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Biomedical subjects

A Seth

Publications and source records attributed to A Seth.

At least 19 recordsLinked to original sources
PubMed2007

Bioconversion of butyronitrile to butyramide using whole cells of Rhodococcus rhodochrous PA-34.

Butyramide is an important chemical commodity, which is used for the synthesis of hydroxamic acids and electrorheological fluids and for the preparation of beta-amodoorganotin compounds. The nitrile hydratase (Nhase) of Rhodococcus rhodochrous PA-34 catalyzed the conversion of butyronitrile to butyramide. The maximum Nhase activity [18 U/mg dry cell weight (dcw)] of whole cells of R. rhodochrous PA-34 was observed at pH 7.0 with 10% (v/v) butyronitrile and 1 mg cells (dcw)/ml reaction mixture at 10 degrees C. The cells of R. rhodochrous PA-34 retained almost 50% activity when incubated for 1 h in the presence of 85% (v/v) butyronitrile. A yield of 597 g of butyramide (6.8 M) was obtained using 60% (v/v) butyronitrile, 1 g cells (dry weight) in a 1-l batch reaction at 10 degrees C for 6 h.

Amides↗
PubMed2006

Transvaginal repair of a vesico-vaginal fistula using a mobilised vaginal flap to form the bladder base: a case report.

We describe a case of a vesico-vaginal fistula in a 32-year-old lady presenting with true urinary incontinence. There was a 1.5 x 1.5 cm deficit in the bladder wall and the left ureteric orifice was very close to the edge of the defect. For a successful transvaginal repair, we used a mobilized vaginal flap to bridge the defect in the bladder wall. This avoided the mobilization of the bladder wall and also prevented the left ureteric orifice from getting entrapped in the suture line. Adjacent wall of vagina was mobilized and stitched over the first layer to achieve water tight repair. Her post operative period was uneventful. The repair healed well and she was discharged in a good condition.

Adult↗
PubMed2006

Tracheal stenosis diagnosed on pulmonary ventilation/perfusion scan.

A 68-year-old woman, who had undergone coronary artery bypass surgery 5 months previously, was presented with cough, breathlessness and an elevated D-dimer. She was initially thought to have suffered a pulmonary embolus. A ventilation/perfusion scan demonstrated tracheal stenosis, which required dilation and endobronchial stent deployment. Tracheal stenosis is a well-recognised complication of endotracheal intubation; however, the onset of symptoms is often insidious and the diagnosis delayed.

Journal Article↗
PubMed2006

Berardinelli-Seip congenital lipodystrophy.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare genetic disorder characterized by lipoatrophy, hypertriglyceridemia, hepatomegaly and acromegaloid features. On the basis of mutational and haplotype analysis, BSCL families have been classified into three types BSCL 1, BSCL2 and BSCLX. We report Berardinelli-Seip congenital lipodystrophy (BSCL2 type) in three subjects from two unrelated Indian families (family1 and family2). The mutation (c.IVS2 11 A GT G ) found in affected members of family1 is a newly identified mutation. We also report the association of renal anomaly with this new mutation.

Child, Preschool↗
PubMed2005

Mechanical force activates eIF-2alpha phospho-kinases in fibroblast.

Mechanical forces can induce differentiation of fibroblasts into myofibroblasts, a process which requires activation of the MAP kinase p38. Currently, the identification of other phospho-kinases involved in myofibroblast differentiation has not been explored. We applied static tensile forces to rat cardiac fibroblasts via collagen-coated magnetite beads and examined activation of protein phospho-kinases by the Kinexus phospho-antibody screening system. Of 75 candidate protein kinases screened, 39 were detected and, of these, 31 phospho-kinases were analyzed. Following force application, 12 out of 31 phospho-kinases exhibited increases of phosphorylation including PKR (>4-fold), MKK3 (3-fold), MKK6 ( approximately 2-fold), and p38 ( approximately 2-fold). In several types of mechanically sensitive, contractile fibroblasts including rat cardiac, human gingival, and Rat-2 fibroblasts, tensile forces increased eIF-2alpha phosphorylation, a downstream effector of PKR. We conclude that phospho-antibody screening is an efficient method for discovery of novel mechanical force-induced phospho-kinases and force can activate eIF-2alpha phospho-kinases in fibroblasts.

Animals↗
PubMed2005

Can propofol precipitate pancreatitis in patients with Cushing's syndrome?

We encountered two cases of acute pancreatitis in patients with Cushing's disease following transnasal transsphenoidal hypophysectomy. In both cases propofol was used in bolus doses, and is thought to be the probable factor for its development. Since elevated cortisol levels in Cushing's disease poses a threat for pancreatitis, there is a possibility that patients with Cushing's disease might be more prone to acute pancreatitis following propofol administration. Anaesthesiologists and physicians dealing with the management of Cushing's disease need to be aware of this possibility.

