Biomedical subjects
Publications and source records attributed to H Hahn.
Technique, advantages and disadvantages of computerized tomographic (CT) mammography are described in various pre- and postoperative conditions. The value of CT mammography is discussed.
Cellular, genetic, and antigenic requirements for granuloma formation in murine listeriosis were determined by using adoptive transfer of granuloma formation. Granuloma formation was restricted by a class I MHC antigen (H-2K) and critically depended on a Ly-2+ (Ly-1+2+) T cell. Expression of granuloma formation required living bacteria; heat-killed bacteria was not sufficient. H-2K-restricted transfer of granuloma formation was associated with a high degree of protection. Markedly less protection, presumably due to macrophage activation by T cells, was found under conditions of H-2 I-A homology. It is concluded that two T cell populations are involved in protection against L. monocytogenes: protection associated with granuloma formation depends on Ly-2+ (Ly-1+2+) T cells, is restricted by H-2K, and requires products of living bacteria to be expressed, whereas protection based on macrophage activation depends on H-2 I-A-restricted T helper cells.
The influence of the orally applicable antibacterial agents, cefaclor (Panoral), doxycycline, erythromycin, and cotrimoxazole on phagocytosis by human neutrophil granulocytes was investigated. Further, the influence of cefaclor, erythromycin, and doxycycline on PHA stimulation of human blood lymphocytes was studied. Doxycycline (1 mg/ml) had strongly suppressive effects on phagocytosis, whereas cefaclor (1 mg/ml cotrimoxazole (0.1 mg/ml), and erythromycin (0.1 mg/ml) did not suppress phagocytosis. PHA-induced lymphocyte stimulation was strongly inhibited by doxycycline (10 micrograms/ml), whereas cefaclor (10 micrograms/ml) did not suppress at all. Erythromycin (10 micrograms/ml) exerted some inhibition (average 12.6%). These results are discussed with respect to immunoneutrality of antibacterial agents.
Monoclonal antibodies anti-Ly 1, anti-Ly 2 and GK1.5 were applied to determine phenotypes of T cells within granulomas formed as a result of infection of mice with the facultative intracellular bacterium Listeria monocytogenes. Early in granuloma formation, equal numbers of Ly 1+, Ly 2+ and L3T4+ cells were found, T cells of different phenotypes being evenly distributed over the lesions. In mature granulomas, numbers of Ly 1+ and L3T4+ cells about doubled as compared to incipient granulomas, Ly 2+ cells, however, remained constant. Whereas Ly 1+ and L3T4+ cells within mature granulomas still were evenly distributed, Ly 2+ cells were predominantly localized in the periphery of the lesions. The data indicate that both, specific Ly 2+ and L3T4+ T cells, display characteristic dynamics within granulomas: Ly 2+ T cells which most likely mature from Ly 1+2+ T cells over time locate to the periphery. Concomitantly, L3T4+ T cells are enriched maintaining their distribution all over the lesions.
In the blind loop syndrome bacterial overgrowth--accompanied by an increase in bile acid deconjugation--is thought to be responsible for the observed morphological alterations of the small intestinal mucosa with its concomitant malabsorption syndrome. Since in this chain of events the bacterial overgrowth is of primary importance, we have performed a complete qualitative and quantitative evaluation of the intraluminal flora in rats with surgically created self-filling blind loops. The results show a significant increase in bacteria of the aerobic growing genera E. coli and Streptococcus (Enterococcus), and of the anaerobic growing genus Bacteroides, in one single rat also of the genera Lactobacillus/Bifidobacterium. In order to elucidate which strains of bacteria are predominantly responsible for the morphological and functional alterations observed in the stagnant loop syndrome, germ-free rats with self-filling blind loops should be contaminated selectively with bacteria of these genera.
Explore the source record for details and available documents.
4-Hydroperoxycyclophosphamide is a derivative of cyclophosphamide which in vitro is converted into an active metabolite of cyclophosphamide. This compound was used to define the relative susceptibilities of T cells involved in the immune response of mice to the intracellular pathogen, Listeria monocytogenes. L. monocytogenes-specific T cell proliferation and interleukin production in vitro, as well as adoptive protection and delayed-type hypersensitivity in vivo, all proved to be markedly resistant to the action of 4-hydroperoxy-cyclophosphamide, indicating a great homogeneity within the cellular immune response to intracellular pathogens.
Using an animal model, a synergism in lethality of infections with Escherichia coli and Bacteroides fragilis is described. This synergism was dependent on certain dosage combinations of the infectious agents. It was demonstrated that animal-passaged, laboratory-passaged, and heat-killed B. fragilis alike were capable of producing this synergism. However, animal-passaged B. fragilis showed superior recovery rates from animal organs.
Lyt phenotypes of peritoneal exudate T lymphocytes from Listeria monocytogenes-immune mice were determined with respect to their capacity to confer protection upon local or systemic transfer. It is shown that, locally, Lyt 1 T cells provide protection, whereas only unselected native populations, containing adequate numbers of Lyt 123 T cells, were effective in transferring systemic protection. When Lyt 1 T cells were the crucial cell type (local transfer), admixture of Lyt 123-containing peritoneal exudate T-lymphocyte-enriched cells did not enhance protection, save for slight additive effects. Likewise, when Lyt 123-containing peritoneal exudate T lymphocyte-enriched cells were the crucial cell type (systemic transfer), admixture of various numbers of Lyt 1 cells was without marked effect. A change in Lyt phenotype from Lyt 123 to Lyt 1 paralleled by an increase of protective capacity upon local transfer was observed when sensitivity of early and late exudate T cells to anti-Lyt 2.2 antiserum plus complement treatment was investigated. The data suggest that (i) the propensity of specific T cells to enter exudates is associated with the Lyt 123 phenotype, (ii) the actual effector cell of antibacterial protection is an Lyt 1 T cell, and (iii) a developmental interrelation exists between Lyt 123 T cells and Lyt 1 T cells in T-cell-dependent protection of mice against L. monocytogenes.
