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Biomedical subjects

R L Peters

Publications and source records attributed to R L Peters.

At least 91 records · Page 5Linked to original sources

Natural immunity in mice to structural polypeptides of endogenous type C RNA viruses.

The immunological responses of inbred mice to structural components of one class of endogenous virus were investigated by means of radioimmunoassays utilizing highly purified viral proteins. Naturally occurring antiviral antibodies were demonstrated only in those strains possessing information for induction of a mouse cell-tropic endogenous virus. Moreover, these antibodies invariably appeared subsequent to the detection of spontaneous replication of this virus in the same animal. The immune responses elicited were much stronger against endogenous viral gp70 than p30, consistent with previous findings of tolerance in the mouse to the major structural antigen of its endogenous virus. However, the demonstration of an immune response to p30 under conditions of both natural and experimental immunization establishes that tolerance to this viral antigen can be overcome.

AKR murine leukemia virus↗

An approach to C-type virus immunoprevention of spontaneously occurring tumors in laboratory mice.

A review of our current progress in C-type virus vaccine research is presented. This includes the findings of C-type virus or its antigen expressions in every naturally occurring tumor of two strains of "low-incidence" laboratory mice, the BALB/cCr mouse and the NIH Swiss mouse. Vaccine preparation methods are described including the inactivation of C-type virus infectivity with optimal maintenance of the antigen titers of at least two of the polypeptides of the C-type virus, gp69/71 and p30. The cell-mediated immune response of the mouse to C-type virus vaccines, as measured by a footpad assay for delayed-type hypersensitivity and an in vitro lymphocyte transformation assay, is described. Studies with two murine C-type viruses (Rauscher leukemia and Gross leukemia) a simian C-type virus, and an avian C-type virus (avian myeloblastosis virus) showed that the cell-mediated immune response of the animal includes type-specific, group-specific, and interspecies-specific reactivity. The mouse gave a cell-mediated immune response to at least one of the polypeptides of the C-type virus, the gp69/71, whether this polypeptide was presented to the immune system of the mouse as whole virus, Tween-ether-treated virus, or a purified polypeptide. One measure of the effectiveness of the C-type virus vaccines was provided by immunization of the mouse with Rauscher leukemia virus preparation that induced resistance to challenge with both live Rauscher leukemia virus and a naturally occurring BALB/c leukemia virus. Evidence is presented that the C-type virus can act as an effective transplantation antigen in syngeneic tumor cell lines resulting in the immunogenicity and loss of tumorigenicity of these cell lines. An approach to the viral immunoprevention of spontaneously occurring tumors is discussed.

Animals↗

Differences in tumor incidence in two substrains of Claude BALB/c (BALB/cfCd) mice, emphasizing renal, mammary, pancreatic, and synovial tumors.

Observations were made on the tumor incidences in two substrains of the BALB/CFCd mouse. A total of 900 mice were examined. They comprised two substrains (families), direct descendants of two different females (designated 916 and 917) of the 31st inbred generation. Offspring of sibling matings of the fourth and fifth generation descendants of these two females were killed when moribund or when they had visible or palpable masses. Complete gross and microscopic examinations were conducted. Renal tumors were noted in 48.1% of those necropsied in family 916 and in 24.6% of those in family 917 (p less than .025). Mammary tumors were found in 13.3% of family 917 and in 3.3% of family 916 (p less than .001). Neoplasms of the reticulo-endothelial system (reticulum cell neoplasms, lymphocytic leukemia, other lymphocytic neoplasms) were found in 20.0% of family 917 but only in 11.2% of family 916 (p less than .005). Tumors of the respiratory system (primarily alveolar adenomas and alveolar adenocarcinomas) were found in 10.2% of family 916 and 16.5% of family 917 (p less than .05). Less commonly observed tumors included synoviomas, 7.6% in family 916 versus 2.1% in 917 (p less than .005), and seven pancreatic acinar adenomas, all but one of which were found in family 916. Also recorded were a total of nine myoepitheliomas, 28 hemangioendotheliomas, two interstitial cell tumors of the testis, a single mesothelioma and a single rhabdomyosarcoma of the esophagus. Degenerative lesions consisting of kyphoscoliosis were noted in 3.7% of mice examined in both families combined.

Adenocarcinoma↗

Immunity to virus-free syngeneic tumor cell transplantation in the BALB/c mouse after immunization with homologous tumor cells infected with type C virus.

