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Biomedical subjects

A Ghosh

Publications and source records attributed to A Ghosh.

At least 235 records · Page 13Linked to original sources
PubMed1994

Interaction of small ribosomal and transfer RNAs with a protein from Leishmania donovani.

Using synthetic antisense RNA from the 5'-untranslated region of the beta-tubulin gene as probe in gel retardation assays, a heat stable RNA-binding factor was identified in promastigotes of the kinetoplastid protozoan Leishmania donovani. The same or similar factors interact with several small ribosomal RNA (srRNA) species and, more weakly, with tRNA, as shown by binding and competition experiments. Deletion analysis indicated involvement of repeated purine-rich motifs on the antisense RNA, in the reaction. Related, conserved motifs occur on at least two of the srRNAs. By a modified Western blot assay, the RNA-binding species was identified as a single, small polypeptide. The activity is apparently specific for the promastigote stage of the parasite, being undetectable in amastigotes. The properties of this RNA-binding factor suggest that it is a novel, previously uncharacterized protein.

Animals↗
PubMed1994

Requirement for BDNF in activity-dependent survival of cortical neurons.

Cultured embryonic cortical neurons from rats were used to explore mechanisms of activity-dependent neuronal survival. Cell survival was increased by the activation of voltage-sensitive calcium channels (VSCCs) but not by activation of N-methyl-D-aspartate receptors. These effects correlated with the expression of brain-derived neurotrophic factor (BDNF) induced by these two classes of calcium channels. Antibodies to BDNF (which block intracellular signaling by BDNF, but not by nerve growth factor, NT3, or NT4/5) reduced the survival of cortical neurons and reversed the VSCC-mediated increase in survival. Thus, endogenous BDNF is a trophic factor for cortical neurons whose expression is VSCC-regulated and that functions in the VSCC-dependent survival of these neurons.

Animals↗
PubMed1994

Expression and characterization of a parasite-specific antigen on macrophages after infection with Leishmania donovani.

A rabbit polyclonal antibody to crude soluble antigen of Leishmania donovani promastigotes recognized a determinant expressed on the surface membrane of mouse peritoneal macrophages and human monocyte derived macrophages infected in vitro. The determinant was recognized on infected macrophage surface only when F(ab')2 fragments of anti-leishmanial antiserum was employed in immunofluorescence. F(ab')2 fragments of human patient sera also could recognize the determinant. The expression of this antigen was not stage-specific for the parasite. Immunochemical analyses revealed this antigen to be of 51 kDa protein. Specific leaching of membrane proteins by trypsin showed three bands of expressed antigens of 26, 11 and 10 kDa, which in all likelihood might be arising from the 51 kDa antigen. The antigen was not expressed until 12 h of post infection, reached a maximum level at 24 h and thereafter attained a steady state level as studied upto 96 h of post infection. This type of antigen might have a great potential in immunodiagnostics and site-specific drug targeting.

Animals↗
PubMed1994

Naturally occurring ether-linked phosphatidylcholine activates phosphatidylinositol 3-kinase and stimulates cell growth.

Phosphatidylcholine (PC) from marine invertebrates is enriched in ether-linked forms. PCs from ray fish, Dasyatis sp., and bivalve, Macoma birmanica, used in the present study, contain 65% and 75% (w/w of total PC) of ether-linked forms, respectively. Ether-linked PCs also occur in mammalian membranes. Agonist-mediated hydrolysis of PC generates second messengers which participate in cellular responses. In this study, we tested whether PCs from marine invertebrates directly affect mammalian cell growth and activity of phosphatidylinositol (Pl-3-kinase). Pl-3-kinase participates in mitogenesis initiated by a variety of growth factors. Pl-3-kinase converts polyphosphoinositides to 3' phosphorylated isomers and these products accumulate in response to mitogenic stimuli. Whether cell membrane lipids regulate Pl-3-kinase activity is not known. The marine animal-derived PCs and dioleoyl DAG (dioleoylglycerol) stimulated growth of murine pre-B lymphocytes, whereas chicken PC (egg lecithin) inhibited growth of these cells. Egg lecithin is also a potent inhibitor of Pl-3-kinase activity in vitro. We studied the effect of PCs and DAG on Pl-3-kinase activity. Unlike egg lecithin, marine animal PCs enhanced Pl-3-kinase activity. We investigated the effect of lipids on Pl-3-kinase substrate utilization. PCs enriched in ether-linked species increased utilization of substrates by Pl-3-kinase. PCs purified from marine organisms also contain a substantially higher percentage of the cis-unsaturated fatty acids, especially of the -omega 3 series (25% and 30% of total fatty acids for Dasyatis sp. and Macoma birmanica, respectively), as compared to vertebrate sources. In spite of differences in fatty acid composition, marine PCs and dioleoyl DAG showed similar effects on cell growth and Pl-3-kinase activity. These findings indicate that ether-linked phospholipids activate Pl-3-kinase and may participate in mitogenic responses.

