Hallucinogens KW - 0 KW - Receptors, Opioid KW - Receptors, sigma KW - Tripelennamine KW - 3C5ORO99TY KW - SK&F 10047 KW - 7619-35-4 KW - Phenazocine KW - J0ND6N0AQC KW - Index Medicus KW - Animals KW - Sensory Thresholds -- drug effects KW - Drug Interactions KW - Autonomic Nervous System -- drug effects KW - Dogs KW - Female KW - Tripelennamine -- pharmacology KW - Behavior, Animal -- drug effects KW - Pain -- physiopathology KW - Phenazocine -- analogs & derivatives KW - Phenazocine -- pharmacology KW - Hallucinogens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79348876?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-29 N1 - Date created - 1989-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Pregnenolone sulfate antagonizes barbiturate-induced hypnosis. AN - 79347655; 2587612 AB - The potential influence of the neurosteroid pregnenolone sulfate (PrS) on barbiturate-induced hypnosis was tested in rats. PrS, when injected intracerebroventricularly or intraperitoneally, significantly shortened the sleep-time produced by pentobarbital. The results suggest an important physiological and pharmacological role for PrS in the regulation of CNS excitability. JF - Pharmacology, biochemistry, and behavior AU - Majewska, M D AU - Bluet-Pajot, M T AU - Robel, P AU - Baulieu, E E AD - Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 701 EP - 703 VL - 33 IS - 3 SN - 0091-3057, 0091-3057 KW - pregnenolone sulfate KW - 04Y4D91RG0 KW - Pregnenolone KW - 73R90F7MQ8 KW - Pentobarbital KW - I4744080IR KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Rats, Inbred F344 KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Male KW - Injections, Intraventricular KW - Pregnenolone -- pharmacology KW - Hypnosis, Anesthetic KW - Pregnenolone -- administration & dosage KW - Pentobarbital -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79347655?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-29 N1 - Date created - 1989-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Novel pyrrolidines in the venom of the ant Monomorium indicum. AN - 79284494; 2809607 AB - New 2,5-dialkylpyrrolidines found in the venom of Monomorium indicum include trans-2-butyl-5-(4-pentenyl)pyrrolidine [1], trans-2-butyl-5-(6-heptenyl)pyrrolidine [4], trans-5-(5-hexenyl)-2-(4-pentenyl)pyrrolidine [6], trans-5-(6-heptenyl)-2-(5-hexenyl)pyrrolidine [8], and trans-5-heptyl-2-hexylpyrrolidine [16], whose structures were confirmed by synthesis. The concomitance of five previously reported trans-2,5-dialkyl-pyrrolidines along with small amounts of the cis isomers and N-methyl analogues makes the venom of M. indicum the most qualitatively diverse blend of alkaloids reported from an ant to date. The toxicities to termites of four of these alkaloids were determined. JF - Journal of natural products AU - Jones, T H AU - Blum, M S AU - Escoubas, P AU - Musthak Ali, T M AD - Laboratory of Chemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892. PY - 1989 SP - 779 EP - 784 VL - 52 IS - 4 SN - 0163-3864, 0163-3864 KW - Ant Venoms KW - 0 KW - Arthropod Venoms KW - Pyrrolidines KW - Index Medicus KW - Animals KW - Insects KW - Magnetic Resonance Spectroscopy KW - Pyrrolidines -- analysis KW - Ant Venoms -- analysis KW - Pyrrolidines -- isolation & purification KW - Pyrrolidines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79284494?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-12-20 N1 - Date created - 1989-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Through the centuries with food and drink, for better or worse. AN - 79232577; 2676718 JF - Allergy proceedings : the official journal of regional and state allergy societies AU - Cohen, S G AU - Saavedra-Delgado, A M AD - National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. PY - 1989 SP - 281 EP - 290 VL - 10 IS - 4 SN - 1046-9354, 1046-9354 KW - Index Medicus KW - History of medicine KW - Bible KW - Humans KW - Foodborne Diseases -- history KW - History, Ancient KW - Food Hypersensitivity -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79232577?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-21 N1 - Date created - 1989-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Metabolite-based internal doses used in a risk assessment of benzene. AN - 79226281; 2792038 AB - Risk assessments of benzene have been based upon both human and animal studies. In this paper, metabolite information is used to construct an internal dose (a surrogate of the biologically effective dose) for a given administered dose. The relationship between the administered dose and this internal dose is nonlinear and is well described by a Michaelis-Menten function. The administered doses from the National Toxicology Program's rodent carcinogenicity study of benzene are transformed into internal doses, and these internal doses are used in conjunction with a multistage model to compare previous estimated virtually safe doses (VSD) associated with small added health risks. The ratio of VSD for the administered dose risk assessment to the VSD from the internal dose risk assessment was approximately 1.0 for the F344/N rats and ranged from 2.5 to 5.0 for B6C3F1 mice in the National Toxicology Program study. For an occupational exposure of 1 ppm, a risk estimate of 0.7 excess cancers/1000 exposed with an upper bound of 3.5/1000 was obtained for a total metabolite internal dose risk assessment. Risk estimates based upon internal doses constructed from levels of the toxic metabolites of benzene are also presented. The implication of a dose-rate study of benzene metabolism for risk assessment is discussed, and finally, suggestions for better characterization of the dose-response function for benzene are provided. JF - Environmental health perspectives AU - Bailer, A J AU - Hoel, D G AD - Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 177 EP - 184 VL - 82 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Benzene KW - J64922108F KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Administration, Oral KW - Risk KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Humans KW - Mice KW - Models, Biological KW - Mathematics KW - Benzene -- administration & dosage KW - Benzene -- metabolism KW - Benzene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79226281?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-02 N1 - Date created - 1989-11-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lancet. 1977 Jul 9;2(8028):76-8 [69157] Arch Environ Health. 1978 Jan-Feb;33(1):3-10 [629594] J Environ Pathol Toxicol. 1978 Sep-Oct;1(1):163-79 [722184] Am J Ind Med. 1981;2(3):217-45 [7345926] Science. 1983 Mar 4;219(4588):1032-7 [6823565] J Toxicol Clin Toxicol. 1982 Aug;19(6-7):781-805 [7161853] Am J Ind Med. 1983;4(5):589-630 [6353911] Toxicol Appl Pharmacol. 1987 Feb;87(2):325-36 [3824388] N Engl J Med. 1987 Apr 23;316(17):1044-50 [3561457] Am J Epidemiol. 1988 Mar;127(3):419-39 [3277397] Environ Health Perspect. 1989 Jul;82:9-17 [2792053] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site. AN - 79225864; 2551666 AB - Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. JF - Environmental health perspectives AU - McKinney, J D AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 323 EP - 336 VL - 82 SN - 0091-6765, 0091-6765 KW - Dioxins KW - 0 KW - Hydrocarbons, Chlorinated KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - Thyroid Hormones KW - Index Medicus KW - Molecular Structure KW - Animals KW - Models, Molecular KW - Computer Graphics KW - Models, Chemical KW - Dioxins -- metabolism KW - Receptors, Drug -- metabolism KW - Hydrocarbons, Chlorinated -- toxicity KW - Hydrocarbons, Chlorinated -- metabolism KW - Thyroid Hormones -- metabolism KW - Dioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79225864?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-02 N1 - Date created - 1989-11-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1981 Nov 24;20(24):6781-9 [6274379] J Biol Chem. 1982 Jan 25;257(2):930-8 [6274872] Annu Rev Pharmacol Toxicol. 1982;22:517-54 [6282188] Int Rev Cytol Suppl. 1983;15:17-48 [6189802] Proc Natl Acad Sci U S A. 1983 Sep;80(18):5749-52 [6310591] J Biol Chem. 1984 Jan 25;259(2):980-5 [6319394] Biochemistry. 1984 Jan 17;23(2):340-9 [6365163] Biochem Pharmacol. 1984 Mar 15;33(6):833-9 [6324800] J Clin Invest. 1985 Jan;75(1):147-54 [3965501] Life Sci. 1985 Feb 18;36(7):695-703 [3881642] Mol Pharmacol. 1985 Feb;27(2):271-6 [2982091] J Med Chem. 1985 Mar;28(3):375-81 [3919186] J Med Chem. 1986 Nov;29(11):2149-53 [3783576] J Med Chem. 1986 Dec;29(12):2451-7 [3097319] J Biol Chem. 1985 May 25;260(10):6481-7 [3922975] Science. 1985 Jul 5;229(4708):23-8 [3892686] Environ Health Perspect. 1985 May;60:57-68 [2992928] Toxicology. 1985 Oct;37(1-2):51-63 [3933144] Environ Health Perspect. 1985 Sep;61:41-53 [2998749] Environ Health Perspect. 1985 Sep;61:5-10 [2998750] J Med Chem. 1986 May;29(5):641-8 [3009810] Biochem Biophys Res Commun. 1986 Apr 14;136(1):294-9 [3707577] Toxicol Appl Pharmacol. 1986 Jun 15;84(1):45-55 [3715868] Toxicol Lett. 1986 May;31(2):151-8 [3012826] Annu Rev Pharmacol Toxicol. 1986;26:371-99 [3013079] Endocrinology. 1986 Sep;119(3):1076-82 [3732155] Proc Natl Acad Sci U S A. 1986 Aug;83(16):5774-8 [2874556] J Biol Chem. 1986 Sep 5;261(25):11613-22 [3745159] Toxicol Appl Pharmacol. 1986 Sep 30;85(3):301-12 [3094194] Science. 1986 Nov 28;234(4780):1081-6 [3775377] J Clin Endocrinol Metab. 1968 Mar;28(3):386-92 [4171084] Biochemistry. 1969 Apr;8(4):1554-7 [4241490] Endocrinology. 1974 Sep;95(3):897-903 [4369384] J Biol Chem. 1974 Nov 10;249(21):6796-805 [4607556] J Biol Chem. 1976 Aug 25;251(16):4936-46 [956169] Endocrinology. 1977 Jul;101(1):292-6 [862558] J Clin Invest. 1977 Sep;60(3):555-62 [197120] Nature. 1977 Jul 14;268(5616):115-20 [201845] Recent Prog Horm Res. 1978;34:437-75 [216059] Cancer Res. 1979 Aug;39(8):3172-6 [455301] J Biol Chem. 1979 Sep 10;254(17):8534-9 [224057] J Biol Chem. 1980 Nov 10;255(21):10271-8 [6253468] Cancer Res. 1980 Oct;40(10):3616-20 [6108157] Endocr Rev. 1980 Spring;1(2):140-66 [6263601] Biochemistry. 1986 Oct 7;25(20):6335-42 [3024707] Nature. 1986 Dec 18-31;324(6098):635-40 [2879242] Nature. 1986 Dec 18-31;324(6098):641-6 [2879243] Endocrinology. 1987 Mar;120(3):1089-96 [3803311] J Med Chem. 1987 Jan;30(1):79-86 [3100800] Biochem J. 1986 Dec 1;240(2):621-2 [3101675] Biochem Pharmacol. 1987 Jan 15;36(2):283-91 [3814171] Science. 1987 Mar 20;235(4795):1478-84 [3823899] Toxicol Appl Pharmacol. 1987 Feb;87(2):337-50 [3824389] Environ Health Perspect. 1986 Dec;70:137-47 [3830099] Endocrinology. 1987 May;120(5):1742-9 [3106010] Annu Rev Pharmacol Toxicol. 1987;27:87-111 [3034142] Cancer Res. 1987 Jun 15;47(12):3052-6 [3581059] Biochem Pharmacol. 1987 Apr 15;36(8):1361-5 [3036167] Toxicol Appl Pharmacol. 1987 Jun 30;89(2):165-74 [3111013] Pharmacol Rev. 1987 Jun;39(2):147-61 [3303065] Chem Biol Interact. 1987;64(1-2):39-60 [3690723] J Med Chem. 1988 Feb;31(2):357-62 [2828621] Science. 1988 May 13;240(4854):889-95 [3283939] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4128-32 [3380784] Science. 1988 Jun 24;240(4860):1759-64 [3289117] J Theor Biol. 1987 Nov 21;129(2):231-41 [3138502] Nature. 1961 Mar 4;189:729-32 [13763782] J Med Pharm Chem. 1962 Nov;91:1307-15 [14056463] Mayo Clin Proc. 1964 Aug;39:560-8 [14198023] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice. AN - 79225763; 2676495 AB - Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F1 mice, and female B6C3F1 mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Environmental health perspectives AU - Huff, J E AU - Haseman, J K AU - DeMarini, D M AU - Eustis, S AU - Maronpot, R R AU - Peters, A C AU - Persing, R L AU - Chrisp, C E AU - Jacobs, A C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 125 EP - 163 VL - 82 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Mutagens KW - Benzene KW - J64922108F KW - Index Medicus KW - Rats KW - Hematologic Diseases -- chemically induced KW - Animals KW - Rats, Inbred F344 KW - Neoplasms, Experimental -- chemically induced KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Mice KW - Neoplasms, Experimental -- pathology KW - Male KW - Female KW - Benzene -- administration & dosage KW - Benzene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79225763?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-11-02 N1 - Date created - 1989-11-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Environ Health Perspect. 1989 Jul;82:43-9 [2792050] Environ Health Perspect. 1989 Jul;82:9-17 [2792053] Environ Health Perspect. 1989 Jul;82:97-108 [2792054] Biochem J. 1953 May;54(2):231-8 [13058864] Cancer. 1961 Nov-Dec;14:1306-15 [14008628] Mutat Res. 1975 Dec;31(6):347-64 [768755] Schweiz Med Wochenschr. 1982 Dec 11;112(50):1858-9 [7156970] Cancer Res. 1983 Mar;43(3):1330-4 [6825102] Mutat Res. 1983 Mar;119(3):355-60 [6828070] Carcinogenesis. 1983;4(3):291-5 [6339095] Environ Res. 1983 Feb;30(1):16-25 [6832104] Helv Med Acta. 1971 Dec;36(1):59-66 [5140811] J Natl Cancer Inst. 1973 Aug;51(2):703-5 [4765384] CRC Crit Rev Toxicol. 1975 Jun;3(3):265-88 [1097190] Cancer Res. 1975 Dec;35(12):3651-5 [1192426] J Natl Cancer Inst. 1975 Dec;55(6):1329-36 [1547] J Natl Cancer Inst. 1976 Jun;56(6):1237-42 [994224] Ann N Y Acad Sci. 1976;271:143-51 [1069497] Mutat Res. 1977 Jan;42(1):19-31 [191747] J Toxicol Environ Health Suppl. 1977;2:23-36 [342714] J Toxicol Environ Health Suppl. 1977;2:69-105 [342717] Mutat Res. 1978;47(2):75-97 [415231] Arch Environ Health. 1978 Jan-Feb;33(1):3-10 [629594] Mutat Res. 1978 May;57(2):163-7 [96337] Toxicology. 1978 Sep;11(1):55-63 [705804] Ann N Y Acad Sci. 1978 Sep 29;298:124-40 [360906] Mol Pharmacol. 1978 Sep;14(5):920-9 [714029] Mutat Res. 1978 Sep;58(1):29-34 [362193] Toxicol Appl Pharmacol. 1978 Oct;46(1):9-18 [725954] Environ Health Perspect. 1978 Dec;27:11-20 [367762] Mutat Res. 1978 Nov;58(2-3):313-6 [370577] J Natl Cancer Inst. 1979 Apr;62(4):957-74 [285297] CRC Crit Rev Biochem. 1979;6(4):401-37 [378536] Tex Rep Biol Med. 1978;37:153-61 [752975] Toxicol Appl Pharmacol. 1979 Jul;49(3):417-23 [473208] Cancer Res. 1979 Oct;39(10):4152-9 [383281] Mol Gen Genet. 1979 Jul 2;174(1):39-46 [384160] Life Sci. 1979 Aug 13;25(7):567-72 [502750] Cancer Res. 1980 Apr;40(4):1189-93 [7357548] Experientia. 1980 Mar 15;36(3):297-9 [7371785] Mutat Res. 1980 Feb;77(2):149-55 [6990240] Proc Natl Acad Sci U S A. 1980 Apr;77(4):2148-52 [6929542] Chem Biol Interact. 1980 May;30(2):241-5 [7389002] Mutat Res. 1980 Jul;76(1):1-50 [6993936] Chem Biol Interact. 1980 Dec;33(1):1-17 [7438288] J Natl Cancer Inst. 1981 Jan;66(1):163-9 [6935456] Am Ind Hyg Assoc J. 1980 Sep;41(9):616-23 [7457381] Chem Biol Interact. 1981 Jan;33(2-3):285-99 [7460069] Med Lav. 1979 Sep-Oct;70(5):352-7 [554913] Toxicology. 1980;15(3):219-232 [7008261] Mutat Res. 1980 Oct;74(5):379-87 [7207475] J Environ Pathol Toxicol. 1980 Nov;4(5-6):123-31 [7012268] Mutat Res. 1980 Nov;79(3):203-12 [7012602] Environ Mutagen. 1981;3(1):11-32 [7021142] Environ Mutagen. 1981;3(4):429-44 [7021147] Environ Health Perspect. 1984 Dec;58:385-92 [6525993] Mutat Res. 1983 Mar;116(3-4):217-38 [6339893] Science. 1983 Jul 15;221(4607):227-36 [6336310] Cancer Res. 1983 Aug;43(8):3660-2 [6305491] Environ Mutagen. 1983;5(2):223-6 [6407826] Drug Metab Rev. 1983;14(3):559-607 [6347595] Toxicol Appl Pharmacol. 1983 Jul;69(3):363-8 [6879607] Mutat Res. 1983 Oct;113(6):467-79 [6621578] Environ Health Perspect. 1983 Oct;52:75-82 [6653540] Mutat Res. 1984 Mar;135(3):203-9 [6708961] Mutat Res. 1984 Mar;135(3):225-43 [6424008] Carcinogenesis. 1984 Jun;5(6):827-32 [6722989] Toxicol Pathol. 1984;12(2):126-35 [11478313] Natl Cancer Inst Monogr. 1968 Jun;28:173-80 [5671401] Acta Med Biol (Niigata). 1970 Mar;17(4):285-91 [5431869] Mutat Res. 1981 Oct;85(5):335-45 [7029261] Environ Mutagen. 1980;2(1):43-50 [7327159] J Toxicol Environ Health. 1981 Jul-Aug;8(1-2):251-80 [7328708] Mutat Res. 1981 Oct;90(2):91-109 [6799819] Mutat Res. 1981 Nov;90(3):273-8 [7329437] Cancer Lett. 1981 Dec;14(3):251-60 [7199376] Chem Biol Interact. 1982 Mar 15;39(2):129-38 [7060224] Mutat Res. 1981 Dec;90(4):399-409 [7038461] Toxicol Lett. 1982 Oct;13(3-4):169-73 [6959383] Toxicol Appl Pharmacol. 1984 Sep 15;75(2):358-61 [6474468] Prog Clin Biol Res. 1985;163B:295-300 [3983155] Cancer Res. 1985 Jun;45(6):2471-7 [3986787] Mutat Res. 1985 May-Jun;143(1-2):55-9 [4000143] Am J Ind Med. 1985;7(5-6):403-13 [3890530] Am J Ind Med. 1985;7(5-6):415-46 [4003403] Mutat Res. 1985 Nov;154(3):153-81 [3930957] J Natl Cancer Inst. 1985 Nov;75(5):975-84 [3863995] J Invest Dermatol. 1985 Dec;85(6):522-6 [4067326] Mol Pharmacol. 1985 Dec;28(6):560-6 [4079912] Environ Mutagen. 1986;8(1):29-40 [3943496] J Natl Cancer Inst. 1986 Feb;76(2):283-9 [3456066] Toxicol Lett. 1985 Dec;29(2-3):161-7 [2418539] Arch Toxicol Suppl. 1985;8:425-30 [3868373] Mutat Res. 1986 May;160(3):259-66 [3960039] Mol Pharmacol. 1986 Jul;30(1):42-7 [3724744] Toxicol Appl Pharmacol. 1986 Sep 30;85(3):464-77 [3764927] Toxicology. 1986 Dec 15;42(2-3):171-81 [3798466] Toxicol Appl Pharmacol. 1987 Feb;87(2):325-36 [3824388] N Engl J Med. 1987 Apr 23;316(17):1044-50 [3561457] Mutat Res. 1987 Jun;188(2):135-40 [3587261] Toxicol Ind Health. 1986 Dec;2(4):445-51 [3590199] Mutat Res. 1987 Jul;179(1):23-31 [3037363] Arch Toxicol. 1987;60(1-3):61-4 [3619644] Toxicol Lett. 1987 Sep;38(1-2):123-33 [3307023] Crit Rev Toxicol. 1987;18(2):141-59 [3311642] Mutat Res. 1987 Dec;192(4):239-46 [3317033] Environ Health Perspect. 1987 Oct;74:229-35 [3691430] Jpn J Cancer Res. 1987 Nov;78(11):1144-9 [3121550] Am J Epidemiol. 1988 Mar;127(3):419-39 [3277397] Mutagenesis. 1987 May;2(3):235-8 [3325750] Mutat Res. 1988 Feb;204(2):203-6 [3278211] Oncogene. 1987 Mar;1(1):59-69 [3438083] Mutat Res. 1988 Jun;203(3):155-76 [2836728] Toxicol Appl Pharmacol. 1988 Jun 15;94(1):128-40 [3376110] Ann N Y Acad Sci. 1988;534:427-40 [3389672] Mutat Res. 1981 Nov;90(3):261-72 [6799821] Environ Health Perspect. 1989 Jul;82:109-24 [2792037] Environ Health Perspect. 1989 Jul;82:193-7 [2676498] Environ Health Perspect. 1989 Jul;82:207-13 [2792042] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Estrogen-induced expression of mouse lactate dehydrogenase-A gene. AN - 79219671; 2676196 AB - The synthesis of lactate dehydrogenase-A isoenzyme was shown to increase significantly in the uterus of immature mice treated by diethylstilbestrol. The expression of the mouse LDH-A promoter and cat fusion gene in Chinese hamster ovary cells was also induced by 17 beta-estradiol and diethylstilbestrol. JF - Cell biology international reports AU - Li, S S AU - Hou, E W AD - Laboratory of Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 619 EP - 624 VL - 13 IS - 7 SN - 0309-1651, 0309-1651 KW - Estrogens KW - 0 KW - Isoenzymes KW - Recombinant Fusion Proteins KW - Diethylstilbestrol KW - 731DCA35BT KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Index Medicus KW - Animals KW - Cricetulus KW - Mice KW - Plasmids KW - Uterus -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Mice, Inbred Strains KW - Ovary -- metabolism KW - Uterus -- cytology KW - Promoter Regions, Genetic -- drug effects KW - Ovary -- cytology KW - Transfection KW - Recombinant Fusion Proteins -- genetics KW - Diethylstilbestrol -- pharmacology KW - Escherichia coli KW - Female KW - Cricetinae KW - Gene Expression -- drug effects KW - Estrogens -- pharmacology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - L-Lactate Dehydrogenase -- genetics KW - L-Lactate Dehydrogenase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79219671?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-30 N1 - Date created - 1989-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Evidence for a decline with age in behavioral responsivity to the serotonin agonist, m-chlorophenylpiperazine, in healthy human subjects. AN - 79197910; 2772095 AB - The functional significance of alterations in brain serotonin (5HT) associated with normal aging in both animals and humans is largely unknown. Using the effects of the 5HT agonist, m-chlorophenylpiperazine (m-CPP), as a measure of central serotonergic responsivity, we compared the behavioral and neuroendocrine responses of older normal volunteers (mean age +/- SD = 62.4 +/- 4.12) to those of younger normal volunteers (mean age +/- SD = 31.6 +/- 5.52). When m-CPP was administered intravenously, older subjects showed decreased behavioral responses but similar neuroendocrine responses, compared to younger subjects. The decreased behavioral responsivity was unrelated to pharmaco-kinetic differences between the groups, since m-CPP plasma levels were similar in both groups. This report is the first in vivo study in humans to demonstrate decreased behavioral responsivity with age following serotonergic stimulation, and may indicate a functionally less responsive 5HT subsystem in older subjects. JF - Psychiatry research AU - Lawlor, B A AU - Sunderland, T AU - Hill, J L AU - Mellow, A M AU - Molchan, S E AU - Mueller, E A AU - Jacobsen, F M AU - Murphy, D L AD - Section on Clinical Neuropharmacology, NIMH Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 1 EP - 10 VL - 29 IS - 1 SN - 0165-1781, 0165-1781 KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Prolactin KW - 9002-62-4 KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Prolactin -- blood KW - Age Factors KW - Substance-Related Disorders -- blood KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Hydrocortisone -- blood KW - Female KW - Receptors, Serotonin -- drug effects KW - Piperazines -- pharmacokinetics KW - Arousal -- drug effects KW - Brain -- drug effects KW - Piperazines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79197910?