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Biomedical subjects

B J Luft

Publications and source records attributed to B J Luft.

106 records · Page 6Linked to original sources

Inhibition of mouse natural killer cell activity by zinc.

The effect of zinc on mouse natural killer (NK) cell activity was evaluated. The inhibition of NK cell activity with zinc was dependent on the concentration of zinc added (range tested: 0-40 micrograms zinc/ml) and occurred at both effector-to-target ratios tested. Zinc-induced inhibition of NK activity was observed with the use of peritoneal or splenic effector cells on Toxoplasma gondii-augmented NK activity. Maximal inhibition of activity was noted when zinc was present for the entire assay period. Inhibition was present but less marked with pretreatment of effector cells with zinc. Pretreatment of target cells with zinc had no measurable effect on NK cytotoxicity. Effector-to-target cell binding as measured by single-cell assays was not significantly altered by zinc. These results indicate that zinc is a potent inhibitor of NK activity.

Animals↗

Toxoplasmic encephalitis in patients with acquired immune deficiency syndrome.

An epidemic of cases of toxoplasmic encephalitis is occurring in patients with acquired immune deficiency syndrome (AIDS). Serological or histopathologic studies were performed on 70 cases with AIDS and toxoplasmic encephalitis. In many cases conventional stains of brain-tissue specimens failed to disclose Toxoplasma organisms; all were positive when stained by the peroxidase-antiperoxidase technique. Except for a single patient, serological titers were not indicative of an acute acquired infection. The ratio of titers in the agglutination test to titers in the Sabin-Feldman dye test seemed to be more predictive of active toxoplasmic encephalitis in patients with AIDS than either test alone. Based on histological and serological data, an approach is presented for diagnosis and treatment of suspected toxoplasmic encephalitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

The adverse effect of pregnancy on macrophage activation.

Recently a remarkable decrease in the resistance to infection with Listeria monocytogenes and Toxoplasma gondii in pregnant mice was demonstrated. Since activated macrophages are important in the resistance against these organisms, studies were performed to determine whether pregnancy has an adverse effect on the activation of macrophages and effector functions of these macrophages. Peritoneal macrophages from normal pregnant and virgin mice or from pregnant and virgin mice previously injected with Corynebacterium parvum to activate peritoneal macrophages were challenged with EL-4 tumor cells to test for macrophage cytotoxicity or with T. gondii to test for the capacity to kill an intracellular pathogen. There was no consistent difference between the enhanced cytotoxic capacity of activated macrophages from pregnant and virgin mice. Macrophages from C. parvum-treated pregnant mice were deficient in their ability to kill or inhibit multiplication of T. gondii when compared to macrophages from C. parvum-treated control mice (P less than 0.001). Activated macrophages from pregnant mice were only able to mildly inhibit multiplication of T. gondii when compared to macrophages from control mice. Thus, there was a dissociation of effector function of activated macrophages from pregnant mice; they were defective in their ability to kill an intracellular pathogen but killed tumor target cells as well as did activated macrophages from virgin mice.

Animals↗

Acute Toxoplasma infection among family members of patients with acute lymphadenopathic toxoplasmosis.

Studies were performed to determine how frequently acute infections with Toxoplasma gondii occur among family members of patients with acute acquired lymphadenopathic toxoplasmosis. In five of the nine families studied, more than one family member had serologic evidence of recent acute infection with T gondii. In three of the families, the immunoglobulin M and immunoglobulin G antibody titers to T gondii among infected family members were similar irrespective of whether lymphadenopathy was present. Lymphadenopathy developed in one family member in each of two families (families VIII and IX) three and eight months after lymphadenopathy had developed in the index case (proband). These results suggest that common-source outbreaks occur with surprising frequency among family members of patients with lymphadenopathic toxoplasmosis and that the humoral response is similar with different manifestations of the infection.

Acute Disease↗

Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis.

