Search PubMed⌕ Search

Biomedical subjects

P Sinha

Publications and source records attributed to P Sinha.

At least 127 records · Page 7Linked to original sources

Interferon-induced growth arrest is mediated by membrane structural changes.

Interferon-gamma (IFN-gamma) is an immunomodulator shown to augment the expression of major histocompatibility (MHC) class I/class II antigens on the cell surface. In previous studies, we have demonstrated that the enhanced expression of these antigens on the cell surface is in part due to IFN-gamma-mediated abrogation of antigen shedding. In this study, we demonstrate that IFN-gamma induces structural changes in the cell membrane by altering the cholesterol/phospholipid ratio. Furthermore, such changes not only mediate enhanced expression of antigen on the cell surface but may drive the cells to growth arrest and apoptosis. These results were obtained by employing x-ray diffraction, electron microscopy, and DNA analysis.

Adjuvants, Immunologic↗

The congested-like tracheae gene of Drosophila melanogaster encodes a member of the mitochondrial carrier family required for gas-filling of the tracheal system and expansion of the wings after eclosion.

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4-kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacW transposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenorhabditis elegans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings.

Amino Acid Sequence↗

Maternal adrenalectomy eliminates a surge of plasma dehydroepiandrosterone in the mother and attenuates the prenatal testosterone surge in the male fetus.

Previous work has established a number of sex-related deficits in immune function, behavior, and endocrine responses to stress in the offspring of dams exposed to ethanol. To examine the potential role of maternal glucocorticoids as a mediator of these sexually dimorphic effects in the fetus, we examined the influence of prenatal alcohol exposure in the presence or absence of maternal glucocorticoids on fetal plasma corticosterone (CORT) production. An additional question to be addressed by these studies was whether maternal adrenalectomy could eliminate the known inhibition by ethanol of the prenatal surge of plasma testosterone in male fetuses. Pregnant dams were adrenalectomized (ADX) or sham-adrenalectomized on gestational day (G) 7 and placed on a liquid diet containing 35% ethanol-derived calories or pair-fed an isocaloric control diet throughout the experiment. On G18, G19, and G21, plasma levels of CORT, testosterone, and dehydroepiandrosterone (DHEA) were measured in male and female fetuses and their mothers. Ethanol administration consistently increased maternal plasma CORT levels but did not significantly alter CORT levels in the fetus. Maternal ADX resulted in compensatory increases in fetal CORT levels that were lower in fetuses of ADX dams on alcohol, suggesting a direct effect of ethanol on fetal pituitary-adrenal activity. There were no significant sex differences in fetal plasma CORT levels in response to any of these manipulations. A novel surge of maternal plasma DHEA was found on G19 that was absent in plasma from ADX dams. In spite of the absence of a surge on G19, plasma DHEA levels of ADX dams rose from very low levels at G18 to levels on G21 that were significantly higher than in Sham dams. A normal testosterone surge was observed in male fetuses on G18 and G19 from sham-adrenalectomized dams administered the pair-fed diet. However, this surge was greatly attenuated in males administered ethanol and also in male fetuses from ADX dams. These results reveal a direct inhibitory influence of ethanol on fetal CORT secretion as well as on the prenatal testosterone surge in males. Furthermore, these studies demonstrate the presence of a surge of DHEA in the pregnant rat. Overall, these data suggest that there is a critical adrenal factor in the rat that regulates the maternal surge of DHEA on G19 and the prenatal testosterone surge of male fetuses on G18-19.

Adrenalectomy↗

The effect of in vitro bacterial association on virulence of Entamoeba histolytica.

When trophozoites of axenic E. histolytica strains NIH : 200 were associated in vitro with Escherichia coli K12 for three hours at 37 degrees C, the virulence was enhanced as shown by increased cytopathogenicity to baby hamster kidney (BHK) cell monolayer. Further, the trophozoites were observed to adhere to the polystyrene surface, a hitherto unreported phenomenon. The co-association of E. histolytica trophozoites with Bacteroides fragilis and Clostridium perfringens for three hours duration at 37 degrees C neither led to increase in cytotoxicity potential nor to adherence phenomenon; in contrast significant inhibition of cytotoxicity was observed. We have thus shown that while co-association of E. histolytica (NIH : 200) with E. coli K12 leads to enhanced amoebic virulence, that with anaerobic bacteric leads to its inhibition.

