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S Sanyal

Publications and source records attributed to S Sanyal.

At least 19 recordsLinked to original sources
PubMed2003

Acute induction of conserved synaptic signaling pathways in Drosophila melanogaster.

Analyses of early molecular and cellular events associated with long-term plasticity remain hampered in Drosophila by the lack of an acute procedure to activate signal transduction pathways, gene expression patterns, and other early cellular events associated with long-term synaptic change. Here we describe the development and first use of such a technique. Bursts of neural activity induced in Drosophila comatosets and CaP60A Kumts mutants, with conditional defects in N-ethylmaleimide-sensitive fusion factor 1 and sarco-endoplasmic reticulum Ca2+ ATPase, respectively, result in persistent (>4 hr) activation of neuronal extracellular signal-regulated kinase (ERK). ERK activation at the larval neuromuscular junction coincides with rapid reduction of synaptic Fasciclin II; in soma, nuclear translocation of activated ERK occurs together with increased transcription of the immediate-early genes Fos and c/EBP (CCAAT element binding protein). The effect of "seizure-stimulation" on ERK activation requires neural activity and is mediated through activation of MEK (MAPK/erk kinase), the MAPKK (mitogen-activated protein kinase kinase) that functions upstream of ERK. Our results (1) provide direct proof for the conservation of synaptic signaling pathways in arthropods, (2) demonstrate the utility of a new genetic tool for analysis of synaptic plasticity in Drosophila, and (3) potentially enable new proteomic and genomic analyses of activity-regulated molecules in an important model organism.

Active Transport, Cell Nucleus↗
PubMed2001

Genetic interaction between shibire and comatose mutations in Drosophila suggest a role for snap-receptor complex assembly and disassembly for maintenance of synaptic vesicle cycling.

NSF is an ATPase required for the fusion of secretory vesicles with plasma membrane. Conditional comatose (Drosophila homolog of N-ethylmaleimide sensitive fusion factor (NSF)) mutations in Drosophila block synaptic transmission at restrictive temperature. Current models hold that NSF-mediated dissociation of SNARE (SNAp REceptor) complexes on mature synaptic vesicles primes them for exocytic release. Paralysis in comt mutants thus reflects defective exocytosis due to buildup of unresolved SNARE complexes. Here, we analyze effects of blocking synaptic vesicle recycling on behavioral, physiological and biochemical phenotypes of comt. Behavioral recovery of comt animals and recovery of comt synapses, as assayed by electroretinograms, after exposure to high temperature is faster if synaptic vesicle recycling is simultaneously blocked using shi(ts) mutants. Concurrently, 7S complex buildup in comt shi double mutants is substantially lower than in comt mutants alone. In addition, we find that 7S complexes can form on presynaptic plasma membrane if NSF is inhibited after synaptic-vesicle depletion. Thus, our experiments demonstrate a need for continuous NSF activity required not only for dissociating cis-SNARE complexes on plasma membrane after exocytosis, but also for maintaining these cis-SNARE complexes in a dissociated state.

Animals↗
PubMed2001

Tyrosine residues 951 and 1059 of vascular endothelial growth factor receptor-2 (KDR) are essential for vascular permeability factor/vascular endothelial growth factor-induced endothelium migration and proliferation, respectively.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) exerts its multiple functions by activating two receptor tyrosine kinases, Flt-1 (VEGFR-1) and KDR (VEGFR-2), both of which are selectively expressed on primary vascular endothelium. To dissect the respective signaling pathways and biological functions mediated by these receptors in primary endothelial cells with two receptors intact, we, recently developed chimeric receptors (EGDR and EGLT) in which the extracellular domain of the epidermal growth factor receptor was fused to the transmembrane domain and intracellular domain of KDR and Flt-1, respectively. With these fusion receptors, we have shown that KDR is solely responsible for VPF/VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration, whereas Flt-1 showed an inhibitory effect on KDR-mediated proliferation but not migration. To further characterize the VPF/VEGF-stimulated HUVEC proliferation and migration here, we have created several EGDR mutants by site-directed mutagenesis. We show that tyrosine residues 1059 and 951 of KDR are essential for VPF/VEGF-induced HUVEC proliferation and migration, respectively. Furthermore, the mutation of tyrosine 1059 to phenylanaline results in the complete loss of KDR/EGDR-mediated intracellular Ca(2+) mobilization and MAPK phosphorylation, but the mutation of tyrosine 951 to phenylanaline did not affect these events. Our results suggest that KDR mediates different signaling pathways for HUVEC proliferation and migration and, moreover, intracellular Ca(2+) mobilization and MAPK phosphorylation are not essential for VPF/VEGF-induced HUVEC migration.

