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Biomedical subjects

R T Williams

Publications and source records attributed to R T Williams.

At least 37 records · Page 2Linked to original sources
PubMed1992

Co-purification of p34cdc2/p58cyclin A proline-directed protein kinase and the retinoblastoma tumor susceptibility gene product: interaction of an oncogenic serine/threonine protein kinase with a tumor-suppressor protein.

Proline-directed protein kinase (PDPK) is characterized as a cytoplasmic oncogenic serine/threonine kinase that is activated by growth factor-mediated mechanisms and is proposed to function in mammalian somatic cells as an S phase promoting factor. The present study was undertaken to assess the hypothesis that p34cdc2/p58cyclinA PDPK is a physiologically relevant form of the p34cdc2 protein kinase that phosphorylates and inactivates the product of the retinoblastoma/osteosarcoma tumor susceptibility gene (Rb protein). In the course of these studies it was determined (fortuitously) that the p34cdc2/p58cyclinA PDPK purified from the cytosol of FM3A mouse mammary carcinoma cells was 'contaminated' by several high molecular weight substrate proteins that essentially co-purified with the protein kinase, one of which was identified as the Rb protein itself (p105Rb). High-resolution fast protein liquid chromatography (FPLC) revealed that the Rb protein co-purified with a particular subset of the PDPK heterodimer, i.e. with a single species of the 58 kDa cyclinA doublet. The subset of PDPK associated with the Rb protein exhibited somewhat lower specific enzyme activity, as judged by in vitro kinase assays and comparative Western blotting. Immunoprecipitation studies confirmed that p105Rb is physically associated with the p34cdc2/p58cyclin A PDPK. Further studies confirmed that the underphosphorylated Rb protein (p105Rb) present in G1 lysates of synchronized human MG63 osteosarcoma cells could be readily phosphorylated by purified PDPK in vitro, resulting in the characteristic shift in the apparent molecular mass (SDS-PAGE) of the Rb protein that is reported to accompany the hyperphosphorylation and functional inactivation of this protein. Moreover, the induction of the cyclin A subunit of PDPK in these synchronized MG63 cells was found to be closely correlated with the cell cycle-dependent phosphorylation of the Rb protein. From these studies it is concluded that the growth factor-sensitive PDPK is a physiological Rb kinase, which may function to inactivate the Rb protein in vivo.

Animals↗
PubMed1990

Early onset of nonalcoholic cirrhosis in patients with familial alcoholism.

The etiology of many forms of liver disease is largely unknown. Recent research has identified certain immunogenetic factors which may play a role in the progression of alcoholic cirrhosis as well as autoimmune forms of cirrhosis. In this study we examined the role of familial alcoholism and HLA status in determining age of liver disease onset. Patients with biopsy-proven nonalcoholic autoimmune cirrhosis and having a history of familial alcoholism experience an earlier age of onset of liver disease than patients without a family history of alcoholism. The same result was true for patients with alcoholic liver disease. This effect may be more prominent in females. Subjects with HLA B-8 also had a younger age of onset of nonalcoholic autoimmune liver disease. The presence of a family history of alcoholism in conjunction with the presence of HLA B-8 and DR-3 also was related to an earlier age of disease onset. These findings suggest that the susceptibility to develop alcoholism and nonalcoholic autoimmune liver disease may be transmitted conjointly and point to potential fruitful areas of research for identifying individuals at risk for developing cirrhosis as well as detecting genetic markers for alcoholism.

Adolescent↗
PubMed1986

Cardiovascular responses and lidocaine absorption in fiberoptic-assisted awake intubation.

Local anesthetic toxicity and cardiovascular stress during fiberoptic-assisted awake tracheal intubation were assessed prospectively in 20 patients with airway management problems. Cardiovascular responses, dose of lidocaine, its systemic absorption, and patient comfort were measured. A standardized topical anesthesia protocol of 4% lidocaine aerosol, topical 2% lidocaine viscous gel, and direct perbronchoscopic laryngeal application was used. Awake intubation produced no significant elevation of blood pressure or pulse rate either during the topical application or after the intubation. Despite a large total dose of topical lidocaine (5.3 +/- 2.1 mg/kg), the mean peak arterial plasma lidocaine concentration was low (0.6 +/- 2.1 micrograms/ml). Patient comfort assessment showed that nine patients had no discomfort, whereas 11 had minimal discomfort. Supplementary sedation used was minimal (fentanyl, 1.4 +/- 0.6 micrograms/kg, and diazepam, 1.9 +/- 1.8 mg). This method of producing topical anesthesia for awake tracheal intubation is recommended as a safe, easy, and comfortable method of managing patients with airway difficulties.

Absorption↗
PubMed1985

Methanogenic bacteria, including an Acid-tolerant strain, from peatlands.

Five pure cultures of methanogenic bacteria were isolated from Minnesota peatlands by enrichment culture techniques. One strain, identified as a member of the family Methanobacteriaceae by antigenic fingerprinting, was acid tolerant and able to produce methane at pH 3.1. Growth could not be demonstrated at pH less than 5.3.

Journal Article↗
PubMed1985

Biphasic changes in 3-methylhistidine excretion in humans after exercise.

We previously reported that 3-methylhistidine excretion was increased in human subjects after a strenuous bout of exercise. Because other investigators have not corroborated this finding, we undertook the present study to investigate the conditions that result in decreased and increased 3-methylhistidine excretion in human subjects after exercise. Four experiments were performed: a cross-sectional study comparing 3-methylhistidine excretion in endurance-trained subjects with untrained controls, a longitudinal study of 3-methylhistidine excretion by female basketball players before the start of the season and again during the competitive season, an experiment to determine changes in 3-methylhistidine excretion as a result of 2 h of exercise each day for 7 consecutive days, and a study to determine changes in 3-methylhistidine excretion during 4-h intervals after a strenuous exercise bout. The 3-methylhistidine-to-creatinine ratio was approximately 20% higher for trained than nontrained subjects. In three separate experiments a biphasic change of 3-methylhistidine excretion was observed in response to exercise with an immediate decrease in the 3-methylhistidine-to-creatinine ratio during exercise followed by a prolonged increase. The magnitudes of the negative and positive responses determine whether one observes an increase, no change, or a decrease in the total daily excretion of 3-methylhistidine.

Creatinine↗
PubMed1984

Methane production in Minnesota peatlands.

Rates of methane production in Minnesota peats were studied. Surface (10- to 25-cm) peats produced an average of 228 nmol of CH(4) per g (dry weight) per h at 25 degrees C and ambient pH. Methanogenesis rates generally decreased with depth in ombrotrophic peats, but on occasion were observed to rise within deeper layers of certain fen peats. Methane production was temperature dependent, increasing with increasing temperature (4 to 30 degrees C), except in peats from deeper layers. Maximal methanogenesis from these deeper regions occurred at 12 degrees C. Methane production rates were also pH dependent. Two peats with pHs of 3.8 and 4.3 had an optimum rate of methane production at pH 6.0. The addition to peat of glucose and H(2)-CO(2) stimulated methanogenesis, whereas the addition of acetate inhibited methanogenesis. Cysteine-sulfide, nitrogen-phosphorus-trace metals, and vitamins-yeast extract affected methane production very little. Various gases were found to be trapped or dissolved (or both) within peatland waters. Dissolved methane increased linearly to a depth of 210 cm. The accumulation of metabolic end products produced within peat bogs appears to be an important mechanism limiting carbon turnover in peatland environments.

Journal Article↗