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Biomedical subjects

M S Hirsch

Publications and source records attributed to M S Hirsch.

At least 199 records · Page 11Linked to original sources
PubMed1982

Alpha interferon and acyclovir treatment of herpes simplex virus in lymphoid cell cultures.

The T-lymphoblastoid cell line CEM, persistently infected with herpes simplex virus type 1, has been used to examine the antiviral efficacy of human alpha interferon and acyclovir, both alone and in combination. Acyclovir and interferon each produced dose-dependent decreases in virus titer at concentration ranges of 1 to 100 microM (approximately 0.225 to 22.5 micrograms/ml) and 10 to 10,000 U/Ml, respectively. Mean reductions in titer of 1.9 and 4.2 log10 PFU/ml were observed with 100 microM acyclovir and 10,000 U of interferon per ml, respectively, on day 10 of treatment. The combination of 100 microM acyclovir and 10,000 U of interferon per ml produced the most rapid fall in virus titer of all regimens examined and elimination of infections virus by day 7. Prolonged treatment (greater than 10 days) with acyclovir or alpha interferon was accompanied by a gradual return of virus titer to control levels despite the continuous presence of drug. Virus preparations isolated from such cultures were tested for antiviral agent sensitivity by a plaque reduction method. Acyclovir-exposed isolates were found to be acyclovir resistant, with 50% inhibitory doses of greater than 200 microM, and to be thymidine kinase deficient. Alpha interferon-exposed isolates were not interferon resistant. These results suggest that, in persistently herpes simplex virus-infected CEM cells: (i) combination treatment with 100 microM acyclovir and 10,000 U of alpha interferon per ml is more effective in reducing virus titer than either agent alone; (ii) prolonged exposure to drug may result in development of resistance by either the virus strain or the host cell system; and (iii) development of acyclovir resistance by herpes simplex virus in lymphoid cells is mediated by thymidine kinase.

Acyclovir↗
PubMed1982

Herpes simplex virus infection of human T-cell subpopulations.

The ability of herpes simplex virus type 1 to productively infect human T-cell subpopulations was examined. Unstimulated helper/inducer (T4+) and cytotoxic/suppressor (T8+) lymphocytes limited herpes simplex virus replication as effectively as unseparated peripheral blood T cells (T3+). Phytohemagglutinin stimulation before infection resulted in equivalently productive herpes simplex virus infections in the three cell fractions.

Adult↗
PubMed1981

Glomerulopathy associated with cytomegalovirus viremia in renal allografts.

We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.

Cytomegalovirus Infections↗
PubMed1981

Herpes simplex encephalitis: vidarabine therapy and diagnostic problems.

To learn more about the treatment of herpes simplex encephalitis with vidarabine, we conducted an uncontrolled study of 132 patients referred to 22 hospitals because of suspected disease. All had a brain biopsy and were started on vidarabine, but only 75 were diagnosed by isolation of virus from a brain-biopsy specimen. Cumulative mortality in the latter group was 39 per cent at one year. Other than therapy, levels of consciousness and age were the major variables that influenced outcome. Of 23 patients under 30 years of age who were lethargic at the initiation of therapy, two died and 16 returned to normal. Of 26 patients over 30 years of age who were lethargic at the outset, nine died and 10 returned to normal. Semicoma and coma were associated with worse outcomes, especially in older patients. Our data suggest that outcome is improved with treatment; they provide more support for the use of brain biopsy to diagnose the infection and indicate a need for better therapy.

Adolescent↗
PubMed1981

The effect of infection on T lymphocyte subpopulations: a preliminary report.

The effect of cytomegalovirus (CMV) infection on T-lymphocyte subpopulations (employing the monoclonal antibody OKT4 to delineate helper cells and OKT8 for suppressor-cytotoxic cells) was studied in 10 normal individuals with CMV mononucleosis and four renal transplant patients with symptomatic primary CMV disease. In both clinical settings, acute CMV infection is associated with a reversal of the normal helper/suppressor-cytotoxic T cell ratio, with both a relative and absolute decrease in T helper cells and an increase in T suppressor-cytotoxic cells observed. With clinical recovery, there is a return of these cell populations toward normal ranges. In two patients, one with chronic CMV infection and one with chronic Epstein-Barr virus infection, the helper/suppressor-cytotoxic cell ratio was found to be reduced four years after the onset of infection. Five patients with febrile illnesses were also studied: two with viral infection and one with a self-limited febrile illness had decreased helper/suppressor-cytotoxic cell ratios, and two with bacterial infection had increased ratios. Thus, delineation of T lymphocyte subpopulations may be of value not only in evaluating the immunologic effects of a particular infectious agent, but also in the clinical evaluation of the febrile patient.

Animals↗
PubMed1981

Mechanisms of immunosuppression in cytomegalovirus mononucleosis. II. Virus-monocyte interactions.

