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ID PMID Title PublicationDate abstract
15057853 Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing. 2004 Mar Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage
14738593 Effect of methotrexate on Th1 and Th2 immune responses in mice. 2003 Dec We investigated the effect of the anti-rheumatic drug methotrexate (MTX) on Th1 and Th2 immune responses in mice. For this investigation, mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0). Varying doses of MTX were orally administered daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon-gamma (IFN-gamma) as indicators of Th1 responses and anti-OVA IgG1 and interleukin-10 (IL-10) as those of Th2 responses were measured. The results showed that treatment with MTX was followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. The anti-rheumatic drug inhibited both anti-OVA IgG2a and IgG1 production, although the inhibitory effect of MTX on the antigen-specific IgG2a production appeared to be greater than that on IgG1 production. IFN-gamma, but not IL-10, secretion was markedly downregulated by MTX. Administration of MTX resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of the joint inflammation by MTX was associated with inhibition of OVA-specific proliferative responses of spleen cells, anti-OVA IgG, IgG2a and IgG1 production, and IFN-gamma and IL-10 secretion, although more pronounced decreases in IgG2a and IFN-gamma were observed compared with those in IgG1 and IL-10 in MTX-treated mice. These results indicate that MTX appears to suppress Th1 and, to a lesser extent, Th2 immune responses and its anti-arthritic effect on human rheumatoid arthritis might be at least in part explained by down-regulation of Th1 responses involved in the disease.
12481925 Neuroendocrine function and chronic inflammatory stress. 2002 Sep The factors regulating susceptibility and severity of autoimmune diseases are poorly understood. That neuroendocrine factors are critical modulators in this regard is self-evident. For example, there are major gender differences in susceptibility with women at greater risk than men of, for example, rheumatoid arthritis (RA) and multiple sclerosis (MS). The hypothalamo-pituitary-adrenal (HPA) axis has rightly attracted a considerable amount of attention. Of particular interest has been the hypothesis that susceptibility to autoimmune disease may be related to an impaired responsiveness of the HPA axis; that is, an inability to mount an appropriate cortisol response with which to down-regulate the immune system might allow the immune system to rampage unchecked and attack self. This hypothesis links regulation of the release from the adrenal gland of the potent anti-inflammatory glucocorticoids to the disease process. Endogenous glucocorticoids are crucial for the regulation of the severity of the disease process. The hypothesis proposing a link between a hyporesponsive HPA axis and susceptibility to disease is compelling. However, evidence from a number of sources has suggested that this may not be the entire story and alterations in the activity of the HPA axis have not been consistently observed in patients with RA. This review will concentrate on recent findings concerning the HPA axis in determining susceptibility to, and in regulating the severity of, inflammatory processes in autoimmune disease. These studies have revealed that a single exposure to endotoxin can confer protection to subsequent development of inflammation in an arthritis model in both neonatal and adult rats. Behavioural differences within a single population of rats are associated with differences in the plasma corticosterone responses to stress. However, relative hyporesponsiveness is not reflected by an increase in the severity of inflammation. In humans with RA the dexamethasone-corticotrophin-releasing factor (CRF) test has revealed two distinct sub-populations of patients. Studies in patients with MS have shown that this is not related to depression but rather to the severity of the disease. A better understanding of these complex neuroendocrine interactions may lead to novel clinical interventions.
14705239 The role of subcutaneous administration of methotrexate in children with juvenile idiopath 2004 Jan OBJECTIVE: To describe the outcome of patients with juvenile idiopathic arthritis (JIA) treated with subcutaneous (Sc) methotrexate (MTX) after failing oral MTX (either because of inefficacy or toxicity) in a clinic population. METHODS: The study cohort was identified from our clinical database, and consisted of 61 children with JIA treated with MTX between 1988-2001. All patients fulfilled International League Against Rheumatism (ILAR) criteria for JIA and had disease duration of >/= 6 months and 3 or more active joints before institution of MTX. All patients had a core set of outcome variables assessed at baseline and at 3 months after achieving both maximum oral and SC MTX. Outcome variables included physician global assessment of disease activity, number of active joints, number of joints with limited range of motion, duration of early morning stiffness, and erythrocyte sedimentation rate (ESR). Improvement was defined as at least 30% improvement from baseline in 3 of 5 variables in the core set, with no more than one of the remaining variables worsening by more than 30%. RESULTS: A total of 61 patients, 43 females and 18 males with JIA were studied. The disease subtypes were systemic 8, polyarticular 25 (12 rheumatoid factor positive), oligoarticular 14, enthesitis related arthritis 5, and unclassified 4. Thirty-one patients were switched to SC MTX, 13 of whom had not improved, and 18 who had improved, but had nausea (11) or insufficient clinical improvement (7). After 3 months of SC MTX treatment, 76% of patients were classified as improved and 23% as not improved. Toxicity on SC MTX was less than on oral MTX. CONCLUSION: Our results suggest that for patients failing oral MTX either because of inefficacy or toxicity, the use of SC MTX has a high likelihood of success with more than 70% of patients achieving clinically significant improvement, without clinically significant toxicity.