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-27 N1 - Date created - 1989-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A phase I trial of recombinant human interferon-gamma in patients with Kaposi's sarcoma and the acquired immunodeficiency syndrome (AIDS). AN - 79182993; 2549086 AB - A Phase I study of recombinant interferon-gamma (rIFN-gamma) was conducted to determine the toxicity and pharmacokinetics of this lymphokine in acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma (KS). Sixteen patients with AIDS/KS were entered into a fixed-dose trial at either 0.001, 0.01, 0.1, or 1.0 mg/m2 of rIFN-gamma. rIFN-gamma was initially administered either as a single 24-hr continuous iv infusion or as a single im injection, followed 4 days later by a 10-day course of daily therapy by the same route. Following a 1-week washout period, this sequence of administration was then repeated, with the drug given by the alternate route. Pharmacokinetic analysis of the 1.0-mg/m2 group revealed that peak serum levels of up to 153 U/ml occurred 2-4 hr after im injection and that steady-state levels of up to 40 U/ml were reached approximately 7-12 hr after beginning iv infusion. Dose-related toxicities in this trial included fever, headache, fatigue, nausea, and hepatitis, all of which were most severe at the two highest doses. Dose-dependent depression of the total white blood-cell (WBC) count, affecting both granulocytes and lymphocytes, was the most common laboratory abnormality. Natural killer (NK)-cell activity was slightly enhanced at a dose of 0.1 mg/m2 but suppressed at 1.0 mg/m2 of drug; monocyte-mediated cytotoxicity, in contrast, was significantly increased only at the highest dose. No dose-related changes were noted in KS lesions, HLA-DR expression by peripheral blood mononuclear cells, lymphocyte blastogenesis, or the ability to culture cytomegalovirus (CMV) from body fluids. We conclude that a maximally tolerated dose (MTD) for this drug is in the range of 0.1-1.0 mg/m2 and that at least modest evidence of systemic immunomodulation may be seen when rIFN-gamma is given at doses at or near this MTD. JF - Journal of clinical immunology AU - Lane, H C AU - Davey, R T AU - Sherwin, S A AU - Masur, H AU - Rook, A H AU - Manischewitz, J F AU - Quinnan, G V AU - Smith, P D AU - Easter, M E AU - Fauci, A S AD - Laboratory of Immunoregulation, NIAID, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 351 EP - 361 VL - 9 IS - 4 SN - 0271-9142, 0271-9142 KW - Adjuvants, Immunologic KW - 0 KW - Recombinant Proteins KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - AIDS/HIV KW - Leukocyte Count -- drug effects KW - Drug Evaluation -- methods KW - Humans KW - Adult KW - Middle Aged KW - Cytotoxicity, Immunologic -- drug effects KW - Adolescent KW - Male KW - Killer Cells, Natural -- drug effects KW - Cytomegalovirus -- drug effects KW - Sarcoma, Kaposi -- drug therapy KW - Interferon-gamma -- toxicity KW - Interferon-gamma -- administration & dosage KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Interferon-gamma -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79182993?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-12 N1 - Date created - 1989-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - TPA-induced neurite formation in a neuroblastoma cell line (SH-SY5Y) is associated with increased IGF-I receptor mRNA and binding. AN - 79180347; 2770453 AB - The neuroblastoma cell line SH-SY5Y was cultured in the presence of TPA for three days. Increased neurite formation was noted as early as 24 hours after TPA was added. These changes were associated with an increase in IGF-I receptor binding as well as increased mRNA for the IGF-I receptor. JF - Brain research. Molecular brain research AU - Ota, A AU - Shen-Orr, Z AU - Roberts, C T AU - LeRoith, D AD - Section of Molecular and Cellular Physiology, NIDDK, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 69 EP - 76 VL - 6 IS - 1 SN - 0169-328X, 0169-328X KW - RNA, Messenger KW - 0 KW - Somatomedins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Binding, Competitive KW - Cell Differentiation -- drug effects KW - Insulin-Like Growth Factor I -- genetics KW - Tumor Cells, Cultured -- cytology KW - Tumor Cells, Cultured -- metabolism KW - RNA, Messenger -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Insulin-Like Growth Factor I -- metabolism KW - Dendrites -- physiology KW - Somatomedins -- metabolism KW - Neuroblastoma KW - Dendrites -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79180347?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-04 N1 - Date created - 1989-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - An 18-mer peptide derived from the retinal S antigen induces uveitis and pinealitis in primates. AN - 79169405; 2475283 AB - S-antigen, a photoreceptor cell protein, induces a predominantly T-cell mediated autoimmune uveitis in many vertebrate animals, including primates. Because of this activity and the finding of immune responses to S antigen in patients with uveitis, this protein has been implicated in the pathogenesis of uveitis in humans. Peptide M, an 18-amino acid component of S antigen, has previously been shown to be highly uveitopathogenic in rats and guinea pigs. We report here that peptide M is immunopathogenic in some monkeys, producing inflammatory changes in eyes and pineal glands similar to those induced by native S antigen. Monkeys with disease also developed intense immune responses to peptide M, measured by the lymphocyte proliferation assay. In addition, lymphocytes from these monkeys reacted against whole S antigen. Furthermore, lymphocytes from certain monkeys immunized with whole S antigen responded well against peptide M, thus indicating that this peptide is an immunodominant epitope in these animals. Two of the four monkeys immunized with peptide M did not develop disease. Lymphocytes from these two animals did not respond in culture against the peptide. Following immunization with the whole protein, these monkeys were capable, however, of developing cellular immunity against S antigen and one of them developed disease. The possible involvement of peptide M in the pathogenesis of uveitis in humans is discussed. JF - Clinical and experimental immunology AU - Hirose, S AU - Singh, V K AU - Donoso, L A AU - Shinohara, T AU - Kotake, S AU - Tanaka, T AU - Kuwabara, T AU - Yamaki, K AU - Gery, I AU - Nussenblatt, R B AD - Laboratory of Immunology, National Eye Institute, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 106 EP - 111 VL - 77 IS - 1 SN - 0009-9104, 0009-9104 KW - Antigens KW - 0 KW - Epitopes KW - Eye Proteins KW - Peptide Fragments KW - peptide M, retinal S antigen KW - Index Medicus KW - Lymphocyte Activation KW - Animals KW - Macaca KW - Inflammation -- etiology KW - Inflammation -- immunology KW - Eye Proteins -- toxicity KW - Peptide Fragments -- toxicity KW - Uveitis -- immunology KW - Antigens -- toxicity KW - Uveitis -- etiology KW - Pineal Gland UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79169405?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-25 N1 - Date created - 1989-09-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Ophthalmol. 1982 Aug;94(2):147-58 [6956239] Curr Top Eye Res. 1980;2:215-302 [7344837] Clin Immunol Immunopathol. 1983 Apr;27(1):81-95 [6872352] Invest Ophthalmol Vis Sci. 1984 Aug;25(8):977-80 [6204954] J Immunol. 1982 Sep;129(3):1209-11 [6179999] Biol Cell. 1984;52(2):195-8 [6241493] Science. 1985 May 17;228(4701):891-3 [2988124] J Immunol. 1986 Jan;136(2):511-5 [2416808] FEBS Lett. 1986 Feb 3;196(1):23-8 [3080338] Invest Ophthalmol Vis Sci. 1986 Aug;27(8):1296-300 [3488297] Nature. 1986 Nov 20-26;324(6094):258-60 [2431317] Curr Eye Res. 1986 Dec;5(12):995-1004 [3492336] Immunol Rev. 1986 Dec;94:5-21 [2948901] Arch Ophthalmol. 1987 Jun;105(6):838-40 [3495256] Proc Natl Acad Sci U S A. 1987 Jul;84(13):4577-80 [2955411] Curr Eye Res. 1987 Jul;6(7):909-19 [3621983] Curr Eye Res. 1987 Sep;6(9):1151-9 [2444394] Proc Natl Acad Sci U S A. 1987 Oct;84(20):6975-9 [3478675] Exp Eye Res. 1987 Nov;45(5):695-702 [3428394] Curr Eye Res. 1988 Jan;7(1):87-92 [3258805] FEBS Lett. 1988 Jul 4;234(1):39-43 [3164688] J Immunol. 1977 Dec;119(6):1949-58 [334977] J Immunol. 1978 Feb;120(2):563-9 [304460] Invest Ophthalmol Vis Sci. 1978 Aug;17(8):774-83 [355185] Am J Ophthalmol. 1980 Feb;89(2):173-9 [7355973] Cell Immunol. 1981 Mar 1;58(2):257-68 [6452218] Arch Ophthalmol. 1981 Jun;99(6):1090-2 [7236108] Invest Ophthalmol Vis Sci. 1981 Nov;21(5):669-80 [7298272] J Fr Ophtalmol. 1981;4(6-7):465-72 [7299063] Ophthalmic Res. 1982;14(4):249-55 [6813787] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Influence of viral infections on body weight, survival, and tumor prevalence of B6C3F1 (C57BL/6N x C3H/HeN) mice in carcinogenicity studies. AN - 79164121; 2767355 AB - Sendai virus (SV), mouse hepatitis virus (MHV), and pneumonia virus of mice (PVM) are common viral infections of mice. Influence of these viral infections on the prevalence of liver tumors, lung tumors, and lymphoma is of concern in chemical carcinogenicity studies. Body weight, survival, and tumor prevalence of B6C3F1 mice with and without viral infections in 33 male and 34 female untreated control groups and 32 male and 32 female low- and high-dose groups of 2-year chemical carcinogenicity studies were evaluated. In male mice, the SV infection was associated with significantly (p less than 0.05) higher survival of control, low-dose, and high-dose groups, and higher prevalence of liver tumors and lymphoma. The increases in tumor prevalence are possibly due to an increase in the survival of male mice that had SV infection. However, when interlaboratory variability and time-related effects were taken into account, the number of significant effects was consistent with the expected false-positive rate inherent to the statistical procedures. The MHV and PVM infections did not cause consistent changes in body weight, survival, and tumor prevalences in the control and chemical treatment groups of male mice. Viral infections did not cause consistent increases or decreases in body weight, survival, or tumor prevalence in the control and chemical treatment groups of female B6C3F1 mice. JF - Fundamental and applied toxicology : official journal of the Society of Toxicology AU - Rao, G N AU - Piegorsch, W W AU - Crawford, D D AU - Edmondson, J AU - Haseman, J K AD - National Toxicology Program-Division of Toxicology Research and Testing, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 156 EP - 164 VL - 13 IS - 1 SN - 0272-0590, 0272-0590 KW - Index Medicus KW - Body Weight KW - Animals KW - Sex Factors KW - Carcinogenicity Tests KW - Mice KW - Diet KW - Male KW - Female KW - Neoplasms, Experimental -- complications KW - Neoplasms, Experimental -- chemically induced KW - Virus Diseases -- physiopathology KW - Virus Diseases -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79164121?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-10 N1 - Date created - 1989-10-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Training under Superfund. AN - 79156854; 2763316 JF - Toxicology and industrial health AU - Dement, J AD - NIEHS, Research Triangle Park, North Carolina. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 103 EP - 10; discussion 111-4 VL - 5 IS - 4 SN - 0748-2337, 0748-2337 KW - Hazardous Waste KW - 0 KW - Index Medicus KW - United States KW - United States Environmental Protection Agency KW - Hazardous Waste -- adverse effects KW - Humans KW - Environmental Exposure KW - Training Support KW - Occupational Medicine -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79156854?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-14 N1 - Date created - 1989-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Experience of the National Cancer Institute. AN - 79156426; 2763325 JF - Toxicology and industrial health AU - Ringen, K AD - National Cancer Institute, Special Populations Studies Branch. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 97 EP - 101; discussion 111-4 VL - 5 IS - 4 SN - 0748-2337, 0748-2337 KW - Index Medicus KW - United States KW - Risk Factors KW - Humans KW - National Institutes of Health (U.S.) KW - Environmental Exposure KW - Research KW - Male KW - Female KW - Occupational Medicine -- trends KW - Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79156426?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-14 N1 - Date created - 1989-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - NIEHS training in environmental toxicology. AN - 79153793; 2763320 JF - Toxicology and industrial health AU - Rall, D P AD - NIEHS, Research Triangle Park, North Carolina. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 35 EP - 7; discussion 79-84 VL - 5 IS - 4 SN - 0748-2337, 0748-2337 KW - Saccharin KW - FST467XS7D KW - Index Medicus KW - United States KW - Rats KW - Animals KW - Humans KW - National Institutes of Health (U.S.) KW - Environmental Exposure KW - Saccharin -- adverse effects KW - Male KW - Urinary Bladder Neoplasms -- chemically induced KW - Education, Medical, Continuing KW - Occupational Medicine -- education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79153793?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-14 N1 - Date created - 1989-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Molecular and genetic organization of the suppressor of sable and minute (1) 1B region in Drosophila melanogaster. AN - 79136042; 2503417 AB - Recessive mutations at the suppressor of sable [su(s)] locus in Drosophila melanogaster result in suppression of second site mutations caused by insertions of the mobile element 412. In order to determine whether su(s) mutations might have other phenotypes, a saturation mapping of the su(s) region was carried out. The screen yielded 76 mutations that comprise ten genetic complementation groups ordered distal to proximal as follows: l(1)1Bh, l(1)1Bi, M(1)1B, su(s), l(1)1Bk, l(1)1Ca, mul, tw, l(1)lDa and brc. Twenty-three of the mutations are su(s) alleles, and all are suppressors of the 412-insertion-caused v1 allele. Although the screen could have detected su(s) mutations causing sex-specific dominant lethality or sterility as well as all types of recessive lethality or sterility, the only other phenotype observed was male sterility that is enhanced by cold temperature. This type of sterility is exhibited only by alleles induced by base-substitution-causing mutagens. Genetic functions of the poly(A+) messages transcribed from the su(s) microregion were identified by the reintroduction of cloned sequences into embryos by P element transformation. su(s) function has been attributed to a 5-kb message. The segment of DNA encoding only this 5-kb message rescues both the suppression and cold-sensitive male sterility phenotypes of su(s). Minute (1) 1B has been provisionally identified as encoding a 3.5-kb message; lethal (1)1Bi encodes a 1-kb message; and lethal (1)1Bk encodes a 4-kb message. The possible functions of su(s) and M(1)1B are discussed. JF - Genetics AU - Voelker, R A AU - Huang, S M AU - Wisely, G B AU - Sterling, J F AU - Bainbridge, S P AU - Hiraizumi, K AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 625 EP - 642 VL - 122 IS - 3 SN - 0016-6731, 0016-6731 KW - Index Medicus KW - Phenotype KW - Animals KW - Alleles KW - Transformation, Genetic KW - Genetic Complementation Test KW - Transcription, Genetic KW - Infertility, Male -- genetics KW - Mutation KW - Genes, Lethal KW - Chromosome Mapping KW - Male KW - Female KW - Drosophila melanogaster -- genetics KW - Suppression, Genetic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79136042?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-18 N1 - Date created - 1989-09-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1986 May;6(5):1520-8 [3023894] Mol Cell Biol. 1986 Jan;6(1):47-53 [3023836] EMBO J. 1987 Dec 20;6(13):4095-104 [2832151] EMBO J. 1987 Dec 20;6(13):4105-11 [3443103] EMBO J. 1988 Apr;7(4):1081-6 [2841109] Genetics. 1962 Jul;47:807-17 [14454469] Genetics. 1969 Jul;62(3):781-95 [5384490] Genetics. 1977 Feb;85(2):259-72 [405273] Biochemistry. 1980 Apr 1;19(7):1425-33 [6770897] Genetics. 1981 Nov-Dec;99(3-4):461-80 [6806144] Mutat Res. 1982 Feb 22;92(1-2):107-15 [6806646] Cell. 1982 Oct;30(3):817-23 [6814765] Proc Natl Acad Sci U S A. 1983 Mar;80(6):1678-82 [6300868] Mutat Res. 1983 Feb;107(2):187-201 [6408464] Cell. 1983 Aug;34(1):59-73 [6309412] Genetics. 1983 Jul;104(3):433-48 [6411520] Cell. 1984 Aug;38(1):135-46 [6088058] Proc Natl Acad Sci U S A. 1984 Oct;81(19):6090-4 [6435123] Mol Cell Biol. 1984 Dec;4(12):2643-52 [6084810] Cell. 1985 Jun;41(2):429-37 [2985277] Mutat Res. 1985 Jun-Jul;150(1-2):261-75 [3923338] Science. 1985 Aug 9;229(4713):558-61 [2992080] Nature. 1985 Oct 10-16;317(6037):555-8 [4047173] Genetics. 1985 Nov;111(3):495-515 [2414153] Proc Natl Acad Sci U S A. 1986 Jan;83(2):404-8 [3001735] Mutat Res. 1986 Aug;162(1):47-54 [3014321] Genetics. 1986 Aug;113(4):869-95 [3091446] Genetics. 1986 Nov;114(3):819-40 [3098623] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - A human rel proto-oncogene cDNA containing an Alu fragment as a potential coding exon. AN - 79131720; 2666912 AB - Two rel-containing cDNA clones were isolated from a library derived from the Daudi human cell line, which is known to express c-rel mRNA. Clone #1 appeared to contain the entire c-rel coding sequence, which differs from v-rel in having three additional N-terminal residues and 111 additional C-terminal residues. In addition, Clone #1 had an internal 32 amino acid exon not found in v-rel or in turkey c-rel. Clone #2 was truncated at its 5' end and did not contain this new exon. Analysis of a genomic clone of human c-rel revealed that the new exon was a portion of an inverted Alu repeat. The occurrence of potential splice sites and of open reading frames in the inverted consensus Alu sequence suggests that the incorporation of Alu fragments as potential coding exons could be a relatively common event in human mRNAs. Whether such messages can be translated is unknown: antiserum raised against a peptide at the predicted C-terminus of the c-rel protein precipitated p82hc-rel, but antiserum raised against a peptide located in the Alu exon did not. JF - Oncogene AU - Brownell, E AU - Mittereder, N AU - Rice, N R AD - Laboratory of Molecular Virology and Carcinogenesis, NCI-Frederick Cancer Research Facility, Maryland 21701. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 935 EP - 942 VL - 4 IS - 7 SN - 0950-9232, 0950-9232 KW - Proto-Oncogene Proteins KW - 0 KW - Proto-Oncogene Proteins c-rel KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Protein Biosynthesis KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Proto-Oncogene Proteins -- analysis KW - Exons KW - DNA -- analysis KW - Repetitive Sequences, Nucleic Acid KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79131720?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-07 N1 - Date created - 1989-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Differential effects of acute and repeated electrically and chemically induced seizures on [3H]Nimodipine and [125I]omega-conotoxin GVIA binding in rat brain. AN - 79126886; 2753000 AB - [3H]Nimodipine and high-affinity [125I]omega-conotoxin GVIA (CgTX) binding were investigated in membranes from rat cerebral cortex, cerebellum, and hippocampus after electrically and chemically induced seizures. Animals were decapitated 30 min after a single electroconvulsive shock (ECS) or lidocaine-induced seizure and 24 h after the last of 10 once-daily ECS or six once-daily lidocaine-induced seizures. After a single ECS, [3H]nimodipine and [125I]CgTX binding sites decreased in cerebral cortex (by 10% and 17%, respectively). A downregulation of [3H]nimodipine binding sites in hippocampus occurred after single and repeated lidocaine-induced seizures (by 24% and 11%, respectively), whereas [125I]CgTX binding remained unaltered. An earlier report on changes in [3H]nitrendipine binding after chronic ECS in cortex and hippocampus was not confirmed. JF - Epilepsia AU - Gleiter, C H AU - Cain, C J AU - Weiss, S R AU - Post, R M AU - Marangos, P J AD - Laboratory of Clinical Studies, D.I.C.B.R., National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland. PY - 1989 SP - 487 EP - 492 VL - 30 IS - 4 SN - 0013-9580, 0013-9580 KW - Calcium Channel Blockers KW - 0 KW - Iodine Radioisotopes KW - Mollusk Venoms KW - Tritium KW - 10028-17-8 KW - Nimodipine KW - 57WA9QZ5WH KW - omega-Conotoxin GVIA KW - 92078-76-7 KW - Lidocaine KW - 98PI200987 KW - Index Medicus KW - Animals KW - Cerebral Cortex -- metabolism KW - Hippocampus -- metabolism KW - Binding Sites KW - Cerebellum -- metabolism KW - Rats KW - Rats, Inbred Strains KW - Electroshock KW - Male KW - Seizures -- chemically induced KW - Calcium Channel Blockers -- metabolism KW - Nimodipine -- metabolism KW - Seizures -- etiology KW - Mollusk Venoms -- metabolism KW - Seizures -- metabolism KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79126886?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-01 N1 - Date created - 1989-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix. AN - 79121270; 2787917 AB - An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints. The higher radiation dose and the concentration of that dose in a smaller area of the body appear to be responsible for the lower rate of persistent aberrations observed in cervical cancer patients. JF - Radiation research AU - Kleinerman, R A AU - Littlefield, L G AU - Tarone, R E AU - Machado, S G AU - Blettner, M AU - Peters, L J AU - Boice, J D AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 176 EP - 190 VL - 119 IS - 1 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Chromosome Deletion KW - Humans KW - Chromosome Inversion KW - Translocation, Genetic KW - Female KW - Bone Marrow KW - Radiation Dosage KW - Chromosome Aberrations KW - T-Lymphocytes -- radiation effects KW - Uterine Cervical Neoplasms -- radiotherapy KW - Uterine Cervical Neoplasms -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79121270?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-28 N1 - Date created - 1989-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Alcoholism treatment in general hospitals. AN - 79118004; 2502688 AB - This article examines recent developments in the role of general hospitals in providing treatment for alcoholism. It employs data on 5,000 U.S. short-term general hospitals and on all patients discharged from a subsample of 400 of these hospitals in the years 1980 through 1985. The article describes the growth in alcoholism treatment resources in short-term hospitals (1980-85) and examines linked hospital and patient data for the 400 hospitals in the subsample to describe patient diagnoses and resource use (1980 and 1985). Patients are classified by the stage of their alcohol problem, and hospital use is examined for patients in different stages. JF - Journal of studies on alcohol AU - Wallen, J AU - Noble, J A AD - Division of Clinical Research and Prevention, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20857. