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Biomedical subjects

W Brehmer

Publications and source records attributed to W Brehmer.

At least 37 records · Page 2Linked to original sources

Inhibition of pulmonary granuloma formation in mice by treatment with Mycobacterial protoplasm and immuno-suppressants and its relation to protection against aerosol infection with virulent Mycobacterium tuberculosis.

Because the pulmonary granuloma formation by mycobacterial cell walls (CW) is likely mediated by cellular immunity, the effect of specific antigens and various immunosuppressants on pulmonary granuloma formation and protection against virulent m. tuberculosis, strain H37Rv was investigated in mice immunized with oil-treated CW from BCG or M. Tuberculosis, strain Aoyama B. Results of desensitization experiments with specific antigens showed that multiple intravenous injections of BCG protoplasm inhibited the footpad delayed hypersensitivity, macrophage migration inhibitory activity of lung cells and pulmonary granuloma formation as well as the enhancement of resistance against aerosol challenge with M, tuberculosis, strain H37Rv. However, treatment with nonspecific immunosuppressants like con A, silica or carrageenan induced only abrogation of footpad delayed hypersensitivity but not prevention of pulmonary granuloma formation or resistance against aerosol challenge. These results suggest a close relationship between pulmonary granuloma formation and protection against H37Rv in mice immunized with oil-treated mycobacterial CW.

Aerosols↗

The effect of Toxoplasma cell fractions and mycobacterial immunostimulants against virulent Toxoplasma gondii in mice.

Toxoplasma gondii tachyzoites were disrupted in a Ribi cell fractionator and separated into cell walls and protoplasm by differential centrifugation. These products were used alone or combined with a mycobacterial glycolipid (P3) and injected either as oil-in-water emulsions or incorporated in Freund's incomplete adjuvant. Mice were vaccinated by intravenous or intradermal routes and challenged intraperitoneally with a highly virulent strain of Toxoplasma gondii. A local granuloma formation was induced after i.d. inoculation of Toxoplasma vaccines containing P3 as this glycolipid enabled an adherence of the antigens on the mineral oil droplets. The adjuvant effect of P3 on antibody formation was also observed. Most of the fractions showed a low, but statistically significant prolongation of survival time. Vaccination by the i.v. route with homologous or heterologous antigens, including Trypanosoma cruzi, were not significantly effective, with the exception of a high dose of Toxoplasma protoplasm associated with P3.

Adjuvants, Immunologic↗

[Immunotherapy with BCG and mycobacterial fractions and its use in bronchogenic carcinoma (author's transl)].

Animal experiments at the Nat. Cancer Inst. have established that only intra-tumorous application of BCG vaccine has a lasting immunotherapeutic effect on transplantable tumours. However, clinical observations have proved that BCG immunotherapy by the intra-tumorous route increases the incidence of complications, such as allergic reactions and generalized spread of BCG, to an unacceptable level. Ribi has produced a vaccine from mycobacterial fractions which is low in protein and which, as proved in clinical pilot studies in cases of melanoma and cancer of the breast, is so well tolerated that it can be injected into the tumour. Since bronchogenic carcinoma is in the majority of cases inoperable, but, on the other hand, can be reached directly via the bronchoscope or the perthoracic route a pilot study with the Ribi vaccine was started in patients with lung cancer. The preliminary results are reported.

BCG Vaccine↗

[Regional suppurative lymphadenitis after BCG vaccination (author's transl)].

In the first half of 1975 there occurred in the Federal Republic of Germany an unusual rise in the incidence of suppurative inguinal lymphadenitis after BCG vaccination of newborns, in immediate time relation with change of the vaccine by its manufacturers, Behringwerke. The attenuated daughter strain Göteborg had been replaced by the effective but also rather aggressive strain Copenhagen 1331. The complication rate was 1.5% in West Berlin. Clinical course, operative technique as well as microbiological and histomorphological features of these cases were analyzed in a joint study. Since it is likely that, after re-admission of the Copenhagen vaccine, such complications may again occur despite reduced micro-organism count, vaccination of newborns should in future be restricted to those at risk.

