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Biomedical subjects

M Sharma

Publications and source records attributed to M Sharma.

At least 73 records · Page 4Linked to original sources
PubMed1987

Role of glycosidases in human ovarian carcinoma cell mediated degradation of subendothelial extracellular matrix.

Penetration of the extracellular matrix (ECM) by tumor cells, an event which occurs at various stages of the metastatic process, involves tumor cell glycosidase mediated hydrolysis of proteoglycans (PG). Recently, we observed that human ovarian carcinoma cell lines (HOCC) derived from primary tumors, peritoneal effusions, and distant metastases possess a varying ability to degrade radiolabeled PG of the ECM, while normal cells (human mesothelial cells or ovarian fibroblasts) fail to do so. To determine whether a quantitative relationship exists between glycosidase activity and degradation of ECM, both intracellular and extracellular glycosidase activities were measured for HOCC and normal cell lines. No relationship was found between intracellular glycosidase activities and the ability of cells to degrade ECM. However, a correlation was observed between extracellular or secretory glycosidase activities and HOCC mediated ECM degradation. In particular, a 5-8-fold increase, as compared to normal cells, was observed for HOCC extracellular beta-N-acetylglucosaminidase (EC 3.2.2.30) activity. The accumulation or secretion of this enzyme from HOCC into culture medium was found to be time dependent and not related to intracellular levels. Purified hexosaminidase derived from invasive HOCC was able to hydrolyze [3H]-glucosamine radiolabeled ECM (up to 30% radiolabel) and resulted in the cumulative release of free [3H]-N-acetylglucosamine. This enzyme mediated hydrolysis could be completely prevented with 2-acetamido-2-deoxy-1,5-D-gluconolactone, a competitive inhibitor (Ki 10(-6) M). Finally, HOCC mediated degradation of radiolabeled ECM was discerned to be dependent upon active hexosaminidase action, since tumor cell mediated degradation of ECM could be inhibited by up to 60% in the presence of this synthetic competitive inhibitor. In summary, these studies indicate a strong association between HOCC solubilization of glycoconjugates present in the ECM and extracellular levels of hexosaminidase.

Acetylglucosamine↗
PubMed1987

Fluorinated carbohydrates as potential plasma membrane modifiers and inhibitors. Synthesis of 2-acetamido-2,6-dideoxy-6-fluoro-D-galactose.

Reaction of benzyl 2-acetamido-3,4-di-O-benzyl-2-deoxy-6-O-mesyl-alpha-D-galactopyran oside with cesium floride gave benzyl 2-acetamido-3,6-anhydro-4-O-benzyl-2-deoxy-alpha-D-galactopyranoside instead of the desired 6-fluoro derivative. Acetonation of benzyl 2-acetamido-2-deoxy-6-O-mesyl-alpha-D-galactopyranoside gave the corresponding 3,4-O-isopropylidene derivative. The 6-O-mesyl group was displaced by fluorine with cesium fluoride in boiling 1,2-ethanediol, and hydrolysis and subsequent N-acetylation gave the target compound. In another procedure, treatment of 2-acetamido-1,3,4-tri-O-acetyl-2-deoxy-alpha-D-galactose with N-(diethylamino)sulfur trifluoride gave 2-acetamido-1,3,4-tri-O-acetyl-2,6-dideoxy-6-fluoro-D-galactose which, on acid hydrolysis followed by N-acetylation, gave 2-acetamido-2,6-dideoxy-6-fluoro-D-galactose.

Cell Membrane↗
PubMed1987

Isolation and characterization of a metallothionein-like protein from monkey brain.

A cadmium-binding protein from monkey brain has been isolated, purified and characterized. The absorption spectrum of this protein indicates the presence of Cu-Zn thionein in the normal monkey brain which has a strong affinity to bind cadmium. On cadmium exposure the protein sequestered most of the cadmium which entered the brain. The apparent molecular weight of this protein as determined on a gel filtration column calibrated with marker proteins has been found to be in the range of 11,500-12,000 Da. The ratio of absorbance at 254 nm/280 nm is more than 1 indicating the presence of cadmium-mercaptide bonds, which was further confirmed by the presence of 15 cysteine residues. Polyacrylamide gel electrophoresis of the protein shows 3 bands indicating the presence of 3 isometallothionein forms. Unlike hepatic or renal thioneins, the cadmium-binding protein in brain is not inducible following administration of cadmium. However, when antibodies raised against hepatic metallothionein were cross-reacted with brain Cd-binding protein, a line of identity was observed, indicating the 2 proteins are immunologically identical and share a high degree of structural similarity.

