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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1999

Overrepresentation of the Fcgamma receptor type IIA R131/R131 genotype in caucasoid systemic lupus erythematosus patients with autoantibodies to C1q and glomerulonephritis.

OBJECTIVE: To test the hypothesis that there is an association between the Fcgamma receptor type IIA (FcgammaRIIA)-H/R131 polymorphism and autoantibodies to the collagenous region (CLR) of C1q in patients with systemic lupus erythematosus (SLE). METHODS: One hundred ninety-five Caucasoid lupus patients were studied. Anti-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and FcgammaRIIA genotype analysis was performed by polymerase chain reaction. Immunoglobulin subclass of the autoantibodies was measured by ELISA. RESULTS: Fifty-six patients were anti-C1q antibody positive, and Ig subclass analysis indicated a predominance of IgG2 anti-C1q antibodies. Analysis of the SLE population as a whole revealed no significant difference in the allele frequencies of R131 and H131 compared with controls. There was, however, a significantly increased frequency of the R131 allele both in the anti-C1q-positive subgroup of patients (chi2 = 7.66, P<0.01) and in the 71 patients with nephritis (chi2 = 7.76, P< 0.01), compared with controls. CONCLUSION: FcgammaRIIA-R131 constitutes a heritable susceptibility factor for the development of SLE with manifestations in the kidney in Caucasoid patients. The close associations demonstrated between this FcgammaRII variant, antibodies to C1q(CLR), and glomerulonephritis may be due to a failure of clearance of the potentially pathogenic IgG2 autoantibody.

Alleles↗
PubMed1999

Maternal stress in caring for children with feeding disabilities: implications for health care providers.

The purposes of this study were to compare the stress experienced by mothers of children with feeding disorders to the stress experienced by mothers of children with other childhood disabilities, to compare the stress experienced by mothers of children who are tube-fed with that of mothers of children with disabilities who do not require tube feeding, to ascertain the types of stressors that mothers in both groups experience, and to determine their coping resources. Subjects were mothers of children with disabilities who had recently been discharged or were receiving outpatient care from a private rehabilitation facility in a Midwestern city. The Short Form of the Questionnaire on Resources and Stress instrument and open-ended questions developed by the researchers were used. Results were analyzed using analysis of variance. Results indicate that mothers of children requiring tube feeding experienced significantly greater stress than mothers of children with disabilities who do not require tube feedings. Mothers of children requiring tube feeding also receive less support from family and friends. To assist dietitians, other health care professionals, and university instructors in developing family-centered treatment programs, we recommend including fathers, friends, or relatives in the care and feeding process; discovering ways to include the tube-fed child in family mealtime activities; increasing public awareness of tube-feeding issues; organizing support groups; and educating dietetics students about the unique stresses experienced by mothers of children who are tube-fed.

Adolescent↗
PubMed1999

The treatment of refractory uveitis with intravenous immunoglobulin.

PURPOSE: To study the treatment of uveitis that has not responded to immunosuppressive medication. Intravenous immunoglobulin (IVIg) effectively treats a variety of autoimmune diseases, but it has not been adequately studied in the treatment of uveitis. METHODS: The trial included patients who satisfied criteria that included noninfectious uveitis, active inflammatory disease, and a failure to respond adequately to immunosuppressive medication. We treated two patients with IVIg (0.5 gm/day, 3 days/mo initial dosage) as a pilot study and then treated an additional eight patients with a similar dosage as part of a formal but uncontrolled protocol. RESULTS: Patients on the protocol have been followed for a median of 11 months and have received a median of 7.5 treatment cycles. Five of 10 patients have had a clinically important and sustained improvement in visual acuity, and two of eight protocol patients have markedly reduced their immunosuppressive medication. CONCLUSIONS: Intravenous immunoglobulin can benefit some patients with uveitis that is otherwise refractory to immunosuppressive therapy. Although our preliminary experience is encouraging, the use of IVIg for uveitis should be limited because of cost, toxicity, the requirement for repeated administration, and the absence of controlled trials that demonstrate efficacy.

Adult↗
PubMed1999

The association of socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between socio-economic status, race, psychosocial factors and outcome in patients with systemic lupus erythematosus (SLE). METHODS: One hundred and ninety-five patients with SLE were studied at two centres in the UK (London and Birmingham). Information about sociodemographics, income, employment status, social support and satisfaction with care was obtained. Outcomes were assessed by end-organ damage, disease activity and employment status. RESULTS: Non-Caucasian race, longer disease duration, higher disease activity and lower level of education were associated with more organ damage in SLE. More satisfaction with access to care and interpersonal aspects of care, but less satisfaction with time spent with doctors, were also associated with more damage. Very long disease duration was associated with higher disease activity. Patients with higher disease activity, lower level of education and from the Birmingham centre were more likely not to be working due to their lupus. CONCLUSION: Race and socio-economic status, as well as clinical and psychosocial factors, determine outcome in SLE.

Adult↗
PubMed1999

A cell line-based neutralization assay for primary human immunodeficiency virus type 1 isolates that use either the CCR5 or the CXCR4 coreceptor.