Syngeneic tumor cell lines free of endogenous type C virus or viral antigen antigen expression were derived from spontaneously occurring tumors of the BALB/cCr mouse. Two cell lines free of endogenous type C virus were examined and found to be highly tumorigenic in tumor growth kinetic studies. In vitro inoculation of these cell lines with Rauscher-murine leukemia virus (R-MuLV) resulted in their chronic infection in which 95 to 100% of the cells were scored as virus positive. These infected lines showed a highly significant increase in their immunogenicity as compared to their uninfected controls. Animals in which these virus-positive tumors regressed were then shown to be highly resistant to challenge with the uninfected tumor cell lines as well as to live R-MuLV. This observed resistance to uninfected tumor cell lines could not be induced by immunization of the mouse with uninfected tumor cells and R-MuLV simultaneously at the same injection site, nor could it be induced with lethally irradiated virus-infected tumor cells, subtumorigenic doses of uninfected cells, or inactivated R-MuLV or Gross leukemia virus (G-MuLV). Cell-mediated cytotoxicity studies revealed that spleen cells obtained from animals whose virus-infected tumors regressed were cytotoxic to homologous infected and uninfected tumor cells as well as to other uninfected tumor cell lines syngeneic to the BALB/c mouse. Correlation of in vitro cytotoxicity with in vivo immunity was provided by the Winn assay, by inoculation into susceptible mice of immune and nonimmune spleen cells premixed with uninfected tumor cells. The immune cells were highly effective in preventing this tumor cell transplantation. It was concluded that type-C virus infection of these syngeneic tumor cells resulted in their acquiring strong transplantation antigens that were in part due to the virion, but were at least in part due to alterations of antigens or haptens that are present in a less immunogenic form on the uninfected tumor cell.

Animals↗

Pregnancy in hepatitis B antigen positive cirrhosis.

Two pregnant women with chronic active viral hepatitis (HBs Ag+) and cirrhosis are described. In the first patient, maternal death occurred postpartum due to bleeding esophageal varices and liver and renal failure. Postmortem examination revealed advanced nodular cirrhosis and thrombosis of the splenic and portal veins. The infant was premature but did well and did not become infected despite the detection of HBsAg in the cord blood. Nine members of the patient's immediate family were tested; the blood of one sibling of the patient was found to be HBsAg+ and samples from 5 other members were found to be anti-HBs+. In the second patient, death due to liver failure occurred in the seventh month of pregnancy and postmortem examination revealed advanced nodular cirrhosis. Examination of multiple fluids from the mother and fetus were negative for HBsAg. In contrast to the apparent lack of effect of pregnancy on cirrhosis of the liver in general, the possibility of an adverse effect in this particular type(HBs Ag+) should be considered.

Adult↗

Lymphocyte stimulation in hepatitis B infections.

Cell-mediated responses in patients with acute and chronic forms of Type B hepatitis were tested by lymphocyte transformation to purified hepatitis surface antigen (HBS Ag) and to phytohemagglutinin, by dinitrochlorobenzene sensitization and by response to skin-test antigens. Although absent during acute Type B hepatitis, lymphocyte transformation by HBS Ag appeared during early convalescence and remained detectable for six years after recovery. Patients with Type B chronic active hepatitis with increased serum transaminase levels showed a partial lymphocyte transformation with HBS Ag, whereas those with normal transaminase values demonstrated no transformation. Patients with Type B chronic persistent hepatitis and carriers of HBS Ag did not have lymphocyte transformation. Normal responses to dinitrochlorobenzene, intradermal skin tests and phytohemmaglutinin were found in all patients with acute, chronic active or chronic persistent hepatitis and carriers. These results indicate that recovery from Type B hepatitis is associated with the ability to elicit a specific lymphocyte response to HBS Ag.

Acute Disease↗

Cirrhosis associated with partial deficiency of alpha-1-antitrypsin: a clinical and autopsy study.

A 63 year old woman with cryptogenic cirrhosis, ascites, portal hypertension, and intermediate levels of alpha-1-antitrypsin of protease inhibitor SZ phenotype who died of esophageal variceal hemorrhage is described. The partial deficiency of alpha-1-antitrypsin and the diagnosis of cirrhosis were suspected one year prior to death because a needle biopsy of liver showed PAS positive, diastase resistant cytoplasmic bodies within hepatocytes. This report illustrates three previously undescribed features: (1) Heterozygous protease inhibitor SZ phenotype may be associated with coarsely nodular cirrhosis in the older adult. (2) The large intracytoplasmic glycoprotein droplets that are distinctive by light microscopy are probably formalin induced aggregates of submicroscopic flocculent material. (3) In the older patients with aberrant alpha-1-antitrypsin the flocculent material is present not only in the granular endoplasmic reticulum but also in smooth endoplasmic reticulum vesicles and cytolysosomes.