Lyt-selected Listeria-immune T lymphocytes from peritoneal exudates and cloned T cells were cocultured with heat-killed listeriae and peritoneal macrophages from nonimmune donors. Supernatants were assayed for: activation of macrophages for tumoristatic and tumoricidal activity via macrophage-activating factors and migration-inhibition factor activity. Peptone-induced peritoneal macrophages were activated by incubation with the supernatants for 24 h. For examination of cytocidal activity, 51Cr-labeled EL4 tumor cells were subsequently added, and 51Cr release was determined. Cytostatic activity was measured by adding unlabeled EL4 tumor cells to the pretreated macrophages and determining [3H]thymidine incorporation 24 h later. Migration-inhibition factor production was examined in an agar microdroplet assay. Only Listeria-specific T cells of the phenotype Lyt 1+2- proved active in these assays, whereas T cells of the phenotype Lyt 1-2+ were not active. When T-cell clones were used, a single clone was capable of inducing macrophage-activating and migration-inhibition factor production at cell concentrations of ca. 10(3)/ml.
Intravenous infection of NMRI mice with a highly virulent strain of Klebsiella pneumoniae induced protracted septicemia with high lethality. Treatment of the animals with specific rabbit immunoglobulins was able to lower mortality significantly if the immunoglobulins were administered no later than 6 hours after infection. In cyclophosphamid-treated mice, even inocula as low as 10-20 organisms proved to be highly lethal. Immunoglobulins were similarly protective under these conditions and significantly lowered mortality even when injected as late as 8 hours after infection. When immunocompromised mice were infected with higher challenge inocula, the therapeutic effect decreased and the time interval allowing efficient therapy became shorter. However, even if immunoglobulin therapy was performed too late, it was able to delay mortality for several days.
The influence of Cefaclor and of Tobramycin on phagocytosis of sheep erythrocytes by murine peritoneal macrophages was investigated. The antibiotics in various concentrations were either added to the cells directly during the phagocytosis period or injected i.v. into cell donor mice at different times before cell harvest and the cells subsequently assayed for phagocytic activity in vitro. When antibiotic was added during the phagocytosis a dose-dependent inhibition of phagocytosis was observed which, however, became significant only at extremely high concentrations of the antibiotic. In all other experimental set-ups, phagocytosis was not influenced by antibiotics. Restrictive usage of either antibiotic in clinical situation does not appear mandatory on the basis of the reported observations.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Cultures of peritoneal exudate T lymphocyte-enriched cells (PETLEC) from Listeria monocytogenes-immune mice, antigen-presenting cells (APC) and heat-killed L. monocytogenes produced high amounts of interferon-gamma (IFN-gamma). High IFN titers were also observed after stimulation of L. monocytogenes-immune cell cultures with the T cell mitogens concanavalin A and phytohemagglutinin. L. monocytogenes-immune PETLEC produced several fold higher IFN titers than normal cell cultures in response to mitogen and antigen. Under both circumstances, APC were required for optimum responses. L. monocytogenes-immune PETLEC participating in IFN production were Lyt 1+23-. IFN-gamma was also produced in cultures of cloned L. monocytogenes-specific T cells. Since the same T cell clone showed antigen-specific proliferative responses and interleukin production in vitro, and could adoptively mediate delayed-type hypersensitivity and anti-listerial protection in vivo, it is suggested that IFN production is a function of specific T cells active in cellular antibacterial immunity.
Pathogenic bacteria fall into two groups with regard to their fate within phagocytes: extracellular bacteria are promptly killed after phagocytosis and facultative intracellular bacteria are resistant to intracellular killing unless macrophages are activated. Extracellular bacteria cause purulent infections, and facultative intracellular bacteria granulomatous ones. Humoral immune mechanisms (antibody, complement) deal mainly with extracellular bacteria, while cellular immune mechanisms (T cells, macrophages) deal with facultative intracellular bacteria. The specific and nonspecific factors and their interactions are discussed with respect to their role in the buildup of an effective antibacterial defence.
Explore the source record for details and available documents.
Mice were sensitized with graded doses of sheep erythrocytes by the intravenous or subcutaneous route and challenged for delayed-type hypersensitivity (DTH) at different times thereafter. The DTH response as assessed by footpad swelling (FPS) was compared to the spontaneous proliferative response of the popliteal lymph node cells (PLNC). Proliferation of PLNC was optimal after sensitization regimens resulting in optimal FPS. The same was true for mice sensitized under cyclophosphamide modulation. Proliferation of PLNC induced by SRBC was antigen-specific, although some crossreactivity with horse red blood cells was observed. Proliferation of PLNC could be abrogated by treatment with anti-Thy-1.2 antiserum plus complement demonstrating the T cell nature of proliferating cells. In accordance with published data, FPS of mice presensitized with a high dose of SRBC as well as FPS of recipients of spleen cells from high-dose-sensitized donors was suppressed. In marked contrast, PLNC proliferation was not diminished in these mice. Although proliferation of PLNC did not parallel FPS under all circumstances, it seems to be a correlate of the cellular immune response to SRBC.