Biomedical subjects
A Bhattacharyya
Publications and source records attributed to A Bhattacharyya.
Differential utilization of Trk autophosphorylation sites.
Tyrosine autophosphorylation controls the catalytic and signaling activities of the neurotrophin receptors, the Trks. To analyze the regulation of distinct tyrosine sites, we generated a panel of antibodies that report the phosphorylation state of individual tyrosines within the Trk cytoplasmic domain. Using pheochromocytoma-derived cell lines, we show that individual tyrosines within the nerve growth factor receptor TrkA are phosphorylated in a non-coordinate fashion following receptor activation. The non-coordinate response of these tyrosines reflects their separate functions in regulating the catalytic and signaling activities of Trk receptors. The differential utilization of distinct sites on Trk receptor tyrosine kinases suggests that the receptor can specify both the timing and the nature of neurotrophin-stimulated signal transduction pathways. Moreover, we show that these Trk autophosphorylation sites, which have hitherto been mapped and characterized only in non-neuronal cell lines, are activated in normal neurons in response to ligand stimulation.
Hadron masses at finite density from the Zimanyi-Moskowski model.
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Efficacy of risperidone in reducing positive and negative symptoms in medication-refractory schizophrenia: an open prospective study.
BACKGROUND: Although risperidone has been shown to be an effective antipsychotic medication in schizophrenia, the clinical studies performed for the Food and Drug Administration's approval process focused on only a mixed group of schizophrenic patients. Most of these studies did not directly address the efficacy of risperidone in chronic nonresponding schizophrenics. To better evaluate whether risperidone has a substantial degree of efficacy in schizophrenic non-responders, we conducted an open prospective study of risperidone in a sample of chronically hospitalized schizophrenic patients. METHOD: Twenty-five patients who met DSM-III-R criteria for schizophrenia or schizoaffective psychosis, who were chronically hospitalized at a tertiary care state facility, and who had not responded to conventional neuroleptics were evaluated before and during treatment with risperidone by using several standard rating scales and adjunctive assessments. RESULTS: Endpoint analysis showed that 36% (N = 9) of the patients were classified as responders on the basis of at least a 20% decrease in total Brief Psychiatric Rating Scale score at final evaluation. A higher percentage of patients were classified as responders when other rating scale criteria were used. Reductions in psychopathology scores were seen in scales reflecting positive symptoms but not in scores of negative symptoms. High baseline negative symptom scores were correlated with poorer response to risperidone as indicated by the decrease in positive symptom scores. CONCLUSION: This study offers evidence that risperidone may reduce positive symptoms of schizophrenia for a subgroup of chronically hospitalized schizophrenic patients who have not responded to conventional neuroleptics. The comparative evaluation of the efficacy of risperidone versus that of clozapine in these types of patients requires further study.
Oral iron chelators.
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Purification and characterization of a low molecular weight endogenous glutamate binding inhibitor (LGBI) in porcine brain.
One of the endogenous substances which modulate glutamate receptor binding was isolated and highly purified from porcine brain. The purification involved extraction of brain tissue with doubled distilled water, followed by gel filtration, anion exchange, cation exchange, and several steps of C18 reverse-phase high performance liquid chromatography (HPLC). A low molecular weight glutamate binding inhibitor (LGBI) was purified to apparent homogeneity as judged from the elution profile of an HPLC column, in which a symmetrical peak was obtained when the eluate was monitored at 220 nm. The LGBI appears to be a small molecule (< 2 kD) that is heat- and acid/base-stable. The highly purified LGBI has no effect on GABAA and benzodiazepine receptor binding. The LGBI is not L-glutamate, L-aspartate or other negatively charged endogenous substances, since they are clearly separated from the LGBI in anion exchange chromatography. The inhibitory effect of the LGBI on [3H]L-glutamate binding is reversible, and it only changes the Bmax while the Kd remains the same. Since the membrane preparations used for [3H]L-glutamate binding assays for the detection of LGBI activity were enriched with quisqualate (QA)-sensitive subtypes, it was suggested that the LGBI could be a modulator of the QA receptor. Some amino acids which produce significant inhibition of glutamate binding activity were also compared with the LGBI, and they all showed no resemblance to the LGBI. The chemical structure of the LGBI remains to be determined.
