Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16020901 Sjögren's syndrome associated with chronic hepatitis C, severe thrombocytopenia, hypertro 2005 Jun A 74-year-old woman with Sjögren's syndrome and chronic hepatitis C (CHC) was admitted to our hospital in October 2003 for treatment of diabetes mellitus. She had the past history of recurrent thrombocytopenia, which was proven to be due to peripheral destruction. Although she had been diagnosed with hypertrophic cardiomyopathy (HCM) for 2 years, she had never felt palpitation. She suddenly died probably of fatal arrhythmia related to HCM during the last hospitalization. Although hepatitis C virus (HCV) infection has been associated with Sjögren's syndrome, thrombocytopenia, HCM, and diabetes mellitus, all these diseases rarely occur in a single patient. It will be necessary to identify similar cases to elucidate the etiopathogenesis of extra-hepatic manifestations of HCV infection.
15692983 Novel role of CD40 in Fas-dependent apoptosis of cultured salivary epithelial cells from p 2005 Feb OBJECTIVE: To determine the role of Fas and CD40 in the molecular mechanism of salivary epithelial cell death in Sjogren's syndrome (SS). METHODS: The expression of Fas and CD40 in SS salivary epithelial cells was analyzed by flow cytometry. Induction of apoptosis with anti-Fas and/or anti-CD40 monoclonal antibodies (mAb) was examined by morphologic analysis, DNA fragmentation, and TUNEL assay. Expression of c-FLIP, Fas-associated phosphatase 1, FADD, Bcl-2, Bcl-x(L), and Bcl-x(S) was determined by Western blot analysis. RESULTS: Expression of Fas and CD40 was significantly higher in SS salivary epithelial cells than in normal cells after interferon-gamma (IFNgamma) stimulation (P < 0.001 for both Fas and CD40). Although neither anti-Fas (CH11) nor anti-CD40 mAb alone could induce typical apoptosis, the two together and preincubation with IFNgamma efficiently induced apoptosis in SS salivary epithelial cells. This apoptosis was almost completely blocked by neutralizing anti-Fas mAb (ZB4), whereas an antagonistic mAb to CD40 (ch5D12) partially inhibited anti-Fas/anti-CD40-induced apoptosis. Also, c-FLIP, an important inhibitory molecule in the Fas death pathway, was strongly expressed in SS salivary epithelial cells, but its expression was down-regulated at the protein level by anti-CD40 mAb. CONCLUSION: CD40 signals promote Fas-dependent death of SS salivary epithelial cells by down-regulating c-FLIP expression. The presence of c-FLIP in these cells may explain their resistance to undergoing apoptosis in response to either anti-Fas or anti-CD40 mAb, despite their surface expression of both proteins. These findings suggest that SS salivary epithelial cell death requires the cooperation of both Fas and CD40.
16496080 Primary biliary cirrhosis (PBC)-CREST overlap syndrome with coexistence of Sjögren's synd 2007 Apr Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, a limited form of systemic sclerosis, is sometimes complicated by primary biliary cirrhosis (PBC). A 52- and 61-year-old Japanese woman with PBC-CREST overlap syndrome accompanied by Sjögren's syndrome, and Hashimoto's thyroiditis, and Graves' disease, respectively, are reported. They had suffered from Raynaud's phenomena, sclerodactyly, morning stiffness, arthralgia, and sicca symptoms during these several years. They exhibited an increased level of alkaline phosphatase, gamma-glutamyl transpeptidase, positive antibodies against mitochondria and centromere, and hyperglobulinemia without any cholestatic symptoms. Histological findings from liver biopsy specimens were consistent with those of PBC. Clinically, they were diagnosed as both asymptomatic PBC and incomplete CREST syndrome. Their human leukocyte antigen typing showed both DR4 and DR8 positive. The association of the four autoimmune conditions is clinically and etiologically important. Although a combination of these diseases is rare, it is of importance to keep in mind that various autoimmune diseases could occur simultaneously. Of critical importance is that an active diagnostic attitude towards them is admirable, and that early diagnosis and therapy are needed.