Animals↗

A multicentre evaluation of the CA 15-3 assay, CA 19-9 assay and CA 125 II assay on the Bayer Immuno 1 System.

The analytical performance of the tumour markers CA 15-3 assay, CA 19-9 assay and Ca 125 II assay on the Bayer Immuno I System was studied according to a revised version of the ECCLS guidelines (Haeckel R. In: Evaluation methods in laboratory medicine, Weinheim, VCH Verlag 1993:47-69) in a multicentre evaluation involving five laboratories. Determination of the 3 analytes generated more than 6000 data. On the Bayer Immuno I System, the imprecisions of the CA 15-3 assay, CA 19-9 assay and CA 125 II assay were better than those found for comparison methods. The median recovery over all five laboratories of system assigned values in control sera was within the 1-s range for the three tumour marker assays. No deviation of linearity could be detected experimentally for all assays. Results for patients' samples showed acceptable agreement between the Bayer Immuno 1 system and several different comparison methods in most cases. One exception was the CA 15-3 assay in comparison with the MCA assay from Roche Diagnostic Systems, where the large difference in values is due to the use of different antibodies and calibrators in the two assays. No carry-over effects could be detected. The selective Bayer Immuno 1 system is fully automated; its practicability was rated as high.

Antigens, Tumor-Associated, Carbohydrate↗

Does Entamoeba histolytica cause irritable bowel syndrome?

BACKGROUND: Symptoms of patients with irritable bowel syndrome (IBS) closely mimic those of patients with non-dysenteric amebic colitis. AIM: To examine the clinical relevance of presence and types of Entamoeba histolytica in stools of patients with IBS. METHODS: IBS was diagnosed by Manning's criteria. Stool examination was done 4-weekly for 48 weeks to detect E. histolytica cysts or trophozoites. Patients underwent initial sigmoidoscopy. Sera of 22 IBS patients, 23 asymptomatic cyst passers and 36 healthy volunteers whose stools were also examined were tested for presence of antiamebic antibodies. Stools were cultured for amebae; positive cultures were subjected to polyacrylamide-gel electrophoresis (PAGE) using hexokinase (HK) isoenzyme to distinguish between pathogenic (fast-moving band) E. histolytica infection and nonpathogenic (slow band) species of Entamoeba dispar. RESULTS: E. histolytica cultured from stool samples of four IBS patients had slow-moving band of HK on PAGE. All patients spontaneously eradicated the infection during the next eight to 24 weeks; all had negative serology for antiamebic antibodies, and normal rectal mucosa on sigmoidoscopy. No change in symptom score occurred on follow up in IBS patients, although all of them cleared the infection. Three additional E. histolytica isolates from IBS patients obtained from another laboratory also showed nonpathogenic isoenzyme pattern. CONCLUSION: Bowel symptoms in IBS patients were not related to E. histolytica infection. The term non-dysenteric amebic colitis thus appears to be inappropriate, since it may be used erroneously for patients with IBS with nonpathogenic ameba, leading to injudicious treatment with antiamebic drugs.

Abdominal Pain↗

Endometrial cancer thirteen years after total abdominal hysterectomy and bilateral salpingo-oophorectomy and hormone replacement therapy: a case report.

We have reported a very interesting, rare case of endometrial adenocarcinoma arising from pelvic endometriosis thirteen years after hysterectomy with bilateral salpingo-oophorectomy, followed with hormone replacement therapy. Our patient presented with history of abnormal vaginal bleeding, which was investigated with abdominal scans, examination under anaesthesia (EUA), and biopsy. Histology of which confirmed malignant transformation. We then proceeded to primary excision of all macroscopic tumour and palpable lymph nodes followed with radiotherapy.

Adenocarcinoma↗

Role of learning in three-dimensional form perception.

One of the most remarkable characteristics of the human visual system is its ability to perceive specific three-dimensional forms in single two-dimensional contour images. This has often been attributed to a few general purpose and possibly innately specified shape biases, such as those favouring symmetry and other structural regularities (Fig. 1). An alternative approach proposed by the early empiricists and since tested suggests that this ability may also be acquired from visual experience, with the three-dimensional percept being the manifestation of a learned association between specific two-dimensional projections and the correlated three-dimensional structures. These studies of shape learning have been considered inconclusive, however, because their results can potentially be accounted for as cognitive decisions that might have little to do with shape perception per se. Here we present an experimental system that enables objective verification of the role of learning in shape perception by rendering the learning to be perceptually manifest. We show that the human visual system can learn associations between arbitrarily paired two-dimensional pictures and (projectionally consistent) three-dimensional structures. These results implicate high-level recognition processes in the task of shape perception.

