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H W Murray

Publications and source records attributed to H W Murray.

At least 91 records · Page 5Linked to original sources
PubMed1992

L-arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes.

The L-arginine-dependent generation of reactive nitrogen intermediates (RNI) has been identified as a key intracellular antimicrobial mechanism of activated mouse macrophages. To determine the role of this mechanism in the activity of human mononuclear phagocytes, monocyte-derived macrophages activated in vitro by interferon (IFN)-gamma and monocytes from patients receiving IFN-gamma as therapy were treated with NG-monomethyl-L-arginine (NMA) or arginase. Neither competitive inhibition of L-arginine metabolism (NMA) nor depletion of L-arginine (arginase) altered intracellular antimicrobial activity against Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani. In contrast, NMA and arginase readily reversed the antimicrobial effect of mouse peritoneal macrophages stimulated either in vitro or in vivo by IFN-gamma, and activated mouse but not human cells could be induced to release enhanced levels of nitrite. These results suggest that the L-arginine-dependent generation of RNI is a species-restricted macrophage mechanism unlikely to participate in the intracellular antimicrobial activity of IFN-gamma-stimulated human mononuclear phagocytes.

Animals↗
PubMed1991

Response to chemotherapy in experimental visceral leishmaniasis: T cell-dependent but interferon-gamma- and interleukin-2-independent.

The capacity of Leishmania donovani-infected BALB/c mice to respond to conventional chemotherapy with pentavalent antimony (Sb) is T cell dependent and, in nude mice, can be restored in part by treatment with the T cell lymphokines, interferon-gamma (IFN-gamma) or interleukin-2 (IL-2). To document the presumed role of endogenous IFN-gamma and IL-2 in responsiveness to antileishmanial chemotherapy in the T cell-intact host, L. donovani-infected euthymic BALB/c mice were treated with anti-IFN-gamma or anti-IL-2 monoclonal antibodies (MAbs) before and after Sb administration. Treatment with MAbs exacerbated visceral infection but did not inhibit the in vivo efficacy of Sb. Thus, while combination therapy of Sb plus IFN-gamma or IL-2 may prove beneficial in T cell-deficient hosts with visceral leishmaniasis, T cell activities other than or in addition to IFN-gamma or IL-2 production may mediate in vivo responsiveness to antileishmanial chemotherapy in the euthymic host.

Animals↗
PubMed1991

Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron.

Iron-saturated transferrin did not reverse the intracellular killing or inhibition of Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani by gamma interferon-activated human macrophages. Deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages. Limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens.

Animals↗
PubMed1990

Effect of continuous administration of interferon-gamma in experimental visceral leishmaniasis.

In experimental visceral leishmaniasis, intermittently administered interferon-gamma (IFN-gamma) induces antileishmanial activity, which is primarily microbistatic. To determine if the efficacy of IFN-gamma immunotherapy could be enhanced by continuous delivery, Leishmania donovani-infected mice were treated using a subcutaneous osmotic pump. Once-daily intraperitoneal injections of 10(5) or 10(6) units of IFN-gamma inhibited the replication of L. donovani within liver macrophages but overall did not reduce liver parasite burdens. In contrast, a comparable dose of IFN-gamma (2.4 x 10(5) units/day) administered continuously induced an enhanced effect and reduced liver burdens by almost 50%. Although pump delivery did not similarly increase the efficacy of antimony chemotherapy in infected mice, continuous treatment with IFN-gamma plus antimony produced an additive antileishmanial effect. These results suggest that continuous infusions of macrophage-activating lymphokines such as IFN-gamma (used alone or in combination with chemotherapy) may be required to optimize in vivo antimicrobial effects.

Animals↗
PubMed1990

Defect in the tissue cellular immune response: experimental visceral leishmaniasis in euthymic C57BL/6 ep/ep mice.

