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Biomedical subjects

I Das

Publications and source records attributed to I Das.

At least 73 records · Page 4Linked to original sources

Role of polyamines in the membrane pathology of schizophrenia. A study using fibroblasts from schizophrenic patients and normal controls.

The polyamines putrescine, spermine, and spermidine play a major role in the regulation of cell growth and differentiation, metabolic pathways, and on cell membrane functions in mammalian systems. It has recently been suggested that polyamines may be involved in the pathophysiology of schizophrenia. Moreover, several reports suggest that schizophrenia may be associated with a generalized cell membrane abnormality. In view of these findings, we measured polyamine levels in cultured skin fibroblasts from schizophrenic patients and normal control subjects. These was a significant increase in the levels of spermidine and in total polyamines in fibroblasts and spermine in the culture medium from schizophrenic patients. This preliminary report suggests that polyamines may play an important role in the membrane abnormalities that have been reported in schizophrenic patients.

Adult↗

Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures.

Repeated kindled seizures induce long-lasting physiological and morphological alterations in the hippocampal formation. In the dentate gyrus (DG), the morphological alterations induced by kindled seizures include loss of polymorphic neurons in the hilus, mossy fiber axon sprouting, and synaptic reorganization of the mossy fiber pathway. In this study, quantitative stereological methods were used to determine the distribution and time course of neuronal loss induced by 3, 30, or 150 kindled generalized tonic-clonic seizures in hippocampal, limbic, and neocortical pathways. Neuronal loss was observed in the hilus of the DG and CA1 after three generalized tonic-clonic seizures, and progressed in these sites to 49% and 44% of controls after 150 seizures. Neuronal loss was also observed in CA3, entorhinal cortex, and the rostral endopyriform nucleus after 30 seizures, and was detected in the granule cell layer and CA2 after 150 seizures. There was no evidence of neuronal loss in the somatosensory cortex after 150 seizures. The time course of the neuronal loss demonstrated selective vulnerability of hippocampal neuronal populations to seizure-induced injury, and suggests that even brief seizures may induce excitotoxic injury in vulnerable neuronal populations. Repeated brief seizures induced neuronal loss in a distribution that resembled hippocampal sclerosis, the most common lesion observed in human epilepsy. The results demonstrated that kindling induces alterations in neural circuitry in a variety of locations in the limbic system, and suggest that hippocampal sclerosis may be acquired in human epilepsy as a consequence of repeated seizures.

Animals↗

Recurrent leiomyoma of the vagina.

A rare case of huge vaginal leiomyoma recurrence is reported. Vaginal leiomyoma is a rare entity and recurrence after its removal is extremely rare. However, if recurrence occurs with intact ovarian function ovariectomy should also be done.

Adult↗

Inositol phospholipid turnover in platelets of schizophrenic patients.

Abnormalities in blood cell membrane phospholipid composition and metabolism from schizophrenic patients have been reported by many groups of investigators. Among membrane phospholipids, inositol phospholipids are of special importance as they are involved in transduction system that generates second messengers such as inositol trisphosphate and diacylglycerol. Our studies on platelet inositol phospholipid turnover suggest a significant increase in platelet phosphatidylinositol 4,5-bisphosphate levels, an increased production of inositol trisphosphate in neuroleptic-treated and neuroleptic-free schizophrenic patients platelets and a reduced calcium release by thrombin in neuroleptic-treated schizophrenic patients platelets. The enhanced production of inositol trisphosphate may be due to an increase in its precursor phosphatidylinositol 4,5-bisphosphate with an associated desensitisation of the intracellular inositol trisphosphate receptor by neuroleptics, which may explain the diminished calcium response to thrombin in schizophrenic patients platelets.

Adult↗

The v-abl, c-fms, or v-myc oncogene induces gamma radiation resistance of hematopoietic progenitor cell line 32d cl 3 at clinical low dose rate.

