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Biomedical subjects

A M Ismail

Publications and source records attributed to A M Ismail.

6 recordsLinked to original sources
PubMed2026

Evaluation of early prophylactic corticosteroid administration on early safety and efficacy outcomes of adeno-associated virus gene therapy in the hemophilia dog model.

BACKGROUND: Prior to commercial withdrawal, adeno-associated virus (AAV) gene therapy was approved for the treatment of adults with severe hemophilia A. Mechanisms underlying variability, durability, and liver transaminitis are largely uncharacterized. OBJECTIVES: To evaluate the effects of prophylactic corticosteroid administration on AAV gene therapy outcomes in dogs with severe hemophilia A. METHODS: Seven dogs with hemophilia A received 6e13 vector genomes/kg of AAV5-canine factor (F)VIII. Four dogs received oral prednisolone (1 mg/kg/day) starting 3 hours preinfusion with dose-tapering over 6 weeks; three control dogs received no corticosteroids. Percutaneous liver biopsies were performed on detection of alanine aminotransferase (ALT) >2-fold the upper limit of normal. RESULTS: All dogs expressed therapeutic FVIII:C (8.7-56.1%), improved whole blood clot time, and decreased bleeding rates (pre = 6.11 vs post = 1.42 bleeds/year, P = .016) over 2 years post-AAV5-canine FVIII. Corticosteroid-treated dogs demonstrated a modest increase in mean FVIII:C at 2 years by chromogenic substrate assay (39.1%) compared with controls (29.5%), driven by one female with markedly elevated FVIII:C from day 54 onward. When analyzed by sex, all female dogs exhibited increased mean FVIII:C chromogenic substrate assay at 2 years (49.3%) compared with males (9.1%), regardless of prophylactic corticosteroid use. Prophylactic corticosteroids did not impact transient posttreatment elevations of proinflammatory cytokines, anti-AAV antibody formation, or ALT levels. One corticosteroid-treated dog experienced ALT > 4.3-fold the upper limit of normal at 18 weeks without impacting long-term FVIII:C expression. A liver biopsy showed diffuse, minimal periportal lymphocyte and neutrophil infiltration, consistent with nonspecific minimal hepatitis. CONCLUSIONS: Prophylactic corticosteroids were not clearly associated with increased transgene expression in dogs with hemophilia A.

adeno-associated virus↗
PubMed1979

Preparation and properties of pectic enzymes produced by Trichoderma lignorum.

Polygalacturonase and protein-methylesterase were isolated from shaken culture of Trichoderma lignorium. Isolation was carried out with various agents. Methanol was the most suitable precipitant for isolating polygalacturonase, yielding enzyme preparations 6.6 times more active than that of culture filtrate. Likewise, tannin afforded active fractions at pH 4 and 0.05% concentrations. Similarly, 50% ammonium sulphate saturation gave active fractions. The least polygalacturonase activity was obtained from ethanol. In any of the organic solvents used, highest enzymic activity was obtained when using only one volume. As regards pectin-methylesterase, no correlation existed between its activity and concentration of the precipitant used. A substrate concentration above 0.8% was a limiting factor for polygalacturonase activity, while optimum enzyme concentration was 40 microgram protein/ml at 40 degrees C and pH 4.45.

Esterases↗
PubMed1976

The role of lymphatics in the formation of ascites complicating schistosomal hepatic fibrosis.

The total protein content in plasma, ascitic fluid, thoracic duct lymph, hepatic and intestinal lymph was studied in a series of 15 patients suffering from schistosomal hepatic fibrosis and intractable ascites. Pure schistosomal cases with presinusoidal resistance to portal blood flow have excessive thoracic duct lymph low in protein. The main source of such excess lymph is the extra-hepatic portal bed. Ascitic fluid in such patients has a low protein content and has the character of a transudate. The bulk of such peritoneal fluid seems to originate largely from the excess extrahepatic portal lymph.

Adult↗
PubMed1976

Percutaneous trans hepatic lymphography: evaluation in schistosomal hepatic fibrosis.

The increased interest in lymph and lymphatics has cast its mantle over the portal circulation. Lymphography has contributed greately to our knowledge. In the present study percutaneous transhepatic lymphography showed some of the factors sharing in the production of portal hypertension in schistosomal hepatic fibrosis, and gave a further evidence that the liver is not a source of excess lymph production in hepatic lesions associated with presinusoidal block to portal blood flow. Hepatic lymphatics were opacified in cases with mixed cirrhosis and schistosomal hepatic fibrosis as the sinusoidal pressure is elevated with subsequent cases increase in hepatic lymph production.

Humans↗