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Biomedical subjects

C M Rogers

Publications and source records attributed to C M Rogers.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of antituberculosis drugs in patients.

The pharmacokinetics of rifampin, isoniazid, and ethambutol were determined in 26 ambulatory male patients (aged 49.5 +/- 9.9 yr) with tuberculosis. Rifampin and isoniazid were given individually or together, with or without ethambutol; studies were done after a single dose and after chronic administration. Under the study conditions, with large variability in the extent of disease and physical status and history of alcohol and tobacco abuse and narrow age range, the pharmacokinetics of these three antituberculosis drugs were not modified significantly by patient age. Furthermore, appreciable drug-drug interactions did not occur when the three drugs were administered concurrently. Self-induction of rifampin clearance by chronic dosing with the drug may lead to subtherapeutic levels of rifampin. Administration of isoniazid and ethambutol in two divided doses resulted in peak plasma concentrations below the accepted therapeutic levels of the two drugs. Our findings indicate that at least in the middle-aged patients with tuberculosis, the current single daily dose, multiple-drug regimen is therapeutically sound pharmacokinetically, and clinicians do not have to make adjustments in dosages of these drugs for age and the extent of disease.

Adult↗

Induction of suppressor cells in vitro by Candida albicans.

Normal splenocytes cultured with Formalin-killed Candida albicans were shown to acquire significant suppressor cell activity in a period of 3 days. These cells were found to suppress both the phytohemagglutinin-induced mitogen response as well as the anti-sheep erythrocyte antibody response. Experiments were carried out to determine the nature of the suppressor cell population. Results showed that these cells were not susceptible to treatment with anti-Thy 1 antibody and complement. Panning experiments showed that the suppressor cells were not plastic-adherent or Mac-1 antigen-positive. The suppressor cells were, however, adherent to anti-mouse immunoglobulin (F(ab')2-fragment)-coated dishes. Additional experiments showed that the suppressor cell activity was susceptible to treatment with monoclonal anti-Lyb 2.1 antibody and complement. These results suggest that the suppressor cell induced in vitro by Candida is a member of the B-lymphocyte lineage.

Animals↗

Microinjected ras family oncogenes stimulate DNA synthesis in quiescent mammalian cells.

Oncogenes of the ras family stimulate DNA synthesis when microinjected into quiescent mouse and hamster fibroblasts, as detected by in situ autoradiography. The molecularly cloned genomes of Harvey and Kirsten sarcoma viruses, the cloned Harvey ras gene, and the product of the v-ras gene, the p21v-rasH protein, stimulate DNA synthesis in quiescent cells. This stimulation is comparable to the stimulatory activity of the microinjected SV40 T-antigen-coding gene. The demonstration that these oncogenes can stimulate transient DNA synthesis in quiescent cells is relevant to understanding the mechanism by which these genes are able to transform cells in vitro and induce tumors in animals.

Animals↗

Effects of Wy-18,251 (3-p-chlorophenyl)thiazolo[3,2-a]benzimidazole- 2-acetic acid), levamisole and indomethacin on the generation of murine T suppressor cells in vitro.

In vitro culture of normal BALB/c spleen cells with staphylococcal enterotoxin B (SEB) activates antigen non-specific suppressor T cells (Ts) which can be assayed by their ability to suppress antibody production in a plaque assay. Addition of the experimental immunomodulatory drug Wy-18,251 (10-100 microM) to cultures of spleen cells plus SEB significantly increased Ts activity relative to cultures without the drug. Similar results were obtained with levamisole, but, in contrast, indomethacin (0.1-10 microM) inhibited SEB-induced suppressor cell activity. The ability of Wy-18,251 to augment Ts activity could be therapeutically useful in the treatment of those autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, in which hyperactive B cell function is a characteristic feature.

Animals↗

T4 phage-coded dihydrofolate reductase. Subunit composition and cloning of its structural gene.

The structures of phage-coded dihydrofolate reductases are of interest because of 1) possible relationship to plasmid-coded dihydrofolate reductases; 2) unusual regulation of enzyme synthesis; and 3) multiple roles and intermolecular interactions involving the protein. To prepare for primary structural studies, we have cloned the T4 frd gene, which codes for dihydrofolate reductase, and we have determined for redetermined some physical properties of the enzyme. The native enzyme has a molecular weight of about 44,500, as determined by sedimentation velocity and gel filtration, and a subunit molecular weight of about 23,000, as determined by aminopterin titration and denaturing gel electrophoresis. We conclude that the enzyme is a dimer, with each subunit containing one methotrexate-binding site. A 1.1-kilobase pair fragment from a HindIII restriction digest of cytosine-substituted T4 DNA was cloned into pBR322, and recombinants were identified by trimethoprim resistance. Cells carrying this recombinant plasmid produce both the host cell and phage-coded dihydrofolate reductases.

Cloning, Molecular↗

Impaired growth hormone secretion in the adult population: relation to age and adiposity.

Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.

Adult↗

Sialic acids of human large bowel mucosa: o-acylated variants in normal and malignant states.

Five sialic acid variants have been demonstrated in normal, 'transitional', and tumour extracts of human large bowel mucosa by thin-layer chromatography. Two-dimensional thin-layer chromatography, with intermediate alkaline hydrolysis, confirmed that the variants were N-acetyl neuraminic acids with additional O-acylation. Cases studied so far show changes in the proportions of these variants in malignancy.

Acylation↗

JC virus, a human polyomavirus associated with progressive multifocal leukoencephalopathy: additional biological characteristics and antigenic relationships.

JC virus, a human polyomavirus, failed to grow or produce cytopathic effects in any of a variety of cells tested other than primary human fetal glial (PHFG) cells. Cells tested included other primary human cells and glial cells from other animals. Only a rare cell in inoculated insusceptible human cell cultures produced T or virion antigen. In PHFG cell cultures JC virus produced subtle cytopathic effects, and the majority of progeny remained cell associated. Only a few cells in the heterogenous PHFG cell cultures contained T antigen at 24 h postinoculation, and virion antigen was not detected until 48 h postinoculation. The infectivity of JC virus was resistant to inactivation by ether and by heating at 50 degrees C for 1 h. A three-way minor antigenic relationship was demonstrated among the virion antigens of JC virus, BK virus, and simian virus 40 by neurtralization and/or hemagglutination inhibition tests. Serological evidence is presented for the existence of JC virus as a distinct entity before the use of simian virus 40-contaminated poliovirus vaccines and for the nonexistence of an animal reservoir for JC virus infection.

Animals↗