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J Sen

Publications and source records attributed to J Sen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Windbeutel is required for function and correct subcellular localization of the Drosophila patterning protein Pipe.

Drosophila embryonic dorsal-ventral polarity originates in the ovarian follicle through the restriction of pipe gene expression to a ventral subpopulation of follicle cells. Pipe, a homolog of vertebrate glycosaminoglycan-modifying enzymes, directs the ventral activation of an extracellular serine proteolytic cascade which defines the ventral side of the embryo. When pipe is expressed uniformly in the follicle cell layer, a strong ventralization of the resulting embryos is observed. Here, we show that this ventralization is dependent on the other members of the dorsal group of genes controlling dorsal-ventral polarity, but not on the state of the Epidermal Growth Factor Receptor signal transduction pathway which defines egg chamber polarity. Pipe protein expressed in vertebrate tissue culture cells localizes to the endoplasmic reticulum. Strikingly, coexpression of the dorsal group gene windbeutel in those cells directs Pipe to the Golgi. Similarly, Pipe protein exhibits an altered subcellular localization in the follicle cells of females mutant for windbeutel. Thus, Windbeutel protein enables the correct subcellular distribution of Pipe to facilitate its pattern-forming activity.

Animals↗
PubMed1999

A NF-kappa B/c-myc-dependent survival pathway is targeted by corticosteroids in immature thymocytes.

Glucocorticoid hormones modulate T cell maturation in vivo. While low levels of hormones are required for appropriate T cell development, high levels of glucocorticoid hormones target immature developing thymocytes for cell death during systemic stress. In this report, we propose a molecular mechanism for the induction of apoptosis in CD4+CD8+ double-positive thymocytes by dexamethasone in vivo. Dexamethasone injection induced the expression of IkappaBalpha and IkappaBbeta in thymocytes and down-regulated NF-kappaB DNA binding activated by intrathymic signals. Down-regulation of NF-kappaB DNA binding preceded cell death, suggesting that NF-kappaB may be important for the survival of immature thymocytes. In addition, ex vivo treatment of thymocyte single-cell suspension with dexamethasone accelerated p65/RelA down-regulation and cell death. Conversely, NF-kappaB induction diminished dexamethasone-induced death. Expression of the c-myc proto-oncogene, a NF-kappaB target, was also reduced in thymocytes of dexamethasone-treated animals, and ectopic transgenic expression of c-myc in mice provided partial rescue of double-positive thymocytes from dexamethasone mediated cell death. These observations suggest that viability of CD4+CD8+ thymocytes may be maintained by an NF-kappaB/c-myc-dependent pathway in vivo.

Animals↗
PubMed1999

Establishment of synchronization in carrot cell suspension culture and studies on stage specific activation of glyoxalase I.

The present report summarizes and compares the effects of three cell cycle inhibitors, viz. aphidicolin, hydroxyurea and mimosine, in inducing synchronization of a rapidly proliferating suspension culture of carrot. These treatments efficiently synchronized the cell cycle as the doubling time of the cell population was roughly equal to the total length of one cell cycle. Protoplasts derived from mimosine treated cell suspension culture were resolved via flow cytometry to get an idea of the temporal organization of the cell cycle events. The biochemical analysis showed a rise in stage specific activity of glyoxalase I, an auxin inducible marker enzyme activated at G2-M. This activity peak could be shifted to an early phase of interphase in response to auxin treatment.

Cell Cycle↗
PubMed1998

Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity.

Expression of pipe in the somatic tissue of the Drosophila ovary is required for the formation of embryonic dorsal-ventral polarity. pipe, which encodes an enzyme similar to the glycosaminoglycan-modifying enzyme heparan sulfate 2-O-sulfotransferase, is expressed in a spatially restricted domain of follicle cells on the ventral side of the egg chamber. Mutations that affect follicular polarity correspondingly alter the spatial pattern of pipe expression. Directed expression of pipe in otherwise pipe mutant females restores embryonic lateral and ventral pattern elements and can orient the dorsal-ventral axis of the embryo. Thus, the localized expression of pipe and the spatially restricted modification of carbohydrate chains play pivotal roles in the mechanisms that establish embryonic pattern and integrate follicular and embryonic polarity.

5' Untranslated Regions↗
PubMed1998

Identification, sequence and developmental expression of invertebrate flotillins from Drosophila melanogaster.

Caveolae are vesicular organelles that represent a sub-compartment of the plasma membrane. Caveolins (Cav-1, -2 and -3) and flotillins (FLO-1 and FLO-2 [also known as epidermal surface antigens (ESAs)] are two families of mammalian caveolae-associated integral membrane proteins. Although a caveolin gene family has recently been described in the invertebrate Caenorhabditis elegans, it remains unknown as to whether flotillin homologues exist in invertebrates. Here, we report the identification, cDNA sequence and embryonic expression pattern of the first invertebrate flotillin, i.e. flotillin from Drosophila melanogaster (FLODm). FLODm is most closely related to mammalian flotillin-1. Remarkably, the invertebrate FLODm protein behaves like mammalian flotillins and is targeted to the caveolae-enriched membrane fraction after transient expression in mammalian cells. Localization of the FLODm message in D. melanogaster embryos reveals that expression of FLODm is confined primarily to the developing nervous system. This is consistent with our previous observation that mammalian flotillin-1 mRNA and protein is expressed abundantly in brain tissue. Interestingly, the FLODm gene is localized to chromosomal region 52 B1-B2. In addition, we find that at least two flotillin-related genes are expressed in D. melanogaster. Our current results provide a starting point and systematic basis for dissecting the role of flotillin in caveolae and neuronal development using Drosophila as a genetic system.

