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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 91 records · Page 5Linked to original sources

Synthesis, modification with N-acetoxy-2-acetylaminofluorene and physicochemical studies of DNA model compound d(TACGTA).

The deoxyhexanucleotide d(TACGTA) was synthesized by a modified phosphotriester method. The modified procedure made rapid synthesis of deoxyoligonucleotide possible in gram quantity. N-Acetoxy-2-acetylaminofluorene (AAAF) modified d(TACGTA). Thin layer chromatography and UV analysis of the acid treated AAF modified hexanucleotide showed that the covalent modification with AAF took place exclusively at C(8) of guanine in d(TACGTA). d(TACGTA) and AAF modified d(TACGTA) were purified by preparative high performance liquid chromatography (HPLC). The pure products were characterized by 1H and 31P-NMR. The circular dichroism (CD) spectrum of d(TACGTA) was consistent with DNA in the B form even in the presence of 4 M NaCl whereas the modified hexamer had nearly inverted spectrum in the absence of any added salt. Both NMR and CD analyses indicated profound alteration of conformation of d(TACGTA) upon covalent modification with AAF. The stabilization of the Z-like conformation in the modified hexamer under physiological conditions of salt and temperature suggests biological relevance.

2-Acetylaminofluorene

Effect of renal failure on laudanosine excretion in man.

Patients with renal failure and undergoing a cadaver renal transplant were found to have plasma concentrations of laudanosine, following the administration of a single bolus dose of atracurium 0.5 mg kg-1, higher than those found in patients without renal failure. Since laudanosine is a known central nervous system stimulant in a variety of animal species, its actions should be investigated further in man, and particularly in patients with renal failure.

Atracurium

A nonimmunomodulatory effect of chronic cadmium exposure on lymphocyte transformation response in rhesus monkeys (Macaca mulatta).

The immunomodulatory effects of cadmium, an environmental pollutant, were assessed in male rhesus monkeys orally exposed to 5 mg cadmium/kg body weight for a period of 4 months. A lymphocyte transformation test was carried out in peripheral blood lymphocytes using different concentrations of phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). Cadmium exposure of monkeys resulted in a statistically nonsignificant increase in [3H]thymidine incorporation in PHA- and Con-A-stimulated lymphocytes. However, there was a nonsignificant decrease in [3H]thymidine incorporation in PWM-stimulated lymphocytes. These results suggest that cadmium may not have immunosuppressive effects in primates which are phylogenetically close to man.

Animals

A comparative study of conventional vs rapid speed of blood transfusion in cases of chronic severe anemia.

Pulmonary capillary 'wedge' pressure (PCWP) was studied in 20 cases of chronic severe anemia before and after transfusing one unit of blood. They were divided into 2 groups of 10 age and sex matched cases. Blood was transfused at a speed of 2 ml/min in group A and 5 ml/min in group B. Pretransfusion PCWP was normal in all the cases. Following blood transfusion (BT) 'wedge' pressure increased significantly (p less than 0.001) in both the groups being 17.2% and 29.2% in group A and B respectively. The difference in the rise of PCWP between the two groups was not statistically significant (p greater than 0.05). All the cases tolerated BT very well. It is therefore, concluded that transfusion of one unit of blood at a speed of 5 ml/min is nearly as safe as when it is transfused at a rate of 2 ml/min (conventional speed) so far as the cardiopulmonary haemodynamics are concerned.

Adult

Depressive disorders in the developing world.

In order to find out whether the finding of different prevalence rates for depression in rural and urban areas of India is supported by a difference in symptomatology as well, 30 rural and 42 urban hospitalized MDP-Depressed patients were compared on Hamilton Depression Scale and Schedule for Standardized Assessment of Patients with Depressive Disorders. Symptoms of guilt, loss of concentration and memory were significantly more in urban patients whereas gastrointestinal somatic symptoms were significantly higher in rural subjects. The difference is probably due to urban subjects being more sophisticated, expressive and familiar with mental disorders as compared to rural patients who being more familiar with somatic illnesses tend to somatize their psychic distress.

Bipolar Disorder

Effect of neonatal undernutrition on rat brain gangliosides.

Effects of age and neonatal undernutrition were studied on total and fractions of gangliosides (GT1, GD1b, GD1a and GM1) in rat brain. GT1, GD1b + GD1a and GM1 are being presented here as polysialo-, disialo-, and monosialo-gangliosides. Undernutrition was induced by feeding mothers a low protein diet during lactation. The concentration of gangliosides increased to its maximum level by the age of 3 weeks and then decreased to its adult value by the age of 8 weeks. Polysialo gangliosides (GT1) comprised the maximum amount of gangliosides at birth (40%) and decreased to an adult value by 3 weeks of age. Disialo ganglioside GD1b increased to its maximum by 2 weeks and then leveled off. Disialo ganglioside GD1a and GM1 showed a decrease by 2 weeks and then reached to its adult value by 4 weeks. Neonatal undernutrition results in a decreased body and brain weight at all ages studied (7, 14 and 21 days) as well as total ganglioside concentration by 36%, 15% and 55% respectively at 7, 14 and 21 days. Polysialo gangliosides (GT1) constitute the major fraction of gangliosides at 21 days in undernourished rats as compared to controls, whereas mono- and di-sialo gangliosides remained decreased at all three ages compared to controls. This indicates the possibility of an underlying metabolic defect in undernourished animals.

Animals

Changes in load bearing in the rheumatoid foot.

A study of peak force exerted under areas of the foot was made in 27 patients with rheumatoid disease and in 30 normal persons. Patients were found to exert considerably less force under their toes and under the first metatarsal head and more force under the 3 outer metatarsal heads. It was possible to correlate these changes with increasing clinical and radiological severity.

Adult

Biochemical characteristics, metabolism, and antitumor activity of several acetylated hexosamines.

We have synthesized several potential inhibitors and/or modifiers of the carbohydrate portion of plasma membrane glycoconjugates. These include fluorinated and actylated analogs of D-glucosamine, D-galactosamine, and D-mannosamine. These compounds have been tested to determine their effects on both[14C] glucosamine and [3H] leucine incorporation into glycoconjugate and on cell growth and viability using P-288 murine lymphoma cells maintained in tissue culture. The most cytotoxic agent tested was 2-acetamido-2-deoxy-1,3,4,6-tetra-O-acetyl-beta-D-glucopyranose or simply beta-pentaacetylglucosamine which prevented cell growth at 10(-4)-10(-3) M. beta-Pentaacetylglucosamine cytotoxicity was correlated with its high lipid solubility, having an octanol/water partition coefficient of 0.424 as compared with 0.278 for the alpha-anomer and 0.017 for N-acetylglucosamine. In vitro metabolism studies with [4C]- and/or [3H]-labeled pentaacetylglucosamine have indicated intracellular de-O-acetylation leading to the biosynthesis of UDP-N-acetylglucosamine, followed by the incorporation of this sugar into cellular glycoprotein. Concomitant with the formation of increased amounts of this nucleotide sugar, intracellular UTP and CTP pools fell to one third normal within 3 h after the administration of 1 mM pentaacetylglucosamine. At present it is unclear whether the cytotoxicity of beta-pentaacetylglucosamine or other similar agents is due to alterations in nucleotide and nucleotide-sugar pools causing a decrease in energy charge and polynucleotide biosynthesis or is due to a direct effect on membrane glycoconjugate biosynthesis.

Cell Division