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Biomedical subjects

F Schaffner

Publications and source records attributed to F Schaffner.

At least 91 records · Page 5Linked to original sources
PubMed1979

Antibodies to ribosomes in chronic active hepatitis.

A recently developed Farr-type radioimmunoassay for the detection of antibodies to tritium-labeled HeLa cell cytoplasmic ribosomes was evaluated as a serologic test in a variety of liver diseases. Ribosomal antibodies were detected in the sera of 31.4% of 70 patients with chronic active hepatitis (CAH) and primary biliary cirrhosis compared with only 4.2% of patients with chronic persistent hepatitis, acute viral hepatitis, alcoholic liver disease, and miscellaneous liver diseases (X2 = 17.89, P less than 0.001). The level of ribosomal binding activity was also significantly higher in sera of patients with CAH and primary biliary cirrhosis (15.4% vs 6.5%; t = 5.61, P less than 0.001). The antibodies were observed almost exclusively in HBsAg-negative CAH with autoimmune features and infrequently at lower titer in HBsAg-positive CAH or CAH without HBsAg or autoantibodies. Inhibition experiments with purified ribosomal RNA suggested that the ribosomal antibodies are in part reactive with ribosomal RNA. Ribosomal antibodies appear to represent another example of the exaggerated immune response associated with CAH and primary biliary cirrhosis.

Autoantibodies↗
PubMed1978

Increased serum thyroid hormone binding and decreased free hormone in chronic active liver disease.

To determine whether chronic inflammatory disease of the liver increases serum thyroid hormone binding, we measured tri-iodothyronine resin binding ratios in nine patient with primary biliary cirrhosis and in nine with chronic active hepatitis. In each group, the average binding ratio was about 50 per cent higher than in control subjects. Thyroxinebinding globulin, measured by immunoassay in three patients, was elevated. Although average total thyroxine and tri-iodothyronine were increased slightly, the corresponding free hormone concentrations were lower than controls, probably because of decreased thyroid function associated with the high incidence of autoimmune thyroiditis in nonalcoholic (autoimmune) liver disease. Thyroid autoantibodies were found in 13 patients. Impaired hepatic thyroxine-to -tri-iodothyronine conversion may have contributed to the low free tri-iodothyronine. Thyrotropin was elevated in four patients. Because of increased serum thyroid hormone binding in these patients total thyroxine and tri-iodothyronine concentration can be normal despite hypothyroidism.

Autoantibodies↗
PubMed1977

Chimpanzee livers after infection with human hepatitis viruses A and B: Ultrastructural studies.

Electron microscopical studies were carried out on coded liver biopsy specimens from chimpanzees inoculated with human hepatitis A or B virus. Hepatitis B was recognized by the presence of hepatitis B core particles in hepatocellular nuclei. Hepatitis A was characterized by unidentified large, dense, and more irregular heterochromatin-like particles in hepatocellular nuclei coincidental with peak aminotransferase activities. As type A hepatitis illness became manifest in the chimpanzees, mitochondrial cristae were curled and attenuated, and clusters of endoplasmic reticulum were tightly packed. In contrast, the livers in viral hepatitis B showed mainly hypertrophy of tubular smooth endoplasmic reticulum. This suggested different pathogenetic mechanisms in A and B chimpanzee viral hepatitis.

Animals↗
PubMed1976

Extrahepatic malignancy in chronic liver disease: report of six cases.

Six patients are described with chronic liver disease, 3 with primary biliary cirrhosis and 3 with chronic active hepatitis, all of whom developed malignant disease in organs other than the liver. Two malignancies were mixed histiocytic-lymphocytic lymphomas. All patients had received corticosteroid or azathioprine therapy. Specific lymphocyte counts and immunoglobulin and antibody determinations failed to reveal a consistent pattern of abnormality to recognize the patient at risk. Several diseases in which the immune responsiveness is disturbed seem to have this potentiality in common, especially if therapy that further alters immunological reactivity is given.

Adrenal Cortex Hormones↗
PubMed1975

Hepatitis B surface antigen and antibody. A prospective study in asymptomatic drug abusers.

The course of reactivity of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) in 238 asymptomatic heroin addicts entering methadone maintenance was followed up for periods of one to four years. On initial determination, HBsAg was seen in 39.1%, anti-HBs in 10.5%, and HBsAg and anti-HBs in 9.2%; only 41.2% of persons tested had no detectable titers of either antigen or antibody. Abnormal liver function was found initially in 83% with no significant difference between those with or without HBsAg and anti-HBs. At the conclusion of each study year, 50% to 60% of persons initially HBsAg-positive reverted to negative with HBsAg absent in all persons followed up through the fourth year of treatment. Anti-HBs persisted in two thirds of persons during the entire study. These results suggest that the HBsAg carrier state in addicts is not maintained if exposure is eliminated.

Adolescent↗
PubMed1975

Cytochrome P-450 in the activation and inactivation of carcinogens.

The capacity of isolate mouse liver microsomes to alter the mutagenicity for bacteria of the primary carcinogen N-methyl-N'-nitro-N-nitrosoguanisine (MNNG) and the secondary one dimethylnitrosamine (DMN) was studied. Microsomal activation of DMN and inactivation of MNNG were decreased by protein- and protein-cholinedeficient diets and were increased by pretreatment with microsomal enzyme inducers. The decrease and increase paralleled the content of cytochrome P-450 present in the different microsomal preparations. With human liver microsomes of differing cytochrome P-450 contents similar correlation was obtained, whereas normal rat liver microsomes did not activate or inactivate DMN or MNNG. Oxidative demethylation of DMN by mouse liver microsomes and the activation of DMN to a mutagen followed similar kinetics. Both reactions were inhibited by carbon monoxide and the inhibition was maximally reversed by monochromatic light at 450 nm. These observations indicate that at least some carcinogens are activated or inactivated by the unspecific cytochrome P-450 dependent enzyme system, suggesting that the extent of this biotransformation may be one factor influencing human carcinogenesis.

Animals↗
PubMed1975

Hepatic drug metabolism and adverse hepatic drug reactions.

Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin.

Adaptation, Biological↗
PubMed1974

Electron microscopy and immunoelectronmicroscopy of cytoplasmic hepatitis B antigen in hepatocytes.

The localization of hepatitis B antigen (HB Ag) and the nature of the virus-like particles in hepatocytes of patients with HB antigenemia are controversial. In many reports, numerous virus-like particles have been demonstrated in hepatocytic nuclei; the few reported in the cytoplasm are insufficient in number to explain the intense cytoplasmic fluorescence after staining with fluoresceinated antibody to HB Ag (HB Ab). We found numerous tubular and circular structures, measuring 20 to 30 nm in diameter, in the cisternae of the excess smooth endoplasmic reticulum (ER) of varying numbers of hepatocytes in 13 of 16 HB Ag carriers and in 4 of 9 patients with HB Ag-positive chronic hepatitis corresponding to cytoplasmic HB Ag-specific fluorescence. Direct immunoelectronmicroscopy using peroxidase-labeled HB Ab revealed that the intracisternal bodies and the surrounding membranes contain HB antigenic determinants. These bodies are an ultrastructural correlate of cytoplasmic HB Ag. It is suggested that they are virally coded coat material rather than the mature hepatitis B virus or its core.

Antigens, Viral↗