Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lyme disease, a tick-transmitted spirochetal illness caused by Borrelia burgdorferi, usually begins with a characteristic erythema chronicum migrans accompanied by flu-like symptoms. This phase may later be followed by meningitis, neuritis, carditis or arthritis. Congenital abnormalities due to maternal infection during pregnancy have been described. We report on a case of a 36-year old V gravida III para. After a normal pregnancy and a Cesarean section the patient developed postpartal an acute Lyme arthritis.
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PMID:[Manifestation of Lyme arthritis in the puerperal period]. 797 2

Several lines of circumstantial evidence support the assumption that protein kinase C (PKC) activation together with elevated levels of cytosolic Ca++ are necessary for T-cell activation and proliferation in response to a physiological stimulus, i.e., MHC class II restricted antigen presentation. By using a potent, cell-permeable and selective inhibitor of PKC, Ro 32-0432, we have tested this hypothesis. Ro 32-0432 inhibits interleukin-2 (IL-2) secretion, IL-2 receptor expression in, and proliferation of, peripheral human T-cells stimulated with phorbol ester together with phytohemagglutin or anti-CD3, but does not inhibit IL-2 induced proliferation in cells already stimulated to express IL-2 receptors. Proliferation of the influenza peptide antigen HA 307-319-specific human T-cell clone (HA27) after exposure to antigen-pulsed autologous presenting cells was also inhibited by Ro 32-0432. Oral administration of Ro 32-0432 inhibited subsequent phorbol ester-induced edema in rats demonstrating the systemic efficacy of the compound to inhibit PKC-driven responses. Induction of more physiologically T-cell driven responses such as host vs. graft responses and the secondary paw swelling in adjuvant-induced arthritis were also inhibited by Ro 32-0432. These data demonstrate the crucial role for PKC in T-cell activation and that selective p.o. bioavailable PKC inhibitors are efficacious in preventing T-cell driven chronic inflammatory responses in vivo. Inhibition of PKC represents an important mechanistic approach to prevent T-cell activation and compounds of this class may have important therapeutic applicability to chronic inflammatory and autoimmune diseases.
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PMID:Ro 32-0432, a selective and orally active inhibitor of protein kinase C prevents T-cell activation. 811 6

Eight HLA B27-restricted influenza A virus nucleoprotein 383-391-specific cytotoxic T lymphocyte (CTL) clones were obtained from three unrelated donors following natural infection. T cell receptor (TcR) usage was studied using the "anchored" polymerase chain reaction. TcR alpha-chain usage was restricted with three predominant V alpha (V alpha 12.1, 14.1, 22) and two predominant J alpha segments. beta-chain variable-region usage was also conserved, with V beta 7 being used by five clones despite contributing less than 2% of peripheral blood lymphocyte V beta sequences of one individual studied. The TcR beta-chain junctional region was highly conserved even between CTL clones from unrelated individuals, with a negatively charged amino acid, contributed to by N-region addition, encoded at position 97 in all but two clones. This study shows that peptide-specific HLA B27-restricted CTL following influenza virus infection use very similar TcR and, when considered with previous studies, suggests a pattern of TcR conservation for major histocompatibility complex class I-restricted responses. No difference in TcR usage was detected between one healthy donor and two with HLA B27-associated arthritis.
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PMID:Conservation of T cell receptor usage by HLA B27-restricted influenza-specific cytotoxic T lymphocytes suggests a general pattern for antigen-specific major histocompatibility complex class I-restricted responses. 839 85

Since 1976 intravesical instillation of bacillus Calmette-Guerin (BCG) has been used after surgical treatment of bladder cancer. Local side effects like cystitis are common, but a small share of the patients develop influenza-like symptoms, arthritis and other complications. We describe two patients with arthritis.
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PMID:[Arthritis after BCG treatment of bladder cancer. A rare complication]. 901 76

The role of viral infections in the aetiology of acute and chronic arthritides of childhood is incompletely understood. The fact that some viruses cause acute arthritis is certain, although in most instances of presumed viral arthritis no agent is identified. The associations of viruses with diseases such as juvenile chronic arthritis (JCA) are limited, and have been difficult to prove with certainty. Rubella, parvovirus B19 and influenza AH2N2 have been shown by culture, serology or epidemiology to be related to at least some cases of JCA in some studies, but not in others. A rationale for pursuing investigations of viral aetiology of chronic arthritis is discussed, and a strategy involving early disease detection and close collaboration between clinicians and scientists is proposed.
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PMID:Viruses and childhood arthritis. 918 31