Animals↗
PubMed1994

Calcium regulation of gene expression in neuronal cells.

Long-term adaptive changes in neurons following brief periods of neuronal activity are likely to involve changes in gene expression. The mechanisms of activity-dependent gene expression have been explored in central neurons and the neuronal cell line PC12. Calcium influx through either NMDA receptors or voltage-sensitive calcium channels leads to the rapid induction of a number of immediate-early genes including c-fos. Promoter analysis indicates that Ca2+ influx through different calcium channels activates distinct signaling pathways that either target the serum response element (SRE) or the calcium response element (CaRE) within the c-fos promoter. Transcription through the CaRE requires the induced phosphorylation of the cAMP response element binding protein (CREB) at Ser133. This site on CREB is also phosphorylated in the suprachiasmatic nucleus in vivo upon light stimulation. These observations suggest Ca2+ can regulate gene expression by multiple signaling pathways including one that involves the Ca(2+)-dependent phosphorylation of the transcription factor CREB.

Animals↗
PubMed1994

Cardiac blood flow studies in fetuses with haemoglobin Bart's disease.

Blood flow across the atrioventricular valves and outflow tracts was measured in 55 normal fetuses and 32 fetuses with haemoglobin (Hb) Bart's disease between 18 and 26 weeks of gestation. The mean velocities remained unchanged in both normal and affected fetuses over the gestations studied. The volume flow across both atrioventricular valves and outflow tracts increased as the gestation advanced in both normal and affected fetuses, but was significantly higher in affected than in normal fetuses. The same magnitude of increased flow was found in both hydropic and non-hydropic fetuses with Hb Bart's disease. These findings suggest that fetuses with severe and long-standing anaemia have a remarkable cardiac compensatory mechanism for the maintenance of tissue oxygenation. In response to anaemia and circulatory loading, the cardiac chambers and outflow tracts enlarge proportionately up to twice the normal values. Because of this response and the operation of the Frank-Starling mechanism, the heart is able to maintain a normal mean velocity of propulsion and the net output is increased to two to three times that in normal fetuses. Hydropic changes in these anaemic fetuses appear unrelated to cardiac failure as cardiac failure is not observed at the time that hydropic changes develop.

Blood Flow Velocity↗
PubMed1994

Subplate pioneers and the formation of descending connections from cerebral cortex.

The adult cerebral cortex extends axons to a variety of subcortical targets, including the thalamus and superior colliculus. These descending projections are pioneered during development by the axons of a transient population of subplate neurons (McConnell et al., 1989). We show here that the descending axons of cortical plate neurons appear to be delayed significantly in their outgrowth, compared with those of subplate neurons. To assess the possible role of subplate neurons in the formation of these pathways, subplate neurons were ablated during the embryonic period. In all cases, an axon pathway formed from visual cortex through the internal capsule and into the thalamus. In half of all cases, however, cortical axons failed to invade their normal subcortical targets. In the other half, targets were innervated normally. Subplate neurons are therefore likely to provide important cues that aid the process by which cortical axons grow toward, select, and invade their subcortical targets.

Afferent Pathways↗
PubMed1994

Effect of fibrosarcoma induction on copper and ceruloplasmin concentration in different organs of the host.

The copper content and ceruloplasmin activity were determined in mice bearing benzo(a)pyrene induced fibrosarcoma. The copper level and ceruloplasmin activity in different organs of fibrosarcomatous mice varied when compared to their controls. Significant changes in copper and ceruloplasmin concentration were observed in the liver and tumor tissue of host mice bearing fibrosarcoma compared to controls. Disturbed copper metabolism at the hepatic level may account for the hypercupremia observed during malignancy.

Animals↗
PubMed1994

Independent control of dendritic and axonal form in the developing lateral geniculate nucleus.

