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Biomedical subjects

G Curtis

Publications and source records attributed to G Curtis.

At least 37 records · Page 2Linked to original sources
PubMed1989

Viral agents in two-stage cervical carcinogenesis: an experimental study in mice.

The role of chemical and viral agents in the development of cervical cancer in mice was studied by repeated carcinogen applications, repeated intravaginal instillations of HSV type II virus, and single carcinogen application as initiating agent followed by repeated instillations of virus as promoter. In all the animals studied, repeated applications of 9,10-dimethylbenzanthracene (DMBA) induced dysplastic conditions of the cervix and vagina, mild, moderate, and severe, as well as a large number of invasive squamous cell carcinomas. DMBA alone as initiating agent did not induce tumors or marked dysplasia; when followed by repeated applications of HSV2 virus only mild dysplastic lesions occurred. Repeated applications of HSV2 alone produced inflammatory changes of the cervix and vagina. It is concluded that repeated intravaginal instillation of HSV2 virus as done in this study does not induce cervical cancer or its precursors, and in a two-stage system is only weakly a promoter of carcinogen-induced latent tumor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Limitations and advantages of the ejection fraction for defining high risk after acute myocardial infarction.

Left ventricular (LV) ejection fraction (EF) is known to be related to prognosis after acute myocardial infarction (AMI), but its role alone and in combination with other factors in the definition of a high-risk group has not been adequately specified. Several recent multicenter studies emphasize that LVEF together with features of ventricular ectopic activity during ambulatory electrocardiography define a group at high risk for death for up to 3 years. However, these high-risk groups comprised only a small fraction of the population (less than 7.5%) and failed to include 75% or more (less than 25% specificity) of observed events. In our study, LVEF was determined close to the time of hospital discharge in 750 patients with AMI enrolled in a collaborative study. Used alone, an LVEF of less than 0.45 best defined a high-risk group (39% of the population) yielding 62% sensitivity and 64% specificity for total cardiac mortality by 1 year; it was 77% sensitive for sudden death alone. In a multivariate analysis together with other factors, LVEF was an independent predictor, but other markers of LV dysfunction entered before LVEF with similar sensitivity for total cardiac deaths, but with increased specificity (75%). When an LVEF of less than 0.45 was used together with the presence of complex arrhythmias to define a high-risk group (19% of the population), sensitivity decreased to 39% and specificity increased to 84%. Thus, LVEF is a simple and effective alternative to multivariate analysis for risk assessment after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗
PubMed1986

Quantitative analysis of the metabolism of benzo(a)pyrene by transformable C3H10T1/2CL8 mouse embryo fibroblasts.

The metabolism of benzo(a)pyrene [B(a)P] to organic soluble and water soluble metabolites by transformable C3H10T1/2CL8 mouse embryo fibroblasts was studied as a function of time, B(a)P concentration, and cell density. The total formation of organic-soluble and water-soluble metabolites increased with incubation time from 4 to 48 h and with B(a)P concentration from 4 to 40 microM. As cell density increased, the metabolic rate decreased for organic-soluble and water-soluble products between 6,300 and 54,000 cells/cm2 probably due to decreases in B(a)P concentrations to values below saturation. Specific organic-soluble metabolites identified were B(a)P-pre-9,10-diols, B(a)P-9,10-diol, B(a)P-7,8-diol, B(a)P-3,6-quinone, B(a)P-3-phenol, and B(a)P-9-phenol. Water-soluble metabolites were subjected to enzymatic hydrolysis with beta-glucuronidase and aryl sulfatase to identify specific conjugated products. The sulfate conjugated metabolites identified were B(a)P-7,8-diol, B(a)P-pre-9,10-diols, B(a)P-9,10-diol, and B(a)P-3,6-quinone. The beta-glucuronic acid metabolites identified were B(a)P-pre-9,10-diols, B(a)P-3,6-quinone, and B(a)P-3-phenol. Patterns of metabolite formation rates are discussed as to their possible effect on morphological transformation rates in C3H10T1/2 cells with respect to incubation time and cell density.

