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Biomedical subjects

A Sarkar

Publications and source records attributed to A Sarkar.

At least 73 records · Page 4Linked to original sources
PubMed1994

Regulation of the expression of annexin VIII in acute promyelocytic leukemia.

Annexin VIII is a calcium-dependent phospholipid-binding protein previously identified as a blood anticoagulant based on in vitro studies. However, the physiologic function of annexin VIII remains unknown. In acute promyelocytic leukemia (APL) the annexin VIII gene is highly expressed, but its expression is undetectable in the blasts of other acute leukemias. In the present investigation, we showed using the APL-derived NB4 cell line that expression of the annexin VIII gene is regulated at the transcription level during induced differentiation by all-trans retinoic acid (ATRA). The half-life of the annexin VIII mRNA is about 5 to 6 hours, as determined by using actinomycin D as a transcription inhibitor. Analysis of the expression of annexin VIII protein in NB4 cells and in APL samples showed a consistent expression of a predominant 36-kD protein and a weak 72-kD protein. After ATRA-induced differentiation of NB4 cells, the annexin VIII protein level reduced gradually, but a detectable level persisted even after 4 days of induction. Because annexin VIII mRNA becomes undetectable after 48 hours of ATRA induction, this result indicates that annexin VIII is a relatively stable protein. A multiple tissue Northern blot analysis was performed, and we found that annexin VIII is normally expressed in the placenta and the lung. Cellular localization of the annexin VIII protein was determined by immunofluorescence staining and subcellular fractionation. These results indicated that annexin VIII is predominantly localized to the plasma membrane. The annexin VIII is neither an extracellular protein nor associated with the cell surface suggesting that it does not play a role in blood coagulation in vivo. The plasma membrane localization and its property as a phospholipase inhibitor suggests that annexin VIII may have a role in the signal transduction pathway in the APL cells.

Annexins↗
PubMed1994

Inhibitory effect of beta-carotene on chronic 2-acetylaminofluorene induced hepatocarcinogenesis in rat: reflection in hepatic drug metabolism.

The dietary administration of beta-carotene (BC; 100 mg/kg food) daily has been found to be highly effective in reducing cancer incidence in male Sprague-Dawley rats fed 2-acetyl-aminofluorene (0.05% in food). BC treatment either before initiation, during initiation and selection/promotion phases of hepatocarcinogenesis have been found to be effective in elevating hepatic microsomal cytochrome b5 (24-50%), P-450 (18-38.5%), NADPH cytochrome c reductase (17.5-43.25%) and cytosolic aryl hydrocarbon hydroxylase (60.5-63.5%) activity to a statistically significant level measured either in the hyperplastic nodule (HN) or in the non nodular surrounding liver parenchyma (NNSP) compared to carcinogen control. Moreover, BC treatment throughout the study decrease the cytosolic 1-chloro-2,4-dinitrobenzene conjugated glutathione S-transferase (38.9-51.22%) and microsomal UDP-glucuronyl transferase (37.3-59.1%) activities to a significant level when compared to carcinogen control rats. A decrease in the number of hyperplastic nodules and their total liver parenchyma occupied were also observed in BC treated groups. Furthermore, a direct correlation between HNs and NNSP liver areas were observed with the hepatic BC and vitamin A contents and also with the rates and patterns of hepatic drug metabolism. Our results confirm the fact that BC is particularly protective in limiting the action of 2-AAF during the initiation phase of hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed1994

Comparative patterns of hepatic drug metabolizing enzymes and their possible correlation with chromosomal aberrations in transplantable murine lymphoma: a time course study.

