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Biomedical subjects

L G Wolfe

Publications and source records attributed to L G Wolfe.

At least 37 records · Page 2Linked to original sources

Epstein-Barr virus (EBV)-induced lymphoproliferative disease in cotton-topped marmosets.

Six cotton-topped marmoset monkeys (Sangiunus oedipus) were inoculated with 10(5) transforming units of B95-8 virus, and two of them developed fatal lymphoproliferative disease. The EBV-carrying tumor cells from these marmosets had the following characteristics: (1) they were polyclonal by surface immunoglobulin and immunoglobulin production in vitro; (2) they had no specific chromosome abnormalities, and (3) they failed to form colonies in large percentages in agarose. It is proposed that a spectrum of phenotypes of EBV-induced lymphoproliferative diseases in the cotton-topped marmosets may be identified and are more akin to fatal infectious mononucleosis or X-linked lymphoproliferative syndrome than to Burkitt's lymphoma.

Animals↗

Effect of chlorine treatment on infectivity of hepatitis A virus.

This study examined the effect of chlorine treatment on the infectivity of hepatitis A virus (HAV). Prodromal chimpanzee feces, shown to induce hepatitis in marmosets (Saguinus sp.), was clarified, and the virus was precipitated with 7% polyethylene glycol 6000, harvested, and resuspended. The suspension was layered onto 5 to 30% linear sucrose gradients and centrifuged; the fractions containing HAV were dialyzed, and a 1:500,000 dilution of this preparation induced hepatitis and seroconversion in 2 of 4 marmosets. A 1:50 dilution of this preparation served as inoculum. Untreated inoculum induced overt hepatitis and seroconversion in 100% (5 of 5) of marmosets inoculated intramuscularly. Inoculum treated for various periods (15, 30, or 60 min) with 0.5, 1.0, or 1.5 mg of free residual chlorine per liter induced hepatitis in 14% (2 of 14), 8% (1 of 12), and 10% (1 of 10) of marmosets, respectively, and induced seroconversion in 29, 33, and 10% of the animals. Inoculum treated with 2.0 or 2.5 mg of free residual chlorine per liter was not infectious in marmosets as determined by absence of hepatitis and seroconversion in the 13 animals tested. Thus, treatment levels of 0.5 to 1.5 mg of free residual chlorine per liter inactivated most but not all HAV in the preparation, whereas concentrations of 2.0 and 2.5 mg of free residual chlorine per liter destroyed the infectivity completely. These results suggest that HAV is somewhat more resistant to chlorine than are other enteroviruses.

Animals↗

Karyotype of Saguinus labiatus labiatus (red-bellied marmosets).

The karyotype of Saguinus labiatus labiatus was determined by the Giemsa-banding technique on leukocytes cultured from 10 marmosets. The diploid chromosome number (2n = 46) was the same and the chromosome complement similar to other marmosets of genus Saguinus. Small karyotypic differences were found between S. l. labiatus and white-lipped marmosets (Saguinus fuscicollis) in the size of the X chromosome and in the banding pattern of one pair of metacentric chromosomes. A karyotypic variant was detected in 1 S. l. labiatus, characterized by a diploid chromosome number of 45 with balanced autosomal translocation involving two pairs of acrocentric chromosomes (T 16/19).

Animals↗

Rapid regression of fetal adrenal zone and absence of adrenal reticular zone in the marmoset.

Developmental changes in plasma dehydropiandrosterone (DHA) and in adrenal histology were studied in several marmoset species (Callithrix jacchus and Saguinus labiatus, nigricollis, and fuscicollis) to evaluate these primates as experimental models for the study of fetal adrenal zone regression. Newborn marmosets had a prominent fetal adrenal zone, plasma DHA levels above 1000 ng/dl, and plasma DHA sulfate (DHAS) levels of 140 micrograms/dl. The fetal zone regressed dramatically during the first week of life, paralleled by a marked decline in plasma DHA, the plasma DHA to cortisol ratio, and plasma DHAS. The adult marmoset, however, had no adrenal reticular zone and no evidence of adrenal DHA secretion; DHA levels in castrate adults were undetectable (less than 25 ng/dl). Thus, the marmoset represents the first example of a primate that has a regressing, DHA- and DHAS-secreting fetal adrenal zone but that does not subsequently develop a DHA-secreting adrenal reticular zone.

Adrenal Glands↗

Chromosomes and cell surface markers of marmoset lymphocytes and Epstein-Barr virus-transformed marmoset cell lines.