Liver histology in anti-HCV-positive persons with normal or minimally elevated aminotransferases.
The significance of a positive hepatitis C virus (HCV) screening test in asymptomatic blood donors with normal or near normal aminotransferases was studied along with the usefulness of HCV RNA polymerase chain reaction (PCR) testing for predicting chronic hepatitis in these individuals. One hundred and thirty-nine volunteer blood donors who were found positive by second generation ELISA for antibodies to HCV agreed to participate in the study. Thirty-one of them were supplemental test positive, had ALT values less than twice normal, and were followed over a minimum of 12 months. Thirteen consented to percutaneous liver biopsy and also had HCV RNA determination by PCR. Ten of the 13 subjects were positive for HCV RNA by PCR. Of the nine who were positive for HCV RNA and had adequate tissue for evaluation, seven had evidence of chronic hepatitis, three with limiting plate necrosis. Lobular inflammation was similar in severity to that found in the portal region. In addition, two had periportal fibrosis, and one had bridging fibrosis. Of the three subjects who were negative for HCV RNA, only one had portal inflammation which was limited to the portal region. None of these three had lobular changes, or periportal or bridging fibrosis. Of the three normal biopsies, two were from subjects who were negative for HCV RNA. The sensitivity and specificity of HCV RNA testing for chronic hepatitis was 87.5% and 50%, respectively, yielding an overall accuracy of 75%. We conclude that asymptomatic blood donors with antibodies to HCV, normal or mildly elevated liver tests, and HCV RNA may have abnormal liver histology indicating the potential for progressive liver disease. HCV RNA testing by PCR may be clinically useful as a noninvasive means to discriminate between those with and without chronic liver disease.
Study of benign superficial cysts by fine needle aspiration cytology.
Fine needle aspiration cytology of 213 cases of different cystic lesions from various regions of body and different superficial organs was analysed in an attempt to present the experience of the authors in the diagnosis of such lesions. The predominant lesion diagnosed by fine needle aspiration cytology was adnexal cyst/sebaceous cyst (41 cases) followed by vascular hamartoma (40 cases) and thyroglossal cyst (9 cases). One hundred fifty-eight (74.2%) out 213 cases were confirmed histopathologically. There was false negative diagnosis in 14 cases (6.6%). The remaining 41 (19.2%) cases did not turn up for further treatment. The fallacies that have been recorded in the diagnosis of thyroid cysts, salivary gland cysts and breast cysts in respect of papillary cystic thyroid carcinoma, muco-epidermoid carcinoma of salivary gland and intraductal carcinoma with fibrocystic disease of breast respectively have been highlighted in the present study.
Pathology consultation services via the Arizona-International Telemedicine Network.
The Arizona-International Telemedicine Network (AITN) links 4 cities in Arizona and two international sites in China and Mexico, into a telepathology diagnostic network. Established in 1993, the Network provides second opinions on surgical pathology and cytopathology cases. Workstations are 486 PC-based computers. Static images (1024 x 774 x 8 pixels) are grabbed with a variable resolution video camera and sent by 14,400 bit per second modems over ordinary telephone lines. Second opinions are either rendered directly by a general telepathologist or triaged to a specialist. Experience with the first 37 cases indicates a high level of success in providing useful information to referring pathologists over the Network.
Fine needle aspiration cytology of bone and joint lesions: an assessment.