Human histocompatibility leukocyte antigen B27 is highly associated with the rheumatic diseases termed spondyloarthropathies, but the mechanism is not known. B27 transgenic rats develop a spontaneous disease resembling the human spondyloarthropathies that includes arthritis and colitis. To investigate whether this disease requires the binding of specific peptides to B27, we made a minigene construct in which a peptide from influenza nucleoprotein, NP383-391 (SRYWAIRTR), which binds B27 with high affinity, is targeted directly to the ER by the signal peptide of the adenovirus E3/gp19 protein. Rats transgenic for this minigene, NP1, were made and bred with B27 rats. The production of the NP383-391 peptide in B27(+)NP1(+) rats was confirmed immunologically and by mass spectrometry. The NP1 product displaced approximately 90% of the 3H-Arg-labeled endogenous peptide fraction in B27(+)NP1(+) spleen cells. Male B27(+)NP1(+) rats had a significantly reduced prevalence of arthritis, compared with B27(+)NP- males or B27(+) males with a control construct, NP2, whereas colitis was not significantly affected by the NP1 transgene. These findings support the hypothesis that B27-related arthritis requires binding of a specific peptide or set of peptides to B27, and they demonstrate a method for efficient transgenic targeting of peptides to the ER.
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PMID:The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats. 1245 60

The association of HLA-B27 with certain forms of arthritis implies a role for MHC class I-restricted T cells in the arthritic process. Our aim was to study CD8(+) T cell responses towards specific antigens localized in joint tissue. Known determinants were introduced into chondrocytes of transgenic (TG) mice, under the control of the cis-regulatory sequences of the human type II collagen gene (COL2A1). Two Escherichia coli beta-galactosidase (beta-gal)-expressing lines were derived (CIIL73 and CIIL64) as well as two lines (CIINP) expressing influenza A virus nucleoprotein (NP). Expression of the antigens could be demonstrated in cartilaginous tissues. The TG lines showed variable degrees of responsiveness towards the transgene-introduced antigens; whilst 75% of CIIL73 mice had an impaired cytotoxic T lymphocyte (CTL) response towards beta-gal, the response in CIIL64 mice was essentially normal. However, both lines displayed normal proliferative and antibody responses to beta-gal. A reduced CTL response was seen to NP in the CIINP lines in approximately 65% of the animals. In spite of the persistence of T cell responses to the transgene antigens in these lines, induction of CTL responses alone has so far failed to induce clinical signs of arthritis. Interestingly, some animals expressing beta-gal were susceptible to arthritis following challenge with type II collagen alone, whilst their non-TG littermates and TG mice from other lines remained unaffected. As beta-gal is expressed by E. coli, a component of the normal gut flora, this suggests a possible role for gut-derived immune responses. We believe these lines could form the basis of a model for studying links between intestinal inflammation and arthritis.
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PMID:Chondrocyte antigen expression, immune response and susceptibility to arthritis. 1128 81

