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Biomedical subjects

N Prasad

Publications and source records attributed to N Prasad.

At least 19 recordsLinked to original sources

Focal nodular hyperplasia-like areas in cirrhosis.

AIMS: Focal nodular hyperplasia-like lesions have rarely been described in cirrhotic livers. We describe five cases of such lesions. METHODS AND RESULTS: Between 1998 and 2001, 146 liver transplants were performed at the Royal Free Hospital for cirrhosis of the liver. Nodular lesions identified in the livers removed at transplantation were defined histologically according to the International Working Party classification (Hepatology 1995; 22; 983). They were present in 63 of these livers, as follows: 36 dysplastic nodules, 121 macroregenerative nodules, and 71 hepatocellular carcinomas. In five patients, an additional 12 nodules (size range 4-23 mm, median 10.5 mm) showed histological features suggestive of focal nodular hyperplasia including mildly inflamed vascular fibrous septa, and ductular proliferation. Pre-transplantation imaging showed features suspicious for hepatocellular carcinoma, in three of these lesions (12, 23 and 23 mm diameter) from two different patients. These lesions were histologically indistinguishable from focal nodular hyperplasia occurring in non-cirrhotic livers, with fibrous scars and septa which contained vascular and ductular structures. CONCLUSIONS: It is important to recognize that these lesions may occur in the context of cirrhosis and that they should be considered in the differential diagnosis with hepatocellular carcinoma, dysplastic nodules and macroregenerative nodules.

Adult↗

Adenocarcinoma of the colon as a second malignancy in a child.

Solid tumors as second malignancies are not common in children who have been managed for lymphoproliferative disorders. We report a case of adenocarcinoma (AC) of the colon as a second malignancy in a patient who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL). In children, primary AC of the colon is very rare; colonic AC occurring as a second malignancy in a child is rarer still. A case of AC of the colon following chemotherapy for ALL has not yet been published.

Adenocarcinoma↗

SH2-containing inositol 5'-phosphatase SHIP2 associates with the p130(Cas) adapter protein and regulates cellular adhesion and spreading.

In a previous study, we found that the SHIP2 protein became tyrosine phosphorylated and associated with the Shc adapter protein in response to the treatment of cells with growth factors and insulin (T. Habib, J. A. Hejna, R. E. Moses, and S. J. Decker, J. Biol. Chem. 273:18605-18609, 1998). We describe here a novel interaction between SHIP2 and the p130(Cas) adapter protein, a mediator of actin cytoskeleton organization. SHIP2 and p130(Cas) association was detected in anti-SHIP2 immunoprecipitates from several cell types. Reattachment of trypsinized cells stimulated tyrosine phosphorylation of SHIP2 and increased the formation of a complex containing SHIP2 and a faster-migrating tyrosine-phosphorylated form of p130(Cas). The faster-migrating form of p130(Cas) was no longer recognized by antibodies to the amino terminus of p130(Cas) and appeared to be generated through proteolysis. Interaction of the SHIP2 protein with the various forms of p130(Cas) was mediated primarily through the SH2 domain of SHIP2. Immunofluorescence studies indicated that SHIP2 localized to focal contacts and to lamellipodia. Increased adhesion was observed in HeLa cells transiently expressing exogenous WT-SHIP2. These effects were not seen with SHIP2 possessing a mutation in the SH2 domain (R47G). Transfection of a catalytic domain deletion mutant of SHIP2 (DeltaRV) inhibited cell spreading. Taken together, our studies suggest an important role for SHIP2 in adhesion and spreading.

Cell Adhesion↗

Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells.