In BALB/c mice, successful defense against visceral leishmaniasis is T cell dependent, expressed by tissue granuloma formation, and probably mediated by macrophages activated by cytokines, including gamma interferon (IFN-gamma). C57BL/6 ep/ep (pale ear) mice, which reportedly exhibit impaired IFN-gamma production, were challenged with Leishmania donovani to determine the outcome of infection in a euthymic host with an apparent defect in lymphokine secretion. In BALB/c and normal C57BL/6 mice, L. donovani liver burdens peaked at 2 weeks and were largely eliminated by 4 weeks. In contrast, in pale ear mice, infection progressed until after 4 weeks and persisted at high levels at 8 weeks. The failure to resolve hepatic infections was not related to deficiencies in (i) Thy-1+, L3T4+, or Lyt-2+ T cells; (ii) IFN-gamma secretion; (iii) liver tissue Ia expression; (iv) macrophage antimicrobial capacity; or (v) antileishmanial antibody production. However, despite the anticipated influx of mononuclear cells into livers, these cells were not properly focused on the parasitized Kupffer cells, the inflammatory infiltrate receded prematurely, and mature granulomas failed to develop. These results suggest that there is a cellular immune defect at the tissue level and emphasize the critical role of granuloma formation in successful resolution of systemic intracellular infections.

Animals↗
PubMed1990

Suppression of T-lymphocyte responses to Entamoeba histolytica antigen by immune sera.

Lymphocytes from patients cured of amebic liver abscesses proliferate and produce gamma interferon upon incubation with soluble Entamoeba histolytica antigen: however, amebic liver abscesses exhibit a relentless progression without treatment. To determine whether suppressive factors are present in sera, we studied T-lymphocyte responses to total soluble E. histolytica antigen by using cells from five patients treated for amebic liver abscesses in the presence of 15 different immune sera and 10 control sera. In the presence of immune sera, E. histolytica antigen-induced lymphocyte proliferation decreased by 63% and production of gamma interferon was reduced by 93.2% (P less than 0.01). Immune sera had no effect on the mitogenic responses of patient lymphocytes to phytohemagglutinin or on the proliferative responses of control lymphocytes to phytohemagglutinin or tetanus toxoid. The suppressive activity of immune sera diminished as the time between therapy for amebic liver abscesses and serum collection increased (P less than 0.05). Suppressive activity did not correlate with the titers of serum anti-amebic antibody and was not affected when serum was absorbed with viable amebic trophozoites. In conclusion, soluble factors present in the sera of amebic liver abscess patients suppressed in vitro lymphocyte responses to E. histolytica antigen and may have contributed to the lack of development of effective in vivo cell-mediated immune responses following the onset of amebic liver abscesses.

Animals↗
PubMed1990

Septic pulmonary embolism complicating a central venous catheter.

Bacteremia is a recognized complication in patients with indwelling central venous catheters. More recently pulmonary embolism in such patients has also been described. Despite abundant clinical experience with these devices, to our knowledge, septic pulmonary embolism has not been reported in adult patients. This case illustrates such a complication.

Adolescent↗
PubMed1989

IFN-gamma and IFN-alpha induce the expression and synthesis of Leu 13 antigen by cultured human endothelial cells.

Leu 13 is a 16 kDa human lymphocyte surface Ag and monoclonal anti-Leu 13 induces T cell aggregation and alters T cell proliferation. In previous studies using anti-Leu 13, Leu 13 Ag has been detected on endothelial cells (EC) of arteries, capillaries, and veins in human tissue sections. In contrast, in this study using the same antibody, Leu 13 Ag could not be detected on unstimulated cultured human umbilical vein endothelial cells (HUVEC) by indirect immunofluorescence, immunoperoxidase staining, or immunoisolation of radiolabeled Ag from labeled endothelial cells. However, when HUVEC were cultured with IFN-gamma, Leu 13 Ag was demonstrable using all three detection techniques. Leu 13 Ag was detectable after 24 h of incubation with IFN-gamma (30 U/ml) and was maximally expressed after 72 h. After removal of IFN-gamma, Leu 13 Ag progressively declined back to basal levels by 4 days. Induction of Leu 13 Ag expression by IFN-gamma was suppressed by cycloheximide. Although Leu 13 Ag expression was also induced by IFN-alpha, PMA, and IL-1 were inactive. When HUVEC were incubated with IFN-gamma, surface-labeled with 125I, and then solubilized, anti-Leu 13 immunoisolated a 16-kDa radioactive band that comigrated with Leu 13 immunoisolated from T cells. Similar results were obtained using HUVEC that were metabolically labeled with 35S-methionine. These results demonstrate that HUVEC stimulated with IFN-gamma and IFN-alpha express Leu 13 Ag on their surface and suggest that exposure of EC to IFN may induce EC to develop new functional properties at sites of inflammatory and immune reactions.

