Search PubMed⌕ Search

Biomedical subjects

S Misra

Publications and source records attributed to S Misra.

At least 73 records · Page 4Linked to original sources
PubMed1999

Neurological manifestations of malaria : an update.

Several neurological complications are associated with complicated and severe falciparum malaria. Cerebral malaria is one of the most dreaded complication. The children are particularly more vulnerable to have this complication. Despite availability of several potent antimalarial drugs in recent past, the mortality status has not changed. A large number of survivors are left with disabling neurological sequelae. Few patients may experience post-malaria neurological syndrome after recovery from complicated falciparum infection. Various psychiatric syndromes have been described either as early manifestation of cerebral malaria or part of post malaria neurological syndrome. From Indian subcontinent several patients of delayed cerebellar ataxia have also been described following recovery from clinical malaria. In paediatric patients, convulsions of cerebral malaria need to be differentiated from febrile convulsions. Falciparum malaria is also associated specifically with convulsions in uncomplicated patients of malaria. Several isolated case reports of various other neurological syndromes like peripheral neuropathies, various movement disorders, myelopathies and stroke like syndrome have been described. However association of these neurological manifestations with malaria remains doubtful.

Brain Diseases↗
PubMed1999

A study of transcranial magnetic stimulation in older (>3 years) patients of malnutrition.

Transcranial magnetic stimulation was performed in 40 subjects. Twenty patients in the age group of 3 to 8 years and having different grades of malnutrition were included in the 'study group' whereas 20 normal children having no complaints comprised the 'control group'. The coil of the magnetic stimulator was applied tangentially over the vertex to stimulate the cortex. The motor evoked potential (MEP) was obtained using root stimulation by applying the coil at the cervical and lumbosacral spines. Recordings were made from the abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles of both sides. Cortical threshold, latency and amplitude of motor evoked potential and central conduction time were recorded. Malnourished children showed significantly increased cortical threshold, prolonged cortical latency and central conduction time and reduction in amplitude of MEP. Observed delay in central motor conduction in malnourished children suggests asymptomatic involvement of corticospinal pathways.

Child↗
PubMed1998

The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP-dependent canalicular transporters in rat liver.

Recent studies indicate that wortmannin, a potent inhibitor of phosphatidylinositol (PI) 3-kinase, interferes with bile acid secretion in rat liver; taurocholate induces recruitment of ATP-dependent transporters to the bile canalicular membrane, and PI 3-kinase products are important in intracellular trafficking. We investigated the role of PI 3-kinase in bile acid secretion by studying the in vivo effect of taurocholate, colchicine, and wortmannin on bile acid secretion, kinase activity, and protein levels in canalicular membrane vesicle (CMV) and sinusoidal membrane vesicle (SMV) fractions from rat liver. Treatment of rats or perfusion of isolated liver with taurocholate significantly increased PI 3-kinase activity in both membrane fractions. Taurocholate increased protein content of ATP-dependent transporters, which were detected only in CMVs, whereas increased levels of p85 and a cell adhesion molecule, cCAM 105, were observed in both fractions. Colchicine prevented taurocholate-induced changes in all proteins studied, as well as the increase in PI 3-kinase activity in CMVs, but it resulted in further accumulation of PI 3-kinase activity, p85, and cCAM 105 in SMVs. These results indicate that taurocholate-mediated changes involve a microtubular system. Wortmannin blocked taurocholate-induced bile acid secretion. The effect was more profound when wortmannin was administered prior to treatment with taurocholate. When wortmannin was given after taurocholate, the protein levels of each ATP-dependent transporter were maintained in CMVs, whereas the levels of p85 and cCAM decreased in both membrane fractions. Perfusion of liver with wortmannin before taurocholate administration blocked accumulation of all proteins studied in CMVs and SMVs. These results indicate that PI 3-kinase is required for intracellular trafficking of itself, as well as of ATP-dependent canalicular transporters.