Acute Disease↗
PubMed2004

Traumatic abdominal wall hernia: a reappraisal.

Traumatic abdominal wall hernia, a rare cause of hernia, has a confusing clinical picture and requires a high index of suspicion for prompt diagnosis and management. Such hernias, if missed, can result in high morbidity and may prove fatal. Distinction from a pre-existing hernia is important as well. We report our experience in two such cases, which had presented in a span of 9 months, and submit a brief analysis of 50 reviewed cases.

Abdominal Injuries↗
PubMed2004

Epidermal growth factor prevents acetaldehyde-induced paracellular permeability in Caco-2 cell monolayer.

BACKGROUND: Intestinal permeability and endotoxemia play a crucial role in the pathogenesis of alcoholic liver disease. Previous studies showed that acetaldehyde disrupts intestinal epithelial barrier function and increases paracellular permeability by a tyrosine kinase-dependent mechanism. In the present study, the role of epidermal growth factor (EGF) in protection of epithelial barrier function from acetaldehyde was evaluated in Caco-2 intestinal epithelial cell monolayer. METHODS: Caco-2 cells on Transwell inserts were exposed to acetaldehyde in the absence or presence of EGF, and the paracellular permeability was evaluated by measuring transepithelial electrical resistance and unidirectional flux of inulin. Integrity of epithelial tight junctions and adherens junctions was analyzed by confocal immunofluorescence microscopy and immunoblot analysis of occludin, zonula occludens (ZO)-1, E-cadherin, and beta-catenin in the actin cytoskeleton. Reorganization of actin cytoskeletal architecture was examined by confocal microscopy. RESULTS: Acetaldehyde increased paracellular permeability to inulin and lipopolysaccharide, and EGF significantly reduced these effects of acetaldehyde in a time- and dose-dependent manner. EGF prevented acetaldehyde-induced reorganization of occludin, ZO-1, E-cadherin, and beta-catenin from the cellular junctions to the intracellular compartments. Acetaldehyde treatment induced a reorganization of actin cytoskeletal network and reduced the levels of occludin, ZO-1, E-cadherin, and beta-catenin associated with the actin cytoskeleton. EGF effectively prevented acetaldehyde-induced reorganization of actin cytoskeleton and the interaction of occludin, ZO-1, E-cadherin, and beta-catenin with the actin cytoskeleton. CONCLUSION: These results indicate that EGF attenuates acetaldehyde-induced disruption of tight junctions and adherens junctions and prevents acetaldehyde-induced reorganization of actin cytoskeleton and its interaction with occludin, ZO-1, E-cadherin, and beta-catenin.

Acetaldehyde↗
PubMed2004

Computer based receptogram approach: an objective way of assessing immunohistochemistry of androgen receptor staining and its correlation with hormonal response in metastatic carcinoma of prostate.

AIMS: To categorise the immunostaining heterogeneity of androgen receptors in metastatic carcinoma of the prostate using a pattern oriented approach and to correlate the results with response to hormonal treatment. METHODS: Paraffin wax embedded tumour sections from 85 patients with metastatic carcinoma of the prostate were processed for immunocytochemistry and stained for the androgen receptor using antiandrogen receptor antibodies. A computer based image analysis system was used to analyse the pattern of nuclear immunostaining in a minimum of 500 nuclei/slide. Depending on the nuclear receptor content and concentration, receptogram patterns were established for each specimen. The receptogram pattern was correlated with clinical response to hormonal treatment. RESULTS: Clinical response to hormonal treatment was documented using prostate specific antigen as the marker into responders (good, fair, stable) and non-responders. Forty four of 48 patients who responded to hormonal treatment had type 1 (35) or type 3 (nine) receptograms, which are characterised by a unimodal peak or multimodal peaks within a narrow concentration range. Thirteen of the 18 patients who stabilised had type 1 or type 3 receptograms. Seventeen of the 19 patients who did not respond to hormonal treatment had either type 2 or type 4 receptograms, which are characterised by skewed or bimodal androgen receptor distribution. Positive and negative predictive values of receptograms were 96.5% and 63%, respectively. CONCLUSIONS: Image analysis of androgen receptor immunostaining with a receptogram oriented approach provides important prognostic information that can be used to predict response to hormone treatment in patients with metastatic carcinoma of the prostate.

Aged↗
PubMed2004

Recent Advances in Alcoholic Liver Disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease.

