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Biomedical subjects

J Worthington

Publications and source records attributed to J Worthington.

At least 91 records · Page 5Linked to original sources
PubMed1997

Linkage and association studies of the natural resistance associated macrophage protein 1 (NRAMP1) locus in rheumatoid arthritis.

OBJECTIVE: To determine if there is any evidence of linkage between the natural resistance associated macrophage protein gene, NRAMP1, and rheumatoid arthritis (RA). METHODS: Two dinucleotide markers, D2S1471, a highly polymorphic marker within 160 kb of NRAMP1, and a less polymorphic marker in the promoter region of NRAMP1, have been analyzed in 115 affected sib-pair RA families (35 with 2 parents, 18 with one parent) from the Arthritis and Rheumatism Council (ARC) National Repository and an additional 85 probands from the ARC National Twin Study and 96 controls. Individuals were typed for both markers by fluorescence based semiautomated polymerase chain reaction analysis. RESULTS: No evidence of increased allele sharing in affected sib-pairs was obtained using identity by descent (IBD), identity by state, and maximum likelihood score (MLS) analysis for the whole data set. A significant increase in allele sharing was observed with marker D2S1471 (LOD 0.74; p 0.05) in the HLA discordant subgroup using IBD and MLS-IBD. No significant differences in allele frequencies were observed for any markers in the association study. CONCLUSION: In a subset of sib-pairs that shared one or zero HLA haplotypes, LOD scores suggestive of linkage were observed. This suggests a role for NRAMP1 polymorphism in a subset of patients who do not possess HLA susceptibility alleles.

Alleles↗
PubMed1997

Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus.

OBJECTIVE: To investigate interleukin 10 (IL-10) gene promoter polymorphisms in systemic lupus erythematosus (SLE) and its clinical subsets. METHODS: DNA from 76 Caucasian patients with SLE and 119 controls as genotyped for 3 defined dimorphic polymorphisms (G or A at position -1082, C or T at position -819, C or A at position -592) in the promoter region of the IL-10 gene, using the polymerase chain reaction to amplify the IL-10 gene promoter and oligonucleotide probes specific for each allelic sequence. The frequency of genotypes was compared between patients with SLE and controls, and between clinical subsets of patients with the disease. RESULTS: There was no significant change in the allele frequency of the three IL-10 gene promoter dimorphic polymorphisms in the SLE group compared with controls. However, when subgrouped according to autoantibody status and clinical features, IL-10 -1082*G, -819*C, and -592*C alleles were increased in patients possessing Ro autoantibodies and those with renal involvement. These alleles are in preferential allelic association, namely GCC, ACC, and ATA haplotypes, and the GCC haplotype was increased in these patient subgroups. CONCLUSION: Polymorphisms within the IL-10 gene promoter that are associated with high IL-10 levels may be important in the development of certain clinical features in SLE.

Adolescent↗
PubMed1996

Are both genetic and reproductive associations with rheumatoid arthritis linked to prolactin?

The risk of rheumatoid arthritis (RA) seems to be associated with reduced fecundity and with breastfeeding; these apparently contradictory risk factors can be explained by their association with high prolactin concentrations. The only consistent genetic association with RA is for genes encoded in the HLA complex, particularly HLA DR4. We have identified some data indicating that the effects of breastfeeding and nulliparity are modified by HLA DR4 status, suggesting an interaction between genetic and reproductive risk factors in the aetiology of RA. The prolactin gene is in close proximity to the HLA region on the short arm of chromosome six. We therefore propose the hypothesis that the associations between DR4 and reproductive risk factors in RA are due to linkage disequilibrium between DR4 and an abnormally regulated prolactin gene polymorphism.

Arthritis, Rheumatoid↗
PubMed1996

Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1*04-bearing haplotypes in rheumatoid arthritis patients.

