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Biomedical subjects

H Repo

Publications and source records attributed to H Repo.

At least 37 records · Page 2Linked to original sources

Luminol-enhanced chemiluminescence of whole blood. Statistical analysis, and comparison of the responses of different subjects.

We studied the effects of different variables on luminol-enhanced chemiluminescence (CL) of whole blood, induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP), opsonized zymosan particles (OZP), or phosphate buffered saline (PBS). Use of correction factor based on blood neutrophil count and hemoglobin concentration decreased interindividual variation and improved normality of the frequency distributions of CL responses. In FMLP- and PBS-induced CL, day-to-day variation was not significant, but it was significant in OZP-induced CL. Although storage of blood samples for 8 hours decreased CL, the decrease was not evident in a study of initial activation, i.e. CL measured at one minute after application of FMLP. Our results suggest that FMLP-induced initial activation is well suited for epidemiological studies because it is easy to determine and is affected neither by day-to-day variation nor by storage of the blood samples for a few hours.

Adult

Chronic osteomyelitislike disease with negative bacterial cultures.

During a seven-year period we observed 14 children who had chronic osteomyelitislike disease. The bacterial cultures from the bone lesions were negative. In eight patients the findings were compatible with chronic recurrent multifocal osteomyelitis (CRMO), in four the findings were compatible with chronic sclerosing osteomyelitis of Garré, and two had osteomyelitis of the clavicle. In patients with CRMO, lymphocyte subpopulations, the responses to mitogens, and the chemotactic and chemokinetic responses showed no consistent abnormalities. After a mean follow-up of 4.5 years (range, one to ten years), all four patients with osteomyelitis of Garré were symptomatic, and two had complications. Only two of the eight patients with CRMO had active disease. The course had been complicated by growth disturbances in one patient and by thoracic outlet syndrome in another. Wegener's granulomatosis later developed in a patient with CRMO.

Adolescent

Reactive arthritis associated with Shigella sonnei infection.

Several studies have failed to show an association between Shigella sonnei dysentery and reactive arthritis. We describe 3 patients who had reactive arthritis and a recent or concurrent S sonnei infection. To our knowledge, this is only the second study to suggest this association. We propose that S sonnei should be considered as a triggering agent for reactive arthritis.

Adult

Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome.

PURPOSE: In order to evaluate the relationship between cachectin/tumor necrosis factor (TNF) and cachexia in the acquired immunodeficiency syndrome (AIDS), we studied the serum levels of endogenous cachectin/TNF in subjects with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: Fifty-three serum samples were obtained from 39 HIV-seropositive patients. The condition of each patient was clinically classified as either asymptomatic, lymphadenopathy syndrome (LAS), AIDS-related complex (ARC), or AIDS. Control sera were obtained from 29 healthy male blood donors. A double antibody radioimmunoassay was used to measure the serum levels of cachectin/TNF. RESULTS: Cachectin/TNF levels were within the reference range of the control values in all (eight of eight) asymptomatic HIV-infected subjects and in 11 of 13 of the patients with LAS. In contrast, all patients with AIDS (nine of nine) and five of nine of the patients with ARC had raised levels of cachectin/TNF. Fluctuation of the levels of cachectin/TNF occurred during follow-up, but initially raised levels remained elevated. CONCLUSION: Since cachectin/TNF suppresses lipoprotein lipase in adipocytes in vitro, and causes weight loss under experimental conditions, the findings of raised levels of cachectin/TNF in patients with AIDS may have relevance to the pathogenesis of cachexia.

AIDS-Related Complex

Complement activation and HLA-B27.

The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopolysaccharide treatment (17.6 (3.7)% v 15.0 (3.8)%). The differences occurred irrespective of previous arthritis, complement C4 or Bf phenotype, or variation in background complement levels. The findings suggest that an increased responsiveness to complement activators may contribute to the pathogenesis of HLA-B27 associated inflammatory diseases.

Adult

Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic migration rates higher than those of control cells of healthy HLA-B27 negative subjects. These functional aberrations may play a part in the development of the patients' inflammatory symptoms.

Adult

Phagocyte function in reactive arthritis.

The pathogenesis of reactive arthritis is multifactorial. The possible pathogenetic mechanisms include the role of microbial antigens which cross-react with the host tissue or trigger cytotoxic immune response. In addition an exaggerated inflammatory response of the host may contribute to the clinical picture of the acute arthritis and its late sequels. In this review, we present data showing that HLA-B27 positive subjects show enhanced neutrophil (PMN) migration and their sera support PMN migration more than HLA-B27 negative sera. Enhanced PMN function is persistent in patients with previous severe reactive arthritis or with late inflammatory sequels. In addition to hyperreactive PMNs, monocytes from patients with previous yersinia arthritis, but also from healthy HLA-B27 positive subjects, respond to stimulation with lipopolysaccharide by enhanced production of inflammatory monokines compared with HLA-B27 negative healthy controls. Thus, hyperreactive phagocytes can contribute to the severe inflammatory complications seen in patients with reactive arthritis. The primed phagocytes can also respond vigorously when stimulated either with endogenous mediators of inflammation or with endotoxin released during a new infection or as a sequel of change in the mucosal permeability described in patients with spondyloarthropathy.

Arthritis, Infectious

[Erythema nodosum].

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Erythema Nodosum

Neutrophil migration in vivo and in vitro in healthy neutropenic subjects.