Adenosine Triphosphate↗
PubMed1998

Structure of type IIbeta phosphatidylinositol phosphate kinase: a protein kinase fold flattened for interfacial phosphorylation.

Phosphoinositide kinases play central roles in signal transduction by phosphorylating the inositol ring at specific positions. The structure of one such enzyme, type IIbeta phosphatidylinositol phosphate kinase, reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to one superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 A basic flat face that suggests an electrostatic mechanism for plasma membrane targeting. Conserved basic residues form a putative phosphatidylinositol phosphate specificity site. The substrate-binding site is open on one side, consistent with dual specificity for phosphatidylinositol 3- and 5-phosphates. A modeled complex with membrane-bound substrate and ATP shows how a phosphoinositide kinase can phosphorylate its substrate in situ at the membrane interface.

Bacterial Proteins↗
PubMed1998

Development of in vitro screening system for assessment of antifilarial activity of compounds.

Evaluation of antifilarial activity of new potential agents in vivo is extremely time consuming and uneconomic. In the present study effort has been made to develop an in vitro screening method using Acanthocheilonema viteae, a subcutaneously dwelling rodent filariid with anaerobic metabolic characteristics like human filariids, W. Bancrofti/Brugia malayi as test parasite. Motility test and tetrazolium (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) based colorimetric assay were used as parameters in in vitro assay. Results showed that 92.3% of compounds (in vivo active) could be picked up in the in vitro assay when both adults and microfilarae (mf) were used simultaneously. Mf and adult stages separately detected, respectively, 84.6 and 69.2% of in vivo active compounds. The adults and mf separately and both the life stages together exhibited, respectively, 80.0, 50.0 and 80.0% false positive results in the in vitro test with in vivo inactive compounds. It is felt that mf stage when used in in vitro test using motility and MTT assays as parameters would be useful in primary screening of new potential filaricides.

Animals↗
PubMed1998

Is absence of pyruvate dehydrogenase complex in mitochondria a possible explanation of significant aerobic glycolysis by normal human leukocytes?

The oxygen consumption of leukocyte mitochondria of both healthy donors and leukemic patients was tested by using different respiratory substrates. The results indicate that pyruvate could not be utilized by mitochondria of normal leukocytes, whereas mitochondria of leukemic leukocytes could use pyruvate as a good respiratory substrate. A search for the possible presence of pyruvate dehydrogenase complex (PDC) in leukocytes indicates that this enzyme is apparently absent in mitochondria of normal leukocytes but is quite active in mitochondria of leukemic leukocytes. The absence of PDC in normal leukocyte mitochondria can explain the phenomenon of significant aerobic glycolysis that has been observed in normal leukocytes.

Acetyl Coenzyme A↗
PubMed1998

Red cell aplasia in children on tacrolimus after liver transplantation.

Hematological toxicity of tacrolimus has been rarely reported. We report two pediatric recipients of liver transplantation with anemia. They were treated with tacrolimus for 8 and 47 months, respectively, before developing pure red cell aplasia (PRCA) confirmed by bone marrow biopsy. The children recovered quickly on withdrawal of tacrolimus. The clinical profile of these children is compared with the only other patient reported in the literature with PRCA due to tacrolimus. All three patients had similar hematological findings. However, the mechanism of the tacrolimus-induced PRCA in these children appears to be different from that reported in the adult patient.

Adult↗
PubMed1998

A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene.