16382698 Low levels of heat shock proteins-60 and -65 autoantibodies in Sjögren's syndrome. 2005 Dec BACKGROUND: Heat shock proteins are highly conserved immunodominant antigens found in various species. Humoral immune responses to mycobacterial HSP65 and human HSP60 have been established in a number of human autoimmune diseases. OBJECTIVE: To assess the prevalence of antibodies to HSP60 kDa and HSP65 kDa in patients with Sjögren's syndrome as compared to normal subjects. METHODS: Thirty-seven patients with SS were compared with normal controls. The antibodies against human HSP60 were measured by the Anti-Human (IgG/IgM) HSP60 ELISA kit. IgGs and IgMs to mycobacterial HSP65 were determined using an enzyme-linked immunosorbent assay with mycobacterial recombinant HSP65 antigens. RESULTS: The levels of both anti-HSP60 and -HSP65 were lower in patients compared with controls. IgG autoantibodies to HSP60 were significantly different between groups: 162 +/- 55.1 ng/ml in controls versus 112.3 +/- 30.6 ng/ml in SS patients (P < 0.001). The levels among controls of anti-HSP65 IgM isotype were also significantly higher than among the SS patients: 111.6 +/- 33.4 U/ml versus 96.1 +/- 8.9 U/ml (P= 0.01). CONCLUSIONS: The results of the present study show that the levels of different isotypes of anti- HSP60 and HSP65 antibodies were lower in patients with SS than in normal subjects. Additional studies in larger patient populations are required to evaluate the prevalence of these autoantibodies in SS patients.
16086064 [Clinical analysis of primary biliary cirrhosis: a report of 42 cases]. 2005 Aug 18 OBJECTIVE: To study the clinical features of primary biliary cirrhosis (PBC) in order to facilitate cognition of the disease. METHODS: Clinical data of 42 patients clinically and/or histologically diagnosed with PBC were reviewed. Anti mitochondrial antibody (AMA) negative/positive patients as well as the patients who were/were not associated with Sjogren Syndrome (SS) were compared in terms of clinical, biochemical and immunological features. RESULTS: Among the 42 patients, 78.6% (33/42) of the cases were females; the mean age at diagnosis was (61.1+/-10.8) years. The most frequent symptoms were fatigue. Serum alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (gamma-GT) and total bile acid (TBA) levels were markedly elevated in the majority of the patients, whereas ALT and AST levels were mildly to moderately elevated. Thirty-one patients had a total bilirubin (TBil) level above normal. The levels of TBil and prothrombin time had positive correlationship with years of the course (P=0.000, r=0.696; P=0.005, r=0.424), whereas serum albumin level had negative correlationship with years of the course (P=0.002, r=-0.462). Thirty-seven patients had elevated serum IgM and 34 patients were AMA/AMA-M(2) positive. AMA negative and AMA positive patients were similar in terms of clinical manifestations and liver biochemistries findings. Serum IgM and IgA levels were significantly lower, whereas total cholesterol level was higher in AMA negative patients when compared with AMA positive cases. Fifteen cases were associated with SS, which were similar in terms of clinical, biochemical and immunological features when compared with the PBC patients were not associated with SS. CONCLUSION: PBC is mostly found in middle aged and old women. Elevated serum ALP, TBA and gamma-GT levels together with positive AMA/AMA-M(2) can help to diagnose PBC. AMA negative PBC patients are characterized by relatively lower serum IgM and IgA levels and higher total cholesterol level. PBC patients who are associated with SS have not substantial differences in the clinical, biochemical and immunological spectra of the disease.
15710261 [Sjögren's syndrome with autonomic failure and epilepsy]. 2005 Feb INTRODUCTION: Primary Sjogren syndrome is considered as the most frequent connective tissue disease. Neurological complications may affect the peripheral nervous system and to lesser extent the central nervous system. Autonomic system nervous dysfunction and epilepsy have been rarely reported. EXEGESIS: We present on case of Sjogren's syndrome with epilepsy and autonomic nervous system dysfunction. The epilepsia respond to valproate. CONCLUSION: Autoimmune investigations for Sjogren's syndrome should be initiated in any patient presenting with unexplained neurologic manifestations.
