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D Mitra

Publications and source records attributed to D Mitra.

At least 19 recordsLinked to original sources

Comparison of image quality, diagnostic confidence and interobserver variability in contrast enhanced MR angiography and 2D time of flight angiography in evaluation of carotid stenosis.

The aim of this study was to compare image quality, level of diagnostic confidence and interobserver agreement in assessment of carotid stenosis with contrast enhanced MR angiography (CE MRA) in comparison with 2D time of flight MR angiography (2D TOF MRA). 60 carotid arteries in 30 patients were examined by three observers. Image quality and diagnostic confidence were assessed on the basis of a visual analogue scale. Interobserver variability was assessed with the help of intraclass correlation coefficient. Median values on the visual analogue scale for image quality and diagnostic confidence were higher for CE MRA compared with 2D TOF MRA for all three observers. Higher intraclass correlation values were recorded for interobserver variability for CE MRA compared with 2D TOF MRA both for visual estimation of carotid stenosis as well as for measurement of carotid stenosis on the basis of North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) criteria. CE MRA provides better image quality, higher level of diagnostic confidence and more interobserver agreement compared with 2D TOF MRA.

Artifacts↗

Correlating sequential homology of Mce1A, Mce2A, Mce3A and Mce4A with their possible functions in mammalian cell entry of Mycobacterium tuberculosis performing homology modeling.

OBJECTIVE: The striking homology of the Mycobacterium tuberculosis mammalian cell entry operons (mce1, mce2, mce3 and mce4) with other mycobacterial species and the proposed role of the mammalian cell entry protein 1A (Mce1A) of M. tuberculosis to facilitate invasion of host cells have led us to look into the finer details of these proteins in order to better understand their structure-function relationship. DESIGN: We performed sequential alignments and secondary structure predictions of Mce1A, Mce2A, Mce3A and Mce4A, and compared these results with results from homology modeling by fold prediction and threading. RESULTS: Sequential alignments showed that Mce1A and Mce2A are highly homologous, close to 70%, while the other combinations gave only about 30% similarities. The major parts of the proteins aligned without gaps and there were striking similarities by secondary structure predictions indicating that the proteins would have similar folds and to be alpha/beta proteins like the previously reported Mce1A model based on Colicin N. Fold prediction showed that the best templates for Mce2A were substrate-binding domain of DnaK and slow processing precursor penicillin acylase from Escherichia coli while the alpha-domains of Mce3A and Mce4A could both be modeled using the cytoplasmic domain of serine chemotaxis receptor as template. CONCLUSION: Although different templates had to be used to model the MceA proteins, functional information may be derived that is relevant for their overall function in M. tuberculosis. The beta-domain is probably involved in binding with the receptors on target cells while the alpha-domain is more likely to be involved in pore formation. As predicted from the folds, Mce3A and Mce4A model structures indicate a lipid bound conformation and therefore may be required in signaling events of the mammalian cell entry process.

Amino Acid Sequence↗

Mitochondrial complex I activity is impaired during HIV-1-induced T-cell apoptosis.

Studies carried out till date to elucidate the pathways involved in HIV-1-induced T-cell depletion has revealed that apoptosis underlie the etiology, however, a clear molecular understanding of HIV-1-induced apoptosis has remained elusive. Although evidences pointing towards the importance of mitochondrial energy generating system in apoptosis exist but it's exact role remains to be clearly understood. Here, we describe for the first time specific downregulation of a complex I subunit NDUFA6 with simultaneous impairment of mitochondrial complex I activity in HIV infection. We also show that NDUFA6 gene silencing induces apoptosis and its overexpression reduces apoptosis in HIV-infected cells. Finally, sensitivity to complex I inhibitor Rotenone is reduced in HIV-1-infected T cells indicating an important role for it in the death process. Our data provide a novel molecular basis as to how the virus might interfere with host cell energy generating system during apoptotic cell death.

Apoptosis↗

Longitudinal study of vertebral type-1 end-plate changes on MR of the lumbar spine.

