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Biomedical subjects

M T Smith

Publications and source records attributed to M T Smith.

At least 235 records · Page 13Linked to original sources
PubMed1986

A clinicopathological study of 323 patients with oligodendrogliomas.

All patients with oligodendrogliomas (554) from the repository of the Armed Forces Institute of Pathology were retrospectively analyzed. The pathological diagnosis was confirmed in 323 patients and each case was graded according to a previously established grading system. The clinical features of these 323 verified cases of oligodendroglioma are presented, analyzed, and compared with findings in previous studies. There is a significant age skew according to tumor grade, with 68% of patients with grade A tumors under 40 years and 83% of patients with grade D tumors over 40 years of age. Headache was the most common symptom, followed by seizure, visual loss, papilledema, paralysis, and dementia. No symptoms showed a statistically significant correlation with tumor grade. However, tumor grading allowed significant prognostic statements to be made. Attention is drawn to several often neglected symptoms of oligodendrogliomas: ataxia, hemorrhage, stroke, and cerebrospinal fluid spread. This is, to our knowledge, the largest clinicopathological study of oligodendrogliomas to date.

Adolescent↗
PubMed1986

Correlations between in vitro dissolution, in vivo bioavailability and hypoglycaemic effect of oral glibenclamide.

A study has been carried out investigating four different marketed oral preparations of glibenclamide, correlating the effectiveness of the drug in these preparations in lowering plasma glucose concentrations with the in vitro dissolution of the drug, measured by the British Pharmacopoeal and Desaga methods, and the in vivo bioavailability, assessed in 12 healthy human volunteers. The two dissolution methods yielded different rank orders of ease of dissolution of the drug from the various preparations; the findings of neither dissolution method correlated adequately with the results of the in vivo bioavailability studies, which correctly predicted the abilities of the preparations to reduce plasma glucose concentrations. Relative to an oral glibenclamide solution the bioavailabilities of the drug from three tablet preparations were 0.69, 0.49 and 0.24. The mean elimination half-life of the drug was 1.5 h and assuming complete bioavailability of the drug from oral solution the mean systemic clearance was 0.095 l kg-1h-1, and the mean apparent volume of distribution was 0.20 l kg-1. It is concluded that it may be unsafe to use in vitro dissolution data as a basis for assessing the bioequivalences of different glibenclamide preparations intended for oral use.

Adult↗
PubMed1986

Prevention of experimental allergic encephalomyelitis by ganglioside GM4. A follow-up study.

The myelin-specific ganglioside GM4, when incubated with myelin basic protein prior to inoculation, prevents experimental allergic encephalomyelitis in the guinea pig. The monosialoganglioside GM1, the predominant ganglioside of mammalian myelin, also prevents experimental allergic encephalomyelitis, whereas a mixture of neural gangliosides rich in polysialogangliosides causes enhanced disease. Guinea pigs inoculated with both myelin basic protein and GM4 develop serum IgG antibodies against basic protein, but not against GM4.

Animals↗
PubMed1986

Mechanism and relevance of glutathione mutagenicity.

The ubiquitous tripeptide glutathione (GSH) has previously been shown to be mutagenic to Salmonella typhimurium TA100 when incubated with kidney subcellular fractions at physiological concentrations (Glatt et al., 1983). Here we report that the mutagenic effect of GSH can be inhibited by the use of the gamma-glutamyl-transpeptidase (gamma-GT) inhibitor anthglutin and by the metal chelators bathocuproine, EDTA and diethyldithiocarbamate. As the chelating agents did not inhibit gamma-GT activity this suggested that the mechanism underlying the mutagenic effect of GSH was at least a two-step process, dependent upon the cleavage of GSH by gamma-GT and the presence of either free transition metals or those contained in enzymes such as glutathione oxidase. As gamma-GT is located on the outer surface of kidney tubule cells and is therefore exposed to relatively low concentrations of GSH, and the precise physiological control of levels of transition metals, this mechanism is unlikely to occur in vivo.

Animals↗
PubMed1986

Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase.