The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT), cytosolic glutathione-S-transferase (GSHT) activities, and major chromosomal aberrations were evaluated over various periods of time, following tumor transplantation in male Swiss Albino mice. Changes in the above markers were studied (1) to monitor the entire carcinogenic process and (2) to test the suitability of chemopreventive exposures in terms of phase and duration of tumor growth. The microsomal cyt. P-450 content and the UDPGT activity were significantly elevated (p < 0.01-0.001) from the early stages of tumor growth while the cytosolic GSHT activity reached its highest level (p < 0.01-0.001) only 10 days after tumor transplantation. During the later stages of tumor growth all the biotransforming enzyme activities showed a downhill trend, which was significantly lower than that of their normal counterparts (p < 0.01-0.001). The frequency of different chromosomal aberrations, which were of major structural, numerical, and physiological types, increased steadily throughout the entire length of the carcinogenic process (30 +/- 2 days).

Animals↗
PubMed1994

Ventricular late potentials after thrombolysis.

High frequency low amplitude signals that prolong the terminal portion of the QRS complex in the electrocardiogram are termed late potentials (LPs). It has been established for quite some time that the presence of LPs after acute myocardial infarction (AMI) is associated with an increased risk of ventricular tachyarrythmias and sudden cardiac death (SCD), and vice versa. It is also known that thrombolytic therapy after AMI significantly decreased the incidence of ventricular tachyarrythmias and SCD. The object of this study was to find out whether thrombolysis in AMI decreased the incidence of LPs. Fifty two male patients of the age group 41-46 years with first anterior wall AMI were studied. Thirty of them presented within 6 hours of chest pain and were given intravenous streptokinase (IVSK) in addition to conventional therapy. The remaining 22 received conventional therapy but no thrombolysis. There was no significant difference in these two groups regarding age, CKMB, hypertension, diabetes, smoking, prior use of beta blockers, and ejection fraction. Eight out of the 30 patients receiving IVSK were positive for LPs as against 13 out of the 22 in the control group. This difference was statistically significant (p > 0.02 < 0.01). Thus thrombolysis in the early hours of anterior AMI diminishes the incidence of LPs.

Adult↗
PubMed1994

Changes in the blood lipid profile after administration of Ocimum sanctum (Tulsi) leaves in the normal albino rabbits.

Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents.

Animals↗
PubMed1993

Effects of fractionated radiation therapy on human brain tumor multicellular spheroids.

We investigated the cytotoxic effects of fractionated radiation therapy on multicellular spheroids of human malignant glioma cell lines U-87 MG, U-251 MG, and U-373 MG. Graded doses of x-rays were administered in 1, 3, 8, 15, and 30 fractions over 15 days. The isoeffect dose for a 1 log cell kill ranged from 4-4.5 Gy for a single fraction to 7-8 Gy for an 8-fraction protocol; no additional dose-sparing was achieved with more fractions. Therefore, the effects of individual doses (1.56 Gy) of the 8-fraction protocol were studied in U-251 MG spheroids. A cell survival assay showed that the first dose of radiation killed 30-50% of the cells; subsequent doses usually killed fewer cells. The cell kill after all 8 doses was about 1.0 log. No consistent relationship between the intracellular glutathione level and fraction number was observed. The 24-hour labeling index of the spheroids did not decrease until after the second fraction. Thus, the higher cell kill of the first dose does not seem to be related to cell cycle synchrony. Multinuclear and mononuclear giant cells were limited almost entirely to the periphery of the spheroids and increased with the number of radiation fractions. We conclude that multicellular spheroids can be used to study the biological effects of fractionated radiation therapy on human brain tumor cells. Although this model cannot be used to evaluate the effect of radiation on normal tissue, it may be useful in developing more effective radiation therapy protocols for human brain tumors.

Brain Neoplasms↗
PubMed1993

The effects of O6-benzylguanine and hypoxia on the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea in nitrosourea-resistant SF-763 cells.

