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Biomedical subjects

S Misra

Publications and source records attributed to S Misra.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sertraline in chronic tension-type headache.

OBJECTIVES: To study the effect of Sertraline, a selective serotonin reuptake inhibitor in chronic tension type headache (CTTH) in a double blind placebo controlled randomized trial. MATERIAL AND METHODS: The study design was a double blind placebo controlled randomized study of 50 patients, over a period of 10 weeks including run-in period of two weeks, treatment period four weeks, and follow-up four weeks. The diagnosis of CTTH was based on criteria given by International Headache Society (IHS). The overall response was graded in terms of headache index, analgesic intake per week and percentage reduction in headache frequency using chi-square and 't' test. Anxiety and depression was assessed using Hamilton Rating Scale. RESULTS: The mean analgesic intake per week declined from 4.34 +/- 0.736 tab/week to 1.07 +/- 0.592 tab/week in sertraline group (p < 0.01) while reduction in placebo group was not significant (3.98 +/- 0.729 tab/week to 2.94 +/- 0.665 tab/week) (p > 0.05). The reduction in headache index and percentage reduction in frequency of headache was not significant in drug treatment group. Side effects were seen in 24.4% of patients nausea, nervousness and dizziness being the commonest. CONCLUSION: The drug treatment group showed a significant decline in analgesic intake per week. The study result shows that sertraline can be a useful alternative to amitryptiline in those patients who fail to respond or cannot tolerate it.

Adult↗
PubMed2002

Induction and transmission of cytogenetic toxic effects of 5-fluorouracil in male germline cells of Swiss mice.

Cytogenetic toxicity after a single intraperitoneal exposure of three different doses (5,10 and 15 mg/kg) of 5-fluorouracil (5-FU) and its transmission in the male germline cells of Swiss mice was assessed. At 24 hrs post-treatment each of the doses of 5-FU induced statistically highly significant number of chromosomal aberrations, mostly random chromatid breaks, in the spermatogonial cells with maximum aberrations in the lowest dose. Primary spermatocytic chromosome analysis at week 4 post-treatment showed the presence of a statistically significant number of aberrant spermatocytes with atypical bivalents, mostly with autosomal and/or XY univalents. Sperm morphology assay at week 8 post-treatment exhibited higher percentages of abnormal sperm, but were not statistically significant. This indicated the gradual decline in the transmission of the induced cytogenetic toxic effects of 5-FU from spermatogonia to sperm, which might be because of gradual elimination of the grossly affected spermatogonial cells during the course of spermatogenesis.

Animals↗
PubMed2001

Recognizing phosphatidylinositol 3-phosphate.

Phosphatidylinositol 3-phosphate directs the endosomal localization of regulatory proteins by binding to FYVE and PX domains. New structures of these domains complexed with the phosphoinositide headgroup show how interactions with phosphate and hydroxyl groups differentiate this lipid from all others.

Endosomes↗
PubMed2001

Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells.

Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of endocytosis as well as in cellular proliferation and transformation. The SH3 domain of its regulatory p85 subunit stimulates the GTPase activity of dynamin in vitro. Dynamin is a GTPase enzyme required for endocytosis of activated growth factor receptors. An interaction between these proteins has not been demonstrated in vivo. Here, we report that dynamin associates with PI 3-kinase in hematopoietic cells. We detected both p85 and PI 3-kinase activity in dynamin immune complexes from IL-3-dependent BaF3 cells. However, this association was significantly reduced in BaF3 cells transformed with the BCR/abl oncogene. After transformation only a 4-fold increase in PI 3-kinase activity was detected in dynamin immune complexes, whereas grb2 associated activity was elevated 20-fold. Furthermore, dynamin inhibited the activity of both purified recombinant and immunoprecipitated PI 3-kinase. In BaF3 cells expressing a temperature-sensitive mutant of BCR/abl, a significant decrease in p85 and dynamin association was observed 4 h after the induction of BCR/abl activity. In contrast, in IL-3-stimulated parental BaF3 cells, this association was increased. Our results demonstrate an in vivo association of PI 3-kinase with dynamin and this interaction regulates the activity of PI 3-kinase.

Animals↗
PubMed2001

Mitogenic signaling by cyclic adenosine monophosphate in chromaffin cells involves phosphatidylinositol 3-kinase activation.

