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Biomedical subjects

D Mitra

Publications and source records attributed to D Mitra.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison between two different modes of oxygen therapy during immediate postoperative period following mitral commisurotomy.

Hypoxaemia is a common postoperative problem after thoracotomy. Oxygen therapy with continuous monitoring by pulse oximetry should be a routine practice. This study was conducted to compare the efficacy between nasal cannula and ventimask for post-thoracotomy oxygen supplementation on 20 patients divided into 2 groups of 10 each undergoing closed mitral commisurotomy. The study period was of 5 months duration from March to July, 1996. The mean oxygen saturation remained above 98% in both the groups receiving oxygen either by nasal cannula or ventimask. As there was adequate oxygenation, the cost benefit ratio favours the use of nasal cannula for routine postoperative oxygen supplementation in the closed mitral commisurotomy patients.

Adolescent↗
PubMed1997

Interaction of pregnancy steroid hormones and zidovudine in inhibition of HIV type 1 replication in monocytoid and placental Hofbauer cells: implications for the prevention of maternal-fetal transmission of HIV.

Zidovudine (AZT) has been shown to reduce maternal-fetal transmission of HIV-1 by more than two-thirds in a variety of clinical settings. However, the mechanism of action of AZT in this setting is unclear. Suppression of vertical transmission has occurred in the absence of an impact on maternal plasma viremia and no lower threshold of viral load for such transmission has been identified. We hypothesized that augmentation of the anti-HIV effect of AZT may occur locally, at the maternal-fetal interface. We report that the pregnancy hormone progesterone at broad concentrations has little effect on acute HIV-1 infection of a monocytic cell line or primary peripheral blood cells. However, the combination of physiologic concentrations of progesterone (10[-7] to 10[-6] M) and low-dose AZT (10[-8] to 10[-9] M) produced markedly synergistic inhibition of HIV-1 replication within acutely infected monocytic cell lines (U937), and additive inhibition of HIV-1 growth within chronically infected monocytic cells (U1) and primary placental macrophages (Hofbauer cells). Anti-HIV effects were not seen with another pregnancy steroid hormone, estrogen. In terms of possible mechanisms of action for progesterone, we demonstrated that it incompletely suppressed tat activation of long terminal repeat (LTR)-driven gene expression in monocytic cells. However, the progesterone-mediated suppession of tat activation was not affected by mutation of the three consensus progesterone/androgen/glucocorticoid response elements within the HIV-1 LTR, previously shown by our group to be involved in glucocorticoid-mediated suppression of LTR-driven transcription. It is likely that progesterone suppresses LTR-driven gene expression through a nontranscriptional mechanism, and augments the efficacy of AZT through enhancement of its phosphorylation.

Anti-HIV Agents↗
PubMed1997

Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells.

Thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremic syndrome (HUS) are thrombotic microangiopathies that occur in the absence of an inflammatory response. Ultrastructural features of tissues involved in TTP/sporadic HUS suggest an apoptotic process. Consistent with these findings, we observed that TTP plasmas induce apoptosis in primary human endothelial cells (EC) of dermal microvascular but not umbilical vein origin (Laurence et al, Blood 87:3245, 1996). We now document the ability of plasmas from both TTP and sporadic HUS patients, but not from a patient with childhood/diarrhea-associated HUS, to induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in restricted lineages of microvascular EC. EC of small vessel dermal, renal, and cerebral origin were susceptible to induction of Fas and an apoptotic cell death. In contrast, microvascular EC of pulmonary and hepatic origin, as well as EC of a large vessel, coronary artery, were resistant to both processes. This dichotomy parallels the in vivo pathology of TTP/sporadic HUS, with notable sparing of the pulmonary and hepatic microvasculature. Apoptotic EC also had some features of a procoagulant phenotype, including depressed production of prostaglandin I2 (prostacyclin). These phenomena support the pathophysiologic significance of microvascular EC apoptosis in TTP, extend it to a related disorder (sporadic HUS), and suggest consideration of apoptosis inhibitors in the experimental therapeutics of these syndromes.

Adult↗
PubMed1997

Transfers of food from adults to infants in tufted capuchins (Cebus apella).

This study examined the behavioral mechanisms that support transfer of food from adults to infants in tufted capuchins (Cebus apella). Two captive groups of capuchins were presented with abundant quantities of unshelled pecans or commercial pellets. Five of 11 infant subjects could not open the nuts. A variety of tolerated interactions were initiated by infants toward adults, and food was frequently transferred. All such interactions were more frequent with nuts (a preferred food) than with pellets. Adult capuchins were equally tolerant of infant capuchins that could open nuts and those that could not. Tolerated interactions during feeding could result in acquisition of dietary information by young capuchins or to important, if intermittent, nutritional support.

Aging↗
PubMed1997

Stable human immunodeficiency virus type 1 (HIV-1) resistance in transformed CD4+ monocytic cells treated with multitargeting HIV-1 antisense sequences incorporated into U1 snRNA.