OBJECTIVE: To investigate 1) tumor necrosis factor (TNF) microsatellite allele frequencies in rheumatoid arthritis (RA), and 2) associations between TNF microsatellites and RA-associated HLA specificities in order to build up extended HLA haplotypes. METHODS: Eighty-five caucasoid patients with RA and 109 healthy caucasoid controls were typed for TNF microsatellites a-d using fluorescent-labeled primers and semiautomated genotyping. A further 56 RA patients who were selected for having certain HLA-DRB1 types were also typed for these TNF microsatellites. Linkage disequilibria between TNF and HLA alleles were calculated, and extended haplotypes were established. RESULTS: The TNFa6 allele frequency was significantly increased in the RA patients compared with the controls (P = 0.0019, odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.3-4.6), an increase that was further evident in patients who were HLA-DRB1*0401 homozygous (P = 0.0003, OR 7.3, 95% CI 2.2-24.4). This increase was found to be due to association with HLA-DRB1*0401. No TNF microsatellite allele was found to be associated with HLA-DRB1*0404. Three HLA extended haplotypes were identified in the RA group: 1) HLA-DRB1*0401;TNFd4;TNFa6;TNFb5;HLA-B44; HLA-Cw5;HLA-A2, 2) HLA-DRB1*0301;TNFd2; TNFa2;TNFb3;HLA-B8;HLA-Cw7;HLA-A1, and 3) TNFd5;TNFc2;TNFa2;TNFb1;HLA-B62;HLA-Cw3. CONCLUSION: TNF microsatellites found to be associated with RA do not appear to be independent of class II HLA associations.

Alleles↗
PubMed1996

Prevalence of panic in patients referred for pulmonary function testing at a major medical center.

OBJECTIVE: The authors examined the prevalence and correlates of panic disorder in a group of patients who were referred for pulmonary function testing. METHOD: Patients (N = 115) were screened for the presence of panic attacks and panic disorder with a self-report questionnaire; a subgroup (N = 25) received structured diagnostic assessment. RESULTS: Of the 115 patients, 41% (N = 47) reported panic attacks and 17% (N = 20) met screening criteria for panic disorder. From the confirmed rate of panic disorder among the subgroup who received structured diagnostic assessment, the overall prevalence rate of panic disorder was estimated to be 11% and included six of the nine patients (67%) who had a diagnosis of chronic obstructive pulmonary disease. There were no significant differences between patients with and without panic in the severity of pulmonary function abnormalities or in the response to bronchodilators. However, patients with panic attacks were significantly more likely to report dyspnea at rest and irritable bowel symptoms and tended to report difficulty swallowing. CONCLUSIONS: This study suggests that panic disorder and subsyndromal panic are relatively common and may be unrecognized and inadequately treated in patients who present with respiratory symptoms.

Airway Obstruction↗
PubMed1996

Fluoxetine treatment of anger attacks: a replication study.

"Anger attacks" are outbursts of anger which are accompanied by intense autonomic arousal and are clearly inappropriate to the situation in which they occur. The Anger Attacks Questionnaire, designed to assess these attacks, was administered to 164 consecutive patients (78 men and 86 women; mean age, 40.5 +/- 11.0 years) diagnosed as having major depression with the Structured Clinical Interview for DSM-III-R. These patients were treated openly with fluoxetine, 20 mg/day for 8 weeks, and the prevalence of anger attacks was assessed before and after treatment. At baseline, 64 (39%) (26 men and 38 women) of these patients reported having anger attacks according to our criteria. Forty-one (64%) of the 64 depressed patients with anger attacks at baseline did not report anger attacks following fluoxetine treatment, while 7 (7%) of the 100 patients who did not have anger attacks at baseline reported these attacks following treatment, with this difference being statistically significant (chi 2 = 22.7, p < .0005).

Adolescent↗
PubMed1995

Lack of influence of non-inherited maternal HLA-DR alleles on susceptibility to rheumatoid arthritis.

OBJECTIVE: To reproduce findings from previous reports that non-inherited maternal HLA class II antigens might contribute to rheumatoid arthritis (RA) susceptibility in the offspring. METHODS: Families were recruited from the Arthritis and Rheumatism Council's National Repository of RA families and HLA-DRB1 alleles were examined in these individuals and their first degree relatives using DNA typing methods. RESULTS: There was no evidence of an increase in either non-inherited maternal HLA-DR4 or the HLA-DRB1 shared epitope as a whole compared with the frequency expected using the non-inherited paternal antigens as controls. CONCLUSIONS: The numbers of probands who were shared epitope negative were small, but we are unable to confirm in these families the findings that non-inherited maternal HLA contributes an additional susceptibility factor to rheumatoid arthritis.

Alleles↗
PubMed1995

Patterns of improvement in depressive symptoms with fluoxetine treatment.

By definition, patients who respond to antidepressant treatment show significant improvements in most, if not all, of their depressive symptoms. We assessed the patterns of change in depressed outpatients treated openly with fluoxetine 20 mg/day for 8 weeks. We studied 62 depressed outpatients with major depressive disorder who showed full response following fluoxetine treatment. Analysis of the data revealed that the symptoms that tended to improve relatively early during treatment were suicidal ideation, excessive guilt, and lack of appetite. Our tentative conclusion from this pilot study was that symptom improvement tends to occur in both cognitive and neurovegetative areas early in treatment as well as later.

