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Biomedical subjects

D Mitra

Publications and source records attributed to D Mitra.

At least 19 recordsLinked to original sources
PubMed2001

Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression.

CD28, described as a T cell costimulatory molecule so far, is expressed on human peripheral blood neutrophils, as shown by cell surface staining and immunoprecipitation with anti-CD28 monoclonal antibody, and by reverse transcription PCR. The phorbol 12-myristate 13-acetate-augmented expression of CD28 on these cells can be blocked by actinomycin D, an RNA transcription inhibitor, and staurosporin, a protein kinase inhibitor. Cross-linking of CD28 results in an early increase in IL-8 receptor A (IL-8RA or CXCR-1) expression and a concurrent increase in IL-8-induced chemotaxis. The expression of CXCR-1 is down-regulated by receptor internalization 3 h after CD28 cross-linking with concurrent decrease in IL-8-induced chemotactic migration. Thus, our results demonstrate for the first time that CD28 is expressed on human peripheral blood neutrophils and that CD28 may play an important role in the regulation of IL-8RA expression and migration of neutrophils in response to IL-8.

Adult↗
PubMed2001

Clinical appraisal of Ascaris lumbricoides, with special reference to surgical complications.

Over a period of 4 years (January 1993-December 1997), 509 patients were treated for abdominal colic with or without intestinal obstruction and a history of passage of adult roundworms either in the stool or in vomitus. All patients were below the age of 10 years, the youngest 6 months old, and were treated successfully with antispasmodics and normal saline enemas. When the pain subsided, an anthelminthic drug was given. Of 209 patients admitted to the hospital, 105 responded to conservative management and 104 (50%) required surgical intervention. The procedures included squeezing out of worms, resection and anastomosis, and treatment of other pathologies like acute appendicitis, tubercular stricture of the small intenstine, etc. Five patients died in the postoperative period due to various complications. There were no deaths among those treated by conservative management. Early recognition of the condition can prevent serious surgical complications and morbidity.

Animals↗
PubMed2000

Enhanced expression of a calcium-dependent protein kinase from the moss Funaria hygrometrica under nutritional starvation.

Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss Funaria hygrometrica, a polymerase chain reaction (PCR)-based approach was adopted to clone the gene. Using degenerate PCR primers against conserved regions of CDPKs, a 900 bp amplicon was obtained from the genomic DNA of Funaria. Southern hybridization under low stringency conditions indicated the presence of several CDPK related sequences in the Funaria genome. This observation is consistent with reports of multigene families of CDPKs in other plants. The 900 bp fragment was subsequently used to isolate a 2.2 kb partial genomic clone of the CDPK gene from Funaria. The genomic clone encodes an open reading frame (ORF) of 518 amino acids. Interestingly, unlike other CDPK genes from plants, the entire 1.5 kb ORF is not interrupted by introns. The deduced amino acid sequence of the Funaria gene shows extensive homology with CDPKs from higher plants, 73% identity with the Fragaria CDPK and 71% identity with CDPK isoform 7 of Arabidopsis. Phylogenetic analysis revealed that the Funaria CDPK is closer to the CDPKs from higher plants like strawberry and Arabidopsis as compared to those from lower plants such as the liverwort Marchantia, the green alga Chlamydomonas or another moss Tortula. Northern analysis shows enhanced expression of the CDPK transcript within 24-48 h of starvation for nitrogen, phosphorus or sulphur. So far the only other kinase which is known to be induced by nutrient starvation in plants is the wpk 4 which is a snf-1 related kinase (SnRKs). To our knowledge this is the first report that implicates a CDPK in the starvation response.

Amino Acid Sequence↗
PubMed2000

Congenital hepatoportal arteriovenous fistula: report of a case.

Fistulae between the hepatic artery and portal vein, known as hepatoportal arteriovenous fistula (HPAVF), most commonly occur secondary to trauma or malignancy. Congenital HPAVF is an extremely rare anomaly and only 11 pediatric cases have been documented to date HPAVF causes portal hypertension with the reversal of flow in the portal circulation, leading to hyperemia and congestion of the bowel, causing severe ascites, gastrointestinal bleeding, anemia, and malabsorption. The diagnosis is first made by Doppler sonography, then confirmed by angiography. HPAVF is most effectively treated by performing either ligation of the hepatic artery or percutaneous transcatheter embolization. We describe herein the case of an 8-month-old boy diagnosed to have congenital HPAVF by duplex Doppler sonography and confirmed by digital subtraction angiography, who was successfully managed by percutaneous transcatheter embolization of the feeding right hepatic artery. A review of the previously reported 11 cases of infants with this unusual anomaly, examining presentation, management, and outcome, is also presented.

