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C B Leevy

Publications and source records attributed to C B Leevy.

26 records · Page 2Linked to original sources

Use of a specific monoclonal antibody to detect Mallory bodies in liver disease.

Mallory bodies (MBs), which are common in alcoholic hepatitis, primary biliary cirrhosis and liver disease associated with Type II diabetes mellitus, are often difficult to find on liver biopsy specimens or to predict from clinical or biochemical studies. Immunofluorescence studies with anti-NMB-1, a Mallory body-specific monoclonal antibody, indicate that this is a sensitive method for recognizing Mallory bodies in cryostat sections of liver from griseofulvin-treated mice or patients with liver disease. Validity of the leukocyte migration test, which facilitates detection and monitoring of patients who harbor Mallory bodies, is confirmed by pretreatment of Mallory bodies with anti-NMB-1. Prevention of Mallory body-induced migration inhibition by addition of anti-NMB-1 indicates that this effect is not due to inactivation of leukocytes by a Mallory body contaminant. Anti-NMB-1, developed using standard hybridoma techniques, does not react with normal hepatocytes or other cells. Investigations with SDS polyacrylamide gel electrophoresis and western blotting reveal that it exhibits binding with 62, 55, 42 kd peptides, and four other bands in the range from 40 to 30 kd from the Mallory bodies. The NMB-1 epitope which facilitates morphologic and clinical detection of Mallory bodies is distinct from cytokeratin and appears to be responsible for its immunogenicity.

Animals↗

Effect of alcohol on urinary glycosaminoglycan and protein excretion in normal and diabetic mice.

The effect of alcohol on urinary glycosaminoglycan (GAG) and protein excretion was studied in one-month-old normal control C57BL/6J (CBL) and genetically diabetic (db/db) mice. Ethyl alcohol (4 g/kg) was given once a day by gavage for 58-64 days. Increased amounts of urinary total GAGs and protein were found in diabetic mice. Alcohol treatment increased urinary excretion of total GAGs, heparan sulfate and protein only in nondiabetic CBL but not in diabetic mice. Also, alcohol increased creatinine clearance only in CBL mice. The reason for the lack of effect of alcohol in diabetic mice is unknown. A significant positive linear relationship was found between urinary total GAG and protein concentrations. Possible significance of this relationship in diabetes is discussed.

Alcohol Drinking↗

Pyridoxal phosphate annuls acetaldehyde inhibition of uridine uptake by hepatocytes.

Methods were evaluated for depressing the acetaldehyde (AcH) inhibition of uridine uptake by Chang liver cells and isolated autologous liver cells, obtained by percutaneous liver biopsy from cases of alcoholic hepatitis. Hepatocytes so obtained were significantly more susceptible to AcH-induced inhibition of uridine uptake than hepatocytes from normal liver, alcoholic fatty liver, stable alcoholic cirrhosis and acute viral hepatitis. Benzylamine (an aldehyde buffer) and pyridoxal-5' phosphate (PLP) counteracted the inhibition of uridine uptake by AcH in vitro. We suggest that benzylamine neutralizes AcH toxicity through a Schiff-base condensation with AcH thus taking AcH out of the field of action. PLP protects against AcH-induced inhibition of uridine uptake by probably forming a Schiff base with cellular amino acids thus blocking further condensation of these amino groups with AcH. In this manner, uridine uptake by liver cells for RNA synthesis can proceed without interference by AcH.

Acetaldehyde↗

Active viral B hepatitis in parenteral drug abusers with acquired immune deficiency syndrome (AIDS).

Eighty-percent of 47 parenteral drug abusers with hepatomegaly and acquired immunodeficiency syndrome had HBV DNA in serum, although only 27% were HBsAg or "e" antigen-positive by polyclonal radioimmunoassay. Liver biopsies from each of 37 HBV DNA seropositive patients showed HBV DNA and were HBcAg-positive. The absence of positive HBsAg and "e" antigen in HBV DNA-positive patients was attributable to the presence of immune complexes; after in vitro dissociation of these complexes there was an increase in HBsAg from 24% to 86%, and of "e" antigen from 19% to 62%. These data indicate that actively replicating hepatitis B virus is common in patients with AIDS, and that precautions should be taken to prevent its dissemination. Therapy in these patients should address both human immunodeficiency and hepatitis B virus infections.

Acquired Immunodeficiency Syndrome↗

Troglitazone-induced fulminant hepatitis: report of a case with autopsy findings.

Troglitazone is an insulin-sensitizing agent used to treat type 2 diabetes mellitus. Several cases have been reported of troglitazone-induced hepatic injury; some requiring transplantation, others resulting in death. We here present a case of troglitazone-induced fulminant hepatic necrosis that led to the death of the patient.

Aged↗

Abnormalities of liver regeneration: a review.

Structural and functional changes during liver regeneration have been studied extensively in experimental animals following partial hepatectomy or hepatic injury induced by noxious substances. These observations have been extended to evaluate abnormalities of liver regeneration which contribute to chronic hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and collagen synthesis, respectively. Such investigations indicate that chronic liver damage is associated with replication of mesenchymal, ductular and parenchymal cells, accompanied by increased fibrogenesis. The regenerative response of the liver after noxious injury in experimental animals and man is associated with the release of cytokines, increase of growth response genes and change in telomerase activity. The ability to monitor morphological, genetic and biochemical parameters provides new information on the kinetics of the reparative process in hepatobiliary disease. Abnormal liver regeneration and its untoward effects including tumorigenesis may be modified by altering nutrients, blocking antigens or receptors, and inhibiting metabolites which regulate cell replication and collagen deposition.

Animals↗