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Biomedical subjects

W Brehmer

Publications and source records attributed to W Brehmer.

At least 19 recordsLinked to original sources
PubMed1990

[Clinical aspects and pathology of mycobacterial infections in AIDS. Pulmonary and extrapulmonary manifestations].

Infections with M. tuberculosis and other mycobacteria (atypical mycobacteria) are frequently found in patients with AIDS. They are almost always disseminated, and are associated with a spectrum of findings that is often unhelpful for the diagnosis. In the case of tuberculosis, typical granulomas are a major finding. The histological correlate of mycobacteriosis is histiocytosis; granulomas are rarely observed, and when they do present, are incompletely developed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Resistance testing of M. avium-intracellulare and M. tuberculosis of AIDS patients with new drugs and drug combinations].

The minimal inhibitory concentration (MIC) of rifabutin for M. tuberculosis was 0.006 to 0.06 micrograms/ml, and 0.12 to 0.25 micrograms/l for clofazimine. Accordingly, M. tuberculosis is inhibited by concentrations of these two medications that are far lower than the levels normally found in the serum. In the case of M. avium, the MIC of the new drugs such as rifabutin and clofazimine are, in contrast to the MICs for M. tuberculosis, merely of the order of the achievable serum concentrations. The minimum bactericidal concentrations of these two substances are much higher than the bacteriostatic concentrations, which probably explains the frequent therapeutic failures, while in the case of ciprofloxacin, the prevailing situation is much more favourable. The growth of all M. avium strains is inhibited (= sensitive) when elevated concentrations (double "breakpoint" concentrations) of a triple-drug combination comprising rifampicin, ethambutol and ciprofloxacin, or a combination of ethambutol, rifampicin, ciprofloxacin and prothionamid are tested at "normal breakpoint" concentrations.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Incidence of infections with mycobacteria in HIV infected patients].

In subjects with HIV infection, mycobacteria are frequently identified. The most commonly seen species are M. avium-M. intracellulare. On the other hand, there is considerable variation in the data regarding the incidence of infections with M. tuberculosis; in fact, these data correspond with the differences in prevalence of tuberculosis in the respective general population.

Cross-Sectional Studies↗
PubMed1989

Mycobacteremia in AIDS patients. Results of a prospective study.

The importance of blood cultures in diagnosing disseminated mycobacteriosis in AIDS patients was evaluated. Blood samples were screened for mycobacteria by culture and microscopic techniques. Mycobacteremia was proven in 20/136 (14.7%) AIDS patients, the agent being M. avium-M. intracellulare (MAI) in 16 cases and M. tuberculosis in four cases. The rate of cases with positive blood samples in disseminated MAI infection was 59.3% (16/27 cases) and in disseminated tuberculosis 57.1% (4/7 cases). To detect mycobacteria buffy-coat was slightly superior to lysated cell pellets, obtained by a lysis-centrifugation technique. In 4/16 cases with MAI bacteremia, the agent was proven by positive blood smears for acid-fast bacilli only; in these four patients MAI was demonstrated at other body sites. These results illustrate the diagnostic role of blood culture and its use in early diagnosis of disseminated mycobacteriosis, with microscopic examination of blood smears being an important adjunct.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Monoclonal antibodies selectively directed against the cell wall surface of Mycobacterium tuberculosis.

In the last few years several monoclonal antibodies against Mycobacterium tuberculosis have been described, but their use as diagnostic tools has been limited. In this study we describe eight monoclonal antibodies against M. tuberculosis for diagnostic purposes. The monoclonal antibodies were selected after enzyme-linked immunosorbent assay screening with whole bacterial suspensions of mycobacteria and other bacterial species. Four monoclonal antibodies (BS100, BS101, BS102, and BS104) reacted with a whole bacterial suspension of M. tuberculosis but not with the other mycobacteria. When tested with a cytoplasmic fraction of mycobacteria the same monoclonal antibodies showed a broad cross-reactivity. Therefore the monoclonal antibodies showed not specific but selective binding to M. tuberculosis. The molecular size of the recognized antigens ranged from 12 to 71 kilodaltons as determined by the immunoblotting technique. The ability to differentiate M. tuberculosis from mycobacteria other than tuberculosis was investigated by enzyme-linked immunosorbent assay with 131 freshly cultured strains of M. tuberculosis from patients and 36 strains of mycobacteria other than tuberculosis. The monoclonal antibody BS104 could clearly distinguish between M. tuberculosis and other mycobacterial species.

Antibodies, Bacterial↗
PubMed1986

Immunobiological activities of nontoxic lipid A: enhancement of nonspecific resistance in combination with trehalose dimycolate against viral infection and adjuvant effects.