Autopsy↗

Post-jejunoileal-bypass hepatic disease. Its similarity to alcoholic hepatic disease.

The authors studied serial hepatic biopsies of five patients who developed hepatic failure following jejunoileal bypass for extreme obesity, with autopsies of two. The hepatic histologic changes included centrilobular or focal alcoholic hyalin, intrasinusoidal collagenosis, fatty hydropic degeneration, and neutrophilic infiltrate. At least two of the patients were abstinent from alcohol, both prior to and after the surgical procedures. The others, after the bypass procedures, had reduced alcohol consumption from previous levels. All patients developed hepatic failure and histologically progressive hepatic disease with alcoholic hyalin and other changes indistinguishable from alcoholic hepatic disease in 21/2 to 5 months, in spite of hyperalimentation and re-establishment of intestinal continuity in four. Nausea, vomiting, abdominal pain and ascites were prominent complaints. Four of the five patients died in hepatic failure. The authors conclude that these cases of progressive hepatic disease with histologic changes simulating those found in livers of alcoholic patients offer evidence that heavy alcohol consumption may affect the liver in an indirect fashion.

Adult↗

Incidence of spontaneous neoplasms in F344 rats throughout the natural life-span.

The age-related incidence of spontaneously occurring neoplasms and degenerative diseases in the F344 inbred rat strain was established from the histologic examination of tissues from 160 male and 192 female rats kept throughout their natural life-span. The most common neoplasms were leukemias (25%), mammary tumors (females, 40.6%; males, 23.1%), pituitary adenomas (females, 35.9%; males, 23.8%), and testicular interstitial cell tumors (males, 85%). Various less common neoplasms were observed: thyroid interstitial cell tumors, adrenocortical adenomas, carcinomas of the genitourinary tract, representative central nervous system tumors, pheochromocytomas, and tumors of mesodermal origin including mesotheliomas, myoblastomas, fibromas, and fibrosarcomas. Multiple tumor types were found in 176 of the rats; metastatic tumors were uncommon. Degenerative diseases including myocardial degeneration and nephrosis were often observed. The incidence rate of these neoplasms and degenerative diseases generally increased with advancing age of the animals.

Adenoma↗

Assay in the mouse for delayed-type hypersensitivity to murine leukemia virus.

Delayed-type hypersensitivity (DTH), assayed by footpad swelling, was induced in 6- to 8-week-old BALB/cCr mice immunized with formalin-inactivated, sucrose-banded murine type-C viruses. The DTH response was inducible with as little as 11.25 mug sensitizing antigen, was greatest after sc sensitization as compared to im and ip sensitization, and was optimally elicited with a 7-day challenge. A statistical evaluation of the DTH assay revealed that the test was consistently reproducible and limited only by biologic variability of the mouse and the standardization of the antigen preparation. The DTH response was specific for type-C virus subtypes because it could distinguish the Rauscher strain of murine leukemia virus from AKR leukemia virus when the challenge antigen was extracted with Tween 80-ether. Immunized mice that gave DTH responses were resistant to challenge with exogenous, live murine leukemia viruses.

Animals↗

Cordycepin inhibition of 3-methylcholanthrene-induced transformation in vitro.

Cordycepin (3-deoxyadenosine), an inhibitor of poly (a) synthesis, was found to inhibit the induction of the endogenous type "C" RNA virus by 5-iodo-2'-deoxyuridine in a line of Fisher rat embryo cells (H43) grown in vitro, and when continuously incorporated into the medium at those same concentrations, it was found to protect the cells from transformation by the chemical carcinogen 3-methylcholanthrene.

Cell Line↗

Sensitive in vivo assay for detection of murine leukemia viruses.

A test is reported for the in vivo detection of the replicative ability of murine leukemia viruses (MLV) in the BALB/c mouse strain. Growth in the spleen was assayed by the complement-fixation assay for MLV group-specific antigen after injection of newborn mice. Low doses of laboratory-derived and wild-type MLV from cell-culture and animal-grown sources were detected as early as 7 to 14 days postinoculation. The sensitivity of this in vivo test compared favorably with in vitro assays for MLV. In vivo detection of MLV replication was correlated with long-term oncogenicity.

Animals↗

Murine C-type RNA virus from spontaneous neoplasms: in vitro host range and oncogenic potential.

Strain BALB/c mice harbor at least two host range variants of marine leukemia virus. One variant, which is host-cell tropic, is the predominant isolate from neoplastic tissues and produced lymphoreticular neoplasms when injected into BALB/c newborn mice. A second variant, whicht is isolated throughout life, grows poorly in host embryonic cells in culture and was not associated with lymphoreticular neoplasm induction when injected into newborn BALB/c mice.

Animals↗