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Biomedical subjects

H Popper

Publications and source records attributed to H Popper.

At least 127 records · Page 7Linked to original sources

Persistent non-A, non-B hepatitis in experimentally infected chimpanzees.

Non-A, non-B (NANB) hepatitis was transmitted to six chimpanzees by intravenous inoculation of antihemophilic (factor VIII) materials, acute-phase chimpanzee liver, and chronic-phase plasma obtained from two NANB hepatitis-infected chimpanzees 10 and 16 months, respectively, after their inoculation. Five of six experimentally infected chimpanzees observed for more than one year demonstrated persistent or intermittent elevations in levels of serum alanine aminotransferase (ALT) indicative of continuing liver dysfunction. Liver biopsy specimens obtained from three chimpanzees with persistent elevations in levels of ALT were positive for hepatocyte cytoplasmic structures associated with NANB hepatitis for as long as 27 months after inoculation. Liver biopsy specimens obtained from four infected animals 13-30 months after inoculation also showed mild but persistent histopathologic lesions of undefined character. The detection of circulating immune complexes in one chimpanzee with persistent elevations in levels of ALT suggests that these complexes may be involved in the pathogenesis of NANB hepatitis.

Animals↗

Non-A, non-B hepatitis in chimpanzees and marmosets.

Nine of 15 specimens of human origin thought to contain non-A, non-B hepatitis agents caused hepatitis in recipient chimpanzees. Two have been further characterized. One inoculum, designated strain F, has been reported to produce unique cytoplasmic changes detected by electron microscopy in liver biopsy specimens; the other, strain H, produced distinctive nuclear changes. It is not yet clear whether these two changes result from infection by different agents; they have been useful markers of non-A, non-B hepatitis in chimpanzees. Strain F was serially passaged six times in chimpanzees, and the infectivity titer of the strain F plasma was estimated to be less than 10(2)/ml. Strain H had an infectivity titer in chimpanzees of at least 10(6)/ml. Both the strain F and strain H agents have been successfully transmitted and serially passaged in marmosets. Although hepatitis was detected in a lower percentage of marmosets than chimpanzees given either the strain F or H inoculum, the infectivity titer of the strain H agent appeared to be greater than or equal to 10(8) marmoset infectious doses/ml.

Acute Disease↗

Vinyl chloride-induced hepatic lesions in man and rodents. A comparison.

Histologic sequences in the liver of rodents exposed by inhalation to gaseous vinyl chloride were compared to the lesions in man exposed to the same agent, mainly in vinyl chloride polymerization plants. An identical sequence, starting with circumscribed proliferation of hepatocytes, soon followed by proliferation of a variety of sinusoidal cells and frequently associated with sinusoidal dilatation, progresses to intralobular and more frequently to trabecular angiosarcoma. Predominantly in young animals and rarely in man, hepatocellular carcinoma develops, but never cirrhosis. The sequence represents a dynamic process of competition between proliferating hepatocytes and sinusoidal cells, of hepatocytes with fibroplasia, between perisinusoidal fibrosis and sinusoidal dilatation, and of proliferation of various sinusoidal cells versus angiosarcoma. The great similarity in the evolution in man and rodents, rarely encountered in other experimental models, supports the prediction of human cancer from animal experiments. The precursor nodules differ from the nodules commonly observed in hepatocarcinogenesis by co-proliferation of sinusoidal cells. The differences in the reactions between man and rodents bespeak a strong fibroblastic reactivity in man. Most important, the precursor lesion of mixed hepatocellular and sinusoidal cell proliferation may be of diagnostic value, being superior to conventional hepatic tests in detection of some initial environmental lesions.

Animals↗

Epidemiology of hepatic angiosarcoma in the United States: 1964-1974.

A nationwide survey of hepatic angiosarcoma (HAS) in the United States during the years 1964 through 1974 identified 168 cases. Of these, 42 cases (25%) were associated with known etiologic factors, such as vinyl chloride monomer exposure during preparation of poly(vinyl chloride), use of Thorotrast in angiography, exposure to inorganic arsenic, and treatment with androgenic-anabolic steroids; 126 cases (75%) are of uncertain etiology. HAS most often affects males (ratio of approximately 3:1), peaks in the sixth and seventh decades of life (somewhat earlier than other sarcomas of the liver) and appears to occur more often in the industrialized Northeast and Midwest (although reporting artifact may be a factor). There is an extraordinary relative risk for poly(vinyl chloride) polymerization workers; there may also be other chemical-industrial associations that require further investigation. Prospective epidemiologic studies of HAS should be considered as a means of identifying other causative factors (e.g., chemicals or drugs) related to HAS.

Adolescent↗

Chronic hepatitis in chimpanzee carriers of hepatitis B virus: morphologic, immunologic, and viral DNA studies.

