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W J Koopman

Publications and source records attributed to W J Koopman.

At least 19 recordsLinked to original sources
PubMed1992

A rheumatoid factor from a normal individual encoded by VH2 and V kappa II gene segments.

OBJECTIVE: To gain insight into the immunoglobulin variable-region repertoire of anti-IgG antibodies (rheumatoid factors [RF]), we characterized the VH and V kappa gene segments utilized in an IgM-RF-secreting lymphoblastoid cell line (SSH23) isolated from a normal individual. METHODS: The cell line SSH23 was established by Epstein-Barr virus transformation of peripheral blood non-T mononuclear cells. First-strand complementary DNA (cDNA) was generated and used for polymerase chain reaction amplification of the heavy and light chain variable domains. The amplified variable domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be identical to a previously described fetal VH2 incomplete cDNA and to differ by only 3 nucleotides from a JH proximal germline VH2 gene segment. To our knowledge, this is the first example of a VH2 rheumatoid factor. The V kappa 2-J kappa 4 light chain contains an uncommon 10-amino acid third complementarity-determining region (CDR 3). CONCLUSION: Utilization of preimmune fetal VH gene segments and unusual light chain junctional diversity appear to be features shared by many physiologic and pathologic rheumatoid factors.

Amino Acid Sequence↗
PubMed1992

The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis.

OBJECTIVE: To analyze the nature of the B cell response in the synovial tissue of a patient with rheumatoid arthritis (RA). Specifically, we sought to determine if the pattern of immunoglobulin expression was consistent with polyclonal stimulation of B cells or an antigen-driven response. METHODS: We generated an unrestricted complementary DNA (cDNA) library from the diseased synovium of a rheumatoid factor (RF)-positive patient with an 18-year history of RA. A random sample of kappa light chain recombinants was identified, and sequence analysis was performed. The variable domains were compared with an extensive database of germline and cDNA kappa sequences. RESULTS: We found a light chain repertoire enriched for kappa transcripts containing 2 V kappa gene segments (Humkv325 and Humkv328) that are frequently associated with paraproteins expressing RF activity. Kappa variable domains from synovium contained numerous somatic mutations which resulted in frequent replacement of amino acids that encode the classic antigen-binding site. Unexpectedly, many of these kappa transcripts contained non-germline-encoded nucleotides (N regions) at the site of V kappa-J kappa joining. The combination of N-region addition and variation in the sites of V kappa-J kappa splicing generated unusually long complementarity-determining region 3 regions and charged amino acids near the V kappa-J kappa splice site. CONCLUSION: The pattern of somatic mutations found in this patient sample supports the hypothesis that these synovium-derived plasma cells are the product of immunoglobulin receptor-dependent (i.e., antigen-driven) selection. The extent of N-region addition raised the additional possibility that these antibodies derive from an unusual set of B lymphocytes that have escaped normal regulation.

Amino Acid Sequence↗
PubMed1992

Efficacy and safety of 10-deazaaminopterin in the treatment of rheumatoid arthritis. A one-year continuation, double-blind study.

OBJECTIVE: To determine the long-term safety and efficacy of 10-deazaaminopterin (10-DAM) in the treatment of rheumatoid arthritis (RA). METHODS: A 1-year continuation of an initial 15-week randomized, double-blind clinical trial of 10-DAM and methotrexate (MTX). RESULTS: 10-DAM (n = 10) and MTX (n = 8) had comparable safety and efficacy profiles. One 10-DAM-treated and 2 MTX-treated patients experienced transient side effects; 1 MTX-treated patient experienced recurrent nausea and discontinued MTX. CONCLUSION: 10-DAM appears to be as beneficial and as safe as MTX for the treatment of RA.

Adult↗
PubMed1992

Scanning electron microscopic evaluation of the arthritis in MRL/lpr mice.

The articular surfaces of disarticulated knee joints from MRL/lpr and MRL/n mice, aged 4-33 weeks were examined by light microscopy (LM) and scanning electron microscopy (SEM). Light microscopy did not reliably predict SEM findings. Most of the abnormalities detected by SEM were related to surface disruption of articular cartilage. However, areas of articular cartilage covered by tightly adherent non-confluent monolayers of stellate-shaped cells with intertwining cytoplasmic processes were observed. In these areas the integrity of the underlying cartilage matrix was disrupted, with exposure of collagen fibers. These findings suggested that outgrowth of proliferating synovial cells in the joints of arthritic MRL/lpr mice may lead to cartilage destruction.

Animals↗
PubMed1992

Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune diseases.

Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean +/- SD, 3.18 +/- 0.66 vs 3.82 +/- 0.41 galactose residues/mole of IgG, P < 0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detectable not only in some members with clinical and serological abnormalities (P < or = 0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P < or = 0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases.

Adult↗
PubMed1992

Long-term treatment of the MRL/lpr mouse with methotrexate and 10-deazaaminopterin.

Female MRL/lpr mice were treated with I.P. doses of methotrexate (MTX) and 10-deazaaminopterin (DAAM) in the range of 1 to 100 mg/kg body weight/week, in two equally divided doses. Treatment began at 7 weeks of age and continued to 30 weeks of age. Joint histopathology scores were tightly correlated with skin lesion-proteinuria scores at 30 weeks of age. MTX at levels of 5, 25, and 100 mg/kg body weight/week and DAAM at a level of 25 mg/kg body weight/week significantly reduced skin lesion-proteinuria scores below controls in a dose dependent manner. Animals receiving MTX at 25 mg/kg body weight/week had a significantly longer median life span and animals receiving MTX at 100 mg/kg body weight/week had a greater than 15% suppression of growth when compared with controls. Longevity and skin lesion-proteinuria scores appeared to be good indicators of drug efficacy while growth suppression appeared to be a good indicator of drug toxicity.

Aminopterin↗
PubMed1992

Recurrent Guillain-Barré syndrome. Clinical and laboratory features.

The clinical and laboratory features of recurrent Guillain-Barré syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barré syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant. Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy. Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.

Adolescent↗
PubMed1992

Controlled trial of methotrexate versus 10-deazaaminopterin in the treatment of rheumatoid arthritis.

A 15 week double blind controlled trial of methotrexate and 10-deazaaminopterin for the treatment of rheumatoid arthritis (RA) was performed in 26 patients. Significant improvement in all measured clinical parameters was observed in the two patient groups. The drugs were well tolerated; only one patient (10-deazaaminopterin) withdrew from the study because of side effects. It is concluded that, in the context of this relatively short clinical trial, 10-deazaaminopterin is at least as beneficial as methotrexate in the treatment of RA.

Aminopterin↗
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↗