12566094 Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoac 2003 Feb 15 Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, reduces joint tissue damage in rats with adjuvant arthritis. Because interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) are central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis, we investigated human monocyte IL-1beta and TNFalpha responses after the addition of AjA to cells in vitro. Peripheral blood and synovial fluid monocytes (PBM and SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AjA (0-30 microM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for mRNA, and supernatants were collected for cytokine assay. Addition of AjA to PBM and SFM in vitro reduced both steady-state levels of IL-1beta mRNA and secretion of IL-1beta in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 microM AjA (P<0.05 vs untreated controls, N=7). AjA did not influence TNFalpha gene expression in or secretion from PBM. Reduction of IL-1beta by AjA may help explain the therapeutic effects of AjA in the animal model of arthritis. Development of nonpsychoactive therapeutically useful synthetic analogs of Cannabis constituents, such as AjA, may help resolve the ongoing debate about the use of marijuana as medicine.
12528081 Autoimmune disease complicating antiviral therapy for hepatitis C virus infection. 2002 Dec OBJECTIVE: To review autoimmune disease complicating therapy with type I interferons (IFNs), specifically in the setting of hepatitis C virus (HCV) infection. METHODS: This study describes 13 reported cases of drug-induced systemic lupus erythematosus (SLE) associated with IFN therapy for the period reported during 1990-2002 by searching MEDLINE. In addition, 2 additional patients are presented, 1 with SLE and 1 with an antineutrophil cytoplasmic antibody (ANCA)-positive nephritis, with long-term follow-up. RESULTS: Of 13 cases of SLE-like syndromes caused by IFN, 2 occurred in patients being treated for HCV infection. Two occurred in patients with rheumatoid arthritis (RA); 1 had Sjogren's syndrome (SS), and 1 laryngeal papillomatosis. The rest were receiving IFN for hematologic malignancies. Symptoms developed between 2 weeks and 7 years after initiation of therapy. Most developed fever and arthralgias/arthritis. Other findings included serositis manifested by tachycardia, dyspnea and pleural effusions, headaches, and hair loss. All had a positive antinuclear antibody (ANA), and the majority had double stranded (ds) DNA antibodies. Two additional patients with chronic HCV infection developed autoimmune disease after combination treatment with IFN-alpha and ribavirin. In each patient, autoimmune disease manifested as severe joint pains, myalgias, fever, rash, and proteinuria. Skin and renal biopsy specimens showed vasculitis and crescentic glomerulonephritis (GN) in the first case, and typical histologic findings of lupus nephritis in the second; clinical and laboratory features were consistent with Wegener's granulomatosis and SLE, respectively. Although both patients had mixed polyclonal cryoglobulins, they were HCV RNA and HCVAb negative. Both received corticosteroids, with gradual clinical and biochemical improvement and without recurrence of viremia. CONCLUSIONS: Autoimmune disorders occur in 4% to 19% of patients receiving IFN-alpha, though SLE-like syndromes are only seen in 0.15% to 0.7%. Clinical and laboratory features of SLE in this setting resemble idiopathic disease, with a generally good outcome after discontinuance of the drug. RELEVANCE: Type I IFNs may cause autoimmune disease such as SLE. As the armamentarium of drugs expands to include other biologics, such as the tumor necrosis factor (TNF)-alpha-inhibiting drugs, the development of autoimmune diseases induced by these drugs is an important consideration for diagnosis and appropriate treatment. Semin Arthritis Rheum 32:163-173.
