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ID PMID Title PublicationDate abstract
10202179 Alpha-amylase functions as a salivary gland-specific self T cell epitope in patients with 1999 May Analyses of T cell receptors (TCR) on T cells infiltrating labial salivary glands of patients with Sjögren's syndrome (SS) indicate that the cells expand by antigen stimulation in context of major histocompatibility complex (MHC). To elucidate the autoantigens recognized by T cells infiltrating in labial salivary glands from patients with SS, proteins derived from human salivary gland cDNA libraries were screened by West-Western method using TCR-CDR3 probe, which is antigen recognition region of TCR on T cells. 13 cDNA clones were detected as proteins binding to TCR-CDR3 region. One was a human alpha-amylase salivary precursor (AA54-407), suggesting that alpha-amylase might be a salivary gland-specific autoantigen. To examine whether alpha-amylase acts as an antigen in labial salivary glands, PBL from 11 patients with SS were incubated with 9 different synthetic amino acids of alpha-amylase or salivary alpha-amylase. SSCP analysis on TCR clearly showed that alpha-amylase reactive T cells were observed in labial salivary glands from 3 of 11 patients with SS (27%). These findings support the possibility that alpha-amylase functions as a salivary gland-specific T cell epitope and induces autoimmunity in SS.
9374934 Hypokalaemic alkalosis, acquired Gitelman's and Bartter's syndrome in chronic sialoadeniti 1997 Oct Two patients with chronic sialoadenitis had features of Bartter's and Gitelman's syndrome, respectively. The main complaints were leg paraesthesiae and acute arthritis. A good response to oral K+ supplementation, allopurinol and low-dose prednisone was obtained. The features of Sjögren's-related renal diseases are reviewed.
10782816 Outcome of total hip replacement for avascular necrosis in systemic lupus erythematosus. 2000 Apr OBJECTIVE: To describe the short and medium term results of total hip arthroplasty (THA) for avascular necrosis in patients with systemic lupus erythematosus (SLE). METHODS: Nineteen patients with SLE and avascular necrosis of the femoral head (AVNFH), who underwent 26 THA were retrospectively reviewed with a minimum followup of 2 years. To determine whether these patients had results similar to those of patients with other conditions, we formed a control group of 19 patients who had 29 THA. They were matched for age, sex, and followup to the patients with SLE. Controls had THA for juvenile rheumatoid arthritis (n = 7), osteoarthritis (5), adult onset rheumatoid arthritis (8), developmental dysplasia of the hip (4), and other diagnoses (5). Outcome measures included a 10 point visual analog scale (VAS) for pain, the Harris hip score, and the SF-36 self-administered health outcome questionnaire. We used the methods of Delee, Harris, and Engh for radiological assessment. RESULTS: Mean age at surgery was 46 years (range 21-71 years) and average followup was 4 years, 7 months (range 1 yr 9 mo to 9 yrs 6 mo), similar in both groups. Technical problems, mostly consisting of small, nonpropagating cracks of the calcar in uncemented stems, were encountered in 4 SLE hips and 1 control hip. Six complications were noted in the SLE group, including 2 early, nonrecurrent dislocations, 1 patient with thigh pain for 1 year, 1 pericarditis, 1 sick-sinus syndrome, and 1 urinary tract infection. There was one case of urinary tract infection in the control group. One SLE patient developed a low grade prosthetic infection and underwent successful revision 2 years after primary surgery. Clinical outcome measures had similar scores in the 2 groups: average VAS pain score = 2.00 in SLE hips (maximum 10) and 1.97 in control hips; mean Harris hip score = 86.7 in SLE patients (maximum 100) and 81.9 in controls; average SF-36 score = 63.4 in SLE patients (maximum 100) and 60.5 in controls. There was no radiological evidence of implant loosening in controls; there was 1 asymptomatic cup migration in the SLE group. CONCLUSION: In the short and medium term, patients with SLE and AVN had good results after THA. Results were similar in patients who had hip replacement for other diagnoses. Less favorable clinical outcomes of hip replacement have been reported in young patients who have AVN of other etiology (e.g., alcoholic, post-traumatic), but this was not the case in our young patients who had AVN and SLE. Thus, AVNFH and SLE should not constitute a contraindication to hip replacement.
