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Biomedical subjects

P Vyas

Publications and source records attributed to P Vyas.

34 records · Page 2Linked to original sources
PubMed1993

Role of upstream DNase I hypersensitive sites in the regulation of human alpha globin gene expression.

Erythroid-specific DNase 1 hypersensitive sites have been identified at the promoters of the human alpha-like genes and within the region from 4 to 40 kb upstream of the gene cluster. One of these sites, HS-40, has been shown previously to be the major regulator of tissue-specific alpha-globin gene expression. We have now examined the function of other hypersensitive sites by studying the expression in mouse erythroleukemia (MEL) cells of various fragments containing these sites attached to HS-40 and an alpha-globin gene. High level expression of the alpha gene was observed in all cases. When clones of MEL cells bearing a single copy of the alpha-globin gene fragments were examined, expression levels were similar to those of the endogenous mouse alpha genes and similar to MEL cells bearing beta gene constructs under the control of the beta-globin locus control region. However, there was no evidence that the additional hypersensitive sites increased the level of expression or conferred copy number dependence on the expression of a linked alpha gene in MEL cells.

Animals↗
PubMed1993

Structure of the human 3-methyladenine DNA glycosylase gene and localization close to the 16p telomere.

We recently reported the presence of four genes lying between the human alpha-globin gene cluster and the telomere of the short arm of chromosome 16 (16p). We now report that one of these genes encodes 3-methyladenine DNA glycosylase, an enzyme important in the repair of DNA after damage by alkylating agents. The gene comprises five exons, representation of which differs in independently isolated cDNA clones. Although the gene is widely expressed, the abundance of its mRNA is considerably higher in a colon adenocarcinoma cell line (HT29) than in other cell lines that were tested. The major positive erythroid-specific regulatory element controlling alpha-globin gene expression lies equidistant between the promoters of the alpha-globin genes and the 3-methyladenine DNA glycosylase gene. Interestingly, in contrast to the alpha-globin genes, expression of the 3-methyladenine DNA glycosylase gene is not influenced by the regulatory element in the human erythroleukemia cell line K562.

Amino Acid Sequence↗
PubMed1993

Non specific orbital inflammatory diseases.

The understanding of 'pseudotumors' has significantly changed with the advent of modern imaging techniques by which the tissues affected in the orbit can be identified, and nonspecific orbital inflammatory disease is classified according to the tissue involved. Twenty cases of nonspecific orbital inflammatory diseases were treated between July 1987 and September 1991. Eight patients had myositis, 6 had diffuse disease, 2 each had dacryoadenitis, periscleritis and perineuritis. Involvement of all four recti in one patient and isolated superior rectus and superior oblique each in 2 others are the unusual forms of myositis. Perineuritis presented as diffuse thickening of the optic nerve on CT scan with disc edema and normal vision in both patients with external ophthalmoplegia in one of them. All patients responded to oral steroids while the patient with myositis of all four recti required radiotherapy in addition. This series documents the spectrum of clinical presentation, diagnosis and management of nonspecific orbital inflammatory disease.

Acute Disease↗
PubMed1993

Post-penetrating keratoplasty glaucoma.

To study the risk factors in the development of glaucoma following penetrating keratoplasty, we retrospectively analysed 190 eyes of 185 consecutive patients who had undergone surgery during 1990. The donor button was larger by 0.2 mm and 0.5 mm in phakia and aphakia/pseudophakia patients, respectively. Over a mean follow-up period of 14.5 months, 52 of the 190 eyes (27.4%) either developed glaucoma de novo or had worsening of preexisting glaucoma. Of these 52 eyes, 38 were managed medically and 14 required surgery. From our study, aphakia (37%), pseudophakia (24%), preexisting glaucoma (81.8%), and regrafting (43.18%) were found to be the significant risk factors in the development of glaucoma following penetrating keratoplasty.

Aphakia, Postcataract↗
PubMed1992

Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells.

Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.

Adenine Phosphoribosyltransferase↗
PubMed1992

Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin.

Current models suggest that tissue-specific genes are arranged in discrete, independently controlled segments of chromatin referred to as regulatory domains. Transition from a closed to open chromatin structure may be an important step in the regulation of gene expression. To determine whether the human alpha-globin cluster, like the beta-globin cluster, lies within a discrete, erythroid-specific domain, we have examined the long-range genomic organization and chromatin structure around this region. The alpha genes lie adjacent to at least four widely expressed genes. The major alpha-globin regulatory element lies 40 kb away from the cluster within an intron of one of these genes. Therefore, unlike the beta cluster, cis-acting sequences controlling alpha gene expression are dispersed within a region of chromatin that is open in both erythroid and nonerythroid cells. This implies a difference in the hierarchical control of alpha- and beta-globin expression.

Animals↗
PubMed1988

The interaction of alpha thalassaemia and sickle cell-beta zero thalassaemia.