We have approached the development of a human immunodeficiency virus type 1 (HIV-1) therapeutic product by producing immune cells stably resistant to HIV-1. Promonocytic CD4+ cells (U937) were made resistant to HIV-1 by the introduction of a DNA construct (pNDU1A,B,C) that contained three independent antisense sequences directed against two functional regions, transactivation response and tat/rev, of the HIV-1 target. Each sequence was incorporated into the transcribed region of a U1 snRNA gene to generate U1/HIV antisense RNA. Stably transfected cells expressed all three U1/HIV antisense transcripts, and these transcripts accumulated in the nucleus. These cells were subjected to two successive challenges with HIV-1 (BAL strain). The surviving cells showed normal growth characteristics and have retained their CD4+ phenotype. In situ hybridization assays showed that essentially all of the surviving cells produced U1/HIV antisense RNA. No detectable p24 antigen was observed, no syncytium formation was observed, and PCR-amplified HIV gag sequences were not detected. Rechallenge with HIV-1 (IIIB strain) similarly yielded no infection at a relatively high multiplicity of infection. As a further demonstration that the antisense RNA directed against HIV-1 was functioning in these transfected immune cells, Tat-activated expression of chloramphenicol acetyltransferase was shown to be specifically inhibited in cells expressing Tat and transactivation response region antisense sequences.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells.

The pathogenesis of thrombotic thrombocytopenic purpura (TTP) is obscure. It is manifested classically by platelet thrombi and localized microvascular endothelial cell (EC) proliferation, in the absence of an inflammatory response. It is statistically associated with human retroviral disease, but pathological studies of TTP lesions have been unable to establish whether perturbation of the endothelium is a primary or secondary event, irrespective of the presence of retroviral infection. We document that plasma from all of four acute TTP patients, with or without human immunodeficiency virus infection, can induce apoptosis in cultured ECs of microvascular but not large vessel origin. This process was documented by three different methods, (1) laser-illuminated light scatter, (2) quantitation of the pre-G1 Ao peak on DNA histograms and direct visualization of chromatin fragmentation by acridine orange and 4'6-diamidino-2-phenylindole staining, and (3) agarose gel electrophoresis of low molecular weight cellular DNA. Apoptosis was independent of tumor necrosis factor-alpha secretion or the presence of CD36 on microvascular ECs but was linked to the rapid induction of Fas (CD95) on these cells. Soluble anti-Fas antibody, normal plasma depleted of cryoprecipitate, and low concentrations (< or = 0.1 micromol/L) of aurintricarboxylic acid were capable of suppressing TPP plasma-mediated EC apoptosis. In conclusion, microvascular EC apoptosis may be of pathophysiological importance in TTP may be susceptible to interruption by blockade of initiating signals for, or final common enzyme pathways leading to, programmed cell death.

Acridine Orange↗
PubMed1996

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors.

Adult↗
PubMed1996

HIV-1 upregulates Fas ligand expression in CD4+ T cells in vitro and in vivo: association with Fas-mediated apoptosis and modulation by aurintricarboxylic acid.

CD4+ T-lymphocyte apoptosis has been associated with human immunodeficiency virus (HIV)-1 infection in vitro, paralleling the expression of Fas (APO-1, CD95) on peripheral blood mononuclear cells from patients with HIV disease. However, the link between Fas induction, T-cell activation, and cell death is unclear. We document, for the first time, marked upregulation of expression of mRNA for the ligand for Fas in peripheral blood mononuclear cells from HIV seropositive individuals, and demonstrate the ability of HIV infection to induce such expression in CD4+ T cells in vitro. We also define the relevance of this expression to HIV-mediated CD4+ T cell death. Our ability to downregulate Fas ligand message and suppress HIV-mediated apoptosis with aurintricarboxylic acid, a clinically used protease inhibitor with known activity against programmed cell death in other systems, may open up a new area of therapy for HIV infection.

Apoptosis↗
PubMed1995

Role of glucocorticoid receptor binding sites in the human immunodeficiency virus type 1 long terminal repeat in steroid-mediated suppression of HIV gene expression.

Dexamethasone inhibited human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR)-directed gene expression in cells of T and B lymphoblastoid lineages, but not in monocytic cells. Suppression required an intact glucocorticoid receptor (GR), as it was amplified by transfection of lymphocytes with a plasmid encoding the human GR and blocked by the receptor antagonist RU486. These results were in direct contrast to the effects of dexamethasone on a murine leukemia retrovirus promoter where, consistent with the findings of others, activation of gene expression was obtained. Potential regions of the HIV-1 LTR mediating these effects were sought, with sequence homologies predicting two new glucocorticoid response element half-sites, GRE-II (nucleotides -6 to -1) and GRE-III (+ 15 to + 20), downstream from a previously identified GR DNA binding domain, GRE-I (-264 to -259). Mutational analyses documented the loss of inhibitory activity attendant on changes in GRE-III and the independence of steroid-mediated effects from GRE-I and GRE-II. Consistent with these findings, electrophoretic mobility shift assays revealed a difference in binding of cellular factors to GRE-III in cells of T and B lymphocyte vs. monocytic lineages. Binding sites for the cellular transcription factor leader binding protein (LBP-1) were found to overlap with GRE-III, and LBP-1 interacted with this element in the HIV LTR only in T and B lymphocytic extracts. We hypothesize that GRE-III sequence-specific effects, including modulation of LBP-GR interactions, underlie the negative regulatory effect of glucocorticoids on HIV-1 gene expression, with some specificity for cell type.