15615495 RANK, RANKL and OPG in inflammatory arthritis and periprosthetic osteolysis. 2004 Sep Elucidation of the receptor activator of nuclear factor kappa B (RANK), its ligand (RANKL) and osteoprotegerin (OPG) as the final effectors of bone resorption has transformed our understanding of metabolic bone diseases and revealed novel therapeutic targets. Activation of the RANK-RANKL signaling pathway is directly responsible for dramatic focal erosions that are observed in inflammatory arthritis and aseptic loosening of orthopaedic implants. While these conditions share many features common to all metabolic bone disorders (e.g., osteoclastic resorption), they exhibit several unique properties, which are highlighted in this review. Most important is the relative inability of bisphosphonate therapy to inhibit osteolysis in joint inflammation and periprosthetic joint loosening and the unexpected effectiveness of anti-cytokine therapy in both rheumatoid and psoriatic arthritis. Herein, we provide a review of the role of RANK, RANKL and OPG in erosive arthritis and periprosthetic osteolysis and discuss the potential of anti-RANKL therapy for these conditions.
12922962 Mental wellbeing and quality of sexual life in women with primary Sjögren's syndrome are 2003 Sep OBJECTIVES: To evaluate the possible effect of androgen status on sexuality and mental wellbeing in patients with primary Sjögren's syndrome (pSS). METHODS: Serum levels of dehydroepiandrosterone sulphate (DHEA-S), testosterone (T), androstenedione, sex hormone binding globulin (SHBG), and the SHBG/T ratio were measured in 21 women with pSS. Sexual life was assessed by a Swedish version of the McCoy scale, which covers sexual experience and responsiveness during the past 30 days. A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine quality of life and psychological symptoms in patients with pSS. RESULTS: Positive correlations were found between DHEA-S serum levels and the total McCoy score (r(s)=0.62; p<0.01), as well as the subscales of this score reflecting arousal (0.59; p<0.05), desire (r(s)=0.52; p<0.05), and satisfaction (r(s)=0.66; p<0.01). Serum DHEA-S concentrations were also related to the total PGWB score (r(s)=0.60; p<0.01) and subscales of this score: depression (r(s)=0.62; p<0.01), wellbeing (r(s)=0.64; p<0.01), general health (r(s)=0.67; p<0.01), and self control (r(s)=0.67; p<0.01). Total McCoy and PGWB scores and their subscales were not related to the serum levels of testosterone and androstenedione or the T/SHBG ratio. CONCLUSIONS: Circulating levels of the weak androgen DHEA-S are positively related to the quality of sexual life and mental wellbeing in women with pSS.
11809167 Chronic sensory neuronopathy associated with human T-cell lymphotropic virus type I infect 2002 Feb 15 We described two patients with chronic sensory neuronopathy who had anti-HTLV-I antibody in serum and cerebrospinal fluid but no signs of myelopathy. A sural nerve specimen revealed severe degeneration of myelinated and unmyelinated axons. The second patient had subclinical Sjögren's syndrome suggestive of a possible link among human T-cell lymphotropic virus type I (HTLV-I), Sjögren's syndrome and sensory neuronopathy, respectively. The broad spectrum of neurologic disorders associated with HTLV-I infection now would include chronic sensory neuronopathy.
12578938 Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. IV 2003 Feb 11 Ataxic sensory neuronopathy with Sjögren's syndrome is a devastating neurologic complication for which there is no established treatment. IV immunoglobulin (IVIG) was given to five patients with severe disabilities for an average of 12 years. Four patients showed remarkable improvement, two of whom responded after the first course. The authors conclude that IVIG is safe and effective to treat even chronically debilitated patients who have the disease, presumably because it ameliorates smoldering inflammation.
11993793 Pulmonary MALT lymphoma with amyloid production in a patient with primary Sjögren's syndr 2002 Apr A 53-year-old woman was admitted to our hospital complaining of cough, low grade fever, chest pain and sicca symptoms. A chest radiograph showed an abnormal shadow and chest computed tomography revealed a tumor in left S6. She was diagnosed as Sjögren's syndrome by sialography and histological findings of labial biopsy. The surgically resected tumor specimen showed proliferation of lymphoid cells with lymphoepithelial lesions, which were positive for CD20 and kappa light chain. Kappa light chain-positive amyloid was found within the tumor. The tumor showed rearranged kappa light chain genes. The diagnosis was pulmonary mucosa associated lymphoid tissue lymphoma with amyloid production.
