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Biomedical subjects

N Kanagasundaram

Publications and source records attributed to N Kanagasundaram.

11 recordsLinked to original sources

Excess vitamin A injures the liver.

Chronic vitamin A intoxication in a 56-year-old female is reported. Some abnormal blood chemistries included elevated transaminase and alkaline phosphatase, increased cerebrospinal fluid and portal pressure, and elevated vitamin A in blood and liver. A liver biopsy indicated histologic evidence of perisinusoidal collagen deposition and noncoalescent fat droplets in Ito cells. Caution against the misdiagnosis of alcoholic cirrhosis for vitamin A intoxication is recommended.

Diagnosis, Differential↗

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↗

Hepatocellular carcinoma in the alcoholic.

The conversion of alcoholic hepatitis into cirrhosis and the eventual development of hepatocellular carcinoma (HCC) has been documented by serial biopsies in patients with uncomplicated alcoholism. Ethanol toxicity, nutritional deficiency and immunological abnormalities in a genetically predisposed individual appear to account for this sequence which can be accelerated by the hepatitis B virus and other noxious agents. Immune deficiency in malnourished alcoholics with liver disease diminishes response to the hepatitis B vaccine and may contribute to the development of HCC. Antigenic moieties in Mallory bodies appear to contribute directly to cytotoxicity and fibrosis in alcoholics, and may act like proto-oncogens. Available Mallory-body-specific monoclonal antibodies will hopefully facilitate diagnosis and treatment. Studies of DNA and collagen synthesis by in vitro perfusion of percutaneous liver biopsies provide information on precursor lesions of HCC. Abstinence, nutrient therapy and drug-induced anabolism lead to repair of liver damage and correction of immunological abnormalities, both of which may contribute to development of HCC in alcoholics with cirrhosis.

Carcinoma, Hepatocellular↗

Alcoholic hyalin antigen (AHAg) and antibody (AHAb) in alcoholic hepatitis.

Complement fixation (CF) and immune adherence (IA) hemagglutination tests demonstrate antigen (Ag) and antibody (Ab) to alcoholic hyalin (AH) in serum of patients with alcoholic hepatitis. Immunoglobulins from postmortem liver of patients dying of alcoholic hepatitis show antibody activity against AH. Isolated purified AH was used to produce AHAb in rabbits. Rabbit antiserum was added to heat-inactivated human serum to detect AHAg; purified AH was added to serum and tissue elutes to detect AHAb. AHAg was present in serum of each of 15 patients with early phase alcoholic hepatitis in CF titers of 8 to 64 and IA titers of 16 to 2048. AHAg became negative within 3 to 5 weeks with abstinence from alcohol and was followed by transient appearance of AHAb. AHAb was present in 11 patients with advanced phases of alcoholic hepatitis in CF titers of 8 to 640 and IA titers of 16 to 4096. Four patients in this group exhibited concomitant AHAb and AHAg. Investigations of liver tissue elute reveal that patients with advanced alcoholic hepatitis or active alcoholic cirrhosis have AHAg-reactive immune complexes containing IgG and IgA immunoglobulins.

Animals↗

Chemical nature of alcoholic hyalin.

Alcoholic hyalin was prepared from postmortem livers of patients with alcoholic liver disease. Alcoholic hyalin was purified by discontinuous sucrose density gradient ultracentrifugation. The purified protein preparation contained about 12% reducing sugar, the remainder being protein. Gel filtration on Sephadex 4B column showed the presence of three peaks. Each peak material thus obtained contained acetylglucosamine, hexosamine, and deoxysugar (calculated as rhamnose). That these protein components followed by scanning the gels at 280 nm, and at 520 nm after staining the gels with periodic acid-Schiff base reagent for the presence of carbohydrate.

Antigens↗