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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1998

No evidence for allelic association of a human CTLA-4 promoter polymorphism with autoimmune thyroid disease in either population-based case-control or family-based studies.

OBJECTIVE: The cytotoxic T lymphocyte associated-4 (CTLA-4) gene is a candidate for T-cell mediated autoimmune disease and polymorphism has been reported to be associated with both type 1 diabetes and autoimmune thyroid disease. A previously unreported polymorphism of the promoter region of the human CTLA-4 gene has recently been described in a sample of a normal control population. We investigated the distribution of this polymorphism, situated at position -318 to the ATG start codon and resulting in a C-T change leading to an Mse I restriction site, in both population based case control studies and family studies in patients with Graves' disease (Caucasian and Hong Kong Chinese), autoimmune hypothyroidism and systemic lupus erythematosus (SLE). DESIGN: Target DNA was amplified using the polymerase chain reaction and the resulting product was digested using the Mse I restriction enzyme. PATIENTS: One hundred and ninety-one white UK Caucasian and 98 Hong Kong Chinese patients with Graves' disease, 78 white UK Caucasian patients with Graves' disease plus family members, 92 white UK Caucasian patients with autoimmune hypothyroidism, 13 white UK Caucasian patients with autoimmune hypothyroidism plus family members, 132 white UK Caucasian patients with systemic lupus erythematosus, 355 white UK Caucasian control subjects and 82 Hong Kong Chinese control subjects. MEASUREMENTS: Frequencies of the C and T alleles were compared between patients and control subjects using the chi 2-test and Fisher's exact test for small numbers. RESULTS: No association with the T allele was observed in any of the patient groups studied. CONCLUSION: These data suggest that the C-T change in exon 1 of the promoter region of the CTLA-4 gene does not play a role, nor is in linkage disequilibrium with a disease causing mutation, in the development of autoimmune disease.

Abatacept↗
PubMed1998

Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome.

Systemic lupus erythematosus and antiphospholipid antibody syndrome are associated with an increased risk of intrauterine growth restriction, miscarriage, stillbirth and premature delivery. Recent advances in therapy during pregnancy have improved the outcome but there is still significant fetal and maternal morbidity and mortality. Treatment of patients failing conventional therapy during the second half of pregnancy is difficult and may be complicated by the development of preeclampsia. The addition of intravenous immunoglobulin therapy offers a low risk strategy for reducing autoantibody mediated disease and improving placental function in severely compromised, growth restricted pregnancies.

Antiphospholipid Syndrome↗
PubMed1998

A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits.

A novel protein complex has been identified in human cells that has a molecular mass of approximately 450 kDa. It consists of at least eight different subunits including JAB1, the Jun activation-domain binding protein 1, and Trip15, the thyroid hormone receptor-interacting protein 15. The purified complex contains COP9 and COP11 protein homologs and is very similar, if not identical, to the plant COP9 complex involved in light-mediated signal transduction. The isolated JAB1-containing particle has kinase activity that phosphorylates IkappaBalpha, the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino-terminal activation domain of c-Jun. The phosphorylation of c-Jun requires the carboxy terminus of the protein containing the DNA binding and dimerization domains. Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence similarities to regulatory components of the 26S proteasome, which could indicate the existence of common substrate binding sites. Immunofluorescence staining reveals that the new complex shows a subcellular distribution similar to that of the 26S proteasome. The functional relationship of the two particles in regulating transcriptional activity is discussed. Considering the putative role of the complex in signal transduction and its widespread occurrence, we suggest the name JAB1-containing signalosome.

Amino Acid Sequence↗
PubMed1997

Mts4, a non-ATPase subunit of the 26 S protease in fission yeast is essential for mitosis and interacts directly with the ATPase subunit Mts2.

We have isolated a fission yeast gene, mts4(+), by complementation of a temperature-sensitive mutation and show that it encodes subunit 2 (S2) of the 19 S regulatory complex of the 26 S protease. mts4(+) is an essential gene, and we show that loss of this subunit causes cells to arrest in metaphase, illustrating the importance of S2 for mitosis. The Mts4 protein is 48% identical to S2 of the human 26 S protease, and the lethal phenotype of the null mts4 allele can be rescued by the human cDNA encoding S2. We provide genetic and physical evidence to suggest that the Mts4 protein interacts with the product of the mts2(+) gene, an ATPase which has previously been shown to be subunit 4 of the 26 S protease.

Adenosine Triphosphatases↗
PubMed1997

Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides.