Virus-monocyte interactions were evaluated in patients with mononucleosis due to cytomegalovirus (CMV). Group 1 patients studied about two weeks after the onset of symptoms had lymphocyte responses to concanavalin A (con A) that were maximally suppressed and unaffected by in vitro culture or reconstitution with monocytes. Lymphocytes from group 2 patients studied about three weeks after the onset of symptoms had less markedly suppressed responses, which were reversed by in vitro culture or by reconstitution with monocytes. Monocyte depletion resulted in a marked diminution of fresh lymphocyte responses of group 2 patients but not of group 1 patients. CMV was isolated from blood monocytes of four patients with mononucleosis; intact, infected monocytes were capable of suppressing responses of cultured autologous lymphocytes to con A. Monocytes from uninfected control donors were infected in vitro with CMV and evaluated for the induction of suppressor activity. CMV-infected monocytes were significantly more suppressive for autologous lymphocyte responses to con A than were uninfected monocytes.

Adult↗
PubMed1981

Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis.

Lymphocyte proliferative responses to mitogens and herpes virus antigens are diminished during cytomegalovirus (CMV) mononucleosis. We analyzed peripheral blood T lymphocytes from patients in the acute and convalescent phases of CMV mononucleosis using monoclonal antibodies directed against the T helper and the T cytotoxic-suppressor cell subsets. Acute CMV infection is associated with a reversal in the normal ratio of helper to suppressor T lymphocytes with relative and absolute decreases in T helper cells and corresponding increases in T suppressor cells. These alterations in T lymphocyte subsets are accompanied by diminished lymphocyte responses to the mitogen concanavalin A (Con A). During convalescence, helper T lymphocytes increase, suppressor T lymphocytes decrease, and Con A responses return to normal.

Acute Disease↗
PubMed1980

Interferon and BK Papovavirus--clinical and laboratory studies.

The effects of human leukocyte interferon on BK papovavirus (BKV) infection in 41 recipients of renal transplants were studied as part of a randomized, double-blind, placebo-controlled trial. Eight transplant recipients demonstrated fourfold or greater rises in antibody to BKV, and three excreted BKV in urine. Neither seroconversion nor excretion was reduced by interferon administration. No clinical syndromes could be clearly linked to BKV infection. BKV was also relatively resistant to the in vitro effects of interferon. Pretreatment of interferon-sensitive human fibroblasts with up to 620 units of interferon/ml resulted in a loss of viral infectivity of one log or less. Continuous exposure of infected cultures to these interferon levels reduced BKV titers by 1.5-2.9 logs, whereas continuous exposure to lower concentrations of interferon had less effects. The levels shown to be marginally effective in vitro were considerably higher than those achieved in these patients' sera.

Animals↗
PubMed1980

Temporal cluster of herpes simplex encephalitis: investigation by restriction endonuclease cleavage of viral DNA.

Eight patients with brain biopsy-proven herpes simplex encephalitis were seen at the Massachusetts General Hospital, Boston, within a three-month period in the summer of 1977. The unusual temporal clustering of these cases engendered a formal epidemiologic investigation. No significant link among these patients was uncovered, and analysis of the cleavage products of seven of the eight viral isolates produced by the restriction endonucleases HsuI and HpaI showed that they were different. This cluster thus appears to have been a random event. Its occurrence, however, emphasizes that herpes encephalitis is not a rare disease in this country. In addition, the utility of restriction enzyme cleavage of DNA in clarifying the epidemiology of viral disease is underscored.

Adolescent↗
PubMed1980

Mechanisms of immunosuppression in cytomegaloviral mononucleosis.

During acute cytomegaloviral (CMV) mononucleosis, mononuclear leukocytes displayed diminished responsiveness to certain mitogens. Responses to phytohemagglutinin were normal in patients with community-acquired CMV illness but were reduced in patients with transfusion-associated infection. Both groups were hyporesponsive to pokeweek mitogen and concanavalin A. Cells from convalescent CMV mononucleosis patients responded as well as cells from normal donors to the three mitogens. Preculture of cells from patients with acute CMV mononucleosis for up to seven days before addition of concanavalin A greatly enhanced the blastogenic response to that mitogen. The effect was increased further by depletion of adherent cells after preculture for seven days and could be markedly reduced by the addition of fresh, autologous adherent cells to the precultured nonadherent cells. Suppressor activity was not observed in the serum of patients with acute CMV mononucleosis. These studies suggest that mitogen hyporesponsiveness in CMV mononucleosis may be mediated by suppressor cells included among the plastic-adherent mononuclear leukocyte population.

Adolescent↗
PubMed1980

Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon.

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.

Antibodies, Viral↗
PubMed1979

Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections.

A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients.

Adult↗