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Biomedical subjects

J C Merrill

Publications and source records attributed to J C Merrill.

At least 19 recordsLinked to original sources
PubMed1988

Role of glutathione in the toxicity of the sesquiterpene lactones hymenoxon and helenalin.

Hymenoxon and helenalin are toxic sesquiterpene lactones present in the toxic range plants Hymenoxys odorata and Helenium microcephalum. Helenalin (25 mg/kg) or hymenoxon (30 mg/kg) administered to immature male ICR mice caused a rapid decrease in hepatic glutathione levels and were lethally toxic to greater than 60% of the animals within 6 d. L-2-Oxothiazolidine 4-carboxylate (OTC), a compound that elevates cellular glutathione levels, administered to mice 6 or 12 h before either helenalin or hymenoxon protected against hepatic glutathione depletion and the lethal toxicity of these toxins. OTC administered at the same time as the sesquiterpene lactones was not protective, suggesting that the critical events against which glutathione is protective occur within the first 6 h. In primary rat hepatocyte cultures, hymenoxon and helenalin (4-16 microM) caused a rapid lethal injury as determined by the release of lactate dehydrogenase. Cotreatment of cultures with N-acetylcysteine at high concentrations (4 mM) afforded significant protection against lethal injury by both toxins. In contrast, BCNU, which inhibits glutathione reductase, or diethylmaleate, which depletes hepatocellular glutathione, potentiated the hepatotoxicity of helenalin and hymenoxon in monolayer rat hepatocytes. These studies suggest that the in vivo and in vitro toxicity of hymenoxon and helenalin is strongly dependent on hepatic glutathione levels, which hymenoxon and helenalin rapidly deplete at very low concentrations.

Acetylcysteine↗
PubMed1987

Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450.

Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450AROM), it was found that the rate of synthesis of cytochrome P-450AROM was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450AROM synthesis were associated with comparable changes in the levels of translatable cytochrome P-450AROM mRNA, as well as with changes in the activity of aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450AROM, and that such changes are likely a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450AROM mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.

Adipose Tissue↗
PubMed1985

The in vitro metabolism of benzo[a]pyrene by polychlorinated and polybrominated biphenyl induced rat hepatic microsomal monooxygenases.

The metabolism of benzo[a]pyrene by halogenated biphenyl-induced rat hepatic microsomal monooxygenases was determined using a high pressure liquid chromatographic assay system. Incubation of benzo[a]pyrene with microsomes from rats pretreated with phenobarbitone or phenobarbitone-type inducers (2,2',4,4',5,5'-hexachlorobiphenyl, 2,2',4,4',6,6'-hexachlorobiphenyl, 2,2',5,5'-tetrachlorobiphenyl, 2,2',4,4',5,5'-hexabromobiphenyl, and 2,2',5,5'-tetrabromobiphenyl) resulted in increased overall metabolism of the hydrocarbon (less than fourfold) into phenolic, quinone, and diol metabolites, with the most striking increase observed in the formation of 4,5-dihydro-4,5-dihydroxybenzo[a]pyrene. In contrast, the metabolism of benzo[a]pyrene by microsomes from rats induced with 3-methylcholanthrene or 3,3',4,4'-tetrachlorobiphenyl resulted in a greater than 10-fold increase in overall benzo[a]pyrene metabolism, with the largest increases observed in the formation of the trans-7,8- and -9,10-dihydrodiol metabolites of benzo[a]pyrene. However, in comparison to control and phenobarbitone-induced microsomes, the oxidative conversion of benzo[a]pyrene by microsomes induced with 3-methylcholanthrene and 3,3',4,4'-tetrachlorobiphenyl into the 6,12-quinone was substantially inhibited. Previous reports have shown that the commercial halogenated biphenyl mixtures, fireMaster BP-6, and Aroclor 1254 are mixed-type inducers and that microsomes from rats pretreated with these mixtures markedly enhance the overall metabolism of benzo[a]pyrene. Not surprisingly, the metabolism of benzo[a]pyrene by microsomes from rats pretreated with the mixed-type inducers, 2,3,3',4,4'-penta-,2,3,3',4,4',5-hexa-, and 2',3,3',4,4',5-hexa- chlorobiphenyl was also increased and the metabolic profile was similar to that observed with fireMaster BP-6 and Aroclor 1254 induced microsomes.

Animals↗
PubMed1984

DRG-based case mix and public hospitals.

The 12 acute care public hospitals in New York City (HHC hospitals) are compared with a matched group of nonpublic hospitals (non-HHC hospitals). The following questions are considered: using DRGs to define case mix, how does the case mix of HHC and non-HHC hospitals differ; to what extent do differences in case mix account for differences in average length of stay (ALOS); can factors other than case mix be identified that may explain differences in ALOS? Although about one half of the 20 most prevalent DRGs are similar in both types of institutions, there are clear case mix differences. The higher percentage of abortion, psychiatric, and chemical dependence discharges and the lower prevalence of surgery in HHC hospitals contribute to this difference. The case load is more concentrated in fewer DRGs in HHC hospitals. HHC hospitals treat more patients in DRGs with a shorter ALOS, but, on the average, patients in the same DRG stay more than 1 day longer in HHC facilities. To some extent, this longer LOS can be explained by differences in payor type, primary diagnosis within a DRG, and, most important, in the percentage of outlier patients.

Costs and Cost Analysis↗
PubMed1984

Health care institutions: survival in a changing environment.

The health care system in the United States has been altered by recent economic and political events, including a major recession and a retrenchment in federal nonentitlement spending programs. The economic recovery and the continuing high federal deficits prompt new questions about both the future expansion and the distribution of health spending. Long-term economic forecasts and public opinion polls suggest that health will consume a growing share of the national resources. Nevertheless, the level of health spending will not grow as rapidly as in the past, and the distribution of that spending may also change. Because of these changes, the growth in health spending will not guarantee the survival of existing institutions. New competitive forces and revised reimbursement mechanisms will lead to a redistribution of the health dollar, and this redistribution will create both risk and opportunity for America's important health care institutions and their health professionals.

Academic Medical Centers↗