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Biomedical subjects

R L Peters

Publications and source records attributed to R L Peters.

At least 73 records · Page 4Linked to original sources

Hepatocellular carcinoma in the U.S.A., etiologic considerations. Localization of hepatitis B antigens.

The serologic and tissue markers of hepatitis B virus (HBV) were studied in 50 patients in whom hepatocellular carcinoma (HCC) was confirmed at autopsy. Serologic and tissue markers included serum hepatitis B surface antigen (HBsAg), tissue HBsAg, tissue hepatitis core antigen (HBcAg), and serum antibody to HBcAg (anti-HBc). Twenty-two patients had HCC arising in alcoholic cirrhosis; 2 of the 22 (9.1%) had one or more of the HBV tissue and serologic markers. This infection rate is similar to the rate of 7.9% observed in 63 control alcoholic cirrhotic patients without HCC. In contrast, 15 of 20 (75.0%) patients with HCC in nonalcoholic chronic active liver disease showed evidence of active HBV infection. One of 8 patients with HCC in normal liver had serum HBV markers. This result indicates that there is an extremely high prevalence of HBV infection among HCC patients with nonalcoholic chronic liver disease in the U.S.A. The prevalence of HBV infection in these patients is as high as that observed in Asia and Africa. Thus, it can be concluded that the lower prevalence rate of active HBV infection in HCC patients in the U.S.A. is the result of statistical dilution of HCC-B-viral disease by the large numbers of the alcoholic cirrhotic patients with HCC, and that if chronic active hepatitis type B were as common in the United States as it is in Africa and Asia, the frequency of occurrence of HCC might also be as high.

Adult↗

In vitro and in vivo indications of the carcinogenicity and toxicity of food dyes.

Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude the the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.

Animals↗

Mammary tumors, hepatocellular carcinomas, and pancreatic islet changes in C3H-Avy Mice.

Studies of tumor incidence and assorted lesions found in 187 C3H-Avy mice throughout their natural life-spans revealed the following: Hepatocellular carcinomas occurred in 54.3% of males, mammary carcinomas in 95% of females, pancreatic islet cell adenomas in 9.4% of males and in no females, and pancreatic islet cell hyperplasia in 41% of males and 23% of fefemales. Islet cell hyperplasia and adenomas appeared to consist predominantly of alpha and delta cells. Multiple tumors, or hyperplasia, or both, of a single site or of multiple sites occurred as frequently in males as they did in females--49.6% and 51.7% respectively. The most frequent neoplasms were hepatocellular carcinomas and islet cell tumors or hyperplasia in males (45.7%) and multiple mammary tumors in females (30%). Heretofore unreported tumors found in this strain of mouse were 12 islet cell adenomas, 2 spindle cell tumors of the meninges and olfactory lobes, a squamous cell carcinoma of the nasal turbinates, and a schwannoma of the spermatic cord.

Adenoma, Islet Cell↗

Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group.

Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.

Alanine Transaminase↗

5-Flourouracil in hepatocellular carcinoma: report of twenty-one cases.

Twenty-one patients with biopsy-proven hepatocellular carcinoma were treated with oral or intravenous 5-Fluorouracil according to a randomized treatment schedule. Twenty-one patients were evaluable for response and toxicity. The two groups were comparable in distribution of pretreatment characteristics. There were no objective responses in either group. This is the largest reported group of patients with hepatocellular carcinoma treated with 5-Fluorouracil. Toxicity occurred in 46% of patients treated, but was tolerable. In contrast to previous reports, we have found that weekly 5-Fluorouracil given orally or intravenously is not of significant value in the treatment of hepatocellular carcinoma.

Administration, Oral↗

Chemical transformation of rat cells infected with xenotropic type-C RNA virus and its suppression by virus-specific antiserum.

Fischer rat embryo cells infected with xenotropic mouse type-C RNA viruses isolated from either NIH Swiss mice or C57L inbred mice were transformed by 4-nitroquinoline oxide or 3-methylcholanthrene under conditions in which neither treatment alone sufficed to induce transformation. Transformation was dependent on the presence of actively growing virus at the time of chemical treatment. Specific antibody to xenotropic virus neutralized the virus and inhibited malignant transformation by 3-methylcholanthrene.

Animals↗

Immunoprevention of x-ray-induced leukemias in the C57BL mouse.

