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R Bose

Publications and source records attributed to R Bose.

At least 19 recordsLinked to original sources
PubMed2001

Hypoxia-ischemia in fetal rabbit brain increases reactive nitrogen species production: quantitative estimation of nitrotyrosine.

Reactive nitrogen species (RNS) cause nitration of protein-bound tyrosine that is used as biomarker for detection. We hypothesized that RNS are formed in fetal rabbit brain following acute placental insufficiency. Near-term pregnant rabbits were randomized to either repetitive uterine ischemia or no ischemia, and fetal brains obtained. Only one electrochemical HPLC method (of three tested) was successful in detecting brain nitrotyrosine. Protein nitrotyrosine was significantly increased following cumulative 40 min ischemia and 20 min reperfusion compared to controls. Repetitive hypoxia-ischemia results in the increased formation of RNS in near-term fetal brains.

Animals↗
PubMed2001

Platelet hyperactivity and abnormal Ca(2+) homeostasis in diabetes mellitus.

We sought to determine the mechanisms for hyperactivity and abnormal platelet Ca(2+) homeostasis in diabetes. The glycosylated Hb (HbA(1c)) level was used as an index of glycemic control. Human platelets were loaded with Ca- green-fura red, and cytosolic Ca(2+) ([Ca(2+)](i)) and aggregation were simultaneously measured. In the first series of experiments, the platelets from diabetic and normal subjects were compared for the ability to release Ca(2+) or to promote Ca(2+) influx. A potent and relatively specific inhibitor of Na(+)/Ca(2+) exchange, 5-(4-chlorobenzyl)-2',4'-dimethylbenzamil (CB-DMB), increased the second phase of thrombin-induced Ca(2+) response, suggesting that the Na(+)/Ca(2+) exchanger works in the forward mode to mediate Ca(2+) efflux. In contrast, in the platelets from diabetics, CB-DMB decreased the Ca(2+) response, indicating that the Na(+)/Ca(2+) exchanger works in the reverse mode to mediate Ca(2+) influx. In the second series of experiments we evaluated the direct effect of hyperglycemia on platelets in vitro. We found that thrombin- and collagen-induced increases in [Ca(2+)](i) and aggregation were not acutely affected by high glucose concentrations of 45 mM. However, when the platelet-rich plasma was incubated with a high glucose concentration at 37 degrees C for 24 h, the second phase after thrombin activation was inhibited by CB-DMB. In addition, collagen-stimulated [Ca(2+)](i) response and aggregation were also increased. Thus in diabetes the direction and activity of the Na(+)/Ca(2+) exchanger is changed, which may be one of the mechanisms for the increased platelet [Ca(2+)](i) and hyperactivity. Prolonged hyperglycemia in vitro can induce similar changes, suggesting hyperglycemia per se may be the factor responsible for the platelet hyperactivity in diabetes.

Amiloride↗
PubMed2001

Low doses of heavy metals disrupt normal structure and function of rat platelets.

Aggregation, an important property of platelets, plays a key role in the coagulation of blood and is potentiated by ADP and adrenaline, whereas cAMP acts as a strong inhibitor. Because of the rise in the heavy metal load in the environment, more studies are necessary to look at its subtle effects in the animal system, wherein platelet structure and function can be targeted. We carried out structural analyses under phase contrast and scanning electronmicroscopy of the platelets prepared from 1/10 LD50 metal-treated rats. After mercury (Hg) and arsenic (As) treatment, the cell margins appeared irregular and wavy, with small pseudopodia-like protrusions from the surface. Cadmium (Cd) treatment caused loss of the general spindle shape, and the platelets assumed a round spongy appearance. All metal treatments effected enhanced collagen-induced aggregation and inhibited ADP- and arachidonic acid-induced aggregation, whereas epinephrine accelerated aggregation in Hg and Cd treatment but inhibited aggregation in As treatment. Cd proved a potent inhibitor of phosphodiesterase, increasing the cAMP level in in vitro treatments at equimolar (5, 10, and 20 pmoles) concentrations. The rate of aggregation was enhanced with all the agonists used in in vitro Hg and As treatments, with concomitant reduction in cAMP, while Cd inhibited platelet aggregation. Thus, we can conclude that cytosolic cAMP, which is decreased by the metal-induced inhibition of phosphodiesterase, is a regulator molecule in platelet aggregation. Furthermore, it is also abundantly clear that equimolar doses of metals are not always equitoxic. Therefore, the action of each xenobiotic is not only due to the concentration used but also to the type of xenobiotic depending on its unique mechanism of action.

Animals↗
PubMed2000

C-reactive protein in the hemolymph of Achatina fulica: interrelationship with sex steroids and metallothionein.

