Biomedical subjects
Publications and source records attributed to E T Jensen.
The interaction of human neutrophils with Pseudomonas aeruginosa biofilms was examined by using a chemiluminescence assay. The biofilms induced an oxidative burst response by polymorphonuclear leukocytes which was slow and only 25% of the response to planktonic bacteria. The reduced response to P. aeruginosa biofilms could play a role in the persistence of bacteria in chronic infections.
The protective effect of primed lymphocytes against a lethal dose of Salmonella typhimurium was studied in athymic and euthymic LEW rats. Primed lymphocytes were obtained by inoculating euthymic and thymus-grafted animals with a non-lethal dose of Salmonella typhimurium. Four weeks after the infection, spleen lymphocytes were separated by panning technique and antibody-coated magnetic microsphere separation using antibodies to pan T and pan B lymphocytes and subsequent sorting in a fluorescence activated cell sorter by means of monoclonal antibodies against CD4+ and CD8+ cells. Euthymic and athymic rats were injected with different doses of primed pan B, pan T, CD4+ and CD8+ T lymphocytes before inoculation with a lethal bacterial dose. Most of the animals treated with pan B, pan T or CD8+ cells died within two weeks. After treatment with primed CD4+ cells, only six of 39 animals died. Doses as low as 10(4) cells from both euthymic or thymus-grafted animals were effective, and athymic and euthymic recipients survived equally well. Four weeks after the infection both athymic and euthymic animals housed very few bacteria and had high antibacterial antibody titres. The percentages of splenic and lymph node CD4+ cells in the athymic rats were comparable to those found in the euthymic animals. The study shows that primed CD4+ lymphocytes even in very low doses are able to induce immunity against a Salmonella typhimurium infection.
Adherence of P. aeruginosa to the lining of the respiratory tract is probably mediated by interaction of pili or alginate with lactosyl and sialosyl residues on the respiratory cells. The toxins produced by P. aeruginosa (for example, elastase and alkaline protease) may play a key role during the initial persistent colonization as they interfere with important defense mechanisms. Neutralizing antibodies are eventually produced, and a poor prognosis is correlated to a pronounced antibody response. The bacteria are protected against the host's defense mechanisms by production of alginate which encapsulates microcolonies of P. aeruginosa in the lungs. During the chronic infection, toxins of P. aeruginosa probably play little if any direct pathogenic role, however, immune complexes seem to be a major trigger of chronic inflammation in the lungs. Proteolytic enzymes and oxygen radicals released from the abundance of neutrophils in the lungs are probably responsible for most of the tissue damage. The individual course of the chronic infection may be explained by regulatory mechanisms, such as cleavage of immune complexes by neutrophil elastase, and by the balance between the different IgG subclass-specific antibody responses.
Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic animals produced antibodies against S.typhimurium, but neither the euthymic nor the athymic animals survived the infection. After non-lethal infection euthymic and thymus-grafted nude rats were not affected by the second and otherwise lethal bacterial dose, and had high antibody titres. All the athymic nude rats died after the second and lethal bacterial challenge. Passive immunization with plasma from immunized euthymic animals did not protect any of the animals against the lethal bacterial dose. However, all animals survived when treated with large doses of spleen cells from immunized euthymic rats. Both athymic and thymus-bearing animals treated with primed spleen cells had high antibody titres. The percentages of splenic and lymph node T lymphocytes in primed spleen cell-treated athymic rats were comparable to those found in euthymic and thymus-grafted animals. Treatment with primed spleen cells from immunized thymus grafted animals provided only limited protective effect, and treatment with cells from athymic animals had no effect. The study shows that although isogeneic thymus-grafted nude rats become resistent to reinfection with S. typhimurium, only large doses of spleen cells from immunized euthymic animals can be used for passive transfer of immunity.
An outbreak of infections due to Flavobacterium meningosepticum type C in a neonatal intensive care unit is described. During a period of two weeks, two infants developed meningitis and a third was colonized in the respiratory tract and had transient bacteremia. The two meningitis patients were treated with clindamycin, rifampicin and cefotaxime systemically, plus rifampicin intraventricularly. Bacteriological eradication was achieved within 48 h, and both infants recovered from the meningitis without apparent neurological sequelae; however, one infant died two months later of unrelated causes. Environmental surveillance cultures failed to demonstrate a reservoir for the epidemic strain, but other Flavobacterium strains were recovered. Two clinically healthy infants were found to be colonized in the nasopharynx with strains that were extremely difficult to differentiate phenotypically from the epidemic strain. Extensive characterization of strains is necessary in order to differentiate between strains and subsequently to determine a certain source of infection.
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The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals became severely septicemic and died within a week of inoculation, irrespective of presence or absence of thymus. In the second experiment the animals were inoculated with 10(6) bacteria, and both euthymic and thymus-grafted animals responded with high titres of anti bacterial antibodies while these were very low in the athymic nude animals. Polyclonal antibody production was only observed in the euthymic animals and only regarding IgG. Athymic rats were not able to clear the infection, while the thymus-grafted animals reacted like euthymic rats: Very few animals housed the bacteria four weeks after inoculation, and no bacteria could be detected after four months. Immunohistochemical studies of lymphoid organs revealed that the infection caused a drop in the percentages of T non-helper cells, indicating low suppressor activity. The study shows that athymic nude rats are well suited for studies of infectious diseases in immune deficient hosts, and that whole neonatally isogeneic thymus grafting is a good way of reconstituting these animals immunologically.
A total of 2,793 courses of treatment with seven beta-lactam antibiotics were administered to 121 cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, and the patients were evaluated with respect to clinical hypersensitivity reactions. Seventy-five patients (62%) experienced 125 reactions, for an overall frequency (based on the number of courses) of 4.5%. Immediate reactions occurred in 34 patients (28.1%) during 53 courses (1.9%). The highest rate of reactions involved piperacillin (50.9% of patients), and the lowest rate involved imipenem and aztreonam (4.0% and 6.5% of patients, respectively); intermediate reaction rates were noted for carbenicillin (23.6% of patients), azlocillin (20.8%), cefsulodin (17.1%), and ceftazidime (13.0%). Cross-reactivity did not appear to be a major problem. Reactions to aztreonam seemed to be restricted to a small group of patients with a high propensity for beta-lactam hypersensitivity.