15234277 Therapeutic effect of cevimeline on dry eye in patients with Sjögren's syndrome: a random 2004 Jul PURPOSE: Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by salivary and lacrimal glandular destruction leading to symptoms of dry mouth and dry eye. Dryness can also occur in the absence of glandular destruction. Patients with SS have autoantibodies that bind to muscarinic acetylcholine receptors in the exocrine glands. Recently, a muscarinic acetylcholine receptor agonist, cevimeline, has been approved for use against symptoms of dry mouth in patients with SS. In this study, the efficacy of cevimeline in improving symptoms of dry eye was examined. DESIGN: Prospective, randomized, double-blind, multi-center clinical study. METHODS: Sixty patients were randomly assigned to three groups-placebo; cevimeline, 20 mg three times daily; or cevimeline, 30 mg three times daily-and received treatment for 4 weeks. Patients were evaluated before treatment, at week 2, at the end of treatment, and at the end of a 2- to 4-week follow-up period. RESULTS: Compared with the placebo, statistically significant differences were seen with cevimeline, 20 mg three times daily, in subjective symptoms, tear dynamics, condition of the corneoconjunctival epithelium, and global improvement rating. No difference was found among the three groups regarding the safe use of the drug. CONCLUSIONS: These results indicate that cevimeline, 20 mg three times daily, is safe and effective in improving symptoms of dry eye in patients with SS. Additional studies, with larger patient populations, are needed to further assess the effectiveness of cevimeline for dry eye.
15111378 Renal tubular acidosis, Sjögren syndrome, and bone disease. 2004 Apr 26 BACKGROUND: There has been disagreement about whether osteomalacia (adult rickets) occurs in adults with type 1 (distal) renal tubular acidosis (RTA1). Therefore, after finding scapular pseudofractures in a patient with RTA1 and Sjögren syndrome, we decided to survey other patients with RTA to learn whether osteomalacia occurred in others and, if it did, whether it was necessarily associated with the presence of Sjögren syndrome. METHODS: We examined the hospital records and laboratory findings of 250 patients with codes for RTA, 124 with codes for osteomalacia, and 20 with codes for Sjögren syndrome who were seen at a university-affiliated acute care municipal hospital since 1990. Further detailed survey was then limited to patients older than 15 years and excluded those with potentially confounding causes of bone disease such as chronic renal insufficiency or sickle cell disease. Seven adults with RTA1 were thereby identified. RESULTS: Two adults with RTA1 had radiological and biochemical findings compatible with osteomalacia, and 1 had findings compatible with Sjögren syndrome. A third patient without Sjögren syndrome had biochemical findings suggestive of osteomalacia. CONCLUSIONS: Osteomalacia seems to occur in some adult patients with RTA1, and not only in association with Sjögren syndrome. We found no biochemical evidence of osteomalacia in the patients with Sjögren syndrome who did not have RTA.
14714969 Severe pulmonary hypertension associated with primary Sjögren's syndrome. 2003 Dec Severe pulmonary hypertension is one of the fetal complications in various connective tissue diseases. We report a case of severe pulmonary hypertension associated with primary Sjögren's syndrome. In a lung biopsy specimen, there were findings of intimal and medial hypertrophy with narrowing vessel lumina and plexiform lesions. Moreover, deposits of immunoglobulin M, immunoglobulin A and complement protein C1q were found in the pulmonary arterial walls. Although pulmonary hypertension was refractory to oral prostacyclin, steroid therapy improved the clinical and hemodynamic conditions. In the present case, the immunological etiology may be related to the mechanisms of pulmonary hypertension associated with Sjögren's syndrome.