11774357 Nitric oxide donors induce large-scale deletion mutations in human lymphoblastoid cells: i 2001 Rheumatoid arthritis (RA) is an inflammatory disease in which high levels of reactive nitrogen oxygen species (RNOS) may be present in the affected joints. RNOS are known to produce small-scale mutational events (transitions, transversions, small insertions, and small deletions) but the ability of these compounds to cause deletion of large segments of genomic DNA has not been previously determined. To address this question, a human lymphoblastoid cell line (WIL2-NS) was exposed to nitric oxide (NO)-donating drugs and hypoxanthine phosphoribosyltransferase (hprt)-negative clones were selected and analyzed by multiplex-PCR. Large-scale deletions accounted for 60-80% of hprt mutations arising in drug-treated cultures compared to 12% in untreated cultures (P-values of 0.006 and 0.0001, respectively, in two experiments). Deletion mutations in untreated cultures affected exon 9, whereas 75% of drug-induced deletion mutations affected exons 2, 3, and 9, and the remainder were very large, ranging from 26 to 1200 kbp. To compare this spectrum of NO-induced mutations in a lymphoblastoid line to that arising in vivo in arthritis patients, T-cells from RA patients, osteoarthritis (OA) patients, and controls were cloned and similarly analyzed. We previously showed that the overall frequency of Hprt mutant clones from patients is appreciably elevated compared to that of control subjects. Large-scale hprt deletions (0.5 to >26 kb) were detected in mutant T-cell clones from both RA and OA patients and also from control subjects. A total of 54 mutant clones from 16 RA patients and 19 mutant clones from 6 OA patients were studied. Of these, 6 clones (from 3 RA and 1 OA patient) had suffered large-scale deletions. A total of 9 control subjects were studied and 62 mutant clones were obtained. Of these, 19 had suffered large-scale deletions, arising in 7 of 9 control subjects. In conclusion, (1) RNOS are capable of inducing large-scale deletion mutations in a human lymphoblastoid cell line and (2) large-scale deletion mutations were found in 10-30% of T-cell clones from RA and OA patients and controls, which we hypothesize may be induced by RNOS.
10759779 Complex pattern of Th1 and Th2 activation with a preferential increase of autoreactive Th1 2000 Apr The central role of CD4+ T cells and the balance between T helper (Th) subpopulations in the pathogenesis of autoimmune diseases have been extensively studied. Proteoglycan (aggrecan)-induced arthritis (PGIA) is a murine model for rheumatoid arthritis (RA), which is characterized by a Th1 dominance at the onset of the disease. In addition to CD4+ T cells, antigen-presenting B cells and autoantibodies seem to play an important role in the development and regulation of PGIA. To identify proteoglycan-specific CD4+ T cell subsets and Th1- and Th2-supported antibody isotypes during the progression of PGIA, spleen cells of proteoglycan-immunized BALB/c mice were harvested at different times of immunization, and at different stages of the disease, and their cytokine production and antigen-specific antibody isotype profiles were determined by enzyme-linked immunospot (ELISPOT) assays. Both Th1 and Th2 cytokine-producing cells, with the predominance of IL-4/IL-5-secreting cells, were detected during the prearthritic stage, and a shift toward a Th1 dominance was observed at the time of onset of arthritis. Tissue homogenates of acutely inflamed joints contained significantly higher levels of interferon-gamma than IL-4. The prearthritic period and both the acute and chronic phases of joint inflammation were characterized by IgG1 dominance in the sera and this correlated with the number of IgG1-secreting B cells in the spleen. However, the ratio of autoreactive IgG1/IgG2a-secreting cells decreased in arthritic animals. These results indicate the activation and possible regulatory roles of both Th1 and Th2 subsets in the autoimmune process, with the necessity of a relative increase of autoreactive Th1 cells for the induction of joint inflammation.
9733470 Juvenile chronic arthritis in urban San José, Costa Rica: a 2 year prospective study. 1998 Sep OBJECTIVE: To find the incidence and prevalence of juvenile chronic arthritis (JCA) in the urban area of San José, Costa Rica. METHODS: During the year preceding our 2 year prospective, population based study, we conducted an educational program on JCA. The physicians caring for children < 16 years of age from all centers in the study area followed the program. They were asked to refer all cases of possible JCA according to EULAR criteria. The children were all evaluated at the National Children's Hospital. RESULTS: Of 189 children referred, 48 fulfilled EULAR criteria for JCA. The 2 year incidence rate for JCA was 13.7 per 100,000 children < 16 years old. This corresponds to an annual incidence per 100,000 children of 6.8 (95% CI 4.1-9.6). The incidence rate for pauciarticular onset JCA was 3.9 per 100,000. At the prevalence date, 122 cases of JCA were recorded, corresponding to a prevalence of 34.9 per 100,000 children < 16 years. When patients in remission were excluded, the prevalence was 31.4 per 100,000 (95% CI 25.5-37.2). The pauciarticular onset form was the most common, 71% of all prevalence cases. The highest incidence and prevalence were noted for pauciarticular girls with late onset JCA. No incidence peak was found in preschool age. The girl-to-boy ratio was 1.5/1. Antinuclear antibodies (ANA) were positive in only 7 cases (6.3%). IgM rheumatoid factor was found in 13 children (10.6%). Chronic iritis was observed in 4 cases, all of them ANA negative and older than 7 years of age at onset of arthritis. CONCLUSION: The incidence and prevalence observed were lower than those reported in other population based studies, but within the confidence intervals of their data. The incidence rate for pauciarticular JCA was significantly lower than that reported in other comparable studies. ANA positive pauciarticular preschool girls and associated uveitis were rarely encountered.
