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Biomedical subjects

R Glaser

Publications and source records attributed to R Glaser.

At least 217 records · Page 12Linked to original sources

Seroconversion against Epstein-Barr virus in two nonhuman primate species infected by the oropharyngeal route.

Transforming Epstein-Barr virus (EBV) was inoculated into eight squirrel monkeys (Saimiri sciureus) by spraying of viral concentrates into the nose and throat. Virus was inoculated into three marmosets (two Saguinus oedipus and one Calithrix jacchus jacchus) by direct injection into nasopharyngeal tissue. Two of these squirrel monkeys seroconverted after repeated inoculation as determined by the presence of EBV-specific antibodies to early antigen and viral capsid antigen. One squirrel monkey had antibody to EBV nuclear antigen only. One S. oedipus marmoset also seroconverted. None of the animals developed disease. The results show that seroconversion can be accomplished in squirrel monkeys after spraying of EBV into the nasopharynx, and in marmosets by direct inoculation of the virus into nasopharyngeal tissue.

Aerosols↗

Renal arteriovenous fistula masquerading as severe valvar heart disease.

Two patients with renal arteriovenous fistulae are described, who presented in high output failure. Murmurs were detected in these patients on routine physical examination years before, and when cardiac failure ensued they were assumed to have decompensated valvar heart disease. Full investigation revealed the arteriovenous fistulae and both patients made a good recovery after surgical ligation.

Aged↗

Athymic nude mice: induction of tumors containing Epstein-Barr virus using Burkitt's-related cell lines.

We studied tumor induction in athymic nude mice by D98/HR-1 cells, an epithelial somatic cell hybrid containing the Epstein-Barr virus (EBV) genome, and by the parental D98 and HR-1 cells. Groups of animals were inoculated with cells grown in culture, with cells from tumors induced by the cell lines, or with cells from lines derived from tumors. The tumors induced by D98/HR-1 cells were undifferentiated carcinomas; those induced by D98 cells were carcinomas and those induced by HR-1 cells were poorly differentiated lymphomas. Preliminary data suggest that the number of EBV genome equivalents was sharply reduced in cells from both D98/HR-1 and HR-1 tumors. Subsequent passage of tumor cells in vitro resulted in a partial recovery in the number of EBV genome equivalents in HR-1 cells and a complete recovery in D98/HR-1 cells. The reduction in the number of EBV genomes in the tumor cells suggests that in vitro passage can influence the number of EBV genomes in these cells.

Animals↗

Expression of latent Epstein-Barr virus genomes in human epithelial/Burkitt's lymphoblastoid hybrid cells.

Expression of latent Epstein-Barr virus genomes in somatic-cell hybrids of Burkitt's lymphoblastoid cells has been studied. Treatment of the hybrid cells, D98/Raji and D98/HR-1, with IUDR induced the formation of EA and VCA and replication of virus DNA, whereas the same treatment of Raji cells induced only the formation of EA. The patterns of transcription of virus genomes in these three cell lines were, however, very similar: 25% without treatment with IUDR, 30% immediately after the treatment and 50% (entire genome transcription) three days after being transferred to fresh medium. The amount of virus RNA in the cells, calculated from DNA-RNA hybridization kinetics, was proportional to the number of virus genomes per cell, suggesting that every copy of virus DNA in these cells is actively transcribed.

Antigens, Viral↗

Transcription of Epstein-Barr virus genomes in human lymphoblastoid cells and in somatic-cell hybrids of Burkitt's lymphoma.

Expression of latent Epstein-Barr virus genomes in lymphoblastoid cells and somatic-cell hybrid of Burkitt's lymphoblastoid cells has been studied. IUDR treatment induced the formation of early antigen (EA), virus capsid antigen (VCA) and virus DNA replication in D98/Raji and D98/HR-1 cells whereas only EA was induced in Raji cells. HR-1 clone No. 9 did not respond to IUDR treatment. The pattern of transcription of virus genomes in these cell lines without IUDR treatment was uniform with 20--25% of virus DNA transcribed. IUDR treatment enhanced the transcription of virus DNA to 50% in D98/Raji, D98/HR-1 and Raji cells but no enhancement of virus genome transcription was observed in HR-1 clone No. 9 The amount of virus RNA in the cells calculated from DNA-RNA hybridization kinetics was found to be proportional to the number of virus genomes per cell indicating that every copy of virus DNA in these cells is actively transcribed.

Burkitt Lymphoma↗

Studies on the association of the Epstein-Barr virus genome with chromosomes in human (Burkitt)/mouse hybrid cells.

We have used somatic-cell hybrids of mouse fibroblast and Burkitt's lymphoblastoid tumour cells to continue our investigation of the association between Epstein-Barr virus (EBV) genome and human chromosomes. A mouse/Burkitt hybrid cell, designated CL1D/HR-1, was cloned in soft agar. Each of 10 clones was assayed for the spontaneous expression of EBV-associated nuclear antigen (EBNA), early antigen (EA) and virus capsid antigen (VCA). Six of 10 clones were EBNA-positive but negative for EA and VCA even after treatment with iododeoxyuridine. One clone, designated M44, contained approximately 90% EBNA-positive cells and 0.3--0.5 EBV genome equivalents per cell. Thirty subclones of clone M44 were obtained and analysed for EBV DNA, EBNA and human chromosomes. Four subclones (three EBNA-positive and one EBNA-negative) were studied in detail. Data obtained thus far indicate that none of the four subclones of clone M44 studied contained any intact human chromosome. Isozyme analysis of these subclones indicated that all four subclones, regardless of the status of the EBV genome, synthesized nucleoside phosphorylase, an enzyme which has been linked to human chromosome number 14.

