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Biomedical subjects

K B Wilson

Publications and source records attributed to K B Wilson.

15 recordsLinked to original sources

Effects of high-dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma.

We studied the effect of inhaled corticosteroids on the increase in bone mineral content in prepubertal children with asthma. Forty-eight asthmatic, prepubertal children receiving either inhaled beclomethasone dipropionate or budesonide were evaluated. Nine children of similar age not receiving inhaled steroids served as controls. The average age of corticosteroid-treated children was 7.8 +/- 2.4 years, and of control children, 8.4 +/- 2.1 years (NS). The average dose of inhaled corticosteroids in the treated children was 0.67 +/- 0.48 mg/m(2)/day, and they were followed over a 9-20-month period. Total bone mineral content (TBMC) was measured at baseline and after 9-20 months. A derived value for 12 months' TBMC was calculated, assuming that changes in TBMC were linear with the passage of time. The change in TBMC over a 12-month period was 264 +/- 68 mg for the corticosteroid-treated children and 330 +/- 84 mg for control children (P < 0.025). In a multiple regression analysis in which adjustments were made for the effects of age, height, and weight, the change in TBMC in corticosteroid-treated children was inversely related to the inhaled steroid dose/m(2)/day (P = 0.016). The increase in the lumbar vertebral bone mineral density in control children was also significantly greater than in the corticosteroid-treated children (P < 0.025). We conclude that inhaled steroids, at an average dose of 0.67 mg/m(2)/day, when used in the treatment of asthma reduce the acquisition of bone mineral in prepubertal children.

Absorptiometry, Photon↗

V gene sequences of human anti-ssDNA antibodies secreted by lupus-derived CD5-negative B cell hybridomas.

V gene sequences encoding two lupus-derived human monoclonal IgMk anti-ssDNA antibodies (2F7 and 1A6) and CD5 mRNA expression by the corresponding hybridomas were investigated. Both antibodies displayed V gene sequences nearly in germline configuration compared with their putative germline counterparts. It appeared that 2F7 used hv3019b9/HUD-3/JH6 and 12La/Jk2, while 1A6 utilized HHG19/D31-HUD-3/JH2 and Humkv328h5/Jk1. Assessment of R/S mutation ratios suggested that 2F7 and 1A6 have not undergone the antigen-driven somatic mutation. The HCDR3 featuring arginine appeared to be important in determining the anti-ssDNA specificity. CD5 mRNA was negative in both hybridomas. Since 2F7 was previously shown to be monospecific and of high affinity, these results provide the molecular basis of such unique immunochemical characteristics of the IgM anti-ssDNA antibody. Germline V genes and N sequences may be selected to confer such anti-ssDNA specificity during V gene rearrangement, which might involve CD5-negative B cells.

Amino Acid Sequence↗

Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients.

Estrogen may participate in the pathogenesis of systemic lupus erythematosus (SLE) via its intracellular receptor. To investigate the presence of various isoforms of the estrogen receptor (ER) in SLE we isolated RNA from mononuclear cells of lupus patients and normal controls. Using RT-PCR we were able to identify both the full length wild-type form and an isoform of the ER which precisely lacks exon V in both patient and normal individuals. Our results, although limited, suggest that normal individuals can express both the wild-type and truncated version at the same time, whereas lupus patients only express either the wild-type or the truncated ER. This finding may lead to a better understanding of the reasons for the prevalence of lupus in females and of the estrogenic effects on SLE disease activity.

Base Sequence↗

Collaborative benchmarking in a healthcare system.

Leading organizations outside of the healthcare industry have benefitted from benchmarking for more than a decade. In the last few years, healthcare organizations also have begun to use benchmarking to achieve breakthrough improvements in their performances. Most of these organizations have conducted their benchmarking studies independently, working one-on-one with outside benchmarking partners. More recently, some organizations have chosen to benchmark processes in conjunction with other healthcare organizations. This article discusses the application of a collaborative benchmarking project conducted by selected facilities within the Catholic Health Corporation (CHC). It reviews the rationale for implementing collaborative benchmarking efforts and the benefits such efforts bring to the organizations involved. Presentation of a work in process--a case study on workers' compensation--provides insights into collaborative benchmarking. The article focuses on the initial phases of the benchmarking process--selecting the project and establishing the benchmarking collaborative.

