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Biomedical subjects

J D Shanley

Publications and source records attributed to J D Shanley.

At least 37 records · Page 2Linked to original sources
PubMed1990

In vivo administration of monoclonal antibody to the NK 1.1 antigen of natural killer cells: effect on acute murine cytomegalovirus infection.

Monoclonal antibody to the NK 1.1 antigen, found on the natural killer cells of a number of strains of mice, specifically suppresses NK cell function when given in vivo. Using this monoclonal antibody, we have examined the effects of specific suppression of natural killer (NK) cells in vivo on acute murine cytomegalovirus (MCMV) infection in C57BL/10ScN mice. Administration of antibody to NK 1.1 substantially lowered the resistance of C57BL/10ScN mice to lethal virus challenge. In addition, antibody administration prior to intraperitoneal infection significantly increased MCMV replication in salivary glands, lungs, and spleens. In C3H/HeN mice, a strain that lacks the NK 1.1 antigen, antibody to NK 1.1 had no effect on virus replication or lethal infection. Thus, in vivo administration of monoclonal antibody to NK 1.1 alters the course of acute MCMV infection. These findings further substantiate the role of NK cells in defense against acute MCMV infection.

Acute Disease↗
PubMed1990

Reovirus type 3 binds to antagonist domains of the beta-adrenergic receptor.

Reovirus type 3 interfered with the binding of beta-adrenergic antagonist ligands to receptors on Y1 adrenal, C6 glioma, and mouse L cells. This inhibition of beta-adrenergic binding was dose related. Reovirus did not interfere with dopaminergic binding or isoproterenol-induced activation of adenylate cyclase. In addition, reovirus infected Y1 cells, which bind beta-adrenergic antagonist ligands but lack agonist-induced activity. These results suggest that reovirus infection is initiated by binding to antagonist (nonfunctional) domains of the adrenergic receptor complex.

Adrenal Gland Neoplasms↗
PubMed1989

The folate antagonist, methotrexate, is a potent inhibitor of murine and human cytomegalovirus in vitro.

Cytomegalovirus (CMV) is a major source of morbidity for immunocompromised patients, such as AIDS patients. The folic acid antagonists have not been explored as potential antiviral agents against CMV. We examined the effects of methotrexate, compared to acyclovir and ganciclovir, on both murine CMV (MCMV) and human CMV (HCMV) in vitro. Using a plaque assay in mouse embryo cells or human foreskin fibroblasts for MCMV and HCMV respectively, we found that methotrexate, in micromolar concentrations, was a potent inhibitor of both viruses. This effect was due to folic acid antagonism since folinic acid abrogated the antiviral effect of methotrexate, but not ganciclovir. Cellular toxicity due to methotrexate appeared insufficient to account for the antiviral effects. The ability of methotrexate to inhibit CMV in vivo merits exploration.

Acyclovir↗
PubMed1989

Effects of L3T4+ lymphocyte depletion on acute murine cytomegalovirus infection.

We examined the role of T lymphocytes bearing the L3T4 phenotype in acute murine cytomegalovirus (MCMV) infection. In vivo administration of rat IgG2b monoclonal antibody (MAb) GK 1.5 was used to deplete mice of L3T4+ lymphocytes during acute MCMV infection. Unlike the saline-treated controls that resolved their infections, mice receiving the MAb developed persistent and high levels of virus in the salivary gland, lung and spleen. The production of antibody to MCMV was delayed and the titres achieved were markedly less than in the controls. Despite the higher levels of virus replication, there was no increase in mortality seen in animals treated with the MAb. Following intraperitoneal challenge with MCMV, depletion of L3T4+ lymphocytes was protective, increasing the dose of MCMV required to produce death. These data indicate that T lymphocytes of the L3T4 phenotype influence the degree of MCMV replication during acute infection and may contribute to mortality following intraperitoneal virus challenge.

Acute Disease↗
PubMed1988

Aerosol administration of antiviral agents to treat lung infection due to murine cytomegalovirus.