The cellular immune response to Toxoplasma gondii has been studied in 23 patients with acute toxoplasma infection. Abnormalities of T cell subpopulations included a marked and significant elevation in suppressor (Leu 2) T cells in patients with prolonged symptoms due to acute infection and either a decrease in the number of T helper cells or an increase in the number of suppressor cells--or both--in patients with asymptomatic lymphadenopathy. There was no significant difference in lymphocyte proliferation to phytohemagglutinin or pokeweed mitogen among the various groups tested. The peak lymphocyte response to toxoplasma antigen, however, was significantly depressed in patients with acute infection compared with that in chronically infected control patients. The kinetics of the depression were consistent with the induction of a non-Leu 2 suppressor cell. These results demonstrate marked quantitative alterations in T lymphocyte subpopulations and functional alterations of T cells to toxoplasma antigen during infection with T. gondii.

Antigens, Protozoan↗

Effect of pregnancy on augmentation of natural killer cell activity by Corynebacterium parvum and Toxoplasma gondii.

Studies were performed to determine the effect of pregnancy on NK cell activity and the augmentation of NK cell activity which normally follows injection of killed C. parvum or live T. gondii. When compared to cells from virgin mice, peritoneal and splenic cells from unstimulated pregnant mice showed no significant difference in NK activity. In contrast, NK activity of peritoneal cells from pregnant mice that received C. parvum or T. gondii was significantly lower than that found in comparably treated virgin mice. This reduced augmentation of NK activity in the peritoneal cells of pregnant mice could not be altered by the removal of plastic-adherent cells or of T cells by treatment with anti-Thy-1.2 antibody and complement. The number of effector-target conjugates was quantitated with a single cell assay, and was found to be comparable between cells from treated pregnant mice and treated virgin controls. However, the magnitude of lysis of target cells by peritoneal and splenic effector cells from pregnant mice previously injected with C. parvum was markedly and significantly reduced when compared to cells from comparably treated virgin mice. Thus, pregnancy is associated with an impaired ability to augment NK activity. This decrease in NK activity was not due to the depletion or dilution of NK cells, but to a functional impairment of the individual NK cells.

Animals↗

Outbreak of central-nervous-system toxoplasmosis in western Europe and North America.

Acute encephalitis caused by Toxoplasma gondii was diagnosed in ten patients in Belgium, the U.S.A., and Canada. None had underlying conditions usually associated with toxoplasmosis. Three had evidence of extraneural infection at necropsy. Nine patients died. Only two of the patients had a history of homosexuality, and one was a heroin addict. Five were Haitian, and four of them had lived in North America for 2-5 years. Eight of the patients had pronounced lymphopenia. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis in the non-immunocompromised host, the protean manifestations of the encephalitis, and a lack of a specific antibody response. The large number of cases appearing in western Europe and North America emphasise the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

Acute Disease↗

Primary and reactivated toxoplasma infection in patients with cardiac transplants. Clinical spectrum and problems in diagnosis in a defined population.

We have attempted to define the serologic criteria for diagnosis of toxoplasmosis in heart transplant recipients. Of 31 patients who were seronegative before transplantation, 4 received a heart from a seropositive donor, and 3 of these 4 had seroconversion and developed life-threatening toxoplasmosis; the remaining 27 did not have seroconversion or develop clinical toxoplasmosis. Of 19 patients who had antibodies to Toxoplasma before transplantation, 10 developed significant increases in test titers of the dye test or double-sandwich IgM enzyme-linked immunosorbent assay but did not develop a clinical illness that could be attributed to toxoplasma infection. Significant serologic changes occurred more often in patients who received azathioprine, corticosteroids, and antithymocyte globulin than in those who received cyclosporine, corticosteroids, and antithymocyte globulin (p less than 0.05). These data show the wide clinical spectrum and differences in kinetics of antibody response of patients who develop toxoplasma infection after transplantation, and suggest that clinical disease occurs in those who have seroconversion but is rare in patients with preexisting antibody who have serologic evidence of recrudescence.