O6-Alkylguanine-DNA alkyltransferase (AGT) activity is associated with resistance of brain tumor cell lines to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). SF-763 cells exhibit high AGT activity and are resistant to BCNU. In this study, we compared the effects of the AGT inhibitor O6-benzylguanine (BG) on the cytotoxicity of BCNU in oxic and hypoxic SF-763 cells; we also measured AGT activity, ornithine decarboxylase (ODC) activity, and polyamine levels to determine if there was any correlation with cell survival as determined by colony-forming efficiency assay. Exponentially growing monolayer cells were pretreated with 10 microM BG for 2 h under oxic or hypoxic (95% nitrogen/5% CO2) conditions and then exposed to graded concentrations of BCNU for 1 h. BG significantly lowered AGT activity but had no cytotoxic effect in oxic or hypoxic cells; hypoxia alone was not cytotoxic. The cytotoxicity of BCNU was 4 times higher in BG-treated hypoxic cells than in oxic cells treated with BCNU alone; the BCNU doses required for a 1-log cell kill were 75 and 300 microM, respectively. ODC activity was lowered by hypoxia alone but was not significantly affected by BG in either hypoxic or oxic cells. Polyamine levels were not significantly affected by hypoxia or BG. These results indicate that pretreatment with BG dramatically lowers AGT activity and increases the cytotoxicity of BCNU in both oxic and hypoxic SF-763 cells. The mechanism of this enhanced cytotoxicity is apparently unrelated to ODC activity or polyamine levels.

Biogenic Polyamines↗
PubMed1993

Hepatitis B vaccination and the rate of seroconversion in high risk contacts.

Twenty-seven employees of a blood transfusion centre, Calcutta were vaccinated with hepatitis B vaccine (recombinant DNA technology), 20 micrograms/1 ml intramuscularly on 0, 8, 32 weeks interval. The seroconversion rate at 8, 32, 40 weeks were 29.6%, 55.5% and 100% respectively. The recombinant hepatitis B vaccine is acceptable and safe. The seroconversion rate is comparable to plasma derived hepatitis B vaccine.

Blood Banks↗
PubMed1993

A novel Yes-related kinase, Yrk, is expressed at elevated levels in neural and hematopoietic tissues.

While screening a chicken kidney cDNA library for the normal homolog of the yes oncogene, we isolated a clone that encodes a novel non-receptor type protein tyrosine kinase of the Src family. We named this gene product Yrk (York), as an acronym for Yes-related kinase. As predicted from the cDNA sequence, the Yrk protein consists of 536 amino acids and has all the canonical features of a Src kinase. At the amino terminus it contains a myristylation signal, followed by a unique domain, SH3 and SH2 motifs, an ATP binding site, a kinase region and a carboxy-terminal sequence with a potential regulatory tyrosine at position 530. The sequence of the Yrk protein showed 79% identity with human Fyn and 72% identity with chicken Yes. To eliminate the possibility that the Yrk protein is an avian homolog of mammalian Fyn, we isolated and sequenced the chicken fyn cDNA. The sequence data together with Southern and Northern blot analyses showed that the chicken yrk gene is distinct from the chicken fyn gene. Antibodies generated against the unique domain of the yrk protein expressed in bacteria precipitated a 60-kDa protein that was active in an immune complex kinase assay and was phosphorylated on tyrosine. Expression of the Yrk protein in adult chicken tissues was elevated in cerebellum and spleen. Relatively high levels of Yrk were also found in lung and skin.

Amino Acid Sequence↗
PubMed1992

Antitumor activity of some metal complexes: effect on hepatic DNA, RNA, and protein synthesis in rats bearing transplanted tumors by Dalton's lymphoma cells.

In order to ascertain the antitumor properties of metal complexes, we have investigated their effect on hepatic DNA, RNA pools, and protein levels in rats bearing transplanted tumors by Dalton's Lymphoma cells because antitumor agents are directed against DNA, RNA transcription, and synthesis. These coordination complexes have been synthesized by the condensation of 2,6-diacetylpyridine with FaHh and DAP-Th2, thereafter they were complexed with nickel, cobalt, and iron. The structure of these metal complexes have been elucidated on the basis of IR, UV, NMR, Mass, EPR, and magnetic studies. The tumor-transplanted rats were treated with these metal complexes and ligands (2 ml of 1 mM sol/Kg body weight, s.c.) for two weeks to study their effect on DNA, RNA pools, and protein levels. The metal complexes have altered the hepatic DNA, RNA pools, and protein levels in the liver, kidney, and spleen of rats.