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 301 EP - 305 VL - 50 IS - 4 SN - 0096-882X, 0096-882X KW - Index Medicus KW - United States KW - Cross-Sectional Studies KW - Alcohol Withdrawal Delirium -- rehabilitation KW - Diagnosis-Related Groups KW - Humans KW - Substance-Related Disorders -- rehabilitation KW - Health Resources -- utilization KW - Bed Occupancy KW - Alcoholism -- rehabilitation KW - Hospitals, General -- utilization KW - Alcoholism -- epidemiology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79118004?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-31 N1 - Date created - 1989-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The biochemical toxicity of perfluorodecanoic acid in the mouse is different from that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 79106164; 2749739 AB - Perfluorodecanoic acid (PFDA) is an industrial surfactant that has been reported to produce signs of toxicity in rats similar to those due to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to characterize the biochemical toxicity of PFDA in the mouse and to determine whether PFDA toxicity is mediated by the Ah locus, congenic female C57BL/6J mice differing only at the Ah locus (normal homozygous responsive Ahb/b, heterozygous responsive Ahb/d, and homozygous nonresponsive Ahd/d) were administered a single oral dose of PFDA. The wild type (Ahb/b) mice were killed 2, 7, 14, or 30 days after administration of 0, 40, 80, 100, 120, or 160 mg PFDA/kg. Mice from the other two congenic strains were killed 30 days after dosing with 0, 40, 80, or 160 mg/kg. PFDA produced a 2.5-fold increase in absolute liver weight, a 5- to 15-fold increase in hepatic fatty acyl Co-A oxidase activity, and a 70% decrease in hepatic ethoxyresorufin O-deethylase (EROD) activity. These effects were dose and time dependent. Total hepatic lipids were increased at an early time point and at the lowest dose. At later time periods and/or higher doses, the lipid concentration was decreased approximately 20% from that of controls. Hepatic protein concentrations were depressed approximately 25% from control levels 30 days after treatment. There was little difference in any of these parameters between responsive (Ahb/b, Ahb/d) and nonresponsive (Ahd/d) mice. These results suggest that the Ah allele has little effect in regulating the toxicity of PFDA in the mouse and that the biochemical response to PFDA in the mouse is markedly different from that of TCDD. Furthermore, the biochemical response to PFDA in the mouse is different from that reported in the rat. JF - Toxicology and applied pharmacology AU - Brewster, D W AU - Birnbaum, L S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 544 EP - 554 VL - 99 IS - 3 SN - 0041-008X, 0041-008X KW - Decanoic Acids KW - 0 KW - Dioxins KW - Fluorocarbons KW - Lipids KW - Polychlorinated Dibenzodioxins KW - Proteins KW - perfluorodecanoic acid KW - 335-76-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Oxidoreductases KW - EC 1.- KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Acyl-CoA Oxidase KW - EC 1.3.3.6 KW - Index Medicus KW - Cytochrome P-450 Enzyme System -- analysis KW - Animals KW - Body Weight -- drug effects KW - Mice, Inbred C57BL KW - Oxidoreductases -- analysis KW - Proteins -- analysis KW - Mice KW - Species Specificity KW - Female KW - Organ Size -- drug effects KW - Lipids -- analysis KW - Polychlorinated Dibenzodioxins -- toxicity KW - Fluorocarbons -- toxicity KW - Dioxins -- toxicity KW - Decanoic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79106164?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-18 N1 - Date created - 1989-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Calcium-dependent effects of maitotoxin on phosphoinositide breakdown and on cyclic AMP accumulation in PC12 and NCB-20 cells. AN - 79104223; 2546052 AB - The marine dinoflagellate toxin maitotoxin (MTX) stimulates phosphoinositide breakdown in pheochromocytoma PC12 cells and in neuroblastoma hybrid NCB-20 cells. In both cell lines, the stimulation of phosphoinositide breakdown by MTX is dependent on extracellular calcium, but it is not reduced by organic or inorganic calcium channel blockers. In PC12 cells, the maximal stimulation of phosphoinositide breakdown occurs at 1.5 mM [Ca2+]o, whereas in NCB-20 cells the maximal stimulation is observed at 2.5-4.5 mM [Ca2+]o. Phosphoinositide breakdown is known to lead to formation of both inositol phosphates and diacylglycerols. The latter, through stimulation of protein kinase C, would, like phorbol esters, be expected to augment cyclic AMP accumulation in PC12 cells and to inhibit receptor-mediated cyclic AMP accumulation in NCB-20 cells. MTX does potentiate forskolin-induced accumulation of cyclic AMP in PC12 cells and does inhibit prostaglandin E2-induced accumulation of cyclic AMP in NCB-20 cells. The effects of MTX on accumulation of cyclic AMP are calcium dependent and the concentrations of calcium required for maximal responses are the same as the ones required for maximal stimulation of phosphoinositide breakdown. MTX increases intracellular calcium in both cell lines, as measured by calcium-quin2 fluorescence. But the effects of MTX on forskolin- and prostaglandin E2-mediated cyclic AMP accumulation are not mimicked by a calcium ionophore and are not blocked by nifedipine, a calcium channel blocker. Translocation of protein kinase C occurs after treatment with MTX in both cell lines; the protein kinase C activity and content are reduced in the cytosol and increased in membranes after exposure to either MTX or a phorbol ester. The results confirm previous studies on the heterogeneous input of protein kinase C to cyclic AMP-generating systems performed with phorbol esters and demonstrate the utility of MTX as a unique tool for studies of systems that involve second messengers generated through stimulation of phosphoinositide breakdown. JF - Molecular pharmacology AU - Gusovsky, F AU - Yasumoto, T AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 44 EP - 53 VL - 36 IS - 1 SN - 0026-895X, 0026-895X KW - Marine Toxins KW - 0 KW - Oxocins KW - Phosphatidylinositols KW - maitotoxin KW - 9P59GES78D KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Animals KW - Tumor Cells, Cultured -- metabolism KW - Adrenal Gland Neoplasms -- metabolism KW - Biological Transport KW - Pheochromocytoma -- metabolism KW - Cricetinae KW - Marine Toxins -- pharmacology KW - Phosphatidylinositols -- metabolism KW - Cyclic AMP -- metabolism KW - Calcium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79104223?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-22 N1 - Date created - 1989-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Human NADPH-P450 oxidoreductase: complementary DNA cloning, sequence and vaccinia virus-mediated expression and localization of the CYPOR gene to chromosome 7. AN - 79102409; 2501655 AB - The cDNA containing the full coding sequence of human NADPH-P450 oxidoreductase was isolated and completely sequenced. The cDNA contained 2398 base pairs, including 9 and 358 base pairs of 5' and 3' noncoding sequences, respectively. The human NADPH-P450 oxidoreductase protein deduced from the cDNA has 677 amino acids, with a calculated molecular weight of 76,656. The cDNA nucleotide and deduced amino acid sequences displayed 83 and 92% similarities, respectively, with those of the rat NADPH-P450 oxidoreductase. By use of somatic cell hybrids, the NADPH-P450 oxidoreductase gene was regionally localized to human chromosome 7 (7p15-q35). The levels of NADPH-P450 oxidoreductase protein and mRNA were analyzed in 13 human liver specimens and less than 3-fold variation was found among the different livers. The NADPH-P450 oxidoreductase cDNA was inserted into vaccinia virus and expressed in cell culture. The cDNA-expressed enzyme was active in reducing the electron acceptor cytochrome c. In addition, the NADPH-P450 oxidoreductase stimulated the enzymatic activity of vaccinia virus-expressed human P3(450) when both recombinant viruses were used to coinfect human cells in culture. An approximate equal mole level of NADPH-P450 oxidoreductase and P3(450) was required to achieve maximal activity for both ethoxycoumarin O-deethylase and aryl hydrocarbon hydroxylase. JF - Molecular pharmacology AU - Yamano, S AU - Aoyama, T AU - McBride, O W AU - Hardwick, J P AU - Gelboin, H V AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 83 EP - 88 VL - 36 IS - 1 SN - 0026-895X, 0026-895X KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Chromosome Mapping KW - Cloning, Molecular KW - Cytochrome P-450 Enzyme System -- analysis KW - NADPH-Ferrihemoprotein Reductase -- genetics KW - Vaccinia virus -- enzymology KW - Cytochrome P-450 Enzyme System -- genetics KW - DNA -- analysis KW - Chromosomes, Human, Pair 7 KW - NADPH-Ferrihemoprotein Reductase -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79102409?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-22 N1 - Date created - 1989-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Fine specificity of xenogeneic antigen recognition by human T cells. AN - 79101857; 2473552 AB - T cell mediated responses play a role in xenograft as well as allograft rejection. In vitro T cell responses to xenogeneic antigens are characterized by T cell recognition of polymorphic determinants of gene products encoded by the major histocompatibility complex of the stimulating cells, but little is known of the fine specificity of this recognition of xenogeneic antigens and its comparability to allogeneic antigen recognition. In order to study the fine specificity of human CTL in the recognition of xenogeneic antigens, long-term lines or clones were established from a secondary mixed lymphocyte response in which the stimulator cells were H-2b murine splenocytes. By comparing the ability of a series of target cells derived from congenic recombinant mouse strains to be lysed by these CTL, it was demonstrated that all isolated lines specifically lysed target cells expressing H-2b or T1a/Qa-1b products. Of the effector populations specific for H-2b cell surface molecules, all recognized class I products with Kb specificity predominating when evaluated for their ability to lyse in vivo-derived class I mutants or cells transfected with class I genes. These human xenoreactive CTL were able to distinguish wild type Kb molecules from those altered by amino acid changes confined to a single molecular domain of Kb. These findings demonstrate that xenogeneic antigen recognition by human T cells is characterized by a fine specificity of antigen recognition comparable to the specificity of recognition of major histocompatibility complex-encoded molecules by murine CTL across allogeneic differences. JF - Transplantation AU - Gress, R E AU - Nathenson, S G AU - Lucas, P J AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 93 EP - 98 VL - 48 IS - 1 SN - 0041-1337, 0041-1337 KW - Epitopes KW - 0 KW - H-2 Antigens KW - Histocompatibility Antigens Class I KW - Q surface antigens KW - Index Medicus KW - Animals KW - Humans KW - Lymphocyte Culture Test, Mixed KW - Histocompatibility Antigens Class I -- immunology KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Cytotoxicity Tests, Immunologic KW - Mice KW - Histocompatibility Antigens Class I -- genetics KW - Cell Line KW - Genes, MHC Class I KW - H-2 Antigens -- genetics KW - T-Lymphocytes, Cytotoxic -- transplantation KW - Epitopes -- genetics KW - Transplantation, Heterologous KW - H-2 Antigens -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Epitopes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79101857?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-18 N1 - Date created - 1989-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Action of phorbol esters, bryostatins, and retinoic acid on cholesterol sulfate synthesis: relation to the multistep process of differentiation in human epidermal keratinocytes. AN - 79098650; 2473132 AB - This study examines the action of phorbol 12-myristate 13-acetate (PMA) on the synthesis of cholesterol sulfate in cultured normal and transformed human epidermal keratinocytes and assesses the antagonistic effects by retinoids and bryostatins on PMA action in relation to the multistep program of squamous differentiation. Treatment of normal human epidermal keratinocytes (NHEK) with PMA induces terminal cell division (irreversible growth-arrest) and causes a time- and dose-dependent increase in the incorporation of Na2(35)SO4 into cholesterol sulfate, a marker for squamous cell differentiation. This stimulation in sulfate incorporation appears specific for cholesterol sulfate and is due to increased levels of cholesterol sulfotransferase activity. The increase in cholesterol sulfate accumulation parallels the increase in transglutaminase type I, another marker for squamous differentiation. Several transformed NHEK cell lines do not exhibit increased levels of cholesterol sulfate and transglutaminase type I activity after PMA treatment, indicating that they acquired defects in the regulation of squamous differentiation. Bryostatins 1 and 2, and several diacylglycerol analogues neither inhibit cell proliferation nor increase cholesterol sulfate synthesis or transglutaminase activity, indicating that these agents do not induce terminal differentiation. In contrast, the bryostatins block the increase in cholesterol sulfate and transglutaminase activity as well as the commitment to terminal cell division by PMA. Bryostatin 1 inhibits the commitment to terminal cell division and the accumulation of cholesterol sulfate significantly even when added 8 h after PMA administration. Retinoids inhibit cholesterol sulfate accumulation and the increase in transglutaminase activity by PMA but do not affect the commitment to terminal cell division. In summary, phorbol esters induce in NHEK cells a program of squamous differentiation. This process of differentiation consists of the commitment to terminal cell division and expression of a squamous phenotype. Expression of this phenotype is accompanied by an accumulation of cholesterol sulfate and increased cholesterol sulfotransferase activity. Bryostatins 1 and 2 and retinoic acid affect this differentiation process at different stages. JF - The Journal of investigative dermatology AU - Jetten, A M AU - George, M A AU - Pettit, G R AU - Herald, C L AU - Rearick, J I AD - Cell Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 108 EP - 115 VL - 93 IS - 1 SN - 0022-202X, 0022-202X KW - Bryostatins KW - 0 KW - Cholesterol Esters KW - Diglycerides KW - Lactones KW - Macrolides KW - bryostatin 1 KW - 37O2X55Y9E KW - Tretinoin KW - 5688UTC01R KW - Keratins KW - 68238-35-7 KW - bryostatin 2 KW - 87745-28-6 KW - cholesteryl sulfate KW - KU576NT9O9 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Diglycerides -- pharmacology KW - Humans KW - Cell Differentiation KW - Cell Line, Transformed KW - Tretinoin -- pharmacology KW - Cholesterol Esters -- biosynthesis KW - Epidermis -- cytology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lactones -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79098650?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-25 N1 - Date created - 1989-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Gestational trophoblastic disease: a case-control study from the People's Republic of China. AN - 79092903; 2546427 AB - A case-control study involving 331 patients with complete hydatidiform mole and 662 community controls matched to the cases on age and timing of pregnancy was conducted in Beijing, China. A history of a term birth was associated with reduced risk (odds ratio = 0.6, 95% confidence interval 0.4 to 0.9), with some evidence of further decrease with multiple births. Previous spontaneous abortions were not related to risk, although those with a prior induced abortion were at elevated risk, particularly if two or more abortions were involved (odds ratio = 2.8, 95% confidence interval 1.4 to 5.7). A history of having sought medical advice for infertility was associated with reduced risk (odds ratio = 0.5, 95% confidence interval 0.2 to 0.8), but those who reported use of herbal medicines during a first trimester of a previous pregnancy were at excess risk (odds ratio = 2.2, 95% confidence interval 1.3 to 3.6). In addition, a statistically significant trend in risk was observed with years of oral contraceptive use (odds ratio = 2.6, 95% confidence interval 0.9 to 6.9 for greater than or equal to 4 years of use). Dietary habits and family histories of cancer or trophoblastic disease were not related to risk in this study. JF - American journal of obstetrics and gynecology AU - Brinton, L A AU - Wu, B Z AU - Wang, W AU - Ershow, A G AU - Song, H Z AU - Li, J Y AU - Bracken, M B AU - Blot, W J AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 121 EP - 127 VL - 161 IS - 1 SN - 0002-9378, 0002-9378 KW - Contraceptives, Oral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Infertility KW - Age Factors KW - Intrauterine Devices KW - Humans KW - Adult KW - Reproduction KW - Diet KW - Female KW - China KW - Pregnancy KW - Pregnancy Complications, Neoplastic KW - Uterine Neoplasms -- chemically induced KW - Uterine Neoplasms -- etiology KW - Trophoblastic Neoplasms -- etiology KW - Trophoblastic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79092903?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-17 N1 - Date created - 1989-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Incineration and monitoring of low-level 35S wastes at a biological research institution. AN - 79092323; 2745082 JF - Health physics AU - Hamrick, P E AU - Wall, B E AU - Simon, S L AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 191 EP - 194 VL - 57 IS - 1 SN - 0017-9078, 0017-9078 KW - Air Pollutants, Radioactive KW - 0 KW - Radioactive Waste KW - Sulfates KW - Sulfur Radioisotopes KW - sodium sulfate KW - 0YPR65R21J KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - Hot Temperature KW - Equipment Contamination KW - Filtration -- instrumentation KW - Air Pollutants, Radioactive -- analysis KW - Refuse Disposal -- methods KW - Radioactive Waste -- analysis KW - Refuse Disposal -- instrumentation KW - Radiation Monitoring KW - Sulfur Radioisotopes -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79092323?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-17 N1 - Date created - 1989-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Infectious papillomavirus in the vapor of warts treated with carbon dioxide laser or electrocoagulation: detection and protection. AN - 79090607; 2545749 AB - Papillomavirus DNA has been reported recently in the vapor (smoke plume) derived from warts treated with carbon dioxide laser; this raises concerns for operator safety. We therefore have studied a group of human and bovine warts to define further the potential risk of wart therapy and to test whether a surgical mask could reduce exposure. Half of each wart was treated with carbon dioxide laser and the other half with electrocoagulation. The vapor produced by each form of therapy was collected with a dry filter vacuum apparatus and analyzed for the presence of papillomavirus. Vapor from human plantar warts was analyzed for the presence of human papillomavirus DNA, because there is no infectivity assay for human papillomavirus. Of plantar warts treated, five of eight laser-derived vapors and four of seven electrocoagulation-derived vapors were positive for human papillomavirus DNA. Greater amounts of papillomavirus DNA were usually recovered in the laser vapor than in the electrocoagulation vapor from the same wart. Bioassay readily detected infectious bovine papillomavirus in the vapor from bovine warts treated with either modality; more virus was present in laser-derived material. A surgical mask was found capable of removing virtually all laser- or electrocoagulation-derived virus, strongly suggesting that such masks can protect operators from potential inhalation exposure to papillomavirus. JF - Journal of the American Academy of Dermatology AU - Sawchuk, W S AU - Weber, P J AU - Lowy, D R AU - Dzubow, L M AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 41 EP - 49 VL - 21 IS - 1 SN - 0190-9622, 0190-9622 KW - Air Pollutants, Occupational KW - 0 KW - DNA, Viral KW - Carbon Dioxide KW - 142M471B3J KW - Index Medicus KW - Animals KW - Cattle KW - Humans KW - Air Pollutants, Occupational -- isolation & purification KW - Environmental Exposure KW - Cattle Diseases -- surgery KW - Volatilization KW - DNA, Viral -- isolation & purification KW - Nucleic Acid Hybridization KW - Bovine papillomavirus 1 -- isolation & purification KW - Cell Transformation, Viral KW - Masks KW - Papillomaviridae -- isolation & purification KW - Laser Therapy KW - Air Microbiology KW - Warts -- surgery KW - Electrocoagulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79090607?