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Biomedical subjects

D O Clegg

Publications and source records attributed to D O Clegg.

At least 91 records · Page 5Linked to original sources
PubMed1987

Diagnostic criteria in rheumatoid arthritis.

For rheumatoid arthritis (RA), criteria have been developed for classification of groups of patients in population surveys, selection for therapeutic trials, inter-institutional comparison of patients, evaluation of diagnostic trials, diagnosis of RA in individual patients, estimation of disease frequency, and assistance in determining prognosis. The American Rheumatism Association (ARA) "Criteria for the Classification of Rheumatoid Arthritis-Diagnostic Criteria for Rheumatoid Arthritis" were published in 1958 and have become a standard. These criteria are empiric and attempt to incorporate reasonable combinations of sensitivity and specificity. Despite the recognition that these criteria should be expected to change with improved knowledge, no further modification has been published. Other criteria such as the ARA "Proposed Criteria for Rheumatoid Arthritis" represent an important effort to encourage uniformity in definitions and use of the term remission. Yet it is well to remember that they have never been tested in prospective studies and are considered preliminary. The Co-operative Systematic Studies in Rheumatic Diseases, when studying slow-acting anti-rheumatic drugs, have chosen to use clinical endpoints such as 50% improvement in joint tenderness and swelling counts (or scores) rather than combined variables which include morning stiffness and changes in laboratory variables. This approach permits the true assessment of drug effects. In summary, current criteria have served us well. Nonetheless, we should not become complacent and should always question their sensitivity, specificity and application.

Arthritis, Rheumatoid↗
PubMed1987

Slow-acting anti-rheumatic drug therapy for rheumatoid arthritis.

Rheumatoid arthritis is a disorder that frequently can be controlled with a program of physical therapy, rest and therapeutic doses of aspirin or another nonsteroidal anti-inflammatory medication. However, some patients' diseases are not controlled on this regimen. These patients are candidates for therapy with slow-acting anti-rheumatic drugs. This article discusses the indications for use of these medications as well as the potential benefits and adverse drug reactions commonly associated with their use.

Arthritis, Rheumatoid↗
PubMed1987

Hematuria in patients with rheumatoid arthritis receiving gold and D-penicillamine.

We reviewed the urinalyses from 2 multicenter controlled randomized trials, one comparing moderate and low dose D-penicillamine to placebo and another comparing gold sodium thiomalate (GSTM), auranofin (AF) and placebo. In the D-penicillamine trial 30% of the 40 patients taking placebo, 34% of the 70 patients receiving 125 mg/day of D-penicillamine and 31% of the 61 patients receiving 500 mg of D-penicillamine had recurrent hematuria. In the GSTM/AF trial, 35% of the 43 placebo treated patients, 35% of the 54 GSTM treated patients and 30% of the 64 AF treated patients had hematuria. No significant difference in the frequency of hematuria between the groups in either trial was apparent. These findings suggest that the traditionally held belief that gold and D-penicillamine cause hematuria should be reconsidered.

Adult↗
PubMed1986

Nerve growth factor gene expression in the developing rat brain.

The regulation of nerve growth factor (NGF) protein and NGF messenger RNA (mRNA) in the developing rat brain has been studied to assess the hypothesis that NGF supports the differentiation of cholinergic neurons in the basal forebrain. In the adult, the major targets of these neurons, the hippocampus and neocortex, contain the highest concentrations of NGF mRNA, but comparatively low ratios of NGF protein to its mRNA. In contrast, a high concentration of NGF protein and a low concentration of NGF mRNA were seen in the basal forebrain, consistent with retrograde transport of NGF protein into this region from the neocortex and hippocampus. In these two target regions NGF and NGF mRNA were barely detectable at birth, their concentrations increased to a peak at day 21, and then NGF mRNA, but not NGF protein, declined threefold by day 35. NGF accumulation in the basal forebrain paralleled that in the target regions and preceded an increase in choline acetyltransferase, suggesting that the differentiation of cholinergic projection neurons is indeed regulated by retrogradely transported NGF. In addition, high ratios of NGF protein to NGF mRNA, comparable to that in the basal forebrain, were seen in the olfactory bulb and cerebellum, suggesting that NGF may be transported into these regions by unidentified neurons.

Animals↗
PubMed1986

Circulating HLA-DR bearing T cells: correlation with genetic rather than clinical variables.