Base Sequence↗
PubMed1995

Quantitative comparison of Acanthamoeba castellanii adherence to rigid versus soft contact lenses.

We evaluated quantitative differences in adherence of Acanthamoeba castellanii trophozoites and cysts to new unworn contact lenses as a function of contact lens type and duration of exposure. Daily wear soft (polymacon), disposable soft (etafilcon A), rigid gas permeable (RGP) (siloxane acrylate), and polymethylmethacrylate (PMMA) contact lenses were exposed to 1 x 10(5)/mL log phase A. castellanii (trophozoite:cyst ratio 90:10) for 10 seconds, 30 minutes, 60 minutes, and 120 minutes. The number of adherent organisms was determined by light microscopy and confirmed by scanning electron microscopy. Rates of cyst adherence were similar among contact lens types. We observed significantly greater adherence of trophozoites to RGP and PMMA lenses compared with soft contact lenses (P < 0.05). This difference in trophozoite adherence was significant at all four time periods (P < 0.05). Our findings show that A. castellanii trophozoites and cysts adhere to both soft and rigid contact lens types. We also found that although trophozoite adherence increases as a function of duration of exposure, adherent organisms were observed with exposure times as brief as 10 seconds. This suggests that all contact lens types may be at risk for Acanthamoeba attachment and that even minimal exposure times may be sufficient for lens contamination.

Acanthamoeba↗
PubMed1995

Prognostic factors in intracerebral haemorrhage.

In a prospective study, the prognostic value of clinical characteristics and CT scan findings in 50 patients of intracerebral haemorrhage (ICH) has been examined. Follow up has been done over 6 months period. Each patient has been individually followed up for 8 weeks. At the end of the follow up period 34% of the patients died, 36% were dependent on outside help for daily living while 30% were capable of independent existence. Age of more than 60 yrs, Glasgow Coma Scale (GCS) Score of 6 or less (in a modified Scale of 10) at the time of admission, ICH volume greater than 30 ml., midline shift in CT scan of more than 3 mm and presence of intraventricular haemorrhage (IVH) and hydrocephalus had an adverse impact on outcome. Young age, GCS score of more than 8, ICH volume of less than 20 ml, presence of lobar haemorrhage and absence of IVH/hydrocephalus were associated with relatively favourable outcome.

Activities of Daily Living↗
PubMed1994

Impaired glucocorticoid induction of mononuclear leukocyte lipocortin-1 in rheumatoid arthritis.

OBJECTIVE: To investigate leukocyte lipocortin-1 production in rheumatoid arthritis (RA). METHODS: Eight control and 8 RA subjects received 100 mg hydrocortisone intravenously. Leukocyte lipocortin-1 was measured by enzyme-linked immunosorbent assay. RESULTS: Hydrocortisone induced significant increases in lipocortin-1 production by control mononuclear cells (MNC) (P = 0.006 versus baseline) but not by RA MNC (P = 0.44 versus baseline). Peak lipocortin-1 levels in control MNC were significantly higher than those in RA MNC (P = 0.014). CONCLUSION: These results indicate that glucocorticoid-induced MNC lipocortin-1 production is impaired in RA.

Annexins↗
PubMed1994

Identification of a novel cell-type and context specific enhancer within the negative regulatory element of the human immunodeficiency virus type 1 long terminal repeat.

One segment of the negative regulatory region of the human immunodeficiency virus long terminal repeat (HIV-LTR), nucleotides -273 to -255, is homologous to positive response elements for interleukin-2 and glucocorticoids. We demonstrate that this sequence, referred to as purine-rich response element (PRRE), acts as a classic enhancer in the context of a heterologous promoter, but serves as a functional repressor in the intact provirus, binding (a) cellular factor(s). These data suggest that certain DNA response elements in the HIV LTR serve as negative regulators only in the context of the intact LTR, presumably through interactions with other transcriptional factors, a phenomenon that might be exploited to interfere with viral gene transcription.

Base Sequence↗
PubMed1994

Clinical and histological features of 'mechanic's hands' in a patient with antibodies to Jo-1--a case report.

The clinical and histological features of 'mechanic's hands' are described in a patient with polymyositis characterized serologically by antibodies to histidyl tRNA synthetase (Jo-1). Although described in the past in association with polymyositis, these distinctive cutaneous lesions have only recently been associated with the 'anti-synthetase syndrome'. It is becoming apparent that recognition of subsets within the spectrum of polymyositis/dermatomyositis characterized by certain clinical and serological features not only have prognostic significance, but also may provide insights into mechanisms of disease.

Aged↗
PubMed1993

The effect of diffusion on two predators exploiting a resource.

This paper deals with the stabilizing effect of diffusion on a system of a living resource supporting two noncompeting predators. It is shown that while the three species mathematical model without diffusion is unstable, the model with diffusion is asymptotically stable provided the diffusion coefficient of the resource exceeds a certain threshold value.

Animals↗