Amino Acid Sequence↗
PubMed1998

Evaluation of various diagnostic signs on percutaneous transhepatic cholangiography in obstructive jaundice.

Twenty patients of obstructive jaundice were subjected to percutaneous transhepatic cholangiography (PTC) of which 17 were operated on. Patients were divided in 4 groups according to the site of obstruction. The diagnostic signs observed were: Complete block with interface having convexity downwards (4), convexity upwards (3), biconcave caudal cut off (6), smooth edged cut off (one), irregular edged cut off (one) and non-specific appearance (one); incomplete block with interface having convexity upwards (one); biconcave caudal cut off (2) and multiple smooth central filling defects (2). In one case there was incomplete obstruction at two sites giving rise to two different signs. PTC was 100% correct in accurately telling the site of lesion. As regards the nature of the lesion the diagnosis on PTC was found correct in 15 out of 17 cases (88.5%).

Cholangiography↗
PubMed1997

High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder.

OBJECTIVE: Higher basal concentrations of intracellular calcium Ca2+ in platelets and lymphocytes from subjects with bipolar affective disorder than in unipolar depressed and healthy subjects implicate abnormal intracellular Ca2+ signaling in bipolar disorder. The purpose of this study was to clarify whether these intracellular Ca2+ abnormalities are trait related. METHOD: Basal Ca2+ concentration was measured by using ratiometric fluorescence assay with fura-2 for T lymphocytes and Epstein-Barr-virus-immortalized B lymphoblasts from physically healthy subjects with DSM-IV diagnoses of bipolar mood disorder (bipolar I, N = 28; bipolar II, N = 11) or major depressive disorder (N = 14), mixed psychiatric patients with non-mood disorders (N = 14), and health subjects (N = 20). Phytohemagglutinin-stimulated (10 micrograms/ml) intracellular Ca2+ levels were also determined in T lymphocytes. RESULTS: The basal Ca2+ concentration was significantly higher in the B lymphoblasts from patients with bipolar I disorder, but not bipolar II disorder or major depression, than in healthy subjects or psychiatric patients with nonmood disorders. There was a significant interaction between gender and diagnosis in the effect on basal Ca2+ levels in T lymphocytes. Contrasts of diagnoses within gender revealed significantly higher basal Ca2+ concentrations in T lymphocytes in male bipolar I patients, but not mean with bipolar II disorder or major depression, than in healthy male comparison subjects. Phytohemagglutinin-stimulated Ca2+ concentrations did not differ among groups, but the percent differences from basal Ca2+ levels were lower in bipolar I and depressed patients than in healthy subjects. CONCLUSIONS: These findings support the occurrence of abnormal calcium homeostasis in bipolar disorder and suggest that trait-dependent factors account, at least partly, for the higher basal lymphocyte Ca2+ concentration in bipolar I subjects.

Adult↗
PubMed1996

Intrathymic signals in thymocytes are mediated by p38 mitogen-activated protein kinase.

Thymocytes develop into mature functional T cells in the inductive environment of the thymus where thymocyte-stromal cell interactions and cytokines provide survival and differentiation signals as cues for thymocyte maturation. Disruption of the thymic microenvironment results in attenuation of T cell maturation, suggesting that intrathymic signals are essential for differentiation and repertoire selection. We have previously shown that several inducible nuclear factors such as AP-1, NF-AT, and NF-kappaB are activated in response to intrathymic signals. Here we demonstrate that in thymocytes p38 mitogen-activated protein (MAP) kinase, a member of the MAP kinase family of proteins that include the extracellular-signal regulated kinases and Jun aminoterminal kinases, is highly activated in response to intrathymic signals in vivo. These studies suggest a role for p38 MAP kinase in T cell survival and differentiation.

Animals↗
PubMed1996

Demonstration of acid-fast bacilli in buffy coat and bone marrow smear--a diagnostic tool in pulmonary tuberculosis.

Buffy coat smears prepared from peripheral blood and bone marrow aspirate obtained from proved 60 untreated cases of pulmonary tuberculosis were stained with Ziehl-Neelsen method and thoroughly screened for presence of tubercle bacilli. Acid-fast bacilli were detected in 55% cases in buffy coat, 48.3% cases in bone marrow, 38.3% cases both in buffy coat and bone marrow and 65% cases either in buffy coat or in bone marrow or in both. Considering the fact that demonstration of acid-fast bacilli may not be possible in more than 25-50% of the suspected cases of tuberculosis, these techniques are recommended for evaluation of their utility in establishing diagnosis of tuberculosis, particularly in reference to sputum negative cases of pulmonary tuberculosis and tuberculosis of inaccessible extrapulmonary sites.