Animals↗
PubMed1985

Insulin regulation of protein biosynthesis in differentiated 3T3 adipocytes. Regulation of glyceraldehyde-3-phosphate dehydrogenase.

The effect of insulin on protein biosynthesis was examined in differentiated 3T3-L1 and 3T3-F442A adipocytes. Insulin altered the relative rate of synthesis of specific proteins independent of its ability to hasten conversion of the fibroblast (preadipocyte) phenotype to the adipocyte phenotype. Although more than one pattern of response to insulin was observed, we focused on the induction of a Mr 33,000 protein which was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Exposure of 3T3 adipocytes to insulin throughout differentiation specifically increased GAPDH activity and protein content by 2- to 3-fold as compared to 3T3 adipocytes differentiated in the absence of insulin. These changes in enzyme activity and content could be accounted for by a 4-fold increase in the relative rate of synthesis of GAPDH and a 9-fold increase in hybridizable mRNA levels. Within 2 h of insulin addition to 3T3 adipocytes differentiated in the absence of hormone, hybridizable GAPDH mRNA levels increased 3-fold, and within 24 h GAPDH mRNA levels increased 8-fold, and [35S] methionine incorporation into GAPDH protein increased 5-fold. The increase in GAPDH mRNA and GAPDH biosynthesis could be demonstrated using physiologic concentrations of insulin (0.24 nM), indicating that these effects are mediated through a specific interaction with the insulin receptor. These studies demonstrate that insulin, as the sole hormonal perturbant, can increase the synthesis of certain 3T3 adipocyte proteins by altering the cellular content of a specific mRNA.

Adipose Tissue↗
PubMed1985

Tricyclics: possible treatment for posttraumatic stress disorder.

The response to tricyclic antidepressants (TCAs) was examined in 17 combat veterans with DSM-III defined posttraumatic stress disorder (PTSD) by means of concurrent and retrospective chart review. Severity and improvement were determined by means of Clinical Global Impressions (CGI) ratings by two independent but nonblind raters who demonstrated satisfactory reliability. Prior to treatment, 82% were rated as markedly or severely ill and 18% as moderately ill. Following treatment, 82% were rated as much improved and 18% as minimally improved. The results support further investigation of TCAs for the treatment of PTSD.

Adult↗
PubMed1982

Relationship of N-arylacetamide metabolism and macromolecular binding to oncogenic transformation of C3H10T1/2CL8 cells.

The C3H10T1/2CL8 mouse embryo oncogenic transformation bioassay system detects a wide variety of chemical carcinogens. However, one carcinogen that does not transform C3H10T1/2CL8 cells is the liver carcinogen N-2-fluorenylacetamide (FAA). Previous reports indicate that an activated form of FAA, N-acetoxy-FAA (N-OAc-FAA), transforms these fibroblasts. In an effort to understand these results, the metabolism and binding to cellular macromolecules of FAA and N-OAc-FAA using C3H10T1/2CL8 cells was investigated. C3H10T1/2CL8 cells metabolized FAA to 7-hydroxy-FAA, 2-fluorenylamine and N-hydroxy-FAA (N-OH-FAA) at rates of 5.03, 2.22 and 3.33 pmol/h/10(6) cells, respectively. N-O-Ac-FAA was bound to the DNA and RNA in C3H10T1/2CL8 cells to the extent of 10.6 and 3.6 FAA residues/10(6) nucleotides, respectively, and to protein at 21.9 pmol FAA residues/mg protein. However, binding of FAA to DNA and RNA at similar concentrations to N-OAc-FAA was less than 0.3 and 0.6 residues/10(6) nucleotides, respectively. These results strongly indicate that the inability of FAA to transform C3H10T1/2CL8 cells residues in the cells' inability to metabolize it sufficiently to the proximate carcinogen N-OH-FAA and not an inherent insensitivity to its activated forms.

2-Acetylaminofluorene↗
PubMed1982

Improved transformation of C3H10T1/2CL8 cells by direct- and indirect-acting carcinogens.

