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Biomedical subjects

D Brackertz

Publications and source records attributed to D Brackertz.

At least 19 recordsLinked to original sources
PubMed2000

Humoral autoreactivity directed against surfactant protein-A (SP-A) in rheumatoid arthritis synovial fluids.

SP-A is found principally in the lung, and has been associated with lamellar bodies also found in the synovial joint. Both SP-A and C1q contain collagen-like regions, and SP-A and C1q have some structural similarities, both having a globular head region and a collagen-like tail. Here we are able to show that (i) autoreactivity to SP-A, as expressed by IgG and IgM autoantibodies, is present in synovial fluid (SF) isolated from patients with rheumatoid arthritis (RA); (ii) in absorption experiments only a limited degree of cross-reactivity between autoantibodies reactive with C1q and SP-A is observed; (iii) there is no cross-reactivity between autoantibodies reactive with type II collagen (CII) and those reactive with SP-A or C1q; (iv) autoantibodies react with polymeric (dimers and larger) SP-A, but not with monomeric SP-A subunits, indicating that a degree of quaternary structure is required for antibody binding. Unlike CII, which not accessible in the normal joint, both SP-A and C1q are available within the SF in patients with RA and may therefore provide antigens driving an autoimmune response directed against collagen-like structures.

Animals↗
PubMed1996

The collagen-like component of the complement system, C1q, is recognized by 7 S autoantibodies and is functionally impaired in synovial fluids of patients with rheumatoid arthritis.

Cross-reactivity between type II collagen (CII) and C1q, the collagen-like subunit of the first component of complement, has been demonstrated in synovial fluid (SF) from rheumatoid arthritis (RA) patients. Many authors have studied autoimmunity to CII in RA, but little work has been done on autoimmunity to C1q in RA. In the data presented here, we have been able to show that in addition to native C1q, an altered form of C1q is present in SF from RA patients. Furthermore, a low molecular weight form of C1q is present in RA SF, although its role, if any, in the pathogenesis of RA is unclear. The presence in these RA SF of C1q-specific antibodies (IgG and IgM) has been studied and we have partially characterized the antibody moieties involved. As well as binding to C1q and fragments representing the collagen-tails from C1q, 7 S IgG autoantibodies against C1q also bind to a C1q molecule altered in vitro by incubation with reactive oxygen species and to the non-apeptide KGEQGEPGA (representing residues 26-34 from the C1q A-chain), which has previously been shown to suppress the onset of CII-induced arthritis in an animal model.

Amino Acid Sequence↗
PubMed1991

C1q-bearing immune complexes detected by a monoclonal antibody to human C1q in rheumatoid arthritis sera and synovial fluids.

Using a monoclonal antibody directed against the C-chain of human C1q, we detected C1q-bearing immune complexes (IC) in sera and synovial fluids of rheumatoid arthritis (RA) patients. In a sandwich-ELISA, C1q-bearing IC were captured by the solid-phase monoclonal antibody and then detected with peroxidase-labeled F(ab')2-antibodies to either human IgG or IgM. The results of this assay were compared to an ELISA-modification of the C1q-solid-phase binding assay (C1q-SPBA). C1q-bearing IC were detected in 81.1% of RA-sera and the 65.2% of RA-synovial fluids. IgG as well as IgM was present in 72.6% of the sera and 70% of the synovial fluids which were positive in both assays. Most RA sera that were only positive for C1q-bearing IC, contained IgG alone (81.5%). The corresponding synovial fluids showed IgG alone (53%) or both IgG and IgM (41.1%). IgM alone (25%) could be detected in sera, e.g. in juvenile forms of RA. The levels of IC were higher in synovial fluid than in paired serum. In comparison to normal human serum (NHS) and patients with osteoarthritis, complement activity (CH50 titers) and C1q-values in patients with RA were frequently elevated. Since the formation of C1q-bearing IC is an indicator for the classical complement pathway activation, an assay with monoclonal anti-C1q antibody may be a useful tool in the diagnosis of rheumatoid diseases.

Antibodies, Monoclonal↗
PubMed1991

[Real time collection of pain profile in treatment with ibuprofen].

In an open three-center pilot study, 17 patients suffering from chronic persistent pain syndrome, due to osteoarthritis of the hip and knee or spondylarthrosis, were treated orally with 1800-2400 mg Ibuprofen per day for 3 weeks. The chronic pain syndrome and joint status were assessed by the physician at the beginning, and after 7, 14 and 21 days. Self-assessments were made by the patients six times daily during the full study period by means of battery-driven electronic diaries (E.D.). The data entered by the patients were stored in the E.D. and after online transfer, processed and evaluated in a PC using appropriate software programs. E.D. were returned by 16 of 17 patients for evaluation. The technical functioning of the instrument was perfect; its use was accepted by patients and physicians. The closely-meshed real-time recording of pain course and other subjective data, such as adverse events or medication, etc., enables the physician to calculate more exactly and reliably improvement rates, as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates. By comparing different kinds of data, each entered at the same time, plausibility checks are possible. The procedure presented here is considered to be a new valuable tool for reviewing subjective data from clinical drug trials.