Years after infection with hepatitis B virus, chimpanzees may have manifestations of the carrier state as described in man. In addition to serologic evidence for persistent viral infection, percutaneous liver biopsy specimens showed hepatitis B virus surface antigen in the cytoplasm and hepatitis B virus core antigen in the nucleus. Four carrier animals had portal inflammatory reaction as seen in human chronic persistent hepatitis. Viral DNA was demonstrated in nucleic acid extracts of liver biopsy specimens by molecular hybridization to cloned plasmic pA01 containing hepatitis B virus DNA sequences. Although a viral molecule of length greater than the putative virus was identified, it did not appear to represent integration of viral DNA into the host genome. The chimpanzee model may serve as a means to study the mechanism of hepatitis B viral persistence and progression to chronic liver disease.

Animals↗

[Bidermal hepatoblastoma in an adult (author's transl)].

Hepatoblastomas are more common in childhood but extremely rare in adults. A further case of hepatoblastoma in an adult is reported: The tumor consisted of two components, epithelial and mesenchymal ones. Both were well-separated from each other and showed different ways of metastasizing in to lymphatic vessels and lymph nodes or in to blood vessels and lung, respectively. It is concluded that hepatoblastomas of mixed type originate from two different cell types: The tubular and, sometimes, acinar malignant cells originate from the epithelium of the foregut and the osteo-osteoid-chondromatous malignant component is derived from mesenchymal cell of the coelomic wall.

Aged↗

Histogenesis of alcoholic fibrosis and cirrhosis in the baboon.

Sequential liver specimens of 18 baboons exposed for up to 6 years to alcohol on a nutritionally adequate diet, as well as those of pair-fed controls, were examined by light microscopy. Whereas control animals failed to develop pathologic changes, in all baboons exposed, ethanol produced initial steatosis and subsequently fibrosis. Emphasis was on the pattern of the fiber accumulations as related to lesions of the hepatocytes. Segmented neutrophilic leukocytes were rarely observed, and the picture of frank alcoholic hepatitis was absent, but diffusely increased mononuclear sinusoidal cells and interstitial clusters of such cells with PAS-positive macrophages were abundant. Fibrosis proceeding to septum formation was associated mainly with large-droplet steatosis. Septum formation was initiated by excess layers of reticulin around steatotic hepatocytes or, more frequently, by linking of fiber accumulations around the clusters of mononuclear cells, in both instances with subsequent deposition of collagen fibers. Both processes were prominent in the centrolobular zone, creating a perivenous net-like fibrosis, but septum formation also started within the lobular parenchyma and eventually linked with the barely altered portal tracts. Fifteen alcohol-fed baboons developed septums, with diffuse septal fibrosis in 5; 4 proceeded to septal cirrhosis and 1 each to micronodular and to mixed micromacronodular cirrhosis. Cirrhosis in the baboons thus develops without the conspicuous polymorphonuclear inflammation characteristic of human alcoholic hepatitis. These observations indicate a pathway to cirrhosis over creeping fibrosis that might play a role also in man, instead of (or supplementing) the one proceeding over alcoholic hepatitis.

Animals↗

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗

The significance of variations in the distribution of copper in liver disease.

Biopsy and autopsy specimens of liver from patients with Wilson's disease in various stages, chronic cholestatic conditions (including primary biliary cirrhosis, extrahepatic biliary obstruction, sclerosing cholangitis, and biliary atresia), chronic active hepatitis, and Indian childhood cirrhosis, as well as normal neonates, were examined by means of histochemical techniques for copper and copper-associated protein. The intracellular localization of copper and the lobular distribution of the metal and its associated protein differed in these conditions. Periportal hepatocytes containing granules (lysosomes) that were reactive for copper and for copper-associated protein were characteristic of cholestasis and neonatal liver. However, in cholestasis extralysosomal copper was often present in the hepatocellular cytoplasm. In contrast, in Wilson's disease, despite very high concentrations of copper in the early stages, the metal was diffuse in the cytoplasm, and the histochemical reactions for granular copper and its associated protein were usually negative. Therefore, a failure to stain for copper does not exclude the diagnosis of Wilson's disease. In the late stages of Wilson's disease staining varied in different nodules. In Indian childhood cirrhosis copper was present throughout the parenchyma, with periportal predominance. Differences in the distribution of copper and the cellular changes associated with its deposition suggest that different pathogenetic mechanisms and possibly different intracellular targets are susceptible to the toxic effects of the metal. For diagnosis, staining for copper and for copper-associated protein may assist in the differentiation of primary biliary cirrhosis from chronic active hepatitis.

Adolescent↗

["Fatty neck." Symmetrical lipomatosis with Madelung's symptom (author's transl)].

The relatively rare disease of symmetrical lipomatosis is described on the basic of six own observations. For many years five patients worked with asphalt and one was a coal-miner. Because of this professional exposition oil and cole products are considered to be reason for this disease. The still unknown aetiology and pathogenesis are discussed and finally the surgical therapy is presented.

Head and Neck Neoplasms↗