An attempt to prevent irradiation-induced thymic lymphomas in C57BL mice was made by inducing active immunity to endogenous type-C virus with inactivated Rauscher murine leukemia virus (MuLV) or inactivated Gross MuLV or by transferring passive immunity to endogenous type-C virus with goat anti-Gross MuLV IgG. Control groups received the following immunogen or treatment: inactivated simian sarcoma virus, complete Freund's adjuvant, normal goat IgG, and diluent, in both irradiated and nonirradiated C57BL mice Active immunity to the 70,000 molecular weight glycoprotein AKR-gp70 by immunization with Rauscher MuLV and passive immunity to AKR-gp70 by passive transfer of goat anti-Gross-MuLV IgG was measurable throughout some of the latent period of tumor development; in these two groups a significant reduction in tumor incidence was observed, as compared to the other experimental and control groups. Thus, the present findings support the concept of a type-C virus etiology of irradiation-induced leukemias and demonstrate the applicability of immunologic techniques directed against the endogenous type-C virus in the prevention of this disease.

Animals↗

Patterns of hepatic morphology in jejunoileal bypass patients.

The close similarity of the hepatic histological pattern in two conditions, I) jejunoileal bypass and 2) chronic alcoholism, is described, including the inconstancy of development of permanent hepatic changes in both conditions. It appears that serious hepatic disease develops in an incidence between 1 and 17% of patients who have received the operation. Hepatic disease presents itself as: 1) acute hepatic failure, 2) insidious development of cirrhosis, or 3) tenous hepatic functional state that reduces hepatic resistance to other insults.

Adult↗

The changing incidence of association of hepatitis B with hepatocellular carcinoma in California.

Two hundred seventy-nine patients who died of hepatocellular carcinoma were autopsied at Los Angeles County--USC Medical Center and the John Wesley--USC Liver Unit from 1949 through 1974, and tissues from 168 of these cases were available for staining for hepatitis B surface antigen (HBSAg). Twenty-one per cent of the livers had stainable HBSAg. There were prominent increases both in total numbers of hepatic cancers and in the percentages that were HBSAg-positive beginning about 1970, but the numbers of hepatocellular carcinomas arising in noncirrhotic livers also increased. From 1969 to 1974, 73% of those who had hepatocellular carcinomas arising to nonalcoholic but cirrhotic livers were HBSAg-positive. Racial differences in the incidences of cirrhosis, the incidences of hepatocellular carcinomas associated with HBSAg were found. The incidences of cirrhosis were: Caucasian 11%; Mexican 12.2%; Negro 5.7:; Oriental 10%. Hepatocellular carcinomas arose in 3.2% of Caucasians who had cirrhosis; 3.6% of Mexicans; 8.3% of Negroes; 47% or Orientals. Ten per cent of Caucasians who had hepatocellular carcinomas in cirrhotic livers were HBSAg-positive; 25% of Negroes; 12% of Mexicans; 47% of Orientals.

Adenocarcinoma↗

Liver replacement for alpha1-antitrypsin deficiency.

A 16-year-old girl with advanced cirrhosis and severe alpha 1-antitrypsin deficiency of the homozygous Pi ZZ phenotype was treated by orthotopic liver transplantation. After replacement of the liver with a homograft from a donor with the normal Pi MM phenotype, the alpha 1-antitrypsin concentration in the recipient's serum rose to normal; it had the Pi MM phenotype. Two and a third years later, chronic rejection necessitated retransplantation. Insertion of a homograft from a heterozygous Pi MZ donor was followed by the identification of that phenotype in the recipient's serum. Neither liver graft developed the alpha 1-antitrypsin glycoprotein deposits seen with the deficiency state. These observations confirm that this hepatic-based inborn error of metabolism is metabolically cured by liver replacement.

Adolescent↗

An immunoperoxidase technic for the demonstration of the hepatitis B surface antigen in human livers.

A sensitive method for demonstrating the site of hepatitis B surface antigen (HBsAg) in fixed tissues embedded in either paraffin or araldite is described. The method employs the peroxidase-rabbit antiperoxidase linkage through goat antirabbit to rabbit anti-HBsAg. In staining hepatitis antigen in agar, comparison of fixation (using three common fixatives) with unfixed precipitation arcs revealed no recognizable differences in antigenicity induced by fixation. The method allows confirmation of positive reaction by appropriate blocking controls. The technic is compared with the orcein stain of Shikata and found to be somewhat more sensitive but slightly more time-consuming.

Antigen-Antibody Complex↗

Development of a lymphocyte transformation microassay for murine leukemia virus.

A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweek mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 mug during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cell infected with MuLV.

Animals↗

Natural occurrence of tumors in mouse strains with different xenotropic and ecotropic endogenous viruses.

Natural tumor incidence and type C virus expression in HIH Swiss and BALB/c mice were investigated. The BALB/c mice showed a moderate incidence of lymphoreticular tumors containing infectious ecotropic virus. A second class of lymphoreticular tumors occurred with approximately the same incidence in both strains; though infectious virus could not be isolated from it, it contained the antigens of a common xenotropic virus. These xenotropic viral antigens were found in all NIH Swiss and BALB/c tumors examined and in normal hematopoietic tissues as well. The relationship between different classes of endogenous viruses and tumor development was discussed.

Age Factors↗