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Biomedical subjects

M S Hirsch

Publications and source records attributed to M S Hirsch.

At least 217 records · Page 12Linked to original sources

Immune response to herpesvirus antigens in adults with acute cytomegaloviral mononucleosis.

The immune response of eight patients with mononucleosis caused by cytomegalovirus (CMV) was measured early in their illness--when virus was present in their urine and/or blood--and subsequently during convalescence. Levels of CMV-specific antibody rose early in the illness, but the proliferative response of mononuclear cells to CMV antigen did not reach the level characteristic of CMV-immune donors until several months later. The production of interferon by mononuclear cells in response to CMV antigen was also low early in the illness. Although these patients had prior immunity to herpes simplex virus and varicella-zoster virus, their mononuclear cells responded poorly to antigens prepared from these viruses. The proliferative response to these antigens returned to normal in parallel with the development of a normal response to CMV. It is suggested that acute CMV mononucleosis suppresses the proliferative response of human mononuclear cells.

Antibodies, Viral↗

Persistent infection of human lymphoid and myeloid cell lines with herpes simplex virus.

Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell line NC37 and myeloid cell line K562 for up to 222 and 374 days, respectively, but led to a significant decrease in the number of viable cells by 7 weeks of infection. The average number of cells producing infectious virus was very low in these cell lines (range, 0.5 to 2.7+) compared with a larger proportion of cells exhibiting HSV antigens by immunofluorescence (range, 24 to 58%). In contrast, null cell line LAZ 221 failed to replicate HSV even though the viral infection led to a cessation of cell growth.

B-Lymphocytes↗

Immunity to antigens associated with primate C-type oncoviruses in pregnant women.

Cell-mediated and humoral immune responses against antigens associated with primate C-type oncoviruses were evaluated in humans by microcytotoxicity and radioimmunoprecipitation assays. Five of six women tested sequentially during pregnancy developed selective cell-mediated reactivity against baboon endogenous virus (BEV)--infected human fibroblasts. Responsiveness peaked during the second and third trimesters and corresponded temporally with elevated antibody levels to BEV antigens. Similar cell-mediated reactivity was not observed in nonpregnant individuals. Selective cell-mediated reactivity directed against cells infected with the simian sarcoma virus-simian sarcoma associated virus complex (SSV--SSAV) was observed in four of 20 healthy adults (three of 14 nonpregnant, one of six pregnant). These observations suggest that cell-mediated reactivity against primate C-type oncoviruses is occasionally detected in healthy nonpregnant adults, but that during pregnancy both cell-mediated and humoral reactivity against BEV may become selectively expressed.

Animals↗

Cytomegalovirus infection in dialysis patients and personnel.

In a 12-month prospective study of cytomegalovirus infection on an acute hemodialysis unit, 10 of 80 patients (13%) and none of 26 staff developed active cytomegalovirus infection. Seven infections were coincidental with renal allograft rejection; three occurred 3 to 6 weeks after the transfusion of multiple units of conventional blood into seronegative patients. No person-to-person transmission was documented. In contrast to the effects of transfusing conventional blood, all 21 patients who entered dialysis without detectable cytomegalovirus antibody and received 2 to 10 U of frozen deglycerolyzed erythrocytes (total of 157 U) remained seronegative. Transmission of cytomegalovirus infection with transfusion with conventional blood is probably secondary to passage of leukocyte-borne virus that is lost during the freezing and deglycerolization procedure. Frozen erythrocytes prepared by cytoagglomeration procedures appear to be free of viable leukocytes and appear to carry a minimal risk of transmitting cytomegalovirus infection.

Acute Disease↗

Replication of herpes simplex virus and cytomegalovirus in human leukocytes.