Increase of intracellular cyclic adenosine monophosphate by the permeant cyclic adenosine monophosphate analog, 8-(4-chlorophenylthio)-adenosine 3':5'- cyclic monophosphate, is mitogenic for normal adult rat chromaffin cells. The mitogenic effect is blocked by the phosphatidylinositol 3-kinase inhibitor, LY294002, and is associated with accumulation of phosphorylated Akt and p70S6 kinase, suggesting that cyclic adenosine monophosphate activates Type l phosphatidylinositol 3-kinase. The mechanism of activation was examined in PC12 pheochromocytoma cells, which are neoplastic chromaffin cells that exhibit many of the biochemical characteristics of their normal counterparts. Incubation of PC12 cells with 8-(4-chlorophenylthio)-adenosine 3':5'- cyclic monophosphate led to a significant increase in total phosphatidylinositol 3-kinase activity that was sensitive to low concentrations of LY294002. The increase was maximal at 1 h and returned to basal levels within six hours. Immunoprecipitation studies showed no increase in phosphatidylinositol 3-kinase activity in anti-phosphotyrosine immune complexes from PC12 cells stimulated by 8-(4-chlorophenylthio)-adenosine 3':5'- cyclic monophosphate, in contrast to cells stimulated by nerve growth factor. Instead, activity was demonstrated in association with p110gamma and p85. These findings suggest that cyclic adenosine monophosphate causes activation of Types IA and IB phosphatidylinositol 3-kinase by a novel mechanism in chromaffin and pheochromocytoma cells. That activation may contribute to chromaffin cell proliferation and to the development and progression of pheochromocytomas. J. Cell. Biochem. Suppl. 36: 89-98, 2001.

Animals↗
PubMed2001

Kinetics and pH dependence of light-induced deprotonation of the Schiff base of rhodopsin: possible coupling to proton uptake and formation of the active form of Meta II.

In this paper we first review what is known about the kinetics of Meta II formation, the role and stoichiometry of protons in Meta II formation, the kinetics of the light-induced changes of proton concentration, and the site of proton uptake. We then go on to compare the processes that lead to the deprotonation of the Schiff base in bacteriorhodopsin with rhodopsin. We point out that the similarity of the signs of the light-induced electrical signals from the two kinds of oriented pigment molecules could be explained by bacteriorhodopsin releasing a proton from its extracellular side while rhodopsin taking up a proton on its cytoplasmic side. We then examined the pH dependence of both the absorption spectrum of the unphotolyzed state and the amplitude and kinetics of Meta II formation in bovine rhodopsin. We also measured the effect of deuteration and azide on Meta II formation. We concluded that the pKa of the counter-ion to the Schiff base of bovine rhodopsin and of a surface residue that takes up a proton upon photolysis are both less than 4 in the unphotolyzed state. The data on pH dependence of Meta II formation indicated that the mechanisms involved are more complicated than just two sequential, isospectral forms of Meta II in the bleaching sequence. Finally we examined the evidence that, like in bacteriorhodopsin, the protonation of the Schiff bases's counter-ion (Glu113) is coupled to the changing of the pKa of a protonatable surface group, called Z for rhodopsin and tentatively assigned to Glu134. We conclude that there probably is such a coupling, leading to the formation of the active form of Meta II.

Azides↗
PubMed2001

Familial intrahepatic cholestasis 1: studies of localization and function.

Mutations in the FIC1 gene constitute the molecular defect in familial intrahepatic cholestasis I (Fic1 [Byler's disease]) and benign recurrent intrahepatic cholestasis. This report describes the localization of Fic1 in rat liver and intestine, as well as biochemical and transfection studies that support its function as an energy-dependent aminophospholipid translocase. Immunocytochemistry of rat liver and immunoblotting of membrane fractions localized Fic1 to the canalicular, but not basolateral, plasma membrane domain. In the small intestine, Fic1 was localized to the apical membrane of epithelial cells. The distribution of Fic1 in liver plasma membrane fractions from control and taurocholate-treated rats correlated positively with adenosine triphosphate (ATP)-dependent aminophospholipid (phosphatidyl-serine) translocase activity. In canalicular membrane vesicles, translocase activity had an initial velocity of 3.3 nmol phosphatidylserine (PS) translocated per milligram of protein per minute and a K(m) (ATP) = 1.2 mmol/L; was inhibited by vanadate, N-ethylmaleimide, sodium azide, and calcium; and was unidirectional (i.e., from the outer to the inner canalicular plasma membrane leaflet). Transient transfection of CHOK1 cells with FIC1 cDNA resulted in appearance of FIC1 in membrane preparations and energy-dependent PS translocation in cells. These studies indicate that FIC1 is a canalicular P-type ATPase that participates in maintaining the distribution of aminophospholipids between the inner and outer leaflets of the plasma membrane. How this process produces cholestasis is under study.

Adenosine Triphosphatases↗
PubMed2001

Single small enhancing computed tomographic (CT) lesions in Indian patients with new-onset seizures. A prospective follow-up in 75 patients.