Catholicism↗

Heterogeneity of the TCR repertoire in synovial fluid T lymphocytes responding to BCG in a patient with early rheumatoid arthritis.

T lymphocytes have been implicated in the pathogenesis of rheumatoid arthritis. Interestingly, many of the activated T cells isolated from the synovial fluid of individuals with rheumatoid arthritis react with antigens from Mycobacterium tuberculosis or BCG. This response is seen to a much lesser extent in the peripheral blood of these patients. To investigate the nature of the T-cell response to BCG in RA, we isolated T cells from the synovial fluid of a patient with early-stage rheumatoid arthritis, stimulated them with BCG and cloned by limiting dilution. Staining with monoclonal antibodies specific for different V beta gene families revealed a statistically significant greater proportion of synovial-derived T-cell clones expressing the V beta 8 gene family product compared with peripheral blood clones. While the antigen specificity of some of the clones could not be determined, several of the clones displayed distinct antigen reactivities. Sequencing the TCR beta chain genes of these T cells suggested that although the V beta 8 gene products appeared to be over-represented in these BCG-specific clones, each clone utilized distinct J beta gene segments and used N segment addition to different extents. In addition, no common motifs were identified in the beta chain CDR3s of the clones sequenced. Analysis of bulk cultured BCG-specific SF T cells and unstimulated peripheral blood T cells for V beta 8 gene expression also revealed a large amount of diversity within the CDR3 region. Thus, the T-lymphocyte response to BCG in this patient with early rheumatoid arthritis appears to be quite heterogeneous.

Adult↗

Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shock protein (hsp) 60 and mycobacterial 65-kDa hsp-reactive T cell clones from rheumatoid synovial fluid.

A commonly held postulate regarding the etiology of rheumatoid arthritis (RA) is that of antigenic mimicry. Recent interest has focused on the mycobacterial 65-kDa heat-shock protein (hsp) as a putative causal agent. The 65-kDa hsp has over 40% sequence homology with the human hsp 60, and elevated synovial T cell responses to both antigens have been demonstrated in RA and juvenile rheumatoid arthritis patients. Such T cells should, therefore, be specific for shared epitopes on the two antigens. To investigate this, we screened synovial fluid mononuclear cells from two early RA patients with peptides of the 65-kDa hsp which have the greatest homology with the human hsp 60. We also raised a panel of T cell clones from one of the patients with the 65-kDa hsp. The synovial T cell population from both patients and one of the T cell clones recognized a peptide representing the amino-acid sequence 241-255. This clone also responded to the peptide of the equivalent human sequence, and was restricted by HLA-DQ. A second T cell clone recognized an adjacent epitope (amino acid sequence 251-265) which is also highly homologous with the human sequence, but this clone was restricted by HLA-DR. The clones utilized different V beta gene segments but the same D beta and J beta gene elements, and both exhibited specific cytotoxicity against autologous antigen-pulsed macrophages. Our findings, therefore, do not disagree with the postulate that autoimmune disease could possibly be triggered by bacterial epitopes with homology to self protein. However, it is also noted that there are alternative interpretations of this data.

Adult↗

Horizontal postrotatory nystagmus response in female subjects with adolescent idiopathic scoliosis.

Quantitative and qualitative assessment of vestibular function was made in 18 female subjects with adolescent idiopathic scoliosis and a control group of 25 female subjects without scoliosis. The Southern California Postrotary Nystagmus Test, which examines postrotatory nystagmus response, was used to assess the vestibular function of subjects in both groups. The results indicated that subjects with adolescent idiopathic scoliosis had a significantly decreased duration of postrotatory nystagmus as well as irregularities in nystagmus form. The recommendation was made that a neurological examination, including assessment of vestibular function, be incorporated into screening methods for scoliosis.

Adolescent↗