Biomedical subjects
Publications and source records attributed to H H Peter.
We present a case of Sneddon's syndrome with high titers of antiphospholipid antibodies (APLA), in which the leading symptom was an incapacitating memory defect. MRI revealed vasculitic lesions of the central nervous system (CNS). Therefore immunosuppressive therapy was started with steroids and cyclophosphamide pulses. The transient beneficial effects of such a therapy will be discussed.
In order to investigate, if complement levels can be used as an indicator of clinical activity in systemic lupus erythematosus (SLE), levels of C3, C4, CH50, and C3d were measured in 79 patients, 41 with inactive, 31 with moderately active and 7 with severely active disease. Our study shows that C3d, and particularly the C3d/C3 ratio, provide sensitive markers for disease activity in SLE. Since C3d is a direct measurement of complement turnover, it reflects complement activation better than C3, C4 and CH50.
The T cell receptor (TCR) V beta gene segment repertoire of T lymphocytes derived from peripheral blood of two healthy individuals and synovial tissue, synovial fluid and peripheral blood of three rheumatoid arthritis (RA) patients was analyzed. A sensitive assay based on the amplification of cDNA by the polymerase chain reaction (PCR) was used to analyze the levels of expression of 20 TCR V beta gene segment families. The relative expression of V beta gene segments in lymphocytes derived from peripheral blood, synovial tissue and synovial fluid was conserved over 155 days in one patient. V beta 9 transcripts were undetectable in the cells of this individual. In the two other patients the frequency of V beta 2 transcripts in synovial T cells of affected joints was significantly higher than in their peripheral blood lymphocytes. Dominance of distinct rearrangements among the V beta 2 transcripts from the synovial cells of these patients support the idea that the synovial T cell response is driven by antigen.
In cases of reactive arthritis, a suspected Chlamydia trachomatis infection is often detected by serological methods. However, mostly tests with genus-specific antigens are used, neglecting the fact that antibodies against Chlamydia pneumoniae are highly prevalent in the adult population. Therefore we tested sera of 129 patients with various rheumatological disorders and of 18 healthy persons in parallel with a genus-specific test (IPAZYME) and with the species-specific microimmunofluorescence test for C. trachomatis and C. pneumoniae antibodies. The data showed that 55% of the 64 IPA-positive results were caused by antibodies (IgG) against Chlamydia pneumoniae, only 6% by anti-Chlamydia trachomatis IgG and 20% by both specificities. For IgA antibodies, the percentages were 44%, 12.5% and 12.5% respectively. In 12 IPA-positive cases, the MIF showed no reaction. 58% of all 147 sera tested with MIF had IgG antibodies against C. pneumoniae, 5% had anti-C. trachomatis IgG and 8% IgG against both species. The percentages for IgA were 29%, 2% and 2%, respectively. IgM positivity in MIF disappeared after absorption with rheumatoid factor absorbent. No significant differences were found between the various groups of patients. The data suggest that due to the high prevalence of anti-C. pneumoniae antibody, genus-species tests cannot be used as screening tests for the serological diagnosis of C. trachomatis infections.
Using a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody-secreting cells (ASC). Under these conditions 25-100% of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG-Fc fragments (RF), the 65-kD heat shock protein of Mycobacterium bovis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p-ASC) able to produce IgM binding to these antigens in frequencies above 0.03% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p-ASC able to produce monospecific or multireactive RF. Whereas most p-ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p-ASC(RF) in healthy control persons are cross-reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease-specific expansion of p-ASC committed to the production of monospecific rheumatoid factors.
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The second exon of the DRB1 gene encoding for the first domain of the HLA-DR beta 1-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.
N-Hydroxy-desferrioxamine B (5), a postulated metabolite of the microbial product desferrioxamine B (1), has been prepared by reduction of the intermediate oxime 6 with sodium cyanoborohydride. The oxime was obtained by selective oxidation of desferrioxamine B with hydrogen peroxide and a catalytic amount of sodium tungstate dihydrate. The iron complex derived from 5 enabled definite proof of the structure of one of four metabolites of desferrioxamine B found in urine samples of patients treated with this drug.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
No other chronic inflammatory disease is currently receiving more attention from basic scientists than rheumatoid arthritis (RA). Topics of intense research are HLA disease association, peculiarities of the synovial T- and B-cell repertoire, changes of synoviocytes and cytokine profiles as well as animal models and new therapeutic strategies.