This study was planned to observe the clinical and radiological course of single small enhancing CT lesions in Indian patients presenting with new-onset-seizures. In this study, 75 patients with new-onset seizures and a single enhancing CT lesion were prospectively followed up for 1 year. All patients fulfilled the criteria of cysticercus granuloma. The repeat CT scans were performed 2 months after the first CT scan. Antiepileptic drug therapy was the only form of treatment given. The majority of patients were below 20 years of age. Simple partial seizure, with or without secondary generalization, was the commonest type of seizure encountered in these patients. In follow-up CT scans 84% of patients showed either disappearance or regression in the size of lesion. The proportion of patients showing complete disappearance of CT lesions was 0.73 (95% CI, 0.61-0.80). In 11 (15%) patients the lesions were calcified. In nine patients, in whom the lesion had persisted or regressed, another follow-up CT scan (6 months after the second scan) revealed either complete disappearance or calcification of the lesions. The majority (86.6%) of patients remained seizure free for 1 year after starting antiepileptic drugs. Ten patients experienced seizure recurrences within the first month of therapy. The proportion of patients who remained seizure free was 0.86 (95% CI, 0.76-0.92). Four patients experienced seizure recurrence even after complete disappearance of CT lesions. In the majority of patients the lesions disappeared spontaneously and in a few the lesions calcified; hence these patients did not require anticysticercal therapy. Antiepileptic therapy was helpful in controlling further recurrences of seizures in most of the patients. A few patients experienced seizures even after disappearance of CT lesions.

Adolescent↗
PubMed2001

Characterization of proteinase activity in stratified Douglas-fir seeds.

We investigated the effect of stratification on the proteinase activity involved in mobilization of the major soluble approximately 45 kDa storage protein during germination of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seeds. Complete hydrolysis of the approximately 45 kDa protein was observed approximately 7 days after exposure of stratified seeds to germination conditions. Coincident with the onset of mobilization, proteinase activity was detected primarily in microsomal extracts from stratified seeds. Microsomal-associated proteinase activity was most active at pH 8.0 and had a molecular mass > 175 kDa as determined by gelatin SDS-PAGE gels. In vitro digestion of soluble protein extracts indicated that, following stratification, there was a significant increase in proteinase activity and hydrolysis of the approximately 45 kDa storage protein. Whether this increase was a result of activation of preexisting proteinase(s) or de novo synthesis remains unknown. In vitro digestion of soluble protein extracts in the presence of various proteinase inhibitors showed that digestion of the approximately 45 kDa storage protein is mediated primarily by a metalloproteinase and to a lesser degree by a serine proteinase. The accumulation of approximately 25 kDa protein products following in vitro digestion suggests that mobilization of the approximately 45 kDa soluble storage protein is mediated by a multi-step process involving the action of different classes of proteinases.

Electrophoresis, Polyacrylamide Gel↗
PubMed2001

S-phase dependent cytogenetic toxicity of 5-fluorouracil in bone marrow cells of mice.

The in vivo cytogenetic toxicity of three different doses (5,10 and 15 mg/kg) of 5-fluorouracil (5-FU) (in Fluracil) was assessed in bone marrow cells of mice. At 24 hrs post-treatment the induced chromosomal aberrations, mostly chromatid breaks and fragments, by all the three different concentrations of 5-FU were found statistically significant. However, mitotic index study at 24 hrs post-treatment indicated it as nonmitotoxic. At 30 hrs posttreatment, all the three doses of 5-FU induced a statistically significant number of micronuclei per thousand polychromatic erythrocytes. This indicated 5-FU as nonmitotoxic but highly clastogenic in bone marrow cells of mice.

Animals↗
PubMed2000

Profile of anemia in children after liver transplantation.

BACKGROUND: Clinical and hematological profile of chronic anemia in children after orthotopic liver transplantation (OLT) is unknown. METHODS: We prospectively studied children after orthotopic liver transplantation (OLT) with hemoglobin levels < 2 standard deviation of age appropriate mean for > 6 months. Investigations included hemogram, reticulocyte count, peripheral blood smear, serum vitamin B-12, folic acid levels, iron studies, Coomb's tests, serum erythropoietin (EPO) levels, and stool and urine tests for occult blood. RESULTS: Fifty-six participants (22 male and 34 female, mean age 82.9 months, range 20-232, mean post-OLT duration 48.8 months, range 6-132) were studied. The causes of anemia were idiopathic (32), iron deficiency (4), viral infections (2, HIV=1, parvovirus=1), and lymphoproliferative disease (2). Fifteen participants showed spontaneous recovery within 1-6 months. Thirty-one children with idiopathic anemia had low or normal EPO levels (mean 7.33 mmicro/L, range <2.5 to 15.9, normal 4-24). When outliers (iron deficiency=4, HIV disease= 1) were excluded, there was no statistical correlation between hematocrits and EPO levels. Serum vitamin B-12 levels (n=52) were elevated (normal 110-930 pg/ml) (mean=1,186 pg/ml) in 32 (61.5%) and were significantly higher in those with abnormal liver function tests. CONCLUSION: Anemia is a common problem in children after OLT. More than half the participants had anemia of unknown etiology with an inappropriate EPO response for the degree of anemia. The normal negative correlation between hematocrit and EPO was lost in these children. The observation regarding serum vitamin B-12 levels requires further study.

