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Biomedical subjects

P Emery

Publications and source records attributed to P Emery.

At least 307 records · Page 17Linked to original sources

Activity of rheumatoid arthritis and levels of collagen antibodies: a prospective study.

Thirty-seven patients with classical or definite rheumatoid arthritis (RA) were studied prospectively over a period of 12 months to assess whether there was a relationship between disease activity and raised levels of antibodies to native or denatured type II collagen. Nineteen patients had inactive RA according to ARA criteria for disease remission and 18 had active RA throughout the study. At the beginning of the study the levels of collagen antibodies were comparable in each group. After 1 year, antibodies to denatured type II collagen in patients with inactive RA had declined to significantly lower levels whereas in patients with active RA the levels of antibodies fluctuated during the period of study and were not significantly different at the end. There was no relationship between levels of antibodies to type II collagen and any specific index of disease activity, severity of X-ray changes in the hands and feet, or progression over 1 year in X-ray changes. The finding of a decline in levels of antibodies to denatured type II collagen in inactive RA suggests that the anticollagen response is an integral component of the rheumatoid process and could have a primary or secondary role in pathogenesis.

Adult↗

HLA A1, B8, DR3 extended haplotypes in autoimmune chronic hepatitis.

Genetic determinants of the autoimmune type of chronic active hepatitis include the major histocompatibility complex alleles HLA-B8 and HLA-DR3, which are usually present as the haplotype A1, B8, DR3. In certain other autoimmune diseases, an extended haplotype including complement alleles confers a greater relative risk than does B8, DR3. Hence, extended haplotypes were ascertained in autoimmune chronic active hepatitis by typing for HLA, complement alleles C4A, C4B, and Bf, and glyoxalase type 1 or 2. Eight of the 10 B8, DR3 haplotypes were A1, B8, DR3. Of the 8, 7 had the extended haplotype A1, B8, C4AQ0, C4B1, BfS, DR3, but this haplotype occurred in four instances with glyoxalase 2 and in three with glyoxalase 1. Thus, we find that in autoimmune chronic active hepatitis there is a high frequency of null alleles for complement but an extended haplotype does not cause any greater risk for disease than B8, DR3 alone.

Alleles↗

High-affinity interleukin-2 receptors on blood lymphocytes are decreased during active rheumatoid arthritis.

The expression of receptors for interleukin-2 (IL-2R) was examined in patients with active or inactive rheumatoid arthritis (RA) and in control subjects. Unstimulated blood lymphocytes from patients with active RA had increased levels of total IL-2R, as measured by Tac-positive cells, compared with the levels found in the other 2 groups. Mitogen-stimulated cells from patients with active RA expressed less IL-2R per cell, but the most striking feature was the failure to express high-affinity IL-2R. These changes could reflect persistent antigenic stimulation and explain the defective cell-mediated immunity in RA patients.

Adult↗

Influences of dopaminergic systems on the blink reflex.

The effect of the anti-dopaminergic drug haloperidol (6 mg/day i.m. for 2 days) on the blink reflex elicited by electric stimulation of supraorbital nerves was investigated in 12 adult volunteers. A significant increase in amplitude of the early component (R1) of the reflex was observed. This increase disappeared within 5 days of stopping the drug. Possible neural systems which might be involved in these effects are considered.

Adult↗

Interferons in rheumatoid arthritis: alterations in production and response related to disease activity.

Various markers associated with the production of and response to interferons (IFNs) were studied in patients with either inactive rheumatoid arthritis (RA) or active RA, and in healthy subjects. The IFN markers assessed were serum and synovial fluid (SF) levels, the activity in peripheral blood leukocytes (PBL) of (2'-5') oligoadenylate synthetase (OAS), and the production in vitro by PBL of IFN-alpha/beta in response to Sendai virus or Poly(I):Poly(C) as inducers, and of IFN-gamma using PHA or Con A as inducers. IFN activity, tested by antiviral assays using two different cell lines, was not demonstrable in the serum of any patient with RA. The activity of (2'-5') OAS in PBL, which may indirectly indicate exposure of leukocytes to IFN, was increased in RA compared with healthy subjects, more so in patients with inactive RA. The production of IFN-alpha/beta by PBL in response to Sendai virus was low in active RA but high in inactive RA, relative to production in healthy subjects. The production of IFN-gamma by PBL in RA was lower than in healthy subjects, more so in active RA. Thus inactive RA (remission status) is marked by evidence of PBL having been influenced by interferon and being a state of augmented inducibility to an IFN-alpha/beta stimulus, whereas active RA is associated with low inducibility of PBL to an IFN stimulus, but no evidence of IFN production in vivo. Our findings underscore the relevance of interferon to remission/activity in rheumatoid arthritis.