The cardiac/slow twitch sarcoplasmic reticulum (SR) Ca2+-ATPase gene (SERCA2 ) encodes a calcium transport pump whose expression is regulated in a tissue- and development-specific manner. Previously we have identified two distinct positive regulatory regions (bp -284 to -72 and -1815 to -1105) as important for SERCA2 promoter activity. Here we demonstrate that the SERCA2 distal promoter region functions like an enhancer by activating a heterologous promoter (TK) in a muscle cell-specific manner. Through deletion analysis a core enhancer region was delimited to the -1467 to -1105 bp fragment. We identified the E box/AT-rich element located at -1115 bp as critical for maximal enhancer activity. Gel mobility shift studies revealed that this E box/AT-rich element specifically binds a protein which is induced during Sol8 myogenesis. This region includes two other cis -acting elements, CArG and MCAT, which also bind specific nuclear protein complexes from Sol8 myotubes. Mutagenesis of each of these sites resulted in decreased SERCA/TK-CAT promoter activity. Based on these data, we propose that the E box/AT-rich element may contribute along with CArG and MCAT elements to the overall activation and regulation of the SERCA2 gene promoter.

3T3 Cells↗
PubMed1998

Sequence and expression of embryogenesis-specific cDNAs encoding 2S seed storage proteins in Pseudotsuga menziesii [Mirb.] Franco.

Differential screening of a cDNA library constructed from polyadenylated RNA from developing Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) seeds resulted in the isolation of four full-length cDNA clones (PM2S1, PM2S2, PM2S3 and PM2S4) encoding isoforms of 2S seed storage proteins. The deduced amino acid sequences had low similarity to the angiosperm 2S storage proteins such as 2S albumin, napin and alpha-amylase/trypsin inhibitor yet contained all conserved cysteines in an arrangement suggestive of a structural similarity between the 2S seed storage proteins from gymnosperms and angiosperms. Southern blot analysis of genomic DNA suggested that the Douglas-fir 2S seed protein genes consisted of at least two sub-families, each including several gene members. Northern blot analysis revealed that all four PM2S mRNAs were present specifically in seeds and temporally during seed development. However, the decline in PM2S2 mRNAs in the megagametophytes occurred before that of the other mRNAs, suggesting that their gene expression was regulated differentially. The accumulation of PM2S transcripts in the haploid megagametophytes started during early embryogenesis and reached a peak before that in diploid zygotic embryos. The mRNAs for PM2S were present in Douglas-fir somatic embryos at the same developmental stages as those in the zygotic embryos, and abscisic acid and osmoticum stress were necessary for the expression of PM2S genes in somatic embryos.

Abscisic Acid↗
PubMed1998

Contribution of proton release to the B2 photocurrent of bacteriorhodopsin.

The contribution of proton release from the so-called proton release group to the microsecond B2 photocurrent from bacteriorhodopsin (bR) oriented in polyacrylamide gels was determined. The fraction of the B2 current due to proton release was resolved by titration of the proton release group in M. At pH values below the pKa of the proton release group in M, the proton release group cannot release its proton during the first half of the bacteriorhodopsin photocycle. At these pH values, the B2 photocurrent is due primarily to translocation of the Schiff base proton to Asp85. The B2 photocurrent was measured in wild-type bR gels at pH 4.5-7.5, in 100 mM KCl/50 mM phosphate. The B2 photocurrent area (proportional to the amount of charge moved) exhibits a pH dependence with a pKa of 6.1. This is suggested to be the pKa of the proton release group in M; the value obtained is in good agreement with previous results obtained by examining photocycle kinetics and pH-sensitive dye signals. In the mutant Glu204Gln, the B2 photocurrent of the mutant membranes was pH independent between pH 4 and 7. Because the proton release group is incapacitated, and early proton release is eliminated in the Glu204Gln mutant, this supports the idea that the pH dependence of the B2 photocurrent in the wild type reflects the titration of the proton release group. In wild-type bacteriorhodopsin, proton release contributes approximately half of the B2 area at pH 7.5. The B2 area in the Glu204Gln mutant is similar to that in the wild type at pH 4.5; in both cases, the B2 current is likely due only to movement of the Schiff base proton to Asp85.

Aspartic Acid↗
PubMed1998

Cellular immune response of Mastomys and gerbils in experimental filariasis.