A significant body of evidence indicates that endotoxemia and endotoxin-mediated hepatocellular damage play a crucial role in the pathogenesis of alcoholic liver disease. A close correlation between endotoxemia and the severity of alcohol-induced liver injury is supported by a number of clinical and experimental studies. Elevated intestinal permeability appears to be the major factor involved in the mechanism of alcoholic endotoxemia and the pathogenesis of alcoholic liver disease. Ethanol and its metabolic derivatives, acetaldehyde in particular, alter intracellular signal-transduction pathways leading to the disruption of epithelial tight junctions and an increase in paracellular permeability to macromolecules. Studies addressing the mechanisms of such epithelial disruption and the protective factors that prevent ethanol and acetaldehyde-mediated disruption of epithelial tight junctions are critically important in the investigations toward the search of preventive and therapeutic strategies for alcoholic liver disease.

Animals↗
PubMed2004

L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer.

Role of L-glutamine in the protection of intestinal epithelium from acetaldehyde-induced disruption of barrier function was evaluated in Caco-2 cell monolayer. L-Glutamine reduced the acetaldehyde-induced decrease in transepithelilal electrical resistance and increase in permeability to inulin and lipopolysaccharide in a time- and dose-dependent manner; d-glutamine, L-aspargine, L-arginine, L-lysine, or L-alanine produced no significant protection. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine failed to affect the L-glutamine-mediated protection of barrier function. L-Glutamine reduced the acetaldehyde-induced redistribution of occludin, zonula occludens-1 (ZO-1), E-cadherin, and beta-catenin from the intercellular junctions. Acetaldehyde dissociates occludin, ZO-1, E-cadherin, and beta-catenin from the actin cytoskeleton, and this effect was reduced by L-glutamine. L-Glutamine induced a rapid increase in the tyrosine phosphorylation of EGF receptor, and the protective effect of L-glutamine was prevented by AG1478, the EGF-receptor tyrosine kinase inhibitor. These results indicate that L-glutamine prevents acetaldehyde-induced disruption of the tight junction and increase in the paracellular permeability in Caco-2 cell monolayer by an EGF receptor-dependent mechanism.

Acetaldehyde↗
PubMed2004

Impact of imaging and thrombus level in management of renal cell carcinoma extending to veins.

OBJECTIVES: To evaluate the role of newer imaging modalities in the diagnosis and evaluation of management according to extent of renal vein (RV) or inferior vena cava (IVC) thrombi in patients with renal cell carcinoma. MATERIAL AND METHODS: Fifty-nine patients with renal cell carcinoma and tumor thrombus extension into the RV or IVC were studied. Diagnosis was based on contrast-enhanced CT, magnetic resonance imaging or color-Doppler ultrasonography. Surgical treatment was contemplated in 42 suitable patients and complete resection could be done in all but 3 cases. RESULTS: There were 48 males and 11 females with mean age of 51.8 years. Isolated RV involvement was seen in 27 cases whereas IVC extension was present in 32 cases. The thrombus extent was infrahepatic in 62.5% (20/32) patients with IVC extension. With the newer imaging modalities like contrast-enhanced CT, color-Doppler ultrasound and/or magnetic resonance imaging, correct diagnosis of the extent of the thrombus was possible in 95% of the patients. The accuracy of color-Doppler ultrasound was same as magnetic resonance imaging in the evaluation of the extent of the thrombus. In the present series a median follow-up of 4 years revealed a high incidence of local and distant recurrences and decreased survival in patients presenting with advanced disease, who had venous wall invasion. CONCLUSIONS: The extent of RV or IVC thrombi can be accurately diagnosed with contrast-enhanced CT scan and in case of doubt color-Doppler ultrasound is a good alternative to magnetic resonance imaging. Management can be planned according to the level of the tumor thrombus. Invasion of the venous wall was found to be a bad prognostic factor affecting survival.

Adult↗
PubMed2004

Characterisation of materials causing discolouration in potable water systems.

Discoloured water is one of the main causes of customer complaints received by UK water suppliers. Flushing is recognised as a means of preventing red water events by mobilising material with the potential to cause discolouration. The understanding of the mechanisms and materials causing discolouration is limited. It is therefore necessary to characterise the materials mobilised by flushing, which are responsible for discolouration. The University of Sheffield and two UK water companies embarked on an in-depth programme of monitoring mains flushing. The programme involves collecting discrete samples during flushing of pipes of differing materials, diameters, age, source water and hydraulic regime. The results show iron to be the dominant material mobilised irrespective of pipe material. All samples indicate a direct correlation between turbidity, iron and manganese, and to a lesser extent with metals lead, copper, aluminium and zinc. Concentration of metals mobilised is independent of pipe material, diameter or age.

Color↗
PubMed2003

The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase.

