Biomedical subjects

S R Singh

Publications and source records attributed to S R Singh.

At least 19 recordsLinked to original sources

PubMed2006

The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance.

Birt-Hogg-Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (BHD) were identified in a panel of BHD families. Using RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either unpaired (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.

Amino Acid Sequence↗

PubMed2005

Central GABAA but not GABAB receptors mediate suppressive effects of caudal hindbrain glucoprivation on the luteinizing hormone surge in steroid-primed, ovariectomized female rats.

The neurochemical mechanisms that link caudal hindbrain glucoprivic-'sensitive' neurones with the forebrain gonadotrophin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) axis remain unclear. Available studies indicate that the amino acid neurotransmitter, gamma-aminobutyric acid (GABA), inhibits reproductive neuroendocrine function, and that caudal fourth ventricular administration of the glucose antimetabolite, 5-thioglucose (5TG), enhances GABA turnover within discrete septopreoptic structures that regulate LH secretion. The current experiments utilized the selective GABA(A) and GABA(B) receptor antagonists, bicuculline and phaclofen, as pharmacological tools to investigate whether one or both receptor subtypes function within neural pathways that suppress GnRH neuronal transcriptional activation and LH release during central glucose deficiency. During the ascending phase of the afternoon LH surge, groups of steroid-primed, ovariectomized female Sprague-Dawley rats were pretreated by lateral ventricular administration of bicuculline, phaclofen, or vehicle only, before fourth ventricular injection of 5TG or vehicle. The data indicate that, 2 h after 5TG treatment, Fos immunoexpression by rostral preoptic GnRH neurones and plasma LH levels were diminished relative to the vehicle-treated controls, and that inhibitory effects of 5TG on these parameters were attenuated by pretreatment with bicuculline, but not phaclofen. These results demonstrate that central GABA(A), but not GABA(B) receptor stimulation during hindbrain glucoprivation, is required for maximal inhibition of reproductive neuroendocrine function by this metabolic challenge. The current studies thus reinforce the view that central GABAergic neurotransmission mediates regulatory effects of central glucoprivic signalling on the GnRH-pituitary LH axis.

Animals↗

PubMed2001

Female remating in Drosophila ananassae: bidirectional selection for remating speed.

In Drosophila ananassae, artificial selection was carried out for fast and slow remating speed for 10 generations. Response to selection resulted in rapid divergence in remating time in each of two replicates of both fast and slow lines. There were significant differences in mean remating time in females among fast, slow, and control lines. Regression coefficients for both fast and slow lines are significantly different from zero. The realized heritability over 10 generations of selection is from 0.26 to 0.33 for two replicates of fast line and from 0.23 to 0.27 for two replicates of slow line. These findings suggest that female remating time in D. ananassae is under polygenic control. Remating frequency of females showed a correlated response in both fast and slow lines. At generation 10, correlated response to selection was also investigated. Mating propensity of D. ananassae of fast and slow lines was observed in an Elens-Wattiaux mating chamber. Fifteen pairs per test showed that on the average, the fast lines (11.20, 11.60) were more successful in mating than those of slow (6.40, 5.60) and control (8.00) lines. Productivity of once-mated females was measured in terms of number of progeny produced per female and the results of productivity analysis indicate that females of fast lines (157.83, 130.83) produced more progeny compared with slow (72.70, 85.83) and control (109.23) lines.

Animals↗

PubMed2001

CD40 expression and function on human dermal microvascular endothelial cells: role in cutaneous inflammation.

CD40 is a member of the tumour necrosis factor (TNF) cell surface receptor family. It plays an important role in T-cell dependent B-cell functions and in dendritic cell development. It has also been identified as a cell surface receptor on endothelial cells. In this manuscript, we report that human dermal microvascular endothelial cells (HDMEC) express cell surface CD40 and that the expression of CD40 is increased by the proinflammatory cytokines TNF-alpha and interferon (IFN)-gamma. Additionally, we demonstrate that engagement of HDMEC CD40 with its recombinant CD40 ligand augments the induction of E-selectin, but not of intercellular or vascular cell adhesion molecules on the surface of HDMEC. Furthermore, we show that IFN gamma stimulation of HDMEC results in increased binding of Jurkat leucocytes to HDMEC by a CD40--CD154 dependent pathway. This study thus provides evidence that CD40 expression in HDMEC is regulated by proinflammatory cytokines, and that CD40 functions as an important mediator of cutaneous inflammation.

CD40 Antigens↗

PubMed2001

Personal and practice-related characteristics of a subsample of US women dermatologists: data from the Women Physicians' Health Study.