BCG Vaccine↗

Immunotherapy with nonviable microbial components.

Structural components of microorganisms have been studied for immunopotentiating effect with the aid of transplantable (line 10) tumors in syngeneic guinea pigs. Microbial components were associated with oil droplets, suspended in Tween-saline, and injected intralesionally. BCG cell walls, given in this way, produced regression and cure of 50-60% of established tumors, as did viable BCG. Lipid extraction markedly reduced the tumor-regressing potency of cell walls, but P3, a trehalose mycolate present in the extract, restored full activity to the cell wall residue. P3 alone was nonsensitizing and had no antitumor activity, but it enhanced the latter property of various other microbial products. For example, the cure rates produced by cell walls of M. tuberculosis, M. bovis, M. phlei, or M. smegmatis were enhanced from 20-60% to as much as 90% by addition of P3. P3 also conferred antitumor activity on products from unrelated microbes, such as cell walls of E. coli, and in combination with endotoxins from rough Re mutant salmonellae, it produced cure rates of up to 93%. These results suggest that P3 is essential to the immunopotentiating activity of mycobacteria and that it may be broadly applicable in immunotherapy of cancer with microbial agents.

Animals↗

Cutaneous granulomatous response to BCG cell walls with reference to cancer immunotherapy.

A chronic inflammatory response produced by cell walls of Mycobacterium bovis strain BCG associated with microscopic oil droplets (BCG CW-O) was studied with reference to the tumor-regressing ability of this preparation. When BCG CW-O was injected intradermally in the footpads of guinea pigs, intense inflammation developed at the site of injection and in the draining popliteal lymph node. This was characterized histologically as granulomatous inflammation. The intensity of the response was related to the dose of BCG CW-O. Cell walls without oil produced the same type of inflammation but much less in degree. Data are presented that demonstrate the immunological nature of this response and classify it as a cell-mediated immune reaction. Ramifications of this chronic inflammatory reaction occurring at the site of a tumor are discussed.

Animals↗

[Fatal course of generalized BCG histiocytosis in congenital immune deficiency (author's transl)].

Severe combined X-linked immune deficiency ended fatally in a six-month-old male infant after generalized BCG infection. Damage in the cell-bound thymus-dependent immune system is decisive in the development of "BCG histiocytosis". As a result of absent immunocompetent sensitized T-lymphocytes there is insufficient information and stimulation of macrophages to kill the micro-organsims. The disorder of bactericidal properties of macrophages results in an overwhelming infection with BCG bacteria with a characteristic morphological picture.

BCG Vaccine↗

Aerosol-Induced Tuberculosis in Subhuman Primates and the Course of the Disease After Intravenous BCG Vaccination.

Suitability of the rhesus monkey (Macaca mulatta) as an experimental host for evaluation of vaccines against airborne infection with Mycobacterium tuberculosis strain H37Rv was investigated. Nonvaccinated monkeys were exposed to estimated doses of 12, 25, or 49 units of H37Rv in a modified Henderson apparatus, and the course of the disease was followed by chest X rays, skin testing with purified protein derivative, body-weight determinations, and autopsy 8 weeks postinfection. These animals developed progressive and extensive tuberculosis with pathological changes proportional to the infecting dose. Four of seven monkeys vaccinated intravenously with 1 mg of live BCG 8 weeks prior to challenge with 40 units of H37Rv had no gross evidence of disease at autopsy 13 weeks postinfection; the other three monkeys had minimal disease. These data demonstrated that (i) reproducible and progressive infection could be induced in rhesus monkeys infected in a manner which simulated natural infection of man and (ii) a high level of resistance to infection could be induced by BCG vaccine in the rhesus monkey, which in nature is highly susceptible to tuberculous infection.

Journal Article↗