Cytomegalovirus (CMV) pneumonia causes significant morbidity and mortality in bone marrow transplant recipients and in patients with AIDS. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine (ganciclovir) and phosphonoformic acid (PFA) demonstrate activity against CMV in human infections, although recurrent CMV and systemic drug toxicity frequently develop. We examined the efficacy of aerosol administration of antiviral agents against murine CMV (MCMV) infection. Animals were inoculated with MCMV intranasally and were treated with oral ganciclovir; with aerosolized ganciclovir, PFA, or ribavirin; or with buffer. MCMV in lung and salivary gland homogenates was quantified by plaque assay. Oral ganciclovir (200 mg/kg per day) reduced titers of MCMV in both tissues by greater than 95%. Aerosolized ganciclovir, 100 and 200 mg/kg per day, reduced lung titers of MCMV by 93% and 97%, respectively. Aerosolized PFA, 20 and 200 mg/kg per day, reduced lung titers of MCMV by 60% and 68%, respectively. Aerosolized ganciclovir and PFA inhibited replication of MCMV in salivary glands substantially less than did oral administration of either agent. Our results suggest that aerosol administration of antiviral agents can potently and selectively inhibit replication of MCMV in the lung.

Acyclovir↗
PubMed1988

Glycoproteins of Pneumocystis carinii: characterization by electrophoresis and microscopy.

Glycoproteins are integral components of cell-surface structure and participate in adherence of pathogenic microbes to host cells. We have initiated studies of the glycoproteins of Pneumocystis carinii. Biotin-conjugated lectins, followed by reaction with avidin-peroxidase, were used to detect glycoproteins in electrophoretically separated proteins of P. carinii and on whole organisms when using light microscopy. Glycoproteins of P. carinii were clearly different from rat cell glycoproteins. Multiple glycoproteins were present in P. carinii and exhibited intense reactivity to both concanavalin A and wheat-germ agglutinin. Those lectins that reacted with the electrophoretically separated proteins also stained both alcohol-fixed P. carinii and the extracellular granular material present only in P. carinii preparations. In electron micrographs of P. carinii, which were stained with colloidal-gold-labeled concanavalin A, we found that the lectin bound to the outer surface of the organisms and to the tubular extensions emanating from the exterior surface.

Animals↗
PubMed1988

Altered threshold for the induction of graft-versus-host immunodeficiency following murine cytomegalovirus infection. Host and donor contributions.

Acute murine cytomegalovirus (MCMV) infection enhances the ability of parental spleen cells to induce graft-vs.-host immunodeficiency (GVHID) in F1 hybrid mice when the two processes occur simultaneously in the recipient. The present study assessed GVHID as the ability of spleen cells to generate in vitro cytotoxic T lymphocyte responses to trinitrophenyl-modified syngeneic cells. The results indicate that MCMV infection not only reduces the number of parental spleen cells required to induce GVHID, but accelerates the onset of GVHID, which occurs as early as 3 days after cell and virus challenge. To determine whether MCMV infection exerts this synergistic effect primarily through the donor or the host component, we examined the effect of MCMV infection of either donor mice or recipient mice at 3, 10, and 17 days prior to spleen cell transfer. Two weeks after cell transfer, splenocytes were tested for their ability to generate CTL. When donor mice were infected with MCMV three days prior to cell transfer, the ability of donor cells to induce GVHID was reduced. In contrast, MCMV infection of the recipients three days prior to cell transfer increased their susceptibility to GVHID induction. Infection of either donor or host mice 10 days or 17 days prior to parental spleen cell transfer had little effect on the ability to induce or resist GVHID when compared with sham-infected mice. Thus, acute MCMV infection can modulate the severity of GVHID depending on whether it is the donor or the host that is infected. The ability of acute MCMV to alter the course and severity of GVHID may be relevant for human bone marrow transplants in which preceding CMV infection has been associated with chronic GVH. In this setting, CMV may lower the threshold necessary to induce a GVH reaction.

Animals↗
PubMed1987

Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition?