Amino Acid Substitution↗
PubMed2001

Lethal comatose mutation in Drosophila reveals possible role for NSF in neurogenesis.

NSF is a cytosolic ATPase implicated in a variety of cellular functions including synaptic vesicle exocytosis. Here we report a lethal mutation in the Drosophila homolog of NSF (dNSF1). Lethality staging and rescue experiments with the wild type dNSF1 transgene show that NSF1 is critically required during early larval stages and during late pupariation. Lethality in larval stages is associated with defects in neurogenesis as evidenced by an overall reduction in synapse size and synapse branching. Moreover, escaper adults, though showing abnormal seizure-like paralytic behavior, are normal in terms of synaptic transmission as assayed by electroretinograms. Taken together, these data indicate a role for NSF in neural growth and branching in addition to its documented role in synaptic transmission.

Animals↗
PubMed1999

Phenotypic interaction between temperature-sensitive paralytic mutants comatose and paralytic suggests a role for N-ethylmaleimide-sensitive fusion factor in synaptic vesicle cycling in Drosophila.

The temperature-induced paralysis of comatose (comt) mutants of Drosophila is suggestive of a function for N-ethylmaleimide-sensitive fusion factor (NSF) in the CNS. Mutations in the para gene encoding the subunit of the voltage-gated sodium channel also result in a similar phenotype. We show that paralysis in comt flies is activity-dependent, and in the doubly mutant comt para flies comt-like paralysis does not set in until the effects of para are reversed by shifting to permissive temperatures. During recording from the thoracic flight muscles, we observed that comt flies showed a burst of spontaneous activity at restrictive temperature. This has been reported earlier as a unique characteristic of comt paralysis. The comt para double mutant showed this burst of activity not at restrictive but only on shifting back to permissive temperature. The unusual behavior and electrophysiology of the doubly mutant flies reported here indicates a role for NSF in synaptic vesicle cycling.

Animals↗
PubMed1999

Initial microbiologic studies did not affect outcome in adults hospitalized with community-acquired pneumonia.

Microbiologic studies (MBSs) fail to identify a specific pathogen in more than 50% of patients with community-acquired pneumonia (CAP). The 1993 American Thoracic Society guideline (ATS-GL) for the management of CAP advised selecting initial antibiotic regimens based on severity of illness and comorbidities. Our study evaluated the role of initial MBS in adult patients hospitalized with CAP and treated according to the ATS-GL. In 184 patients hospitalized at our facility for CAP in 1996, and treated according to the ATS-GL, 25 (14%) failed to respond to initial antibiotic regimens. In these nonresponders, there was no difference in mortality between those in whom antibiotics were changed empirically, and those with MBS-guided changes. We conclude that initial MBS may not be warranted in many adult patients admitted for CAP. Exceptions include patients with conditions that predispose to less common, more resistant pathogens.

Adolescent↗
PubMed1998

Dopamine D2 and D4 receptor ligands: relation to antipsychotic action.

Since the discovery that the antipsychotic action of phenothiazines was mediated by dopamine D2 receptors, the dopamine system has been scrutinized for schizophrenia related abnormalities. The focus has been to create neuroleptics with improved antipsychotic profiles and reduced side effects. With the identification of multiple dopamine receptor subtypes, the hypotheses regarding the role of dopamine in schizophrenia and antipsychotic action of neuroleptics have been refined. Even after the molecular identification of newer dopamine D2-like receptor subtypes (D3 and D4), the dopamine D2 receptor is still considered the predominant site for antipsychotic action. However, there has been much debate concerning the modulatory role of other dopamine receptor sites in the mechanism of action of antipsychotic drugs. Specifically, the dopamine D4 receptor has received much attention in this regard, since the atypical antipsychotic agent, clozapine, preferentially blocks this receptor subtype as compared with dopamine D2 and D3 receptors. In this review we will highlight some of the observations and arguments regarding the involvement of the dopamine D2 and D4 receptor sites in the therapeutic efficacy of antipsychotic medication.

Animals↗
PubMed1998

Is nitroglycerin detrimental in patients with coronary artery ectasia? A case report.

During the management of acute myocardial infarction, we observed that clinical and electrocardiographic indications of myocardial ischemia worsened upon nitroglycerin infusion and were promptly relieved upon streptokinase infusion. Subsequent coronary angiography revealed diffuse ectasia with no significant stenosis. We discuss the possible pathophysiologic mechanisms by which nitroglycerin might exacerbate ischemia in patients with non-stenotic ectasia, and we present supporting data from other sources. We also attempt to identify the characteristics of patients whose acute myocardial ischemia might be worsened by the administration of nitroglycerin.

Coronary Angiography↗
PubMed1998

Humoral immunity status in neonates born to pre-eclamptic toxaemia mothers.

