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Biomedical subjects

B L Kidd

Publications and source records attributed to B L Kidd.

At least 37 records · Page 2Linked to original sources
PubMed1995

Changes in preprotachykinin mRNA expression and substance P levels in dorsal root ganglia of monoarthritic rats: comparison with changes in synovial substance P levels.

We have measured changes in the expression of gamma-preprotachykinin mRNA and levels of the neuropeptide substance P in the lumbar 4 and 5 dorsal root ganglia at various time points following the induction of an antigenic monoarthritis in the rat knee. The results were compared with changes in substances P levels in the knee joint synovium during acute and chronic phases of the disease. On day 3 post-induction, there was a significant increase in the expression of gamma-preprotachykinin mRNA in the dorsal root ganglia. Concomitant with this increase in message was a rise in the levels of substance P in the dorsal root ganglia. On days 7, 10 and 21, mRNA expression had returned to control values whereas ganglion peptide levels were significantly below controls. In contrast there was little change in the total substance P levels in the synovium on days 1 and 3 despite the observed changes in the ganglia. By day 10, however, synovial levels had risen significantly above control values and remained elevated thereafter. Our results show a transitory increase in substance P synthesis after induction of an antigenic monoarthritis. This response is not mirrored in the periphery where there is no initial change in total substance P levels perhaps reflecting increased degradation be enzymes known to be present within inflamed tissue. Paradoxically synovial substance P levels are increased in the latter phases of the model which may serve to modify the inflammatory response.

Animals↗
PubMed1995

Streptozotocin-induced diabetes decreases substance P levels in experimental arthritis in the rat knee.

Diabetic patients with sensory neuropathy are predisposed to disorders of the musculoskeletal system. It has been postulated that altered neurogenic inflammation, involving the neuropeptide substance P, may play a part in this phenomenon. We investigated the effect of streptozotocin-induced (STZ) diabetes on the development of an antigenic (mBSA) monoarthritis in the rat with particular reference to changes in substance P levels in dorsal root ganglia (DRG) and knee joint synovium. We found that STZ-induced diabetes of 24 weeks duration reduced the substance P content of L4/L5 DRG and knee joint synovial tissue. Induction of mBSA arthritis in diabetic rats resulted in diminished increases in synovial substance P and knee joint swelling compared to non-diabetic arthritic controls. The results show that chronic STZ diabetes reduces neurogenic inflammatory responses in the rat knee which may render the joint more susceptible to arthritic attack.

Animals↗
PubMed1995

Familial aggregation of undifferentiated spondyloarthropathy associated with HLA-B7.

OBJECTIVE: To report multiple cases of recurrent seronegative arthropathy, enthesopathy, or both, occurring in a single family in the absence of the HLA-B27 tissue type, coexistent psoriasis or inflammatory bowel disease. METHODS: Three generations of one family together with their general practitioners completed a standard questionnaire. All subjects with a positive questionnaire and two randomly chosen subjects with negative questionnaires were then examined by a single observer. HLA tissue typing and standard sacroiliac radiographs were performed. RESULTS: Seven of 12 family members with a positive questionnaire had early onset oligo- or polyarthritis, enthesitis, or both, and fulfilled established criteria for spondyloarthropathy, although none had radiological evidence of sacroiliitis. The mean age at first symptom in this group was 22 years with only one individual having the first symptom over the age of 30 years. All subjects were rheumatoid factor negative. Histocompatibility studies showed a strong association with the HLA-B7 antigen. CONCLUSIONS: The observations provide further support for the existence of 'undifferentiated' spondyloarthropathy and suggest that this can be associated with genetic factors other than HLA-B27.

Adolescent↗
PubMed1995

Assessment of cutaneous sensory and autonomic axon reflexes in rheumatoid arthritis.