Antibodies, Monoclonal↗
PubMed1989

Experimental visceral leishmaniasis: role of endogenous IFN-gamma in host defense and tissue granulomatous response.

The capacity of BALB/c mice to acquire resistance to and eliminate intracellular visceral Leishmania donovani is T cell dependent, associated with a granulomatous tissue reaction, and correlates with the ability to secrete the macrophage-activating lymphokine, IFN-gamma. These responses appear by 4 wk after infection and are fully established by 8 wk. To examine the role of endogenous IFN-gamma, BALB/c mice were injected with anti-IFN-gamma mAb before and for 8 wk after infection. At 4 wk, mAb treatment inhibited the acquisition of resistance to L. donovani and abolished mature granuloma formation. Although liver parasite burdens in mAb-treated mice were fivefold higher than in controls at 8 wk, continually treated mice nevertheless began for form tissue granulomas and decreased their parasite loads by 50% from peak values. The levels of anti-IFN-gamma antibody in the serum of mice injected for 8 wk were appreciably reduced, thus raising the possibilities of either insufficient neutralization of endogenous IFN-gamma at this time point or a pathway independent of IFN-gamma. Although the role of IFN-gamma and the potential effect of an IFN-gamma-independent mechanism in the resolution of visceral infection remain to be defined, these results indicate that IFN-gamma plays a critical role in the early immune response that both optimally controls L. donovani infection and induces the tissue granuloma.

Animals↗
PubMed1989

Progression to AIDS in patients with lymphadenopathy or AIDS-related complex: reappraisal of risk and predictive factors.

PURPOSE: In 1985, we reported that acquired immunodeficiency syndrome (AIDS) developed in 14 of 81 (17%) men with generalized lymphadenopathy followed prospectively for an average of 13 months. The presence of oral thrush or constitutional symptoms, or both, or severely impaired T4+ cell responses to specific antigen (interferon-gamma production) accurately identified patients at immediate risk for AIDS. The purpose of the current report is to describe the progress of these 81 patients during the three and a half years since enrollment and to include new data on initial serum levels of beta 2 microglobulin and human immunodeficiency virus (HIV) p24 antigen. PATIENTS AND METHODS: The mean age of the 81 patients was 35.4 years; 79 were homosexuals and two were drug abusers. Immunologic testing was performed once at the time of enrollment in all patients. Seventy-seven of the 81 patients were seropositive for HIV antibody. Frozen samples of serum, also obtained at initial study, were assayed in 1988 for beta 2 microglobulin and HIV p24 antigen. The clinical status of patients was determined six, 14, and 36 months after enrollment was closed (June 1984) by either interview and examination or telephone contact with private physicians. RESULTS: After three and a half years of follow-up, 42 patients have developed AIDS, including (1) 77% who had had thrush or symptoms, or both, (2) 80% to 88% of those who originally demonstrated marked immunologic abnormalities (skin test anergy, less than 200 T4+ cells/mm3, T4/T8 cell ratio of less than 0.5, severely impaired interferon-gamma production [less than 25 U/mL], or elevated serum beta 2 microglobulin level [greater than 3.0 mg/L], and (3) 95% of patients with HIV p24 antigenemia. However, AIDS also developed in 51% of patients who had had more apparently benign initial manifestations (lymphadenopathy alone, herpes zoster), in 41% to 54% despite normal initial results for either T4+ cell number, interferon-gamma secretion, beta 2 microglobulin, or skin testing, and in 44% of those whose sera did not contain HIV antigen. CONCLUSION: These updated results demonstrate the remarkably poor prognosis of patients with generalized lymphadenopathy or AIDS-related complex irrespective of initial clinical, immunologic, and serologic findings, and suggest that essentially all such persons may be candidates for antiviral therapy.

AIDS-Related Complex↗