C-reactive protein in Achatina fulica (ACRP) is a normal component of the hemolymph. Its concentration varied from 1mg/ml in the newly hatched male, 3-5 mg/ml in the most active hermaphrodite and 1.5-2.8 mg/ml in the sedentary female showing a direct relationship of the protein with the active phase of the animal. ACRP has a molecular mass of 400 kDa and showed high absorbance in the region of 200-230 nm. It has four subunits with relative molecular masses of 110, 90, 62 and 60 kDa, respectively. Interestingly, rat platelet aggregation in vitro was significantly enhanced by ACRP in presence of 10 microM ADP and 2 mM Ca(2+) suggesting a probable role of ACRP in the aggregation of amoebocytes during the formation of plug in injured tissue. Like other vertebrate CRPs, ACRP also acts as a scavenger of chromatin fragments as evidenced by its binding to poly-L-arginine. Among the sex steroids, 4-androstenedione induces ACRP synthesis in the newly hatched male reaching the level found in the most active hermaphrodite phase (4 mg/ml). A very high molar ratio (5) of mercury binding to ACRP confirmed its sequestration property of heavy metals as observed in vertebrates. The level of metallothionein (MT) in the hemolymph gradually increased from the male to the hermaphrodite to the female, a pattern distinctly different from that of the ACRP titer. Since both MT and ACRP can sequester inorganic mercury, the high level of MT compensates functionally for the low titer of ACRP in the sedentary female.

Androstenedione↗
PubMed1998

Ceramide generation by the Reaper protein is not blocked by the caspase inhibitor, p35.

The Reaper (Rpr) gene encodes a 65-amino acid protein that induces apoptosis in Drosophila by an unknown mechanism. A previous study reported that Rpr expression induced generation of the lipid second messenger ceramide and through use of the peptide caspase inhibitor N-benzyloxycarbonyl-VAD-fluoromethylketone(zVAD.fmk ) ordered ceramide generation downstream of caspases in SL2 cells (Pronk, G. J. , Ramer, K., Amiri, P., and Williams, L. T. (1996) Science 271, 808-810). The present study re-evaluates these events in SL2 cells transfected with cDNA for Rpr, with or without the baculovirus caspase inhibitor p35, under the control of the metallothionein promoter. Following copper addition, Rpr protein was detected at 1.5 h and maximal at 2.5 h. Ceramide generation and caspase activation occurred nearly simultaneously, each detectable at 2-2.5 h and maximal at 6 h. Ceramide levels increased from a base line of 5 pmol/nmol lipid phosphorus to a maximum of 10 pmol/nmol lipid phosphorus. Identical increases in ceramide were detected using the enzymatic 1,2-diacylglycerol kinase assay or the non-enzymatic o-phthalaldehyde derivatization high pressure liquid chromatography assay. In contrast, diacylglycerol levels were not increased by Rpr expression. Apoptosis, first detected at 4 h, was maximal at 16 h. Co-expression of p35 did not affect Rpr-induced ceramide generation, whereas caspase activation and apoptosis were abolished. In contrast, zVAD.fmk inhibited ceramide generation and apoptosis. These data show that Rpr-induced ceramide generation is upstream or independent of p35-inhibitable caspases and demonstrate differences in the actions of peptide and p35 caspase inhibitors.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Autoantibodies to DEK oncoprotein in a patient with systemic lupus erythematosus and sarcoidosis.

A patient was identified with an unusual autoimmune syndrome consisting of systemic lupus erythematosus and sarcoidosis. Her serum contained extremely high levels of autoantibodies to the DEK protooncogene product. The patient's serum was used to clone a dek complementary DNA, which was expressed as a histidine-tagged fusion protein in Escherichia coli. Using affinity-purified recombinant DEK protein, anti-DEK autoantibodies were found in the patient's serum at a titer of 1:10(6) by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies revealed marked variations in anti-DEK autoantibody levels over time. Although it has been suggested that anti-DEK autoantibodies are a marker for pauciarticular juvenile rheumatoid arthritis with iridocyclitis, the present data suggest that they may be associated with other disease subsets as well. The quantitative ELISA technique will be useful for defining these subsets further and for examining the relationship between anti-DEK titers and disease activity.

Adolescent↗
PubMed1998

Tumour necrosis factor-alpha, but not septic plasma depresses cardiac myofilament contraction.

PURPOSE: In sepsis, myocardial depression may be caused by mediators released as part of the inflammatory reaction, lumour necrosis factor alpha (TNF alpha) is one mediator that may contribute to this depression. In the present study, we contrasted the effects of TNF alpha and septic plasma fraction (SP) obtained from an E. coli model on contractile tension in intact and skinned canine ventricular trabecular (VT) preparations. The objectives were to determine whether SP or TNF alpha could impair contractile tension at the level of the myofilaments, and to determine the extent to which TNF alpha may account for myocardial depression found in E. coli sepsis. METHODS: Measurements of isometric tensions were made after TNF alpha and SP (10,000 to 30,000 MW fraction) were added to respective intact or skinned canine VT preparations. In the skinned preparation, trabeculae were chemically skinned with Triton X-100. RESULTS: Septic plasma caused a decrease in contraction in the intact preparation compared with preseptic plasma (50 +/- 7 vs 33 +/- 7%, P < 0.05), but had no effect in the skinned preparation. On the other hand, TNF alpha (30 ng.ml-1) caused an approximately 50% reduction in tension (29 +/- 2 mg vs 16 +/- 5 mg) in the skinned preparation (P < 0.05), but had no effect in the intact preparation. CONCLUSION: These results suggest that TNF alpha and SP act through different mechanisms. While SP requires an intact membrane, TNF alpha impairs function by a direct effect on the myofilaments.