Nm23-H1 and nm23-H2 are putative metastasis suppressor genes that encode nucleoside diphosphate kinase (NDPK) A and B. NDPKs form oligomers distributed between soluble and particulate fractions of cells and therefore may exert their effects as either soluble or bound proteins. To determine whether metastasis-related functions of NDPKs are mediated by their catalytic activity in membrane bound or soluble complexes, we have stably transfected highly metastatic human melanoma Line IV Cl 1 cells with wild-type and catalytically inactive (H118Y) nm23-H1 and nm23-H2 genes and assayed their metastatic potential in nude mice. Transfection with wild-type nm23-H1 and nm23-H2 genes and catalytically inactive nm23-H1 did not significantly (all p > 0.10) alter the metastatic potential of Line IV Cl 1 cells while transfection with catalytically inactive nm23-H2 significantly (p < 0.01) reduced their metastatic potential. The lack of effect of transfection with wild-type and catalytically inactive nm23-H1 suggests that neither soluble nor membrane bound NDPK A affect the metastatic potential of Line IV Cl 1 cells. The metastasis suppressive effect of catalytically inactive NDPK B overexpression suggests that competition with bound complexes containing catalytically active NDPK B inhibits metastasis of Line IV Cl 1 cells. These results imply that bound NDPK B promotes metastasis and suggest that inhibition of its function or of its binding to critical sites may be a useful approach to limit the development of metastases in human melanoma.

Amino Acid Substitution↗

Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 (PDK1).

Phosphoinositide-dependent kinase (PDK1) regulates a number of pathways involved in responses to stress and in growth factor signaling; however, little is known concerning the mechanisms governing the activity of PDK1. In this report, we find that oxidative stress (H(2)O(2)) and vanadate induce tyrosine phosphorylation of PDK1. These effects of H(2)O(2) and vanadate were found in 293T cells and CH310T1/2 cells expressing exogenous PDK1 and in A20 lymphoma cells expressing endogenous PDK1. Exogenously expressed PDK1 was also tyrosine-phosphorylated in response to NGF treatment of 293T expressing TrkA. H(2)O(2) induced a more rapid tyrosine phosphorylation of PDK1 relative to vanadate, and only vanadate-induced tyrosine phosphorylation of PDK1 was sensitive to pretreatment of cells with wortmannin. In vitro, PDK1 could be tyrosine-phosphorylated by both the c-Src and Abl tyrosine kinases. Both H(2)O(2) and vanadate treatments increased the activity of PDK1 when the serum/glucocorticoid regulated kinase (SGK) was used as substrate. Vanadate treatment appeared to bypass the requirement for phosphatidylinositol 3,4,5-trisphosphate when Akt was used as substrate for PDK1. Tyrosine phosphorylation of PDK1 by the Abl tyrosine kinase also increased the activity of PDK1 toward SGK and Akt. These data suggest a novel mechanism through which PDK1 activity may be regulated.

3-Phosphoinositide-Dependent Protein Kinases↗

Comparative evaluation of early vs. deferred vitrectomy in Eales' disease.

METHODS: 40 cases of vitreous haemorrhage secondary to Eales' disease were taken up for vitrectomy. Depending upon duration of vitreous haemorrhage patients were divided into two groups: Group I (20 eyes) - early vitrectomy group with duration between 3-6 months; Group II (20 eyes) - deferred vitrectomy group with duration of more than 6 months. All patients were followed up for a minimum period of 3 months following vitrectomy. RESULTS: Eyes in Group I showing a preoperative ultrasonic picture of complete posterior vitreous detachment, less mobility of organised vitreous haemorrhage and mid vitreous organisation on kinetic echography achieved a final visual acuity of 6/9 or better in 13 (65%) eyes as compared to 4 (20%) eyes in Group II (p<0.01). Poor visual outcome in the deferred group was secondary to cystoid macular oedema, macular scar, macular pucker formation and macular degeneration. CONCLUSION: Improved visual outcome in the early vitrectomy group was probably because the haemorrhagic blood and its toxic products had less time to damage the macula, a lesser incidence of macular traction and cystoid macular oedema.

Humans↗

Craniofacial asymmetry and temporomandibular joint internal derangement in female adolescents: a posteroanterior cephalometric study.

Unilateral or bilateral pathology of the osseous components of the temporomandibular joint (TMJ) can result in pronounced facial asymmetry because of dissimilar size and shape of the right and left sides of the mandible. To date, it is unknown whether abnormalities of the soft tissues of the TMJ are associated with greater than normal craniofacial asymmetry. In this study, we investigated the amount of craniofacial asymmetry in female orthodontic patients with unilateral or bilateral TMJ internal derangement (TMJ ID) relative to the amount in female patients without TMJ ID. The total sample consisted of 80 female adolescents. Bilateral TMJ magnetic resonance images were used as a database for objectively scoring the severity of TMJ ID. Craniofacial asymmetry was measured from posteroanterior cephalograms. Females with bilateral TMJ ID had significantly greater asymmetry in the vertical position of the antegonion. If the TMJ ID was more advanced on the right side, the ipsilateral ramus was shorter, resulting in significant asymmetry in this region. In all other craniofacial regions, the amount of asymmetry was not significant between females with normal TMJs and those with TMJ ID. The results indicate that a female orthodontic patient with bilateral TMJ ID or unilateral right TMJ ID may present with or develop a vertical mandibular discrepancy.