It has been recently reported that intralesional therapy with alpha interferon 2B resulted in significant improvement of both objective and subjective complaints (penile curvature, pain, plaque size, sexual function) associated with Peyronie's disease. Vitamin E, with its antioxidant properties, may play a role in reducing the inflammatory response. This study was designed to determine the safety and effectiveness of a high dose of alpha INF-2B injected weekly into the Peyronie's plaque combined with oral Vitamin E therapy. Twenty-nine patients with Peyronie's disease were evaluated with penile duplex Doppler for degree of penile curvature, deformity, and plaque size both prior to and after treatment. Each patient then received 4.0 x 10(6) units of alpha INF-2B in 10 cc of normal saline after appropriate local anesthesia. Injections were given once per week directly into the Peyronie's plaque for a period of 10 weeks. Patients also received 400 units of Vitamin E by mouth twice a day. Subjective data was obtained via a questionnaire prior to and at the conclusion of the study. Preliminary results demonstrated improvement of penile curvature in 39% of patients, with one patient experiencing complete resolution. Significant decreases in plaque sizes were noted in 11 of these patients, with softening of the plaques noted in all patients completing the study. Seven patients dropped out of the study prior to completing the 10 weeks: three with severe disease proceeded to surgery, two were lost to follow-up, one had exascerbation of his arthritis symptoms, and one quit secondary to flu-like symptoms. Subjective data from questionnaires revealed improvement in sexual function in those men with decreased curvature and plaque size. Weekly intralesional injections with 4.0 x 10(6) units improved plaque consistency and decreased curvature and plaque size (P < 0.5). Overall subjective sexual performance was reportedly improved. Increased dosage of alpha INF-2B resulted in increased severity of flu-like symptoms when compared to the lower (1 x 10(6) units) biweekly dosage. No significant difference was noted with the addition of oral Vitamin E therapy.
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PMID:Combined intralesional interferon alpha 2B and oral vitamin E in the treatment of Peyronie's disease. 1151 19

The human leukocyte antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides collectively known as the spondyloarthritides. We have set out to define the natural immunological function of HLA-B27, and then to apply this knowledge to understand its pathogenic role. Human leukocyte antigen class 1 molecules bind antigenic peptides for cell surface presentation to cytotoxic T lymphocytes. HLA-B27 binds and presents peptides from influenza, HIV, Epstein-Barr virus, and other viruses. This leads to vigorous and specific cytotoxic T lymphocyte responses, which play an important role in the body's immune response to these viruses. HLA-B27 thus carries out its natural function highly effectively. Although many theories have been proposed to explain the role of HLA-B27 in the pathogenesis of spondyloarthropathy, we favour those postulating that the pathogenic role of HLA-B27 stems from its natural function. For example, the 'arthritogenic' peptide hypothesis suggests that disease results from the ability of HLA-B27 to bind a unique peptide or a set of antigenic peptides. Additionally, a number of lines of evidence from our laboratory and other laboratories have suggested that HLA-B27 has unusual cell biology. We have recently demonstrated that HLA-B27 is capable of forming disulfide-bonded homodimers. These homodimers are expressed on the cell surface and are ligands for a number of natural killer and related immunoreceptors, expressed on a variety of cell types including natural killer cells, T lymphocytes and B lymphocytes, and members of the monocyte/macrophage lineage. We are currently investigating the possibility that such interactions could be involved in disease pathogenesis.
Arthritis Res 2002
PMID:HLA-B27: natural function and pathogenic role in spondyloarthritis. 1211 Jan 34

The human major histocompatibility complex (MHC) class I allele HLA-B27 is strongly associated with seronegative spondyloarthropathies including ankylosing spondylitis and reactive arthritis. Although of unknown aetiology, one hypothesis suggests that a cytotoxic T cell (CTL) response against a self-antigen at sites of inflammation, such as entheses or joints may be involved. The chondrocyte is one of the major specialized cell types found both in articular cartilage and cartilaginous entheses and therefore is a possible source of such an antigen. CTL recognition of these cells is a potential mechanism for inflammation and cartilage damage, both through direct lysis of chondrocytes and the secretion of pro-inflammatory cytokines such as tumour necrosis factor and interferon-gamma (IFN-gamma). We test the feasibility of this hypothesis by examining the ability of chondrocytes to present antigen to CTL in vitro. Chondrocytes isolated from the ribcages of mice did not constitutively express detectable levels of MHC class I by fluorescence-activated cell sorting analysis. In addition, they were resistant to lysis by alloreactive and influenza A virus nucleoprotein (NP)-specific CTL. However, treatment of chondrocytes with IFN-gamma up-regulated MHC class I expression and rendered the cells susceptible to lysis by CTL. Similarly, IFN-gamma-treated chondrocytes infected with influenza A virus were recognized by NP-specific CTL, though with variable efficiency. Thus, we suggest that under certain circumstances CTL-mediated lysis of chondrocytes is potentially a potent mechanism for cartilage damage in vivo, but that low levels of MHC class I on healthy chondrocytes protects from immune recognition in health.
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PMID:Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions. 1270 12


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