We describe here a cell line-based assay for the evaluation of human immunodeficiency virus type 1 (HIV-1) neutralization. The assay is based on CEM.NKR cells, transfected to express the HIV-1 coreceptor CCR5 to supplement the endogenous expression of CD4 and the CXCR4 coreceptor. The resulting CEM.NKR-CCR5 cells efficiently replicate primary HIV-1 isolates of both R5 and X4 phenotypes. A comparison of the CEM.NKR-CCR5 cells with mitogen-activated peripheral blood mononuclear cells (PBMC) in neutralization assays with sera from HIV-1-infected individuals or specific anti-HIV-1 monoclonal antibodies shows that the sensitivity of HIV-1 neutralization is similar in the two cell types. The CEM.NKR-CCR5 cell assay, however, is more convenient to perform and eliminates the donor-to-donor variation in HIV-1 replication efficiency, which is one of the principal drawbacks of the PBMC-based neutralization assay. We suggest that this new assay is suitable for the general measurement of HIV-1 neutralization by antibodies.

CD4 Antigens↗
PubMed1999

The CC-chemokine RANTES increases the attachment of human immunodeficiency virus type 1 to target cells via glycosaminoglycans and also activates a signal transduction pathway that enhances viral infectivity.

We have studied the mechanisms by which the CC-chemokine RANTES can enhance the infectivities of human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses, when present at concentrations in excess of 500 ng/ml in vitro. Understanding the underlying mechanisms might throw light on fundamental processes of viral infection, in particular for HIV-1. Our principal findings are twofold: firstly, that oligomers of RANTES can cross-link enveloped viruses, including HIV-1, to cells via glycosaminoglycans (GAGs) present on the membranes of both virions and cells; secondly, that oligomers of RANTES interact with cell-surface GAGs to transduce a herbimycin A-sensitive signal which, over a period of several hours, renders the cells more permissive to infection by several viruses, including HIV-1. The enhancement mechanisms require that RANTES oligomerize either in solution or following binding to GAGs, since no viral infectivity enhancement is observed with a mutant form of the RANTES molecule that contains a single-amino-acid change (glutamic acid to serine at position 66) which abrogates oligomerization.

Animals↗
PubMed1999

Defects in components of the proteasome enhance transcriptional silencing at fission yeast centromeres and impair chromosome segregation.

Fission yeast centromeres are transcriptionally silent and form a heterochromatin-like structure essential for normal centromere function; this appears analogous to heterochromatin and position effect variegation in other eukaryotes. Conditional mutations in three genes designated cep (centromere enhancer of position effect) were found to enhance transcriptional silencing within centromeres. Cloning of the cep1(+) and cep2(+) genes by functional complementation revealed that they are identical to the previously described genes pad1(+) and mts2(+), respectively, which both encode subunits of the proteasome 19S cap. Like Mts2 and Mts4, epitope-tagged Cep1/Pad1 localizes to or near the nuclear envelope throughout the cell cycle. The cep mutants display a range of phenotypes depending on the temperature. Silencing within the central domain of centromeres is increased at 36 degrees C. This suggests that the proteasome is involved in regulating silencing and thus centromeric chromatin architecture, possibly by lowering the level of some chromatin-associated protein by ubiquitin-dependent degradation. This is the first report of defective proteasome function affecting heterochromatin-mediated transcriptional silencing. At 36 and 32 degrees C, the cep mutants lose chromosomes at an elevated rate, and at 18 degrees C, the mutants are cryosensitive for growth. Cytological analysis at 18 degrees C revealed a defect in sister chromatid separation while other mitotic events occurred normally, indicating that cep mutations might interfere specifically with the degradation of inhibitor(s) of sister chromatid separation. These observations suggest that 19S subunits confer a level of substrate specificity on the proteasome and raise the possibility of a link between components involved in centromere architecture and sister chromatid cohesion.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed1999

The A-G polymorphism in exon 1 of the CTLA-4 gene is not associated with systemic lupus erythematosus.

OBJECTIVES: Factors contributing to the development of systemic lupus erythematosus (SLE) remain largely unknown although are likely to include both environmental and genetic components. Studies on murine lupus have indicated a role for an antibody that blocks binding of cytotoxic T lymphocyte associated-4 (CTLA-4) to B7 on antigen presenting cells in the treatment of disease, suggesting that CTLA-4 may play an important part in the disease process. This study, therefore, investigated the frequency of a previously described A-G polymorphism in exon 1 of the CTLA-4 gene, the G allele of which has shown to be associated with both Graves' disease and type I diabetes, to determine whether this polymorphism was playing a part in the development of SLE. METHODS: One hundred and twenty six SLE patients and 363 control subjects were genotyped for the A-G polymorphism in exon 1 of the CTLA-4 gene. Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the BbvI restriction enzyme. RESULTS: No differences in allele or genotype frequencies were observed between patients with SLE and control subjects. CONCLUSION: These data suggest that the A-G polymorphism in exon 1 of the CTLA-4 gene does not play a part in the genetic susceptibility to the development of SLE.