15381790 Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with 2005 Jan OBJECTIVE: To analyse the prevalence and clinical significance of hypocomplementaemia in a large series of patients with primary Sjogren's syndrome (SS), focusing on the association of low complement levels with clinical manifestations, immunological features, lymphoproliferative disorders and mortality. METHODS: Complement determinations (C3 and C4 levels, CH50 activity) were made in 336 consecutive patients with primary SS (313 women and 23 men, mean age 58.5 yr). We also analysed complement levels in 46 patients with SS associated with hepatitis C virus (HCV) infection and 184 with HCV-related cryoglobulinaemia as control groups. RESULTS: Hypocomplementaemia was detected in 81 (24%) of patients with primary SS, low CH50 being detected in 51 (15%), low C3 values in 42 (12%) and low C4 values in 39 (12%). In the multivariate analysis, patients with low C4 levels showed a higher prevalence of peripheral neuropathy, cutaneous vasculitis, RF, cryoglobulins and lymphoma compared with those with normal C4 levels. The analysis of the 218 SS patients followed prospectively since 1994 showed a lower probability of survival in patients with hypocomplementaemia (with low C3, C4 or CH50 levels) at protocol entry. SS-HCV patients presented a higher frequency of hypocomplementaemia than patients with primary SS (76 vs 24%, P<0.001); nine (20%) of these patients had persistent, unquantifiable complement levels. CONCLUSION: Hypocomplementaemia is closely associated with systemic expression and adverse outcomes (lymphoma development and death) in patients with primary SS. Our results support the inclusion of complement determination at diagnosis as a predictor of the outcome of patients with primary SS and its routine determination in the clinical follow-up.
16728458 Progression of salivary gland dysfunction in patients with Sjogren's syndrome. 2007 Jan BACKGROUND: Salivary gland dysfunction is one of the key manifestations of Sjögren's syndrome. OBJECTIVES: (1) To assess prospectively loss of function of individual salivary glands in patients with primary and secondary Sjögren's syndrome in relation to disease duration and use of immunomodulatory drugs. (2) To study changes in sialochemical and laboratory values and subjective complaints over time. METHODS: 60 patients with Sjögren's syndrome were included in this study. Whole and gland-specific saliva (parotid and submandibular/sublingual (SM/SL)), samples were collected at baseline and after a mean of 3.6 (SD 2.3) years of follow-up. Disease duration was recorded for all patients. RESULTS: Patients with Sjögren's syndrome with short disease duration had significantly higher stimulated flow rates at baseline than those with longer disease duration (p<0.05). When compared with healthy controls, the decrease in SM/SL flow rates at baseline was more prominent than that in parotid flow rates (p<0.05). Over time, there was a significant further decrease of stimulated flow rates, especially of the parotid gland, accompanied by increasing problems with swallowing dry food (p<0.05). The decrease was independent of the use of corticosteroids or disease-modifying antirheumatic drugs (DMARDs). Sialochemical variables remained stable. CONCLUSIONS: Early Sjögren's syndrome is characterised by a decreased salivary gland function (parotis>SM/SL), which shows a further decrease over time, regardless of the use of DMARDs or steroids. Patients with Sjögren's syndrome with longer disease duration are characterised by severely reduced secretions of both the parotid and SM/SL glands. These observations are relevant for identifying patients who would most likely benefit from intervention treatment.
17106166 Mixed connective tissue disease associated with MPO-ANCA-positive polyangiitis. 2006 The patient was a 42-year-old woman diagnosed as having MCTD and Sjögren's syndrome in 1989, and who was taking oral prednisolone. Proteinuria and microscopic hematuria were pointed out for the first time in December 2004. She was referred to our hospital because of massive hemoptysis. Advanced renal failure, anemia and pulmonary alveolar hemorrhage were diagnosed on admission. She was positive for serum MPO-ANCA. The patient was started on a therapy that included steroids, cyclophosphamide and plasmapheresis. However, her respiratory condition was untreatable and she died on the 16th day of hospitalization. The autopsy revealed alveolar hemorrhage in the lungs and crescentic glomerulonephritis. This patient was considered as a rare case of MCTD associated with MPO-ANCA-positive microscopic polyangiitis.
16014676 Basal lamina disorganisation of the acini and ducts of labial salivary glands from patient 2006 Feb OBJECTIVE: To study the expression of laminin and type IV collagen as biomarkers of the organisation of the basal lamina of acini and ducts in labial salivary glands from patients with Sjögren's syndrome, and to relate this organisation to inflammatory cell invasion of acini and ducts. METHODS: Immunohistochemistry for laminin and type IV collagen was undertaken on sections of labial salivary glands from 30 patients with Sjögren's syndrome, 10 control subjects, and 24 controls with chronic sialoadenitis. Immunohistochemistry reaction, alterations to cell morphology, and the presence of inflammatory cells in acini and ducts were evaluated and scored using a semiquantitative method. RESULTS: Changes in the expression of laminin and type IV collagen in the basal lamina of acini and ducts of labial salivary glands from patients with Sjögren's syndrome were more pronounced than in labial salivary glands from control groups. A remarkable characteristic was the disorganisation of the basal lamina in the labial salivary glands in Sjögren's syndrome. The pattern of immunoreactivity of the basal lamina of other structures (for example, blood vessels) did not change. In Sjögren's syndrome, invasion of cytotoxic T lymphocytes was only observed in acini and ducts which had a disorganised basal lamina. CONCLUSIONS: The high state of disorganisation of the basal lamina of acini and ducts could allow invasion of cytotoxic T lymphocytes in Sjögren's syndrome, contributing to cell death and ductal hyperplasia.