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-22 N1 - Date created - 1989-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Elevation of pi class glutathione S-transferase activity in human breast cancer cells by transfection of the GST pi gene and its effect on sensitivity to toxins. AN - 79088298; 2747627 AB - Increased expression of the glutathione S-transferase (GST; E.C.2.5.1.18) pi class isozyme is associated with both malignant transformation and drug resistance, as well as with decreased estrogen receptor content in breast cancer. In order to further characterize the role of this enzyme in drug resistance, we cloned the cDNA encoding the human isozyme GST pi and developed two eukaryotic expression vectors using this cDNA and either the human metallothionein IIa or cytomegalovirus immediate-early promoters. These GST pi expression vectors were cotransfected with pSV2neo into drug-sensitive MCF-7 human breast cancer cells, which have low amounts of GST activity and which do not express GST pi. The transfected cells were selected for G418 resistance and individual clones were screened for GST activity. Three clones that demonstrated increased GST activity were selected for further study. Immunoprecipitation studies demonstrated that the increase in GST activity in these clones was due to expression of GST pi. Although the total GST activity of the positive clones was increased as much as 15-fold over that in wild-type MCF-7 cells, there was no change in glutathione peroxidase activity, as measured using cumene hydroperoxide as a substrate. Immunoblot studies revealed that the increased GST enzyme produced in the transfected cells was identical in size to endogenous GST pi. Southern blot analysis demonstrated the incorporation of the GST pi expression vector into the genome of the positive clones and Northern blot analysis showed that the transfected genes made a hybrid GST pi RNA that was slightly larger than the endogenous GST pi RNA. Primer extension studies demonstrated that this increase in length corresponded to the added length of the 5' leader sequence of the expression vector. The effect of increased GST pi activity on the sensitivity of the transfected clones to several cytotoxic agents was assessed by colony-forming assay. The transfected clones were slightly more resistant (1.3-4.1-fold) to benzo(a)pyrene and its toxic metabolite benzo(a)pyrene-(anti)-7,8-dihydrodiol-9,10-epoxide, as well as to ethacrynic acid (3.1-to 4.4-fold). Although increased GST pi expression is found in MCF-7 cells selected for doxorubicin resistance, the transfected clones were not consistently more resistant to doxorubicin than control cells. In addition, the transfected cells were not resistant to either melphalan or (cis)-platinum, even though conjugation with glutathione is known to play a role in the detoxification of both of these drugs.(ABSTRACT TRUNCATED AT 400 WORDS) JF - Molecular pharmacology AU - Moscow, J A AU - Townsend, A J AU - Cowan, K H AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 22 EP - 28 VL - 36 IS - 1 SN - 0026-895X, 0026-895X KW - Isoenzymes KW - 0 KW - Doxorubicin KW - 80168379AG KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Ethacrynic Acid KW - M5DP350VZV KW - Index Medicus KW - Doxorubicin -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Ethacrynic Acid -- toxicity KW - Drug Resistance KW - Female KW - Isoenzymes -- analysis KW - Glutathione Transferase -- physiology KW - Transfection KW - Glutathione Transferase -- genetics KW - Glutathione Transferase -- analysis KW - Breast Neoplasms -- enzymology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79088298?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-22 N1 - Date created - 1989-08-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Oncogenes and their applications in epidemiologic studies. AN - 79071593; 2662757 JF - American journal of epidemiology AU - Taylor, J A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 6 EP - 13 VL - 130 IS - 1 SN - 0002-9262, 0002-9262 KW - Carcinogens KW - 0 KW - Index Medicus KW - Neoplasms -- diagnosis KW - Humans KW - Prognosis KW - Data Collection KW - Neoplasms -- therapy KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Oncogenes KW - Epidemiologic Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79071593?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-04 N1 - Date created - 1989-08-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Epidemiol. 1990 Jun;131(6):1099-100 [2140491] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - The National Cancer Institute's Smoking, Tobacco, and Cancer Program. AN - 79063695; 2737004 JF - Chest AU - Cullen, J W AD - Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Md 20892-3100. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 9S EP - 13S VL - 96 IS - 1 Suppl SN - 0012-3692, 0012-3692 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Life Style KW - Behavior Therapy KW - Humans KW - Male KW - Female KW - National Institutes of Health (U.S.) KW - Tobacco Use Disorder -- prevention & control KW - Neoplasms -- prevention & control KW - Smoking -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79063695?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-03 N1 - Date created - 1989-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Phenytoin withdrawal and seizure frequency. AN - 79062969; 2739918 AB - We withdrew phenytoin from 17 inpatients maintained on combination therapy with carbamazepine for complex partial seizures and analyzed seizure occurrence in relation to plasma levels and time from initiation of withdrawal. The ratio of maximum to mean weekly seizure frequency did not vary with initial level or rate of withdrawal. The week with most frequent seizures began a median of 10 days after phenytoin levels became undetectable, and mean daily seizure frequency was higher at undetectable than at falling levels for the entire 2- to 10-week study period. Four patients had a total of 6 clusters of generalized tonic-clonic seizures; only 2 occurred while levels were falling and the other 4 at 3, 9, 28, and 42 days after reaching undetectable levels. Our data argue against the occurrence of withdrawal seizures in these patients and suggest that worsening of seizures following phenytoin discontinuation more likely reflects loss of therapeutic drug effect than a true abstinence phenomenon. JF - Neurology AU - Bromfield, E B AU - Dambrosia, J AU - Devinsky, O AU - Nice, F J AU - Theodore, W H AD - Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 905 EP - 909 VL - 39 IS - 7 SN - 0028-3878, 0028-3878 KW - Carbamazepine KW - 33CM23913M KW - Phenytoin KW - 6158TKW0C5 KW - Diazepam KW - Q3JTX2Q7TU KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Diazepam -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Carbamazepine -- therapeutic use KW - Male KW - Female KW - Epilepsy, Temporal Lobe -- physiopathology KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - Substance Withdrawal Syndrome KW - Epilepsy, Temporal Lobe -- chemically induced KW - Phenytoin -- therapeutic use KW - Phenytoin -- blood KW - Phenytoin -- adverse effects KW - Epilepsy -- drug therapy KW - Epilepsy, Temporal Lobe -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79062969?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-03 N1 - Date created - 1989-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. A phase II randomized, placebo-controlled trial. AN - 79060863; 2735626 AB - To evaluate the toxicity, effects on immune function, antitumor effects, antiretroviral effects, and pharmacokinetics of zidovudine therapy in patients with early human immunodeficiency virus (HIV) infection and Kaposi sarcoma. Randomized, double-blind, placebo-controlled trial. National Institutes of Health, a referral-based research institution (single site). Physician-referred volunteer patients with HIV infection, Kaposi sarcoma, CD4+ lymphocyte counts greater than 0.2 x 10(9)/L, and no systemic symptoms or history of opportunistic infection. Of 41 patients enrolled, 4 had not met all entry criteria and were therefore not evaluable. Patients were randomized to one of four treatment groups for an initial 12-week treatment period: oral placebo (9 patients); zidovudine, 250 mg orally every 4 hours (9 patients); zidovudine, 0.5 mg/kg body weight intravenously every 4 hours (9 patients); and zidovudine, 2.5 mg/kg intravenously every 4 hours (10 patients). After at least 12 weeks of therapy at their assigned dose, patients were treated with oral zidovudine, generally 250 mg every 4 hours, with a mean 42-week follow-up. Anemia and granulocytopenia were the major toxicities. Significant increases in platelet counts and declines in serum HIV antigen and IgG and IgM levels occurred in treated patients. Treated patients were more likely than those on placebo to clear HIV from the cerebrospinal fluid. There were no differences in tumor progression or CD4+ or CD8+ lymphocyte counts among the groups. Zidovudine was well tolerated and had antiretroviral activity in patients with early HIV infection and Kaposi sarcoma but it had no significant effect on the extent of Kaposi sarcoma or on immune function. JF - Annals of internal medicine AU - Lane, H C AU - Falloon, J AU - Walker, R E AU - Deyton, L AU - Kovacs, J A AU - Masur, H AU - Banks, S AU - Kirk, L E AU - Baseler, M W AU - Salzman, N P AD - National Institutes of Health, Bethesda, Maryland. Y1 - 1989/07/01/ PY - 1989 DA - 1989 Jul 01 SP - 41 EP - 50 VL - 111 IS - 1 SN - 0003-4819, 0003-4819 KW - Zidovudine KW - 4B9XT59T7S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Leukocyte Count -- drug effects KW - HIV -- drug effects KW - Drug Evaluation KW - Prospective Studies KW - Double-Blind Method KW - Random Allocation KW - Humans KW - Anemia -- chemically induced KW - Adult KW - Granulocytes -- drug effects KW - Middle Aged KW - Male KW - Zidovudine -- therapeutic use KW - Sarcoma, Kaposi -- drug therapy KW - Acquired Immunodeficiency Syndrome -- complications KW - Zidovudine -- pharmacokinetics KW - Zidovudine -- adverse effects KW - Acquired Immunodeficiency Syndrome -- immunology KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Sarcoma, Kaposi -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79060863?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-18 N1 - Date created - 1989-07-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Ann Intern Med 1990 Mar 1;112(5):388 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Quality control procedure for 6-[18F]fluoro-L-DOPA: a presynaptic PET imaging ligand for brain dopamine neurons. AN - 79060242; 2500503 AB - The goal of the current study was to establish a quality control procedure for clinical use of 6-[18F]fluoro-L-DOPA (6-[18F]-DOPA) as a selective presynaptic positron emission tomographic (PET) imaging ligand for brain dopamine neurons. A high performance liquid chromatographic procedure using a 5-mu C-18 reverse phase column and ion-pairing mobile phase was used for the quantification of 6-[18F]-DOPA. The radiochemical purity of 6-[18F]-DOPA was measured by 18F radioactivity in HPLC fractions while the chemical purity was determined by an amperometric electrochemical detector with a sensitivity of 25 pg. Quality control of eight consecutive batches of highly purified 6-[18F]-DOPA sample used in a pre-clinical trial revealed that the chemical and/or radiochemical purity of the PET imaging ligand, 6-[18F]-DOPA was greater than 97 +/- 0.5% with a specific activity of 365 +/- 31 mCi/mmol. The knowledge and assurance of radiochemical purity of PET ligands are essential for the interpretation of clinical PET imaging results. The assurance of such quality control would enable comparisons of 6-[18F]-DOPA/PET data obtained from various medical centers using different radiopharmaceutical procedures. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Chen, J J AU - Huang, S J AU - Finn, R D AU - Kirk, K L AU - Francis, B E AU - Adams, H R AU - Cohen, R M AU - Chiueh, C C AD - Clinical Brain Imaging Section, National Institute of Mental Health, Bethesda, Maryland 20892-1000. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 1249 EP - 1256 VL - 30 IS - 7 SN - 0161-5505, 0161-5505 KW - Pyrogens KW - 0 KW - fluorodopa F 18 KW - 2C598205QX KW - Dihydroxyphenylalanine KW - 63-84-3 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Drug Stability KW - Humans KW - Electrochemistry KW - Quality Control KW - Chromatography, High Pressure Liquid KW - Dihydroxyphenylalanine -- standards KW - Dihydroxyphenylalanine -- analysis KW - Tomography, Emission-Computed KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Dihydroxyphenylalanine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79060242?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-10 N1 - Date created - 1989-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Nucl Med. 1990 Dec;31(12):2076-7 [2125067] J Nucl Med. 1991 May;32(5):894-5 [1902510] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Testosterone selectively influences protein kinase-C-coupled secretion of proluteinizing hormone-releasing hormone-derived peptides. AN - 79057134; 2661212 AB - LHRH and GnRH-associated peptide (GAP) are two major pro-LHRH-derived peptides which are secreted from median eminence (ME) nerve terminals in vitro. The purpose of the present experiment was to determine whether manipulation of gonadal steroid levels in vivo influenced selectively the in vitro secretion of LHRH and GAP under basal or K+ and phorbol ester (PDBu) stimulation. Secretion of both peptides under each of these three conditions was reduced at least 2-fold in 2-week orchidectomized (ORDX) rats relative to the level in intact controls. Tissue stores of LHRH and GAP were also depressed in the ME of ORDX relative to control rats. When the data were expressed in terms of the percentage of peptide secreted per ME, both groups secreted similar percentages of the peptides into the medium under basal and K+-stimulated conditions. Interestingly, PDBu-activated secretion of LHRH and GAP remained depressed in ORDX animals. The nerve terminals from ORDX animals were not susceptible to a more rapid depletion of releasable peptides, since both groups secreted similar percentages of the peptides during repeated K+ depolarization. By comparison, protein kinase C (PKC)-coupled secretion from ORDX rats was selectively affected, since secretion of pro-LHRH-derived peptides became even more depressed with successive activation with PDBu. Immediate replacement with testosterone after ORDX fully restored the peptide levels in tissue and the LHRH and GAP secretory response to PKC activation. Since testosterone influenced both tissue stores and PDBu-stimulated secretion of LHRH and GAP, this steroid may selectively regulate biosynthesis and secretion of pro-LHRH-derived peptides through activation of the metabolic cascade involving the PKC system. JF - Endocrinology AU - Wetsel, W C AU - Negro-Vilar, A AD - Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 538 EP - 547 VL - 125 IS - 1 SN - 0013-7227, 0013-7227 KW - Protein Precursors KW - 0 KW - gonadotropin releasing hormone associated peptide KW - 124375-77-5 KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - Testosterone KW - 3XMK78S47O KW - Protein Kinase C KW - EC 2.7.11.13 KW - Potassium KW - RWP5GA015D KW - Abridged Index Medicus KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Animals KW - Median Eminence -- secretion KW - Potassium -- pharmacology KW - Male KW - Phorbol 12,13-Dibutyrate -- pharmacology KW - Orchiectomy KW - Protein Kinase C -- metabolism KW - Testosterone -- pharmacology KW - Protein Precursors -- secretion KW - Gonadotropin-Releasing Hormone -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79057134?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-02 N1 - Date created - 1989-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung. AN - 79051537; 2567993 AB - Activation of protooncogenes and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer (23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Furthermore, in 7 of these 8 squamous-cell carcinomas, loss of heterozygosity from chromosome 17 was accompanied by loss of DNA sequences from chromosome 11. The spectrum of allelic sequences lost from chromosome 11 was, however, similar in every type of carcinoma studied, and the data show two regions commonly deleted from chromosome 11 (11pter-p15.5 and 11p13-q13) that may have a role in the pathogenesis of all these types of non-small-cell bronchogenic carcinoma. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous-i.e., informative. These data included only 6 of 16 cases where loss of heterozygosity involved a chromosomal locus previously shown to be lost consistently in small-cell lung cancer (DNF15S2). Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Weston, A AU - Willey, J C AU - Modali, R AU - Sugimura, H AU - McDowell, E M AU - Resau, J AU - Light, B AU - Haugen, A AU - Mann, D L AU - Trump, B F AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 5099 EP - 5103 VL - 86 IS - 13 SN - 0027-8424, 0027-8424 KW - Index Medicus KW - Heterozygote Detection KW - Polymorphism, Restriction Fragment Length KW - Humans KW - Proto-Oncogenes KW - Chromosomes, Human, Pair 17 KW - Chromosomes, Human, Pair 3 KW - Chromosome Deletion KW - Carcinoma, Squamous Cell -- genetics KW - Lung Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Chromosomes, Human, Pair 13 KW - Carcinoma, Small Cell -- genetics KW - Chromosomes, Human, Pair 11 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79051537?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-10 N1 - Date created - 1989-08-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Nature. 1986 Oct 16-22;323(6089):643-6 [2877398] Nature. 1983 Oct 13-19;305(5935):641-3 [6312329] Cancer Genet Cytogenet. 1985 Feb 15;15(3-4):335-47 [2982476] Nature. 1985 Jul 25-31;316(6026):330-4 [2991766] Annu Rev Genet. 1986;20:231-51 [2880556] Science. 1987 Mar 13;235(4794):1394-9 [3823889] Am J Hum Genet. 1987 May;40(5):413-20 [2883892] Nature. 1987 Jun 25-Jul 1;327(6124):721-4 [2885753] Proc Natl Acad Sci U S A. 1987 Aug;84(15):5419-23 [3037550] Nature. 1987 Aug 13-19;328(6131):616-9 [2886919] N Engl J Med. 1987 Oct 29;317(18):1109-13 [2821398] Nature. 1987 Oct 1-7;329(6138):451-4 [2821400] Nature. 1987 Oct 15-21;329(6140):645-7 [3657988] Science. 1987 Oct 9;238(4824):193-7 [2889267] Cancer Res. 1987 Nov 1;47(21):5518-27 [2889524] Nature. 1987 Dec 10-16;330(6148):578-81 [2825033] Cancer Res. 1988 Feb 1;48(3):682-5 [2891438] Nature. 1988 Jan 21;331(6153):273-7 [2827040] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9252-6 [2892196] Proc Natl Acad Sci U S A. 1987 Dec;84(24):9275-9 [2892198] Jpn J Cancer Res. 1987 Dec;78(12):1302-8 [2892820] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1571-5 [2894030] Nature. 1988 Mar 3;332(6159):85-7 [2894610] Science. 1988 Jul 15;241(4863):353-7 [2838909] J Clin Invest. 1988 Aug;82(2):502-7 [2900253] Oncogene Res. 1988;3(4):401-8 [3067190] Science. 1989 Apr 14;244(4901):217-21 [2649981] Mol Carcinog. 1988;1(3):151-60 [2855021] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6216-20 [2994066] Nature. 1985 Nov 28-Dec 4;318(6044):377-80 [2999610] Proc Natl Acad Sci U S A. 1985 Dec;82(24):8592-6 [3001710] Annu Rev Biochem. 1986;55:831-54 [3017198] Nature. 1986 Aug 14-20;322(6080):644-7 [3092103] Hum Genet. 1981;57(3):300-6 [6114032] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cardiac morphologic and functional changes induced by epirubicin chemotherapy. AN - 79048174; 2738625 AB - Cardiac toxicity was evaluated in 24 patients who received epirubicin as a single chemotherapeutic agent, in doses of either 30 mg/m2 every week (11 patients) or 90 mg/m2 every 3 weeks (13 patients). The total doses of epirubicin ranged from 180 mg/m2 to 918 mg/m2 (mean, 491 +/- 187). No patient had prior heart disease, hypertension, mediastinal irradiation, or chemotherapy with other anthracycline agents. None of the patients developed overt heart failure, significant arrhythmias, ECG alterations, or roentgenographic changes in heart size. There was no significant change in the mean value of echocardiographic percent fractional shortening before and after epirubicin therapy. Patients receiving epirubicin doses less than 450 mg/m2 had minimal hemodynamic disturbances; however, no cut-off point separating two significantly different subpopulations could be demonstrated. Endomyocardial biopsy was performed on all patients; 20 biopsies were evaluable. Histologic and ultrastructural changes were similar to those caused by other anthracycline agents. A strong correlation was demonstrated between total dose of epirubicin and pathologic change as quantified using the Billingham scale (r = .7, P = .0006). A cut-off point beyond which there was a probability of increased pathologic damage was statistically defined at 450 mg/m2 of epirubicin. Severe pathologic alterations and moderate hemodynamic changes were observed in only one patient, who received 918 mg/m2 of epirubicin. Patients who are expected to receive epirubicin in excess of 450 mg/m2 should be monitored for cardiac toxicity, and continuation of epirubicin therapy beyond 900 mg/m2 should be based on the results of monitoring. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dardir, M D AU - Ferrans, V J AU - Mikhael, Y S AU - el-Grindy, M S AU - el-Aasar, A B AU - el-Zawahry, H M AU - Alling, D W AU - Banks, S M AU - el-Mawla, N G AD - Ultrastructure Section, National Heart, Lung and Blood Institute, Bethesda, MD. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 947 EP - 958 VL - 7 IS - 7 SN - 0732-183X, 0732-183X KW - Epirubicin KW - 3Z8479ZZ5X KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Humans KW - Adult KW - Urinary Bladder Neoplasms -- drug therapy KW - Middle Aged KW - Male KW - Female KW - Epirubicin -- therapeutic use KW - Heart Diseases -- chemically induced KW - Epirubicin -- adverse effects KW - Heart Diseases -- physiopathology KW - Heart Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79048174?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-01 N1 - Date created - 1989-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer. AN - 79047814; 2661735 AB - The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Swain, S M AU - Lippman, M E AU - Egan, E F AU - Drake, J C AU - Steinberg, S M AU - Allegra, C J AD - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 890 EP - 899 VL - 7 IS - 7 SN - 0732-183X, 0732-183X KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Fluorouracil -- administration & dosage KW - Leucovorin -- administration & dosage KW - Humans KW - Adult KW - Neoplasm Metastasis KW - Clinical Trials as Topic KW - Aged KW - Middle Aged KW - Fluorouracil -- metabolism KW - Thymidylate Synthase -- metabolism KW - Leucovorin -- metabolism KW - Menopause KW - Female KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Breast Neoplasms -- enzymology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79047814?