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Biomedical subjects

M Blackstone

Publications and source records attributed to M Blackstone.

12 recordsLinked to original sources

Role of heat shock protein 90 in bradykinin-stimulated endothelial nitric oxide release.

Previously we described ENAP-1, a 90-kDa protein that is tyrosine-phosphorylated in endothelial cells in response to bradykinin (BK) stimulation and is associated with endothelial nitric oxide synthase (eNOS). Subsequently, other investigators demonstrated that eNOS interacts with heat shock protein 90 (Hsp90) following stimulation of endothelial cells with vascular endothelial growth factor (VEGF), histamine, or fluid shear stress. Therefore, we tested the hypotheses that ENAP-1 and Hsp90 are the same protein and that BK activation of eNOS is dependent on Hsp90. Immunoblotting of immunoprecipitated Hsp90 with anti-phosphotyrosine antibody shows that Hsp90 is tyrosine-phosphorylated in response to BK stimulation of bovine aortic endothelial cells (BAECs). Coimmunoprecipitation of Hsp90 with anti-eNOS antibody reveals a Hsp90-eNOS complex in endothelial cells under basal conditions that is increased following BK stimulation. Taken together with the tyrosine phosphorylation data, these data suggest that ENAP-1 is Hsp90. BK-stimulated nitric oxide (NO) release is completely blocked by pretreatment with geldanamycin, a specific inhibitor of Hsp90, illustrating the importance of the Hsp90-eNOS interaction. In vitro binding assays with Hsp90-glutathione-S-transferase fusion proteins show direct binding of eNOS with the middle domain (residues 259-615) of Hsp90.

Animals↗

Candida (Torulopsis glabrata) liver abscesses eight years after orthotopic liver transplantation.

The authors report the case of a 48-year-old man in whom candida (Torulopsis glabrata) liver abscesses developed 8 years after liver transplantation. After a week of fever, computed tomography and Doppler ultrasonography showed several fluid-filled loculations in the left lobe of the liver and hepatic arterial stenosis. Aspirates from the abscesses contained T. glabrata organisms. This complication probably developed because hepatic arterial stenosis resulted in bile infarcts (bilomas), which were contaminated via the biliary tract with candida from the biliary-enteric anastomosis. Catheter drainage and administration of amphotericin B for 10 weeks permitted successful retransplantation. T. glabrata liver abscesses, a life threatening complication that can occur long after liver transplantation, can be successfully managed by aggressive medical treatment followed by retransplantation.

Candidiasis↗

Rapidly progressive sclerosing cholangitis following surgical treatment of pancreatic pseudotumor.

Two patients with sclerosing cholangitis presented with a distal stricture of the common bile duct in association with pancreatic pseudotumors. Jaundice resolved following surgery to correct biliary obstruction, but diffuse cholangiographic abnormalities and clinical evidence of sclerosing cholangitis became evident 2 and 4 months later. Rapid progression of symptomatic disease necessitated liver transplantation in one patient, but the other had a complete response to methotrexate therapy. The rapid disease progression in these two patients may have been triggered by surgery that resulted in a generalized fibroproliferative response of the biliary tree, already affected with localized sclerosing cholangitis contiguous to a pancreatic pseudotumor. We suggest that localized sclerosing cholangitis associated with pancreatic pseudotumors may be a unique variant that can progress rapidly but respond dramatically to antiinflammatory therapy.

Adult↗

Pancreatic fistula: management guided by endoscopic retrograde cholangiopancreatography.

A patient with a persistent external pancreatic fistula was studied by endoscopic cholangiopancreatography (ERCP). The ERCP demonstrated the probable site of the fistula and a high-grade, main pancreatic ductal stricture. This information prompted early, successful surgical correction of the pancreatic fistula by drainage into a Roux-en Y jejunal loop.

Abscess↗