The ability of nontoxic monophosphoryl lipid A (MPL) to stimulate nonspecific resistance against viral infection was investigated. Mice pretreated intravenously with squalane-in-water emulsions of MPL, alone or in combination with other immunostimulants, were given an aerosol of influenza virus three weeks after the pretreatment. Complete protection against lethal influenza virus infection was conferred when MPL was combined with trehalose dimycolate (TDM). The protective activity of MPL plus TDM combination was corroborated by a significant reduction of the lung virus titers. Combination of lower doses of MPL with TDM extracted from Mycobacterium bovis, but not with that of M. phlei, induced significant resistance to influenza virus. Preparations containing MPL alone, or combined with mycobacterial cell wall skeleton or muramyl dipeptide, were not effective. The adjuvant activity of MPL on bivalent influenza subunit vaccine was also studied. The primary antibody responses to influenza A and influenza B antigens were enhanced by the addition of MPL and were higher than the vaccine associated with aluminum hydroxide. The adjuvant activity of MPL was confirmed by the elevated secondary response. High levels of circulating antibodies were still present in the MPL group when antibody titers in the controls were waning.

Adjuvants, Immunologic↗
PubMed1985

Trehalose dimycolate from various mycobacterial species induces differing anti-infectious activities in combination with muramyl dipeptide.

Significant resistance against influenza virus and Mycobacterium tuberculosis infections was induced when trehalose dimycolate from M. tuberculosis or M. bovis but not M. avium was combined with muramyl dipeptide. Trehalose dimycolate from M. tuberculosis, in contrast to that from M. avium, could confer resistance against Toxoplasma gondii infections.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Stimulation of chemiluminescence and resistance against aerogenic influenza virus infection by synthetic muramyl dipeptide combined with trehalose dimycolate.

The effect on respiratory burst of splenic cells from mice pretreated with oil-in-water emulsions of muramyl dipeptide (MDP), trehalose dimycolate (TDM), or the combination of MDP with TDM was studied by luminol-dependent chemiluminescence in response to stimulation by zymosan. Spleen cells from mice pretreated with TDM, but not those of mice treated with MDP, generated increased chemiluminescence. Spleen cells from animals pretreated with the combination of MDP and TDM exhibited markedly enhanced chemiluminescence activity. The effect of enhanced activity of preparations containing MDP combined with TDM was further examined in vivo by an aerosol infection of pretreated mice with a mouse-pathogenic influenza virus. Pretreatment with 6-O-acyl analogs and one ubiquinone derivative of MDP alone did not induce any resistance against influenza virus. Significant protection was conferred only when MDP and certain analogs were combined with TDM. The enhancement of nonspecific resistance to influenza virus infection was related to the chemical structure of the synthetic immunostimulant. A greater degree of protection was induced by the combination of TDM with the lipophilic derivatives like B 30-MDP and L-18 MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Protective effect of muramyl dipeptide analogs in combination with trehalose dimycolate against aerogenic influenza virus and Mycobacterium tuberculosis infections in mice.

The effects of two aminobutyryl and four seryl analogs of the synthetic muramyl dipeptide (MDP) against aerosol infections with influenza virus and Mycobacterium tuberculosis were studied. Regardless of the MDP analog employed, there was no evidence that the resistance against viral and bacterial aerosol infections was enhanced in the treated mice. In parallel studies, significant protection against influenza virus and M. tuberculosis infections was induced by the combination of MDP or analogs with the mycobacterial glycolipid trehalose dimycolate (TDM). Resistance conferred by the MDP + TDM combination against influenza virus was present 1 week after pretreatment and could be abrogated by macrophage inhibitory agents silica, dextran sulfate, and carrageenan. Splenic cells from MDP + TDM-pretreated animals generated markedly enhanced levels of luminol-dependent chemiluminescence in response to influenza A and B viruses.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Effects of mycobacterial fractions and muramyl dipeptide on the resistance of mice to aerogenic influenza virus infection.

The nonspecific protective effect in mice of pre-exposure to mycobacterial components and muramyl dipeptide three weeks before aerosol infection with influenza virus A/PR/8/34 (H1N1) was studied. Muramyl dipeptide, when combined with trehalose dimycolate and emulsified in an oil-in-water emulsion, conferred complete protection comparable to specific immunization with a high dose of formalin inactivated A/PR/8/34 influenza viral vaccine. Animals pre-exposed to muramyl dipeptide plus trehalose dimycolate showed a marked reduction in lung virus titres, an earlier clearance of detectable infectious virus, and an earlier onset of antibody production in comparison to control mice. Resistance to infection was also observed with BCG-cell wall skeleton combined with trehalose dimycolate and trehalose dimycolate alone when given as oil-in-water preparations. The route of administration of nonspecific stimulants was crucial. Only intravenous but not intradermal inoculation produced significant protection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Stimulation of chemiluminescence by synthetic muramyl dipeptide and analogs.

