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Biomedical subjects

M Ray

Publications and source records attributed to M Ray.

At least 145 records · Page 8Linked to original sources

Cytostatic action of methylmercuric chloride on mammalian duodenal cells.

Adult male mice of the ICR/Swiss Webster strain received a single intragastric administration of methylmercuric chloride 1,000 ppm, at dose levels of 5,10,15,20,25 and 30 mg/kg of body weight. The animals were killed six hours later. Tissue samples from the duodenum were fixed in 10% neutral buffered formalin for light microscopy. Chromosome clumping was observed in dividing cells at all dose levels, resembling a C-mitotic effect. It would lead to reduced mitotic cell formation on account of the subsequent lysis of the arrested metaphases. The cytostatic effect was brought about by the inactivation of the microtubule spindle fiber polymerization mechanism induced by methylmercuric chloride. There was a direct positive correlation between the varying dose levels of methylmercury and the proportion of cells arrested in metaphase in the crypts of the duodenum.

Administration, Oral↗

Relative bioavailability of a new transdermal nitroglycerin delivery system.

The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.

Administration, Cutaneous↗

Distribution of sister chromatid exchanges in chromosomes of normal Chinese hamster and its cell lines exposed to BrdU and MMC.

Sister chromatid exchanges (SCEs) were investigated in chromosomes from normal male Chinese hamster (CH) and its cell lines (CHW, 1102 and 1103). The fibroblasts were grown for two replication cycles in medium containing BrdU and mitomycin C (MMC) at concentrations of 0.01, 0.02 and 0.03 micrograms/ml of medium. The difference in SCEs/cell between male CH and CHW was negligible, but the difference between CHW and 1102 was about 2.6-fold. It is suggested from karyotypic differences between CHW and 1102, that the control of SCEs might be due partly or completely to chromosome 5 in Chinese hamster. The lines CHW and 1102 were less responsive than normal Chinese hamster cells when exposed to different MMC concentrations. It is suggested that the lines CHW and 1102 might be slightly resistant to MMC. The frequency of SCEs decreased with the decrease of chromosome size. SCEs are not preferentially distributed on any autosomal chromosomes. No SCEs were found in normal X-chromosomes. The majority of exchanges appear to be either interband regions or very near band-interband junctions.

Animals↗

[Influence of idrocilamide on the metabolism of theophylline].

The pharmacokinetics of theophylline as a sirup (5 or 6 mg . kg-1 bodyweight) were studied in 6 volunteers before and after association with idrocilamide. The results showed an increase in theophylline half-life, a decrease in clearance and a slight decrease in volume of distribution.

Drug Interactions↗

Analysis of replication patterns in chromosomes of normal Chinese hamster and its cell lines.

Replication patterns of the normal male Chinese hamster chromosomes and the three cell lines CHW, 1102 and 1103, were determined using fluorescent, plus Giemsa or acridine orange, techniques. The individual chromosomes or chromosomal segments were consistent in the replication patterns of normal Chinese hamster chromosomes and all the transformed cell lines. Late DNA replication was regularly identified in the long arm of the X chromosome, the entire Y chromosome, the short arms of chromosomes 6 and 7, and the paracentromeric regions of chromosomes 8, 9 and 10. A similar consistency was demonstrated in the large late replicating areas of chromosomes X and Y. Each cell line had specific marker chromosomes by which the cell line was identified and their replication patterns have been described. The chromosome analysis in cell line 1103 indicated that chromosomes 2, 3, 8 and 9 were more stable than others, of which chromosome 2 was extremely stable. The markers M4 and M5 in cell line 1103 are very interesting. The cytogenetic behaviour of marker M4 indicated a new phenomenon of translocation by simple association. The marker chromosome M5 indicated that inactivation spread to the early replicating distal region. These cell lines are very useful tools for studying replication patterns and providing a basic understanding of mammalian cytogenetics.

Animals↗

L-Threonine dehydrogenase from goat liver. Feedback inhibition by methylglyoxal.

L-Threonine dehydrogenase, which forms aminoacetone from L-threonine and NAD, has been extensively purified from goat liver. A feedback inhibition of this enzyme has been observed with methylglyoxal. Kinetic data and other experiments indicate that methylglyoxal acts at a site other than the active site of the enzyme. The enzyme contains a single subunit of Mr 89,000. The apparent Km values of the enzyme for L-threonine and NAD were found to be 5.5 and 1 mM, respectively.

Alcohol Oxidoreductases↗

Colitis cystica profunda: presenting with complete intestinal obstruction and recurrence.

An unusual case of colitis cystica profunda is described. The patient presented with intestinal obstruction due to a polypoid mass in the descending colon, which was diagnosed as colitis cystica profunda after the patient underwent colectomy. Three other separate lesions were present in the ascending, transverse, and sigmoid colon. There was no antecedent or associated colonic disease. The disease recurred 1 yr later in the remaining colon and rectum.