The purpose of this study was to investigate the temporal evolution of type-1 end-plate changes on MRI in patients with degenerative disease of the lumbar spine and to evaluate whether any correlation exists between such evolution and the change in patients' symptoms. Forty-four patients with 48 Modic type-1 end-plate changes (low TI signal and high T2 signal) were studied. All patients had an initial and a follow-up non-contrast lumbar MRI with variable intervals between the studies (12-72 months). Severity of the end-plate changes was assessed by eyeball estimation. Correlation with patients' symptoms was studied with the help of the Visual Analogue Score (VAS), Oswestry Questionnaire Score (OQS) and patients' subjective assessment. Of the 48 disc levels with type-1 changes, 18 (37.5%) converted fully to type 2 (high T1 signal and intermediate to high T2 signal), 7 (14.6%) partially converted to type 2, 19 (39.6%) became worse (i.e. type 1 changes became more extensive) and 4 (8.3%) showed no change. Higher average VAS (5.7) and OQS (42.3) scores were noted in patients where there was worsening type-1 change and lower scores (3.8 and 27, respectively) were seen in those where there was conversion to type-2 change. These trends, however, did not reach statistical significance (P values 0.16 and 0.09 for VAS and OQS, respectively). The statistical relationship was stronger after exclusion of patients with confounding factors (i.e. changes in lumbar MRI other than end-plate changes that could independently explain the evolution of patients' symptoms) with P-values of 0.08 and 0.07 for VAS and OQS, respectively. Type-1 end-plate change represents a dynamic process and in a large majority of cases either converts to type-2 change or becomes more extensive. The evolution of type-1 change relates to change in patient's symptoms, but not to a statistically significant level.

Adult↗

Longitudinal study of high intensity zones on MR of lumbar intervertebral discs.

AIM: To study the temporal evolution of high intensity zones (HIZ) on MRI in patients with degenerative disease of the lumbar spine, and to evaluate whether any correlation exist between such evolution and in patient's symptoms. MATERIALS AND METHODS: HIZs in the MRI of 56 patients were included in the study. Each Patient had an initial and a follow-up scan performed at various time intervals. Scans were assessed for any change in HIZs by two observers (D. M. and I. W. M.). Patients' symptoms were assessed for by visual analogue score (VAS), the Oswestry Questionnaire Score (OQS) and patients' subjective assessment of change in symptoms. Any MRI feature, apart from HIZs, which could independently explain a patient's change in symptoms, was considered to be a confounding factor. Data were analysed separately in the whole group as well as in the group without confounding factors. RESULTS: On follow-up MRI, HIZs were found to have resolved in 17 lumbar disc levels (26.6%), improved in 9 (14%), worsened in 12 (18.8%) and remained unchanged in 26 (40.6%) at lumbar disc levels. Chi-square testing did not demonstrate any correlation between HIZ changes and evolution of patients' subjective symptoms (p = 0.26 for the whole group; p = 0.07 for the group without confounding factors). Similar lack of meaningful relationship was noted between HIZ changes and the VAS and OQS scores. CONCLUSION: We conclude that HIZs either do not change or improve spontaneously in a large proportion of cases over a period of time. Furthermore, there is no statistical correlation between HIZ changes and change in a patient's symptoms.

Adult↗

Immunodominant B-cell epitope in the Mce1A mammalian cell entry protein of Mycobacterium tuberculosis cross-reacting with glutathione S-transferase.

The TB1-5 76C monoclonal antibody raised against a synthetic 60-mer peptide in the N-terminal part of the Mce1A mammalian cell entry protein of Mycobacterium tuberculosis has previously been shown to react with a linear epitope in the KRRITPKD region, residues 131-138 in Mce1A, and to cross-react with Mce1F. Six additional monoclonal antibodies raised against the same peptide were also shown to cross-react with Mce1F. Four of them reacted with a linear epitope in the same area, indicating that this area is immunodominant but showed distinct differrences in fine specificity. Two monoclonal antibodies did not react with synthetic peptides from this region on the solid phase in enzyme-linked immunosorbent assay, indicating greater influence of conformation on reactivity. None of the monoclonal antibodies reacted with 14-mer synthetic peptides from the corresponding area in Mce2A, Mce3A, Mce4A, M. avium, M. smegmatis or M. leprae. The reaction pattern of the monoclonal antibodies was analysed in relation to our model of the Mce1A molecule (AK Das et al. Biochem Biophys Res Commun 2003;302:442-7). The epitope is located on the surface of Mce1A, at the distal beta-strand-loop region in the beta-domain supporting its potential role in promoting uptake of M. tuberculosis in host cells. Monoclonal antibody TB1-5 19C cross-reacted with glutathione S-transferase of Schistosoma japonicum containing a PKE triplet. Monoclonal antibody TB1-5 76C gave a major band at about 44 kDa in Western blotting of M. tuberculosis sonicate, whereas polyclonal rabbit anti-Mce1A peptide antibodies reacting with the extended TTPKNPTKRRITPKDVI area of Mce1A showed a distinct band above the 160 kDa molecular mass standard.

Amino Acid Sequence↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