BACKGROUND: The number of women dermatologists has increased dramatically over the past few decades. Despite this, there have been few studies examining the personal or professional characteristics of women dermatologists practicing in the USA. METHODS: A representative random sample of active, part-time, professionally inactive, and retired US women physicians, aged 30-70 years, was studied; this article compares data from the 95 responding dermatologists with data from 4350 other respondents. RESULTS: Women dermatologists were more likely to be US born, white, and married to a physician than were other women physicians; they were similar to other women physicians in age, marital status, children, amount of stress at home, political self-characterization, and personal health behavior. Women dermatologists were more likely to be board certified and to practice in solo or two-person practices than were other women physicians. They had fewer nights on call, were less likely to state that they worked too much, reported less stress at work, were more satisfied with their careers, and reported higher household incomes. With the decided exception of skin cancer prevention and screening, they were unlikely to have considerable training, confidence, or interest in routine prevention-related screening or counseling for patients. CONCLUSIONS: Women dermatologists are unlikely to be part of a minority group, likely to be married to another physician, and likely to have a high household income. They report reasonable work stress and high career satisfaction. Given these findings, it is not surprising that only 10% would consider changing their specialty were they to relive their lives.

Adult↗

PubMed2001

Behaviour of the adult seven spot ladybird, Coccinella septempunctata (Coleoptera: Coccinellidae), in response to dimethoate residue on bean plants in the laboratory.

The sub-lethal effects of dimethoate residue on the distribution and locomotor activity of adults of Coccinella septempunctata Linnaeus on Vicia faba plants were investigated in the laboratory. The presence of dimethoate residues on the upper half of the plant caused C. septempunctata to spend significantly less time on the plants overall. When given a choice of treated and untreated surfaces, C. septempunctata spent proportionately more time on the untreated areas of the plant. The locomotor activity of C. septempunctata was also altered following encounter with dimethoate residues resulting in a significant increase in the proportion of time spent walking and a reduction in the proportion of time spent resting. The proportion of time spent on plant parts was also affected, with a reduction in the time spent on the apex and an increase in the proportion of time spent on the stem, indicating a possible avoidance response. The proportion of time spent on the adaxial leaf surface was significantly increased following dimethoate treatment. The implications for integrated pest management are considered.

Animals↗

PubMed2000

Biochemical and bacteriological study of urinary calculi.

Biochemical and bacteriological study of urine, nidus and chemical analysis of 100 calculi from 100 patients admitted in the Regional Institute of Medical Sciences, Imphal from November, 1997 to October 1999 were done. About 47% of the cases had positive urine culture and nidus culture. Escherichia coli was the commonest bacteria isolated both in the urine and nidus of calculi. The commonest radical present in the calculi was calcium while the rarest was uric acid. The stones were composed mainly of calcium oxalate and/or phosphate followed by struvite, then mixed stone.

Calcium Oxalate↗

PubMed1999

Multiple cutaneous metaplastic synovial cysts.

The cutaneous metaplastic synovial cyst is a recently described lesion that characteristically presents as a solitary, tender subcutaneous nodule. On histopathologic examination, the lesion is characterized by a cystic structure with villous-like projections and a lining resembling hyperlastic synovium. The cause of cutaneous metaplastic synovial cysts is unclear, but trauma is presumed to be a precipitating factor, as most reported cases have a history of antecedent cutaneous injury. Here we present a case of multiple, bilateral cutaneous metaplastic synovial cysts in a 72-year-old white man with rheumatoid arthritis. This is the first reported case of a patient with multiple lesions. The characteristic clinical and pathologic features of this lesion, along with proposed cause, are reviewed herein.

Aged↗

PubMed1999

Human keratinocytes constitutively express interleukin-18 and secrete biologically active interleukin-18 after treatment with pro-inflammatory mediators and dinitrochlorobenzene.

Interleukin-18 is a potent inducer of interferon-gamma by activated T cells, macrophages, and monocytes and is synthesized as an inactive precursor. Pro-interleukin-18 must be cleaved by interleukin-1-beta-converting enzyme for secretion of the biologically active form. We report that among selected non-bone marrow derived skin cells, interleukin-18 mRNA is constitutively expressed by human keratinocytes and not by dermal microvascular endothelial cells, dermal fibroblasts, or melanocytes. Interleukin-18 mRNA and intracellular protein levels are neither changed in human keratinocytes nor induced in human dermal microvascular endothelial cells, dermal fibroblasts, or melanocytes by exposure to pro-inflammatory stimuli. Exposure of human keratinocytes to phorbol 12-myrisate 13-acetate, lipopolysaccharides or the contact sensitizer DNCB results in the secretion of immunoprecipitable interleukin-18 protein. Human keratinocyte-secreted interleukin-18 is biologically active, in that conditioned media from phorbol 12-myrisate 13-acetate, lipopolysaccharide and DNCB-treated human keratinocytes induce interferon-gamma expression by peripheral blood mononuclear cells. This bioactivity is neutralized by anti-interleukin-18, but not anti-interleukin-12 antibodies. By immunohistochemistry, interleukin-18 protein is detected in basal keratinocytes of normal human skin, but its expression is markedly upregulated in suprabasal keratinocytes in psoriasis. These findings indicate that human keratinocytes are a source of biologically functional interleukin-18 and thus are capable of playing an initiating part in the local interferon-gamma-dependent inflammatory processes through expression, activation, and secretion of interleukin-18.