A variety of viral and cellular oncogenes have been described with differing mechanisms of action but with the common property of inducing morphologic alteration of cells in culture. Subclonal lines of oncogene expressing cells have been shown to produce tumors in vivo. Expression of the N-ras oncogene in embryo fibroblast NIH/3T3 cells has been demonstrated to increase radioresistance in vitro, and these results have been confirmed and extended to human cell lines expressing the c-raf oncogene. In the present report, we have examined the effects of expression of the c-fms, v-abl, or v-myc oncogene in a clonal hematopoietic progenitor cell line 32D cl 3. The 32D cell line is nonmalignant in vivo and is dependent upon a source of Interleukin-3 (IL-3) for growth in vitro. The radiation survival of 32D cl 3 cells transfected and expressed in the c-fms oncogene showed significant increase in the radioresistance at both 5 cGy/min and 116 cGy/min. A clone of 32D cl 3 transfected and expressing the v-myc oncogene demonstrated increased radioresistance at both dose rates. Results of split dose experiments suggested significant repair of sublethal irradiation damage of 32D-v-abl cells. Results were compared with expression of the same v-abl oncogene in the NIH/3T3 embryo fibroblast cell line. The data demonstrate that gamma irradiation resistance is significantly increased by each oncogene expressed in 32D cl 3 cells. The data on cell line 32D cl 3 may correlate with the radioresistance of v-abl expressing human hematopoietic cell malignancies treated by irradiation therapy.

Animals↗

Determination of bupivacaine in plasma by high-performance liquid chromatography. Levels after scalp infiltration in children.

The local anaesthetic bupivacaine could be very useful for analgesia in pediatric neurosurgery. Since systemic toxic reactions to bupivacaine are correlated with high plasma levels it was important, as an adjunct to clinical evaluation, to measure plasma bupivacaine. This report describes a high-performance liquid chromatography (HPLC) method for the quantitation of plasma bupivacaine. Sample preparation involves extraction into ether followed by back-extraction into HCl. After evaporation, the acid extract is redissolved and separated by reversed-phase chromatography. The assay is linear to 5 mg bupivacaine/L and shows excellent recovery and precision. With samples from children undergoing brain surgery following scalp infiltration with either 0.125% or 0.25% bupivacaine, plasma levels peak within 10 min, then fall rapidly to a plateau by 30 min. This plateau is maintained for at least 120 min. In no case did we find supposed toxic levels of bupivacaine.

Brain↗

Study of lupus anticoagulant in pregnant women with recurrent abortion.

The relation between lupus anticoagulant (LA) and repeated abortions was evaluated in a case-controlled study of 50 women with 3 or more unexplained spontaneous abortions compared with 50 control subjects who had 2 or more normal pregnancies and no previous spontaneous abortion or fetal deaths. LA was detected in 5 of 50 cases (10%, 95% confidence limits 1.69% to 18.31%) but in none of the 50 controls. There was an indication that missed abortions may be more frequent in LA positive women. The women who had recurrent abortions but were LA negative had prolonged prothrombin time values (though within normal range) compared to the control group. LA being a treatable cause of idiopathic recurrent abortion should be sought for in women with unexplained fetal losses.

Abortion, Habitual↗

The platelet polyphosphoinositide system in schizophrenia: the effects of neuroleptic treatment.

Signal transduction, mediated by the thrombin-stimulated polyphoshoinositide (PPI) turnover was studied in platelets from 44 schizophrenic patients and 33 healthy volunteers. The stimulated generation of inositol phosphates in the schizophrenic group was significantly greater than that in the control group. There was a lack of correlation between this augmented response and a variety of clinical parameters. The response in 9 drug-naive schizophrenic patients was not significantly different from that in controls. The response was significantly augmented in patients receiving neuroleptic treatment and in patients who had been off neuroleptics for at least 4 months. These results indicate that neuroleptic treatment may produce a long-term modification of signal transduction via the PPI system. Further studies are required to elucidate the exact nature of this modification and to explore the possibility that this effect of the neuroleptics may provide a novel approach to understanding the neurochemistry of schizophrenia and to monitoring the neuroleptic treatment.

Adult↗

Cholesterol esterification and Niemann-Pick disease: an approach to identifying the defect in fibroblasts.