Fine needle aspiration cytology and subsequent correlation with histology and therapeutic follow-up was done in 198 cases of bone and joint lesions. Overall accuracy was found to be 87.34%; false diagnosis was recorded in 4.5% of cases; 8.08% cases were excluded from correlation as they did not turn up for further treatment or follow-up after the diagnosis. False diagnosis was encountered mostly with inflammatory lesions and primary neoplasms, diagnosing osteosarcoma and Ewing's sarcoma as chronic inflammatory lesion, chondroma as chondrosarcoma and vice versa. The possible cause of default has been discussed. The benign cystic lesions could be diagnosed with almost 100% accuracy by fine needle aspiration cytology where 10% cases were excluded as they could not be followed up.
A study of aggregation of 9-(dicyano-vinyl)julolidine.
Di(cyano vinyl)julolidine (DCVJ) is a fluorescent probe which has been used to monitor the local mobility of its binding sites on proteins. It shows a concentration dependence of its emission spectrum in water. At higher DCVJ concentrations, a longer wavelength band appears. The latter increases relative to the shorter wavelength band as a function of increased DCVJ concentration. Absorption and excitation spectra indicate that the concentration dependent emission in the longer wavelength is a consequence of association in the ground state and subsequent excimer formation. DCVJ forms two types of complexes with gamma-cyclodextrin, one of which shows the longer wavelength emission band. Analysis of stoichiometry of association also suggests that longer wavelength emission band may be a consequence of association of two molecules of DCVJ in the gamma-cyclodextrin cavity. Possible uses of such excimer formation in biological systems have also been discussed.
Architecture of telomerase RNA.
Telomerase, an essential ribonucleoprotein reverse transcriptase, adds telomeric DNA to the ends of eukaryotic chromosomes. We examined the conformational properties of the naked RNA moiety of telomerase from two related ciliates, Tetrahymena thermophila and Glaucoma chattoni. As well as finding evidence for features proposed previously on the basis of phylogenetic comparisons, novel conserved structural properties were revealed. Specifically, although the region around helix III was previously proposed to form a pseudoknot, our results indicate that in the naked RNA this region maintains a level of 'plasticity', probably in an equilibrium favoring one of two helices. In addition, these studies reveal that the templating domain is not entirely single-stranded as previously proposed, but is ordered due to constraints imposed by other parts of the RNA. Finally, our results suggest that the GA bulge in helix IV may introduce a structurally conserved kink. We now propose a 'two-domain' structure for the telomerase RNA based on function: one conformationally flexible domain, which includes the template and the region around helix III, involved with enzymatic function, and a second largely helical domain, including helices I and IV and the proposed kink, which may serve as a scaffold for protein binding.
Axons arrest the migration of Schwann cell precursors.
The neural crest gives rise to a variety of cell types including Schwann cells of the peripheral nervous system. Schwann cell precursors begin to differentiate early and migrate along specific pathways in the embryo before associating with nerve trunks. To determine whether motor axons direct the migration of Schwann cell precursors along specific pathways, we tested the effect of ablating the ventral half of the neural tube, which contains motor neuron cell bodies. The ventral neural tube was removed unilaterally from lumbar regions of chicken embryos at stage 17, when neural crest cells are just beginning to migrate and before motor axons have extended out of the neural tube. At several stages after ventral tube ablation, sections of the lumbar region of these embryos were stained with anti-acetylated tubulin to label developing axons, HNK-1 to label migrating neural crest cells and 1E8 to label Schwann cell precursors. In many embryos the ablation of motor neurons was incomplete. The staining patterns in these embryos support the idea that some Schwann cells are derived from the neural tube. In embryos with complete motor neuron ablation, at stage 18, HNK-1-positive neural crest cells had migrated to normal locations in both control and ablated sides of the embryo, suggesting that motor axons or the ventral neural tube are not required for proper migration of neural crest cells. However, by stage 19, cells that were positive for HNK-1 or 1E8 were no longer seen in the region of the ventral root, nor ventral to the ventral root region. Because Schwann cell precursors require neural-derived factors for their survival in vitro, we tested whether neural crest cells that migrate to the region of the ventral root in ventral neural tube-ablated embryos then die. Nile Blue staining for dead and dying cells in ventral neural tube-ablated embryos provided no evidence for cell death at stage 18. These results suggest that motor axons arrest the migration of Schwann cell precursors during neural crest migration.