OBJECTIVE: To develop and validate the Vasculitis Damage Index (VDI) for the standardized clinical assessment of damage in the systemic vasculitides. METHODS: Using a nominal group consensus approach, the Birmingham Vasculitis Group generated guiding principles for assessment of damage in all systemic vasculitides. Damage was defined as irreversible change resulting from scars. Consensus principles were developed into the VDI, including guidelines for use, a list of items of damage, and a glossary. RESULTS: For 100 surviving patients with systemic vasculitis, the median VDI score at last observation was 3 (range 0-8). Within the Wegener's granulomatosis subgroup, the median VDI score for 12 non-survivors was higher than for 47 survivors (non-survivors median score 7, interquartile range 5-8 versus survivors median score 4, interquartile range 2-5; P = 0.003). VDI scores for 100 patients with systemic vasculitis increased from initial presentation to last observation by a median score of 3 (range 1-4; P < 0.001). The VDI assesses more items and is more sensitive to change than other indices of damage (P < 0.001). Using the VDI, trained observers can produce moderately consistent damage scores. CONCLUSION: The VDI is a sensitive, reproducible, comprehensive, and credible clinical tool for quantifying damage. The data presented herein should enable further validation and testing of the VDI in specific vasculitic syndromes, and should facilitate the comparison of different therapies.

Humans↗
PubMed1997

The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in patients with systemic lupus erythematosus.

OBJECTIVE: To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE. METHODS: Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design. RESULTS: The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI. CONCLUSION: Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.

Adult↗
PubMed1997

Damage occurs early in systemic vasculitis and is an index of outcome.

Because death after acute systemic vasculitis is now uncommon, alternative measures of outcome are required. A significant component of patient morbidity is disease-related damage, which can be quantified by the Vasculitis Damage Index (64 items in 11 organ-based systems). We investigated serially the time-course of damage in 120 patients with systemic vasculitis, to determine the earliest indicators of outcome. High damage scores at 2 years after presentation were characteristic of fatal disease (OR 8.1-12.4). Significant damage occurred within 6 months of presentation, and was a feature of fatal disease. More damage occurred after presentation than after relapse. Lung and multi-system damage were early indicators of poor outcome in severe non-fatal disease. Damage occurs early in systemic vasculitis, and is an indicator of poor outcome. This novel observation, together with evidence of persistent subclinical disease activity and the high frequency of relapse, suggests a need for new treatment strategies. Analogy with the management of acute leukaemia suggests a strategy of early diagnosis and intensive induction of remission, with early escalation of treatment for resistant disease.

Acute Disease↗
PubMed1997

Health promotion for seniors: what is over the horizon?

The health care industry is experiencing tremendous change in terms of health care delivery systems and fiscal pressure to provide high-quality health care at an affordable cost. A significant step forward in this change process will be the recognition of the value of comprehensive health promotion and disease prevention. The managed care model of health care is an excellent vehicle for a systematic health promotion program to flourish and succeed. This article surveys the literature on the topic of health promotion and its impact on the wellness of Medicare managed care beneficiaries and the senior population. The authors address issues, facilitators, benefits, and barriers within the context of health promotion and its potential to greatly impact both the quality and cost of health care for the rapidly growing senior population in the coming years.

Aged↗
PubMed1997

Telematics for clinical guidelines: a conceptual modelling approach.

PRESTIGE is a project for applying telematics to assist the dissemination and application of clinical practice guidelines and protocols. Previous publications have described PRESTIGE's technical approach, including the use of a generic model for representing the knowledge content of clinical guidelines. This approach offers the possibility of 'plug-and-play' electronic distribution of clinical guidelines produced by multiple authoring bodies for use on multiple healthcare clinical management software platforms. A recent joint workshop held with the Section on Medical Informatics, Stanford University School of Medicine compared the European consensus approach developed in PRESTIGE with a parallel series of projects for computer-assisted protocol-based healthcare undertaken at Stanford and other American centres over the past, which confirmed the convergence and complementarity of our approaches, and holds out prospects of world-wide standardization in healthcare protocol knowledge representation. This paper summarises PRESTIGE conceptual model set which is the design of the project's approach.

Artificial Intelligence↗
PubMed1997

The place of SGML and HTML in building electronic patient records.

The authors are concerned that, although popular, SGML (Standard Generalized Markup Language) is only one approach to capturing, storing, viewing and exchanging healthcare information and does not provide a suitable paradigm for solving most of the problems associated with paper based patient record systems. Although a discussion of the relative merits of SGML, HTML (HyperText Markup Language) may be interesting, we feel such a discussion is avoiding the real issues associated with the most appropriate way to model, represent, and store electronic patient information in order to solve healthcare problems, and therefore the medical informatics community should firstly concern itself with these issues. The paper substantiates this viewpoint and concludes with some suggestions of how progress can be made.