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-01 N1 - Date created - 1989-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Family history of alcoholism in violent offenders and impulsive fire setters. AN - 79047318; 2472125 AB - Fifty-six of 58 violent offenders and impulsive fire setters fulfilled the DSM-III criteria for alcohol abuse. Information necessary for evaluation of family history of alcoholism was obtained on 54 subjects. Forty-four of the 54 subjects had first- or second-degree blood relatives with alcoholism. Thirty-five had alcoholic fathers. Subjects with alcoholic fathers had a lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration and were more often impulsive than subjects without alcoholic fathers. JF - Archives of general psychiatry AU - Linnoila, M AU - De Jong, J AU - Virkkunen, M AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 613 EP - 616 VL - 46 IS - 7 SN - 0003-990X, 0003-990X KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Abridged Index Medicus KW - Index Medicus KW - Sex Factors KW - Humans KW - Adult KW - Fathers -- psychology KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Male KW - Female KW - Disruptive, Impulse Control, and Conduct Disorders -- genetics KW - Firesetting Behavior -- genetics KW - Firesetting Behavior -- cerebrospinal fluid KW - Impulsive Behavior -- cerebrospinal fluid KW - Criminal Psychology KW - Impulsive Behavior -- genetics KW - Alcoholism -- genetics KW - Violence KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79047318?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-27 N1 - Date created - 1989-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Modulation of CD3- large granular lymphocyte functions by agonist and antagonists of protein kinase C: effects on NK and lymphokine-activated killer activity and production of IFN-gamma. AN - 79044957; 2543702 AB - The biochemical mechanisms involved in the activation and killing of tumor targets by large granular lymphocytes (LGL) have not yet been clearly defined. This laboratory has investigated these processes by analyzing the effects of protein kinase C (PKC) inhibitors (1-(5-isoquinolinesulfonyl)2-methyl-piperazine-dihydrochloride and retinol) on LGL cytotoxicity and IFN-gamma production. We now report that PKC inhibitors block the LGL functions of 1) NK activity, 2) IFN-gamma production, and 3) LAK activity induced by IL-2. Complete inhibition of cytotoxic activity occurs rapidly because only 2.5 h treatment of the LGL with the inhibitors was required. However, the inhibition of NK activity by the PKC inhibitors could be reversed by IL-2 or the synthetic diacylglycerol, L-gamma-1-oleyl-2-acetol-sn-3-glycerol (OAG), but not by IFN-alpha. The reversal of inhibition observed with OAG indicates that, in these studies, (1-(5-isoquinolinesulfonyl)2-methyl-piperazine-dihydrochloride is inhibiting PKC activity and not the activity of other cellular kinases. Furthermore, inhibition of LGL functional activity with PGE2 could not be reversed with OAG, supporting the contention that PG inhibition of NK activity is mediated by a pathway that does not directly involve PKC. These results indicate, in addition to IL-2-mediated events, that basal NK activity is under PKC regulatory control. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ortaldo, J R AU - Young, H A AU - Varesio, L AD - Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD 21701-1013. Y1 - 1989/07/01/ PY - 1989 DA - 1989 Jul 01 SP - 366 EP - 371 VL - 143 IS - 1 SN - 0022-1767, 0022-1767 KW - Antigens, CD3 KW - 0 KW - Antigens, Differentiation, T-Lymphocyte KW - Diglycerides KW - Interleukin-2 KW - Isoquinolines KW - Piperazines KW - Receptors, Antigen, T-Cell KW - Vitamin A KW - 11103-57-4 KW - Interferon-gamma KW - 82115-62-6 KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine KW - 84477-87-2 KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Dinoprostone KW - K7Q1JQR04M KW - Abridged Index Medicus KW - Index Medicus KW - Isoquinolines -- pharmacology KW - Dinoprostone -- pharmacology KW - Diglycerides -- pharmacology KW - Humans KW - Vitamin A -- pharmacology KW - Cytotoxicity Tests, Immunologic KW - Cyclic AMP -- physiology KW - Piperazines -- pharmacology KW - Protein Kinase C -- metabolism KW - Lymphocyte Activation -- drug effects KW - Protein Kinase C -- antagonists & inhibitors KW - Interferon-gamma -- biosynthesis KW - Cytotoxicity, Immunologic -- drug effects KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - Killer Cells, Natural -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79044957?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-21 N1 - Date created - 1989-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Effective pharmacotherapy of alcoholic amnestic disorder with fluvoxamine. Preliminary findings. AN - 79027836; 2472126 AB - Ten patients with alcoholic chronic organic brain disease were categorized as having alcohol amnestic disorder, or Korsakoff's psychosis (n = 6), dementia associated with alcoholism (n = 3), or compensated alcoholic liver disease (n = 1). All patients had severe deficits in memory for recently acquired information (episodic memory). Patients with alcohol dementia also showed global intellectual decline, including decreased performance on measures of semantic (knowledge) memory and reduction in levels of cerebrospinal fluid somatostatin. In a 4-week double-blind crossover design, the serotonin-uptake blocker fluvoxamine maleate (100 to 200 mg/d) was found to improve episodic memory in only the patients with alcohol amnestic disorder. These improvements in memory were significantly correlated with reductions in levels of cerebrospinal fluid 5-hydroxyindoleacetic acid, suggesting that facilitation of serotonergic neurotransmission may ameliorate the episodic memory failure in patients with alcohol amnestic disorder. JF - Archives of general psychiatry AU - Martin, P R AU - Adinoff, B AU - Eckardt, M J AU - Stapleton, J M AU - Bone, G A AU - Rubinow, D R AU - Lane, E A AU - Linnoila, M AD - Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 617 EP - 621 VL - 46 IS - 7 SN - 0003-990X, 0003-990X KW - Oximes KW - 0 KW - Serotonin Antagonists KW - Somatostatin KW - 51110-01-1 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Fluvoxamine KW - O4L1XPO44W KW - Abridged Index Medicus KW - Index Medicus KW - Somatostatin -- cerebrospinal fluid KW - Double-Blind Method KW - Memory -- drug effects KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Wechsler Scales KW - Middle Aged KW - Psychoses, Alcoholic -- blood KW - Psychoses, Alcoholic -- psychology KW - Psychoses, Alcoholic -- drug therapy KW - Female KW - Male KW - Serotonin Antagonists -- therapeutic use KW - Oximes -- blood KW - Oximes -- therapeutic use KW - Serotonin Antagonists -- blood KW - Alcohol Amnestic Disorder -- psychology KW - Alcohol Amnestic Disorder -- cerebrospinal fluid KW - Alcohol Amnestic Disorder -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79027836?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-27 N1 - Date created - 1989-07-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Arch Gen Psychiatry. 1990 Oct;47(10):978-9 [2121117] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype. AN - 79025808; 2731181 AB - The risk of lung cancer in smokers was examined based on the debrisoquine metabolic phenotype and on exposure to occupational lung carcinogens, specifically asbestos and polycyclic aromatic hydrocarbons. Extensive metabolizers of debrisoquine are at a 4-fold increased risk for lung cancer compared to poor metabolizers, after adjustment for age, sex, and smoking (pack-years), when only occupationally unexposed subjects are considered. Increased risk related to the debrisoquine metabolic phenotype was greatest for squamous and small cell histologies, and least for the adenocarcinoma subtype. Men with a history of exposure to occupational carcinogens had significantly increased risk of lung cancer (relative risk = 2.8), after adjustment for age and smoking. Considering the combined effect of the high risk extensive metabolizers debrisoquine metabolic phenotype and likely occupational exposure to asbestos, the relative excess risk for lung cancer was 18-fold. This finding is consistent with a synergism in risk between the ability to extensively metabolize debrisoquine and occupational exposure to lung carcinogens in male smokers. Debrisoquine phenotyping has potential for identifying carcinogen-exposed workers at high risk of lung cancer. JF - Cancer research AU - Caporaso, N AU - Hayes, R B AU - Dosemeci, M AU - Hoover, R AU - Ayesh, R AU - Hetzel, M AU - Idle, J AD - Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/07/01/ PY - 1989 DA - 1989 Jul 01 SP - 3675 EP - 3679 VL - 49 IS - 13 SN - 0008-5472, 0008-5472 KW - Isoquinolines KW - 0 KW - Polycyclic Compounds KW - Asbestos KW - 1332-21-4 KW - Debrisoquin KW - X31CDK040E KW - Index Medicus KW - Oxidation-Reduction KW - Smoking KW - Risk Factors KW - Humans KW - Lung Diseases, Obstructive -- epidemiology KW - Male KW - Female KW - Lung Neoplasms -- epidemiology KW - Debrisoquin -- metabolism KW - Isoquinolines -- metabolism KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79025808?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-27 N1 - Date created - 1989-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Conditions associated with hepatocellular carcinoma. AN - 79018332; 2542707 AB - The most important condition associated with hepatocellular carcinoma is chronic hepatitis B virus infection. This article summarizes the information linking hepatocellular carcinoma with conditions other than hepatitis B virus infection. JF - The Medical clinics of North America AU - Lisker-Melman, M AU - Martin, P AU - Hoofnagle, J H AD - Liver Diseases Section, National Institutes of Health, Bethesda, Maryland. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 999 EP - 1009 VL - 73 IS - 4 SN - 0025-7125, 0025-7125 KW - Aflatoxins KW - 0 KW - Androgens KW - Estrogens KW - Thorium Dioxide KW - 9XA7X17UQC KW - Abridged Index Medicus KW - Index Medicus KW - Thorium Dioxide -- adverse effects KW - Hepatitis, Chronic KW - Hepatitis C -- complications KW - Humans KW - Androgens -- adverse effects KW - Estrogens -- adverse effects KW - Male KW - Female KW - Aflatoxins -- adverse effects KW - Liver Diseases -- complications KW - Carcinoma, Hepatocellular -- etiology KW - Liver Neoplasms -- chemically induced KW - Metabolic Diseases -- complications KW - Liver Diseases -- classification KW - Liver Neoplasms -- etiology KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79018332?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-07 N1 - Date created - 1989-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences. AN - 79017752; 2786091 AB - One potent transcriptional activator of human T-cell leukemia virus type I (HTLV-I) is virally encoded protein Tax (p40x). p40x trans-activates HTLV-I through the long terminal repeat (LTR) by using a triply repeated 21-base-pair sequence as the target. In this report we have characterized the induction of the HTLV-I LTR by 12-O-tetradecanoylphorbol-13-acetate (TPA). By assaying progressively deleted mutations in the HTLV-I LTR, we have delimited a 60-base-pair sequence in the LTR which is capable of conferring TPA responsiveness, but not p40x responsiveness, to heterologous promoters in a position-independent fashion. This HTLV-I TPA-responsive element is specifically recognized by preexisting factors from uninfected cells. We show that activation of this sequence by phorbol ester does not require de novo cellular protein synthesis. When the HTLV-I LTR was simultaneously activated by both Tax and TPA, an additive effect was seen. This suggests the use of distinct regulatory pathways by the two respective trans-activators. JF - Journal of virology AU - Radonovich, M AU - Jeang, K T AD - Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 2987 EP - 2994 VL - 63 IS - 7 SN - 0022-538X, 0022-538X KW - HTLV-I Antigens KW - 0 KW - Trans-Activators KW - Transcription Factors KW - Cycloheximide KW - 98600C0908 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - HeLa Cells -- metabolism KW - Base Sequence KW - Transcription, Genetic -- drug effects KW - Humans KW - Cycloheximide -- pharmacology KW - Genes -- drug effects KW - Molecular Sequence Data KW - Repetitive Sequences, Nucleic Acid KW - Transcription Factors -- physiology KW - Human T-lymphotropic virus 1 -- genetics KW - HTLV-I Antigens -- physiology KW - Human T-lymphotropic virus 1 -- drug effects KW - Genes, Viral -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Transcription Factors -- genetics KW - HTLV-I Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79017752?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-13 N1 - Date created - 1989-07-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1987 Jul;7(7):2610-3 [3475568] Nature. 1987 Apr 16-22;326(6114):711-3 [3031512] Science. 1987 Sep 11;237(4820):1324-9 [2888190] Nature. 1987 Oct 15-21;329(6140):648-51 [2821407] Cell. 1987 Jun 19;49(6):729-39 [3034432] Cell. 1987 Jun 19;49(6):741-52 [3034433] J Virol. 1987 Jul;61(7):2175-81 [3035218] J Biol Chem. 1987 Jun 25;262(18):8743-7 [3036825] Nature. 1987 Jul 9-15;328(6126):175-8 [2885756] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845-9 [3498942] Mol Cell Biol. 1987 Oct;7(10):3759-66 [3500398] Science. 1987 Dec 11;238(4833):1575-8 [2825351] Proc Natl Acad Sci U S A. 1988 Mar;85(5):1457-61 [2830620] J Virol. 1988 Apr;62(4):1339-46 [2831395] Nature. 1988 Jun 9;333(6173):504 [2836736] Nature. 1988 Jun 23;333(6175):776-8 [2838755] Science. 1988 Jul 1;241(4861):89-92 [2838905] Cell. 1988 Aug 12;54(4):541-52 [3135940] Cell. 1988 Aug 12;54(4):553-60 [3135941] Nature. 1988 Aug 11;334(6182):494-8 [2900470] Cell. 1988 Sep 23;54(7):1033-42 [3416354] Science. 1988 Sep 23;241(4873):1652-5 [2843985] Science. 1988 Oct 28;242(4878):540-6 [3140380] J Virol. 1988 Dec;62(12):4499-509 [3263510] Proc Natl Acad Sci U S A. 1988 Nov;85(21):7922-6 [2847147] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8291-5 [2847157] Genes Dev. 1988 Sep;2(9):1055-62 [2847958] Genes Dev. 1988 Oct;2(10):1216-26 [3144478] Nucleic Acids Res. 1978 Sep;5(9):3157-70 [212715] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Nucleic Acids Res. 1981 Jul 10;9(13):3047-60 [6269071] Nucleic Acids Res. 1981 Dec 11;9(23):6505-25 [6275366] Mol Cell Biol. 1982 Sep;2(9):1044-51 [6960240] Proc Natl Acad Sci U S A. 1982 Nov;79(22):6899-902 [6294664] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618-22 [6304725] J Virol. 1983 Oct;48(1):135-48 [6310141] Cell. 1983 Dec;35(3 Pt 2):603-10 [6606489] J Virol. 1984 Jan;49(1):183-9 [6690710] Nature. 1984 Apr 19-25;308(5961):693-8 [6232463] Science. 1984 Oct 5;226(4670):57-61 [6089350] Nature. 1984 Oct 4-10;311(5985):433-8 [6090941] Virology. 1984 Dec;139(2):340-5 [6097028] Cell. 1985 May;41(1):3-5 [2986847] J Biol Chem. 1985 Sep 25;260(21):11852-8 [3930485] Science. 1986 Jul 18;233(4761):305-12 [3014651] Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558-62 [3018737] Proc Natl Acad Sci U S A. 1986 Sep;83(18):6682-6 [2875459] Nature. 1986 Oct 9-15;323(6088):555-8 [3020435] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7192-6 [3020538] Virology. 1986 Oct 30;154(2):249-58 [3639669] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112-6 [3022280] EMBO J. 1986 Nov;5(11):2883-8 [3024966] Cell. 1987 Jan 30;48(2):251-60 [3026638] J Virol. 1987 Mar;61(3):708-13 [3027397] Cell. 1987 Apr 10;49(1):47-56 [3030566] Nature. 1987 Sep 3-9;329(6134):73-5 [2442617] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Chemoimmunotoxin therapy against a human colon tumor (HT-29) xenografted into nude mice. AN - 79011914; 2499420 AB - The efficacy of intracavitary chemoimmunotoxin therapy for cancer treatment was evaluated using the human colon carcinoma (HT-29) which had been xenografted i.p. into nude mice. Mice bearing HT-29 were treated with an immunotoxin consisting of the monoclonal antibody OVB3 coupled to Pseudomonas exotoxin (OVB3-PE), with cyclophosphamide (Cy), or with both OVB3-PE plus Cy. Mice given injections i.p. of 3 x 10(6) HT-29 ascites cells developed a localized disease that presented as both malignant ascites and solid tumor confined to the peritoneal cavity. All mice died within 30 to 40 days. Mice that received either three or six injections of OVB3-PE at a dose of 0.5 micrograms every other day beginning 3 days post-tumor inoculation exhibited significantly increased median survival times (MSTs) (P = 0.002) of 62 and 68 days, respectively, as compared to a MST of 33 days for the controls. OVB3 alone or an irrelevant monoclonal antibody conjugated to PE exhibited no antitumor activity. The therapeutic effects of the immunotoxin could be blocked by giving a large amount of unconjugated OVB3 at the same time. Treatment of mice with Cy alone at the maximal tolerated dose (250 mg/kg) on Days 10 and 17 after tumor inoculation increased the MST from 33 days to 54 days. The maximum tolerated dose could be increased to 300 mg/kg per injection if the Cy treatment was preceded by 100 mg/kg of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721), a sulfhydryl compound that selectively protects normal tissue against the toxicity of radiation and alkylating agents. Cy plus WR-2721 treatment on Days 10 and 17 increased the MST from 35 to 61 days (P = 0.002). Interestingly, groups of mice that received either two, four, or seven treatments of OVB3-PE following Cy plus WR-2721 therapy exhibited a further increase (P less than 0.002) in MSTs to 81, 87, and 96 days, respectively. Thus, the combination of cytoreductive chemotherapy with the OVB3-PE was significantly more effective for the intracavitary treatment of established HT-29 colon cancer xenografts than either chemotherapy or immunotoxin therapy alone. JF - Cancer research AU - Pearson, J W AU - FitzGerald, D J AU - Willingham, M C AU - Wiltrout, R H AU - Pastan, I AU - Longo, D L AD - Laboratory of Experimental Immunology, NCI-Frederick Cancer Research Facility, Maryland 21701. Y1 - 1989/07/01/ PY - 1989 DA - 1989 Jul 01 SP - 3562 EP - 3567 VL - 49 IS - 13 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Virulence Factors KW - Cyclophosphamide KW - 8N3DW7272P KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Animals KW - Combined Modality Therapy KW - Humans KW - Drug Resistance KW - Mice KW - Mice, Nude KW - Antibodies, Monoclonal -- immunology KW - Neoplasm Transplantation KW - Cyclophosphamide -- therapeutic use KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Ascites KW - In Vitro Techniques KW - Pseudomonas aeruginosa KW - Antigens, Neoplasm -- immunology KW - Exotoxins -- administration & dosage KW - Colonic Neoplasms -- therapy KW - Immunotoxins -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79011914?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-27 N1 - Date created - 1989-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Activation of the c-H-ras proto-oncogene by retrovirus insertion and chromosomal rearrangement in a Moloney leukemia virus-induced T-cell leukemia. AN - 78992102; 2542606 AB - A rearrangement of the c-H-ras locus was detected in a T-cell line (DA-2) established from a Moloney leukemia virus-induced tumor. This rearrangement was associated with the high-level expression of H-ras RNA and the H-ras gene product, p21. DNA from DA-2 cells transformed fibroblasts in DNA transfection experiments, and the transformed fibroblasts contained the rearranged H-ras locus. The rearrangement involved one allele and was present in tissue from the primary tumor from which the cell line was isolated. Cloning and sequencing of the rearranged allele and comparison with the normal allele demonstrated that the rearrangement was complex and probably resulted from the integration of a retrovirus in the H-ras locus between a 5' noncoding exon and the first coding exon and a subsequent homologous recombination between this provirus and another newly acquired provirus also located on chromosome 7. These events resulted in the translocation of the coding exons of the H-ras locus away from the 5' noncoding exon region to a new genomic site on chromosome 7. Sequencing of the coding regions of the gene failed to detect mutations in the 12th, 13th, 59th, or 61st codons. The possible reasons for the complexity of the rearrangement and the significance of the activation of the H-ras locus to T-cell transformation are discussed. JF - Journal of virology AU - Ihle, J N AU - Smith-White, B AU - Sisson, B AU - Parker, D AU - Blair, D G AU - Schultz, A AU - Kozak, C AU - Lunsford, R D AU - Askew, D AU - Weinstein, Y AD - Molecular Mechanisms of Carcinogenesis Laboratory, National Cancer Institute-Frederick, Cancer Research Facility, Maryland 21701. Y1 - 1989/07// PY - 1989 DA - July 1989 SP - 2959 EP - 2966 VL - 63 IS - 7 SN - 0022-538X, 0022-538X KW - DNA Transposable Elements KW - 0 KW - Membrane Proteins KW - Proto-Oncogene Proteins KW - RNA, Viral KW - HRAS protein, human KW - EC 3.6.5.2 KW - Proto-Oncogene Proteins p21(ras) KW - Index Medicus KW - Animals KW - Immunoblotting KW - Humans KW - Gene Rearrangement KW - Mice KW - Nucleic Acid Hybridization KW - Cloning, Molecular KW - Alleles KW - Base Sequence KW - Transfection KW - Restriction Mapping KW - Molecular Sequence Data KW - RNA, Viral -- genetics KW - Cell Line KW - Cell Transformation, Neoplastic KW - Genes, ras KW - Leukemia, T-Cell -- genetics KW - Leukemia, T-Cell -- microbiology KW - Moloney murine leukemia virus -- genetics KW - Gene Expression Regulation KW - Membrane Proteins -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Leukemia, Experimental -- microbiology KW - Leukemia, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78992102?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-13 N1 - Date created - 1989-07-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - M27193; GENBANK N1 - SuppNotes - Cited By: Exp Cell Res. 1977 Mar 1;105(1):109-17 [65290] Cell. 1988 Sep 9;54(6):831-40 [2842066] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Virology. 1978 Oct 1;90(1):23-35 [82294] Science. 1979 Apr 6;204(4388):69-71 [219475] J Virol. 1979 Apr;30(1):255-66 [480454] Biochemistry. 