Animals↗
PubMed1992

Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter.

The role of nitric oxide in relaxation of the internal anal sphincter (IAS) in response to the rectoanal reflex was studied in the opossum. Resting pressures in the IAS (IASP) were monitored using low-compliance continuously perfused catheters. The NO-synthase inhibitor L-NG-nitro-arginine (L-NNA) caused significant and dose-dependent suppression of the decrease in IASP in response to the reflex mimicked by the rectal balloon distention. NO-synthase inhibitor blocked IAS relaxation in response not only to rectoanal reflex but also to other neural stimuli such as sacral nerve stimulation, local intramural stimulation, and the nicotinic ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium. Suppression of the neurally mediated IAS relaxation by L-NNA was stereoselective; D-NNA had no effect on the relaxation. The suppression of the rectoanal reflex-induced IAS relaxation by L-NNA was completely reversed by NO precursor L-arginine stereoselectively as D-arginine failed to reverse the suppressed IAS relaxation. Sodium nitroprusside caused a decrease in IASP that was modified neither by the neurotoxin tetrodotoxin nor by L-NNA. Furthermore, the decrease in IASP by the direct-acting beta-adrenoceptor agonist isoproterenol was also not modified by the inhibitor of NO synthase. It is concluded that NO or an NO-like substance is an important mediator of IAS relaxation in response to noradrenergic, noncholinergic nerve stimulation.

Anal Canal↗
PubMed1992

Calcium as a counteractive agent to streptomycin induced respiratory depression: an in vivo electrophysiological observation.

Effect of streptomycin on respiratory function in cats was studied. It was observed that streptomycin at a dose of 40 mg/kg body weight intravenously (i.v.) caused respiratory failure or streptomycin induced respiratory depression (SIRD). This respiratory failure is not linked with Herring-Breuer stretch receptors because the effect remained unaltered in artificially ventilated cats. The involvement of central structures in SIRD can be discarded since intracarotid and intraventricular administration of streptomycin failed to produce any change in respiration. Studies on monosynaptic reflex, dorsal and ventral root activities of spinal phrenic and intercostal nerves, and on fusimotor and alpha-motor neuron activities of spinal intercostal and phrenic nerves in decerebrated cats indicated clearly that respiratory depression is not only due to blockade at neuromuscular junction but due to functional depression at the level of muscle receptors and spinal cord motor neurons. The respiratory depression induced by streptomycin was more or less completely reversed when calcium was administered intravenously from external source. It is speculated that streptomycin induced respiratory depression may be mediated through calcium inhibition which can be treated with external calcium in conjunction with artificial respiration.

Animals↗
PubMed1992

Effect of malathion on antioxidant defence system in human fetus--an in vitro study.

Malathion under in vitro condition even at lower concentration (250 ppm) altered the level of enzymes associated with glutathione cycle and antioxidant defence system in human fetal brain and liver. Such changes involved alterations in glutathione status and extent of lipid peroxidation. The inhibitory effect of malathion was dose dependent in case of human fetal brain and was more vulnerable than fetal liver. This alteration (inhibition or activation) was maximum in case of tissues from fetuses of early period of development, suggesting greater susceptibility of human fetus towards this organophosphorus insecticide.

Age Factors↗
PubMed1992

Effects of organophosphorus insecticide phosphomidon on antioxidant defence components of human erythrocyte and plasma.

