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Biomedical subjects

H Singh

Publications and source records attributed to H Singh.

At least 91 records · Page 5Linked to original sources

Spectrum of gut immunologic reactions: selective induction of distinct responses to Vibrio cholerae WO7 and its toxin.

Past studies with Vibrio cholerae have shown that cholera toxin (CT) is mainly responsible for inducing T helper type 2 (Th2) responses with systemic IgG1, IgE and mucosal secretory IgA (sIgA) antibodies. In this study, V. cholerae WO7, which produces novel toxin unrelated to CT, was given orally to mice in order to determine whether the strain V. cholerae WO7 differs from V. cholerae 569B, which produces CT, in the nature of responses generated at the gut and splenic level. The analysis of immune responses evoked by V. cholerae WO7 in the gut of mice revealed striking differences as compared to those elicited by V. cholerae 569B infection. To assess the T helper cell type responses, lymphocytes from Peyer's patches and the spleen were stimulated in vitro for studying the cytokine patterns. PP and SP lymphoid cells from V. cholerae WO7 infected animals elaborated significant amounts of IL-2, IFN-gamma and IL-12 by 7 days p.i., suggesting a Th1 type of response. However by 15 days p.i., the PP and SP lymphoid cells secreted only IL-6 and IL-10 with traces of IFN-gamma. On the other hand, infection with V. cholerae 569B yielded mainly Th2 type responses at Peyer's patches as well as the splenic level. Infection with both V. cholerae WO7 and 569B induced toxin-specific IgA secreting cells at the gut and splenic level along with IgG1 secreting cells, indicating that both V. cholerae WO7 and 569B evoke an antigen-specific Th2 type of response in the gut as well as spleen. The persistence of IgA along with Th1-type cytokines indicates an alternate induction mechanism since mucosal IgA responses are usually associated with Th2-type responses. These observations are suggestive of a common mechanism employed by the host to clear different strains of V. cholerae infection (569B and WO7 in this case), while the nature of toxins elaborated failed to modulate the net outcome of the infection caused by V. cholerae.

Animals↗

pING family of conjugative plasmids from the extremely thermophilic archaeon Sulfolobus islandicus: insights into recombination and conjugation in Crenarchaeota.

A novel family of conjugative plasmids from Sulfolobus comprising the active variants pING1, -4, and -6 and the functionally defective variants pING2 and -3, which require the help of an active variant for spreading, has been extensively characterized both functionally and molecularly. In view of the sparse similarity between bacterial and archaeal conjugation and the lack of a practical genetic system for Sulfolobus, we compared the functions and sequences of these variants and the previously described archaeal conjugative plasmid pNOB8 in order to identify open reading frames (ORFs) and DNA sequences that are involved in conjugative transfer and maintenance of these plasmids in Sulfolobus. The variants pING4 and -6 are reproducibly derived from pING1 in vivo by successive transpositions of an element from the Sulfolobus genome. The small defective but mobile variants pING2 and -3, which both lack a cluster of highly conserved ORFs probably involved in plasmid transfer, were shown to be formed in vivo by recombinative deletion of the larger part of the genomes of pING4 and pING6, respectively. The efficient occurrence of these recombination processes is further evidence for the striking plasticity of the Sulfolobus genome.

Base Sequence↗

Descriptive epidemiology of asthma in Trinidad, West Indies.

This cross-sectional study documents the demographic features of asthmatics seeking acute asthma care at four institutions on the island of Trinidad from January 1 to December 31, 1997. More than 15,000 (15,035) different patients made 27,353 visits during the study period. Pediatric and adolescent male patients outnumbered females, but this was reversed in patients aged 20-69 years. Frequency of visits per patient ranged from 1 to 242. Significant variation in monthly admissions was observed; admission rates were highest in the last quarter of the year but were lowest in July and August. The overall crude prevalence rate was estimated at 1.71 per 100 (range 1.16-2.34).

Adolescent↗

Postradiation squamous cell cancer of the breast.

Primary squamous cell carcinoma of the breast is a rare clinical entity. We diagnosed a patient who presented with a pure squamous cell cancer of the breast 12 years after local radiation for a primary adenocarcinoma of breast. Previously reported cancers related to radiation of the breast have been squamous cell of skin and esophagus and sarcomas, especially angiosarcomas, and on literature review this is the first reported case of primary squamous carcinoma of the breast related to previous radiation. Although our observation suggests a possible link, no established cause and effect relationship is known at this point.