Actin Cytoskeleton↗
PubMed1998

Taurine indirectly increases [Ca]i by inducing Ca2+ influx through the Na(+)-Ca2+ exchanger.

Recent studies in heart cells have shown taurine to induce a sustained increase of both intracellular Ca2+ and Na+. These results led us to believe that the increase in Na+ by taurine could be due to Na+ entry through the taurine-Na+ cotransporter which in turn favours transarcolemmal Ca2+ influx through Na(+)-Ca2+ exchange. Therefore, we investigated the effect of beta-alanine, a blocker of the taurine-Na+ cotransporter and low concentrations of CBDMB (a pyrazine derivative, 5-(N-4chlorobenzyl)-2',4'-dimethylbenzamil), a Na(+)-Ca2+ exchanger blocker on taurine-induced [Ca]i increase in embryonic chick heart cells. Using Fura-2 Ca2+ imaging and Fluo-3Ca2+ confocal microscopy techniques, taurine (20 mM) as expected, induced a sustained increase in [Ca]i at both the cytosolic and the nuclear levels. Preexposure to 500 microM of the blocker of the taurine-Na+ cotransporter, beta-alanine, prevented the amino acid-induced increase of total [Ca]i. On the other hand, application of beta-alanine did not reverse the action of taurine on total [Ca]i. However, low concentrations of the Na(+)-Ca2+ exchanger blocker, CBDMB, reversed the taurine-induced sustained increase of cytosolic and nuclear free calcium (in presence or absence of beta-alanine). Thus, the effect of taurine on [Ca]i in heart cells appears to be due to Na+ entry through the taurine-Na+ cotransporter which in turn favours transarcolemmal Ca2+ influx through the Na(+)-Ca2+ exchanger.

Amiloride↗
PubMed1997

Specific binding of inorganic mercury to Na(+)-K(+)-ATPase in rat liver plasma membrane and signal transduction.

Specific binding of Hg2+ to ouabain-sensitive Na(+)-K(+)-ATPase of rat liver plasma membrane was demonstrated with a Ka of 2.64 x 10(9) and Bmax of 1.6 nmole mg-1 protein. The binding of mercury to the enzyme also causes significant inhibition of the enzyme, which is greater than its ouabain sensitivity. In the cytosol Hg2+ binding to reduced glutathione (GSH) is stimulated by GSH-S-transferase (GST), the activity of which was found to be significantly enhanced by 15 mM Na+ and 10 mM Hg2+. It is proposed that the transport of Hg2+ inside the cell takes place by increased dissociation of Hg2+ from the membrane due to greater avidity of Hg2+ towards cytosolar GSH binding. The GSH-Hg complex enters the nucleus where it dissociates to bind the metal response element (MRE) of the metallothionein (MT) gene to induce MT transcription.

Animals↗
PubMed1997

Evidence for a high free radical state in low-grade astrocytomas.

OBJECTIVE: It is postulated that reactive oxygen species may play an inductive role in neuro-oncogenesis. However, data pertaining to the redox state of astrocytomas are limited, which prompted us to undertake this study. METHODS: Intraoperative snap-frozen samples were obtained from the surface and core of 8 low-grade and 11 high-grade astrocytomas. Small portions of each specimen were fixed in 10% neutral formalin or cacodylate-buffered glutaraldehyde. Lipid peroxidation was estimated by measuring thiobarbituric acid-reactive substances, and total glutathione levels were determined. Light microscopy was performed to define the relevant histopathology, and electron microscopy was used to quantitate peroxisomal content. RESULTS: Thiobarbituric acid-reactive substance values for low-grade astrocytomas were significantly elevated compared to those for malignant lesions, as was the case for total glutathione. This discrepancy was especially marked at the tumor surface. Peroxisomes predominated in the low-grade category. CONCLUSION: We speculate regarding malignant transformation as a possible consequence of this decline in antioxidant capacity, as well as regarding the role of seizures and astrocytoma glutamate receptors in the initiation of free radical cascades. The therapeutic and teleological implications are considerable.

Adolescent↗
PubMed1997

Psychiatry and the popular conception of possession among the Bangladeshis in London.

Two detailed case histories of young people possessed by spirits are presented to show that expressions of distress are shaped by cultural beliefs from the very inception. It stands in marked contrast to the Western psychiatric view of possession beliefs as cultural explanations offered for underlying pathological processes. This has serious implications for the practice of psychiatry in increasingly multi cultural societies.

Adolescent↗