A prospective study on 90 neonates born to age matched normal mothers (set I) and mothers (set II) with pre-eclamptic toxaemia (PET) was undertaken to assess and compare the humoral immunity status of the neonates. All of them had normal vaginal delivery. IgG, IgA and IgM were estimated by radial immunodiffusion technique from cord blood of neonates. It was observed that IgA and IgM levels were insignificant in the cord blood. IgG level was low in normal birth weight (NBW) neonates born to PET mothers, when compared to that of NBW neonates born to normal mothers. Again low birth weight (LBW) babies of both the sets showed lower values of IgG than that of NBW babies. Apgar scoring showed direct relationship with IgG levels e.g., higher the Apgar score higher the level of IgG. Thus the IgG level was directly related to the birth weight of the neonates of the respective sets as well as with the Apgar scoring of the neonates.

Adolescent↗
PubMed1997

Synaptic growth in the rod terminals of mice after partial photoreceptor cell loss: a three-dimensional ultrastructural study.

Following partial loss of photoreceptor cells in the retina of mice afflicted by mutant genes, damaging light exposure, or old age, some of the remaining rod cells exhibited a process of growth in their synapses with the second order retinal neurons. This growth was recognized by the presence of multiple synaptic sites in some of the rod terminals in the outer plexiform layer. In this study, a comparative analysis of the microanatomical changes in the synaptic structures of the rod terminals in the retina of normal, rds homozygous and heterozygous mutant and light exposed albino mice was undertaken by using a computer-aided three-dimensional reconstruction. A rod terminal normally showed the presence of 1 synaptic complex consisting of a single synaptic ribbon located between 2 processes of horizontal cells and 2 bipolar cell dendrites. In a rod terminal showing an enlarged synaptic complex, 2 or 3 separate synaptic ribbons formed the centres of separate synaptic sites; each of the sites was characterized by the presence of 2 laterally placed horizontal cell processes and 2 bipolar cell dendrites. However, these processes from the multiple synaptic sites were observed to arise from the 2 horizontal and the 2 bipolar cell elements that were normally present in the rod terminal. Thus proliferation of synaptic sites in the rod terminals occurred through growth and sprouting from the processes of the second order neuronal components present within the terminals. The altered synaptic complexes in the variously affected groups were structurally comparable and appeared to have resulted from similar microanatomical changes. The increase in the frequency of rod terminals with multiple synaptic sites occurred as a sequel to increasing photoreceptor cell loss that was recorded at different age points in the different experimental groups. It is concluded that rod synapses in the adult mammalian retina possess structural plasticity that permits compensatory growth.

Aging↗
PubMed1997

A modification of split-skin graft.

A modification of the conventional split-skin graft is presented. This modification provides a gain in the length of the donor skin up to a maximum of 1:1.92. The gain in length is achieved in a very short period during an emergency operation. No special instrument is required. This technique has been proved to be useful in burn cases having much less donor site than recipient area. Earlier recovery, shortened hospital stay, earlier rehabilitation, less scar contracture and less morbidity could be achieved with this type of simple modification of a sheet graft.

Burns↗
PubMed1997

Dopamine D4 receptor-mediated inhibition of cyclic adenosine 3',5'-monophosphate production does not affect prolactin regulation.

Under physiological conditions, PRL synthesis and secretion are predominantly under negative control by dopamine acting through dopamine D2 receptors present in the pituitary lactotroph cells. To investigate the role of D4 receptors in the regulation of PRL synthesis and secretion, we stably transfected the human D4 receptor complementary DNA into the somatomammotrophic cell line GH4C1. The pharmacological characteristics of D4 expressed in GH4C1 were in close agreement with previous D4 receptor studies in Chinese hamster ovary and COS-7 cells. In GH4C1 cells, activation of D4 receptor variants (D4.2, D4.4, and D4.7) resulted in a similar level of reduction in forskolin- and vasoactive intestinal peptide (VIP)-stimulated cAMP levels (33% and 50%, respectively). In addition, the forskolin-stimulated activity of cAMP response elements fused to the VIP promoter driving the lacZ reporter gene could be blocked by D4 activation. However, quinpirole treatment had a minimal effect on transiently expressed luciferase reporter gene driven by a proximal PRL promoter in one of the D4-expressing cell lines. In contrast, the dopamine D2short receptor expressing GH4ZR7 cells treated with quinpirole displayed a significant decrease (51.3 +/- 4.1%) in PRL promoter activity. VIP-stimulated PRL release was not affected by D4 receptor activation, whereas in GH4ZR7 cells, a significant decrease in VIP-stimulated PRL levels was observed. Neither PRL promoter activity nor PRL secretion levels were affected in control untransfected GH4C1 cells. From this study it appears that although the D4 receptor may be expressed in the anterior pituitary, it does not have a major effect on PRL promoter activity or PRL secretion in GH4C1 cells despite its ability to reduce cAMP production. This might explain why D4- over D2-preferring antipsychotics such as clozapine do not cause hyperprolactinemia.