Sera of 90 patients fulfilling the criteria of the American Rheumatism Association for the rheumatoid arthritis (RA) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. All sera were also tested for rheumatoid factor (Waaler-Rose-Test, WRT), C-reactive protein (CRP), antinuclear autoantibodies (ANA) on HEp-2 cells. 40% of the 90 sera showed ANCA-positive reactions. c-ANCA and p-ANCA types were both observed but the latter was by far more common (91%). The peculiarity of the p-ANCA pattern was a fine granular perinuclear staining. Antibodies against myeloperoxidase (MPO) were negative in all RA sera tested. So far we found a significant relationship between positive ANCA staining, functional Steinbrocker grades, and rheumatoid factor. No significant correlation was observed with extraarticular manifestation, CRP, therapeutic modalities (gold) or MHC antigens. Currently the nature of the neutrophil antigen involved is under investigation.
In a 49-year-old patient with acute thrombangitis obliterans, several vascular risk factors and associated features of collagen vascular disease, we observed anti-centriole autoantibodies and a strongly elevated neuron-specific enolase (NSE). The latter could not be attributed to an underlying malignant or neuroendocrine disease. The recent identification of NSE as a centrosomal protein suggests a causal relationship between anti-centriole autoantibodies and elevated serum NSE levels.
Oxidative burst was defective in 50% of peripheral blood neutrophils in a case of Sweet syndrome with leukemoid granulocytosis. Phagocytosis was normal. We suggest that the decreased ability to produce oxygen radicals observed in this patient might lead to a compensatory recruitment of hematopoietic growth factors. Consecutive activation, increased chemotaxis and adhesion of polymorphonuclear granulocytes might be the cause of the neutrophilic dermal infiltrate of Sweet syndrome.
Ten CVID patients with an in vitro defect for IL-2-synthesis were treated for 12 months in a placebo-controlled double-blind crossover therapy study with human natural IL-2 s.c. There were no severe side effects of n-IL-2 recorded. Serum levels of soluble IL-2 receptors were unaffected by the therapy. Serum IL-2 levels were only measurable in single patients during the therapy phase. Since verum and placebo groups did not differ with respect to requirement for intravenous gammaglobulin substitutions, n-IL-2 therapy was uneffective in switching on IgG synthesis in vivo. Nevertheless, there was an elevation in vitro of IgM synthesis in 5 patients and of IgG synthesis in 4 patients during n-IL-2 therapy after stimulation of patients' lymphocytes with staphylococcus aureus Cowan I (SAC) plus n-IL-2 or with Pokeweed Mitogen (PWM) without n-IL-2. Additionally, an elevated IL-2-synthesis in vitro was recorded after OKT3 stimulation for 3 CVID patients. There was a significant reduction of severe infections from 25 during the first 6 months of the study to 7 infections during the following 6 months, in the group of patients which received n-IL-2 first. In the second group, which received placebo first, there were no significant differences between placebo and n-IL-2 therapy phase detectable (25 infections during the first 6 months of the study and 24 severe infections in the second phase).(ABSTRACT TRUNCATED AT 250 WORDS)
Raynaud's phenomenon (RP) is an episodic digital ischemia provoked by internal and/or external stressors. While the primary RP occurs independently of other diseases and appears to be mediated by a vegetative imbalance of the peripheral vasomotor tone, the secondary RP is often part of an underlying disorder, especially of collagen-vascular diseases such as SLE or scleroderma. Vascular involvement in the pathogenesis of connective tissue diseases is well known but poorly understood. Endothelium injury by autoantibodies and circulating immune complexes may play a central but not sufficient role in the pathogenesis of secondary RP. In this review, epidemiology and diagnosis of RP secondary to connective tissues diseases are described and new pathogenic concepts are discussed in view of current knowledge on endothelial function.
A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented. The studies were performed in both a non-iron-overloaded, bile duct-cannulated rat model and an iron-loaded Cebus monkey model. All three drugs performed well in the rodent, promoting the excretion of iron in both the urine and the bile, with total iron output efficiencies of 2.8%, 1.2%, and 7.1%, respectively. The efficiency of DFO increased slightly in the Cebus model, while that of the hydroxypyridones was essentially the same in the monkey, with total iron output efficiencies of 5.5%, 2.1%, and 7.4%, respectively. Iron balance studies showed that both DFO and CP94 were able to maintain the animals in a negative iron balance, while CP20 had little impact.