Arteriovenous Fistula↗
PubMed2000

N-acetylcysteine replenishes glutathione in HIV infection.

BACKGROUND: Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. DESIGN: Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. SUBJECTS: HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. RESULTS: Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. CONCLUSION: NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

Acetylcysteine↗
PubMed2000

The prevalence of vertebral fractures in mild ankylosing spondylitis and their relationship to bone mineral density.

OBJECTIVE: To determine bone mineral density (BMD) in patients with mild ankylosing spondylitis (AS), to establish the prevalence of vertebral fractures and fracture risk in these patients, and to determine the relationship between BMD and vertebral fractures. METHODS: Sixty-six men with mild AS were studied. BMD of the lumbar spine and femoral neck was measured by dual X-ray absorptiometry (DXA) and radiographs of the thoracic and lumbar spine were obtained in all subjects. From the radiographs, vertebral fractures were characterized by a morphometric technique using established criteria. Thirty-nine healthy male subjects aged 50-60 yr, recruited from primary care registers, had spinal radiographs performed and served as controls for vertebral fractures. RESULTS: In patients with AS, BMD was reduced in both the lumbar spine 0.97 (0.1) g/cm(2) [T score -1.10 (1.3), 95% confidence interval (CI) -0.50, +0.14] and femoral neck 0.82 (0.1) g/cm(2) [T score -1.40 (1.2), 95% CI -0.51, +0.09]. There was no correlation between BMD of either the lumbar spine or femoral neck and duration of disease in patients with AS. Eleven of 66 (16.7%) patients with AS had a vertebral fracture, compared with one of 39 (2.6%) controls; odds ratio 5.92 (95% CI 1.4, 23.8). AS patients with fractures were not significantly older (mean age 41.4 vs 37.8 yr, P=0.17), but had significantly longer disease duration (12.4 vs 9.3 yr, P<0.05) than patients without fractures. No significant difference was found in the visual analogue scores for pain in AS patients with fractures compared with those without. No significant correlation was observed between BMD of the lumbar spine or femoral neck and vertebral fractures in patients with AS. In addition, there was no significant difference in the lumbar spine or femoral neck BMD in AS patients with fractures compared with those without. CONCLUSIONS: Spinal and hip osteopenia and vertebral fractures are a feature of mild AS. However, there was no correlation between BMD and vertebral fractures in these patients. AS patients with mild disease had a higher risk of fractures compared with the normal population and this increased with the duration of disease.

Absorptiometry, Photon↗
PubMed1999

Biochemical markers of bone metabolism in mild ankylosing spondylitis and their relationship with bone mineral density and vertebral fractures.

