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Vishal Sharma

Publications and source records attributed to Vishal Sharma.

5 recordsLinked to original sources
PubMed2024

Severe pulmonary arterial hypertension in congenital sideroblastic anemia from PUS1 mutation - a case report.

BACKGROUND: Myopathy, lactic acidosis and inherited sideroblastic anemia (MLASA) are a group of rare intriguing disorders with wider pathophysiological implications. One of the causes of MLASA is the mutation in PUS1 gene that encodes for pseudouridine synthase. This PUS1 mutation results in MLASA in which anemia and myopathy predominate. Severe pulmonary arterial hypertension has not been previously reported in patients with PUS1 gene mutation. CASE REPORT: A 17 year old girl with congenital sideroblastic anemia presented with worsening of breathlessness. Severe pulmonary artery hypertension was documented on investigations. A homozygous variant in exon 3 of gene PUS1,( chromosome 12:g.131932301 C > T c.430 C > T) was found on sanger sequencing. CONCLUSION: We document severe pulmonary arterial hypertension in a patient of congenital sideroblastic anemia from PUS1 gene. We hypothesis that cross talk with TGFb pathways might occur in PUS1 mutation, and that might cause severe PAH. This observation might have therapeutic implications.

Humans↗
PubMed2006

Combinatorial activation of FAK and AKT by transforming growth factor-beta1 confers an anoikis-resistant phenotype to myofibroblasts.

Transforming growth factor-beta (TGF-beta) is a prototypical tumour-suppressor cytokine with cytostatic and pro-apoptotic effects on most target cells; however, mechanisms of its pro-survival/anti-apoptotic signalling in certain cell types and contexts remain unclear. In human lung fibroblasts, TGF-beta1 is known to induce myofibroblast differentiation in association with the delayed activation of focal adhesion kinase (FAK) and protein kinase B (PKB/AKT). Here, we demonstrate that FAK and AKT are independently regulated by early activation of SMAD3 and p38 MAPK, respectively. Pharmacologic or genetic approaches that disrupt SMAD3 signalling block TGF-beta1-induced activation of FAK, but not AKT; in contrast, disruption of early p38 MAPK signalling abrogates AKT activation, but does not alter FAK activation. TGF-beta1 is able to activate AKT in cells expressing mutant FAK or in cells treated with an RGD-containing peptide that interferes with integrin signalling, inhibits FAK activation and induces anoikis (apoptosis induced by loss of adhesion signalling). TGF-beta1 protects myofibroblasts from anoikis, in part, by activation of the PI3K-AKT pathway. Thus, TGF-beta1 co-ordinately and independently activates the FAK and AKT protein kinase pathways to confer an anoikis-resistant phenotype to myofibroblasts. Activation of these pro-survival/anti-anoikis pathways in myofibroblasts likely contributes to essential roles of TGF-beta1 in tissue fibrosis and tumour-promotion.

Animals↗
PubMed2006

Evaluation of Epsilon amino-caproic acid (EACA) and autologous blood as blood conservation strategies in patients undergoing cardiac surgery.

BACKGROUND: To evaluate the effects of autologous blood and Epsilon amino-caproic acid on intra-operative and post-operative blood loss and homologous blood product requirements in patients undergoing cardiac surgery. METHODS: Patients were randomly allocated to two groups of 30 each. In the Epsilon amino-caproic acid (EACA) group, the drug was administered in a loading dose of 100 mg/kg before skin incision followed by an infusion of 1/5 th the loading dose hourly and terminated 3 h after heparin neutralization. In the autologous transfusion (AT) group, 10% of the calculated whole blood volume was collected intra-operatively before cardiopulmonary bypass and re-infused after its termination. RESULTS: Haemoglobin values were comparable pre-operatively, on cardiopulmonary bypass, off cardiopulmonary bypass and post-operatively on day two in both groups. Intra-operative blood loss was not significantly different (643.3+/-129.14 ml in group EACA versus 710+/-145.5 ml in group AT, p = 0.66). Although the chest drainage was more in group AT during 0-3 h (71.3+/-54.3 ml versus 112.6+/-79.3.6 ml, p = 0.006) it was comparable amongst in the first 24 h (231.1+/-98.3 ml in group AT versus 235+/-101.4 ml in group EACA, p = 0.88). Homologous blood product requirements were similar in both groups. CONCLUSION: Autologous blood is as efficacious as Epsilon amino-caproic acid for blood conservation in cardiac surgery.

Adult↗