Effect of organophosphorus insecticide, phosphomidon (250 and 500 ppm) on human erythrocyte and plasma were studied in vitro to get insight into the cellular antioxidant defence mechanism and malondialdehyde formation. The antioxidant defence system of erythrocyte was altered as evident by depression of glutathione reductase, glucose 6 phosphate dehydrogenase, whereas the level of reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxidedismutase and catalase were stimulated. In the case of plasma fraction, glutathione reductase, glutathione peroxidase, glutathione-s-transferase, glucose-6-phosphate dehydrogenase, superoxide dismutase and levels of reduced glutathione were significantly depressed and the malondialdehyde formation and catalase activity were elevated indicating the less adaptive response of plasma to protect it from oxidative damage.

Adult↗
PubMed1990

Occurrence and role of cis peptide bonds in protein structures.

It has been widely assumed that the occurrence of cis peptide bonds in proteins is quite rare due to unfavorable contacts between adjacent amino acid residues in this isomeric form. To investigate this assumption, the Brookhaven Protein Data Bank was examined for the occurrences of cis peptide bonds. Out of 31,005 amide bonds, only 17, or 0.05%, are cis, while 99 of the 1534 imide bonds (X-Pro), or 6.5%, are cis. These figures are considerably less than the distribution predicted on the basis of the potential energy difference between the cis and trans isomeric forms and experimental data on small peptides. It is not known whether the lower than expected occurrence of cis peptide bonds arises from constraints imposed by the protein environment, or from assumptions made in the solution of the X-ray crystal structures. However, when the occurrence of cis bonds in the data base is examined relative to the resolution of the structures, the number of cis bonds increases with increasing resolution. The distributions seen for these peptide omega bonds in the data base are not the same shape as the distributions predicted from simple potential energy barriers. They are sharper in the main, but they are also broader at the base with significant numbers of nonplanar peptide bonds. Cis peptide bonds are found primarily in bends and turns and, in the case of cis imide bonds (X-PRO), this correlation is so high that it suggests a specific role for cis imide groups in such structures.

Animals↗
PubMed1990

Effect of hypoxia on 1,3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity in 9L cells.

The cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on 9L rat brain tumor cells were studied under oxic and hypoxic conditions. Acute hypoxia was produced by gassing exponentially growing monolayer cells with 95% nitrogen/5% CO2 for 2 h, after which cells were treated with graded concentrations of BCNU for 1 h. Cell survival was assayed with a colony forming-efficiency assay and the extent of DNA cross-linking was measured with the alkaline elution assay. BCNU was more cytotoxic to hypoxic than to oxic cells. There were far more interstrand cross-links formed in hypoxic than in oxic cells, and the number of cross-links could be measured readily in hypoxic cells at very low concentrations of BCNU. This allowed cell survival and cross-linking to be compared at the same dose levels, a correlation not possible for oxic cells in which cross-links are not measurable at low doses. The total intracellular levels of glutathione were lower in hypoxic cells, but the reduced glutathione levels may not be related to the enhanced cell kill because survival of oxic cells treated with BCNU was not affected when cells were depleted of glutathione with buthionine sulfoximine. These results indicate that the additional cell kill produced in 9L cells under hypoxic conditions is related to increased cross-link formation.

Animals↗
PubMed1990

Cardiac arrhythmias and electrocardiographic changes during upper and lower gastrointestinal endoscopy.

Ninety-two patients undergoing upper and lower gastrointestinal endoscopy were monitored with holter recording for electrocardiographic changes during the procedures. The electrocardiographic changes were seen in 20.6% of the patients. These included cardiac arrhythmias in 16.2% and ischemic ST-T changes in 4.4% of the patients. The incidence of these changes was more in patients with cardiac (36%) or pulmonary disease (25%) than in patients with no clinical cardiac or pulmonary problem (16%). The patients with baseline electrocardiographic abnormalities also showed higher incidence of such electrocardiographic changes during the endoscopic procedures when compared with patients with normal baseline electrocardiograms (32% vs. 16%).

Adult↗