Adolescent↗
PubMed2000

Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes.

VHS domains are found at the N-termini of select proteins involved in intracellular membrane trafficking. We have determined the crystal structure of the VHS domain of the human Tom1 (target of myb 1) protein to 1.5 A resolution. The domain consists of eight helices arranged in a superhelix. The surface of the domain has two main features: (1) a basic patch on one side due to several conserved positively charged residues on helix 3 and (2) a negatively charged ridge on the opposite side, formed by residues on helix 2. We compare our structure to the recently obtained structure of tandem VHS-FYVE domains from Hrs [Mao, Y., Nickitenko, A., Duan, X., Lloyd, T. E., Wu, M. N., Bellen, H., and Quiocho, F. A. (2000) Cell 100, 447-456]. Key features of the interaction surface between the FYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain, are conserved in the VHS domain of Tom1, even though Tom1 does not have a FYVE domain. We also compare the structures of the VHS domains of Tom1 and Hrs to the recently obtained structure of the ENTH domain of epsin-1 [Hyman, J., Chen, H., Di Fiore, P. P., De Camilli, P., and Brünger, A. T. (2000) J. Cell Biol. 149, 537-546]. Comparison of the two VHS domains and the ENTH domain reveals a conserved surface, composed of helices 2 and 4, that is utilized for protein-protein interactions. In addition, VHS domain-containing proteins are often localized to membranes. We suggest that the conserved positively charged surface of helix 3 in VHS and ENTH domains plays a role in membrane binding.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Comparative genomics of the eukaryotes.

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Animals↗
PubMed2000

Characterization and expression of the Douglas-fir luminal binding protein (PmBiP).

The endoplasmic reticulum (ER) molecular chaperone, BiP, plays a role in the cotranslational translocation and subsequent folding and assembly of newly synthesized proteins targeted to the ER and secretory pathway. The sequence encoding a Douglas-fir (Pseudotsuga menziesii [Mirb] Franco) BiP homologue (PmBiP) was identified by differential screening of a seedling cDNA library. Southern blotting indicated that PmBiP is most likely present as a single copy. The deduced amino acid sequence of PmBiP contains an HEEL tetrapeptide sequence which functions to retain PmBiP in the ER and is different from HDEL commonly found in angiosperm plant BiPs. Amino acid sequence alignment and phylogenetic analysis show that PmBiP is highly similar to other plant BiPs yet forms a distinct phylogenetic subgroup which is separate from the angiosperm BiPs. Northern and western blotting revealed that PmBiP is subject to developmental regulation during seed development, germination, and early seedling growth and is seasonally regulated in needles of young seedlings.

Amino Acid Sequence↗
PubMed2000

Single-enhancing CT lesions in Indian patients with seizures: a review.

Single enhancing CT lesions are the commonest radiological abnormality in Indian patients with new-onset partial seizures. In few patients the lesions may be 'tuberculoma' (especially in presence of evidence of tuberculosis elsewhere). However, histopathological studies have proved that neurocysticercosis is the most frequent cause for these lesions. Acute inflammation in and around the cerebral lesions of cysticercosis manifests as acute seizure disorder. These cysticercal granulomas represent 'colloidal' and 'nodular-granular' stages of Escobar's pathological classification of natural evolution of a parenchymal cysticercus cyst. In 8-12 weeks time majority of these lesions spontaneously disappear, few may calcify. As albendazole therapy is of controversial value, these patients, possibly, need to be treated only with antiepileptic drugs. Associated seizure disorder is also benign in nature and remit in majority within 6-8 months, recurrences are usually infrequent. Antiepileptic drug may be withdrawn once follow-up CT scan shows resolution of the lesion. If seizures recur after resolution of the lesion, CT lesion persists or CT lesion calcified, a long-term (2-3 years) antiepileptic therapy may be required. The single enhancing CT lesions which persist despite anticysticercal or antituberculous therapy may need histopathological evaluation to establish the correct diagnosis.

Algorithms↗