Animals↗
PubMed1987

Continuous infusion of vecuronium: the effect of anesthetic agents.

The authors studied the effects of enflurane, isoflurane, and fentanyl, each in combination with 60% nitrous oxide, on the vecuronium infusion rate necessary to maintain constant 90% depression of control muscle twitch tension. Thirty healthy surgical patients were given an initial 0.1 mg/kg bolus of vecuronium, followed by an infusion of vecuronium at an initial rate of 1.0 microgram . kg-1 . min-1. After 1 h of steady-state 90% twitch depression, plasma vecuronium concentrations (Css90) were measured by capillary column gas chromatography. Total plasma clearance of vecuronium was estimated using Css90 values. Vecuronium infusion rates (mean +/- SD) were similar for patients given enflurane (0.28 +/- 0.13 microgram . kg-1 . min-1) and isoflurane (0.30 +/- 0.13 microgram . kg-1 . min-1), but significantly higher in patients given fentanyl (0.92 +/- 0.37 microgram . kg-1 . min-1). Values for Css90 in the patients receiving enflurane and isoflurane were similar (71 +/- 34 and 72 +/- 44 ng/ml, respectively), but significantly higher in those receiving fentanyl (165 +/- 48 ng/ml). Total plasma clearance was similar during enflurane, isoflurane, and fentanyl anesthesia (4.4 +/- 2.6, 4.6 +/- 1.2, and 5.6 +/- 1.9 ml X kg-1 min-1, respectively). The authors conclude that patients receiving isoflurane and enflurane require markedly lower vecuronium infusion rates to achieve 90% neuromuscular blockade than those receiving fentanyl. The enhancement of neuromuscular blockade by isoflurane and enflurane represents a change in the pharmacodynamics of vecuronium-induced neuromuscular blockade, rather than a change in pharmacokinetics.

Anesthetics↗
PubMed1987

Evaluation of enzymes in serum and cerebrospinal fluid in cases of cerebrovascular accidents.

Gamma glutamyl transpeptidase (GGTP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were measured serially in the serum and cerebrospinal fluid (CSF) of 22 patients with fresh stroke and an equal number of age- and sex-matched healthy control subjects. It was observed that levels of these enzymes in the CSF of control subjects were very low but were significantly elevated (p less than 0.001) in both serum and CSF in patients with stroke. The elevation was greater in the CSF than in the serum and was maximum during the first four days of stroke. Thereafter, the enzymatic activity declined. Of all these enzymes, GGTP in CSF correlated best with the clinical picture. It was possible to differentiate between the ischemic and hemorrhagic type of stroke on the basis of CSF levels of GGTP (greater than 60.0 units in hemorrhagic stroke). There was no correlation between GGTP levels in CSF and serum or among GOT, GPT, and GGTP in CSF. It can be concluded, therefore, that estimation of GGTP in CSF is helpful not only in predicting the degree of cerebral damage and functional outcome of the patient following stroke but also in differentiating the type of stroke.

Alanine Transaminase↗
PubMed1986

Purification and characterization of metallothionein from liver of cadmium exposed rhesus monkeys (Macaca mulatta).

Metallothionein (MT) a low molecular weight, Cd-binding, cysteine rich, cytosolic protein has been isolated, purified and characterized from cadmium exposed Rhesus monkeys maintained on protein calorie malnourished (PCM) diet. Metallothionein was resolved into three isoforms i.e. MTa, MTb and MTc. The ratio of Cd, Zn and Cu varied in these isometallothioneins. MTc was the major isometallothionein. U.V. Spectra of MTc revealed the presence of mercaptide bonds and absence of aromatic amino acids. These observations were further confirmed by amino acid analysis of MTc which demonstrated high cysteine content (22.6) followed by serine, glycine and lysine. The molecular weight of MTc as determined by gel filtration and amino acid analysis was 13,000 and 6398 daltons respectively. This demonstrates that MTc is a nonglobular ellipsoid polypeptide. MTc showed a unique property of binding selenium. Monkey liver metallothionein was immunologically identical with human metallothionein. All the characteristics of MTc obtained in the present study reveal a similarity between monkey and human metallothionein probably due to closer phylogenetic relationship between the two species.

