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Biomedical subjects

W J Koopman

Publications and source records attributed to W J Koopman.

At least 91 records · Page 5Linked to original sources
PubMed1992

Detection of hereditary motor sensory neuropathy type I in childhood.

Clinical signs and slowed motor nerve conduction velocities were found in 17 of 36 children under 10 years of age who had one parent with hereditary motor sensory neuropathy type I (HMSN I). Four children had slowed conduction velocities at one year or less. Clinical signs were subtle and included pes planus, distal foot wasting, weakness of ankle eversion and dorsiflexion and areflexia. HMSN I can be detected reliably in children, even before one year of age.

Child↗
PubMed1992

Digital subtraction radiography for the assessment of bone changes in rheumatoid arthritis.

A digital subtraction radiography (DSR) method was developed to assess changes of bony erosions in the hands of patients with rheumatoid arthritis (RA). The method initially was validated in vitro using simulated lesions in cadaver hands. The sensitivity, specificity and accuracy in detecting simulated lesions were 84.6, 100, and 92.3%, respectively. This technique was then pilot tested clinically using 17 patients with RA and 5 controls with no arthritis. All subjects received the nonsteroidal antiinflammatory drug, flurbiprofen, during the 6-month study period. No progressive changes in bone were observed in the control group; however, 18% of the target joints studied in the group with RA showed significant erosive changes (positive or negative) which correlated with the clinical assessment. The results indicate that DSR may be useful in detecting small changes in erosions on hand/wrist radiographs of patients with RA.

Adult↗
PubMed1992

Infection as a cause of reactive arthritis, ankylosing spondylitis, and rheumatic fever.

Recent advances in understanding the role of infectious agents in the etiology of reactive arthritis (Reiter's syndrome), ankylosing spondylitis, and rheumatic fever are reviewed. The reader is referred to other reviews in this section for discussions of septic, spirochetal, mycobacterial, and fungal arthritis, and human immunodeficiency virus-related connective tissue diseases.

Animals↗
PubMed1992

Expressing our inner thoughts: how to organize and write a clinical research project grant application.

Securing funding for clinical research projects is becoming increasingly difficult. At present, scientific merit is an essential but not necessarily sufficient attribute of a successful research proposal. It is the premise of this article that each section of the application contributes important information to the reviewer and that carelessness or inattention to detail in any section may be a critical factor in the lack of success of an application. Each section of the standard NIH application is analyzed and suggestions are provided with regard to their organization and execution.

Peer Review↗
PubMed1992

Forearm P-31 nuclear magnetic resonance spectroscopy studies in oculopharyngeal muscular dystrophy.

Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr+Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/PCr+Pi) fell quickly to values less than controls (p less than 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr+Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy.

Acidosis, Lactic↗
PubMed1991

Rheumatology.

Explore the source record for details and available documents.

DNA↗
PubMed1991

Genetic studies of four highly homologous rheumatoid factor-associated Vk genes in rheumatoid arthritis patients and normal individuals.

Rheumatoid factors (RFs) are autoantibodies directed against IgG molecules. They are present in increased quantity in most patients with rheumatoid arthritis (RA), and are implicated in tissue damage in this disease. Paradoxically, recent studies of RFs have revealed that these autoantibodies are likely a physiological component of the immune system, and may play a role in the development and function of the B cell repertoire. Previously, we found that a significant fraction of RA patients express RF bearing the 6B6.6 cross-reactive idiotype, which is a phenotypic marker of the Humkv328-like genes. In order to elucidate the possible genetic factors that may contribute to the abnormal production of RFs in RA patients, we studied restriction fragment length polymorphisms (RFLP) of four highly homologous RF-related kappa light chain variable region (Vk) genes (i.e. Humkv328, Humkv328h2, Humkv328h5 and Humkv329) in RA patients and normal controls. The results show that kv328, kv328h2 and kv329 are likely to be alleles of the kv328 locus, while kv328h5 is a highly homologous Vk gene residing in a separate locus; and that deletion in one copy of either the kv328 or the kv328h5 loci, but not both loci, occurs in several individuals. However, the frequencies of various RFLP patterns of these two Vk gene loci are similar in patients and normals.

Arthritis, Rheumatoid↗
PubMed1991

Infection as a cause of arthritis.

The etiology of most rheumatic tissues is unknown; however, recent investigation into this area is rapidly providing new clues to the pathogenesis of many of these diseases. This article reviews several infectious agents (Epstein-Barr virus, parvoviruses, and mycobacteria) and the data supporting their roles in the etiology of rheumatoid arthritis. In addition, current data on the potential roles of Epstein-Barr virus and retroviruses in the etiologies of Sjögren's syndrome and Kawasaki disease are also reviewed. Finally, the reactive arthritides, for which there is stronger evidence of an infectious etiology, are reviewed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cellular origins of human polymeric and monomeric IgA: enumeration of single cells secreting polymeric IgA1 and IgA2 in peripheral blood, bone marrow, spleen, gingiva and synovial tissue.