15652773 Hepatitis C virus, Sjögren's syndrome and B-cell lymphoma: linking infection, autoimmunit 2005 Jan An increased prevalence of hematologic malignancies is often described in patients with Sjögren's syndrome (SS). Viruses have been proposed as possible etiologic or triggering agents of systemic autoimmune diseases (SADs), with hepatitis C virus (HCV) being one of the viruses most frequently associated with autoimmune features and with systemic autoimmune diseases such as mixed cryoglobulinemia or SS. Moreover, the association between HCV infection and hematologic malignancies, mainly non-Hodgkin's lymphoma (NHL), is supported by several studies. For these reasons, the recognized association of specific systemic autoimmune diseases (mainly SS and mixed cryoglobulinemia) with HCV infection, added to the possible evolution of any one of these entities into a B-cell NHL, suggests the possibility of a close relationship among SS, HCV and B-cell lymphoproliferative disorders, especially in patients with type II mixed cryoglobulinemia.
16378833 Increase in platelet non-integrin type I collagen receptor in patients with systemic scler 2006 Microvascular injury is one of the major pathogenetic processes involved in systemic sclerosis (SSc). Interaction of the platelet types I and III collagen receptors with their respective ligand in the exposed subendothelial stroma as a result of ongoing microvascular injury in SSc patients results in platelet activation and aggregation with the release of mediators, which contribute to vascular damage and inflammation. We have found that there is a twofold increase in radiolabeled type I collagen binding to washed platelets from patients with SSc compared to platelets obtained from normal volunteers. Western blot analyses showed that the non-integrin platelet type I collagen receptor protein (65 kDa) is increased dramatically in lysates of platelet from patients with SSc. However, the integrin (alpha(2)beta(1)) and other non-integrin receptors such as glycoprotein VI, glycoprotein IV, and the platelet receptor for type III collagen remain unchanged. In addition, platelet lysates from rheumatic disease controls (rheumatoid arthritis, osteoarthritis, gout, and systemic lupus erythematosus) do not show any significant increases. There is no nitrotyrosylation on 65 kDa in patients with SSc compared to controls, suggesting this might also contribute to binding of CI to the 65-kDa CIR. These results suggest that there is a specific increase in the number of platelet type I collagen receptors in SSc patient's platelets. In addition, the activity of nitric oxide synthase is decreased in patients' platelet lysates compared to controls. The increase in platelet expression of the 65-kDa non-integrin platelet type I collagen receptor may explain the enhanced aggregation of platelets from patients with SSc to CI in vitro and microvascular thrombosis in the disease in vivo.
17107772 The pro-inflammatory oxidant hypochlorous acid induces Bax-dependent mitochondrial permeab 2007 Apr At sites of chronic inflammation, such as in the inflamed rheumatoid joint, activated neutrophils release hydrogen peroxide (H(2)O(2)) and the enzyme myeloperoxidase to catalyse the formation of hypochlorous acid (HOCl). 3-chlorotyrosine, a marker of HOCl in vivo, has been observed in synovial fluid proteins from rheumatoid arthritis patients. However the mechanisms of HOCl-induced cytotxicity are unknown. We determined the molecular mechanisms by which HOCl induced cell death in human mesenchymal progenitor cells (MPCs) differentiated into a chondrocytic phenotype as a model of human cartilage cells and show that HOCl induced rapid Bax conformational change, mitochondrial permeability and release of intra-mitochondrial pro-apoptotic proteins which resulted in nuclear translocation of AIF and EndoG. siRNA-mediated knockdown of Bax substantially prevented mitochondrial permeability, release of intra-mitochondrial pro-apoptotic proteins. Cell death was inhibited by siRNA-mediated knockdown of Bax, AIF or EndoG. Although we observed several biochemical markers of apoptosis, caspase activation was not detected either by western blotting, fluorescence activity assays or by using caspase inhibitors to inhibit cell death. This was further supported by findings that (1) in vitro exposure of recombinant human caspases to HOCl caused significant inhibition of caspase activity and (2) the addition of HOCl to staurosporine-treated MPCs inhibited the activity of cellular caspases. Our results show for the first time that HOCl induced Bax-dependent mitochondrial permeability which led to cell death without caspase activity by processes involving AIF/EndoG-dependent pathways. Our study provides a novel insight into the potential mechanisms of cell death in the inflamed human joint.