12233883 Possible function of salivary gland epithelial cells as nonprofessional antigen-presenting 2002 Sep OBJECTIVE: To explore the potential of salivary gland epithelial cells to act as nonprofessional antigen-presenting cells (APC) in the development of Sjögren's syndrome (SS). METHODS: Expression of HLA-DR antigens, costimulatory molecules, and adhesion molecules on epithelial cells was immunohistochemically examined in labial salivary glands from patients with SS. An association with the expression of T cell derived cytokine messenger RNA (mRNA) was observed. The expression of these molecules was confirmed using cultured salivary gland epithelial cells. The ability of the salivary gland epithelial cells as nonprofessional APC was examined in a mixed culture system using the salivary gland epithelial cells and allogeneic lymphocytes. RESULTS: Expression of HLA-DR antigens, CD80, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin was immunohistochemically detected on duct cells from all patients; however, the expression of CD86 was limited to only some patients. Concomitant expression of CD80 on duct cells and Th1 cytokine mRNA, and CD86 on duct cells and Th2 cytokine mRNA, was observed. Interferon-gamma (IFN-gamma) induced the cultured salivary gland epithelial cells to express HLA class I antigens, HLA-DR antigens, CD80, and ICAM-1, while tumor necrosis factor-alpha (TNF-alpha) induced the expression of HLA class I antigens, CD80, CD86, and VCAM. Cultured salivary gland epithelial cells treated with either IFN-gamma or TNF-alpha also caused allogeneic lymphocytes to proliferate. CONCLUSION: The ability of salivary gland epithelial cells to express HLA-DR antigens, costimulatory molecules, and adhesion molecules and thus to act as nonprofessional APC was suggested. CD80 and CD86 expression of these cells was also suggested to be involved in the activation of Th1 and Th2, respectively.
12149393 Sicca syndrome associated with Tropheryma whipplei intestinal infection. 2002 Aug The case of a 61-year-old woman with Whipple's disease-associated sicca complex is reported. Tropheryma whipplei infection was diagnosed by histological and ultrastructural examination of the jejunal mucosa and sequence analysis of the bacterial 16S ribosomal DNA. The role of vitamin A malabsorption in sicca complex secondary to Whipple's disease is discussed.
15188374 17 beta-estradiol regulates cytokine release through modulation of CD16 expression in mono 2004 Jun OBJECTIVE: Macrophages release cytokines, such as tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and IL-6, which modulate the symptoms of rheumatoid arthritis (RA). Macrophage release of these cytokines can be modulated by estrogen. Fc gamma receptor type IIIA (CD16a) is a receptor expressed on macrophages that selectively binds IgG molecules, an important rheumatoid factor in RA. Binding of CD16 by anti-CD16 monoclonal antibodies stimulates macrophage cytokine release. We undertook this study to test the hypothesis that decreased concentrations of estrogen (17 beta-estradiol) directly cause an increase in CD16 expression, resulting in increased release of proinflammatory cytokines from monocytes and/or macrophages upon receptor binding. METHODS: THP-1 cells and female human primary monocytes and monocyte-derived macrophages were treated with no 17 beta-estradiol, physiologic levels (1 x 10(-8)M) of 17 beta-estradiol, or 1 x 10(-8)M 17 beta-estradiol followed by withdrawal of 17 beta-estradiol. Surface expression of CD16 and CD16 messenger RNA was measured using fluorescence-activated cell sorting (FACS) and semiquantitative reverse transcription-polymerase chain reaction, respectively. Cytokine release from 17 beta-estradiol-treated or untreated monocytes was then quantitated by enzyme-linked immunosorbent assay and FACS after crosslinking the receptor with anti-CD16 antibodies. RESULTS: CD16 transcript significantly increased in macrophage-like THP-1 cells and in primary, peripheral blood macrophages in the absence of 17 beta-estradiol, and the observed increase in message was dependent on transcription. CD16 receptor levels on CD14+, transforming growth factor beta-treated primary monocytes also increased in cells deprived of 17 beta-estradiol. Analysis of the cytokines released showed that CD16 crosslinking stimulated significant increases in TNF alpha, IL-1 beta, and IL-6 due to the absence of estrogen. CONCLUSION: Estrogen can modulate proinflammatory cytokine release from activated monocytes and/or macrophages, in part through modulation of CD16 expression.