Using modified ELISA and spot-ELISA, which permit the parallel determination of heavy chain subclass and the presence of covalently linked J chain, we analysed IgA found in cell culture supernatants or secreted by individual cells from peripheral blood, spleen, bone marrow, gingiva and synovial tissue, with respect to its polymeric or monomeric IgA form (pIgA, mIgA) and IgA1 or IgA2 subclass. The ELISA for determination of J chain in tissue culture supernatants was specific and highly sensitive (detection limit in pg). The results demonstrated that IgA1-producing cells predominated in the tissues examined, and that J chain could be detected in association with the majority of IgA1 and IgA2 secreted by individual cells. With respect to the frequency of cells secreting polymeric, J chain-containing IgA, only 20-30% of cells from the bone marrow were engaged in the synthesis of PIgA. In other tissues the frequency of cells secreting pIgA1 and pIgA2 was considerably higher. Peripheral blood mononuclear cells secreting pIgA2 were easily inducible during stimulation with T cell-dependent pokeweed mitogen, whereas Epstein-Barr virus-transformed cells secreted preferentially mIgA1. When the frequencies of pIgA-, pIgA1- or pIgA2-secreting cells (determined by spot-ELISA technique) from different tissues were correlated with the proportion of pIgA to mIgA (and IgA subclasses) secreted in tissue culture supernatants, data obtained suggest that many individual IgA-producing cells could be engaged in simultaneous secretion of mIgA and pIgA.

Adult↗
PubMed1991

Apolipoprotein A-I decreases neutrophil degranulation and superoxide production.

Neutrophils participate in the acute phase response and are often associated with tissue injury in a number of inflammatory disorders. The acute phase response is accompanied by alterations in the metabolism of apolipoprotein A-I and high density lipoprotein (HDL). Structural considerations led to studies investigating the effect of purified HDL and apolipoprotein A-I on neutrophil degranulation and superoxide production. Apolipoprotein A-I but not HDL inhibited IgG-induced neutrophil activation by about 60% as measured by degranulation and superoxide production. This suggests that the lipid-associating amphipathic helical domains of apolipoprotein A-I mediate this effect. In support of this was finding inhibitory effects with two synthetic model lipid-associating amphipathic helix peptide analogs. Apolipoprotein A-I, containing tandem repeating amphipathic helical domains, was approximately ten times more effective than the two peptide analogs and inhibited neutrophil activation at well below physiologic concentrations. Competitive binding studies indicate that resting neutrophils have approximately 190,000 (Kd = 1.7 x 10(-7)) binding sites per cell for apolipoprotein A-I, consistent with a ligand-receptor interaction. These observations suggest that apolipoprotein A-I may play an important role in regulating neutrophil function during the inflammatory response.

Acute-Phase Reaction↗
PubMed1990

Dissociation of expression of two rheumatoid factor cross-reactive kappa L chain idiotopes in rheumatoid arthritis.

mAb 6B6.6 and 17.109 recognize two distinct kappa III L chain cross-reactive idiotopes (CRI) present on approximately 2/3 of IgM kappa rheumatoid factor (RF) paraproteins. To determine the distribution of these two CRI and their relationship to each other among polyclonal RF, sera from 86 RA patients and 49 controls were analyzed for the presence of 6B6.6- and 17.019-bearing RF by using sensitive solid phase ELISA. Levels of CRI(+) RF were estimated by using 6B6.6(+) and 17.019(+) RF standards. Detectable levels (greater than or equal to 195 ng/ml) of CRI(+) RF were rarely present in the control sera (8% for 6B6.6; 0% for 17.109), whereas 59% of RA sera contained measurable CRI(+) RF (48% for 6B6.6; 35% for 17.109; 21% for both). Where detected, CRI(+) RF were present in low concentrations (6B6.6: 1.21 +/- 1.56 micrograms/ml; 17.109: 1.20 +/- 1.15 micrograms/ml) and constituted a small fraction of the total IgM RF in these sera (6B6.6: 0.9 +/- 2.2%; 17.109: 0.8 +/- 0.9%). There was no correlation between either RF CRI and levels of IgM RF (r less than 0.1, p greater than 0.5). Levels of 6B6.6(+) RF did not correlate with 17.109(+) RF (r = -0.11, p = 0.47). In selected sera that contained both RF CRI, it was possible to selectively absorb 6B6.6(+) RF. Taken together, these data indicate the mutual independence of these two RF CRI among polyclonal RF and suggest the presence of distinct regulatory mechanisms governing their expression. Moreover, that these two CRI constitute a small proportion of polyclonal RF, in contrast to their striking predominance among monoclonal RF paraproteins, argues for the importance of other germline VL genes contributing to polyclonal RF production or the presence of extensive somatic mutation among polyclonal RF in RA.