16769661 Anti-Jo-1 antibody positive polymyositis--successful therapy with leflunomide. 2006 May Idiopathic inflammatory myopathies (IM), including dermatomyositis (DM) and polymyositis (PM), are a group of systemic rheumatologic diseases of unknown etiology characterized by chronic myositis. Antisynthetase antibodies such as the anti-Jo-1 antibody are known to be highly specific for inflammatory myopathies. Patients with this antibody frequently show a combination of symptoms including interstitial lung disease, fever, polyarthritis, myositis, Raynaud's phenomenon and "mechanic's hands". In the management of PM with anti-Jo-1 antibody, immunosuppressive agents are used to control the disease. Leflunomide is a new immunosuppressive drug recently introduced in the treatment of rheumatoid and psoriatic arthritis. Here, we report two cases of female patients with PM and anti-Jo-1 antibodies, who were successfully treated with leflunomide.
17146306 Postoperative cervical kyphosis after atlantoaxial fixation and cervical expansive laminop 2006 Dec Cervical kyphotic deformity is one of the well-known complications after atlantoaxial fixation or cervical expansive laminoplasty, but to our knowledge there is no information about postoperative cervical kyphosis after performing these operations simultaneously. The aims of this study were to evaluate the changes in the cervical alignment after simultaneous atlantoaxial fixation and cervical expansive laminoplasty, and to discuss the risk factors of this deformity. Five patients (1 man and 4 women) who underwent the simultaneous procedure were examined. Their mean age at surgery was 68.4+/-3.4 years, and the mean follow-up period was 30.8+/-9.5 months. Their underlying diseases were rheumatoid arthritis, and one of them had athetosis, too. On neutral lateral cervical radiographs, tangents were drawn to the inferior endplates of C2 to C5, respectively, and we measured the angles between C2 and C3, C3 and C4, C4 and C5, and C2 and C5 just after surgery and at the latest follow-up. The mean angles were 2.1, -1.9, 1.8, and 1.2 degrees, respectively, just after surgery; and 2.1, -3.5, -2.6, and -5.8 degrees, respectively, at the latest follow-up. Although the mean angle between C2 and 3 hardly changed postoperatively, the mean angle between C2 and C5 significantly decreased postoperatively. In summary, atlantoaxial fixation and cervical expansive laminoplasty may be an unsuitable combination because cervical kyphosis after the simultaneous procedure developed as a complication during the short-term follow-up.
17095227 Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kina 2007 Feb 1 The Type 1 PI3Kinases comprise a family of enzymes, which primarily phosphorylate PIP2 to give the second messenger PIP3, a key player in many intracellular signaling processes [Science, 2002, 296, 1655; Trends Pharmacol. Sci.2003, 24, 366]. Of the four type 1 PI3Ks, the gamma-isoform, which is expressed almost exclusively in leukocytes [Curr. Biol., 1997, 7, R470], is of particular interest with respect to its role in inflammatory diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) [Mol. Med. Today, 2000, 6, 347]. Investigation of a series of 4,6-disubstituted-4H-benzo[1,4]oxazin-3-ones has led to the identification of single-digit nanomolar inhibitors of PI3Kgamma, several of which had good cell based activity and were shown to be active in vivo in an aspectic peritonitis model of inflammatory cell migration.
17048276 Development of an anti-IL-17A auto-vaccine that prevents experimental auto-immune encephal 2006 Nov IL-17 has been associated with multiple inflammatory disorders such as rheumatoid arthritis, asthma and multiple sclerosis. As these diseases require long-term treatment we turned to an auto-vaccine strategy for IL-17 neutralization in vivo. Mouse IL-17A was covalently linked to ovalbumin and used to immunize C57BL/6 mice. This vaccine induced the production of antibodies that blocked IL-17A bioactivity in vitro but did not react with the other IL-17 isoforms, including IL-17F. As the half-life of the Ab titers after the last immunogen administration was approximately 4 months, the vaccine provides for long lasting and selective inhibition of IL-17A activity in vivo. A monoclonal Ab (mAb) derived from these mice showed the same specificity for IL-17A. To test the ability of the vaccine to confer protection against an IL-17-dependent disorder, SJL mice were vaccinated with IL-17-OVA and encephalomyelitis (EAE) was induced by proteolipid protein (PLP) peptide 139-151. Vaccinated mice were completely protected against the disease. The above-mentioned anti-IL-17A mAb also prevented EAE development. The absence of clinical symptoms contrasted with unaltered PLP-induced cytokine production in vitro and unmodified anti-PLP IgG titers and isotypes. These results suggest that an anti-IL-17A auto-vaccine offers new perspectives for therapy of autoimmune diseases.