Cecum↗

A case of de novo trisomy 12p syndrome.

We described a case of complete trisomy 12p syndrome (non-mosaic) originating de novo in a first born child to healthy 26 year old nonconsanguineous parents. The 12p syndrome has been confirmed by clinical, cytogenetic and gene dosage studies.

Abnormalities, Multiple↗

Purification and partial characterization of a methylglyoxal reductase from goat liver.

An enzyme which catalyzes the reduction of methylglyoxal to lactaldehyde has been isolated and purified from goat liver to apparent homogeneity. NADH was found to be a better substrate than NADPH for methylglyoxal reduction. Stoichiometrically equivalent amounts of lactaldehyde and NAD are formed from methylglyoxal and NADH. Enzyme activity was located only in the soluble supernatant fractions of liver cells. Of the various carbonyl compounds tested, methylglyoxal was found to be the best substrate. The pH optimum of the enzyme was found to be 6.5, and Km for methylglyoxal was 0.4 mM. The molecular weight of the enzyme was found to be 89000 by gel filtration on a Sephadex G-200 column. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel revealed that the enzyme is composed of two subunits. The enzyme is highly sensitive to sulfhydryl group reagents. The inactivation by p-chloromercuribenzoate could be substantially protected by methylglyoxal in combination with NADH, indicating a possible involvement of one or more sulfhydryl group(s) at the active site of the enzyme.

Alcohol Oxidoreductases↗

Oxidation of lactaldehyde by cytosolic aldehyde dehydrogenase and inhibition of cytosolic and mitochondrial aldehyde dehydrogenase by metabolites.

An enzyme fraction which oxidizes lactaldehyde to lactic acid has been purified from goat liver. This enzyme was found to be identical with the cytosolic aldehyde dehydrogenase. Lactaldehyde was found to be primarily oxidized by this enzyme. Almost 90% of the total lactaldehyde-oxidizing activity is located in the cytosol. Methylglyoxal and glyceraldehyde 3-phosphate were found to be strong competitive inhibitors of this enzyme. Aldehyde dehydrogenase from goat liver mitochondria has also been partially purified and found to be strongly inhibited by these metabolites. The inhibitory effects of these metabolites on both these enzymes are highly pH dependent. The inhibitory effects of both the metabolites have been found to be stronger for the cytosolic enzyme at pH values higher than the physiological pH. For the mitochondrial enzyme, the inhibition with methylglyoxal was more pronounced at higher pH values, whereas stronger inhibition was observed with glyceraldehyde 3-phosphate at physiological pH.

Aldehyde Dehydrogenase↗

Control of measles by annual pulse immunization.

In a village with a population of more than 2,000, with measles outbreaks in alternate years, annual single-day measles immunization campaigns were conducted during four winter seasons. Measles vaccine was offered to children 1 year of age and older, with no previous measles or immunization. There has been no outbreak of measles since the introduction of immunization to date. Four cases of introduced measles did not result in any secondary case. This vaccine delivery strategy (annual pulse immunization), designed to improve coverage and simplify cold chain management, was shown to be suitable for the control of measles in rural communities in the Third World.

Child↗

Interstitial deletion of the short arm of chromosome 4.

A 17 year old girl investigated for mental retardation and minor anomalies was found to have an interstitial deletion of 4p. Her clinical and cytogenetic findings are compared with previous reported case of interstitial 4p deletion and with terminal 4p--deletions (Wolf-Hirschhorn syndrome).

Abnormalities, Multiple↗

In vivo generation and selection of variants with altered sensitivity to natural resistance (NR): a model of tumor progression.

The stability of a cloned murine tumor for sensitivity to NR was examined following growth in vivo in order to test the hypothesis that tumor progression proceeds through the generation and selection of variants. Clonal sensitivity to the [131I]-dUrd elimination assay of NR was assessed for the L5178Y-F9 tumor grown in syngeneic DBA/2 mice or maintained solely in tissue culture. Subclones derived from a tumor obtained from the injection site 3 1/2 weeks after the s.c. inoculation of 25 cells were less sensitive to NR in comparison with subclones derived from cells grown only in vitro. Subclones from the cells grown in vivo exhibited increased heterogeneity in sensitivity to NR in addition to their expanded range of susceptibility to complement-mediated lysis by CBA serum natural antibodies. The extent of the heterogeneity argues against tumor "adaptation" forming the basis for the phenotypic alteration while chromosomal studies eliminate the possibility that a new tumor was induced. These data support the hypothesis that tumor progression proceeds through the random generation of variants and host-mediated selection for the proliferation of clones with an increased ability to survive.

Animals↗