[Infections due to foreign bodies].
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Biomedical subjects
Publications and source records attributed to H Repo.
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Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell counts. The present results give credence to the view that the hyperreactive neutrophils and the vasodilatory prostaglandins produced by them can together trigger a vicious circle which results in increased inflammatory symptoms in patients with yersinia arthritis who have HLA B27 as compared with those who lack this antigen.
Ankylosing spondylitis and reactive arthritis triggered by either enteritis or urethritis are both associated with human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve immune function and inflammatory responsiveness of the host. Evidence has accumulated that neutrophils of HLA-B27 positive subjects show high chemotactic responses both in vitro and in vivo. Such a hyperreactivity may result in an exaggerated inflammatory response and thereby contribute to the pathogenesis of HLA-B27 associated diseases. We have extended the studies of phagocyte function by examining superoxide production and yersinicidal activity of neutrophils from patients with previous yersinia arthritis; the results show no gross differences, between patients and healthy subjects on one hand and between subjects with and without HLA-B27 on the other.
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Ankylosing spondylitis, acute anterior uveitis and reactive arthritides, including enteroarthritis and uroarthritis , are all associated with the human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve inflammatory responsiveness of the host. In an acute inflammatory reaction, neutrophils are considered to cause tissue injury by both liberating lysosomal enzymes and generating toxic oxygen-derived free radicals. Furthermore, they may regulate both capillary permeability and the rate of vasodilatation at the site of inflammation. Evidence has accumulated that neutrophil responses to a phlogistic stimulus are enhanced in HLA-27 positive subjects. We suggest that hyperreactive neutrophils trigger a vicious circle of inflammation and render the subjects susceptible to exaggerated tissue injury.
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The occurrence of circulating immune complexes (CIC) was studied in 9 patients with Yersinia arthritis and 7 with Yersinia enteritis (YE) without extraintestinal symptoms by the platelet-iodinated protein A (PIPA) technique and by a solid phase Clq-binding enzyme-linked immunosorbent assay. CIC were detected by both techniques in all the patients with Yersinia arthritis during the acute disease and in 3 of them after recovery. CIC were also found in 5 of the 7 patients with uncomplicated YE, suggesting that CIC were associated with YE irrespective of the development of arthritis.
Chemotaxis, phagocytosis and bactericidal activity of neutrophils obtained from eight patients with Shwachman syndrome were studied repeatedly over a 9 year period. In a membrane filter the patient neutrophils migrated both toward casein and toward zymosan activated serum significantly less than did the control cells. Chemokinetic migration in casein was likewise significantly impaired. As determined by agarose assay, random locomotion of the patient neutrophils was significantly depressed. The differences in phagocytosis and bactericidal activity between the patients and the control subjects were not significant. However, phagocytosis by neutrophils obtained from healthy subjects was significantly impaired in sera from four patients, compared with that in control sera. The follow-up study showed the neutrophil migration defect to be constant in repeated tests, whereas infectious episodes diminished in number after the patients reached the age of 3-7 years.
Immune function was studied in normocalcemic breast cancer patients with bone metastases treated with either dichloromethylene diphosphonate (Cl2MDP) or placebo. The results showed no significant difference between the two patient groups. This suggests that Cl2MDP does not markedly impair the host's defense mechanisms, and in this respect can be safely used in the treatment of patients with resorptive bone disease.
The pathogenesis of HLA-B27 linked diseases, including reactive enteroarthritides, is not known. Differences in immune response, cross-reaction between microbial antigens and host cell structures, attachment of microbial components on the host cell surfaces with subsequent autoimmune reaction, and inflammatory responsiveness of the host may be involved. In this contribution we present evidence to show that HLA-B27 positive subjects may be prone to an exaggerated inflammatory response, as compared with HLA-B27 negative subjects.
We report here on the first two patients with acquired immune deficiency syndrome (AIDS) in Finland. The first patient, a 37-year-old man, had Kaposi's sarcoma and the other, a 26-year-old man, had pneumonia due to Pneumocystis carinii. Both patients were homosexuals and showed a marked defect in cell-mediated immunity consistent with the definition of AIDS. Both patients were found in a screening survey of homosexual men in Helsinki.
Chemotactic and chemokinetic migration of polymorphonuclear leukocytes in sera from patients with previous yersinia arthritis and from healthy subjects with or without HLA--B27 were studied by the leading front method. Irrespective of yersinia arthritis, zymosan-activated sera from subjects who were HLA--B27 positive were significantly more chemokinetic than were HLA--B27 negative zymosan-activated sera from healthy control subjects. The chemotactic activities of zymosan-activated sera that were HLA--B27 positive or negative, as determined by chemotactic increments, were much the same. The results suggest that zymosan-activated serum that is HLA--B27 positive stimulates random migration of polymorphonuclear leukocytes, but not their directional migration, more than does HLA--B27 negative serum that has been zymosan activated. This may contribute to accumulation of polymorphonuclear leukocytes at the site of inflammation in vivo and thereby to inflammatory symptoms in yersinia arthritis patients with HLA--B27.
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Distance of migration and cumulative cell count were determined in parallel to quantitate migration of polymorphonuclear leukocytes (PMNs) of healthy volunteers in the chemotaxis-under-agarose assay. The cumulative percent distributions of the rates of spontaneous migration in the absence of an attractant, of chemokinetic migration in zymosan-activated human serum (ZAS) incorporated in agarose, and of chemotactic migration toward ZAS were approximately normal. Cord blood PMNs are known to respond poorly to ZAS in vitro; this was used to determine whether the chemotactic indices (CI: ratio of migration toward ZAS to spontaneous migration) and the chemotactic differentials (CD: difference between migration toward ZAS and spontaneous migration) correlated with impaired chemotaxis under agarose. Both CI and CD values of cord PMNs were significantly low, indicating a positive correlation. The CI values of healthy volunteers correlated negatively with spontaneous migration, whereas the correlation of the CD values was neither negative nor positive. Since spontaneous migration of PMNS varies, the results support the use of CD values when comparing chemotactic responses of PMNs from different donors; e.g., the CD values were determined to evaluate the responsiveness of HLA-B27-positive PMNs, which we recently found to migrate under agarose toward ZAS more than HLA-B27-negative PMNs. The CD values of HLA-B27-positive PMNs were significantly high, indicating that the cells were high responders.