alpha-chymotrypsin and Hepatitis

Topics: Adult; Aged; Amylases; Bromelains; Cholecystitis; Chymotrypsin; Clioquinol; Colonic Diseases, Functional; Female; Gastrointestinal Diseases; Hepatitis; Humans; Male; Middle Aged; Pancreatin; Pancreatitis; Quinolines; Trypsin

Primary malignant fibrous histiocytoma (MFH) of the liver remains extremely rare with only several cases having been reported in literature. We report a case of hepatic MFH in a 53-year-old man who presented with upper abdominal pain, and weight loss for one month. Ultrasound and computed tomography (CT) scan showed a large mass with fine tumor vessels over the left lobe of the liver. Histopathological findings indicated a mesenchymal tumor consisting of spindle cells in storiform pattern intermingled with histiocyte-like cells and giant cells. Immunohistochemically, most tumor cells expressed vimentin, alpha-1 anti-chymotrypsin, alpha-1 antitrypsin and CD68. Morphological and immunohistochemical findings support that the tumor should be classified as a primary malignant fibrous histiocytoma. The literatures is briefly reviewed.

Topics: alpha 1-Antitrypsin; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Chymotrypsin; Fatal Outcome; Hepatitis; Histiocytoma, Malignant Fibrous; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Male; Middle Aged; Recurrence; Tomography, X-Ray Computed; Vimentin

Conformational diseases are caused by a structural rearrangement within a protein that results in aberrant intermolecular linkage and tissue deposition. This is typified by the polymers that form with the Z deficiency variant of alpha 1-antitrypsin (Glu-342 --> Lys). These polymers are retained within hepatocytes to form inclusions that are associated with hepatitis, cirrhosis, and hepatocellular carcinoma. We have assessed a surface hydrophobic cavity in alpha1-antitrypsin as a potential target for rational drug design in order to prevent polymer formation and the associated liver disease. The introduction of either Thr-114 --> Phe or Gly-117 --> Phe on strand 2 of beta-sheet A within this cavity significantly raised the melting temperature and retarded polymer formation. Conversely, Leu-100 --> Phe on helix D accelerated polymer formation, but this effect was abrogated by the addition of Thr-114 --> Phe. None of these mutations affected the inhibitory activity of alpha 1-antitrypsin. The importance of these observations was underscored by the finding that the Thr-114 --> Phe mutation reduced polymer formation and increased the secretion of Z alpha 1-antitrypsin from a Xenopus oocyte expression system. Moreover cysteine mutants within the hydrophobic pocket were able to bind a range of fluorophores illustrating the accessibility of the cavity to external agents. These results demonstrate the importance of this cavity as a site for drug design to ameliorate polymerization and prevent the associated conformational disease.

Topics: alpha 1-Antitrypsin; Animals; Binding Sites; Carcinoma, Hepatocellular; Chymotrypsin; Crystallography, X-Ray; Cysteine; Fibrosis; Glycine; Hepatitis; Hepatocytes; Hydrogen-Ion Concentration; Models, Molecular; Mutation; Oocytes; Phenylalanine; Polymers; Potassium Chloride; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins; Temperature; Threonine; Time Factors; Xenopus

Topics: Amylases; Cholestasis; Chymotrypsin; Clinical Enzyme Tests; Diagnosis, Differential; Feces; gamma-Glutamyltransferase; Hepatitis; Humans; L-Lactate Dehydrogenase; Pancreatitis

Topics: Antifibrinolytic Agents; Blood Platelets; Cholestasis; Chymotrypsin; Fatty Liver; Fibrinolysin; Hepatitis; Humans; Hypersplenism; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Diseases; Trypsin Inhibitors

Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Cholecystitis; Chymotrypsin; Colorimetry; Duodenal Ulcer; Female; Hepatitis; Humans; Intestinal Diseases; Liver Cirrhosis; Lung Diseases; Lung Diseases, Obstructive; Male; Middle Aged; Neoplasm Metastasis; Pancreatitis; Pregnancy; Respiratory Tract Infections; Trypsin Inhibitors