Adolescent↗

Optimum seat pan and back-rest parameters for a comfortable tractor seat.

An experimental set up was fabricated to measure the pressure distribution on the seat pan and back-rest of a tractor seat. Experiments were conducted with four different seat pans having radius of curvatures of 60, 75, 90 and infinity cm, four back-rests with radius of curvatures of 30, 60, 90 and infinitity cm, and three back-rest inclinations of 0 degrees , 5 degrees and 10 degrees on representative Indian tractor operators. The subjective assessment of perceived comfort at the seat-operator interface was also recorded. Experiments were conducted in a randomized block design and the data obtained were analysed using suitable computer packages. Results indicate that all the parameters, namely seat pan, back-rest profile curvatures and the back-rest angle of inclination, affect the pressure distribution. It is concluded that a seat pan with radius of curvature 75 cm, back-rest with radius of curvature 30 cm and back-rest inclination of 10 degrees are the most suitable parameters for Indian tractor operators.

Adolescent↗

Phosphorylation of Bcl-2 and mitochondrial changes are associated with apoptosis of lymphoblastoid cells induced by normal immunoglobulin G.

Normal human immunoglobulin G induces apoptosis in human lymphoblastoid cells which involves antibody-mediated Fas ligation and the activation of caspases. Here, we show that Bcl-2 is phosphorylated on serine upon treatment of CEM T cells with normal IgG and that the overexpression of Bcl-2 in stable transfectants of CEM T cells prevents IgG-induced cell death. Treatment of CEM cells with normal IgG also results in a reduction in mitochondrial transmembrane potential and in the release of cytochrome c (Cyt c) into cytosol. The findings are concordant with earlier observations that apoptosis induced by IgG is associated with the activation of caspases. Our results demonstrate that Bcl-2 controls apoptosis induced by normal IgG and support a central role for Bcl-2 and mitochondria in antibody-mediated selection of lymphocyte repertoires.

Apoptosis↗

Short- and long-term outcome of balloon angioplasty for compromised side branches after intracoronary stent deployment.

During coronary stent deployment there is a risk of compromising side branches, which can result in chest pain. Compromised side branches can be reopened by balloon angioplasty through the side of the stent. In a consecutive series of 10 patients with side-branch compromise and chest pain, balloon angioplasty through the side of the stent resolved the ischemia in all cases. The stented segment showed no deterioration following side-branch angioplasty. Six-month follow-up angiography showed a restenosis in the branch vessel of eight patients. The stented parent vessel restenosed in four patients. Therefore, side-branch balloon angioplasty after coronary stenting for ongoing ischemia is technically feasible and immediately effective. Restenosis of the branch occurs in most cases.

Adult↗

Duplication of the urethra.

Accessory urethra or duplication of the urethra is a rare anomaly. The vast majority occur in the sagittal plane; however, collateral or side-by-side duplications in the absence of bladder duplication also exist. We report six cases of urethral duplications. The mode of presentation and the importance of complete examination are discussed.

Child↗

Cardiology fellowship subspecialty training opportunities in Canada.

Overseas experience broadens horizons, provides a different perspective on medicine and enhances a doctor's professional credibility. This article covers cardiology subspecialty training opportunities in Canada and offers advice on finding a job, the application process and acclimatization into Canadian life.

Canada↗

Haemangiopericytoma of the adult male breast.

Haemangiopericytoma is an uncommon, usually benign, soft tissue tumour which has been rarely reported to occur in the female breast. Haemangiopericytoma of the adult male breast has been reported only once before. We report another such case.

Breast Neoplasms, Male↗

Atrial natriuretic peptide increases urinary albumin excretion in men with type 1 diabetes mellitus and established microalbuminuria.

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.

Adult↗