Adult↗
PubMed1989

[Osteoporosis: a case report].

A 56-year-old female patient was admitted to our hospital because she was suffering from severe osteoporosis. The patient had experienced repeated spontaneous fractures for 1.5 years such as serial rib fractures, fractures of the sternum and most recently fracture of the neck of the femur after a minimal trauma. Histology revealed a low-turnover-osteoporosis. Subsequent radiologic examination showed extreme osteoporosis of the skeleton with numerous compression fractures of the vertebral bodies as the most outstanding finding. The bone histology and the relatively short history of spontaneous fractures led us to investigate endogenous hypercortisolism as a possible cause although clinical signs were absent. An attenuated diurnal variation of cortisol levels and lack of suppressibility of cortisol was found. Furthermore, magnetic resonance tomography showed a microadenoma of the pituitary gland. Computerized tomography of the adrenals was normal. Transsphenoidal surgery confirmed the tentative diagnosis and histological examination revealed a bilateral adenoma of the pituitary gland.

Adenoma↗
PubMed1989

OM-8980 in rheumatoid arthritis: a 6-month double blind placebo controlled multicenter study.

A new immunomodulating drug, OM-8980, was compared to placebo in a 6-month double blind multicenter trial including 107 patients with active rheumatoid arthritis. Ritchie index, number of swollen joints and the pain scale improved significantly more with OM-8980 than with placebo. Grip strength, duration of morning stiffness and erythrocyte sedimentation rate improved more markedly with OM-8980 than with placebo, but the difference did not reach statistical significance. The use of analgesic and antiinflammatory drugs diminished significantly more with OM-8980 than with placebo. Clinical tolerance was good with 7 side effects reported in 3 of the 52 patients included in the OM-8980 group and 11 in 8 patients of the 55 in the placebo group (mostly gastrointestinal troubles and skin reactions). In the overall evaluation by both patients and physicians OM-8980 was significantly superior to placebo.

Arthritis, Rheumatoid↗
PubMed1988

Enzymatic alteration of C1q, the collagen-like subcomponent of the first component of complement, leads to cross-reactivity with type II collagen.

Native serum C1q, the collagenous-like subcomponent of the first component of complement, is not recognized by polyclonal anti-collagen type II antibodies. However, when purified C1q was subjected to limited proteolysis by collagenase it showed antigenic cross-reactivity with collagen type II. The same cross-reactivity was observed with hemolytically active C1q in synovial fluids of patients with rheumatoid arthritis (RA), whereas C1q from synovial fluids of patients with osteoarthritis (OA), villo-nodular synovitis and ankylosing spondylitis was not recognized by this antibody. However, incubation of synovial fluid C1q of OA patients with synovial fluid leucocytes from RA patients led to an alteration of OA-C1q which was now recognized by the anti-collagen type II antibody.

Animals↗
PubMed1988

[Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo-controlled study of 119 patients].

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

Adjuvants, Immunologic↗
PubMed1988

Results of a multicenter placebo-controlled double-blind randomized phase III clinical study of treatment of rheumatoid arthritis with recombinant interferon-gamma.

In a multicenter placebo-controlled double-blind randomized clinical study, 91 patients with rheumatoid arthritis were given 28 days' treatment with recombinant interferon-gamma (50 micrograms daily for 20 days, then 50 micrograms each second day up to day 28, given by subcutaneous injection). The aim of the study was to provide a methodologically clear demonstration of the efficacy of treatment with interferon-gamma, using criteria that could be handled by statistical tests. Evaluatable documentation was available for 79 patients, of whom 40 were treated with the active compound. The principal criterion for the statistical evaluation of the therapeutic success was improvement of the Ritchie "joint pain index" or Lansbury "joint pain index" by at least 30% within 28 days. The chi-square test showed superiority of the interferon arm over the placebo arm with an error probability of alpha less than 1%. In addition, efficacy of interferon-gamma was demonstrated in respect of practically all parameters investigated. The frequency of side-effects, including febrile reactions, was the same for the active compound and the placebo. During interferon treatment the daily maximum body temperature was raised by 0.3 degrees C on average, but was below 37.2 degrees C at all times.

Adolescent↗
PubMed1988

HLA-DP in rheumatoid arthritis.