Humans↗

The coherence of subjective gratings.

Two differently oriented moving gratings when superimposed, are often seen to move coherently in a direction quite different from that of either grating's. By varying the characteristics of the component gratings researchers have been able to study specific aspects of the motion processing mechanisms in the primate visual system. Here we report the results of experiments performed with a class of subjective gratings. We find that observers perceive coherence and are able to accurately report pattern velocity with our stimuli. These results have implications for some key issues concerning strategies and mechanisms for motion estimation in the human visual system.

Discrimination, Psychological↗

Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics of lethal(2)giant larvae (lgl), a tumor suppressor gene of Drosophila.

Homozygosity for lethal(2)giant larvae (lgl), a mutation in a tumor suppressor gene of Drosophila, induces neoplasia of the imaginal discs. To explore the developmental capacities of lgl mutant cells, we have investigated their growth and differentiation in genetic mosaics. Adult wings mosaic for lgl displayed abnormal growth and differentiation of the lgl mutant and neighboring wild-type cells, suggesting aberrant cell-cell interactions during development. lgl mutant clones also straddled the anteroposterior boundary of the wing imaginal disc, apparently due to failure of the cells of the anterior and the posterior compartment to segregate at the boundary. To further test if anteroposterior compartmentalization takes place in the neoplastic imaginal discs of lgl mutant larvae, we studied the expression of an engrailed (en)-specific lacZ reporter gene during progressive stages of their tumorous growth. Our results show that en is activated in the posterior compartments of the neoplastic imaginal discs. However, during later stages of tumorous overgrowth, the en-expressing and nonexpressing cells appear to show extensive intermixing. These observations suggest that neoplastic transformation of imaginal discs involves loss of their normal cell-cell interactions and signaling.

Animals↗

Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics.

Lethal mutations in the giant discs (lgd) and fat (ft) tumor suppressor genes of Drosophila cause epithelial hyperplasia in all imaginal discs. By contrast, mutations in the vestigial (vg) gene adversely affect cell viability in the wing imaginal discs and consequently cause loss of pattern in the adult wings. However, combining homozygous lgd or ft mutations with homozygous vg1 increases the size of the wing imaginal discs and partially restores the bristle pattern in the wings of pharate adults. Comparable pattern restoration in vg1 wings is also induced by a newly isolated weak hypomorphic lgd3 allele. Further, mosaic analysis revealed that whereas lgd clones generated by the Minute technique display abnormal differentiation, those induced in a homozygous vg1 background exhibit autonomous restoration of wing pattern. These results suggest that pattern restoration in vg1 wings can serve as an assay for hyperplasia induced by mutations in Drosophila tumor suppressor genes.

Animals↗

The mcm2-1 mutation of yeast causes DNA damage with a RAD9 requirement for repair.

The minichromosome maintenance mutation, mcm2-1, has been found to synthesize damaged DNA at 35 degrees C. Growth at this temperature rendered the mutant strain more sensitive to killing by ultraviolet irradiation. DNA damage could also be detected by pulsed-field gel electrophoresis, where a higher fraction of the DNA loaded was retained in the inserts at the wells. During the exponential phase of growth at this temperature about 50% of the cells had large buds, with the nucleus at or near the neck of the bud in most cases. The incorporation of the rad9 deletion in the mcm2-1-carrying strain caused a reduction in the percentage of large-budded cells and a moderate loss of cell viability. The results are consistent with mcm2-1 causing DNA damage leading to the arrest of cells in the S/G2 phase of the cell cycle, which was partially dependent on the RAD9 gene product.

Cell Cycle↗

An improved method for chemical devitellinization of X-gal stained Drosophila embryos.

In Drosophila developmental biological studies, X-gal staining is commonly employed to study the spatio-temporal expression of the lacZ reporter gene in the transformed flies or their embryos. Study of the lacZ pattern in embryos often suffers from the lack of an efficient and high yielding technique for devitellinization of X-gal stained embryos. Devitellinization techniques employed during antibody staining, in situ hybridization or embryonic cuticular preparations generally do not give satisfactory results when used for similar purpose in X-gal stained embryos. This results in the flaky appearance of the blue stain. We present here an improved chemical devitellinization technique which gives a high yield of devitellinized embryos and a better resolution of the X-gal staining pattern.