The effect on respiratory burst of murine splenic cells after in vitro exposure to synthetic muramyl dipeptide (MDP) and 6-O-acyl and quinonyl derivatives was studied at an early phase of interaction by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. The MDP molecule enhanced CL, but the degree of CL response varied with the kinds of fatty acids introduced in the chemical structure of synthetic glycopeptide analogs. A 6-O-acyl derivative possessing an alpha-branched fatty acid chain, B30-MDP, stimulated maximum levels of CL activity. High CL responses were obtained with L8-MDP having a short chain of linear fatty acids and with QS-10-MDP-66 containing a ubiquinone compound. CL was also stimulated by MDP and its analogs in the spleen cells of nude mice lacking mature T lymphocytes, but the extent of stimulation was decreased compared with that of normal spleen cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of Mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well-characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsion and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculo-protein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1982

Mycobacterial antibodies after tuberculin testing, BCG- vaccination, BCG-immunotherapy and against cross-reacting antigens in a solid-phase radioimmunoassay.

A solid-phase radioimmunoassay (SPRIA) was used to investigate several factors influencing false positive and negative results in serodiagnostic test for tuberculosis, Unheated cytoplasmic fractions of mycobacteria, and other microorganisms were bound to polystyrol and antibody binding of sera from tuberculous, non tuberculous hospitalized patients and healthy adults was tested by the SPRIA-method. The level of antibody concentration in the SPRIA reflects roughly cross-reactivity between the antigens. Similar antibody binding occurred with M. tuberculosis, M. bovis, M. ulcerans and several "atyical" mycobacteria as test antigens, while other mycobacterial species and one of two tested tuberculin preparation (PPD) showed less antibody binding capacity. Significant cross-reactivity of fourty to sixty per cent was found between M. tuberculosis and N. asteroides but no cross-reaction was observed with C. parvum, S. typhi, S. paratyphi, C. Albicans or Aspergillus niger. Heating of mycobacterial cytoplasmic antigen resulted in a decrease of the test specifity. Tuberculin testing and intracutaneous BCG-vaccination in healthy adults had no distinct influence on the antibody response against several mycobacterial test antigens. However, a rapid increase of antibody levels was documented in melanoma patients after BCG-immunotherapy by sacrification with a more concentrated vaccine.

Antibodies, Bacterial↗
PubMed1982

Analysis of the soluble cytoplasmic components of Mycobacteria and Nocardia by crossed immunoelectrofocusing.

Soluble cytoplasmic components of Mycobacterium tuberculosis, strain H 37 Ra, and Washington II, Mycobacterium bovis, strain BCG and Nocardia asteroides were analysed by isoelectric focusing, crossed immunoelectrophoresis, and crossed immunoelectrofocusing. Using con A-affinity chromatography con A-reactive polysaccharides could be separated from the cytoplasmic fraction which improved the focusing effect. The isoelectric focusing patterns of the various mycobacterial strains were similar, however, concentration differences of the respective components might occur. N. asteroides had a different pattern. By crossed immunoelectrofocusing it was shown that most of the bands of the focusing pattern had antigenic character. Con A-reactive polysaccharides were located near to the cathode, and the con A-nonbound antigens occured close to the anode. Cross-reaction between mycobacteria and N. asteroides was remarkable. In crossed-line immunoelectrophoresis four line in N. asteroides antigens were identical with the highest peaks of M. bovis, strain BCG antigens.

Antigens, Bacterial↗
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsions and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculoprotein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1982

Cellular regulation of lung granuloma formation and delayed- type hypersensitivity induced with BCG cell walls. Further evidence of involvement of cellular immunity in lung granuloma formation.

We have previously showed several evidences in which cellular immunity is involved in lung granuloma formation induced with oil-associated BCG cell wall (CW) vaccine. In the present study, we examined in mice the effects of thymectomy, splenectomy and the administration of cyclophosphamide on lung granuloma formation as well as BCG CW-induced footpad reactions to PPD, a prototype of delayed-type hypersensitivity (DTH). The results presented herein provide further evidence that cellular immunoregulatory mechanisms control the development of lung granuloma and DTH, and that lung granuloma formation is thymus- and spleen-dependent.

Animals↗