OBJECTIVE: To assess sensory function in skin overlying the joints of patients with rheumatoid arthritis, in relation to the pain and tenderness which commonly arises in structures not directly involved in the inflammatory process. METHODS: An intradermal injection of capsaicin 0.05 microgram in 10 microliters was made over the wrists and forearms of 40 patients with rheumatoid arthritis and 46 control subjects. Axon reflex vasodilatation was measured using laser Doppler flowmetry. Cholinergic sympathetic function was assessed by measuring axon reflex sweating induced by a single intradermal injection of nicotine 0.5 microgram in 0.1 ml. RESULTS: Capsaicin induced axon reflex vasodilation over the wrists was found to decrease with age in normal subjects (r = -0.62, p < 0.001). In patients with rheumatoid arthritis, capsaicin induced axon reflex vasodilatation was significantly greater over the wrists, but not the forearms, when compared with age matched normal controls (p < 0.01). A minimal correlation between axon reflex vasodilatation and visual analogue pain score was apparent in the rheumatoid group (r = -0.37, p < 0.05). Nicotine induced sweating responses were similar in the rheumatoid and normal groups, and both showed a linear age related decline. CONCLUSIONS: The results show a selective increase of capsaicin induced vasodilatation in skin overlying joints in patients with rheumatoid arthritis. This suggests that the activity of a sub-population of periarticular small sensory fibres is altered, which may explain, at least in part, some of the clinical findings in this disorder.

Adult↗
PubMed1994

The role of bradykinin B1 receptors in the maintenance of intra-articular plasma extravasation in chronic antigen-induced arthritis.

1. The role of bradykinin B1 and B2 receptors in bradykinin- and des-Arg9-bradykinin-induced plasma extravasation in normal and inflamed rat knee joints was investigated by use of an antigen-induced model of chronic arthritis. A modification of an Evans blue extraction technique allowed the unstimulated (basal) plasma extravasation to be assessed in this model. The contributions of bradykinin B1 and B2 receptors towards basal synovial plasma extravasation were determined. 2. In normal knees, intra-articular injection of bradykinin (BK) induced plasma extravasation in a potent, dose-dependent manner with a threshold of 0.01 nmol and an ED50 of 0.1 nmol. In day 5 arthritic knees, basal plasma extravasation was substantially enhanced. Lower doses of BK had no demonstrable effect and increases above basal extravasation were first observed at 0.1 nmol. Thereafter the dose-response mirrored the response in normal knees and the maximal response was unaltered. 3. The B1 agonist, des-Arg9-BK, induced slight but significant plasma extravasation in normal knees but was less potent than bradykinin. This response was inhibited by the B1 receptor antagonist, des-Arg9, [Leu8]-BK. Lower doses of des-Arg9-BK bradykinin did not significantly increase basal extravasation in day 5 arthritic knees but, in contrast to BK, the maximal response was significantly enhanced. 4. The B2 antagonist, Hoe 140, inhibited BK-induced plasma extravasation in normal joints over a dose-range of 0.1-1.0 nmol but was relatively inactive in day 5 inflamed knees. The B1 receptor antagonist, des-Arg9, [Leu8]-BK, was relatively inactive in normal joints but showed increased potency against BK-induced plasma extravasation in day 5 arthritic joints.5. Hoe 140 and des-Arg9,[Leu8]-BK both inhibited basal extravasation in arthritic joints on days 1 and 5 post-challenge in a dose-dependent fashion. Whilst Hoe 140 was the more potent inhibitor on day 1, it was less potent than des-Arg9,[Leu8]-BK on day 5.6. Although the majority of responses to BK in normal tissue are mediated via B2 receptors, a small population of B1 receptors may exist in normal joint tissues. The data presented in this study suggest an evolving role for B1 receptors in the mediation of plasma extravasation in inflamed joint tissues. A role for BK antagonists in the treatment of arthritis is also suggested.

Animals↗
PubMed1994

Effect of three animal models of inflammation on nerve fibres in the synovium.

OBJECTIVES: Both sensory and sympathetic nerve fibres are depleted in the synovium in rheumatoid arthritis (RA). The hypothesis that the induction of an inflammatory response in the synovium is capable of causing depletion of nerve fibres was tested. METHODS: To investigate this phenomenon experimental arthritis in the rat was induced by three different methods and the synovium was examined for evidence of nerve depletion by immunocytochemistry. RESULTS: In a synovitis induced by latex spheres, a mainly macrophage foreign body type reaction, no nerve depletion was seen. In contrast both in an antigen-induced and a hydrogen peroxide-induced model of arthritis nerve fibre depletion was observed. This appeared to affect sensory and sympathetic nerve fibres equally. Nerve fibre depletion was only seen in areas of inflammatory cell infiltration indicating that a mixed lymphocyte and macrophage population of cells may be necessary for this effect. CONCLUSIONS: An inflammatory response, containing lymphocytes and macrophages, in the synovium is capable of the depletion of the finely myelinated and unmyelinated neuropeptide-containing nerves.

Animals↗
PubMed1993

Generation of substance P carbamate in neutral aqueous solution. Relevance to inflammatory joint diseases.