15212936 Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes 2004 Jul 15 In joint diseases of both the inflammatory (rheumatoid arthritis, or RA) or the degenerative variety (osteoarthritis, or OA), matrix metalloproteinases (MMPs) are essential mediators of irreversible tissue destruction. MMP-9 is secreted as a stable, inactive zymogen and is proteolytically converted to the active enzyme. To understand the activation mechanism of MMP-9 in joint diseases, the process was investigated in serum-free cocultures of human articular chondrocytes and macrophages. Macrophages extensively expressed and secreted pro-MMP-9 whereas chondrocytes failed to produce the enzyme. However, efficient activation of pro-MMP-9 required soluble and membrane-associated chondrocyte proteinases. Two alternative activation pathways mainly involved MMPs and, marginally, serine or cysteine proteinases. MT1-MMP (MMP-14), the only MT-MMP expressed in chondrocytes, converted pro-MMP-13 which, in turn, cleaved pro-MMP-9. Alternatively, pro-MMP-9 was activated less efficiently by MMP-3, which was converted by autocatalysis or by serine or cysteine proteinases. Both pathways were triggered by chondrocytes from OA, but not normal joints. Therefore, articular chondrocytes are not innocent bystanders in joint diseases. They not only produce destructive enzymes guided by environmental cues but also they can instruct inflammatory cells or cells from surrounding tissues to do so by converting in several ways zymogens produced but not activated by these cells themselves.
15087120 Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters revea 2004 Apr 14 Peptidylarginine deiminases (PADs) convert arginine residues in proteins into citrullines. They are suspected to be involved in multiple sclerosis and rheumatoid arthritis pathophysiology, and they play a role in epidermis homeostasis and possibly in regulation of gene expression through histone modification. In humans, four isoforms encoded by the genes PADI1-4 are known so far. We here report the characterization and comparative analysis of the human (355 kb) and mouse (240 kb) PAD gene clusters on chromosomes 1p35-36 and 4E1, respectively. We characterized an as yet unknown human PADI6 gene, and cloned the corresponding cDNA encoding a 694-amino-acid protein. RT-PCR analysis showed a rather restricted pattern of tissue-specific expression, mainly in ovary, testis and peripheral blood leukocytes. Nucleotide substitution rates suggest that PADI genes are under purifying selection. Comparative analysis of the human and mouse sequences identified 251 conserved non-coding segments predominantly clustered within the promoter regions, the large (>10 kb) first intron of each of the genes PADI1-3, and an 8 kb PADI1-2 intergenic region. The presence of numerous transcription factor binding sites suggests the segments are putative regulatory elements. This study is the first description of the human PADI6 gene and encoded protein, and the first step towards a better understanding of the coordinated regulation of PADI gene expression.
15565537 [Inpatient aftercare in rheumatic diseases--concept, trial, and acceptance]. 2004 Dec BACKGROUND: A one-week booster group treatment in rheumatic diseases (rheumatoid arthritis, spondylarthropathies, fibromyalgia) was developed in order to stabilize rehabilitation effects after medical rehabilitation. The program took place in an inpatient setting 3 - 5 months after rehabilitation, aimed at refreshing and deepening already learnt contents as well as teaching new subjects (e. g. about dietetics). Training and educational elements are given priority in this concept. METHOD: A total of 140 patients participated in 19 booster weeks. At the end of each booster week the acceptance was assessed by questionnaire and in a round-table discussion. RESULTS: Comprehensibility and group atmosphere were judged very positively. The course was also considered very helpful, helpfulness being rated with marks about 2 (1 = very helpful, 6 = not at all helpful). Participants especially appreciated the course's framework as a group setting emphasising the exchange of experience with co-patients. At the same time, however, participants wished more individualized treatment such as physiotherapy or massage. With regard to the quantity of the various therapy elements, participants would have preferred more traditional spa therapy, more medical treatment by a physician, more group physiotherapy and sports. They would also have liked more breaks. In general fewer psychological elements, less discussion and reflection but more physical activity was wished for. Little difference was found between the various diagnoses, but the program was rated slightly more positively by the patients with spondylarthropathies. CONCLUSION: Overall, the great number of people participating in the program and their acceptance of the booster week are positive. Patients appreciated the group setting and the possibilities of exchanging experience on a high level. But it was difficult to change patients' traditional expectations concerning medical rehabilitation to a behaviour-orientated course like ours. It is worth thinking about whether this concept should play a greater role in traditional medical inpatient rehabilitation programming.