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Biomedical subjects

D McClure

Publications and source records attributed to D McClure.

36 records · Page 2Linked to original sources
PubMed1992

Pseudohyperphosphataemia in patients with multiple myeloma.

The phosphate concentrations were measured in 41 patients who had multiple myeloma with paraproteinaemia using four different methods to compare the incidence of pseudohyperphosphataemia. The direct acid/molybdate method produced the highest number of anomalous results. The erroneously high phosphate concentration was attributable to the presence of turbidity in the reaction mixture. No association was found between paraprotein type and occurrence of turbidity. The direct acid/molybdate method was unreliable in patients with serum paraproteins and should therefore not be used for the measurement of phosphate concentration in such patients.

Biochemistry↗
PubMed1991

Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2.

Phospholipases A2 (PLA2s) play a key role in inflammatory processes through production of precursors of eicosanoids and platelet-activating factor. Recently, we described the purification of a novel approximately 100-kDa cytosolic PLA2 (cPLA2) from human monoblast U937 cells that is activated by physiological (intracellular) concentrations of Ca2+ (Kramer, R. M., Roberts, E. F., Manetta, J., and Putnam, J. E. (1991) J. Biol. Chem. 266, 5268-5272). Here we report the isolation of the complementary DNA encoding human cPLA2 and confirm its identity by expression in bacteria and in hamster cells. The predicted 749-amino acid cPLA2 protein has no similarity to the well known secretory PLA2s, but contains a structural element homologous to the C2 region of protein kinase C. The molecular cloning of cPLA2 will allow further studies defining the structure, function, and regulation of this novel PLA2.

Amino Acid Sequence↗
PubMed1990

Cleavage of amyloid beta peptide during constitutive processing of its precursor.

The amyloid beta peptide (A beta P) is a small fragment of the much larger, broadly distributed amyloid precursor protein (APP). Abundant A beta P deposition in the brains of patients with Alzheimer's disease suggests that altered APP processing may represent a key pathogenic event. Direct protein structural analyses showed that constitutive processing in human embryonic kidney 293 cells cleaves APP in the interior of the A beta P, thus preventing A beta P deposition. A deficiency of this processing event may ultimately prove to be the etiological event in Alzheimer's disease that gives rise to senile plaque formation.

Amino Acid Sequence↗
PubMed1983

Effects of propranolol on blood lipids and lipoproteins in myocardial infarction.

The effects of propranolol on lipids and lipoproteins were investigated in survivors of a recent myocardial infarction who were enrolled in the double-blind Beta-Blocker Heart Attack Trial. Nonfasting serum samples were obtained in more than 2800 patients assigned randomly to either propranolol or placebo. The propranolol-treated group had high-density lipoprotein cholesterol levels 3-4 mg/dl less and triglyceride concentrations 30-40 mg/dl higher than the placebo group. These effects occurred in men and women in all age categories.

Adult↗
PubMed1982

Bromocriptine therapy in oligozoospermic infertile men.

A prospective, randomized double-blind study with crossover using bromocriptine and placebo was performed on a group of 17 infertile males with idiopathic oligozoospermia. Twelve patients completed the duration of this study of eight months by receiving 5 mg of bromocriptine per day for four months followed by four months of placebo or vice versa. Prior to treatment, the sperm count was 8.76 +/- 1.32 (10(6)/ml). The hormonal profile was performed prior to treatment and included estimation of prolactin, T3, T4, thyroid stimulating hormone (TSH), testosterone, follicle stimulating hormone (FSH), and plasma LH. Stimulation studies using LHRH and TRH were also performed. All hormonal estimations were within normal limits. Compared to placebo, bromocriptine had no significant effect on sperm analysis, or basic hormonal profile. The stimulation test with luteinizing hormone releasing hormone (LHRH) was unchanged except for the basic plasma testosterone, which increased. The prolactin decreased following the thyrotropin releasing hormone (TRH) stimulation. Two pregnancies were noted four to six weeks following the end of treatment. Bromocriptine did not seem to be more effective than placebo in the treatment of idiopathic oligozoospermia.

Adult↗
PubMed1982

Primary infertility: correlation between sperm migration test and humoral immunity.

Eleven couples with unexplained primary infertility were studied. The only abnormality appeared to be a poor sperm migration test (P.S.M.T.). The importance of circulating immune factors in these couples was assessed using a modified Kibrick test. Control sera included four provided by the WHO, four of our known positive samples, 49 sera obtained prevasectomy, and 17 sera collected from infertile couples with organic female pathology. A positive titer was found in one out of 49 control sera before vasectomy and in four out of 17 control coupled with organic female factors. In the 11 couples with poor sperm migration test, the titer was positive in two female and three male subjects. The wives of two of these male subjects with a positive titer became pregnant without any therapy. These results cast some doubts about the predictive value of such a test.

Agglutination Tests↗
PubMed1980

Effects of a serum spreading factor on growth and morphology of cells in serum-free medium.

A heat-sensitive, trypsin-sensitive factor that promoted growth and spreading of cells in serum-free, hormone-supplemented medium was partially purified from human serum. The major portion of the proteins in these preparations migrated upon SDS-polyacrylamide gel electrophoresis with a mobility consistent with molecular weights between 60,000 and 90,000. The spreading activity, which we have termed serum spreading factor, stimulated growth and spreading of a wide variety of cell types. The serum spreading factor was similar to fibronectin in that it showed an affinity for the plastic cell culture substrate but was shown to be distinct from fibronectin by several criteria. This factor may prove useful in studies of cell attachment and spreading and in studies of the relationship of cell shape and cell proliferation.