Elevated levels of circulating HLA-DR bearing (activated) T cells have been reported in a variety of conditions. The role played by these cells in the pathogenesis of disease is not established. We found elevated levels of activated T lymphocytes in patients with rheumatoid arthritis (RA), dermatitis herpetiformis, gluten sensitive enteropathy, as well as presumed healthy persons with HLA-B8 antigen. We could not show any change in the concentration of these cells with disease activity, therapy, or in a case of dermatitis herpetiformis, challenge with the presumed antigen, gluten. Our studies do not suggest an apparent causal relationship between activated T lymphocytes and the above disorders.

Arthritis, Rheumatoid↗
PubMed1985

Characterization of T cells bearing HLA-DR antigens in rheumatoid arthritis.

It has been demonstrated that T cells bearing HLA-DR antigens on their surface are actively involved in an immune response. In diseases of disordered immunoregulation, including rheumatoid arthritis (RA), there are elevated numbers of circulating HLA-DR+ T cells. In this study, we examined the cellular physiology of these T cells in RA patients. Using tritiated thymidine incorporation, we found that, in most patients, HLA-DR+ cells do not account for a significant amount of spontaneous proliferation found in peripheral blood T cells. RNA hybridization studies, using a cloned HLA-DR alpha chain gene probe, indicate that the T cells actively synthesize HLA-DR antigens rather than passively adsorbing them. The cell surface phenotype of the HLA-DR+ T cells was analyzed using double immunofluorescence and a variety of monoclonal antibodies. The expression of T cell differentiation antigens T4, T6, T8, and T10 varied markedly from patient to patient. In some patients, a significant number of cells expressed both T4 and T8 antigens. Most HLA-DR+ cells also express antigens defined by the following antibodies: anti-Tac (the interleukin-2 receptor), J2 (a glycoprotein found on T cell blasts), and ILR-1 (a class II major histocompatibility complex antigen). Activated T cells bearing HLA-DR antigens may play a role in the development of RA. Our data demonstrate that although these cells are not lymphoblasts, they possess a distinct cell surface phenotype.

Antigens, Surface↗
PubMed1985

Erosive arthritis in a patient with amyloid arthropathy.

Amyloid arthropathy is said to be distinguished roentgenographically from rheumatoid arthritis by the absence of joint space narrowing and the absence of articular erosions. We present a patient with multiple myeloma with swelling, stiffness and firm synovial thickening of the wrists, metacarpophalangeal joints and proximal interphalangeal joints whose hand radiographs showed articular erosions of the carpal joints and ulnar styloid and joint space narrowing of the proximal interphalangeal joints and metacarpophalangeal joints. Synovial biopsy of the left wrist showed amyloid deposits with no inflammation. Previous reports of X-ray changes in amyloid arthropathy note preservation of joint spaces or widening. Erosions when noted are of non-articular bone rather than of the articular surface. This is the first case report of erosive articular disease in amyloid arthropathy.

Aged↗
PubMed1985

Chlorambucil therapy in rheumatoid arthritis: clinical experience in 28 patients and literature review.

Our clinical experience in 28 patients receiving chlorambucil for rheumatoid arthritis (RA) and the reports on chlorambucil therapy are reviewed. Our study population and other reports generally represent patients with severe RA who had either failed to improve or developed significant toxicity during previous treatment with conventional slow acting anti-rheumatic drugs (SAARDs). Seventy-two percent of patients had a significant clinical improvement during chlorambucil therapy and reports of complete remission are given, although the incidence of remission is unknown. Hematologic complications are often reported, but appeared more frequently in our experience than previously reported. Hematologic toxicity required that chlorambucil be discontinued in the majority of our cases. Two deaths from suspected drug induced malignancies are reported. Although chlorambucil appears to be effective in the control of active RA, the potential for drug induced toxicity and malignancies may outweigh the benefit of continued use of this experimental therapy in RA.

Adult↗
PubMed1985

Identification of a bacterial sensing protein and effects of its elevated expression.

The Escherichia coli flaA gene product (also called cheC) plays a crucial role in switching flagellar rotational direction during chemotactic responses. Wild-type and mutant alleles have been cloned onto plasmid vectors, and the gene product has been identified as a 37,000-dalton protein. The flaA product appeared as a soluble protein in the cytoplasm when overproduced in minicells and maxicells. The protein could not be detected in flagellar basal structures purified from a wild-type strain. To assess the effects of altered flaA expression, the gene was fused to a synthetic tac promoter that could be regulated by the addition of an inducer. Overproduction resulted in strong counterclockwise flagellar rotational bias and partial paralysis of flagellar motors. These results suggest that the flaA protein provides the interface between the flagellar machinery and the chemotaxis signaling system in a motor structure external to the basal body.