Adolescent↗
PubMed1994

Pregnancy and multiple sclerosis--a 3-year prospective study.

A prospective study of the level of disability, severity and distribution of relapses in 15 women with multiple sclerosis prior to, during and up to 3 years following pregnancy was undertaken. The pregnant group was compared with 22 nulliparous women attending the same clinic and matched for age and severity and duration of disease. In the pregnant group, relapses were more frequent and severe than expected values during the first 6 months post partum, but were below expected values 6-24 months post partum. Over the total study period, therefore, there were no significant differences in relapse number, Expanded Disability Status Score or functional scores between the two groups. Babies born during the study showed normal distributions of weight and head circumference.

Adult↗
PubMed1993

Epitopes on the CB-11 peptide of type II collagen recognized by antibodies from patients with rheumatoid arthritis.

Using the technique of epitope scanning, the binding sites of antibodies to the CB-11 peptide of type II collagen, which is known to induce an inflammatory arthritis in animal models, have been investigated. Sera from seven patients have been tested against 272 peptides representing the CB-11 sequence, each patient produced a different profile of antibody binding and a number of epitopes have been identified. The specific nature of this binding has been established by the reduction in binding by absorption with type II collagen. The reactivity of sera from a further 13 patients, to peptides representing the two most frequently recognized epitopes, has been assessed.

Amino Acid Sequence↗
PubMed1993

Lack of association of increased antibody levels to mycobacterial hsp65 with rheumatoid arthritis: results from a study of disease discordant twin pairs.

OBJECTIVES: To investigate the role of humoral immunity to mycobacterial hsp65 in the aetiology of rheumatoid arthritis. METHODS: Levels of IgG antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples of 152 twin pairs discordant for RA and in serum samples from 62 normal blood donors. RESULTS: No significant differences between antibody levels in the subjects with RA compared either with their unaffected twins or with a group of normal blood donors was observed. In the monozygotic twins there was a strong but negative association between levels of antibody to hsp65 and disease status. Zygosity, sex, and HLA status did not significantly affect levels of antibody to hsp65. CONCLUSION: Previous reports of an association between hsp65 and RA were not confirmed.

Antibodies, Bacterial↗
PubMed1992

Monoclonal antibody epitopes of mycobacterial 65-kD heat-shock protein defined by epitope scanning.

The binding sites for MoAbs to the 65-kD heat-shock protein (hsp65) of mycobacteria have been investigated by epitope scanning. Five hundred and twenty-six 8-mer peptides representing the complete sequence of Mycobacterium tuberculosis hsp65 were synthesised in duplicate using the Epitope Scanning Kit (CRB Ltd.). The epitopes of six MoAbs raised to the hsp65 of M. tuberculosis or M. leprae were investigated. We have identified the epitope of a new MoAb (DC16); this epitope is continuous, hydrophilic in nature and 11 amino acids long. We have also confirmed the location of the epitopes of three MoAbs (IIH9, ML30 and IIC8). Thus the epitope scanning technique has proved suitable for the detection of continuous epitopes of hsp65.

Amino Acid Sequence↗
PubMed1992

Antibody to a 63 kilodalton insect protein in ankylosing spondylitis.

Ankylosing spondylitis (AS) is associated with antibodies to a heat shock puff on drosophila chromosomes. This observation was investigated by immunoblotting using extracts of the Schneider insect cell line and HeLa cells, before and after heat shock. An insect protein of 63 kilodaltons (but no equivalent human protein) was recognised by 21 (46%) of 46 serum samples from patients with AS, one of two patients with Reiter's syndrome, four (7%) of 60 patients with systemic lupus erythematosus, and two (4%) of 50 control subjects, but not by serum samples from patients with rheumatoid arthritis (RA). Previous heat shock did not appear to affect the strength of reaction, but ML-30, a monoclonal antibody to the mycobacterial 65 kilodalton heat shock protein (hsp65), also recognised an insect protein of 63 kilodaltons by immunoblotting. Antibodies to recombinant mycobacterial hsp65 were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from patients with AS and RA. IgA binding to hsp65 was increased in 41% of AS and 19% of RA serum samples, but there was no correlation with detection of antibody to the insect 63 kilodalton protein.

Animals↗