Dinitrochlorobenzene↗

PubMed1999

Mating activity and fitness of a few wild type strains of Drosophila ananassae.

Courtship time, duration of copulation and fertility were tested in six wild type strains of D. ananassae originating from different geographical localities. The results indicate that there is significant variation among the strains tested with respect to courtship time, duration of copulation and fertility. The strains showing a longer duration of copulation produce more progeny. These findings suggest that there is a positive correlation between duration of copulation and fertility in D. ananassae.

Animals↗

PubMed1995

Antigenic determinants of the OmpC porin from Salmonella typhimurium.

The antigenic determinants of Salmonella typhimurium OmpC were investigated by the analysis of cyanogen bromide (CNBr)-generated porin peptides with antiporin monoclonal antibodies (MAbs). We identified six bands (f1 to f6) with estimated molecular masses of 35.5, 31.0, 25.0, 22.5, 13.8, and 10.0 kDa, respectively. In addition, two small fragments (f7 and f8; 3.0 to 6.0 kDa) were detected only infrequently. The OmpC monomer or its CNBr-generated peptides were electrophoretically transferred to a polyvinylidene difluoride membrane and then subjected to amino acid composition analysis and N-terminal sequencing. A comparison of the amino acid composition data with known compositions of Escherichia coli and Salmonella typhi OmpC showed some differences; however, the amino acid sequences of 71 residues identified in S. typhimurium showed 88 and 98% identity with OmpC from E. coli and S. typhi, respectively. The screening of CNBr peptides with the 12 anti-(S. typhimurium) OmpC MAbs by Western blot (immunoblot), in conjunction with the prediction of the OmpC folding pattern based on the known three-dimensional structure of E. coli OmpF, showed that four MAbs reacted with surface-exposed epitopes on loops L2, L8, and L4 to L7, four MAbs reacted with a region in the eyelet structure on loop L3, and four MAbs reacted with the buried epitopes on transmembrane beta strands. The MAbs reacting with surface-exposed loops showed no cross-reaction with E. coli OmpC, whose sequence has diverged extensively from that of S. typhi and (probably) S. typhimurium OmpC only in regions of the externally exposed loops. In contrast, MAbs reacting with transmembrane beta strands, whose sequence is strongly conserved, showed strong cross-reaction with E. coli OmpC. These results show that comparison with the E. coli OmpF structure predicts the folding pattern of S. typhimurium OmpC rather accurately and that evolutionary divergence in sequences is confined to the external loops. The possible roles of these surface-exposed and buried epitopes as potentially useful antigenic regions for diagnostic assays and vaccine development are discussed.

Amino Acid Sequence↗

PubMed1992

Structural relatedness of enteric bacterial porins assessed with monoclonal antibodies to Salmonella typhimurium OmpD and OmpC.

The immunochemistry and structure of enteric bacterial porins are critical to the understanding of the immune response to bacterial infection. We raised 41 monoclonal antibodies (MAbs) to Salmonella typhimurium OmpD and OmpC porin trimers and monomers. Enzyme-linked immunosorbent assays, immunoprecipitations, and/or Western immunoblot techniques indicated that 39 MAbs (11 anti-trimer and 28 anti-monomer) in the panel are porin specific and one binds to the lipopolysaccharide; the specificity of the remaining MAb probably lies in the porin-lipopolysaccharide complex. Among the porin-specific MAbs, 10 bound cell-surface-exposed epitopes, one reacted with a periplasmic epitope, and the remaining 28 recognized determinants that are buried within the outer membrane bilayer. Many of the MAbs reacting with surface-exposed epitopes were highly specific, recognizing only the homologous porin trimers; this suggests that the cell-surface-exposed regions of porins tends to be quite different among S. typhimurium OmpF, OmpC, and OmpD porins. Immunological cross-reaction showed that S. typhimurium OmpD was very closely related to Escherichia coli NmpC and to the Lc porin of bacteriophage PA-2. Immunologically, E. coli OmpG and protein K also appear to belong to the family of closely related porins including E. coli OmpF, OmpC, PhoE, and NmpC and S. typhimurium OmpF, OmpC, and OmpD. It appears, however, that S. typhimurium "PhoE" is not closely related to this group. Finally, about one-third of the MAbs that presumably recognize buried epitopes reacted with porin domains that are widely conserved in 13 species of the family Enterobacteriaceae, but apparently not in the seven nonenterobacterial species tested. These data are evaluated in relation to host immune response to infection by gram-negative bacteria.

Antibodies, Monoclonal↗

PubMed1989