1979 Nov 27;18(24):5294-9 [518835] Science. 1985 Dec 20;230(4732):1378-81 [2999983] Proc Natl Acad Sci U S A. 1986 Mar;83(6):1651-5 [3513183] EMBO J. 1986 Feb;5(2):301-9 [3011401] Science. 1986 Jun 13;232(4756):1410-3 [3012774] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5010-4 [3014527] Eur J Biochem. 1987 May 15;165(1):7-12 [3494605] J Virol. 1987 Jul;61(7):2339-43 [2884332] J Virol. 1987 Aug;61(8):2489-98 [3037111] Mol Cell Biol. 1987 Aug;7(8):2933-40 [3670300] Methods Enzymol. 1980;65(1):499-560 [6246368] J Virol. 1980 Nov;36(2):408-20 [6253666] Proc Natl Acad Sci U S A. 1980 Jul;77(7):3937-41 [6254003] Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201-5 [6159641] Cell. 1981 Feb;23(2):311-22 [6258797] Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328-32 [6267583] Proc Natl Acad Sci U S A. 1981 Jun;78(6):3418-22 [6267589] J Virol. 1981 Jul;39(1):1-10 [6268802] Nature. 1982 Jun 10;297(5866):479-83 [6283358] J Exp Med. 1982 Sep 1;156(3):873-87 [6286838] J Virol. 1982 Jul;43(1):294-304 [6287003] Nature. 1982 Nov 11;300(5888):143-9 [6290897] Nature. 1982 Nov 11;300(5888):149-52 [7133135] J Virol. 1982 Oct;44(1):19-31 [7143566] Science. 1982 Dec 10;218(4577):1122-5 [6293052] Nature. 1982 Dec 23;300(5894):762-5 [7177195] Nature. 1983 Mar 3;302(5903):33-7 [6298635] Science. 1983 Jul 8;221(4606):155-7 [6344220] J Virol. 1983 Jul;47(1):217-20 [6864883] Nature. 1983 Jun 30;303(5920):775-9 [6866079] Proc Natl Acad Sci U S A. 1984 Jan;81(1):202-5 [6582476] Proc Natl Acad Sci U S A. 1984 Jul;81(13):4008-12 [6330729] J Virol. 1985 Mar;53(3):984-7 [2983103] Annu Rev Genet. 1984;18:553-612 [6397126] Proc Natl Acad Sci U S A. 1985 Oct;82(19):6687-91 [2995979] J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] J Virol. 1988 Mar;62(3):788-94 [3276924] Somatic Cell Genet. 1975 Oct;1(4):371-82 [1235912] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3). AN - 79081280; 2748347 JF - Nucleic acids research AU - Yamano, S AU - Nagata, K AU - Yamazoe, Y AU - Kato, R AU - Gelboin, H V AU - Gonzalez, F J AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda 20892. Y1 - 1989/06/26/ PY - 1989 DA - 1989 Jun 26 SP - 4888 VL - 17 IS - 12 SN - 0305-1048, 0305-1048 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - DNA -- isolation & purification KW - Genes KW - Cytochrome P-450 Enzyme System -- genetics KW - Cytochrome P-450 Enzyme System -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79081280?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-25 N1 - Date created - 1989-08-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - X13929; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1985 Feb;82(4):983-7 [3856261] DNA. 1989 Jan-Feb;8(1):1-13 [2651058] J Biol Chem. 1988 Mar 25;263(9):4166-71 [3346244] J Biol Chem. 1987 Feb 25;262(6):2787-93 [3818621] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - T cell activation induces rapid tyrosine phosphorylation of a limited number of cellular substrates. AN - 79042294; 2786526 AB - Activation of murine T cells by antigen, antibodies binding the T cell antigen receptor, or stimulatory anti-Thy-1 antibodies results in rapid phosphorylation of the T cell receptor zeta chain on tyrosine residues. The T cell receptor is itself unlikely to be a tyrosine kinase; rather, it is probable that this receptor is coupled to a nonreceptor tyrosine kinase. To understand further this protein kinase pathway, additional targets of the tyrosine kinase have been sought by comparing anti-phosphotyrosine antibody immunoblots of cellular proteins from unactivated and activated T cell hybridomas. In addition to the T cell receptor zeta chain, two proteins of 53 and 62 kDa are phosphorylated on tyrosine residues after T cell activation. These phosphorylations require stimulatory anti-Thy-1 antibodies, antigen, or antireceptor antibody stimulation. The 53-kDa protein is preferentially phosphorylated by antigen or antireceptor antibody. Of interest is that variants of the murine T cell hybridoma lacking the T cell receptor zeta chain or lacking surface antigen receptor can nonetheless be stimulated by anti-Thy-1 antibodies to phosphorylate the 62-kDa substrate. In contrast to the tyrosine kinases of oncogenic viruses, the kinase coupled to the T cell antigen receptor appears to have a limited number of targets. These proteins are candidates for critical substrates in this protein tyrosine kinase pathway. JF - The Journal of biological chemistry AU - Hsi, E D AU - Siegel, J N AU - Minami, Y AU - Luong, E T AU - Klausner, R D AU - Samelson, L E AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892. Y1 - 1989/06/25/ PY - 1989 DA - 1989 Jun 25 SP - 10836 EP - 10842 VL - 264 IS - 18 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Ethers KW - Macromolecular Substances KW - Receptors, Antigen, T-Cell KW - Ionomycin KW - 56092-81-0 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Hybridomas -- metabolism KW - Animals KW - Phosphorylation KW - Ethers -- pharmacology KW - Electrophoresis, Polyacrylamide Gel KW - Kinetics KW - Electrophoresis, Gel, Two-Dimensional KW - Hybridomas -- immunology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Mice KW - Substrate Specificity KW - Antibodies, Monoclonal -- immunology KW - Lymphocyte Activation KW - T-Lymphocytes -- metabolism KW - Receptors, Antigen, T-Cell -- metabolism KW - Protein-Tyrosine Kinases -- metabolism KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79042294?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-18 N1 - Date created - 1989-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. AN - 79039806; 2732228 AB - Immunoblotting analysis of human liver microsome preparations revealed that human cytochrome P-450 PCN1 (hPCN1, Mr approximately 52,000) was expressed in each of 40 individual specimens examined. In about 10-20% of the livers, an immunologically related protein having a lower electrophoretic mobility (Mr approximately 52,500) was also detected. A single liver was found that expressed only the lower mobility protein, designated hPCN3, and RNA isolated from this liver was used to construct a lambda gt11 library. The library was screened with an hPCN1 cDNA probe resulting in the isolation of a unique full-length cDNA that was sequenced and shown to encode hPCN3. The deduced amino acid sequence of this cDNA contained 502 residues, a calculated molecular mass of 57,115 daltons, and displayed 84% similarity with hPCN1. The deduced amino-terminal sequence of hPCN3 was identical to that of HFLa, a major cytochrome P-450 expressed in human fetal liver that is immunologically cross-reactive with several family III cytochrome P-450s. hPCN1 and hPCN3 cDNAs were expressed in Hep G2 cells using a vaccinia virus expression system and shown to encode active enzymes, both characterized by reduced CO-binding spectra with lambda max at 450 nm. Enzymatic analysis revealed that both cytochrome P-450s were similarly active in catalyzing oxidation of the calcium channel blocking drug nifedipine. Both enzymes also catalyzed 6 beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione, although hPCN1 exhibited several-fold higher expressed activity than hPCN3. Several minor oxidation products of these steroids (e.g. 15 beta-hydroxytestosterone), comprising up to approximately 20% of the total metabolites, were formed by hPCN1 but not hPCN3, indicating that hPCN3 is a more highly regiospecific monooxygenase catalyst with steroid substrates. Clear differences were also detected in their catalytic activities toward the immunosuppressive drug cyclosporine, with two hydroxylated metabolites (M1 and M17) and one demethylated metabolite (M21) formed by hPCN1 but only one metabolite (M1) formed by hPCN3. These studies establish that hPCN3 is a newly described cytochrome P-450 that is differentially expressed in the adult human population and that has overlapping substrate specificity compared to hPCN1 for metabolism of steroid and drug substrates. JF - The Journal of biological chemistry AU - Aoyama, T AU - Yamano, S AU - Waxman, D J AU - Lapenson, D P AU - Meyer, U A AU - Fischer, V AU - Tyndale, R AU - Inaba, T AU - Kalow, W AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/06/25/ PY - 1989 DA - 1989 Jun 25 SP - 10388 EP - 10395 VL - 264 IS - 18 SN - 0021-9258, 0021-9258 KW - Cyclosporins KW - 0 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - CYP3A4 protein, human KW - EC 1.14.13.67 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - CYP3A5 protein, human KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Vaccinia virus -- genetics KW - Immunoblotting KW - Animals KW - Base Sequence KW - Cyclosporins -- metabolism KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Substrate Specificity KW - Species Specificity KW - Cloning, Molecular KW - Mixed Function Oxygenases -- metabolism KW - Genes KW - Cytochrome P-450 Enzyme System -- genetics KW - Microsomes, Liver -- enzymology KW - DNA -- genetics KW - Cytochrome P-450 Enzyme System -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79039806?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-18 N1 - Date created - 1989-07-18 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - J04813; GENBANK N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cellular processing of a ricin-antibody conjugate. A kinetic analysis of the rate-limiting step. AN - 79021579; 2786524 AB - Upon exposure to holoricin-antibody conjugates, target cells display a period of no measurable intoxication followed by a concentration-dependent exponential decline in protein synthesis. The rate of this decline is increased by conjugate structural variables such as addition of a second ricin to the antibody or introduction of a peptide spacer between the toxin and antibody. Additionally, the rate is enhanced by the addition of ammonia or monensin. The relationship between immunotoxin concentration and the rate of protein synthesis inhibition is shown to obey typical Michaelis-Menten kinetics. By displacing bound immunotoxin with native antibody, it was demonstrated that the rate-limiting saturable process is not due to antibody-surface antigen interaction. Although addition of a second ricin as well as addition of ammonia elevated the measured rate of protein synthesis inhibition, curve-fitting techniques indicated that they did not elevate the maximal rate; however, introduction of a peptide spacer into the conjugate or addition of monensin increased the maximal rate of this saturable process. Additionally, the kinetic examination of the potentiation effects of ammonia and monensin indicates that they operate on different cellular processes involved with the intracellular routing toward intoxication. An equational model is developed which helps interpret the known features of the conjugate intoxication process. JF - The Journal of biological chemistry AU - Marsh, J W AD - Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892. Y1 - 1989/06/25/ PY - 1989 DA - 1989 Jun 25 SP - 10405 EP - 10410 VL - 264 IS - 18 SN - 0021-9258, 0021-9258 KW - Immunotoxins KW - 0 KW - Protein Synthesis Inhibitors KW - Ammonia KW - 7664-41-7 KW - Ricin KW - 9009-86-3 KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Ammonia -- pharmacology KW - Protein Biosynthesis KW - Kinetics KW - Leucine -- metabolism KW - Cell Line KW - Immunotoxins -- pharmacology KW - Ricin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79021579?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-18 N1 - Date created - 1989-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue. AN - 79045853; 2733794 AB - As a family of structurally-related enzymes, cytochrome P450 (P450) monooxygenases exhibit paradoxical characteristics: although collectively the enzymes display a broad range of substrate specificities, individually they are characterized by a high degree of substrate and product selectivity. Mouse P45015 alpha and P450coh, for example, which are expressed in female liver and male kidney cells, catalyse 15 alpha-hydroxylation of delta 4 3-ketone steroids, such as testosterone and 7-hydroxylation of coumarin, respectively. In spite of their divergent catalytic activities, however, these enzymes differ by only 11 amino acids within their 494 residues. To determine the structural basis of the different substrate specificities of P45015 alpha and P450coh we therefore altered each of these 11 residues by site-directed mutagenesis, expressing the mutant cytochromes in COS-1 cells. We report that the activities of both cytochromes depend critically on the identities of the amino acids at positions 117, 209 and 365 and, moreover, that a single mutation in which Phe 209 is substituted by Leu is sufficient to convert the specificity of P450coh from coumarin to steroid hydroxylation. JF - Nature AU - Lindberg, R L AU - Negishi, M AD - Pharmacogenetics Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/06/22/ PY - 1989 DA - 1989 Jun 22 SP - 632 EP - 634 VL - 339 IS - 6226 SN - 0028-0836, 0028-0836 KW - Amino Acids KW - 0 KW - Coumarins KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - coumarin KW - A4VZ22K1WT KW - Steroid Hydroxylases KW - EC 1.14.- KW - Index Medicus KW - Animals KW - Coumarins -- metabolism KW - Amino Acids -- genetics KW - Molecular Sequence Data KW - Steroid Hydroxylases -- metabolism KW - Mice KW - Amino Acid Sequence KW - Mutation KW - Cell Line KW - Cytochrome P-450 Enzyme System -- genetics KW - Substrate Specificity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79045853?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-20 N1 - Date created - 1989-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Polyacrylamide-streptavidin: a novel reagent for simplified construction of soluble multivalent macromolecular conjugates. AN - 79077439; 2738413 AB - We have developed a soluble macromolecular conjugation reagent, polyacrylamide-streptavidin (PASA), for the simplified preparation of multivalent protein-protein conjugates. Soluble linear polyacrylamide, with a molecular weight of approximately 10(6), has carboxyl groups generated by limited alkaline hydrolysis. It is then activated with carbodiimide, separated from excess carbodiimide, and conjugated to streptavidin. The resulting conjugate, which has approximately 20 streptavidin residues per molecule, can bind biotinylated proteins to produce homo- or heteroconjugates of known composition. We have used this technique to prepare soluble multivalent heteroligating antibody conjugates that can bind either of two antigenically distinct cell lines, as well as reagents that specifically label murine tumor cells with different MHC class I antigens. The method is potentially useful for making multivalent arrays of epitopes for measuring low affinity interactions such as that between the T cell receptor and MHC molecules, as well as for making immunotoxins, tumor labelling conjugates, and complex immunogens. JF - Journal of immunological methods AU - Nardelli, B AU - McHugh, L AU - Mage, M AD - Division of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/06/21/ PY - 1989 DA - 1989 Jun 21 SP - 233 EP - 239 VL - 120 IS - 2 SN - 0022-1759, 0022-1759 KW - Acrylic Resins KW - 0 KW - Antibodies KW - Bacterial Proteins KW - Carbodiimides KW - H-2 Antigens KW - Ligands KW - Macromolecular Substances KW - Biotin KW - 6SO6U10H04 KW - polyacrylamide KW - 9003-05-8 KW - Streptavidin KW - 9013-20-1 KW - Index Medicus KW - Chemistry KW - Chemical Phenomena KW - H-2 Antigens -- immunology KW - Flow Cytometry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79077439?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-08-02 N1 - Date created - 1989-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Tumorigenicity of human mesothelial cell line transfected with EJ-ras oncogene. AN - 79025989; 2733039 AB - We performed this study to determine whether human mesothelial cells are capable of undergoing neoplastic change in vitro and to observe their interaction with the activated c-Ha-ras (HRAS1) oncogene EJ-ras, which has a role in the development of many malignant human tumors. Mesothelial cells are presumed to be the progenitor cells of malignant mesothelioma, a cancer strongly correlated with asbestos exposure. Previously, we established a non-tumorigenic cell line, MeT-5A, from normal human mesothelial cells after transfection with a plasmid containing the simian virus 40 (SV40) early-region genes. In the present study, we performed transfection of a plasmid containing the EJ-ras gene and the neomycin-resistance gene into these cells and selected a population resistant to G418, a neomycin analogue. Cells from this cell line formed rapidly growing sc tumors in NIH Swiss athymic nude mice, but untransfected with the vector DNA and selected for G418 resistance formed no tumors. The tumors formed by EJ-ras-transfected cells were established in vitro, and cells from these tumor cell lines exhibited a characteristic altered morphology. The cells had the same isoenzyme phenotype as the parent cells, and they expressed the mutant EJ-ras p21 protein. This first demonstration of malignant transformation of human mesothelial cells in vitro may permit molecular analysis of mesothelial carcinogenesis. JF - Journal of the National Cancer Institute AU - Reddel, R R AU - Malan-Shibley, L AU - Gerwin, B I AU - Metcalf, R A AU - Harris, C C AD - Division of Cancer Etiology, National Cancer Institute, Bethesda, MD. Y1 - 1989/06/21/ PY - 1989 DA - 1989 Jun 21 SP - 945 EP - 948 VL - 81 IS - 12 SN - 0027-8874, 0027-8874 KW - Gentamicins KW - 0 KW - antibiotic G 418 KW - A08F5XTI6G KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Drug Resistance -- genetics KW - Transfection KW - Humans KW - Mice, Nude KW - Mice KW - Cell Line, Transformed KW - Gentamicins -- pharmacology KW - Oncogenes KW - Mesothelioma -- genetics KW - Mesothelioma -- pathology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79025989?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-18 N1 - Date created - 1989-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Characteristics of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced endotoxin hypersensitivity: association with hepatotoxicity. AN - 79030546; 2472021 AB - Hepatic clearance is a major route of endotoxin detoxification. In the present study, the potential relationship between TCDD-induced endotoxin hypersensitivity and hepatotoxicity was examined. Acute doses of 50, 100, or 200 micrograms TCDD/kg body weight induced an endotoxin hypersensitive state in B6C3F1 mice as demonstrated by increased mortality 24-48 h following i.v. injection of endotoxin. This hypersensitive state occurred when endotoxin was administered 7 days following TCDD exposure, but not 1 day post-TCDD exposure. TCDD did not affect endogenous serum endotoxin levels. However, clearance of injected endotoxin was significantly inhibited following exposure to TCDD. Six hours post endotoxin treatment serum triglycerides were significantly increased in TCDD/endotoxin-treated mice compared to either treatment alone. Methylprednisolone and uridine were both examined in this model due to their roles in inflammation and RNA synthesis, respectively. Both compounds significantly reversed the mortality associated with the combined exposure. [3H]Uridine incorporation into liver was decreased following TCDD treatment alone, further suggesting impaired RNA synthesis. Studies performed on congenic mice indicate that the observed effects segregate with the Ah locus. The ability of methylprednisolone and uridine to reverse the mortality associated with TCDD/endotoxin treatment is consistent with an inflammatory response and impaired hepatic detoxification mechanisms. Thus, changes in hepatic handling of endotoxin, caused by progressive TCDD-induced liver dysfunction, may be responsible for the endotoxin hypersensitivity. JF - Toxicology AU - Rosenthal, G J AU - Lebetkin, E AU - Thigpen, J E AU - Wilson, R AU - Tucker, A N AU - Luster, M I AD - National Institute of Environmental Health Sciences, Systemic Toxicology Branch, Research Triangle Park, NC 27709. Y1 - 1989/06/16/ PY - 1989 DA - 1989 Jun 16 SP - 239 EP - 251 VL - 56 IS - 3 SN - 0300-483X, 0300-483X KW - Blood Glucose KW - 0 KW - Dioxins KW - Endotoxins KW - Lipids KW - Polychlorinated Dibenzodioxins KW - Receptors, Aryl Hydrocarbon KW - Receptors, Drug KW - RNA KW - 63231-63-0 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Methylprednisolone KW - X4W7ZR7023 KW - Index Medicus KW - Lipids -- blood KW - Receptors, Drug -- genetics KW - Animals KW - Drug Interactions KW - Blood Glucose -- metabolism KW - Mice KW - Blood Urea Nitrogen KW - RNA -- biosynthesis KW - Liver Diseases -- metabolism KW - Mice, Inbred DBA KW - Alanine Transaminase -- blood KW - Methylprednisolone -- pharmacology KW - Mice, Inbred C57BL KW - Female KW - Endotoxins -- metabolism KW - Chemical and Drug Induced Liver Injury KW - Polychlorinated Dibenzodioxins -- toxicity KW - Dioxins -- toxicity KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79030546?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-25 N1 - Date created - 1989-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - No evidence for a role of alcohol or other psychoactive drugs in accelerating immunodeficiency in HIV-1-positive individuals. A report from the Multicenter AIDS Cohort Study. AN - 78995953; 2524608 AB - In a multicenter cohort study of homosexual men, the proportion of seropositives at enrollment who developed the acquired immunodeficiency syndrome (AIDS) during the following 18 months ranged from 5.5% to 8.2% in 1597 alcohol drinkers vs 9.2% in 109 nondrinkers with no clear trend according to use, and from 6.3% to 9.6% for 1662 users vs 7.2% for 83 nonusers of psychoactive drugs prior to enrollment. Among seropositive men with low initial T helper lymphocyte counts, those who continued to use drugs showed no significantly higher 18-month risk of AIDS than nonusers (13% vs 10%); the corresponding risks were 13% and 15%, respectively, for continued heavier vs continued lighter consumption of alcohol. No other manifestations of immunodeficiency were positively associated with substance use prior to enrollment. Prior use was not associated with low mean T helper cell counts at enrollment, and continued drug or alcohol use after enrollment was not associated with greater subsequent decline in counts. As used in a large cohort of homosexual men, psychoactive substances did not enhance the progression of human immunodeficiency virus infection. JF - JAMA AU - Kaslow, R A AU - Blackwelder, W C AU - Ostrow, D G AU - Yerg, D AU - Palenicek, J AU - Coulson, A H AU - Valdiserri, R O AD - National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892. Y1 - 1989/06/16/ PY - 1989 DA - 1989 Jun 16 SP - 3424 EP - 3429 VL - 261 IS - 23 SN - 0098-7484, 0098-7484 KW - Psychotropic Drugs KW - 0 KW - Ethanol KW - 3K9958V90M KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Multicenter Studies as Topic KW - Risk Factors KW - Humans KW - Cohort Studies KW - Acquired Immunodeficiency Syndrome -- immunology KW - Homosexuality KW - Time Factors KW - T-Lymphocytes, Helper-Inducer -- immunology KW - Male KW - Leukocyte Count KW - Ethanol -- adverse effects KW - HIV-1 -- immunology KW - Psychotropic Drugs -- adverse effects KW - HIV Seropositivity -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78995953?