Adenocarcinoma↗

Intracranial and intraspinal meningeal melanocytosis.

We describe a 35-year-old man with a history of remote closed head injury who presented with new neurologic deficits. A noncontrast head CT scan showed hyperattenuation involving both temporal lobes, frontal lobes, basal meninges, and cerebellum. A subsequent contrast-enhanced MR examination of the brain showed enhancement in the basal cisterns extending into the upper cervical spine and throughout the spinal canal. Gross, histologic, and immunohistochemical analysis revealed meningeal melanocytoma.

Adult↗

Iodinated natural rubber latex: preparation, characterisation & antibacterial activity assessment.

Natural Rubber (NR) in both its latex and dried form was treated with iodine to make it antibacterial in nature. The NR latex was dried and washed, dissolved in toluene, iodinated and cast into films. In a different approach, NR in its latex form (emulsion) was blended with aqueous solution of povidone-iodine complex (PVP-I) and films were cast. Phase separation of PVP-I was observed in the films prepared using NR latex; whereas the film prepared using NR solution in toluene and molecular iodine were homogeneous, transparent light brown. Solubility assessment of the films revealed that unlike pure NR, the iodinated NR failed to go into solution completely. The films obtained from both the approaches were evaluated for release of iodide ions. On immersion in water, PVP-I blended latex did not retain iodine while sustained release of iodide ion was observed in case of dried NR dissolved in toluene and treated with iodine. The FT-IR spectra of the iodinated films revealed that iodine attaches covalently to the double bonds in the isoprene units of NR. The films were also evaluated for their antibacterial properties and it was observed that the films prepared from both the approaches, acquired antimicrobial properties.

Anti-Bacterial Agents↗

Pulmonary manifestations in malaria.

Malaria, a major killer of mankind, apart from classical ague presentation, may present with respiratory manifestations. This may be misdiagnosed and important time may be lost in instituting antimalarials leading to higher morbidity and mortality. Present work was undertaken to study the clinical presentations of malaria with special reference to respiratory system and to evaluate the effect of antimalarials to such atypical presentation. One hundred slide positive cases of malaria were taken and detailed for respiratory involvement. Response to antimalarials was seen in these cases and associated complications (if any) were looked for. Mean age of the cases was 29.3 years with a male predominance. Positivity of peripheral smear read as: P vivax(53%), P falciparum (36%) and mixed infection (11%). Twenty-six patients had presented with respiratory manifestations-bronchitis (15), pneumonia (4), asthmatic bronchitis (1), adult respiratory distress syndrome (ARDS) (4) and pulmonary tuberculosis (2). Of these 26 cases, presenting symptoms noticed were cough (77%), dyspnoea (32%), expectoration (29%) and chest pain (15%). Twenty-five (96%) of these 26 patients were positive for P falciparum. Response to antimalarials was not significantly different in these 26 patients as compared to the rest (74 cases). All patients developing ARDS expired. The present study concludes that malarial atypical respiratory presentations are far higher in incidence than reported in literature. Peripheral smear examination in all patients of high grade fever with chills and rigors and having respiratory manifestations may unmask malarial infection and warrant early antimalarial treatment resulting in decreased morbidity and mortality.

Adult↗

Chromatin and cancer: causes and consequences.

In this review, we discuss recent evidence implicating chromatin structure in the etiology of cancer. In particular, we present evidence indicating that inappropriate regulation of chromatin structure inhibits normal cell differentiation pathways and stimulates uncontrolled cell proliferation, with the outcome being oncogenesis. Such inappropriate chromatin structures arise as a consequence of (i) chromosomal rearrangements that fuse gene-specific activators with global co-regulators, drastically altering activator function; (ii) hypermethylation of tumor suppressor gene promoters, resulting in their inactivation; or (iii) mistargeted nuclear compartmentalization of growth-control genes and their regulators, resulting in the up- or down-regulation of such genes. How does chromatin silence genes? Recent results from model in vivo systems argues that chromatin can repress transcription at two levels: (i) by sterically interfering with the binding of transcription factors to the promoter, thereby blocking initiation; and (ii) at a step subsequent to the binding of activators and recruitment of the preinitiation complex. J. Cell. Biochem. Suppl. 35:61-68, 2000.

Animals↗

Visual quantification of DNA double-strand breaks in bacteria.