Bacterial Proteins↗
PubMed1985

Circulating immune complexes containing secretory IgA in jejunoileal bypass disease.

Thirteen patients were studied after jejunoileal bypass (JIB) surgery. Seven developed arthritis and six did not. Circulating immune complexes containing IgG and IgA were detected in the sera of patients with and without arthritis. IgA complexes were shown to contain secretory component, a protein predominantly associated with intraluminal IgA, in significantly higher levels in patients with arthritis. Analytical ultracentrifugation showed complexes of approximately 10 X 8S, consistent with the size of secretory IgA. Arthritis after JIB appears to be associated with circulating immune complexes containing secretory IgA.

Acute Disease↗
PubMed1985

Methotrexate and the liver.

The findings of liver studies in 29 patients who were treated with low dose pulse methotrexate for rheumatoid arthritis (RA) are described. The biopsy specimens of 22 patients (76%) showed liver abnormalities, but cirrhosis did not develop in any patient. There were no statistically significant differences in age, duration of treatment, or cumulative dose between patients in whom abnormal liver histology developed and those in whom it did not. Our findings showed that isolated elevations of the aminotransferase enzymes or alkaline phosphatase levels did not predict liver disease, nor did the absence of elevation of these enzymes assure the absence of liver disease. Serial elevations of the aminotransferase and/or alkaline phosphatase enzyme levels and the development of hypoalbuminemia during treatment were specific indicators of the development of liver disease. In the patients studied, significant liver disease did not develop before 2 years of therapy or with a cumulative dose of methotrexate of less than 1500 mg.

Adult↗
PubMed1984

Susceptibility and resistance to 6-sulfanilamidoindazole-induced arthritis among inbred strains of rats.

Inflammation induced by 6- sulfanilamidoindazole (6-SAI) in aged, outbred rats is predictably produced, but the pathogenesis is not understood. We demonstrate the variable resistance of 15 inbred rat strains to 6-SAI arthritis. Susceptibility to 6-SAI arthritis is not directly linked to the major histocompatibility complex, although resistance is related to the major histocompatibility complex in other experimental forms of rat arthritis. The genetic background of these inbred rat strains appears to have a major role in 6-SAI arthritis susceptibility.

Animals↗
PubMed1984

The role of a signaling protein in bacterial sensing: behavioral effects of increased gene expression.

A recombinant DNA approach has been used to study intracellular signaling in the bacterial sensing system. The Escherichia coli cheY gene, whose function is unknown, has been subcloned behind the synthetic inducible tac promoter. The resulting plasmid directs the synthesis of the Y protein in response to isopropyl beta-D-thiogalactoside, independent of its usual operon control. When this construct was introduced into wild-type and mutant cells, the Y protein caused a clockwise rotational bias in the flagellar motors. This effect was observed even in heavily biased counterclockwise strains lacking most of the central chemotaxis processing genes. The results show that the Y protein has a direct influence on flagellar rotation not requiring other processing genes of the sensing system. The Y protein appears to bind directly to a part of the flagellar motor, probably the flaA gene product, and it is probably the key element in biasing the motor toward the clockwise rotational direction.

Base Sequence↗
PubMed1982

Tandem duplication and multiple functions of a receptor gene in bacterial chemotaxis.

The aspartate receptor in bacterial sensing, previously identified with the tar gene, has been shown to be duplicated in tandem in Escherichia coli. Each gene, which we refer to as tar and tap, respectively, codes for a 60,000-dalton protein. By genetic engineering experiments in which each gene is introduced separately into E. coli strains, it is shown that each transmembrane receptor can respond to the small molecule aspartate, to the maltose-protein-chemoeffector complex, and to repellents.

Aspartic Acid↗
PubMed1981

Molecular cloning and amplification of the adenylate cyclase gene.

A segment of DNA containing cya, the gene for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1], has been isolated from Salmonella typhimurium. The phage lambda gt4 was used as a cloning vector and adenylate cyclase-positive hybrid phages were isolated that complemented adenylate cyclase-negative bacteria. The cloned DNA fragment encodes a polypeptide of molecular weight 81,000 that gives rise to adenylate cyclase activity. This protein represents a functional mutant of the bacterial adenylate cyclase. When the cya gene was amplified by inserting into a multicopy plasmid, the enzyme activity was overproduced 20-fold, but the cyclic AMP level increased only 60%, suggesting several probable regulatory mechanisms. Overproduction of enzymes by recombinant DNA techniques can be a useful probe of relationships in the metabolizing organism in vivo.

Adenylyl Cyclases↗