Disseminated Hormographiella aspergillata infection with involvement of the lung, brain, and small intestine following allogeneic hematopoietic stem cell transplantation: case report and literature review.

Disseminated infection by Hormographiella aspergillata is extremely rare and small intestine involvement has not been reported previously. A 51-year-old man with myelodysplastic syndrome developed pneumonia after cord blood cell transplantation. Fungal growth from the biopsied lung was identified as H. aspergillata by morphology and the gene analysis. Although antifungal agents including voriconazole and liposomal amphotericin B were administered, he died of disseminated H. aspergillata infection. We review the literature and discuss the treatment and prognosis.

Inhibitor of plasminogen activator in human arterial wall. I. Histochemical study.

An inhibitor of urokinase, human urinary plasminogen activator, was found in the media of human arteries using a histochemical method (fibrin slide sandwich technique). Arteriosclerotic lesions, especially atherosclerosis, apparently contained the urokinase inhibitor. The inhibitor did not alter plasmin activity. This inhibitor of urokinase may be involved in regulation of fibrinolysis in arterial wall and thus a significant role in atherogenesis.

Inhibitor of plasminogen activator in human arterial wall. II. Biochemical characterization.

Fibrinolytic inhibitor was prepared from human aortas and some of its biochemical properties were investigated. The fibrinolytic inhibitor suppressed urokinase activity, but did not inhibit plasmin activity when assayed by fibrin plate method and synthetic fluorogenic substrate method. The urokinase inhibitor was a glycoprotein and migrated similar to alpha-globulin upon fibrin-agar electrophoresis. The molecular weight determined by gel filtration was approximately 98,000. The urokinase inhibitor was immunologically different from other known plasma protease inhibitors, such as alpha 2-plasmin inhibitor, alpha 2-macroglobulin, and alpha 2-antitrypsin. The interaction of urokinase with the inhibitor was dose-dependent. Progressive inactivation of urokinase occurred by increasing time of incubation with the inhibitor at 37 degrees C, and over 90% inhibition of urokinase required 30 min of incubation. The inhibitor of plasminogen activator in human aorta may be noteworthy in relation to thrombogenesis and atherogenesis.

Purification and characterization of human kidney plasminogen activator dissimilar to urokinase.

The tissue activator was extracted with 2 M ammonium thiocyanate and purified by L-arginine methyl ester, concanavalin A and ion-exchange chromatographies, and Sephacryl S-200 gel filtration in buffers containing Triton X-100 and/or ammonium thiocyanate. The final preparations had specific activities of 25 000-40 000 IU/mg protein and were shown to be a single band with an apparent molecular weight of 54 00 by SDS-polyacrylamide gel electrophoresis with or without reducing agent. When subjected to isoelectric focusing, its major component had an isoelectric point of approx. 8.2 with minor components. (7.8-8.6). The purified tissue activator was a serine protease, dissimilar to urokinase in some respects including antigenicity, strong affinity to insoluble fibrin monomer and hydrolytic activities for synthetic substrates. The crude extract contained another plasminogen activator with antigen identity to urokinase, which constituted approx. 15% of the total activity in crude extract. These findings indicated that human kidney would produce at least two plasminogen activators, namely, the tissue activator as a major plasminogen activator and urokinase.

Permeability enhancing and chemotactic activities of lower molecular weight degradation products of human fibrinogen.

Fibrinogen degradation products were investigated for leukocyte chemotactic activity and for enhancement of vascular permeability. Both activities increased progressively with plasmin digestion of fibrinogen. Active fragments were partially purified from 24 hr-plasmin digests. Molecular weights of the permeability increasing and chemotactic activity fractions were 25,000-15,000 and 25,000 respectively. Both fractions had much higher activities than the fragment X, Y, D or E. Electron microscopic observations of the small blood vessels in rabbit skin correlated increased permeability with the formation of characteristic gaps between adjoining endothelial cells and their contraction. These findings suggest that lower molecular weight degradation products of fibrinogen may be influential in contributing to granulocytic infiltration and enhanced permeability in lesions characterized by deposits of fibrin and/or fibrinogen.

Fibrinolysis-inhibitory activity of cultured human cancer cell lines.

Fibrinolysis-inhibitory activity was estimated in the lysates of 21 lines of cultured human cancer cells, from which plasminogen activator activity had veen effectively eliminated by affinity chromatography. Inhibitory activity against urokinase varied from one line to another. Three lines of lung cancer and 1 line of urinary bladder cancer showed high inhibitory activity against urokinase. Two lines of lung cancer, 3 lines of gastric cancer, 1 line of renal cancer and 1 line of renal pelvic cancer showed moderate inhibitory activity. Since inhibitory activity against plasmin was not apparent in all the cell lines tested, this activity seemed to be directed selectively towards urokinase. No inhibitory activity against urokinase was detected in 4 lines of lung cancer, 5 lines of gastric cancer and 1 line of renal cancer. There was no specific correlation between the degree of inhibitory activity against urokinase and the histological cell types of the original tumors of the cultured cell lines.