Animals↗
PubMed1976

Mechanism of inactivation of phenylalanine hydroxylase by p-chlorophenylalanine in hepatome cells in culture. Two possible models.

The mechanism by which p-chlorophenylalanine specifically reduces phenylalanine hydroxylase activity in rat liver in vivo and in Reuber H4 hepatoma cells in culture has been investigated. Chromatography on hydroxylapatite of liver extract from rats injected with p-chlorophenylalanine showed that the compound differentially affected the three normal phenylalanine hydroxylase isoenzymes (I, II, and III); isoenzymes II and III were completely absent after the treatment, but isoenzyme I was only reduced in quantity compared with normal adult rats. Normal Reuber H4 cells only possess isoenzyme I; treatment with p-chlorophenylalanine yielded a reduced level of enzyme activity which appeared to be noraml isoenzyme I by both chromatographic and kinetic criteria. There is evidence, based on immunochemical techniques, that cultures grown in the presence of p-chlorophenylalanine have significantly reduced levels of phenylalanine hydroxylase antigen, and that p-chlorophenylalanine inactivates phenylalanine hydroxylase at or near the time of enzyme synthesis. The bulk of enzyme synthesized prior to the addition of the compound appears unaffected by it. There is no indication that protein synthesis itself is affected by p-chlorophenylalanine. In addition, p-chlorophenylacetate was found to inactivate phenylalanine hydroxylase in an apparently identical manner with p-chlorophenylalanine, which almost certainly eliminates from consideration any mechanism of inactivation specifically requiring an amino acid. Finally, effects of cycloheximide and chlorophenylalanine were compared. Taken together, the data lead to two possible models for the inactivation of the enzyme. The model most consistent with all data requires (predicts) the existence of a proenzyme form of phenylalanine hydroxylase which can be specifically inactivated by p-chlorophenylalanine.

Animals↗
PubMed1976

The pharmacology of flazalone: a new class of anti-inflammatory agent.

The anti-inflammatory activity of flazalone, a unique chemical drug, is described. In acute irritant anti-inflammatory tests, flazalone exhibited a wide spectrum of activity. The compound was active in affecting the course of paw swelling in adjuvant arthritis when given daily either at the outset of the polyarthritis or after induction. The most unusual aspect of this compound is its ability to inhibit graft rejection in goldfish and rabbits. The pattern of anti-inflammatory activity does not allow one to classify this drug in the usual groups.

Adrenal Glands↗
PubMed1975

p-Chlorphenylalanine effect on phenylalanine hydroxylase in hepatoma cells in culture.

We have investigated the p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase activity in cultured hepatoma cells. The similarity of the effect of p-chlorophenylalanine on phenylalanine hydroxylase in the hepatoma cells and that reported from studies in vivo indicates that the loss of phenylalanine hydroxylase activity is due to a direct interaction of the amino acid analogue with the liver. We can find no evidence that the loss of phenylalanine hydroxylase activity is due to: a direct inactivation of the hydroxylase by p-chlorophenylalanine or an inhibitor produced by p-chlorophenylalanine treatment; an effect similar to that of p-fluorophenylalanine; or leakage of enzyme from the cells during p-chlorophenylalanine treatment. The data presented indicate: (a) the p-chlorophenylalanine effect is rather specific for phenylalanine hydroxylase; (b) following p-chlorophenylalanine removal, new protein synthesis is necessary for restoration of the hydroxylase activity; (c) the rate of loss of phenylalanine hydroxylase activity after the addition of p-chlorophenylalanine is much faster than the rate of restoration of the hydroxylase activity after removal of p-chlorophenylalanine; (d) even in the presence of p-chlorophenylalanine, hydrocortisone greatly stimulates the hydroxylase activity; (e) the cell density-dependent increase of phenylalanine hydroxylase activity is blocked by p-chlorophenylalanine. A discussion of the possible mechanisms of p-chlorophenylalanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low leanine-dependent loss of phenylalanine hydroxylase is presented. To measure very low levels of phenylalanine hydroxylase activity, a new procedure, based on isotope dilution, was developed for isolating the tyrosine formed during the enzymatic reaction.

Animals↗
PubMedDate not supplied

Improving estimates of exposures for epidemiologic studies of plutonium workers.

Epidemiologic studies of nuclear facilities usually focus on relations between cancer and doses from external penetrating radiation, and describe these exposures with little detail on measurement error and missing data. We demonstrate ways to document complex exposures to nuclear workers with data on external and internal exposures to ionizing radiation and toxic chemicals. We describe methods for assessing internal exposures to plutonium and external doses from neutrons; the use of a job exposure matrix for estimating chemical exposures; and methods for imputing missing data for exposures and doses. For plutonium workers at Rocky Flats, errors in estimating neutron doses resulted in underestimating the total external dose for production workers by about 16%. Estimates of systemic deposition do not correlate well with estimates of organ doses. Only a small percentage of workers had exposures to toxic chemicals, making epidemiologic assessments of risk difficult.

Colorado↗