Antibodies, Monoclonal↗
PubMed1990

Correlation of serologic indicators of inflammation with effectiveness of nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis.

Forty-seven patients with rheumatoid arthritis (mean duration 5.7 years) who were receiving neither disease-modifying drugs nor corticosteroids were enrolled in a 12-week, multicenter study of the relationship between clinical and serologic measures of disease activity in patients taking nonsteroidal antiinflammatory drugs. After a 2-week drug washout period, patients received flurbiprofen (200 mg/day) or sustained-release ibuprofen (2,400 mg/day) for a 10-week trial. Clinical response was assessed biweekly using standard clinical parameters, including 50-foot walk time, tender joint score, duration of morning stiffness, and global assessment of disease activity and pain (by both the patient and the physician). Patients were classified as responders if there was greater than or equal to 30% improvement in at least 3 of the 4 clinical measures of disease activity. Thirty patients completed at least 8 weeks of therapy; there were 12 responders and 18 nonresponders. Of the laboratory parameters examined, the responders, but not the nonresponders, demonstrated significant reductions (from postwashout values) in levels of IgM rheumatoid factor and C-reactive protein (CRP), along with significant increases in the number of circulating lymphocytes and decreases in the number of circulating granulocytes (P less than or equal to 0.05). In contrast, the nonresponders demonstrated either no change or worsening of the laboratory correlates of disease activity. The responders also appeared to have more aggressive disease at baseline, with significantly more painful joints, greater 50-foot walk times, elevated CRP values, and elevated erythrocyte sedimentation rates (P less than or equal to 0.05). These data suggest that there is a subset of rheumatoid arthritis patients in whom clinical improvement with nonsteroidal antiinflammatory drug therapy is associated with significant reductions in IgM rheumatoid factor and CRP levels.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Monoclonal antibody 6B6.6 defines a cross-reactive kappa light chain idiotope on human monoclonal and polyclonal rheumatoid factors.

Mouse monoclonal antibody (MAb) 6B6.6 was raised against a cross-reactive idiotope (CRI) present on the light chains of 2 human IgM paraproteins with rheumatoid factor (RF) activity. The MAb inhibited the IgG-binding activity of these proteins, and thus appears to react with an epitope located at or near the RF-binding site. Enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting studies indicate that the 6B6.6 CRI is associated with kappa IIIa sub-subgroup light chains, is not related to the Wa, Po, and Bla RF cross-idiotypic specificities, and is clearly distinct from the kappa IIIb-associated CRI detected by MAb 17.109. Using an ELISA, we detected 6B6.6 CRI in 59% of 107 sera and 48% of 50 synovial fluids from patients with seropositive rheumatoid arthritis (RA). However, the quantities of CRI-positive RF were small, and the amount of CRI-positive RF did not correlate with the amount of IgM-RF. The 6B6.6 CRI was shown to occur primarily in the IgM fraction of RA sera by both chromatographic studies and isotype-specific ELISA, although small quantities appeared to be associated with IgA and IgG in some sera. The presence of 6B6.6 CRI on both monoclonal and polyclonal RF is consistent with the view that both are derived, at least in part, from a common gene pool. However, its occurrence in relatively low levels suggests that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression in RA.

Antibodies, Monoclonal↗
PubMed1990

Lupus-inducing drugs alter the structure of supercoiled circular DNA domains.

We analyzed the effects of procainamide (PROC), hydralazine (HYD), N-acetylprocainamide (NAPA), and L-canavanine (CAN) on circular supercoiled plasmids as models for chromosomal loop domains. The supercoil-dependent B-Z equilibrium in recombinant plasmids was used as an indicator of structural changes induced in circular DNA. Two-dimensional gel electrophoresis showed that PROC and HYD strongly inhibited supercoil-induced Z-DNA formation, whereas NAPA caused less pronounced changes in the B-Z equilibrium, and CAN had no effect. Gel retardation assays showed that the binding of a Z-DNA-specific autoimmune antibody to a Z-DNA-containing plasmid was strongly perturbed by HYD, but not influenced by CAN. Both PROC and NAPA showed moderate inhibition of antibody binding. Our results demonstrate the different potentials of these 4 drugs to interact with DNA and to alter the tertiary topology of DNA domains. It is conceivable that the in vivo capacity of PROC and HYD to induce antinuclear antibodies may be related to their ability to influence structural features in chromosomal DNA domains or nucleosomes, thus liberating antigenic structural epitopes in DNA and/or DNA-associated proteins.