Dye Dilution Technique↗

IgM and IgG antibody response in two immunosuppressed patients with Legionnaires' disease. Evidence of reactivation of latent infection.

Two patients in whom pneumonia due to Legionella pneumophila developed while they were receiving immunosuppressive therapy had serologic evidence of prior infection with the same serogroup of L. pneumophila two and eight months prior to their clinical pneumonia. This suggests that the pneumonia in these patients may have been due to the reactivation of a latent infection, possibly due to their immunosuppressed state. A new enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG and IgM antibodies to L. pneumophila, and the kinetics of these antibody responses were useful diagnostically.

Adult↗

Effect of pregnancy on resistance to Listeria monocytogenes and Toxoplasma gondii infections in mice.

Studies of the effect of pregnancy on the capacity of mice to resist Listeria monocytogenes and Toxoplasma gondii infection revealed significantly diminished resistance of pregnant mice to infection by both agents as measured by mortality. The development of immunity to listeria was assessed by studying the kinetics of listeria growth in the livers and spleens of virgin and pregnant mice infected intravenously with a sublethal dose of listeria. In both virgin and pregnant mice there was a rise in the number of listeria colony-forming units per organ during the first 3 days after infection. Thereafter, there was a decline in colony-forming units in these organs in virgin mice but a persistence of listeria in spleens and livers of pregnant mice. Paradoxically, during the first 3 days after infection, listeria counts in spleens of virgin mice were significantly higher than those in pregnant mice. Nonspecific resistance to listeria conferred by chronic infection with T. gondii was significantly diminished in pregnant mice when measured by mortality and quantitative cultures of listeria in livers and spleens. These studies demonstrate a remarkably decreased resistance of pregnant mice to two intracellular organisms and a diminished capacity of pregnant mice to develop immunity to listeria. This decrease in resistance may play an important role in congenital transmission of these organisms.

Animals↗

Immunologic aspects of Lyme borreliosis.

Immune responses to Borrelia burgdorferi infection are now well characterized. Following infection there is an early T cell response and a more slowly evolving B cell response. IgM antibodies appear first and are followed by IgG and IgA. Early antibodies are primarily against a 41-kilodalton flagellum-associated antigen; responses to other spirochetal antigens develop later. Serologic assays that use whole B. burgdorferi preparations are not always able to detect an early rise in antibodies above a background of crossreactive antibodies present in most uninfected individuals. Moreover, some individuals with neurologic involvement who lack diagnostic levels of serum antibody to B. burgdorferi have high levels of the antibody in their cerebrospinal fluid. Specific T cell blastogenesis to B. burgdorferi can further document infection. Analysis of T cell subsets in Lyme arthritis demonstrates a marked decrease in the CD4+2H4+ subpopulation in the synovial fluid, although normal numbers of these cells are present in peripheral blood. Immunologic measurements are useful in evaluating and treating a wide array of patients who may be infected with B. burgdorferi.

Antibodies, Bacterial↗

A perspective on the treatment of Lyme borreliosis.

Lyme borreliosis has become the most common tick-borne infection in the United States. Although both beta-lactam and tetracycline antibiotics have been shown to be effective in the treatment of this spirochetosis, the development of optimal therapeutic modalities has been hampered by the lack of reliable microbiologic or immunologic criteria for the diagnosis or cure of this infection. In vitro sensitivity studies have been performed by several laboratories, but there has been no standardization of the methodology for measuring either inhibitory or bactericidal levels. Clinical studies have documented the efficacy of antibiotics, but therapy has failed in as many as 50% of cases of chronic infection. Although new antibiotic regimens appear promising, the optimal treatment of this infectious disease remains to be determined. In this report we review the clinical and experimental rationale for the antibiotic regimens that we currently use and the need for a more standardized approach to treatment trials.

Animals↗