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-06-29 N1 - Date created - 1989-06-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1990 Jan 19;263(3):371-3 [2322330] N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Methylene blue for neutralization of heparin. AN - 79212111; 2781510 AB - Patients with protamine allergy present a difficult dilemma when reversal of heparin is required for excessive bleeding. Premedication with steroids and antihistamines has not been shown to effectively prevent anaphylactic reactions in patients with hypersensitivity to protamine. Other heparin antagonists are either not available or are too toxic for human use. This report describes a patient in whom methylene blue was used effectively to neutralize heparin and decrease bleeding due to heparinization. In vitro testing was then done to further define the interaction of heparin and methylene blue. This testing demonstrated that methylene blue neutralized heparin levels of 1 u/ml as well as 10 u/ml. Methylene blue acted as an anticoagulant when present at levels of 3000 micrograms/ml. However, it acted as a coagulant when present in intermediate levels of 800 micrograms/ml and 1600 micrograms/ml. The plasma levels necessary for neutralization of heparin levels of 1 unit/ml (the levels achieved in patient therapeutically anticoagulated) are easily achieved using doses routinely used in treatment of methemoglobinemia. Although the toxicity of methylene blue has been well defined at the lower doses of 2-4 mg/Kg, work still needs to be done to determine safety of the drug at the higher doses necessary to neutralize heparin levels achieved in bypass patients. JF - Thrombosis research AU - Sloand, E M AU - Kessler, C M AU - McIntosh, C L AU - Klein, H G AD - National Institutes of Health, Department of Transfusion Medicine, Bethesda, MD. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 677 EP - 686 VL - 54 IS - 6 SN - 0049-3848, 0049-3848 KW - Heparin Antagonists KW - 0 KW - Methylene Blue KW - T42P99266K KW - Index Medicus KW - Humans KW - Adult KW - Prothrombin Time KW - Female KW - Partial Thromboplastin Time KW - Methylene Blue -- pharmacology KW - Heparin Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79212111?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-10-26 N1 - Date created - 1989-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Cellular alterations and enhanced induction of cleft palate after coadministration of retinoic acid and TCDD. AN - 79030445; 2734792 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and retinoic acid (RA) are both teratogenic in mice. TCDD is a highly toxic, stable environmental contaminant, while RA is a naturally occurring form of vitamin A. Exposure to TCDD induces hydronephrosis and cleft palate, and exposure to RA induces limb defects and cleft palate. Teratology studies previously have shown that the incidence of clefting is higher after exposure to RA + TCDD than would be observed for the same doses of either compound given alone. This study examines the cellular effects which result in cleft palate, after po administration on gestation Day (GD) 10 or 12 of RA + TCDD in corn oil (10 ml/kg total volume). Exposure on GD 10 to 6 micrograms TCDD + 40 mg RA/kg inhibited early growth of the shelves and clefting was due to a failure of shelves to meet and fuse. This effect on mesenchyme was observed in previous studies to occur after exposure on GD 10 to 40 mg/kg RA alone, but not after TCDD alone. After exposure on GD 12 to 6 micrograms TCDD + 80 mg RA/kg, clefting was due to a failure of shelves to fuse after making contact, because the medial cells differentiated into an oral-like epithelium. This response was observed in previous studies to occur after exposure to TCDD alone, but RA alone on GD 12 resulted in differentiation toward nasal-like cells. The interaction between TCDD and RA results in RA-like clefting after exposure on GD 10 and TCDD-like clefting after exposure on GD 12, and this clefting occurs at higher incidences than would occur after the same levels of either agent alone. After exposure on either GD 10 or 12 to RA + TCDD, the programmed cell death of the medial cells does not occur, and these cells continue to express EGF receptors and to bind 125I-EGF. The effects of RA and TCDD may involve modulation of the cells responses to embryonic growth and differentiation factors. JF - Toxicology and applied pharmacology AU - Abbott, B D AU - Birnbaum, L S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 287 EP - 301 VL - 99 IS - 2 SN - 0041-008X, 0041-008X KW - Dioxins KW - 0 KW - Iodine Radioisotopes KW - Polychlorinated Dibenzodioxins KW - Tritium KW - 10028-17-8 KW - Tretinoin KW - 5688UTC01R KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Receptor, Epidermal Growth Factor -- drug effects KW - Administration, Oral KW - Animals KW - Mice, Inbred C57BL KW - Mice KW - Drug Synergism KW - Autoradiography KW - Female KW - Pregnancy KW - Cleft Palate -- chemically induced KW - Cleft Palate -- pathology KW - Tretinoin -- toxicity KW - Polychlorinated Dibenzodioxins -- toxicity KW - Dioxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79030445?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-25 N1 - Date created - 1989-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - TCDD alters medial epithelial cell differentiation during palatogenesis. AN - 79028635; 2734791 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widely distributed, persistent environmental contaminant that is teratogenic in mice, where it induces hydronephrosis and cleft palate. The incidence of clefting has been shown to be dose dependent after exposure on either gestation Day (GD) 10 or 12, although the embryo is more susceptible on GD 12. TCDD-exposed palatal shelves meet but do not fuse, and programmed cell death of the medial epithelial cells is inhibited. The mechanism of action through which TCDD alters the program of medial cell development has not been examined in earlier studies, and it is not known whether the mechanism is the same regardless of the dose or developmental stage of exposure. In this study, C57BL/6N mice, a strain sensitive to TCDD, were dosed orally on GD 10 or 12 with 0, 6, 12, 24, or 30 micrograms/kg body wt, in 10 ml corn oil/kg. Embryonic palatal shelves were examined on GD 14, 15, or 16. The degree of palatal closure, epithelial surface morphology, and cellular ultrastructure, the incorporation of [3H]TdR, the expression of EGF receptors, and the binding of 125I-EGF were assessed. After exposure on GD 10 or 12, TCDD altered the differentiation pathway of the medial epithelial cells. The palatal shelves were of normal size and overall morphology, but fusion of the medial epithelia of the opposing shelves did not occur. TCDD prevented programmed cell death of the medial peridermal cells. The expression of EGF receptors by medial cells continued through Day 16 and the receptors were able to bind ligand. The medial cells differentiated into a stratified, squamous, keratinizing epithelium. The shift in phenotype to an oral-like epithelium occurred after exposure on either GD 10 or 12. At the lower dose (6 micrograms/kg), fewer cleft palates were produced, but those shelves which did respond had a fully expressed shift in differentiation. Whether the exposure begins on GD 10 or 12 or whether the dosing level produces only a few cleft palates within a litter, TCDD produced cleft palate by altering the differentiation program of the medial cells. JF - Toxicology and applied pharmacology AU - Abbott, B D AU - Birnbaum, L S AD - Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 276 EP - 286 VL - 99 IS - 2 SN - 0041-008X, 0041-008X KW - Dioxins KW - 0 KW - Iodine Radioisotopes KW - Polychlorinated Dibenzodioxins KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Administration, Oral KW - Animals KW - Receptor, Epidermal Growth Factor -- immunology KW - Cell Division -- drug effects KW - Mice KW - Pregnancy KW - Thymidine -- metabolism KW - Phenotype KW - Receptor, Epidermal Growth Factor -- drug effects KW - Mice, Inbred C57BL KW - Cell Differentiation -- drug effects KW - Female KW - Palate -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Palate -- cytology KW - Dioxins -- toxicity KW - Palate -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79028635?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-25 N1 - Date created - 1989-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Identification of a selenocysteyl-tRNA(Ser) in mammalian cells that recognizes the nonsense codon, UGA. AN - 78988689; 2498338 AB - The presence of a unique opal suppressor seryl-tRNA in higher vertebrates which is converted to phosphoseryl-tRNA has been known for several years, but its function has been uncertain (see Hatfield, D. (1985) Trends Biochem. Sci. 10, 201-204 for review). In the present study, we demonstrate that this tRNA species also occurs in vivo as selenocysteyl-tRNA(Ser) suggesting that it functions both as a carrier molecule upon which selenocysteine is synthesized and as a direct selenocysteine donor to a growing polypeptide chain in response to specific UGA codons. [75Se]Seleno[3H]cysteyl-tRNA(Ser) formed by administering 75Se and [3H]serine to rat mammary tumor cells (TMT-081-MS) in culture was isolated from the cell extract. The amino acid attached to the tRNA was identified as selenocysteine following its deacylation and reaction with iodoacetate and 3-bromopropionate. The resulting alkyl derivatives co-chromatographed on an amino acid analyzer with authentic carboxymethylselenocysteine and carboxyethylselenocysteine. Seryl-tRNA(Ser) and phosphoseryl-tRNA(Ser) (Hatfield, D., Diamond, A., and Dudock, B. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6215-6219), which co-migrate on a reverse phase chromatographic column with selenocysteyl-tRNA(Ser), were also identified in extracts of TMT-018-MS cells. Hence, we propose that a metabolic pathway for selenocysteine synthesis in mammalian cells is the conversion of seryl-tRNA(Ser) via phosphoseryl-tRNA(Ser) to selenocysteyl-tRNA(Ser). In a ribosomal binding assay selenocysteyl-tRNA(Ser) recognizes UGA but not any of the serine codons. Selenocysteyl-tRNA(Ser) is deacylated more readily than seryl-tRNA(Ser) (i.e. 58% deacylation during 15 min at pH 8.0 and 37 degrees C as compared to 41%). JF - The Journal of biological chemistry AU - Lee, B J AU - Worland, P J AU - Davis, J N AU - Stadtman, T C AU - Hatfield, D L AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 9724 EP - 9727 VL - 264 IS - 17 SN - 0021-9258, 0021-9258 KW - Codon KW - 0 KW - RNA, Messenger KW - RNA, Transfer, Amino Acyl KW - RNA, Transfer, Ser KW - Selenium Radioisotopes KW - selenocysteinyl-tRNA KW - Tritium KW - 10028-17-8 KW - Serine KW - 452VLY9402 KW - Selenious Acid KW - F6A27P4Q4R KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Rats KW - Selenium -- metabolism KW - Ribosomes -- metabolism KW - Animals KW - Base Sequence KW - RNA, Transfer, Ser -- metabolism KW - Mammary Neoplasms, Experimental -- metabolism KW - Serine -- metabolism KW - RNA, Transfer, Ser -- genetics KW - Cell Line KW - RNA, Transfer, Amino Acyl -- metabolism KW - RNA, Transfer, Amino Acyl -- genetics KW - RNA, Transfer, Amino Acyl -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78988689?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-13 N1 - Date created - 1989-07-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Human tumor infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. AN - 78979760; 2723437 AB - Tumor infiltrating lymphocytes (TIL) isolated from 12 patients with metastatic malignant melanoma, renal cell carcinoma, or breast adenocarcinoma were expanded in rIL-2 for 22 to 45 days (median 33 days) and analyzed for lymphokine mRNA expression and patterns of TCR gene rearrangement. All TIL cultures were significantly enriched for T cells, with CD3+ CD8+ cells predominant in 8 of 10 cases tested, and demonstrated an oligoclonal (rather than polyclonal) pattern of TCR gene rearrangement. Nine of 12 cultures could effectively lyse the autologous targets in short term chromium release assays. IL-2 expanded-TIL expressed mRNA for TNF-alpha and TNF-beta (lymphotoxin) and, in 5 of 9 (41%) cases, granulocyte/macrophage-colony stimulating factor mRNA but not IL-1 beta or IL-2 transcripts. Cultured TIL deprived of rIL-2 for 4 days did not constitutively express mRNA for any of the lymphokines tested. One long term TIL line in culture was followed and periodically tested for lytic activity and TNF-mRNA expression. Loss of the specific cytolytic but not proliferative activity at day 85 was associated with disappearance of TNF mRNA. Profiles of lymphokine secretion may provide a useful marker for functionally characterizing different T cell subsets and may provide correlates of the in vivo anti-tumor effects of these cells when TIL are adoptively transferred into cancer-bearing patients. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Belldegrun, A AU - Kasid, A AU - Uppenkamp, M AU - Topalian, S L AU - Rosenberg, S A AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 4520 EP - 4526 VL - 142 IS - 12 SN - 0022-1767, 0022-1767 KW - Lymphokines KW - 0 KW - RNA, Messenger KW - Abridged Index Medicus KW - Index Medicus KW - Melanoma -- analysis KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- therapy KW - Humans KW - Kidney Neoplasms -- analysis KW - Gene Rearrangement KW - Nucleic Acid Hybridization KW - Phenotype KW - Carcinoma -- therapy KW - Melanoma -- pathology KW - Tumor Cells, Cultured KW - Carcinoma -- pathology KW - Carcinoma -- analysis KW - Cytotoxicity Tests, Immunologic KW - Melanoma -- therapy KW - Lymphocytes -- pathology KW - Cell Movement KW - Lymphokines -- metabolism KW - RNA, Messenger -- metabolism KW - Immunotherapy KW - Lymphokines -- genetics KW - Lymphocytes -- classification KW - Lymphocytes -- analysis KW - Neoplasms -- therapy KW - RNA, Messenger -- isolation & purification KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78979760?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-06 N1 - Date created - 1989-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Mechanism of lysis by large granular lymphocyte granule cytolysin: generation of a stable cytolysin-RBC intermediate. AN - 78978040; 2723433 AB - The effect of ionic strength and pH on the hemolytic activity of large granular lymphocyte granule cytolysin was examined in detail. Cytolysin-mediated lysis of RBC was inhibited by either low ionic strength or low pH. Under these conditions a nonlytic cytolysin-RBC intermediate was formed as revealed by hemolysis when cytolysin pretreated cells were washed and resuspended at physiologic ionic strength and pH. Formation of the cytolysin-RBC intermediate at low ionic strength (250 mM sucrose), pH 7.3, required greater than 0.1 mM calcium. In contrast, formation of the intermediate at physiologic ionic strength (150 mM NaCl), pH 6.0, was calcium independent. Both types of intermediates were stable at 37 degrees C and required calcium to induce subsequent lysis. The degree of lysis of the intermediate generated at low ionic strength was similar to that measured under standard conditions with the use of either whole granule preparations or purified cytolysin. However, lysis of intermediates formed at pH 6.0 was much less efficient. Our data indicate that a stable cytolysin-RBC intermediate can be formed in which cytolysin is present in an unreactive state on the RBC surface; under conditions of physiologic ionic strength and calcium concentrations this intermediate rapidly lyses. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kuta, A E AU - Reynolds, C R AU - Henkart, P A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 4378 EP - 4384 VL - 142 IS - 12 SN - 0022-1767, 0022-1767 KW - Cytotoxins KW - 0 KW - Killer Factors, Yeast KW - Proteins KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Osmolar Concentration KW - Animals KW - Rats, Inbred F344 KW - Hydrogen-Ion Concentration KW - Calcium -- physiology KW - Cell Communication KW - Cytotoxins -- isolation & purification KW - Cytotoxicity, Immunologic KW - Cytotoxins -- physiology KW - Hemolysis KW - Cytoplasmic Granules -- physiology KW - Cytoplasmic Granules -- immunology KW - Erythrocytes -- physiology KW - Killer Cells, Natural -- physiology KW - Proteins -- physiology KW - Killer Cells, Natural -- immunology KW - Erythrocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78978040?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-06 N1 - Date created - 1989-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Prognostic variables in recurrent limb melanoma treated with hyperthermic antiblastic perfusion. AN - 78969374; 2720604 AB - Between October 1969 and December 1986, 136 patients with recurrent limb melanoma were treated with hyperthermic antiblastic perfusion (HAP). This retrospective analysis is aimed at identifying tumor-related and treatment-related variables likely to influence tumor response, locoregional control, disease-free survival, and overall survival. Independent factors predicting a complete response (CR) were the number of lesions (P less than 0.0001) and the minimum tumor temperature (minT) (P = 0.03). Only a positive trend was observed for the drug dose (P = 0.08). However, the proportion of CR was significantly higher (57.7%; P = 0.02) in patients who had a minT of 41.5 degrees C or greater and who were given a dose equal to or greater than the standard dose than in patients treated with lower temperatures and/or lower drug doses. The occurrence of a CR significantly increased the rates of locoregional control (77%; P = 0.007), disease-free survival (55.6%; P = 0.006), and overall survival (68.6%; P = 0.03). Treatment optimization may provide further therapeutic improvements by increasing the incidence of CR. However, the overall survival rates also were influenced by the number of lesions (P = 0.0014), sex (P = 0.04), and the number of previous relapses (P = 0.01). Therefore, tumor aggressiveness also is crucial in determining the outcome of the disease, and only early treatment with HAP can reduce the risk of distant metastases. JF - Cancer AU - Di Filippo, F AU - Calabrò, A AU - Giannarelli, D AU - Carlini, S AU - Cavaliere, F AU - Moscarelli, F AU - Cavaliere, R AD - III Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 2551 EP - 2561 VL - 63 IS - 12 SN - 0008-543X, 0008-543X KW - Melphalan KW - Q41OR9510P KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasm Staging KW - Lymphatic Metastasis KW - Humans KW - Retrospective Studies KW - Prognosis KW - Aged KW - Extremities KW - Prospective Studies KW - Aged, 80 and over KW - Adult KW - Melphalan -- therapeutic use KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Female KW - Male KW - Remission Induction KW - Melanoma -- mortality KW - Melanoma -- secondary KW - Hyperthermia, Induced KW - Skin Neoplasms -- therapy KW - Melanoma -- therapy KW - Chemotherapy, Cancer, Regional Perfusion -- methods KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Skin Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78969374?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-06 N1 - Date created - 1989-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Case-control study of colorectal cancer and fecal mutagenicity. AN - 78953247; 2655896 AB - Fecal mutagenicity was measured in 68 patients with colorectal cancer and in 114 controls, using Salmonella tester strains TA98 and TA100 with and without S9 activation. Samples were also tested for fecapentaenes by high-performance liquid chromatography, to permit the separation of fecapentaene and non-fecapentaene mutagenicity. Overall, no significant case-control differences in fecal mutagenicity were observed. However, when samples containing high concentrations of fecapentaenes were excluded, non-fecapentaene TA98 mutagenicity was observed in eight cases (12%) and only four controls (4%), resulting in an estimated relative risk of 4.4 (95% confidence interval = 1.0-21.1). The association of colorectal cancer risk with non-fecapentaene TA98 mutagenicity could not be explained as an artifact of diagnostic workup or gastrointestinal bleeding among the cases. Smoking could also be excluded as a source of the TA98 mutagenicity seen, but possible dietary origins are still being explored. JF - Cancer research AU - Schiffman, M H AU - Andrews, A W AU - Van Tassell, R L AU - Smith, L AU - Daniel, J AU - Robinson, A AU - Hoover, R N AU - Rosenthal, J AU - Weil, R AU - Nair, P P AD - Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/06/15/ PY - 1989 DA - 1989 Jun 15 SP - 3420 EP - 3424 VL - 49 IS - 12 SN - 0008-5472, 0008-5472 KW - Mutagens KW - 0 KW - Index Medicus KW - Reference Values KW - Mutagenicity Tests KW - Humans KW - Salmonella typhimurium -- drug effects KW - Rectal Neoplasms -- physiopathology KW - Feces -- analysis KW - Adenocarcinoma -- physiopathology KW - Colonic Neoplasms -- physiopathology KW - Mutagens -- analysis KW - Mutagens -- isolation & purification KW - Mutagens -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78953247?