Animals↗

Studies on the aetiology of coeliac disease: no evidence for lectin-like components in wheat gluten.

In an approach to examine the lectin-hypothesis in the pathogenesis of coeliac disease, the presence of lectin-like components in three wheat gluten preparations known to induce coeliac disease, gliadin, Frazer fraction III and an acetic acid/ethanol extract of gluten, was investigated. Lectin-like components in these wheat gluten preparations were traced in binding studies employing a variety of model glycoproteins glycosylated with the different types of N-linked oligosaccharides, i.e., those of the high mannose-, complex- and hybrid-type. Binding affinity of wheat proteins to these glycoproteins was analyzed by affinity dotting and blotting techniques and was compared to that of the well characterized lectins Galanthus nivalis agglutinin, Concanavalin A and wheat germ agglutinin. Though the three wheat gluten preparations exhibited binding reactivity for distinct model glycoproteins, no correlation was found between the type of N-glycosylation of the model glycoproteins and their binding capability to the different wheat gluten preparations. Moreover, binding of the three gluten preparations to the model glycoproteins could not be inhibited by competitive saccharides (methyl-alpha-D-mannopyranoside, N-acetyl-D-glucosamine, mannan). Enzymatic deglycosylation of the ligand glycoproteins with endo-beta-N-acetylglucosaminidase H (Endo H, EC 3.2.1.96) or peptide N-glycosidase F (PNGase F, EC 3.5.1.52) abolished their binding reactivity for the plant lectins, but did not affect binding of the wheat gluten preparations. These results give no evidence for the presence of lectin-like components in wheat gluten preparations and do question the 'lectin hypothesis' of coeliac disease.

Amidohydrolases↗

Analysis of haemoglobin variants using immobilized pH gradients.

We present a new method for analysis of haemoglobin variants in immobilized pH gradients. The isoelectric fractionation is performed in polyacrylamide gels with copolymerized pH gradients between pH 7.0 and 8.0. The common haemoglobin variants (HbA, HbF, HbS, HbC, HbE and HbA2) are clearly resolved within this pH range. The high resolving power and reproducibility of immobilized pH gradients combined with extremely short separation times make this fractionation technique superior to all electrokinetic procedures used for haemoglobin analysis. At present, isoelectric focusing in immobilized pH gradients is a complementary tool for haemoglobin analysis when classical electrophoretic techniques do not provide sufficient resolution. We hope that in the future this technique will gain the popularity it deserves.

Evaluation Studies as Topic↗

A 5-year study of caesarean hysterectomy cases.

There were 53 cases where caesarean hysterectomy was done during the last 5 years at Eden Hospital, Calcutta. Majority of the cases were in the age group of 22-32 years and parity varied from 0 to 6. There were 54.71% cases which were due to rupture of previous caesarean section scar mostly lower uterine segment done in teaching institutions. Seventy per cent cases were booked. Only 8 babies survived following caesarean hysterectomy. Maternal mortality was nil. By good intranatal monitoring, more vigilance, performing less caesarean section and better health education one can lower the incidence of caesarean hysterectomy.

Adult↗

The mcm2 mutation of yeast affects replication, rather than segregation or amplification of the two micron plasmid.

We have studied the maintenance of the endogenous two micron (2 mu) plasmid in a strain of yeast carrying the nuclear mutation mcm2. This mutation, earlier shown to affect the maintenance of yeast minichromosomes in an ARS-dependent manner, also affected the copy number of the 2 mu plasmid. The effect was more pronounced at 35 degrees C leading to the elimination of the plasmid from the cells cultured at this temperature. The mutant cells could be efficiently cured of the circle by transformation with 2 mu ORI-carrying hybrid vectors, an observation consistent with the low copy number of the endogenous plasmid. A chromosomal revertant of this mutant for another ARS(ARS1) was found also to confer stability on the 2 mu ORI-carrying minichromosomes and had elevated levels of the endogenous plasmid. The mutation neither affected the segregation nor the amplification process mediated by site-specific recombination at FRT sites requiring the FLP gene-encoded protein action. ARS131C, an ARS that was unaffected in the mutant at 25 degrees C, could elevate the copy number of a 2 mu hybrid vector in the mutant cells. In view of these results, some aspects of segregation and copy number control of the endogeneous plasmid have been discussed. We propose that the mutation impairs the 2 mu ORI function, leading to its loss.

Cell Division↗