The G-banded karyotypes of both normal lymphocytes and Epstein-Barr virus (EBV)-transformed lymphocytes of cotton-topped marmosets (Saguinus oedipus) were examined. The marmoset lymphocytes and EBV-transformed lymphoblastoid cells had normal diploid chromosomes (2n = 46) with no specific cytogenic change associated with transformation in vitro. EBV-transformed marmoset lymphocytes expressed the cell surface markers of B lymphocytes and EB viral antigens.

Animals↗

Syncytium-forming virus of common marmosets (Callithrix jacchus jacchus).

This communication describes the isolation and characterization of a new syncytium-forming virus of common marmosets (Callithrix jacchus jacchus). The virus, isolated from skin explants and peripheral leukocytes of healthy animals, induced syncytia and subsequent cytolysis of several human, simian, and rodent fibroblastic cultures and induced a carrier state in mixed fibroblastic-epithelial or epithelial cell lines. Cytoplasmic and nuclear viral antigen was demonstrated in infected cells by indirect immunofluorescence tests using serum obtained from persistently infected common marmosets. Abundant virus particles were detected within cisternae of endoplasmic reticulum of lytically infected cells by electron microscopy. The virus incorporated [3H]uridine, banded at a density of 1.14 to 1.16 g/cm3 in sucrose, and possessed ribonucleic acid-dependent deoxyribonucleic acid polymerase. No antigenic cross-reactivity was detected between the marmoset virus and simian foamy virus serotypes 1 to 8 in neutralization and immunofluorescence assays. A seroepidemiological survey of a marmoset colony revealed that 53.5% of common marmosets contained antibodies against the virus, whereas other species of marmosets maintained in the same colony remained free of antibodies.

Animals↗

Herpesvirus saimiri: protective effect of attenuated strain against lymphoma induction.

An attenuated strain of Herpesvirus saimiri (A-HVS) induced a persistent, latent infection in common marmosets. Virus was recovered from circulating lymphocytes of infected animals and antibody response to virus-specified antigens was demonstrated over 3-12 months PI. A-HVS-infected common marmosets and animals without previous A-HVS exposure were challenged with oncogenic HVS (125-825 PFU); marmosets without A-HVS infection developed malignant lymphoproliferative disease and died 3 weeks PI whereas all persistently-infected animals have survived 38-43 months post challenge.

Animals↗

Role of elevated temperature in malignant transformation of mammalian cells in vitro.

Rat embryo cells subjected in vitro to transient incubation at an elevated temperature (39 degrees C) became transformed and induced fibrosarcomas in both homologous and heterologous hosts. Malignant transformation correlated with the occurrence of karyotypic changes which appeared long after incubation at 39 degrees C and subsequent return to 37 degrees C. Control cultures incubated at only 37 degrees C did not show similar chromosomal changes or induce tumors and remained predominantly diploid during the same observation period. In contrast to rat embryo cells, marmoset monkey cell cultures incubated at 39 degrees C did not develop characteristics of transformed cells.

Animals↗

Isolation of a virus closely related to gibbon ape leukaemia virus from cells infected with virus (HL-23V) released by human leukaemic cells.

Canine thymus cells infected with virus (HL-23V) produced by human acute myelogenous leukaemia cells in culture were shown in previous reports to produce transforming and non-transforming type C virus similar or identical to the simian sarcoma virus complex SSV(SSAV) and to induce tumours in marmoset monkeys (Bergholz et al. 1977a). In these earlier studies the appearance of breakthrough foci at low dilutions of antiserum in neutralization tests with high-titred anti-SSV(SSAV) serum suggested the presence of another virus, distinct from SSV-(SSAV). We now report the isolation of this component and, by comparative neutralization analysis, demonstrate that it is most closely related to gibbon ape leukaemia virus (GALV). It is distinguished from SSV(SSAV) by kinetics of neutralization and molecular hybridization experiments. This component was readily cloned both from virus produced by HL-23V chronically-infected canine thymus cells established by Teich et al. (1975) when HL-23V was first isolated and from virus produced by HL-23V-induced marmoset tumour cells in culture. The presence of this component in the original leukaemic cell cultures is discussed.

Animals↗

Isolation of a cytomegalovirus from salivary glands of white-lipped marmosets (Saguinus fuscicollis).