Oncogenic transformation of C3H10T1/2CL8 cells was improved by treating the cells 5 days after seeding. Benzo[a]-pyrene-induced transformation was increased 3.5-fold by this method, compared with treating the cells 1 day after seeding. N-Methyl-N'-nitro-N-nitrosoguanidine, which does not transform asynchronous cultures of C3H10T1/2CL8 cells when administered 1 day after seeding, produced on average of 1 focus/dish, with 61% of the dishes exhibiting foci, when administered 5 days after seeding. Propane sultone and aflatoxin B1 also produced marked transformation responses when administered 5 days after seeding. However, 4-dimethylaminoazobenzene did not induce transformation when administered either 1 day or 5 days after seeding. With all chemicals examined, clonal cytotoxicity was reduced when they were administered 5 days after seeding. These results indicate the utility of this new procedure for the qualitative analysis of the transforming ability of chemicals.

Aflatoxin B1↗
PubMed1981

Left ventricular size and function after subcutaneous administration of terbutaline.

To assess the response of the left ventricle to subcutaneously administered terbutaline sulfate, a proposed beta-2 selective agonist, we evaluated 12 patients who had suffered previous myocardial infarctions using equilibrium radionuclide angiography. Six patients (group 1) had normal global left ventricular ejection fraction at rest less than 0.49). All patients had a marked decline in end-diastolic volume and end-systolic volume with a significant (P less than 0.01) increase in ejection fraction after terbutaline injection. Cardiac output increased 30 percent in group 2 patients because of an increase in stroke volume, with little change in heart rate (plus or minus 3.1 beats per minute, P equals NS). Cardiac output increased 7 percent in the patients in groups 1, due primarily to an increase in heart rate in 7 beats per minute (+9 percent) with little change in stoke volume. Systemic vascular resistance decreased significantly more in the patients with compensated heart failure than the subjects in group 1 (342 plus or minus 84 vs 90 plus or minus 35 dynes-sec cm(-5), P less than 0.05). We conclude that terbutaline exerts its most beneficial effect on the left ventricle in patients with depressed resting global function, and may prove to be a useful agent in the treatment of congestive heart failure.

Aged↗
PubMed1980

Mutagenesis and morphological transformation of mammalian cells by a non-bay-region polycyclic cyclopenta(cd)pyrene and its 3,4-oxide.

Cyclopenta(cd)pyrene, a constituent of environmental emissions, has been found to mutate and transform mammalian cells in culture. Cyclopenta(cd)pyrene 3,4-oxide, a presumed metabolite, was found to be a direct-acting mutagen and to transform mammalian cells. These results suggest that cyclopenta(cd)pyrene 3,4-oxide may be an ultimate mutagenic form of the parent hydrocarbon.

Animals↗
PubMed1979

Incubation of 3,4-benzo(s)pyrene with serum fractions: effect on tumor production.

The effect on tumor formation in Swiss mice of incubation of 3,4-Benzo(a)pyrene [B(a)P]either with saline or saline containing serum, gamma-globulin or albumin (form mouse or rabbit) was investigated. A high incidence of sarcomas (80--100%) was obtained in Swiss mice by B(A)P incubated in vitro with rabbit serum, rabbit gamma-globulin, mouse serum, mouse gamma-globulin, and saline. A lower incidence (60--65%) was obtained with B(a)P incubated with mouse serum, mouse albumin, and rabbit albumin. The data suggest that binding of B(a)P to protein, particularly to albumin, significantly decreases the biological activity of B(a)P.

Animals↗
PubMed1979

Benzo[alpha]pyrene antibody inhibition of benzo[alpha]pyrene-induced mutageneis.

An antibody to benzo[alpha]pyrene (BP) was prepared. The isolated antibody showed a specificity for BP and a low reactivity with another carcinogenic hydrocarbon, 7,12-dimethylbenz[alpha]anthracene (DMBA). The BP-antibody inhibited the in vitro cytotoxic and mutagenic activity of BP in both a rat embryo fibroblast- and a rat lung cell-mediated mutagenesis system. A possible correlation of these in vitro findings to the in vivo carcinogenesis situation is discussed.

9,10-Dimethyl-1,2-benzanthracene↗