The conventional explanation for the high fatality rate due to cytomegalovirus (CMV) pneumonitis among allogeneic transplant recipients is that immunosuppression renders the host unable to control replication of this opportunistic agent. However, evidence from studies in man and the murine model of CMV show that virus replication in the lung is unrelated to the development of pathological effects, and that a host immune response is required for the induction of pneumonitis. Thus the hypothesis is that limited CMV replication in the lungs leads to display of a virus-coded protein, which is recognised by host T-cells, and that the pneumonitis is due to an uncontrolled accumulation and recruitment of such cells in the lungs. The reason why CMV is found in the lungs of patients with the acquired immunodeficiency syndrome (AIDS) without producing pneumonitis is probably because these patients cannot mount the pathogenic T-cell response. According to the hypothesis stated here, if the immune capabilities of AIDS patients can be restored, life-threatening CMV pneumonitis may develop.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Review of 59 patients hospitalized with animal bites.

We reviewed the charts of 59 pediatric and adult patients hospitalized because of animal bites (46 dog bites, 10 cat bites, 3 monkey bites). The bites of 40 of the 59 patients were infected at the time of admission. Gram-stained specimens correctly predicted the infecting bacteria in only 5 of 20 cases. Eighty-three percent of the bacterial isolates were penicillin-susceptible. Before admission 14 patients had received outpatient antibiotic prophylaxis and the infections in 11 of these 14 patients were caused by bacteria susceptible to the prophylactic antibiotic. Complications were more common if antimicrobial therapy had not been altered according to susceptibility testing results. Of the 59 patients 19 were admitted immediately after being bitten because of severe uninfected bites. Of these 19 patients 18 received prophylactic antibiotics and none developed a serious complication.

Animals↗
PubMed1987

Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays.

We have compared murine cytomegalovirus (MCMV) antibody determination by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. A comparison of antibody detection with 146 serum samples at a 1:20 dilution showed 100% agreement (60 negatives and 86 positives) between the assays. There was close agreement of endpoint determinations of sera by both methods. After experimental MCMV infection, antibody to MCMV was detected by both assays as early as day 7, and high titers persisted as late as 6 months. In contrast to immunocompetent littermates, athymic nude mice did not develop antibody after infection. Mice lacking antibody detectable by ELISA were susceptible to lethal MCMV challenge. In a survey of animals from five commercial sources, MCMV antibody was not detected unless mice were experimentally infected. MCMV antibody determination by ELISA is a convenient method, comparable to the indirect immunofluorescence assay in sensitivity and specificity.

Animals↗
PubMed1987

Modification of acute murine cytomegalovirus adrenal gland infection by adoptive spleen cell transfer.

Homozygous (nu/nu), athymic nude mice, infected with murine cytomegalovirus (MCMV), develop unremitting and ablative virus infection involving both the adrenal cortex and medulla. During acute infection, adoptive transfer of MCMV-immune, but not naive, spleen cells suppressed virus replication in the adrenal glands, but not the lungs or salivary gland. T lymphocytes, not macrophages or B cells, were responsible for limiting viral replication. The effect by donor cells was restricted by compatibility at the major histocompatibility locus. Restriction of MCMV replication in the adrenal gland was associated with T lymphocytes of the L3T4 phenotype. Thus, T-cell immunity is critical in regulating MCMV replication in the adrenal glands, and T lymphocytes restricted by class II major histocompatibility antigens mediate this effect.

Adrenal Gland Diseases↗
PubMed1987

Interstitial pneumonitis during murine cytomegalovirus infection and graft-versus-host reaction. Characterization of bronchoalveolar lavage cells.