In this paper, we describe a method for the visualization of double-strand breaks in a single electrostretched Escherichia coli DNA molecule. We also provide evidence that electrostretched or migrated DNA under neutral microgel electrophoresis conditions is made up of individual chromosomes. Using the neutral microgel electrophoresis technique, DNA migration (stretching) was measured and the number of DNA double-strand breaks were counted following exposure of E. coli cells to 0, 12.5, 25, 50, or 100 rad of X-rays. The use of an intense fluorescent dye, YOYO and custom-made slides have helped us in visualizing individual bacterial DNA molecules. Bacterial DNA appears similar in structure compared to electrostretched DNA from human lymphocytes. We were able to detect changes in DNA migration (stretching) induced by an X-ray dose as low as 12.5 rad and an increase in the number of DNA breaks induced by a dose as low as 25 rad. The extent of DNA migration and number of breaks were directly correlated to X-ray dosage.

Benzoxazoles↗

Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers.

Gene expression in higher eukaryotes appears to be regulated by specific combinations of transcription factors binding to regulatory sequences. The Ets factor PU.1 and the IRF protein Pip (IRF-4) represent a pair of interacting transcription factors implicated in regulating B cell-specific gene expression. Pip is recruited to its binding site on DNA by phosphorylated PU.1. PU.1-Pip interaction is shown to be template directed and involves two distinct protein-protein interaction surfaces: (i) the ets and IRF DNA-binding domains; and (ii) the phosphorylated PEST region of PU.1 and a lysine-requiring putative alpha-helix in Pip. Thus, a coordinated set of protein-protein and protein-DNA contacts are essential for PU.1-Pip ternary complex assembly. To analyze the function of these factors in vivo, we engineered chimeric repressors containing the ets and IRF DNA-binding domains connected by a flexible POU domain linker. When stably expressed, the wild-type fused dimer strongly repressed the expression of a rearranged immunoglobulin lambda gene, thereby establishing the functional importance of PU.1-Pip complexes in B cell gene expression. Comparative analysis of the wild-type dimer with a series of mutant dimers distinguished a gene regulated by PU.1 and Pip from one regulated by PU.1 alone. This strategy should prove generally useful in analyzing the function of interacting transcription factors in vivo, and for identifying novel genes regulated by such complexes.

Amino Acid Sequence↗

Metabolism of trideuterated iso-lignoceric acid in rats in vivo and in human fibroblasts in culture.

Saturated very long chain fatty acids (fatty acids with greater than 22 carbon atoms; VLCFA) accumulate in peroxisomal disorders, but there is little information on their turnover in patients. To determine the suitability of using stable isotope-labeled VLCFA in patients with these disorders, the metabolism of 22-methyl[23,23,23-2H3]tricosanoic (iso-lignoceric) acid was studied in rats in vivo and in human skin fibroblasts in culture. The deuterated iso-VLCFA was degraded to the corresponding 16- and 18-carbon iso-fatty acids by rats in vivo and by normal human skin fibroblasts in culture, but there was little or no degradation in peroxisome-deficient (Zellweger's syndrome) fibroblasts, indicating that its oxidation was peroxisomal. Neither the 14-, 20-, and 22-carbon iso-fatty acids nor the corresponding odd-chain metabolites could be detected. In the rat, the organ containing most of the iso-lignoceric acid, and its breakdown products, was the liver, whereas negligible amounts were detected in the brain, suggesting that little of the fatty acid crossed the blood-brain barrier. Our data indicate that VLCFA labeled with deuterium at the omega-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal beta-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their beta-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.

Animals↗

Health care for the disadvantaged: some preliminary observations of health centres in Trinidad and Tobago.

This study seeks to identify background characteristics of the people who utilise health centre services in Trinidad and Tobago and to investigate their perceptions of the services offered. Data were obtained through a survey of health centre users distributed throughout Trinidad and Tobago. Multi-stage sampling was used to select 1500 health centre users and structured interviews were conducted on regular clinic days by trained personnel. Results indicate that there are fairly high levels of patient satisfaction with health centres in Trinidad and Tobago and that the more disadvantaged groups (the elderly, women and the unemployed) utilise these services more frequently. Results also show variations with respect to care received, frequency of attendance, amount willing to pay, services that need improving and doctor's willingness to listen to problems.

Efficiency, Organizational↗

Left leg paralysis in a renal transplant.

The postoperative course of renal transplant patients is often complicated by opportunistic infection. Up to 4% of posttransplant infections are caused by Nocardia species. We present an unusual case of a nocardial spinal cord abscess that caused left leg paralysis.

Abscess↗