High-field proton (1H) nuclear magnetic resonance (NMR) spectroscopy has been employed to evaluate the formation of substance P carbamate in aqueous solution. Equilibration of substance P with physiologically relevant concentrations of bicarbonate (2.50 x 10(-2) mol.dm-3) at pH 7.00 generated a new multiplet signal centred at 4.13 ppm in its NMR spectrum, characteristic of the alpha-proton of peptide carbamate species. High-field 1H NMR spectroscopy also demonstrated that the model dipeptide, Arg-Gly, formed a carbamate in neutral aqueous solutions containing 2.50 x 10(-2) mol.dm-3 HCO3-. The physiological significance of these results is discussed in view of the central roles of vasoactive neuropeptides in human joint diseases and the hypercapnic environment of the inflamed rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1993

Monoarthritis in the rat knee induces bilateral and time-dependent changes in substance P and calcitonin gene-related peptide immunoreactivity in the spinal cord.

Bilateral changes in the spinal cord and dorsal root ganglion content of the sensory peptides substance P and calcitonin gene-related peptide have been previously reported in animal models of arthritis which affect many joints within the body. The central nervous system has been implicated in the symmetry of joint involvement in human rheumatoid arthritis. We aimed to determine whether unilateral inflammation of the knee joint can also induce bilateral changes in the spinal cord. We have induced a monoarthritis in the knee joint of the rat and used quantitative immunocytochemistry to look at changes of these peptides in the dorsal horn of the spinal cord and the dorsal root ganglia. Furthermore we have examined the responses during the acute (three days) and the chronic (21 days) phases of the model. The data show that in the acute phase of the monoarthritis there is both an ipsilateral and contralateral response which increases the immunoreactive substance P and calcitonin gene-related peptide in the L4 level of the dorsal horn of the spinal cord. In the chronic phase of the monoarthritis, the contralateral side of the dorsal horn returned to control values whilst the ipsilateral side showed reduced amounts of immunoreactive substance P and calcitonin gene-related peptide compared to controls. We propose that the acute response, at three days, to unilateral inflammation is appropriate and has evolved to protect an organism against the original insult ipsilaterally, and the possibility of subsequent insult contralaterally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of calcitonin gene-related peptide on formation of intra-articular oedema by inflammatory mediators.

1. The temporal and quantitative effects of inflammatory mediators on plasma extravasation in the rat knee were investigated by use of a perfusion technique. 2. Intra-articular perfusion of substance P (SP), bradykinin or histamine over a 5 min test period produced rapid-onset and prolonged plasma extravasation in a dose-dependent fashion. The rank order of potency was bradykinin greater than SP greater than histamine. 3. Calcitonin gene-related peptide (CGRP) did not induce plasma extravasation but enhanced substance P-induced plasma extravasation in a dose-dependent fashion. A 5 min co-perfusion of the two agents produced short-term enhancement lasting 10 min while continuous co-perfusion produced enhancement for the duration of the perfusion. 4. A 5 min perfusion of CGRP enhanced plasma extravasation when co-perfused with bradykinin but not histamine. However, when CGRP and histamine were continuously co-perfused over a 20 min test period, an enhanced response was apparent. 5. The results indicate that intra-articular perfusion of CGRP enhances synovial plasma extravasation induced by agents that increase vascular permeability, but suggest that the response is not uniform and is critically dependent on the duration of perfusion within the joint.

Animals↗
PubMed1992

Immune complexes in ankylosing spondylitis.

Immune complexes have been reported in ankylosing spondylitis (AS) and may implicate infectious agents. Serum samples from 49 patients with AS were assayed for immune complexes by polyethylene glycol precipitation, followed by radial immunodiffusion and pepsinogen binding immunoassay. Both methods showed increases in IgA containing immune complexes, which correlated with serum IgA and with IgA rheumatoid factor concentrations, but did not show increases in other immune complex components. Increased immune complexes were associated with peripheral joint synovitis, but showed no correlation with other clinical or laboratory indices of disease activity. Immune complexes from nine AS serum samples and one AS synovial fluid were electrophoretically separated then probed with anti-Klebsiella pneumoniae, but AS specific antigens were not identified. This study did not suggest a major role for immune complexes in AS without peripheral disease, nor provide serological evidence for the involvement of klebsiella antigens.

Antigen-Antibody Complex↗
PubMed1992

Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis.