OBJECTIVE: To determine mitogenic and antigen-specific cellular immune responses of two species of rodents, viz. Meriones unguiculatus and Mastomys coucha to assess the usefulness of the A. viteae/Mastomys model for cellular immune studies in experimental filariasis. METHODS: Lymphocyte blast transformation test (LTT) using spleen cells of normal and A. viteae infected animals. RESULTS: The proliferative response of gerbils was much higher than that of Mastomys to both ConA and filarial antigens. Cells of both species of rodents did not respond to microfilarial (mf) antigen, however, their mitogenic response differed during infection. Some degree of nonspecific suppression was observed in gerbils during prepatent and patent stages of infection, while Mastomys revealed highest proliferation during patent microfilaraemia. Mastomys cells did not respond to adult or mf antigen, while adult-specific proliferation was detected in the case of gerbils. CONCLUSION: The A. viteae/gerbil model shows more similarity to human filarial infection regarding cellular immune response. Markedly low responsiveness of a high percentage of Mastomys and wide variations in the cellular response to nonspecific mitogen limit the usefulness of Mastomys coucha in immunological studies, especially cellular immunity.

Animals↗
PubMed1998

Secretory acetylcholinesterase of Setaria cervi microfilariae and its antigenic cross-reactivity with Wuchereria bancrofti.

Setaria cervi, a bovine filarial parasite, secretes acetylcholinesterase during in vitro cultivation. A significant amount of enzyme activity was detected both in culture media and somatic extracts of different developmental stages of the parasite. The microfilarial stage showed a higher level of AChE activity than adult worms, with females being considerably more active than males. The secretory enzyme from microfilariae preferentially utilized acetylthiocholine iodide as substrate and showed two electrophoretically distinct isoforms in native PAGE. Secretory enzyme was purified from the excretory/secretory products of microfilariae using edrophonium chloride linked to epoxy-activated sepharose. Analysis of purified acetylcholinesterase by SDS-PAGE revealed the existence of two proteins of 75kD and 45kD under nonreducing conditions. These secretory enzymes are antigenic and cross-reactive with Wuchereria bancrofti-infected asymptomatic microfilaraemic human sera when tested by enzyme linked immunosorbent assay and immunoblotting. The secretory AChE(s) from S. cervi microfilariae may be utilized for diagnosis of early filarial infections.

Acetylcholinesterase↗
PubMed1998

Sacral chordomas: a 10-year study.

A retrospective analysis of 14 cases of sacral chordoma seen between 1984 and 1993 at the Kidwai Memorial Institute of Oncology is reported. The mean patient age was 54 years, with 13 males and one female. Seventy-one per cent of patients presented with symptoms related to a painful sacral mass. Eight patients underwent radical surgery and two had adjuvant radiotherapy. One patient had a partial tumour resection. Three patients received radical radiotherapy. Two patients were offered only pain relief medication. The median follow-up was 33 months. The actuarial overall survival (OS) at 5 years was 48%. In the 12 patients in whom curative therapy was attempted, the 5-year OS was 56% and progression-free survival was 36%. Four patients developed local recurrence and three developed distant metastasis.

Chordoma↗
PubMed1998

Positive and negative regulation of Easter, a member of the serine protease family that controls dorsal-ventral patterning in the Drosophila embryo.

The sequential activities of four members of the trypsin family of extracellular serine proteases are required for the production of the ventrally localized ligand that organizes the dorsal-ventral pattern of the Drosophila embryo. The last protease in this sequence is encoded by easter, which is a candidate to activate proteolytically the ligand encoded by spätzle. Here, we demonstrate biochemically that the zymogen form of Easter is processed in vivo by a proteolytic cleavage event that requires the three upstream proteases. Processed Easter is present in extremely low amounts in the early embryo because it is rapidly converted into a high molecular mass complex, which may contain a protease inhibitor. Easter zymogen activation is also controlled by a negative feedback loop from Dorsal, the transcription factor at the end of the signaling pathway. Each of these regulated biochemical processes is likely to be important in generating the ventral-to-dorsal gradient of Dorsal protein that organizes cell fates in the early embryo.

Animals↗