Animals↗

Enhanced oncogenic behavior of human and mouse cells after cellular hybridization with Burkitt tumor cells.

Studies were made of the expression of the Epstein-Barr virus (EBV) in somatic hybrids of Burkitt tumor cells and human or mouse cells to determine whether EBV genetic information associated with the capacity to transform leukocytes of human and non-human primates could be maintained and expressed in nonlymphoblastoid cells. Data obtained thus far suggest that at least one characteristic associated with cellular transformation (loss of contact inhibition) is expressed only in nonlymphoblastoid cells in which the EBV genome is maintained. In addition, we have demonstrated that human epithelial/Burkitt hybrid cells (D98/HR-1 and D98/Raji) are more oncogenic in nude (athymic) mice than are cells of the human epithelial parental line, D98, or one of the Burkitt lymphoblastoid parent cell lines (Raji); the HR-1 Burkitt parent cell line was as oncogenic as the hybrid cell lines but the time required to induce tumors was much longer. Thus, human epithelial cells show alteration of growth properties in vitro and in vivo after cellular hybridization with Burkitt tumor cells.

Animals↗

Partial characterization of a herpes-type virus (K9V) derived from Kaposi's sarcoma.

A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts.

Antigens, Viral↗

Cell surface markers on epithelial-Burkitt hybrid cells superinfected with Epstein-Barr virus.

Attempts were made to superinfect two epithelial-Burkitt hybrid cell lines, designated D98/HR-1 and D98/Raji, with Epstein-Barr virus (EBV) and to investigate the expression of some cell surfacr markers including histocompatibility antigens, and the presence of B-cell markers, such as receptors for the third complement component and for monkey red blood cells. Successful superinfection of D98/HR-1 cells with EBV was made evident by the expression of early antigen and, to a lesser extent, virus capsid antigen. Only a rare D98/Raji cell was found to be positive for early antigen. The histocompatibility antigens of the parental cell lines D98, HR-1, and Raji were expressed on the surfaces of the hybrid cells. Receptors for third complement components b and d were not detected on the hybrid cells or on the D98P OR HR-1 cell lines; they were found, however, on the Raji cells, indicating that EBV receptors and complement receptors can be separated. The significance of the infection of the hybrid cells with EBV and the expression of cell surface markers is described.

Antigens, Viral↗

Scanning electron microscopy of the surfaces of hamster embryo cells transformed by herpes simplex virus.

The surfaces of normal hamster embryo fibroblast (HEF) cells were examined by scanning electron microscopy. Surface characteristics of HEF cells were compared to those of cells derived from a primary tumor induced in hamsters following s.c. inoculation of herpes simplex virus type 1-transformed HEF cells (14-012-8-1) and to the surfaces of cells derived from a metastatic tumor to the lung induced by the same cells. The most obvious difference in the surface characteristics of the examined cells was the morphology of the microvilli. In the few HEF cells that possessed microvilli, the distribution was uneven, and the lengths of the microvilli and the filopodia were variable. However, the surfaces of both tumor cell lines showed large numbers of microvilli which were evenly distributed over the surface of the cells, giving an almost "hairy" appearance. Long filopodia were occasionally observed on the surface of the primary tumor cell line and on the cell line derived from the metastatic tumor. Ruffles and blebs were occasionally observed on HEF cells and on the primary tumor cells but were not seen on the cells of the metastatic tumor.

Animals↗

[Sedimentation rate of erythrocytes as an indicator for phase transitions in the membrane].

Temperature dependent sedimentation measurements with human erythrocytes showed that the sedimentation velocity at 21 degrees C in Krebs-Ringer-solution, pH 7.4, has a peak shaped minimum [1]. In further investigations it could be shown that a phase transition of membrane lipids is the main reason of this peak. Membrane proteins influence the sedimentation behavior of the erythrocytes only by changing the interaction with membrane lipids.

Blood Sedimentation↗

Selective growth of transformed cell lines by rat liver perfusate.

Perfused rat liver releases growth-promoting activity for viral, spontaneous, and chemically transformed cells. After 5 days of incubation with perfusate, cell lines 3T12-NY (a spontaneous fibroblast transformant), NQ-T1 (a chemically transformed fibroblast line), W-8 (a chemically transformed epithelial rat liver cell line increase in cell growth above controls. Their respective normal counterparts: 3T3 Cl 42, A31-714, K-16, and HEF are not so stimulated. Within another set, the virally transformed mouse fibroblast cell line, SV3T3, exhibits a 27-fold increase in growth; however, 3T3 (mouse, fibroblasts), Py3T3 (polyomatransformed 3T3 cells), SV-Fl2-101 (a flat revertant line), and SV-Py-3T3 (a doubly transformed line) are nonresponsive. Perfused rat liver also release survival activity for SV-3T3 cells. The growth-stimulating activity in liver perfusate is selective for transformed cells. It is suggested that the liver may play a role in suporting neoplasia in vivo.

Animals↗