The neuropeptide substance P is found in perivascular and free unmyelinated nerve fibres in human synovial tissue. Quantitative receptor autoradiography was used to show specific, high affinity (Kd = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (Bmax = 27.8 (7.9) amol/mm2) binding sites for substance P Bolton Hunter-labelled with iodine-125 localised to vascular endothelial cells in human synovial tissue. The binding could be saturated, was reversible, and was dependent on the magnesium concentration. Unlabelled substance P and neurokinin A competitively inhibited specific binding with 50% inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively. Neurokinin B (mumol/l) and calcitonin gene related peptide (1 mumol/l) did not inhibit binding. These binding sites show characteristics of the neurokinin 1 tachykinin receptor subtype. This provides further evidence that substance P may play a part in the vascular control of human synovium and may influence inflammatory processes in joints.

Adult↗
PubMed1992

Localization of the enzyme neutral endopeptidase to the human synovium.

Neuropeptides, contained within sensory nerve fibers in the synovium, are present in inflammatory joint fluids. The potency of these peptides in vitro has led to the hypothesis that enzyme degradation systems are operative in vivo. To address this question we localized neutral endopeptidase (NEP; EC 3.4.24.11) in human synovium. The normal human synovium failed to show any immunoreactivity for NEP. In the disease groups there was intense staining of cells surrounding blood vessels. Our data are consistent with the hypothesis that a proportion of synovial fibroblasts are the major source of this enzyme in the arthritic joint.

Adult↗
PubMed1990

Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis.

By means of antisera to cytoplasmic components of nerve fibres and neuropeptides which are known to be present in sensory or sympathetic nerves we have examined the distribution of both total and different types of nerve fibres in normal and inflamed human synovial tissue. Samples of synovia were obtained at surgery from five normal and five rheumatoid patients (age range 10-77 years). In order to map the overall neural innervation of the synovium, antiserum to the general neuronal marker protein gene product 9.5 was employed. Substance P and calcitonin gene-related peptide antisera were employed to identify sensory fibres and antisera to the C-flanking peptide of neuropeptide Y to distinguish sympathetic nerves. In normal synovium protein gene product 9.5-immunoreactive fibres were numerous, in particular, the vasculature was densely innervated. Free protein gene product 9.5-immunoreactive fibres were less numerous but were present in all synovia examined, and in many cases these extended to the intimal layer. Neuropeptide immunostaining was predominantly found in perivascular networks. Fibres immunoreactive for the C-flanking peptide of neuropeptide Y were exclusively located around blood vessels whereas free fibres were immunoreactive for substance P or calcitonin gene-related peptide. As with free protein gene product 9.5-immunoreactive fibres, fibres expressing substance P or calcitonin gene-related peptide immunoreactivity were often seen in the intimal cell layer. In rheumatoid arthritis a similar innervation to that seen in normal synovium was apparent in the deep tissue but fibres immunoreactive for protein gene product 9.5, the C-flanking peptide of neuropeptide Y, substance P or calcitonin gene-related peptide were not visible in the more superficial tissues or the intimal cell layer. In addition, immunostaining of neuropeptides in the deep tissue was weaker in the diseased tissues than in normal controls. The data unequivocally demonstrate that synovial tissues are richly innervated and confirm the presence of both sensory and sympathetic nerves. The absence of nerves which innervate the superficial synovium in rheumatoid arthritis might suggest that there is increased release of substance P, calcitonin gene-related peptide and the C-flanking peptide of neuropeptide Y, reducing the stores in the nerves to levels below that detectable by immunocytochemistry. However, since protein gene product 9.5-immunoreactive nerves were not seen in the inflamed tissue it is probable that synovial growth outflanks neural growth and consequently as the disease progresses neural structures become restricted to deeper tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Specific antibody response to the mycobacterial 65 kDa stress protein in ankylosing spondylitis and rheumatoid arthritis.

Immune responses to conserved, immunogenic homologues of the mycobacterial 65 kDa stress protein (SP65) have been implicated in inflammatory arthritis. Serum anti-SP65 was measured in AS, RA and healthy controls using an indirect enzyme immunoassay with recombinant SP65. IgA anti-SP65 was elevated in 19 of 59 AS patients, but the elevation in median level was not statistically significant. Anti-SP65 of all isotypes was increased in RA, but achieved significance (P less than 0.01) for IgA only. Adjusting specific antibody results for elevations in total serum Ig levels reduced AS and RA anti-SP65 to near normal levels, suggesting that a major component of the increased anti-SP65 may be secondary to polyclonal activation.

Antibodies↗