The effects of alpha thalassaemia on sickle cell-beta zero thalassaemia have been studied by comparing haematological and clinical features in four subjects homozygous for alpha thalassaemia 2 (2-gene group), 27 heterozygotes (3-gene group), and 55 with a normal alpha globin gene complement (4-gene group). Alpha thalassaemia was associated with significantly higher haemoglobin levels and lower reticulocyte counts independent of the presence of splenomegaly. Contrary to expectation, alpha thalassaemia was associated with small but significant increases in mean cell volume and mean corpuscular haemoglobin concentration. Splenomegaly at age 5 years and episodes of acute splenic sequestration were significantly more frequent in the 4-gene group. There were no significant differences in painful crises, acute chest syndrome, or other clinical features.

Adolescent↗
PubMed1985

Allergic bronchopulmonary aspergillosis and sensitization to Aspergillus fumigatus in chronic bronchiectasis in adults.

Fifty adult subjects for whom a diagnosis of idiopathic bronchiectasis (excluding those secondary to tuberculosis or hypogammaglobulinaemia) had been confirmed previously were investigated by: questionnaire; blood eosinophil count; sputum culture for Aspergillus fumigatus and eosinophil count; chest radiography; skin-prick tests with several aeroallergens and four preparations of A. fumigatus, including a reference extract; measurement of specific IgE antibodies; precipitin testing and self-crossed immunoelectrophoresis with A. fumigatus. Five subjects were possible cases of allergic bronchopulmonary aspergillosis in whom the condition had been previously misdiagnosed or in whom sensitization to A. fumigatus had occurred after the onset of bronchiectasis. These five subjects had positive immediate skin reactions to A. fumigatus and a history of recurrent pneumonias. Four had a previous history of asthma and the others showed increased bronchial responsiveness to inhaled methacholine. At the time of the survey, A. fumigatus grew in the sputum of one out of five subjects. These subjects had increased levels of specific IgE. Two had precipitins by double diffusion and three subjects were positive on self-crossed immunoelectrophoresis. It is concluded that allergic bronchopulmonary aspergillosis or evidence of sensitization to A. fumigatus can be identified in a significant proportion of adult subjects with so-called idiopathic bronchiectasis.

Adult↗
PubMed1984

Intravenous nitroglycerin in transfusion therapy for severe anemia. Association with congestive heart failure.

The risk of aggravated heart failure due to expanded blood volume and augmented left-ventricular filling pressure poses a challenge when transfusion is indicated by severe anemia complicating congestive heart failure. Intravenous (IV) nitroglycerin therapy produces a favorable redistribution of circulating blood volume and may be used to surmount these hemodynamic constraints during transfusion. In four patients with severe anemia and cardiac failure, IV nitroglycerin permitted rapid and large-volume blood transfusion without compromising cardiac function. In two of the four patients, recalcitrant unstable angina abated after the correction of anemia.

Aged↗
PubMed1982

The "lead tug" sign for the diagnosis of early and inapparent lead fracture.

The cause of pacemaker malfunction in a patient having intermittent pacing failure associated with diminished pacer stimuli was not determined during conventional intraoperative electrical testing. A modest manual pull on the lead, termed the "lead tug" sign, induced an inordinately high lead impedance and established lead fracture as the etiology. The "lead tug" maneuver is proposed as a useful procedure during stimulation studies for the detection of early lead fracture, not apparent from the x-ray film or usual testing protocol.

Aged↗
PubMedDate not supplied

Expression of nitric oxide synthase in human peripheral blood mononuclear cells and neutrophils.

It has been clearly demonstrated in rodents that nitric oxide (NO) plays an important role in host defense and immunity. However, evidence that human leukocytes express inducible nitric oxide synthase (iNOS) or its products has been inconclusive and a source of controversy. We report that iNOS could not be detected in human monocytes, HL-60 cells, neutrophils, and T cells by Western blotting analysis (< or = 10 pg) or by radiolabeled L-arginine-to-L-citrulline conversion (< or = 20 pmol L-citrulline) under conditions sufficient to induce iNOS in the rodent system and in human hepatocytes, which include activation with cytokines, endotoxins, and/or chemoattractants. However, sensitive methods such as RT-PCR and Northern blot analysis show "constitutively expressed" iNOS mRNA from human monocytes, neutrophils, Jurkat cells, and HL-60 cells. This iNOS mRNA is 4.4 kb and is similar to that seen in human hepatocytes and rodent macrophages. In spite of the constitutive expression of mRNA in neutrophils and the lack of detectable NOS activity (based on Western blotting and L-arginine-to-L-citrulline conversion assay), stimulation of human neutrophils unit FMLP in vitro induced the ADP-ribosylation of an intracellular NO target, glyceraldehyde-3-PO4 dehydrogenase (GAPDH), in a NO-dependent manner. These studies indicate that low levels of NOS protein are expressed in neutrophils (and perhaps T cells and monocytes) and produce NO following stimulation. The data indicate that, in addition to its phagocytic and tumoricidal activity. NO may also function as an autacoid signaling molecule within the cells.

Adenosine Diphosphate Ribose↗