fibrin and Liver-Diseases--Parasitic

Lysyl oxidase (LO) initiates the first step in the crosslinking of collagens and elastin and has also been shown to function as a tumor suppressor. The purpose of the present work was to determine whether the products of a newly described LO-like gene (LOXL) that encodes a close homolog of LO, the LO-like (LOL) protein, is associated with extracellular matrix remodeling during fibrotic disorders. Specific antibody against LOL identified proteins of approximately 30, 42, 52 and 68 kd in various cells and in bovine aorta. These proteins were immunochemically distinct from the recombinant LO expressed by fibroblasts and from the bovine aorta LO. The LO gene (LOX) and LOXL were transiently up-regulated at early stages of liver granuloma development in Schistosoma mansoni-infected mice, although the peak of LOL mRNA synthesis preceded that of LO. LOL protein and LO were colocalized at sites of fibrogenesis in human lung fibrosis and in the stromal reaction of bronchiolo-alveolar carcinomas and of in situ ductal breast tumors. In conclusion, the LOL protein was identified as a secreted protein and localized in the extracellular matrix in active fibrotic diseases and in the early stromal reaction of breast cancer.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Animals; Carcinoma, Ductal, Breast; Cattle; Cell Line; Female; Fibrin; HeLa Cells; Humans; Liver Diseases, Parasitic; Lung; Lung Neoplasms; Mammary Neoplasms, Animal; Mice; Peptide Fragments; Protein-Lysine 6-Oxidase; Pulmonary Fibrosis; RNA, Messenger; Schistosomiasis mansoni; Stromal Cells

To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis.. The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out.. The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature.. These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.

Topics: Adolescent; Adult; Ascites; Female; Fibrin; Fibrinolysin; Fibrinolysis; Hematemesis; Hepatitis, Viral, Human; Humans; Liver Diseases, Parasitic; Male; Middle Aged; Plasminogen; Schistosomiasis mansoni; Severity of Illness Index

Hepatic fibrin-ring granulomas and leishmania parasites were found in the liver biopsy specimens of 3 patients with prolonged fever and hepatosplenomegaly. It was recognition of the leishmanias in the liver biopsy specimen that prompted the diagnosis in all cases. There was no evidence of Q fever, Hodgkin's disease, cytomegalovirus hepatitis, or allopurinol treatment, which are the recognized causes of hepatic fibrin-ring granulomas. This report extends the range of etiologies of hepatic fibrin-ring granulomas. As a result, leishmaniasis should always be a consideration to the pathologist and the clinician in the differential diagnosis of fibrin-ring granulomas.

Topics: Aged; Biopsy; Diagnosis, Differential; Female; Fibrin; Granuloma; Humans; Infant; Leishmaniasis, Visceral; Liver; Liver Diseases, Parasitic; Male; Middle Aged; Q Fever