Amino Acids↗
PubMed1986

An integrated model for the interaction of muscle relaxants with their antagonists.

An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions. Edrophonium arterial concentrations and twitch tension of the anterior tibialis muscle were measured. Both the integrated and the naive model were fit to the twitch tension data using a model with a hypothetical "effect" compartment. The integrated model consistently fit the twitch tension data better than the naive model; the sum of squared deviations was lower by 46, 45, 87, and 69%, respectively, with the integrated model than with the naive model. Also, in contrast to the naive model, the integrated model is capable of describing the interaction of the anticholinesterase agent and the neuromuscular blocking agent when the concentration of either varies with time.

Animals↗
PubMed1986

Effect of different amounts of blood transfusion given at different speeds on left ventricular filling pressure in cases of chronic severe anemia.

Pulmonary capillary 'wedge' pressure (PCWP) was measured before and after transfusion of 1 and 2 units of blood @ 5 and 10 ml/min. in 40 adult cases of chronic severe anemia (CSA). The cases were randomly divided into 4 subgroups of 10 cases each. Following blood transfusion (BT), PCWP increased significantly in all the 4 subgroups (p less than 0.001). The highest rise in PCWP was recorded when 2 units of blood were transfused at a rate of 10 ml/min, and the rise was minimum when 1 unit of blood was transfused @ 5 ml/min. Out of the two variables--speed and amount of BT--the amount was more important. It is, therefore, concluded that administration of 2 units of blood in case of CSA at a rate of 5 or 10 ml/min is not desirable and that transfusion of 1 unit of blood @ 5 ml/min is quite safe.

Adolescent↗
PubMed1986

Furosemide supplemented blood transfusion in cases of chronic severe anemia.

Pulmonary capillary 'wedge' pressures (PCWP) were measured in 20 adult cases of chronic severe anemia (CSA) before and after transfusion of 700 ml of whole blood at a rate of 5 ml/min. The cases were randomly divided into 2 groups of 10 cases each. Group II also received 40 mg of furosemide immediately before the start of transfusion. The majority of the cases had hemoglobin values less than 4 g% and serum albumin values less than 2.5 g%. Pretransfusion intracardiac pressures were normal in all the cases. Following blood transfusion (BT), appreciable rises (p less than 0.001) in hemoglobin and arterial and venous oxygen saturation were observed. PCWP increased significantly after BT in Group I (p less than 0.001). Although it decreased by 3.75% in Group II, this was not statistically significant (p greater than 0.05). This study implies that a blood transfusion of 700 ml, given at a speed of 5 ml/min in patients with CSA, results in sufficient hemodynamic stress to cause a significant rise in PCWP, and that this is completely prevented by simultaneous administration of 40 mg of furosemide.

Adult↗
PubMed1986

Left ventricular performance after blood transfusion in cases of chronic severe anemia. A study of systolic time intervals.

Left ventricular performance was studied by measuring systolic time intervals (STIs) in 15 adult cases of chronic severe anemia (CSA) before and after transfusion of 350 and 700 ml of whole blood at a moderately rapid rate of 5 ml/min. Cases with systemic disease and congestive heart failure were excluded. STIs before blood transfusion (BT) showed wide variations, but these were within normal limits in 80% of the cases. Following BT, left ventricular ejection time (LVET) increased significantly (p less than 0.001) without much change in the pre-ejection phase (PEP). There was no significant change in the PEP/LVET ratio after BT. It is concluded that transfusion of 700 ml of whole blood at a rate of 5 ml/min to patients with CSA is devoid of any risk, so far as myocardial contractile function is concerned.

Adolescent↗
PubMed1986

An outbreak of typhoid fever in Chandigarh, North India.

An outbreak of typhoid fever occurred among 54 hospital nurses after a picnic. The salient features were fever (100%), nausea and vomiting (46%), loose motions and abdominal pain (13%), and palpable splenomegaly (63%). None of the patients had any major complications. Blood cultures for Salmonella typhi were positive in 81%, blood Widal was positive (1:320 or more) in 43% and suggestive (1:160) in 25% of the blood culture positive patients. A comparable number of patients were administered chloramphenicol or co-trimoxazole and no differences in response were observed. Bacteriological examination of samples of water from the likely sources revealed it to be unfit for human consumption due to gross faecal contamination.

Adolescent↗