Abatacept↗
PubMed1999

Quality of life and economic evaluation in SLE clinical trials.

Outcome in SLE patients should include assessment of disease activity and chronic damage and also measurement of health-related quality of life and the economic impact of the disease. This paper reviews the methods available for doing this and the results of existing studies in SLE patients.

Anxiety↗
PubMed1999

Factors involved in the pathogenesis of neutrophilic vasculitis in MRL/Mp-lpr/lpr mice: a model for human microscopic angiitis.

Anti-neutrophil cytoplasm antibodies (ANCA) directed against myeloperoxidase (MPO) are detected in patients with microscopic angiitis. Human MPO autoantibodies stimulate neutrophil degranulation in vitro and are thought to be pathogenic. We have previously shown that MRL-lpr mice with MPO autoantibodies have a higher incidence of vasculitis than their seronegative littermates. The aim of the present study is to determine the relationship between MPO autoantibodies and microscopic angiitis. The neutrophil binding properties of anti-MPO monoclonal antibodies (mAbs) from MRL-lpr mice were tested using murine heterophils (neutrophils) present in blood and induced peritoneal exudates. MRL anti-MPO mAbs selectively bind activated neutrophils which express MPO in vitro. The pathogenicity of an IgG2b anti-MPO mAb, C6, was investigated in vivo. Anti-MPO mAb, C6 was administered to young MRL mice which had been primed with exogenous TNF alpha to induce neutrophil activation and expression of MPO. Neutrophilic vasculitis similar to microscopic angiitis occurred in 33% of MRL mice which had been treated with anti-MPO mAb. The lesions were mainly restricted to sites of previous endothelial insult which suggests an active role for injured endothelium in this pathology.

Animals↗
PubMed1999

An international perspective on the well being and health care costs for patients with systemic lupus erythematosus. Tri-Nation Study Group.

OBJECTIVE: To compare health care expenditure and health status for patients with systemic lupus erythematosus (SLE) between nations with distinct mechanisms for funding and delivering health care services. METHODS: Seven hundred eight patients with SLE from 2 centers in each of 3 countries (Canada 229, United States 268, United Kingdom 211) underwent physician assessment of disease activity and damage and reported on physical and psychosocial well being, satisfaction, social support, and health resource utilization. To compare overall utilization, constant prices (1997 Canadian dollars) were applied across countries for each service, enabling diverse resources to be collapsed into a single expression. RESULTS: After adjusting for important patient covariates, Canadian, compared to American and British patients, reported significantly superior health status in 3 of 8 Medical Outcome Survey Short Form-36 (SF-36) subscales, the SF-36 physical component summary score, and the visual analog scale of general health status. There was no consistent trend in patient satisfaction. Overall annual resource utilization did not vary significantly, with mean annual per patient expenditures (adjusted for demographics, disease duration, activity, damage, social support, health status, patient satisfaction, and age and sex adjusted country-specific SF-36 general population norms) totalling $4853, $5285, and $4760 for Canada, US, and the UK, respectively. However, within each resource category, differences were observed. Canadians saw more specialists than the British, the British more generalists. Canadians and Americans were more frequent users of the emergency room; Americans of laboratory/imaging procedures. Canadians had higher hospital costs than Americans. CONCLUSION: After adjustment, Canadian patients reported better well being than their counterparts. Despite considerable differences in the mechanisms of health care funding and service mixture, overall resource utilization did not vary significantly between the countries, although there was a trend towards more intense use of inpatient services in Canada and outpatient services in the United States.

Adult↗
PubMed1999

Associates of health status in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the health status of patients with systemic lupus erythematosus (SLE) and to identify the associations of this domain. METHODS: One hundred ninety-five consecutively attending patients with SLE were studied at 2 centers. Health status was measured by 8 composite scales of the Medical Outcomes Study Short Form 36 (SF-36). The mean scores for each subscale of the SF-36 for patients with SLE were compared to those of a healthy population. The effect of patients' age, sex, ethnic origin, marital status, education level, disease duration, disease activity (assessed by the Systemic Lupus Activity Measure), end organ damage (assessed by the Systemic Lupus International Coordinating Clinics/American College of Rheumatology Damage Index), social support (using the Interpersonal Support Evaluation List), and patients' satisfaction with medical care (using the Patient Satisfaction Questionnaire) on each SF-36 subscale was determined. Student's unpaired t test and multiple regression analysis were applied for statistical analysis. RESULTS: Patients with SLE had significantly lower scores in each subscale of the SF-36 compared to a control population. Higher disease activity was associated with worse physical function, role-physical, bodily pain, general health, vitality, and social function. Greater social support was associated with higher scores in physical function, bodily pain, general health, vitality, social function, role-emotional, and mental health. Increasing total end organ damage determined worse physical function and general health. Higher patient general satisfaction with care was associated with better general health. CONCLUSION: The health status of patients with SLE may be improved by increasing patients' social support and satisfaction with health care, as well as controlling SLE disease activity and preventing organ damage.

Adolescent↗