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Biomedical subjects

J S Harris

Publications and source records attributed to J S Harris.

At least 55 records · Page 3Linked to original sources
PubMed1991

Health care economic factors and the effects of benefits plan design changes.

Medical benefits costs now exceed 13% of payroll, up from 5% in the early 1980s. Full reimbursement for more expensive hospital-based care, a technology and specialist supply explosion funded by Medicare and Medicaid, and cost shifting from these programs to private insurance have fueled this rapid growth. Benefits plans, which had provided essentially free care, have been changed slowly and incrementally to increase cost sharing and, thus, cost sensitivity on the part of employees. Many insurance plans also limit coverage by requiring that treatment be "nonexperimental" and "medically necessary." Long-term inquiry demonstrates that total expenditures, hospitalization rates, ambulatory visit rates, dental visits, and prescription drug use were significantly higher for free care than for plans with substantial copayments. A study sponsored by a business coalition in Houston showed that increased deductibles shifted care to the inpatient setting, raising total costs. Higher contribution rates reduced both inpatient and outpatient costs. Caps on payment for certain services, such as mental health care, reduced costs significantly with apparently minimal adverse effects on health.

Deductibles and Coinsurance↗
PubMed1990

Why doctors do what they do: determinants of physician behavior.

Direct payments to physicians account for about 20% of the medical care dollar, but physician decisions cause over 80% of the costs of medical care. Decision making can be viewed in a number of ways: as pure information processing, as an interaction with various stimuli, including financial penalties and incentives, and as social behavior, interacting with and reacting to peer and leadership influence. The model that accounts for the greatest amount of the available data is a multifactorial one that takes all of these views into account. The most successful behavior change efforts use a variety of mutually reinforcing approaches, and must be present constantly or behaviors revert to highly variable (lower quality) actions and decisions. This appears to be a behavioral version of the second law of thermodynamics (entropy increases spontaneously). The best practice model to manage costs and quality appears to be one in which physicians and administrators have adequate up to date information available, make group decisions, develop and continuously improve agreed upon methods of practice, interact and think before acting, and have rewards for such behavior.

Behavior↗
PubMed1986

The prevalence of health risks in an employed population.

To optimize use of the limited resources of the Tennessee State Employee Health Service, health risk and abnormality rates were tabulated for employees screened in the multiphasic screening program in 1983. Histories and health questionnaires revealed many more preventable or correctable health risks and abnormalities than did laboratory or physiologic tests or physical examinations. No previously unknown abnormalities were located by physical examination alone. The authors conclude that health history, risk appraisal, and counseling may be the most productive elements of a preventive screening program for employed groups, as well as for the general population.

Adult↗
PubMed1983

Guanosine 5'-diphosphate 3'-diphosphate levels, carbon source, and ribonucleic acid synthesis in a mutant strain of Escherichia coli.

We have previously described a mutant strain of Escherichia coli (2S142) which shows a specific inhibition of stable RNA synthesis at 42 degrees C. The temperature-sensitive lesion mimics a carbon source downshift (diauxie lag). We therefore measured RNA synthesis and levels of ppGpp (guanosine 5'-diphosphate 3'-diphosphate) on a number of different carbon sources. There is a 6-fold variation in ppGpp levels at 42 degrees C, depending on the carbon source present. Much of the variation in ppGpp levels at 42 degrees C can be explained by variations in the decay rate of ppGpp at 42 degrees C. The rates of ribosomal RNA and total RNA synthesis also vary with the carbon source at 42 degrees C. Linear regression analysis shows only a moderately good correlation (correlation coefficient = 0.62, P = 0.0001) between the ppGpp level at 42 degrees C and the rate of rRNA synthesis at 42 degrees C. In fact, ppGpp levels are a slightly better predictor of the rate of total RNA synthesis (correlation coefficient = 0.69, P = 0.0001) at 42 degrees C. Other variables such as rate of carbon source uptake appear to have very little, if any, relationship to the rate of rRNA synthesis on the different carbon sources. Segmented linear regression analysis indicates that ppGpp levels and rates of RNA synthesis correlate best when the carbon sources are divided into two groups: 6- and 12-carbon sugars and other carbon sources. The rate of rRNA synthesis in 2S142 at 42 degrees C appears to be relatively insensitive to ppGpp levels with 6- and 12-carbon sugars as the carbon source. These data raise the possibility that carbon source may affect rRNA synthesis in a manner that is at least partially unrelated to ppGpp levels.

Carbohydrate Metabolism↗
PubMed1983

Specific effects of 5-fluoropyrimidines and 5-azapyrimidines on modification of the 5 position of pyrimidines, in particular the synthesis of 5-methyluracil and 5-methylcytosine in nucleic acids.