Acecainide↗
PubMed1990

Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression.

Suppression of rheumatoid factor (RF) production in rheumatoid arthritis (RA) has been variably attributed to the use of remittive agents per se or to clinical improvement associated with their use. There have been conflicting reports with regard to the influence of methotrexate (MTX) on serum RF levels in RA. We determined IgM-RF and IgA-RF levels in paired serum samples (obtained at study entry and completion) from RA patients enrolled in multicenter trials with the Cooperative Systematic Studies of Rheumatic Diseases program. After exclusion of the 14 IgM-RF-negative sera, there were samples from 30 MTX-treated patients and 52 placebo-treated patients. Changes in IgM-RF and IgA-RF levels were weakly associated with each other. Significant decreases in IgM-RF levels were observed in the MTX-treated patients, but not in the placebo group. These changes were most significant in the MTX-treated patients who improved clinically. There were significant decreases in IgA-RF levels at study completion among MTX-treated patients who had improved clinically and those who had not improved clinically, but not in the placebo group. The contributions of clinical improvement and MTX treatment to changes in serum IgM-RF and IgA-RF levels were examined using a logistic regression model. Changes in IgM-RF were strongly related to MTX treatment and, to a lesser extent, to clinical improvement; changes in IgA-RF were related only to MTX treatment. These results indicate that MTX treatment per se decreases both IgM-RF and IgA-RF levels, whereas clinical improvement correlates with decreased IgM-RF levels only.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1990

Structural characterization of the second major cross-reactive idiotype group of human rheumatoid factors. Association with the VH4 gene family.

Rheumatoid factors (RF) are the most common type of functional antibodies among naturally occurring human monoclonal IgM proteins. A large subset of these autoantibodies use structurally homologous light chains of the kappa III subgroup, which bear the 6B6.6 cross-reactive idiotype (CRI). Although antibody binding activity requires both heavy and light chains, information about the heavy chains used by these autoantibodies is limited. To investigate these proteins, the murine monoclonal antibodies, 5-14 and 6-10, were generated by immunization with the heavy chains of the 6B6.6 CRI-positive RF, COR and LEW. These antiidiotypic antibodies reacted with 8 of 11 autoantibodies that coexpressed the 6B6.6 CRI. All 8 RF had heavy chains from the VH4 gene family, as assessed by reactivity with a VH4-specific primary sequence-dependent antibody. The same RF were also identified by the previously described murine monoclonal antiidiotype, LC1. Further experiments revealed that the LC1 antibody delineates a subfamily of VH4 heavy chains that is preferentially used in kappa III-6B6.6 CRI-positive IgM-RF. The cumulative data suggest that 13-22% of RF express both the kappa III-6B6.6 and VH4-LC1 CRI. These findings document that RF autoantibody activity requires specific VL-VH pairing, and that a subset of idiotypically related VH4 heavy chains is commonly expressed in disease-associated monoclonal IgM-RF.

Antibodies, Monoclonal↗
PubMed1990

Occurrence of a rheumatoid factor cross-reactive kappa light-chain idiotope in rheumatoid arthritis families.

The occurrence of IgM rheumatoid factor (RF) and RF-associated kappa-III light-chain idiotope identified by monoclonal antibody 6B6.6 in the serum from 22 patients with rheumatoid arthritis (RA) and 68 relatives without connective tissue diseases in 15 families was determined by solid-phase enzyme-linked immunosorbent assays. Serum IgM RF was present in 19 RA patients from 12 families and 12 arthritis-free relatives of 4 families. It was not found in any of 9 spouses included in the study or in 44 of 45 unrelated healthy adult controls. RF-associated 6B6.6 idiotope was detected in 42% of the IgM RF(+) RA patients and in 50% of the IgM RF(+) arthritis-free relative, but not in the adult controls, spouses, and IgM RF(-) RA patients and relatives. It was present in one RA serum from each of 8 families and 6 sera from arthritis-free relatives of 2 families (5 of whom were from one family). Where present, the idiotope-positive RF represented only a small fraction of the serum IgM RF of the RA patients (0.1-2.1%) and relatives (1.5-14%). The increased frequency of IgM RF(+) individuals, with and without RA, in family groups suggests a genetic predisposition for expression of RF. The small proportion of RF bearing the 6B6.6 idiotope in both RA patients and unaffected family members supports the view that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression, whether idiopathic or associated with RA. In addition, nonuniform expression of the idiotope in RF within family groups indicates that the various clones of RF producing cells are to a large extent independently regulated.

Arthritis, Rheumatoid↗