Migration of polymorphonuclear leukocytes (PMN) was studied in six healthy subjects with neutropenia (peripheral blood neutrophil count less than or equal to 1.5 X 10(9)/1). Determined as migration differentials, chemotactic and chemokinetic responsiveness tended to be higher in the neutropenic group. Despite this slight tendency to increased responsiveness in vitro, migration in vivo proceeded more slowly in the neutropenic group than in the control group: at 12 hours the leukocyte counts in the skin chamber media were significantly lower, whereas at 24 hours they were nearly normal. Our results show that PMN migration in healthy neutropenic subjects is different from that in healthy non-neutropenic subjects. These differences should be taken into account in the evaluation of the role of aberrant PMN migration in the development of infectious episodes in a neutropenic patient.

Agranulocytosis

Production of tumour necrosis factor and interleukin 1 by monocytes of patients with previous Yersinia arthritis.

We studied production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by using purified peripheral blood monocytes of patients with previous yersinia arthritis (YA) and of healthy HLA-B27 positive and negative controls. Lipopolysaccharide-exposed cells of HLA-B27 positive and negative patients, and those of HLA-B27 positive controls, generated significantly more TNF than did HLA-B27 negative control cells. There was a positive correlation between the levels of TNF and IL-1. Our results give credence to the view that augmented production of phlogistic mediators may contribute to inflammatory symptoms in patients with HLA-B27 associated disease.

Adult

Prenatal diagnosis of X-linked chronic granulomatous disease using restriction fragment length polymorphism analysis.

Prenatal diagnosis of X-linked chronic granulomatous disease (CGD) was performed with restriction fragment length polymorphism (RFLP) analysis using probes flanking the gene. The male fetus and an affected male displayed the same haplotype for RFLPs belonging to six linked loci extending from DXS164 to DXS7, which encompass the CGD locus, and for which the mother was heterozygous. Diagnosis of an affected fetus was confirmed after termination of the pregnancy by the study of fetal granulocytes using the nitroblue tetrazolium reduction test. In informative families prenatal diagnosis of CGD can be made earlier by RFLP analysis than by fetal blood sampling.

DNA

Superoxide dismutase isoenzymes, glutathione peroxidase and selenium in blood from HLA-B27-positive and -negative subjects.

We studied the activity of superoxide dismutase (SOD) isoenzymes (CuZnSOD, cyanide-resistant MnSOD and extracellular SOD), the concentration of plasma selenium (P-Se), and the activities of CuZnSOD and glutathione peroxidase (GSHPx) in erythrocytes of 10 HLA-B27-positive and 10 HLA-B27-negative subjects whose sera had shown high and low chemokinetic activity, respectively, on migration of polymorphonuclear leukocytes (PMN) in vitro. No significant difference was found between the groups, suggesting that the enhanced chemokinetic activity of HLA-B27-positive sera does not derive from an aberration in serum anti-oxidant potentials. The results were also analysed on the basis of HLA-DR specificities; HLA-DR4-positive plasma samples had significantly lower levels of Se than HLA-DR4-negative ones. We therefore carried out a second series of experiments with sera of 37 subjects; the levels of P-Se in HLA-DR4-positive and -negative groups were much the same, as were the activities of GSHPx. The data suggest that there is no gross aberration in P-Se concentration in HLA-DR4-positive subjects.

Chemotaxis, Leukocyte

Antibody- and complement-dependent cell injury assayed by 51Cr release from human peripheral blood mononuclear cells pretreated with lipopolysaccharide.

Exposure of human peripheral blood mononuclear (MN) cells to deesterified (alkali-treated) lipopolysaccharide (LPS-OH) and then to 51Cr rendered the cells susceptible to 51Cr release in the presence of specific antibody and complement. The assay was optimized by using rough (Rb2 or Re) LPS. 51Cr release did not occur from cells preexposed to untreated or electrodialyzed LPS. Studies of isolated monocytes and lymphocytes revealed that the majority of the 51Cr released was derived from monocytes. The optimum concentration of LPS-OH was 10 micrograms/ml. Antiyersinia agglutinin-positive serum, but not a negative serum, obtained from patients with reactive yersinia arthritis caused 51Cr release from MN cells pretreated with yersinia LPS-OH. This implies that during yersinia infection antibodies are generated that can attack the cell membrane--LPS-OH complex. We conclude that the method provides a tool to demonstrate binding of LPS to MN cells in a manner that leads to cell injury in an immune host.

Adult

Polymorphonuclear leucocyte function and previous yersinia arthritis: enhanced chemokinetic migration and oxygen radical production correlate with the severity of the acute disease.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, binding of chemotactic peptide, and aggregation) were studied in HLA-B27 positive patients with previous yersinia arthritis (YA). PMNs of patients whose disease had been severe showed chemokinetic and chemiluminescence responses significantly higher than the PMNs of those with a mild disease. The results support the view that enhanced PMN function contributes to inflammatory symptoms in patients with YA.

Acute Disease

Defects in phagocytic functions.

Phagocytic cells play a critical role in host defence against bacterial infections, often seen as frequent infectious episodes in patients with granulocytopenia, a quantitative phagocytic disorder encountered not infrequently in clinical practice, and in the more rare patients who have a clinically significant qualitative disorder, i.e., a normal number of phagocytes but defects in phagocyte function. In addition to infective agents, phagocytes can be activated by noninfectious structures such as immune complexes. In either case, phagocyte activation, also, inevitably results in destruction of the host's own tissues. Consequently, the degree of phagocyte activity is a double-edged sword: hypoactivity renders the host susceptible to infections while hyperactivity leads to undue phagocyte-mediated tissue injury. This review will discuss the physiology and qualitative defects, including hypoactivity, hyperactivity and inappropriate activation of phagocyte function, as well as the management of the patients.

Bacterial Infections