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Biomedical subjects

I Millman

Publications and source records attributed to I Millman.

At least 55 records · Page 3Linked to original sources

The relation of infection with the hepatitis B agent to primary hepatic carcinoma.

In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

Africa↗

Australia antigen: detection and transmission in shellfish.

Australia antigen was found in clams contaminated by drainage of untreated sewage from a coastal hospital. In closed-system aquariums, the antigen was ingested by clams and transmitted to previously uninfected clams. In opensystem aquariums, the titer of Australia antigen decreased with time, suggesting viral concentration rather than replication.

Animals↗

Australia antigen and primary biliary cirrhosis.

Sera from 64 patients with primary biliary cirrhosis have been examined for Australia antigen (Au). On immunodiffusion and immunoelectrophoresis all sera were negative. Using a radioimmunoprecipitation technique 15.6% of sera contained antigen compared with an incidence of 3.1% in matched controls, a significant difference (p = 0.015). Anti-Au was found in 9.4% of patients and in 7.8% of controls. In lymphocyte transformation studies lymphocytes from one of 24 patients with primary biliary cirrhosis transformed on stimulation with an Au-rich serum.

Antibodies, Viral↗

Virus-like particles in Australia antigen-associated hepatitis. An immunoelectron microscopic study of human liver.

IN A PREVIOUS REPORT (HUANG SN: Hepatitis-associated antigen hepatitis: an electron microscopic study. Am J Pathol 64:483-500, 1971) liver biopsies of renal transplant patients who developed chronic progressive viral hepatitis associated with persistence of Australia antigenemia [Au(1)] while under immunosuppressive therapy were studied. Predominantly intranuclear 210-250 A spherical, virus-like particles were revealed in 12 of 13 biopsies examined by electron microscope. No such particles were found in biopsies from Australia antigen negative patients. To investigate the relationship of these virus-like particles to Australia antigen, 2 of the Au(1) hepatitis renal transplant patients were restudied 6 to 8 months later. Liver biopsy material was prepared for light microscopy, immunofluorescent microscopy, electron microscopy and immunoelectron microscopy. The specificity of the anti-Au(1) serum used in this study was ascertained by immunodiffusion and immunoelectrophoresis, and by immunoelectron microscopic studies of the antigen-antibody complex prepared in vitro by mixing the ferritin-conjugated anti-Au(1) reagent with the purified Au(1) particles. Electron microscopy of biopsies from liver not treated with antibody showed that virus-like particles persisted in liver cells. Immunofluorescent microscopy of teased liver biopsy suspensions showed nuclear and some cytoplasmic fluorescence, indicating the cellular localization of Au(1). The immunoelectron microscopic preparations showed agglutination of the virus-like particles and the presence of antibody coupled ferritin in the intranuclear and cytoplasmic particle agglutinates. No virus-like particles were seen in the biopsy from a control patient without Au(1) antigenemia, and results of the immunoelectron microscopic procedure were negative. Our observations that massive amounts of Au(1)-associated particles are located in liver cell nuclei of individuals with chronic active hepatitis strengthen the hypothesis of Blumberg et al that Au(1) is an infectious agent and/or the antigenic determinant of a hepatitis virus.

Antigen-Antibody Complex↗