Bacteriological Techniques↗
PubMed1995

Expression and induction of nuclear factor-kappa B-related proteins in thymocytes.

Thymocytes mature in response to the cues from the thymic micro-environment, which regulate stage-specific gene expression during development. We find that several proteins that bind the kappa B sequence in vitro are constitutively activated in freshly isolated thymocytes. These include the rel-related p50 homodimers, p50/p65 heterodimers, low levels of c-rel, and two other factors that may be thymus specific. Disruption of the thymic micro-environment resulted in loss of DNA-binding, suggesting that lymphocyte-stromal cell interactions induce and maintain these proteins in a DNA-binding form. Phorbol ester and ionomycin treatment induced p50, p65, and p68 c-rel kappa B DNA-binding activity. Expression of p68 c-rel protein, but not p50 or p65, was suppressed by the immunosuppressive drug FK506. Because FK506 specifically inhibits the appearance of mature single-positive thymocytes, gene expression regulated by p68 c-rel may play a role in selection and maturational signals involved in the double-positive to single-positive transition.

Animals↗
PubMed1994

Nuclear factors that mediate intrathymic signals are developmentally regulated.

Thymocytes mature through several stages of development, defined by cell surface markers such as CD3, CD4, and CD8, in response to environmental cues. Signal transduction resulting from lymphocyte-stromal cell interactions is likely to activate inducible transcription factors which in turn govern stage-specific gene expression. In this report we show that inducible transcription factors such as AP-1 and NF-AT are constitutively nuclear, in response to intrathymic signals, in freshly isolated thymocytes at all stages of maturation. In CD4+CD8+ double positive (DP), but not in the more immature CD4-CD8- double negative (DN) thymocytes, constant stimulus from the thymic environment is required to maintain nuclear AP-1. Thus, disruption of the thymus and incubation of thymocytes at 37 degrees C downregulates DNA binding by nuclear factors AP-1 and NF-AT. Similar treatment of thymocytes has previously been shown to downregulate CD3 zeta chain phosphorylation and increase T cell receptor CD3 expression on DP thymocytes, which is a feature of repertoire selection. Since mature T cells maintain inducible nuclear factors in an inactive form until an encounter with antigen, we propose that downregulation of nuclear DNA binding proteins may reflect another feature of this stage of T cell maturation.

Aging↗
PubMed1994

Identification of upstream signals regulating interleukin-6 gene expression during in vitro treatment of human B cells with pokeweed mitogen.

The present studies have characterized the regulation of interleukin-6 (IL-6) gene expression during pokeweed mitogen (PWM)-driven human B-cell differentiation. PWM induced an early and transient increase in the expression of immediate-early response genes of the jun/fos leucine zipper family (c-jun, jun B, c-fos, and fos-B). The induction of c-jun mRNA by PWM was concentration dependent. Nuclear run-on assays showed that PWM treatment is associated with an increased rate of c-jun gene transcription. The induction of c-jun mRNA precedes the induction of IL-6 gene expression and IL-6 secretion by the B cells. c-Jun antisense, but not sense, oligodeoxynucleotide (ODN) significantly decreases PWM-related B-cell (1) proliferation; (2) IL-6 mRNA induction; (3) IL-6 secretion; and (4) nuclear extract binding to AP-1 in electrophoretic mobility shift assay. In contrast, c-Fos anti-sense ODN did not effect either IL-6 mRNA induction or IL-6 secretion triggered in B cells by PWM. The results further show activation of c-Raf-1 kinase in PWM-treated B cells. Raf-1 acts upstream to mitogen-activated protein (MAP) kinase; therefore, studies were performed to assay for MAP kinase activation in these cells. The results show an increase in phosphorylation of myelin basic protein (MBP) and c-Jun "Y" peptide in PWM-treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signaling cascade in normal human splenic B cells, which, at least in part, involves serine/threonine protein kinases. These results show transient induction of immediate-early response genes in B cells and support a potential role for the c-jun gene product in regulation of IL-6 transcription and secretion.

B-Lymphocytes↗
PubMed1994

Clinico-haematological profile in acute and chronic Plasmodium falciparum malaria in children.

The clinicohaematological findings of acute state (Group A, 30 patients) and chronic state (Group B, 34 patients) of falciparum malaria in paediatric patients are compared. The children with chronic falciparum malaria were apyrexic and presented with features of moderate to severe anaemia with hepato-splenomegaly. Greater severity of anaemia and haemolysis, higher incidence and severity of neutropenia, atypical lymphocytosis, monocytosis and thrombocytopenia were observed in patients with chronic falciparum malaria as compared to patients with acute falciparum malaria despite lesser degree of parasitaemia in the former as compared to the latter. While mechanical destruction of parasitised RBC's, ineffective and dysplastic erythropoiesis either due to unmasking of border line dierty folic acid deficiency or otherwise, transient hypoplasia of bone marrow, impaired utilization of iron and immune destruction of RBCs with hypersplenism may be the mechanisms for anaemia, transient hypoplasia of bone marrow and hypersplenism may be the factors responsible for thrombocytopenia and neutropenia.

Acute Disease↗