16997584 MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a 2007 Feb OBJECTIVE: Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis. METHODS: Two immunoassays were developed: (1) the G1/G2 sandwich assay employing a monoclonal antibody (F-78) both as a capturing and a detecting antibody, and (2) the 342-G2 sandwich assay substituting the capturing antibody in the G1/G2 test with a monoclonal antibody, AF-28 recognizing the 342FFGVG neo-epitope generated by MMP cleavage. These assays were compared to the commercially available glycosaminoglycan (GAG) assay. RESULTS: In supernatants of Oncostatin M and Tumor Necrosis Factor alpha (OSM/TNFalpha) stimulated explants, high levels of G1/G2 fragments and GAGs were released in the initial phase (days 2-5), followed by low levels in the intermediate (days 9-12) and late phase (days 12-21). MMP-generated fragments were detected in the late phase only. In the presence of the general MMP inhibitor GM6001, 342-G2 was not detected, whereas the G1/G2 profile remained virtually unchanged. In patients with rheumatoid arthritis (RA), the release of G1/G2 molecules was decreased (27.3%), and that of the 342-G2 fragments increased compared to healthy controls (33.3%). CONCLUSION: The stimulation of bovine articular cartilage explants with OSM/TNFalpha released aggrecan fragments both in an MMP and non-MMP-mediated route. These immunoassays carry a potential as diagnostic tools for the quantitative assessment of the cartilage turnover in RA patients in addition to their utility in ex vivo explant cultures.
16987757 Transient exposure of fibroblast growth factor-2 induced proliferative but not destructive 2006 Fibroblast growth factor-2 (FGF-2) has the potential to regenerate damaged articular cartilage tissue due to its exerting anabolic effects on chondrocytes. However, FGF-2 is involved in pathogenesis of rheumatoid arthritis, where the joint is destructed. The study aims at clarifying the effects of FGF-2 on joints. When radiolabeled FGF-2 was injected into knee joints of C57Bl/10 mice, a transient binding was observed in the superficial and intermediate zones of the articular cartilage as well as in the synovium and perichondrium. An FGF-2 injection (5 microg) caused synovial hyperplasia adjacent to the articular cartilage on day 7, cartilage formation adjacent to the articular cartilage on day 14, and osteophyte on day 21. The intensity of safranin-O staining of the articular cartilage increased on day 14. These changes were dose-dependent. No destructive changes in the joints were observed. In a joint, transient exposure of FGF-2 caused proliferative changes, but not destructive changes.
16906330 Immunoregulatory role of endogenous catecholamines synthesized by immune cells. 2006 Aug 25 It has been well known that catecholamines (CAs) in the body, including norepinephrine (NE), epinephrine (E) and dopamine (DA), are synthesized and secreted by neurons and endocrine cells and mainly modulate visceral activities such as cardiovascular, respiratory and digestive functions. The studies over the past nearly 30 years have shown that CAs can also regulate immune function. The immunomodulation of CAs is generally considered as a role mediating the regulation of nervous and endocrine systems. However, recent studies reveal that immune cells can also synthesize CAs, which is an update of traditional concept. A classical metabolic pathway of CAs shared by the nervous and endocrine systems is present in the immune cells, i.e., the immunocytes have the enzymes for synthesis of CAs [e.g. tyrosine hydroxylase (TH)] and the enzymes for degradation of CAs [e.g. monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)]. The endogenous CAs synthesized by immune cells can regulate many immune functions, including cellular proliferation, differentiation, apoptosis and cytokine production. These roles of the endogenous CAs may be mediated by an autocrine/paracrine pathway via relevant receptors on the immunocytes and intracellular cAMP. Intracellular oxidative mechanism may also be involved in immunoregulation of endogenous CAs in immune cells. In addition, some metabolic abnormalities of CAs in the immune cells probably induce some autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis. These findings not only provide evidence for the new concept that the immune system is possible to become the third CA system other than the nervous and endocrine systems, but also extend our comprehension on functional significance of the endogenous CAs synthesized by immune cells.