Fallacies of the fine needle aspiration cytology of surgical lesions of liver.
Seventy-six cases of surgical hepatomegaly were subjected to fine needle aspiration cytology (FNAC) for initial diagnosis. Primary malignancies, as suspected clinically with adjunction of other investigative procedures, were 29 cases of whom 25 were confirmed by biopsy or therapy. Secondary deposits in liver were 27 of whom 15 were confirmed by therapy. Inflammatory lesions were 9 of whom 6 were confirmed by therapeutic response with specific therapy. Benign lesions were 10 of whom 5 were confirmed by surgery. Diagnosis of malignancies of liver is rather easier than that of benign lesions like hydatid cysts of liver which were Casoni's test negative; and hepatocellular adenoma, as the aspirate in the former is clear fluid and that of the latter is only normal looking liver cells. Thus, in respect of benign lesions of liver, FNAC diagnosis may be clinched after due consideration to the clinical findings, radiological and ultrasonographic findings and ultimately confirmed by exploration. Thus the fallacy lies in aspiration of normal looking liver cells whereby the histology may prove it to be hepatocellular adenoma, well differentiated hepatocellular carcinoma and secondary deposits where the exact site has not been hit. Ultrasonogram (USG) guidance helps in these cases where the same facility is available. This fallacy can again be avoided, where USG guidance is not available, by imparting due importance to clinical findings, USG findings and also by repeat smear.
Epidemiological studies of blood groups in the district of Bankura with special reference to tribals.
Distribution of ABO blood groups was studied in 4301 subjects, both tribals and non-tribals of the district of Bankura in West Bengal. It was observed that group 'O' blood was found in most cases and group 'AB' was seen in least number of cases. It was also found that there was no significant difference in distribution of blood groups between the tribals and non-tribals.
Stromal sarcoma of uterus; report of two cases.
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A study of colchicine tubulin complex by donor quenching of fluorescence energy transfer.
The utility of collisional quenching of energy donors in fluorescence energy transfer is described. In multi-donor single acceptor systems, which contain different classes of donors (as distinguished by their accessibility towards a collisional quencher), donor quenching may be used to assess the fraction of energy transfer from each class of donor. The tubulin-colchicine complex was used as a donor-acceptor system to show that two inaccessible tryptophans are at or near the colchicine binding site.
Neuron-Schwann cell signals are conserved across species: purification and characterization of embryonic chicken Schwann cells.
A monoclonal antibody, 1E8, which recognizes the peripheral myelin protein, P0, specific for chicken Schwann cells and their precursors (Bhattacharyya et al., Neuron 7:831-844, 1991), was used to immunoselect Schwann cells from embryonic day 14 (E14) chicken sciatic nerve. When cultured, these immunoselected cells displayed properties characteristic of perinatal rodent Schwann cells, including S100-immunoreactivity and O4 antigen-immunoreactivity. In addition, the purified chicken Schwann cells divided slowly when cultured alone, but when co-cultured with chicken or rat sensory neurons, they bound to axons and proliferated. Proliferation was also stimulated by the addition of bovine brain membrane extracts or chicken brain membranes. The 1E8 monoclonal antibody was also used to test the effect of axonal contact on P0 expression. Chicken Schwann cells purified using the 1E8 monoclonal antibody gradually lost P0 when cultured alone. These cells remained 1E8-negative even after prolonged co-culture with embryonic rat dorsal root ganglion neurons or chicken sensory ganglia. These results demonstrate that chicken Schwann cells behave like rodent Schwann cells in their expression of specific antigens, interactions with axons, and regulation of P0 expression. In addition, chicken Schwann cells respond to neuronal signals from the rat and cow, illustrating the cross-species conservation of these signals.