2',5'-Oligoadenylate Synthetase↗

Leg exchange of amino acids during exercise in patients with arterial insufficiency.

Intermittent claudication is associated with adaptation in muscle metabolism. This study has evaluated the metabolism of amino acids at rest and during non-steady state exercise in patients with arterial insufficiency of at least six months duration in comparison with matched control individuals. The exchange of amino acids were measured during two periods of acute exercise; one initial exercise period with a standardized work load and exercise time and a second exercise period which continued until further exercise was impossible due to pain in the patients and exhaustion in the controls. The maximum blood flow was reduced by 40% in the patients but the maximum oxygen uptake per unit power developed was almost the same in patients and controls. The patients had significantly lower concentrations of glutamine, lysine and taurine at rest compared with the controls. The exchange of amino acids across the resting leg did not differ between the two groups. Exercise increased the efflux of amino acids in both patients and controls. The efflux of glutamine (896 +/- 205 vs. 48 +/- 359 nmol/100 ml/min/watt) was higher in the patients compared to the controls at the first exercise period with inverse changes in the opposite direction of asparagine (149 +/- 105 vs. 799 +/- 121 and 27 +/- 70 vs. 633 +/- 334 nmol/100 ml/min/watt at the first and second exercise, respectively. Alanine release did not differ between the groups. The complementary patterns of glutamine and asparagine during hypoxic exercise in the patients may reflect the fact that these amino acids share a common carrier system. The similarity in the efflux of non-metabolized amino acids, such as methionine, phenylalanine, tyrosine and 3-methylhistidine, indicated that muscle hypoxia in claudication patients did not promote net degradation of either globular or myofibrillar proteins, although exercise increased the efflux of 3-methylhistidine three- to fourfold in both patients and control individuals (from 1 +/- 0.4 to 4 +/- 1.8 and from 0 +/- 0.7 to 6 +/- 2.5 nmol/100 ml/min/watt, respectively). The exercise-induced alterations in leg exchange of amino acids were restored within 10-20 min following exercise regardless of hypoxia. The results demonstrate that patients with arterial insufficiency have altered intermediary metabolism of amino acids during exercise. However, muscle hypoxia in such patients does not seem to promote a negative protein balance or induce serious alterations in cell membrane integrity.

Aged↗

Synovial fluid neutrophils of patients with rheumatoid arthritis have membrane antigen changes that reflect activation.

The level of expression of surface antigens was studied on neutrophils from paired samples of blood and synovial fluid of patients with rheumatoid arthritis (RA). By measuring the immunofluorescence of labelled monoclonal antibodies it was shown that on joint neutrophils there was an increase in expression of complement receptor 3 (CR3) and granulocyte functional antigens 1 and 2 compared with blood neutrophils, whereas the expression of GpIIb-IIIa was reduced. The pattern of expression was the same as that seen with in vitro activation and strongly suggest that activation is occurring within the joint.

Antigens, Surface↗

Plasma exchange in dermatomyositis/polymyositis: beneficial effects in three cases.

We describe ameliorative effects of plasmapheresis in three patients with dermatomyositis-polymyositis resistant to other therapy, particularly prednisolone. Serologically, the cases were marked, respectively, by a weakly-reactive speckled-type ANA; a strongly reactive speckled-type ANA and an unidentifiable precipitin line by CIEP; and an antibody to cytoplasm and to Jo1. The remission induced by plasmapheresis was temporary in one case and lasting, with low doses of prednisolone, in two. The nuclear autoantibody in case two became undemonstrable after plasmapheresis but recurred during a subsequent relapse. This experience with plasmapheresis in myositis supplements a substantial reported experience of benefit from this therapy.

Adult↗

Interleukin 2 inhibitor in synovial fluid.

Since evidence for the presence of IL-2 activity in rheumatoid synovial fluid is conflicting, we have assayed IL-2 activity in synovial fluid from patients with rheumatoid arthritis (RA) and other articular diseases (OAD). Using the IL-2-dependent murine T cell line CTLL, IL-2 activity was not demonstrable in synovial fluid tested at concentrations ranging from 50% to 0.02%. There was an inhibitory effect on IL-2 activity in the bioassay of synovial fluid from 16 of the 22 patients with RA and 15 of the 16 with OAD. This inhibitory activity was heat-labile, precipitable by ammonium sulphate, reversible with excess IL-2 and was not significantly altered by preincubation of synovial fluid with CTLL. The mean inhibitory activity of synovial fluid from patients with RA was significantly reduced in comparison with that of synovial fluid from patients with OAD. Sera also had an inhibitory effect on IL-2 activity; however sera from patients with RA were less inhibitory than control sera but were more inhibitory than sera from patients with systemic lupus erythematosus. The deficiency in synovial fluid of an inhibitor of IL-2 activity may be relevant to the pathogenesis of RA.

Adult↗