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Biomedical subjects

C M Rogers

Publications and source records attributed to C M Rogers.

At least 19 recordsLinked to original sources
PubMed1992

Localisation of the mitogenic epitope of staphylococcal enterotoxin B.

Limited digestion of staphylococcal enterotoxin B (SEB) with trypsin resulted in the generation of a 12-Kda amino-terminal fragment and a 17-Kda carboxy-terminal fragment which were isolated by preparative iso-electric focusing. The carboxy-terminal fragment exhibited significant mitogenic activity for murine splenocytes, whereas the isolated amino-terminal fragment possessed little detectable mitogenic activity. Monoclonal antibodies (MAbs) specific for the carboxy-terminal fragment neutralised most of the mitogenic activity of both the intact toxin and the carboxy-terminal fragment. MAbs specific for the amino-terminal fragment had no detectable neutralising activity. These results support the hypothesis that the epitope(s) responsible for mitogenic activity is located in the carboxy-terminal region of SEB.

Amino Acid Sequence↗
PubMed1989

Calmodulin is associated with microtubules forming in PTK1 cells upon release from nocodazole treatment.

To investigate the association of calmodulin (CaM) with microtubules (MTs) in the mitotic apparatus (MA), the distributions of CaM and tubulin were examined in cells in which the normal spindle organization had been altered. A fluorescent CaM conjugate with tetramethylrhodamine isothiocyanate (CaM-TRITC) and a dichlorotriazinyl aminofluorescein conjugate with tubulin (tubulin-DTAF) were injected into cells that had been treated with the MT inhibitor nocodazole. With moderate nocodazole concentration (0.3 micrograms/ml, 37 degrees C, 4 h) in live cells, CaM-TRITC and tubulin-DTAF concentrated identically on or near the centrosomes and kinetochores. In serial sections of these cells, small MT segments were observed by transmission electron microscopy (TEM) in the regions where fluorescent protein had concentrated. When a higher drug concentration was used (3.0 micrograms/ml, 37 degrees C, 4 h), no regions of CaM-TRITC or tubulin-DTAF localization were observed, and no MTs were observed when serial sections were examined by TEM. However, following release from the high-concentration nocodazole block, CaM-TRITC colocalized with newly formed MTs at the kinetochores and centrosomes. Later in the recovery period, when chromosome-to-pole fibers had formed, CaM association with kinetochores diminished, ultimately attaining its normal pole-proximal association with kinetochore MTs in cells that progressed through mitosis. We interpret these observations as supporting the hypothesis that in the MA, CaM attains a physical association with kinetochore MTs and suggest that CaM-associated MTs may be inherently more stable.

Animals↗
PubMed1988

Calmodulin stabilization of kinetochore microtubule structure to the effect of nocodazole.

To investigate the function of calmodulin (CaM) in the mitotic apparatus, the effect of microinjected CaM and chemically modified CaMs on nocodazole-induced depolymerization of spindle microtubules was examined. When metaphase PtK1 cells were microinjected with CaM or a CaM-TRITC conjugate, kinetochore microtubules (kMTs) were protected from the effect of nocodazole. The ability of microinjected CaM to subsequently protect kMTs from the depolymerizing effect of nocodazole was dose dependent, and was effective for approximately 45 min, with protection decreasing if nocodazole treatment was delayed for more than 60 min after injection of CaM. The CaM-TRITC conjugate, similar to native CaM, displayed the ability to activate bovine brain CaM-dependent adenylate cyclase in a Ca++-dependent manner and showed a Ca++-dependent mobility shift when subjected to PAGE. A heat-altered CaM-TRITC conjugate also protected kMTs from the effect of nocodazole. However, this modified CaM was not able to activate adenylate cyclase nor did it display a Ca++-dependent mobility shift when electrophoresed. In a permeabilized cell model system, both CaM analogs were observed to bind to the spindle in a Ca++-independent manner. In contrast, a performic acid-oxidized CaM did not have a protective effect on spindle structure when microinjected into metaphase cells before nocodazole treatment. The oxidized CaM did not activate adenylate cyclase and did not exhibit Ca++-dependent mobility on polyacrylamide gels. These results are interpreted as supporting the hypothesis that CaM binds to the mitotic spindle in a Ca++-independent manner and that CaM may serve in the spindle, at least in part, to stabilize kMTs.

Animals↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMedDate not supplied

Innervation patterns in rat saccular macula. A structural basis for complex sensory processing.

Serial sections through the anterior part of rat saccular macula were reconstructed as montages. Findings are that type II hair cells are integrated into the neural circuitry of type I cells, chiefly by synapses with neighboring calyces and their collaterals; and that complex interactions between afferent- and efferent-type nerve elements take place. Three basic types of nerve/calyx pattern are present: U-type nerves lose their myelin before they enter the macula and have complex calyces with several collaterals; M-type nerves are myelinated up to the calyx, which lacks collaterals; and M/U-type nerves have short, unmyelinated segments proximal to their calyces, which have few collaterals. Both afferent- and efferent-type collaterals spring from calyces, chiefly from those of U-type nerves. Type II cells are presynaptic both to electron-lucent and to vesiculated terminals; some synapses are reciprocal. Electron-lucent boutons sometimes are presynaptic to calyces and to type II hair cells; and morphologically afferent-to-afferent kinds of synapses occur in the neuroepithelium. The anatomical findings indicate that complex information processing must occur in mammalian gravity receptors.

Animals↗