The oxidation of phenol catalyzed by human myeloperoxidase and horseradish peroxidase resulted in extensive binding of phenol-derived metabolites to boiled rat liver protein. This binding paralleled closely the removal of phenol from the incubations and was inhibited from 83 to 99% by the addition of the antioxidants, ascorbate and glutathione, suggesting that metabolism and binding were occurring via a one-electron oxidation pathway. Metabolic studies employing both human myeloperoxidase and horseradish peroxidase resulted in the identification of 4,4'-biphenol and diphenoquinone as the principal identifiable metabolites. The addition of reduced glutathione to incubations containing horseradish peroxidase resulted in the formation of two conjugate species. These conjugate species were identified by fast atom bombardment mass spectrometry to be glutathione conjugates of diphenoquinone. The major gluthathione conjugate was identified as 3-(glutathion-S-yl)-4,4'-biphenol by NMR spectroscopy. These results suggest that the formation of highly reactive species through the peroxidase-mediated metabolism of phenol and other phenolic compounds could play an important role in the hematopoietic toxicity observed during chronic benzene exposure.

Biotransformation↗
PubMed1985

Metabolism of diethylstilbestrol by horseradish peroxidase and prostaglandin-H synthase. Generation of a free radical intermediate and its interaction with glutathione.

Diethylstilbestrol is carcinogenic in rodents and in humans and its peroxidatic oxidation in utero has been associated with its carcinogenic activity. Horseradish peroxidase-catalyzed oxidation of [14C]diethylstilbestrol and [14C]diethylstilbestrol analogs induced binding of radiolabel to DNA only when the compound contained a free hydroxy group (Metzler, M., and Epe, B. (1984) Chem. Biol. Interact. 50, 351-360). We have found that horseradish peroxidase or prostaglandin-H synthase-catalyzed oxidation of diethylstilbestrol in the presence of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide caused the generation of an ESR signal indicative of a free radical intermediate (aN = 14.9 G, aH = 18.3 G). The identity of the trapped radical could not be identified on the basis of published hyperfine coupling constants, but the observation that horseradish peroxidase-catalyzed oxidation of 1-naphthol produced an identical ESR signal suggests that the radical was either a phenoxy or phenoxy-derived radical. During horseradish peroxidase-catalyzed oxidation of diethylstilbestrol in the presence of glutathione the thiol reduced the diethylstilbestrol radical to generate a thiyl radical. This was shown by a thiol-dependent oxygen uptake during horseradish peroxidase-catalyzed oxidation of diethylstilbestrol and the observation of an ESR signal consistent with 5,5-dimethylpyrroline-N-oxide-glutathionyl radical adduct formation. A diethylstilbestrol analog devoid of free hydroxy groups, namely diethylstilbestrol dipropionate, did not produce an ESR signal above control levels during horseradish peroxidase-catalyzed metabolism in the presence of 5,5-dimethylpyrroline-N-oxide. Thus, free radicals are formed during peroxidatic oxidation of diethylstilbestrol and must be considered as possible determinants of the genotoxic activity of this compound.

Carbon Radioisotopes↗
PubMed1985

Inhibition of microsomal lipid peroxidation by naphthoquinones: structure-activity relationships and possible mechanisms of action.

Menadione (2-methyl-1,4-naphthoquinone) is a remarkably potent inhibitor of microsomal lipid peroxidation, effective at submicromolar concentrations. Its possible mechanism of action and the relationship between naphthoquinone structure and antioxidant activity were the topics of this investigation. In the microsomal lipid-peroxidizing system dependent on NADPH and ferric pyrophosphate, menadione, at concentrations of 50 microM or higher virtually eliminated the accumulation of malondialdehyde and lipid hydroperoxides. In the NADPH-independent, cumene hydroperoxide-dependent system, menadione was also an effective antioxidant, but only in the presence of reducing equivalents. These and other observations indicate that a reduced form of menadione, either the hydroquinone or semiquinone, is the active antioxidant, and suggest that it may trap hydroperoxy radicals, alkoxy radicals, or other free radicals involved in propagating lipid peroxidation. Moreover, these results show that electron diversion per se cannot account for the antioxidant effects of menadione. A comparison of the antioxidant activities of eight 1,4-naphthoquinones indicated that methyl substitution of C-2, lack of steric hindrance at C-3 or C-5, and (in the case of weak acids) a relatively high pKa are favorable structural features associated with strong antioxidant activity.

Animals↗
PubMed1985

Blastobotrys, Sporothrix and Trichosporiella: generic delimitation, new species, and a Stephanoascus teleomorph.

The morphological and physiological characters of the species of Blastobotrys, and of a number of similar species of Sporothrix, Trichosporiella and Candida were studied. Blastobotrys is defined as having mother cells (primary conidia) which form distinct, secondary conidia. Sporothrix has non-catenulate conidia, or the conidia are catenulate without marked differentiation of conidia of first and second order. Trichosporiella is delimited from Candida by a stronger coherence between hyphal cells, arthroconidia being absent. Four new Blastobotrys species are described, and two unnamed species; two new combinations are proposed in Trichosporiella. Related species in other genera are briefly discussed. A new Stephanoascus teleomorph is described in two strains originally identified as Sp. fungorum. Two diagnostic keys to the described taxa, using either morphological or physiological characters, are given.