5-Fluoropyrimidines and 5-azapyrimidines were found in our laboratory to be specific inhibitors of modification reactions taking place at the 5 position of pyrimidines in nucleic acids. Thus, 5-fluorouracil and 5-fluorouridine specifically inhibit the formation of 5-methyluracil, pseudouridine, and 5,6-dihydrouracil in tRNA. 5-Fluorocytidine, which is partially biotransformed to 5-fluorouracil derivatives in mammalian cells, inhibits the formation of 5-methyluracil, pseudouridine, 5,6-dihydrouracil, and 5-methylcytosine, and 5-azacytidine is a specific inhibitor of the formation of 5-methylcytosine in tRNA and DNA. Inhibitory effects on tRNA modifications require RNA synthesis, as shown by the observation that various inhibitors of RNA synthesis block the drug effects. An inhibitory low-molecular-weight (4-7S) RNA, consisting mainly of tRNA and pre-tRNA, was isolated from livers of mice after treatment with 5-azacytidine. This RNA, when added to an in vitro tRNA methyltransferase assay, specifically interfered with the formation of 5-methylcytosine in substrate tRNA. Similarly, a DNA inhibiting the synthesis of 5-methylcytosine in an in vitro DNA methylation assay was isolated from L1210 leukemic cells treated with a high dose of 5-azacytidine for a short time. Our data are consistent with the hypothesis that incorporation of 5-azacytosine into positions that are normally occupied by C residues destined to become methylated is required for the inhibition to occur, and a similar situation probably applies to the 5-fluoropyrimidine analogs. Analog base moieties occupying such sites are likely to bind strongly, perhaps irreversibly, to the active sites of the particular modifying enzymes. All our observations with the 5-fluoro- and 5-azapyrimidines are in accord with this hypothesis. It was also observed that administration of 5-azacytidine to mice led to strong inhibition of tRNA cytosine-5-methyltransferase, while at the same time the activities and capacities of purine-specific tRNA methyltransferases became strongly elevated after an initial lag period. We speculate that such increases may represent a response of the cell to the methylation defect induced by the drug. Undermodified tRNAs present in neoplastic cells may also trigger an increased synthesis of modifying enzymes. A scheme has been presented which explains increased tRNA turnover and increased activities of modifying enzymes in neoplastic cells as a consequence of a primary defect in tRNA modification.

5-Methylcytosine↗
PubMed1981

Responses of Fanconi anemia fibroblasts to adenine and purine analogues.

Fanconi anemia (FA) fibroblasts are known to be exceptionally sensitive to the cytotoxic action of mitomycin C (MMC). The survival of FA cells was enhanced significantly when 0.5 mM caffeine or 0.5 mM adenine was added for 72 h after the cells were exposed to MMC. In other experiments in which MMC was not used, FA fibroblasts were shown to be significantly more sensitive than control cells to 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and 6-azauridine (6-AU). These observations offer a new approach to defining the basic biochemical defect in FA.

Anemia, Aplastic↗
PubMed1978

Aminoacylation of undermethylated mammalian transfer RNA.

To study the role of 5-methylcytidine in the aminoacylation of mammalian tRNA, bulk tRNA specifically deficient in 5-methylcytidine was isolated from the livers of mice treated with 5-azacytidine (18 mg/kg) for 4 days. For comparison, more extensively altered tRNA was isolated from the livers of mice treated with DL-ethionine (100 mg/kg) plus adenine (48 mg/kg) for 3 days. The amino acid acceptor capacity of these tRNAs was determined by measuring the incorporation of one of eight different 14C-labeled amino acids or a mixture of 14C-labeled amino acids in homologous assays using a crude synthetase preparation isolated from untreated mice. The 5-methylcytidine-deficient tRNA incorporated each amino acid to the same extent as fully methylated tRNA. The tRNA from DL-ethionine-treated livers showed an overall decreased amino-acylation capacity for all amino acids tested. The 5-methylcytidine-deficient tRNA from DL-ethionine-treated mice were further characterized as substrates in homologous rate assays designed to determine the Km and V of the aminoacylation reaction using four individual 14C-labeled amino acids and a mixture of 14C-labeled amino acids. The Km and V of the reactions for all amino acids tested using 5-methylcytidine-deficient tRNA as substrate were essentially the same as for fully methylated tRNA. However, the Km and V were increased when liver tRNA from mice treated with DL-ethionine plus adenine was used as substrate in the rate reaction with [14C]lysine as label. Our results suggest that although extensively altered tRNA is a poorer substrate than control tRNA in both extent and rate of aminoacylation, 5-methylcytidine in mammalian tRNA is not involved in the recognition of the tRNA by the synthetase as measured by aminoacylation activity.

Amino Acids↗
PubMed1978

Guanine nucleotide metabolism in a mutant strain of Escherichia coli with a temperature sensitive lesion in rRNA synthesis.

We have described a mutant of Escherichia coli (designated 2S142) which shows specific inhibition of rRNA synthesis at 42 degrees C. ppGpp levels increase at the restrictive temperature, as expected. However, when the cells are returned to 30 degrees C, rRNA synthesis resumes before ppGpp levels have returned to normal. Furthermore, when ppGpp levels are decreased by the addition of tetracycline or choramphenicol, rRNA synthesis does not resume at 42 degrees C. Also, a derivative of 2S142 with a temperature-sensitive G factor (which cannot synthesize either protein or ppGpp at 42 degrees C) shows identical kinetics of rRNA shut-off at 42 degrees C as 2S142. Thus, the elevated ppGpp levels in this mutant do not appear to be directly responsible for the cessation of rRNA synthesis at 42 degrees C.

Escherichia coli↗