Frequencies of HLA-DR, Dw and DPw specificities were compared between rheumatoid arthritis (RA) patients, Felty's syndrome (FS) patients and normal controls. It was confirmed that the frequency of DR4 was increased in RA patients (54% (n = 111) vs 23% (n = 272), relative risk (RR) = 3.98, P less than 0.001). Cellular typing showed a highly significant increase in HLA-Dw14 in the entire RA population (17% (n = 32) vs 2% (n = 242), RR = 11.90, P less than 0.001), and a tendency towards an increase of HLA-Dw14 in DR4+ RA patients compared to DR4+ controls (28% (n = 32) vs 11% (n = 47), RR = 3.29, P less than 0.05). Regarding DPw specificities, the only significance was for a negative association with DPw3 (13% vs 22% (n = 254), RR = 0.51, P less than 0.05), with an additional tendential decrease of DPw1 (11% vs 19%, RR = 0.53, not significant (NS]. The decrease of DPw3 was more marked in DR4- RA patients (RR = 0.33, P less than 0.05) than in DR4+ RA patients (RR = 0.69, NS). In FS patients, 96% of whom were DR4+, decreased DPw1 was very marked, whereas the frequency of DPw3 was unaltered compared to DR4+ normals. These alterations in frequencies were not caused by linkage disequilibria between HLA-DR and -DP alleles. Thus, taken together, these data suggest that, in the presence of the major DR4-associated "susceptibility" gene(s) for RA, DPw1 may have "protective" effects, whereas in the absence of DR4, the presence of DPw3 has significant "protective" activity.

Arthritis, Rheumatoid↗
PubMed1986

Granulocyte elastase as a new biochemical marker in the diagnosis of chronic joint diseases.

Human granulocyte elastase (EC 3.4.21.37) is released from granulocytes in large amounts in chronic inflammatory joint diseases and is therefore of special pathogenic and diagnostic importance. In order to examine the diagnostic significance of this enzyme as a clinico-chemical parameter, we determined the concentration of granulocyte elastase in complex with alpha 1-proteinase inhibitor by an enzyme immunoassay in synovial fluids and plasma of patients with chronic joint diseases. In inflammatory synovial fluids the concentration of complexed elastase correlates well with the granulocyte number and may increase to an extremely high level. In 90% of patients with manifest rheumatoid arthritis increased elastase levels are also observed in the plasma, probably due to the large gradient between the synovial fluid and plasma concentration, whereas in osteoarthrosis normal plasma concentrations were observed. Thus, these results indicate that normal plasma concentrations in patients with chronic joint diseases exclude the diagnosis of rheumatoid arthritis with high probability. The simultaneous determination of complexed elastase in plasma and synovial fluid improves the nosological differentiation of chronic joint diseases. Elastase activity on a specific chromogenic substrate, which was found in many inflammatory synovial fluids, is mainly attributed to elastase alpha 2-macroglobulin complexes. In some purulent synovial fluids, however, we were able to detect free elastase, which has been shown to play an important role in the destruction of articular cartilage.

Adolescent↗
PubMed1982

Population studies of HLA-linked SB antigens and their relative importance in primary MLC typing. Analysis of HLA-D homozygous typing cells and normal heterozygous populations.

SB phenotyping was undertaken on 96 HLA-D homozygous typing cells (HTCs) and 129 normal unselected heterozygous donors in the German population, using Interleukin-2-propagated primed lymphocyte typing (PLT) reagents. The results showed that the SB antigens in the normal population behave as a system of alleles at a single locus in Hardy-Weinberg equilibrium (p approximately equal to 0.20). Estimated gene frequencies in the German population appeared to be significantly different (p less than 0.002) from the North American Caucasian population: the principal differences were increased frequencies of the specificities SB1 and SB4, and decreased frequencies of blanks. Of HLA heterozygous donors 41% typed for two distinct SB specificities; 57% typed for one; and 2% were blank. In the HTC group, 20% typed for two specificities; 68% typed for one; and 12% were blank. Thus, a significant proportion of HLA-D homozygous test cells were, nonetheless, heterozygous for HLA-linked SB antigens. Performance of checkerboard mixed leukocyte cultures (MLCs) between 16 SB typed HLA-Dw3 HTCs, however, did not indicate that the observed mutual or one-way responses were influenced in any simple way by SB antigens; neither heterozygosity nor assumed homozygosity for SB antigens appeared to influence the frequency of MLC typing responses of HLA-Dw3-positive donors on these HTCs. These results add further confirmation of the genetic and functional independence of the SB gene product(s) and the HLA-D/DR gene product(s).

Genes, MHC Class II↗