Minced salivary glands from seven white-lipped marmosets (Saguinus fuscicollis and Saguinus nigricollis) and one cotton-topped marmoset (Saguinus oedipus) were cocultivated with marmoset cell cultures. A viral agent, designated SSG, was isolated from two Saguinus fuscicollis. Slowly progressing foci of rounded, vacuolated, refractile cells were first observed at 40-43 days incubation. Electron microscopy revealed intranuclear herpesvirus nucleocapsids and intracytoplasmic and extracellular enveloped particles. Infected cells stained with hematoxylin and eosin contained eosinophilic intranuclear and cytoplasmic inclusion bodies. SSG could be passaged in cell cultures only using viable whole cells; infectious cell-free virus was not detected in either culture supernatants or cell lysates. SSG replicated in marmoset fibroblastic but not in marmoset epithelioid or human fibroblastic cell cultures. Plasma antibodies to SSG were detected by indirect immunofluorescence assays in 16 of 56 (28.6%) adult wild-caught marmosets but were absent in 40 colony-born, hand-reared marmosets. Antigenic cross-reactivity of SSG with a rhesus monkey (Macaca mulatta) cytomegalovirus (bidirectional) and with a human cytomegalovirus (unidirectional) was also demonstrated by indirect immunofluorescence assays. SSG was identified as a herpesvirus by morphology and was classified as a cytomegalovirus by its site of isolation, biologic properties in vitro, and antigenic characteristics.

Animals↗

Thermal treatment and infectivity of hepatitis A virus in human feces.

The susceptibility of white-lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28--100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG-BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1 : 3 dilution. A HAV-baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3 : 1 by centrifugation of the GBG-BM pool); one group was treated at 140 degrees F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heat-treated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish-associated hepatitis A and retain the palatability of the shellfish.

Animals↗

Oncogenicity of the C-type virus HL-23V in marmosets and characterization of virus isolated from an HL-23V-induced marmoset tumor: comparison with simian sarcoma virus type 1.

Dog thymus cells chronically infected with HL-23V, a C-type virus isolated from human acute myelogenous leukemia cells, produced both transforming and nontransforming virus indistinguishable from simian sarcoma virus type 1 (SSV-1/SSAV-1) and induced fibromas in newborn marmosets. All inoculated marmosets developed anti-HL-23V antibodies. A cell line established from a tumor biopsy produced transforming virus identical to SSV-1 and HL-23V at early passages. However, at later passages the cell line and a cell line established from residual tumor tissue removed at autopsy, produced virus which was neutralized only at low dilutions of anti-SSV-1 serum (1:32) relative to SSV-1 (1:1,024). This virus (BFV) was also distinguished from SSV-1 and HL-23V by XC tests, and by membrane immunofluorescence and serum cytotoxicity tests.

Animals↗

Susceptibility of marmosets to Epstein-Barr virus-like baboon herpesviruses.

Epstein-Barr virus (EBV)-like herpeviruses, strains of Herpesvirus papio (HVP), have recently been isolated from lymphomatous (HVP-L) and from normal baboons (HVP-N). Both HVP isolates infect some species of marmosets, HVP-L inoculated adult animals develop a mild to severe and sometimes fatal lymphoproliferative disease whereas newborn marmosets of the same species do not develop a measureable disease after inoculation with HVP-l. HVP-N infects adult marmosets but does not cause disease.

Animals↗

Overview of viral oncology studies in Saguinus and Callithrix species.

Marmoset monkeys are highly susceptible to tumor induction by type C sarcoma viruses and primate lymphotropic herpeviruses. Six experimental models were reviewed, three sarcoma models induced by Rous, feline or simian sarcoma viruses and three models of lymphoproliferative disease induced by Herpevirus saimiri, H. ateles or Epstein-Barr virus. Relative susceptibility of cotton-topped (Saguinus oedipus oedipus), white-lipped (S. nigricollis, S. fuscicollis subspecies) and commone (Callithrix jacchus jacchus) marmosets to the different viruses was compared.

Age Factors↗

Human spongiform encephalopathies in marmoset monkeys (Saguinus sp.).

Brain homogenates (10% w/v) from five of seven kuru patients inoculated intracerebrally (i.c., 0.1 ml) into marmosets (Saguinus sp.) induced a rapidly progressive CNS disease 26, 31, 36, 76 and 94 months postinoculation. Serial marmoset passages of kuru were accomplished by i.c. inoculation of neonatal marmosets with brain homogenates from marmosets with experimentally induced kuru. The incubation periods ranged from 1.5 to 11 months (average 7.3) in 19 animals, 20-25 months in four animals and greater than 26 months in two animals. Symptoms and brain lesions of the induced disease were compatible with kuru as observed in humans and other nonhuman primates. Creutzfeldt-Jakob disease (CJD) has been induced by i.c. inoculation of marmosets with brain homogenates from two of four human CJD patients with incubation periods of 43 and 54 months and is in serial passage.

Animals↗