Adenylyl Cyclase Inhibitors↗
PubMed1997

Study of myopathies by histological and histochemical methods with special reference to staining for desmin expression.

An attempt was made to study the histological and histochemical changes as well as immunohistochemical changes in desmin expression occurring in four types of clinical myopathies e.g. Chronic ischaemic myopathy due to Buerger's disease (Group I), Carcinomatous myopathy (Group II), Metabolic myopathy (Group III) and Muscular dystrophy (Group IV). The number of cases studied were 16 cases, 15 cases, 4 cases and 5 cases respectively. The study revealed: (i) a combination of normal, degenerated, necrotic and regenerating fibres in different proportions in all the four groups having maximum number of degenerated fibres in Group I and Group IV, relatively more number of regenerating fibres in groups III and absence of necrotic fibres in Group I. (ii) Altered tinctorial property in most of the fibres indicating degenerated and regenerating fibres in all the groups with Masson's trichrome staining against inconstant staining with PTAH appear to be a good indicator for myopathy. (iii) The Desmin expression was week and irregular in most of the cases with most of the fibres probably due to reduction of desmin content probably indicating degenerated fibres, appear to be a good indicator for myopathy. (iv) Chronic ischaemic myopathy showed close resemblance with muscular dystrophy though no typical or distinct distinguishing feature could be identified in these four groups.

Desmin↗
PubMed1997

Cell mediated immune status in malignancy--pretherapy and post-therapy assessment.

Twenty-eight cases of malignancies of different kinds were studied to assess T-cell activity and population before and after institution of therapy. Fifteen cases were diagnosed as non-metastasising squamous cell carcinoma of larynx, pharynx, laryngopharynx, hypopharynx and tonsils. Seven cases were non-metastasising infiltrating duct carcinoma of breast and 6 cases were non-Hodgkin's lymphoma (NHL). It was observed that 3 out of 15 cases (20%) of squamous cell carcinoma cases were Mantoux test (MT) negative with a T-cell population of less than 40%, 2 out of 7 cases (28.6%) of infiltrating duct carcinoma of breast were MT negative with a T-cell population of less than 40% and 3 out of 6 cases (50%) of NHL were MT negative with a T-cell population of less than 40%. The normal controls, consisting of apparently normal healthy adults, had a T-cell population of more than 40% and were all MT positive. The patients who showed a negative skin test and a T-cell population less than 40% were further subjected to assessment of T-cell population and activity after appropriate therapy, and clinical cure of the disease. It was observed that 2 out of 3 cases (66.66%) of squamous cell carcinomas, 2 out of 2 cases (100%) of adenocarcinomas and one out of 3 cases (33.33%) of NHL showed positive conversion with a T-cell population of more than 40%.

Adult↗
PubMed1997

A comparative study of silver binding nucleolar organiser regions (AgNORs) of breast lesions in histological sections and fine needle aspiration smears.

The study presents a comparative profile of AgNOR dot counting in different types of breast lesions in histopathological (HP) sections and fine needle aspiration cytology (FNAC) smears. The breast lesions chosen were non-neoplastic lesion like fibroadenosis, benign neoplastic lesion like fibroadenoma and malignant neoplastic lesion like infiltrating duct carcinoma-grade 2. The AgNOR counts of non-neoplastic lesion were significantly less in number than the neoplastic lesions--both benign and malignant, in both the HP section and FNAC smear. But the counts did not show significant difference in the two neoplastic lesions eg, fibroadenoma and infiltrating duct carcinoma-grade 2, in both the HP section and FNAC smear. The appearance of the dots, as felt by the observers, were more discriminating between the three lesions, eg, uniform small compact centrally placed in fibroadenosis; mostly uniform small compact but occasional large irregular in fibroadenoma and large irregular marginally located in infiltrating duct carcinoma. Counting was easier and the appearance of the dots more easily discernible in FNAC smear than the HP section as the smear was monolayer and the malignant cells were easily detected from macrophages and stromal cells. But the tissue fluid or secretions or blood when present in the smear gave the smear a dirty background which was disturbing to the observers. Thus this AgNOR technique, when applied in HP section or FNAC smear, appears cost ineffective, lengthy and tedious procedure; did not offer absolute histochemical discriminant for malignancy from benignancy. But the shape and size distribution and appearance of the dots showing much variability in FNAC smear than the HP section, might be of some help in the diagnosis of malignancy and discriminating from benignancy.

Biopsy, Needle↗