Human peripheral blood leukocytes, lymphocyte subpopulations, and hemic cell lines were examined for their ability to supprot HSV and CMV replication. Mitogen-stimulated mononuclear leukocytes, B lymphocytes, and T lymphcytes supported the replication of HSV to high titers over 3 to 5 days of infection. HSV replicated in unstimulated mononuclear leukocyte cultures of one of five donors, and to a limited degree in untreated B lymphocytes of three of five donors; HSV replication was not detected in unstimulated T lymphocytes (five donors). There was no evidence of enhanced uptake of 3H-thymidine in the untreated donor cells that replicated HSV. CMV replication was not detected during 9 to 10 days of infection in untreated or mitogen-treated mononuclear leukocytes and lymphocyte subpopulations from the same adult donors or in neonatal cord blood leukocytes. The ability of the cells to support HSV or CMV replication did not correlate with the presence of specific antiviral antibodies in the donor serum. HSV replication in B, T, and myeloid cell lines to high titers over 5 days of infection, whereas CMV failed to replicate in any of the hemic cell lines. A persistent HSV infection has been established in a T cell line (CEM) with high titers of infectious virus being produced concurrently with growth of the cells over the first 11 weeks of infection.

Antibodies, Viral↗

Autoimmunity, oncornaviruses, and lymphomagenesis.

The interactions between aberrant immune responses and C-type oncornaviruses in mice are complex. These viruses may be activated during certain immune responses, e.g., histocompatibility reactions, in the face of chronic immunosuppression. Oncornaviruses, themselves, may induce autoaggressive cell-mediated responses in certain lymphoid subpopulations, and these autoimmune reactions may be important in subsequent lymphomagenesis. Parallel events may occur in other animal models, e.g., the NZB mouse, and in certain human disorders, e.g., Sjögren's syndrome, systemic lupus erythematosus, and myasthenia gravis.

Animals↗

Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus.

Cytomegalovirus (CMV) was isolated from hemic cells from seven of seven patients with acute CMV mononucleosis and from one of six patients with mononucleosis during convalescence. CMV was isolated from the mononuclear leukocyte fraction, the polymorphonuclear leukocyte fraction, or both cell fractions. Virus was not detected in washed erythrocytes, plasma, or leukocyte lysates. Mononuclear leukocytes from patients with acute CMV mononucleosis displayed an elevated level of incorporation of [3H]thymidine on the day of donation compared with that in cells from convalescent patients or normal donors. Responses to pokeweed mitogen and concanavalin A were significantly lower in patients with CMV mononucleosis than in normal donors. There were no significant differences among the acute, convalescent, and normal donor groups in response to phytohemagglutinin or in the one-way mixed leukocyte reaction. These findings suggest that in patients with CMV mononucleosis virus infects and may persist within peripheral blood leukocytes and that the lymphocytes of these patients are selectively hyporesponsive to certain mitogens.

Adult↗

Use of interferon in cytomegalovirus infections in man.

Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway.

Adult↗

Immunologic mechanisms in the pathogenesis of virus-induced murine leukemia. III. Target cell specificity of autoreactive thymocytes.

Thymocytes from preleukemic mice persistently infected with Moloney murine leukemia virus (MuLV-M-carriers) were vigorously autoaggressive toward normal syngeneic target cells; they exhibited a graded response to allogeneic cells, but they spared xenogeneic cells or syngeneic cells infected with MuLV-M or MuLV-G (Gross). Syngeneic target cells infected with nononcogenic lymphocytic choriomeningitis virus (LCMV), or transformed by the chemical carcinogen 3-methylcholanthrene were not similarly spared. This phenomenon, apparently induced by MuLV-M, is not associated with all persistent virus carrier states. Thymocytes from mice persistently infected with LCMV or with the lactic dehydrogenase virus (LDHV) failed to demonstrate an autoaggressive behavior. That transplantable lymphoma cells (derived from MuLV-M-carriers) were autoreactive in a pattern similar to thymocytes from preleukemic mice suggests a unique role for MuLV in the events leading from altered recognition of "self" to lymphoma.

Animals↗