To identify mechanisms that regulate neuronal form in the mammalian CNS, we have examined dendritic development in the lateral geniculate nucleus (LGN) during the period of segregation of retinal ganglion cell axons. The tracer Dil was used to label retrogradely LGN neurons that send their axons to primary visual cortex at different ages between embryonic day 36 (E36) and E60 in the cat. LGN neurons grow extensively during this period, in concert with the progressive restriction of ganglion cell axons from the two eyes to their appropriate eye-specific layers. At E36 neurons have simple bipolar morphology; by E60 all have acquired complex multipolar dendritic trees. During this period, soma size increases by 190% and total dendritic length increases 240%. Dendritic complexity, as measured by dendritic branch points, also increases. As dendrites grow, the number of spines increases, but their density remains constant at 0.015/micron throughout this period. Since it is known that blockade of action potential activity significantly alters the branching pattern and extent of retinal ganglion cell axonal arbors within the LGN, we also investigated whether the dendritic development of the postsynaptic LGN neurons is similarly susceptible. Following 2 weeks of the intracranial minipump infusion of TTX between E42 and E56, the morphology of LGN neurons was examined. Surprisingly in view of the striking effect of the treatment on the morphology of retinal ganglion cell axons, dendritic growth and development were essentially normal. However, the density of dendritic spines increased almost threefold, suggesting that this specific feature of dendritic morphology is highly regulated by action potential activity. These observations indicate that normally during this period of development, the previously described changes that occur in the morphology of the presynaptic inputs to LGN neurons are accompanied by a progressive growth of post-synaptic dendrites. Because the intracranial TTX infusions have almost certainly blocked all sodium action potentials, our results suggest that the basic dendritic framework of LGN neurons can be achieved even in the absence of this form of neural activity. Moreover, since the same treatment causes a profound change in the morphology of the presynaptic axons, at least some aspects of axonal and dendritic form must be controlled independently during this prenatal period of development.

Animals↗
PubMed1994

Segregation of geniculocortical afferents during the critical period: a role for subplate neurons.

To investigate the cellular interactions within the mammalian visual cortex that are important in ocular dominance column formation, we have examined the role of subplate neurons in this process. LGN axons segregate in layer 4 of the cat's visual cortex between the third and sixth postnatal weeks to give rise to the adult pattern of ocular dominance columns. Subplate neurons are a transient population of neurons that sit in the white matter but have extensive projections into the overlying cortex, particularly layer 4, during neonatal life. Many subplate neurons are present at birth, but most are gone by the end of the period of LGN axon segregation. To examine whether these neurons are required for the segregation of LGN axons, we deleted them by intracortical injections of kainic acid either just after LGN axons had grown into layer 4 (first postnatal week) or later, just before the onset of segregation (third postnatal week). The consequences for the patterning of geniculocortical terminals were evaluated by transneuronal transport of 3H-proline injected into one eye at times when segregation would normally be complete. Following deletion of subplate neurons at either age, LGN axons failed to segregate into ocular dominance columns. Following the late deletions only, geniculocortical axons lost their laminar restriction to layer 4 and projected to layers 2 and 3 as well. Deletion of subplate neurons also resulted in long-term changes in the cytoarchitecture of layer 4. These observations suggest that the interactions that mediate segregation of LGN axons within layer 4 of visual cortex are susceptible to influences from subplate neurons. Although the mechanisms by which subplate neurons exert their effect are not yet clear, these experiments strongly suggest that interactions between LGN axons and layer 4 neurons are not sufficient for column formation, and that subplate neurons most likely play a critical role in interactions leading to ocular segregation.

Aging↗
PubMed1993

Phospholipid asymmetry of goat sperm plasma membrane during epididymal maturation.

The phospholipids and their fatty acids of the inner and outer plasma membrane leaflets of the maturing goat caput-, corpus-and cauda-epididymal spermatozoa were analyzed by treating the intact spermatozoa with phospholipase C and trinitrobenzene sulphonate. The inner and outer membrane showed marked differences in the phospholipid composition at all stages of epididymal sperm maturation. The outer membrane was rich in phosphatidylcholine (PC) and sphingomyelin (SPH) whereas the inner leaflet was dominated by phosphatidylethanolamine (PE). Although the ratio of PE/PC in the inner membrane was similar in both the mature cauda sperm and the immature caput sperm, it decreased significantly in sperm undergoing maturation in the corpus-epididymis. The distribution of the saturated and unsaturated fatty acids in the phospholipid fractions of both the membrane leaflets underwent profound alterations during the epididymal maturation. The data demonstrate asymmetry of phospholipids and their fatty acids in the sperm inner and outer plasma membranes and this lipid asymmetry is greatly altered during epididymal maturity of the male gametes.

Animals↗