Acute murine cytomegalovirus (MCMV) infection alters the course of graft-vs-host (GVH) disease involving major histocompatibility (MHC) antigens and induces interstitial pneumonitis. F1 (B10 x B10.BR) mice given 20 x 10(6) B10.BR spleen cells and MCMV (1 x 10(5) plaque-forming units [PFU]) develop severe, diffuse pneumonitis not seen with either MCMV or GVH alone. As one index of the host immune processes operating in the lungs during MCMV/GVH pneumonitis, we examined the types of cells recovered from the lung by bronchoalveolar lavage (BAL) during pneumonitis. During MCMV/GVH pneumonitis, the total cells recovered significantly increased, due primarily to an influx of Thy 1.2 lymphocytes. Characterization of cells using multiparameter flow cytometric analysis revealed that greater than 80% of all BAL cells were Thy 1.2-positive lymphocytes of donor origin. In addition, donor Thy 1.2-positive cells were of both the L3T4+ (43% of BAL cells) and Lyt 2+ (38% of BAL cells) phenotype. Thus, MCMV infection during GVH to MHC antigens induces interstitial pneumonitis, characterized by an influx of T lymphocytes (both helper and suppressor/cytotoxic) from the donor. The antigenic specificity of these cells is not known.

Animals↗
PubMed1987

Periodic sharp complexes in herpes simplex virus encephalitis: survival in an elderly man.

For the electroencephalographer, focal temporal periodic complexes have been strongly associated with herpes simplex virus encephalitis (HSVE). The appearance and subsequent disappearance of these complexes has generally been held to herald a poor prognosis. This report involves an elderly man with HSVE who survived with no neurologic deficits despite the presence and later disappearance of periodic sharp complexes. This supports the view that the periodic complexes are more a function of the pathophysiologic changes caused by HSVE as opposed to a marker of tissue injury.

Acyclovir↗
PubMed1986

Human cytomegalovirus replicates in gamma-irradiated fibroblasts.

Because of the unique interdependence of human cytomegalovirus (HCMV) and the physiological state of the host cell, we evaluated the ability of human foreskin fibroblasts (HFF), exposed to gamma radiation, to support HCMV growth. Irradiation of HFF with 2,500 rADS prevented cellular proliferation and suppressed cellular DNA, but not RNA or protein synthesis. Treatment of HFF cells with 2,500 rADS 6 or 48 hours prior to infection did not alter the time course or virus yield during HCMV replication. Virus plaquing efficiency in irradiated cells was comparable to that of nonirradiated cells. As judged by thymidine incorporation and BUdR inhibition of virus replication, HCMV infection induced both thymidine kinase activity and host cell DNA synthesis in irradiated cells. In addition, virus could be recovered from HFF exposed to radiation 0-2 days after infection with HCMV. These studies indicate that the damage to cells by gamma irradiation does not alter the capacity of host cells to support HCMV replication.

Cells, Cultured↗
PubMed1986

Encephalomyocarditis virus can bind to and transfect non-permissive cells.

Mouse embryo fibroblasts and mouse adrenal tumor cells support the replication of encephalomyocarditis (EMC) virus, whereas rat glial and rat hepatoma cells are non-permissive. These differences in susceptibility were not due to the lack of virus attachment to rat cells. The findings that rat cells could be transfected with RNA derived from EMC virus indicates that the block in viral replication in these cells occurs at some point between attachment and uncoating of virus, probably at the level of uncoating.

Animals↗
PubMed1986

Murine cytomegalovirus adrenalitis in athymic nude mice.

During studies of the pathogenesis of murine cytomegalovirus (MCMV) infection in athymic nude mice, we noted striking virus involvement of the adrenal glands. Because patients with the acquired immunodeficiency syndrome (AIDS) have recently been reported to have adrenal necrosis and evidence of infection of the adrenal gland with human cytomegalovirus (HCMV), we have further evaluated adrenal gland involvement during MCMV infection. Following virus inoculation, MCMV replicated to high titer in the adrenal glands of T-cell deficient, homozygous nude mice, but not heterozygous littermates with intact T-cell function. Concomitant with the high titers of virus, there appeared overt histological evidence of herpes-virus virus infection accompanied by patchy necrosis of adrenal cortical and medullary tissues. Acyclovir, which inhibits growth of MCMV, reduced virus replication in the adrenal gland. Similarly, virus replication was diminished in homozygous nude mice immunologically reconstituted by infusion of normal spleen cells three weeks prior to infection. Thus, in the absence of functioning T lymphocytes, MCMV can infect and replicate in adrenal tissues causing a progressive destructive adrenalitis.

Acyclovir↗