Mitosporic Fungi↗
PubMed1985

Ultrastructure in septa in Blastobotrys and Sporothrix.

Transmission electron micrographs of septa in Blastobotrys species invariably showed central micropores. Septa of species of Sporothrix, however, exhibited three types of pores: micropores which were central if single, or scattered; central simple pores with Woronin bodies; dolipores. The results confirm the heterogeneity of the genus Sporothrix.

Cell Wall↗
PubMed1985

Conspecificity of Hanseniaspora nodinigri and Hanseniaspora vineae: comparison by DNA reassociation.

Hanseniaspora nodinigri Lachance 1981, found in black knots (caused by Dibotryon morbosum) of Prunus virginiana, was described as a new species, some time after publication of the extensive study by Meyer et al. (1978) on the systematics of Hanseniaspora Zikes and its imperfect counterpart Kloeckera Janke. Lachance delimited the species from other members of the genus because of absence of growth on glucono-delta-lactone. He also stated that this species, although evidently similar in many ways to H. vineae van der Walt et Tscheuschner and H. osmophila (Niehaus) Phaff et al., has 'diverged from them, possibly in its adaptation to growth in association with black knots'.

Ascomycota↗
PubMed1985

Role of extracellular Ca2+ in toxic liver injury: comparative studies with the perfused rat liver and isolated hepatocytes.

The role of extracellular Ca2+ in toxic liver injury was examined in two in vitro models of the rat liver, the isolated perfused liver and isolated hepatocytes. The toxins t-butylhydroperoxide and carbon tetrachloride, as well as the Ca2+ ionophore, heptafluorodimethyloctanedione (FOD), were employed to induce cellular injury and death. Lipid peroxidation was also measured as the formation of thiobarbituric acid-reactive products. Cell death was measured by the release of lactate dehydrogenase in the perfused liver model and by the uptake of trypan blue in isolated hepatocytes. Toxin-induced cellular injury and death occurred in both in vitro models in the presence and absence of extracellular Ca2+, indicating that an influx of Ca2+ was not essential for toxic liver injury. The degree of toxicity seen in the perfused liver model was independent of increases or decreases in the total calcium concentration present in the liver tissue, providing further evidence that cell death is not dictated solely by changes in cellular calcium content. Isolated hepatocytes differed from the perfused liver, however, undergoing more lipid peroxidation and toxin-induced cell death when incubated in the absence of extracellular Ca2+ than in its presence. While suggesting that extracellular Ca2+ concentrations may have some influence on the expression of toxicity, these results demonstrate the nonessential role extracellular Ca2+ plays in the events leading to toxic liver injury.

Animals↗
PubMed1985

Cloning and localization of the Bacillus subtilis chromosome replication terminus, terC.

A 10.9-kb segment of the Bacillus subtilis 168 chromosome has been cloned in an Escherichia coli plasmid and shown to contain terC (the replication terminus of the chromosome). The terC-containing portion of this plasmid has been subcloned within each of two overlapping fragments of DNA, 1.75 and 1.95 kb, again in E. coli plasmids. These have afforded a more precise definition of the location of terC in the B. subtilis chromosome and provided material for a detailed analysis of the structure and functioning of this site.

Bacillus subtilis↗
PubMed1985

Measurement of the diene conjugated form of linoleic acid in plasma by high performance liquid chromatography: a questionable non-invasive assay of free radical activity?

It has been previously reported that the main diene-conjugated fatty acid in human plasma is a non-oxygen containing linoleic acid isomer (PL-9, 11-LA'). It has also been proposed that this isomer can be used as a specific marker of free radical-mediated lipid peroxidation in humans. Here we report that the in vitro induction of lipid peroxidation in human and rat blood with either UV irradiation or phenylhydrazine failed to increase the plasma levels of this isomer. The induction of lipid peroxidation in vivo in rats pretreated with either phenylhydrazine or bromotrichloromethane also failed to increase the plasma levels of this isomer. These findings demonstrate that PL-9, 11-LA' cannot be used as an in vivo marker of free radical-mediated lipid peroxidation in rats and casts doubts on its validity as a specific marker in humans.

Animals↗