OBJECTIVE: To determine the relationship of biochemical markers of bone metabolism in patients with mild ankylosing spondylitis (AS) with disease activity, bone mineral density (BMD), and vertebral fractures. METHODS: A total of 56 male patients with mild AS were studied. All patients had BMD measured by dual x-ray absorptiometry of the lumbar spine and hip and radiographs of the thoracic and lumbar spines. Radiographs of patients with AS were evaluated morphometrically and vertebral fractures were defined using established criteria. Serum osteocalcin, total and bone alkaline phosphatase (ALP, BALP, respectively), 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), urinary deoxypyridinoline (Dpyr), and pyridinoline (Pyr) were measured in the patients with AS and compared with 52 age and sex matched controls. Thirty-nine healthy male subjects aged 50-60 years, recruited from primary care registers, had spinal radiographs and served as controls for vertebral fractures. RESULTS: Patients with AS had reduced BMD of the lumbar spine, 0.98 (0.1) g/cm2 [T score = -1.14 (1.2) and Z score = -1.01 (1.2)], and femoral neck, 0.83 (0.1) g/cm2 [T score = -1.44 (1.2) and Z score = -0.73 (1.1)]. Of the 56 patients with AS, 11 (19.6%) had a vertebral fracture, whereas only one of 39 control subjects did (2.6%). Patients with AS had significantly lower mean serum osteocalcin compared with controls [9.03 (2.7) microg/l vs 11.05 (2.33) microg/l; p < 0.001], and significantly higher mean serum ALP [73.09 (19.5) U/l vs 53.02 (16.7) U/l; p < 0.001] and BALP [38.54 (9.9) U/l vs 30.35 (8.28) U/l; p < 0.001]. There was no significant difference in the excretion of Dpyr and Pyr between patients with AS and controls [4.90 (3.9) nmol/mmol vs 4.00 (3.6) nmol/mmol, and 15.66 (10.8) nmol/mmol vs 12.24 (10.3) nmol/mmol, respectively]. There were no significant differences in the mean 25-OHD and PTH levels in patients with AS compared to controls [20.03 (1.6) micromol/l vs 18.9 (2.9) micromol/l and 3.31 (1.5) pmol/l vs 2.63 (0.4) pmol/l, respectively]. The biochemical markers of bone formation and resorption correlated well with inflammatory indices of disease activity (acute phase reactants), but not with BMD of the lumbar spine or femoral neck. No significant difference was seen in any marker of bone turnover when AS patients with vertebral fractures were compared with those without. CONCLUSION: Bone turnover in patients with mild AS is characterized by low serum osteocalcin and ALP in the presence of normal calciotropic hormones. Biochemical markers of bone metabolism do not correlate with BMD or vertebral fractures. The disparity between osteocalcin and alkaline phosphatase in patients with AS needs further evaluation.

Adult↗
PubMed1999

Testosterone and testosterone free index in mild ankylosing spondylitis: relationship with bone mineral density and vertebral fractures.

OBJECTIVE: To determine the androgen status of men with mild ankylosing spondylitis (AS) and to evaluate the relationship of sex hormones with bone mineral density (BMD) and vertebral fractures. METHODS: Fifty-six male patients with mild AS were studied. All patients had BMD measured by dual x-ray absorptiometry (DXA) of the lumbar spine and hip, and had radiographs of the thoracic and lumbar spines. Radiographs were evaluated morphometrically, and vertebral fractures were defined using established criteria. Serum total testosterone, sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), and luteininzing hormone (LH) were measured in the patients with AS and 52 age matched controls. Testosterone free index (TFI) was calculated. RESULTS: There was a small, not significant reduction in serum total testosterone in patients with AS compared to controls [16.02 (5.0) vs 21.0 (6.2) nmol/l]. Serum SHBG was significantly lower in patients with AS [27.29 (10.6) vs 35.0 (13.0) nmol/l; p < 0.001] compared to controls. There was no significant difference in the mean TFI between patients and controls [58.7 (21.2) vs 60 (22.2) nmol/l; p > 0.05] or in the levels of LH and FSH. No significant correlation was found between sex hormones, BMD, and vertebral fractures in patients with AS. CONCLUSION: Sex hormones are not altered significantly in patients with mild AS and do not appear to be related to BMD or vertebral fractures. Osteopenia in men with mild AS is therefore unlikely to be secondary to hypogonadism.

Adult↗
PubMed1998

Role of caspases 1 and 3 and Bcl-2-related molecules in endothelial cell apoptosis associated with thrombotic microangiopathies.

We have defined an in vitro model for the study of microvascular endothelial cell (EC) apoptosis mediated by plasma from patients with various forms of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). This system reproduces a variety of histopathologic and ultrastructural features of tissue EC involved in TTP/sporadic HUS, suggesting that apoptotic EC injury is a primary pathophysiologic event in the thrombotic microangiopathies. We now document the ability of tetrapeptide-based inhibitors of interleukin 1beta-converting enzyme (ICE)-like caspase 1 and cysteine protease protein (CPP)-32-like caspase 3, two members of a novel class of cysteine proteases involved in final pathways to apoptosis, to block TTP/sporadic HUS plasma-mediated apoptosis. Overexpression of Bcl-X(L) via gene transfer suppressed this apoptosis by 70%. Transduction of EC with the Bcl-2 homolog A1 had a more limited protective effect. These findings support a role for apoptosis-linked cysteine proteases in the pathophysiology of TTP and sporadic HUS, and raise the possibility that specific apoptosis inhibitors may have a role in the experimental therapeutics of these syndromes.

Apoptosis↗
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↗