Fibroblasts from 13 patients with the clinical phenotype of type IIS, Niemann-Pick disease were evaluated for their ability to incorporate oleic acid into cholesterol esters via an LDL responsive mechanism. Eight patients displayed a severe deficiency (less than 8% of normal) of cholesterol ester (CE) synthesis while a clinically less affected group displayed intermediate levels (36% of normal) of synthetic capacity with no detectable overlap between these groups and the control range. There was no deficiency in cholesterol ester production in fibroblasts from a patient with Zellweger's disease, a disorder characterized by altered peroxisomes and abnormal peroxisomal cholesterol metabolism, while in I-cell disease, characterized by a primary deficiency of a phosphotransferase which results in altered targeting of lysosomal hydrolases, it was reduced to 25% of the control level. To further implicate lysosomal proteins in the etiology of type IIS, Niemann-Pick disease we measured the effect of correction (conditioned) medium, and the lysosomotropic agent, NH4Cl on cholesterol ester synthesis in fibroblasts. NH4Cl completely inhibited incorporation into CE by normal cells, thus mimicking the CE defect in type IIS, Niemann-Pick cells. Conditioned medium had no effect on incorporation into CE synthesis but medium conditioned in the presence of 10 mM NH4Cl stimulated incorporation into CE in the control but not in Niemann-Pick cells. When Niemann-Pick cells cultured in the presence of NH4Cl were challenged to synthesize CE in the absence of NH4Cl, a significant enhancement of CE synthesis was noted in representative cell lines from both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗

Expression of transfected recombinant oncogenes increases radiation resistance of clonal hematopoietic and fibroblast cell lines selectively at clinical low dose rate.

To determine the effect of oncogene expression on gamma radiation sensitivity of hematopoietic compared to fibroblastic cells, we selected clonal sublines of an interleukin-3 (IL-3)-dependent hematopoietic progenitor cell line 32D cl 3 and NIH/3T3 embryo fibroblastic cells following transfection with each oncogene linked to the mycophenolic acid resistance gene. Each mycophenolic acid-resistant subclone demonstrated high levels of specific poly(A)+ mRNA for each oncogene. The parent line 32D cl 3 demonstrated similar radiosensitivity at 116 cGy/min (D0 126, n 1.17) compared to 5 cGy/min (D0 123, n 1.65). This pattern was not altered in subclones of 32D cl 3 cells transfected with the epidermal growth factor (EGF) receptor gene and grown in EGF (at 116 cGy/min D0 104, n 0.998, at 5 cGy/min D0 115, n 1.09), or in 32D cl 3 cells expressing the v-sis oncogene (at 116 cGy/min D0 122.4, n 1.79, at 5 cGy/min D0 135, n 1.43). In contrast, expression of the transfected oncogenes v-erb-B, v-abl, or v-src conferred significant radioresistance at 5 cGy/min dose rate (D0 194, n 1.77; D0 165.5, n 1.56; D0 171, n 1.28, respectively). With the exception of v-sis, oncogene expression resulted in nonautocrine factor independence of 32D cl 3 subclones, and production of donor origin tumors in syngeneic new-born or adult mice. Two rare spontaneous factor-independent subclones of 32D cl 3 were also tested. Nonautocrine clone 32D cl 2 demonstrated significantly increased radioresistance at low dose rate (D0 186, n 1.63), while autocrine (IL-3 producing) subclone 32D cl 4 revealed no significant increase in radioresistance at 5 cGy/min. The parent fibroblast cell line NIH/3T3 showed an intrinsic relative radioresistance at low dose rate (at 5 cGy/min D0 157.3, n 1.81, compared to 116 cGy/min D0 134.3, n 1.57). Expression in NIH/3T3 of transfected oncogenes v-abl, v-fms, v-fos, or H-ras increased radioresistance at low dose rate (D0 208.6, n 1.61; D0 206.6, n 1.51; D0 167.5, n 1.85; and D0 206.8, n 1.08, respectively). Thus expression of each of several oncogenes induces resistance to gamma irradiation at 5 cGy/min in hematopoietic and fibroblast cell lines. These data may help explain the clinical recurrence of oncogene-expressing leukemia and lymphoma cells after marrow stem cell ablative doses of low-dose-rate total-body irradiation.

Animals↗

Stimulation of inositol phosphate production by propranolol in human neutrophils.

1. Propranolol has been reported to be beneficial in treating patients suffering from a variety of diseases including migraine, psychosis and schizophrenia. The mode of action of propranolol in the treatment of the above diseases is not clear. 2. An investigation into the possible effect of propranolol on receptor activated inositol phospholipid hydrolysis was carried out using human neutrophils. Receptor activated inositol phosphate production by formyl-methionyl-leucyl-phenylalanine has also been studied. 3. DL-propranolol caused a time and concentration dependent increase in inositol phosphate generation which was similar to that obtained for chemotactic peptide in neutrophils. The EC50 for propranolol was 2 microM compared to 0.5 microM for chemotactic peptide. 4. These results indicate the possibility that propranolol has a direct action on inositol phospholipid hydrolysis in addition to its beta-blocking effect.

Adult↗