Computer Communication Networks↗
PubMed1997

The effect of cancer pain on quality of life in different ethnic groups: a literature review.

Pain influences the quality of life (QOL) of the majority of people with cancer. The way that pain is perceived and the way it is dealt with is largely influenced by the ethnocultural background of the individuals and families experiencing the pain. This article stresses the need for more research by advanced practice nurses (APN) into ethnocultural influences and the way these influences will affect the care we give and the outcomes of pain management.

Attitude to Health↗
PubMed1997

Consistency and validity of patient administered assessment of quality of life by the MOS SF-36; its association with disease activity and damage in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the metric properties and validity of the assessment of quality of life by the MOS Short Form 36 (SF-36) in patients with systemic lupus erythematosus (SLE) and to examine the effect of disease on quality of life. METHODS: Cross sectional study of 150 patients with SLE (age: mean 39.7 yrs, SD 11.4 yrs; 95% female) attending 2 specialist lupus clinics between November 1994 and April 1995. Shortly before or after the consultation patients completed the SF-36 and the MOS SF-20 with an additional question about fatigue (SF-20+) in random order. Disease activity was measured by the British Isles Lupus Activity Group System (BILAG), disease damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SLICC). RESULTS: SF-36 domains were shown to be internally consistent (Cronbach's coefficient alpha > or = 0.71). Significant associations of the SF-36 domains with the corresponding domains of the SF-20+ and with global disease activity measured by BILAG were observed. SF-36 scores in patients with SLE were significantly lower than in controls. Different disease activity levels were significantly associated with different quality of life scores, with excellent ability to record the continuum from good health to serious illness by the SF-36. Disease activity had greater effect on quality of life than age, cumulative damage, or disease duration. CONCLUSION: This study shows the SF-36 is internally consistent and proves construct, discriminatory, and criterion validity for the SF-36 and construct validity for the SF-20+ in patients with SLE. The SF-36 is preferred because of its broader scope of questions, its widespread use, and previous international validation for a wide variety of diseases.

Adult↗
PubMed1996

Characteristics of 26 S proteases from fission yeast mutants, which arrest in mitosis.

We have isolated the 26 S protease from the fission yeast Schizosaccharomyces pombe. The affinity-purified enzyme contains the two regulatory ATPases mts2+, a homolog of human S4, and CIM5, a homolog of human MSS1 = S7. We show that mts3+, a homolog of the budding yeast NIN1 protein and human S14, is a true component of the 19 S regulatory complex from the fission yeast. The 26 S proteases purified from two thermosensitive mutants, mts2-1 and mts3-1, which arrest in cell cycle at the restrictive temperature (37 degrees C), have been compared with the wild-type enzyme after growing cells at permissive (25 degrees C) and non-permissive temperatures. We demonstrate that mutated mts2 protein is integrated into the protease complex prepared from mts2 cells, whereas mutated mts3 is not present in the 19 S regulatory complex from mts3 cells. The two mutant 26 S proteases isolated after growing cells at 37 degrees C remain stable for two hours at 37 degrees C as measured by ATP-dependent cleavage of the fluorogenic peptide sucLLVY-MCA. At the restrictive temperature, the mutant 26 S proteases do not degrade ubiquitin-[125I]lysozyme conjugates in an ATP-dependent manner, indicating that mts2+ and mts3+ are essential for ubiquitin conjugate degradation. This explains the conditional lethality of the mutants and the cell-cycle arrest in metaphase to anaphase transition. In addition, our data demonstrate that the ATPases of the 26 S enzyme are not redundant.

Adenosine Triphosphate↗
PubMed1996

A conditional lethal mutant in the fission yeast 26 S protease subunit mts3+ is defective in metaphase to anaphase transition.

We have isolated a conditional lethal mutant mts3 in the fission yeast Schizosaccharomyces pombe which at the permissive temperature is resistant to the mitotic poison MBC and at the restrictive temperature is defective in metaphase to anaphase transition. The predicted amino acid sequence of mts3+ is 36% identical with the budding yeast gene NIN1. NIN1 cloned into a fission yeast expression vector can rescue both mts3 temperature-sensitive and null alleles demonstrating that NIN1 is the budding yeast homologue of the fission yeast mts3+ gene. The phenotype of the mts3 null is identical with the mts3 ts mutant demonstrating that the phenotype of the mts3 ts mutant is due to loss of mts3+ function. The deduced amino acid sequences of both mts3+ and NIN1 show homology to peptide sequences obtained from subunit 14 of the 26 S protease purified from bovine or human cells.

Amino Acid Sequence↗