The breast cancer-associated T2A10 clone was originally isolated from a cDNA library enriched for tumour messenger ribonucleic acids. Our survey of 125 microarrayed primary tumour tissues using affinity purified polyclonal antibodies has revealed that corresponding protein is overexpressed in invasive breast cancer and is weakly expressed in kidney and prostate tumours. Now known as RNF11, the gene encodes a RING-H2 domain and a PY motif, both of which mediate protein-protein interactions. In particular, the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFbeta receptor complex. Using various mutants of RNF11 in GST pulldown and immunoprecipitation assays, we found that RNF11 interacts with Smurf2 through the PY motif, leading to ubiquitination of both proteins. Smurf2 plays an active role in the repression of TGFbeta signalling, and our data indicate that overexpression of RNF11, through its interaction with Smurf2, can restore TGFbeta responsiveness in transfected cells.

Breast Neoplasms↗
PubMed2003

Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts.

The myocardium responds to chronic pressure or volume overload by activation and proliferation of cardiac fibroblasts and their differentiation into myofibroblasts. Because alpha-smooth muscle actin (SMA) expression is the classical marker for myofibroblast differentiation, we examined force-induced SMA expression and regulation by specific MAPK pathways. Rat cardiac fibroblasts were separated from myocytes and smooth muscle cells, cultured, and phenotyped by using the presence of SMA, vimentin, and ED-A fibronectin and the absence of desmin as myofibroblast markers. Static tensile forces (0.65 pN/microm2) were applied to fibroblasts via collagen-coated magnetite beads. In neonatal cardiac fibroblasts cultured for 1 day, immunostaining and Western and Northern blotting showed very low basal levels of SMA. After the application of force, there were 1.5- to 2-fold increases of SMA protein and mRNA within 4 h. Force-induced SMA expression was dependent on ERK phosphorylation and on intact actin filaments. In contrast to cells cultured for 1 day, cells grown for 3 days on rigid substrates showed prominent stress fibers and high basal levels of SMA, which were reduced by 32% within 4 h after force application. ERK was not activated by force, but p38 phosphorylation was required for force-induced inhibition of SMA expression. These results indicate that mechanical force-induced regulation of SMA content is dependent on myofibroblast differentiation and by selective activation of MAPKs.

Actins↗
PubMed2003

ETS2 overexpression in transgenic models and in Down syndrome predisposes to apoptosis via the p53 pathway.

ETS2 is a transcription factor encoded by a gene on human chromosome 21 and alterations in its expression have been implicated in the pathophysiological features of Down syndrome (DS). This study demonstrates that overexpression of ETS2 results in apoptosis. This is shown in a number of circumstances, including ETS2-overexpressing transgenic mice and cell lines and in cells from subjects with DS. Indeed we report for the first time that the ETS2 overexpression transgenic mouse develops a smaller thymus and lymphocyte abnormalities similar to that observed in DS. In all circumstances of ETS2 overexpression, the increased apoptosis correlated with increased p53 and alterations in downstream factors in the p53 pathway. In the human HeLa cancer cell line, transfection with functional p53 enables ETS2 overexpression to induce apoptosis. Furthermore, crossing the ETS2 transgenic mice with p53(-/-) mice genetically rescued the thymic apoptosis phenotype. Therefore, we conclude that overexpression of human chromosome 21-encoded ETS2 induces apoptosis that is dependent on p53. These results have important consequences for understanding DS and oncogenesis and may provide new insights into therapeutic interventions.

Animals↗
PubMed2003

Impact of primary tumour characteristics on the survival of patients with lymph node metastases in bladder cancer following radical cystectomy.

BACKGROUND AND OBJECTIVE: Patients with carcinoma urinary bladder with metastasis to the lymph nodes have been believed to have a poor prognosis. The various factors affecting survival in this subset of patients are not well understood. To analyze, these factors, we retrospectively analyzed patients who had undergone radical cystectomy at our center in the last 10 years. METHODS: From Jan. 1991 to May 2001, 158 patients underwent radical cystectomy at our center. 38 of these were found to have metastasis in the regional lymph nodes (i.e. stage D). A multivariate regression analysis was done to look for factors, which predict a better survival in this group of patients. Patients were studied for age, sex, morphology of tumour (papillary or nodular), grade of tumour, local extent of the disease (T1 T3A OR T3B), lymph nodal involvement, chemotherapy (whether received or not) and no. of TUR resection before radical cystectomy. SPSS software was used and the actuarial disease specific survival calculated for each variable. RESULTS: There were 33 males and 5 females with an age range of 34-75 years (mean 56). Overall survival was 7 months to 84 months with mean of 32 months. Patients with polypoidal disease had better survival (66 months vs 15 months). Also patients with organ-confined disease (T2, T3a) had better survival than those with perivesical spread (T3b). The mean survival in N1 and N2 disease was 36 and 10 months respectively. The benefits of adjuvant chemotherapy (methotrexate and cisplatin) could not be assessed as most of the patients received chemotherapy. CONCLUSION: Patients with positive lymph nodes for metastases have fairly good survival with radical cystectomy especially those who have a lower T stage (organ confined), papillary morphology and N1 disease.

Adult↗