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-06 N1 - Date created - 1989-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Forskolin stimulates pinealocyte cGMP accumulation. Dramatic potentiation by an alpha 1-adrenergic----[Ca2+]i mechanism involving protein kinase C. AN - 79049158; 2544448 AB - The effect of forskolin on cGMP regulation was investigated using dispersed rat pinealocytes. Forskolin stimulated cGMP accumulation in a concentration-dependent manner; this response was strongly potentiated by an alpha 1-adrenergic----[Ca2+]i mechanism involving protein kinase C. These findings provide further evidence that activation of two receptor-regulated signal transduction mechanisms may be commonly required for maximal stimulation of cGMP accumulation, and establish a new experimental approach to the study of cGMP regulation. JF - FEBS letters AU - Ho, A K AU - Chik, C L AU - Klein, D C AD - Section on Neuroendocrinology, National Institute of Child Health and Human Development, Bethesda, MD 20892. Y1 - 1989/06/05/ PY - 1989 DA - 1989 Jun 05 SP - 207 EP - 212 VL - 249 IS - 2 SN - 0014-5793, 0014-5793 KW - Cations, Divalent KW - 0 KW - Receptors, Adrenergic, alpha KW - Colforsin KW - 1F7A44V6OU KW - Phenylephrine KW - 1WS297W6MV KW - Calcimycin KW - 37H9VM9WZL KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Cyclic GMP KW - H2D2X058MU KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Adenylyl Cyclases -- metabolism KW - Calcimycin -- pharmacology KW - Rats KW - Rats, Inbred Strains KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Potassium -- pharmacology KW - Female KW - Phenylephrine -- pharmacology KW - Protein Kinase C -- metabolism KW - Calcium -- metabolism KW - Pineal Gland -- metabolism KW - Cyclic GMP -- metabolism KW - Colforsin -- pharmacology KW - Pineal Gland -- cytology KW - Receptors, Adrenergic, alpha -- metabolism KW - Pineal Gland -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79049158?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-28 N1 - Date created - 1989-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Site-directed mutagenesis of beta-adrenergic receptors. Identification of conserved cysteine residues that independently affect ligand binding and receptor activation. AN - 78993608; 2542304 AB - Using site-directed mutagenesis of the human beta 2-adrenergic receptor and continuous expression in B-82 cells, the role of 3 conserved cysteines in transmembrane domains and 2 conserved cysteines in the third extracellular domain in receptor function was examined. Cysteine was replaced with serine in each mutant receptor as this amino acid is similar to cysteine in size but it cannot form disulfide linkages. Replacement of cysteine residues 77 and 327, in the second and seventh transmembrane-spanning domains, respectively, had no effect on ligand binding or the ability of the receptor to mediate isoproterenol stimulation of adenylate cyclase. Substitution of cysteine 285, in the sixth transmembrane domain of the receptor, produced a mutant receptor with normal ligand-binding properties but a significantly attenuated ability to mediate stimulation of adenylate cyclase. Mutation of cysteine residues 190 and 191, in the third extracellular loop of the beta 2 receptor, had qualitatively similar effects on ligand binding and isoproterenol-mediated stimulation of adenylate cyclase. Replacement of either of these residues with serine produced mutant receptors that displayed a marked loss in affinity for both beta-adrenergic agonists and antagonists. Replacement of both cysteine 190 and 191 with serine had an even greater effect on the ability of the receptor to bind ligands. Consistent with the loss of Ser190 and/or Ser191 mutant receptor affinity for agonists was a corresponding shift to the right in the dose-response curve for isoproterenol-induced increases in intracellular cyclic AMP concentrations in cells expressing the mutant receptors. These data implicate one of the conserved transmembrane cysteine residues in the human beta 2-adrenergic receptor in receptor activation by agonists and also suggest that conserved cysteine residues in an extracellular domain of the receptor may be involved in ligand binding. JF - The Journal of biological chemistry AU - Fraser, C M AD - Section of Receptor Biochemistry and Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892. Y1 - 1989/06/05/ PY - 1989 DA - 1989 Jun 05 SP - 9266 EP - 9270 VL - 264 IS - 16 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Receptors, Adrenergic, beta KW - Serine KW - 452VLY9402 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - L Cells (Cell Line) -- metabolism KW - Humans KW - L Cells (Cell Line) -- physiology KW - Amino Acid Sequence KW - GTP-Binding Proteins -- physiology KW - Mice KW - Membrane Proteins -- genetics KW - Serine -- genetics KW - Cloning, Molecular KW - Extracellular Space -- physiology KW - Extracellular Space -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Molecular Sequence Data KW - Receptors, Adrenergic, beta -- genetics KW - Cysteine -- genetics KW - Receptors, Adrenergic, beta -- physiology KW - Mutation KW - Signal Transduction KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78993608?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-05 N1 - Date created - 1989-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Transcription of Xenopus selenocysteine tRNA Ser (formerly designated opal suppressor phosphoserine tRNA) gene is directed by multiple 5'-extragenic regulatory elements. AN - 78987815; 2524488 AB - A tRNA gene whose product is aminoacylated with serine and the serine moiety is then phosphorylated to form phosphoseryl-tRNA (see Hatfield, D. (1985) Trends Biochem. Sci. 10, 201-204 for review) has now been shown to form selenocysteyl-tRNA; hence the corresponding gene is designated as selenocysteine tRNA Ser (B. J. Lee, P. J. Worland, J. N. Davis, T. C. Stadtman, and D. Hatfield (1989) J. Biol. Chem. 264, in press). In the present study, we show that the expression of this unique tRNA gene is governed by at least three upstream regulatory elements. In initial studies, the relative efficiencies of transcription of the human, rabbit, chicken, and Xenopus selenocysteine tRNA genes were compared in vivo in Xenopus oocytes and in vitro in HeLa cell extracts. The Xenopus gene was severalfold more actively expressed, both in vivo and in vitro, than the human and rabbit genes, whereas the chicken gene was poorly expressed. Exchange of the 5'-flanking regions of the Xenopus and chicken genes, which have identical gene sequences, reversed their levels of transcription, demonstrating that a regulatory site or sites exist upstream of these genes. Deletion-substitution mutants in the Xenopus gene and its 5'-flanking sequence show in in vitro assays that 1) the level of transcription is reduced substantially when a GC-rich stretch that is immediately upstream of a TATA box in the -30 region is removed; 2) the level of transcription is virtually abolished when the TATA box is removed; and 3) deletions up to and further upstream of the GC-rich region do not affect the level of transcription. The same deletions, when used in in vivo assays, demonstrate a step-down in expression with the deletion removing the GC-rich region, a further step-down in expression with the deletion removing the TATA box, but the most pronounced reduction in expression was observed with a deletion removing an AT-rich region between nucleotides -62 and -76. Thus, a regulatory site was identified in vivo which was not detected in vitro, and transcription of the selenocysteine tRNA Ser gene is determined by multiple upstream regulatory elements. JF - The Journal of biological chemistry AU - Lee, B J AU - Kang, S G AU - Hatfield, D AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/06/05/ PY - 1989 DA - 1989 Jun 05 SP - 9696 EP - 9702 VL - 264 IS - 16 SN - 0021-9258, 0021-9258 KW - RNA, Transfer, Amino Acid-Specific KW - 0 KW - RNA, Transfer, Ser KW - Selenocysteine KW - 0CH9049VIS KW - RNA Polymerase III KW - EC 2.7.7.6 KW - Selenium KW - H6241UJ22B KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Chromosome Deletion KW - Chickens KW - Base Sequence KW - Genes KW - Humans KW - Molecular Sequence Data KW - Rabbits KW - Amino Acid Sequence KW - Mutation KW - Xenopus -- genetics KW - Selenium -- metabolism KW - Regulatory Sequences, Nucleic Acid KW - Cysteine -- metabolism KW - RNA, Transfer, Ser -- metabolism KW - RNA, Transfer, Amino Acid-Specific -- genetics KW - Transcription, Genetic KW - RNA, Transfer, Ser -- isolation & purification KW - RNA, Transfer, Ser -- genetics KW - Cysteine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/78987815?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-07-05 N1 - Date created - 1989-07-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma. AN - 85285132; pmid-2542193 AB - In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma. JF - International Journal of Radiation Oncology, Biology, Physics AU - Deutsch, M AU - Green, S B AU - Strike, T A AU - Burger, P C AU - Robertson, J T AU - Selker, R G AU - Shapiro, W R AU - Mealey, J AU - Ransohoff, J AU - Paoletti, P AD - Clinical and Diagnostic Trials Section, Biometry Branch, NCI, Bethesda, MD 20892. PY - 1989 SP - 1389 EP - 1396 VL - 16 IS - 6 SN - 0360-3016, 0360-3016 KW - Glioblastoma KW - Support, U.S. Gov't, P.H.S. KW - Astrocytoma KW - Random Allocation KW - Combined Modality Therapy KW - Human KW - Carmustine KW - Prognosis KW - Aged KW - Streptozocin KW - Supratentorial Neoplasms KW - Comparative Study KW - Radiotherapy Dosage KW - Adult KW - Multicenter Studies KW - Misonidazole KW - Middle Age KW - Glioma KW - Adolescent UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85285132?accountid=14244 LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Habituation and maternal encouragement of attention in infancy as predictors of toddler language, play, and representational competence. AN - 85164807; pmid-2737021 AB - In a longitudinal study, infants' habituation and mothers' encouragement of attention were assessed at 5 months, and toddlers' language comprehension, language production, and pretense play and mothers' encouragement of attention were assessed at 13 months. Structural equation modeling was used to examine the unique contributions of infant habituation and maternal stimulation to toddlers' cognitive abilities. Habituation predicted language comprehension, pretense play, and a latent variable of language and play after the influences of both 5- and 13-month maternal encouragement of attention were partialed. Likewise, early maternal encouragement of attention explained unique variance in toddlers' language comprehension and the language-and-play latent variable after infant habituation was controlled. These findings indicate that links between early habituation and later cognitive development are direct and not solely mediated by maternal stimulation, and that maternal stimulation of young infants influences the development of children's representational competence over and above infants' own information-processing abilities. JF - Child Development AU - Tamis-LeMonda, C S AU - Bornstein, M H AD - National Institute of Child Health and Human Development, Bethesda, MD 20892. PY - 1989 SP - 738 EP - 751 VL - 60 IS - 3 SN - 0009-3920, 0009-3920 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85164807?accountid=14244 LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of sodium bromate on ionic concentrations and osmolalities of the cochlear fluids in guinea pigs. AN - 85142890; pmid-2753829 AB - Effects of sodium bromate on cochlear potentials and electrolyte composition of the cochlear fluids in guinea pigs were investigated following administration of sodium bromate into the cochlea, using perilymphatic perfusion. Cochlear microphonics and the whole nerve action potential of the auditory nerve were markedly suppressed. The K+ and Cl- activities in the endolymph as well as the endocochlear dc potential (EP) decreased significantly and irreversibly, in proportion to the concentration of sodium bromate. A negative EP never developed during the monitoring of 120 min. Microsamples of the endolymph showed substantial decreases of K+ and Cl- concentrations and an increase in the concentration of Na+. Osmolality of the endolymph was much lower than that of the perilymph. The severe edema of the stria vascularis and collapse of Reissner's membrane were histologically evident. These events suggest a breakdown of the endolymph-perilymph barrier, coincident with an inhibition of the strial active transport, as a result of the ototoxic action of sodium bromate. The possible ion and water movement across the endolymph-perilymph barrier in the presence of sodium bromate is discussed. JF - Hearing Research AU - Muratsuka, Y AU - Ueda, H AU - Konishi, T AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina. PY - 1989 SP - 241 EP - 249 VL - 39 IS - 3 SN - 0378-5955, 0378-5955 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85142890?accountid=14244 LA - English DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The uniform carcinogenic action of alkylnitrosoureas in Syrian hamsters. AN - 79355237; 2590502 AB - The carcinogenic effects of a number of alkylnitrosoureas in Syrian golden hamsters have been compared by administering them by gavage as solutions in corn oil/ethyl acetate. The compounds were methyl-, ethyl-, 2-hydroxyethyl-, 2-oxopropyl-, and 2-phenylethylnitrosourea and the dialkylnitrosoureas dimethyl- and diethylnitrosourea, ethylnitrosohydroxyethylurea, ethylnitroso-2-oxopropylurea, 2-oxopropylnitrosochloroethylurea, and hydroxyethylnitrosoethylurea. All were given at approximately equimolar doses and, in most cases, to male and female hamsters. Most of the hamsters died with tumors associated with the treatments. Methylnitrosourea, ethylnitrosourea, and hydroxyethylnitrosourea, but not oxopropylnitrosourea, gave rise to a high incidence of tumors of the forestomach, while the dialkylnitrosoureas produced smaller numbers of forestomach tumors. All of the alkylnitrosoureas induced hemangiosarcomas of the spleen, which was the most common tumor produced by these carcinogens. Tumors of other types were uncommon, except that ethylnitrosourea and ethylnitrosohydroxyethylurea induced tumors of the cervix in about half of the animals and ethylnitrosooxopropylurea induced some nervous system tumors. The small number of common target organs of alkylnitrosoureas in hamsters contrasted sharply with the broad spectrum of tumors they induced in rats, depending on the nature of the alkyl groups, and with a quite different order of potency in the latter species. JF - Biomedical and environmental sciences : BES AU - Lijinsky, W AU - Kovatch, R M AD - BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, Frederick 21701. Y1 - 1989/06// PY - 1989 DA - June 1989 SP - 167 EP - 173 VL - 2 IS - 2 SN - 0895-3988, 0895-3988 KW - Carcinogens KW - 0 KW - Nitrosourea Compounds KW - Index Medicus KW - Animals KW - Carcinogenicity Tests KW - Mesocricetus KW - Male KW - Female KW - Cricetinae KW - Nitrosourea Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79355237?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-25 N1 - Date created - 1990-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Carcinogenesis by nitrosamines and azoxyalkanes by different routes of administration to rats. AN - 79353865; 2590501 AB - The effects of administering similar doses of some simple alkylating agents to rats by different regimens have been compared. Two of the compounds were methylating agents, nitrosodimethylamine and azoxymethane; two were ethylating agents, nitrosodiethylamine and azoxyethane; and nitrosomethylethylamine was both a methylating and an ethylating agent. The treatments gave rise to tumors in almost all treated rats. The results indicate the importance of pharmacokinetics in determining which organs are the targets of the alkylating carcinogens. JF - Biomedical and environmental sciences : BES AU - Lijinsky, W AU - Kovatch, R M AD - NCI-Frederick Cancer Research Facility, BRI-Basic Research Program, Maryland 21701. Y1 - 1989/06// PY - 1989 DA - June 1989 SP - 154 EP - 159 VL - 2 IS - 2 SN - 0895-3988, 0895-3988 KW - Alkylating Agents KW - 0 KW - Azo Compounds KW - Nitrosamines KW - Index Medicus KW - Rats KW - Administration, Oral KW - Animals KW - Rats, Inbred F344 KW - Sex Factors KW - Intubation, Gastrointestinal KW - Carcinogenicity Tests KW - Male KW - Female KW - Administration, Intravesical KW - Nitrosamines -- administration & dosage KW - Nitrosamines -- toxicity KW - Azo Compounds -- administration & dosage KW - Azo Compounds -- toxicity KW - Alkylating Agents -- toxicity KW - Alkylating Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79353865?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1990-01-25 N1 - Date created - 1990-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Use of colloidal gold cytochemistry in the study of the basic cell biology of cancer. AN - 79200753; 2570523 AB - We are currently investigating the morphologic aspects of two areas of the basic cell biology of cancer: tumor-specific surface antigens as targets for immunotoxins, and the phenomenon of multidrug resistance in chemotherapy of human tumors. Colloidal gold cytochemistry has provided a useful method for the electron-microscopic cytochemical detection of materials endocytosed by cells in culture. This technique has been used to study the internalization pathway of ligands bound to the surface of cancer cells, particularly antibodies for use as immunologic targeting reagents for the construction of immunotoxins. These colloidal gold conjugates with monoclonal antibodies have demonstrated the internalization of these immunologic reagents through coated pits and receptosomes, which is a necessary step in the delivery of immunotoxins into the cell where they can mediate their cell-killing functions. Morphologic methods have been employed for the screening and selection of monoclonal antibodies reactive with the surface of human ovarian cancer cells for use as immunotoxins and have demonstrated the in vivo activity of immunotoxins made with these antibodies and Pseudomonas exotoxin in a nude mouse model system. In other studies, we have employed such reagents for the immunocytochemical detection of the surface expression of P170, the cell-surface efflux pump protein responsible for the phenotype of multidrug resistance in tumor cells, and to investigate the distribution of this protein by using immunocytochemistry in normal human tissues. These results have suggested a role for P170 in normal cell membrane transport of metabolites in various organ systems. JF - The American journal of anatomy AU - Willingham, M C AD - Ultrastructural Cytochemistry Section, National Cancer Institute, Bethesda, Maryland 20892. PY - 1989 SP - 109 EP - 127 VL - 185 IS - 2-3 SN - 0002-9106, 0002-9106 KW - Clathrin KW - 0 KW - Immunotoxins KW - Epidermal Growth Factor KW - 62229-50-9 KW - Gold KW - 7440-57-5 KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Index Medicus KW - Endosomes -- physiology KW - Horseradish Peroxidase -- pharmacokinetics KW - Endosomes -- ultrastructure KW - Endocytosis KW - Clathrin -- metabolism KW - Humans KW - Temperature KW - Drug Resistance KW - Microinjections KW - Immunotoxins -- metabolism KW - Endosomes -- metabolism KW - Epidermal Growth Factor -- pharmacokinetics KW - Neoplasms -- pathology KW - Neoplasms -- physiopathology KW - Immunohistochemistry -- methods KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79200753?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-26 N1 - Date created - 1989-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-17 ER - TY - JOUR T1 - Pharmacokinetics of subcutaneous azidothymidine in rhesus monkeys. AN - 79157708; 2764527 AB - The pharmacokinetics of subcutaneous bolus and continuous infusion azidothymidine (AZT) was studied in rhesus monkeys. Three animals received 100 mg/m2 as a bolus injection both intravenously and subcutaneously, with the order of administration randomly determined. Two animals received a continuous subcutaneous infusion of 25 mg/m2 per h for 12 or 24 h. AZT was measured in plasma by a reverse-phase high-pressure liquid chromatographic assay. Following intravenous bolus administration, AZT elimination was rapid, with a mean half-life of 1.2 h and a mean clearance of 318 ml/min per m2 (range, 200 to 441 ml/min per m2). The bolus subcutaneous dose was rapidly (time to peak concentration, 15 to 30 min) and nearly completely (fraction absorbed, 92%) absorbed without evidence of local tissue toxicity. With continuous subcutaneous infusion of AZT, the steady state was attained within 4 h and steady-state concentrations in plasma in the two animals exceeded 3.0 mumol/liter. No local tissue toxicity was observed at the infusion site. The subcutaneous route may be a practical alternative to intravenous administration of AZT and deserves further clinical study. JF - Antimicrobial agents and chemotherapy AU - Balis, F M AU - McCully, C AU - Gough, L AU - Pizzo, P A AU - Poplack, D G AD - Pediatric Branch, National Cancer Institute, Bethesda, Maryland 20892. Y1 - 1989/06// PY - 1989 DA - June 1989 SP - 810 EP - 812 VL - 33 IS - 6 SN - 0066-4804, 0066-4804 KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Injections, Intravenous KW - Injections, Subcutaneous KW - Macaca mulatta KW - Male KW - Biological Availability KW - Zidovudine -- pharmacokinetics KW - Zidovudine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/79157708?accountid=14244 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1989-09-21 N1 - Date created - 1989-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1987 Jul 23;317(4):185-91 [3299089] Cancer. 1988 Jul 15;62(2):407-11 [2454724] N Engl J Med. 1988 Oct 6;319(14):889-96 [3166511] J Clin Oncol. 1988 Dec;6(12):1882-6 [3199171] Clin Pharmacol Ther. 1987 Apr;41(4):407-12 [3549120] Lancet. 1976 Dec 11;2(7998):1278-80 [63749] J Pharm Sci. 1982 Mar;71(3):372-3 [7069