11140894 Frequency and predictive value of the clinical manifestations in Sjögren's syndrome. 2001 Jan The purpose of this study was to examine the frequency and predictive value of glandular and extraglandular manifestations in S ogren's syndrome (SS). The clinical profiles of 169 SS patients were compared to those of 44 non-SS controls. The specific symptoms examined were oral, ocular, vaginal, gastric, pulmonary, skin, joint and muscle pain. Statistical analyses were performed on both individual and grouped symptoms. Chi-squared analyses showed that the frequency of all symptoms was significantly higher among patients than controls. Stepwise discriminant analysis of individual symptoms suggests that the combined symptoms of dry mouth, sore mouth, and dry eyes correctly classified 93% of SS and 97.7% of the controls. While grouped gastric, muscle, psychological, vaginal, skin, nasal, and thyroid symptoms correctly classified 64.3% of SS and 86.1% of the controls. This is the first study to examine the diagnostic value of multi-system manifestation in SS. The overall results suggest that a comprehensive questionnaire of various symptoms may assist the diagnosis of SS. The high predictive value of the combined symptoms confirms their value in the evaluation of SS.
10193515 Identification of a novel PTEN mutation (L139X) in a patient with Cowden disease and Sjög 1998 Dec Cowden disease is an autosomal dominant disorder associated with an increased risk of breast, thyroid, and skin cancer in which germline mutations in a candidate tumour suppressor gene (PTEN) have been identified previously. Sjögren's syndrome is a chronic inflammatory and autoimmune disorder of exocrine glands for which the genetic basis is unknown. This report describes a novel PTEN mutation (L139X) in a patient with Cowden disease and Sjögren's syndrome. This observation raises the possibility of a link between mutations in the PTEN gene and Sjögren's syndrome.
9504814 Establishment of the human reflex tear two-dimensional polyacrylamide gel electrophoresis 1997 Dec To understand the changes in protein expression associated with various physiological states as well as the development of pathological eye disease, we have begun to map the protein components of normal human reflex tears. An analytical reference map of normal human reflex tears was created using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) with pH 3.5-10 immobilized pH gradients (IPGs). Micropreparatively loaded gels were transferred to polyvinylidene difluoride (PVDF) and analysed by a combination of N-terminal sequence tagging and amino acid compositional analysis. Thirty spots were sequence tagged, resulting in identification of six different proteins (lipocalin, lysozyme, lactotransferrin, zinc-alpha-2 glycoprotein, cystatin S, cystatin SN) that matched to entries in the SWISS-PROT database. A group of N-terminally blocked proteins was clearly identified from SWISS-PROT by amino acid analysis, isoelectric point (pI) and molecular weight (Mr). A number of highly expressed protein components remain unidentified despite being subjected to amino acid analysis and Edman sequencing. A majority of the abundant proteins showed varying degrees of charge heterogeneity attributed to post-translational processing such as glycosylation and N-terminal truncation. We have identified a previously undescribed protein that we have named lacryglobin. This protein displays strong homology with mammaglobin, a protein overexpressed in breast cancer. The discovery of this homologue in tears offers the potential for disease diagnosis by screening tear fluid proteins.
9256028 [Treatment with pilocarpine hydrochloride for sicca symptoms in Sjögren's syndrome]. 1997 Jun We studied the efficacy of oral pilocarpine hydrochloride (9 mg/day, three times daily) on sicca symptoms in 21 patients with Sjögren's syndrome (SS) of the patients, 19 continued the treatment for at least one month, and subjective improvement of dry mouth and dry eye was observed in 10 patients (53%) and 5 patients (26%), respectively. As adverse effects, diaphoresis was most frequently recognized, but it was generally mild and tolerable. In the four patients who have been taking pilocarpine for 12 months, any severe side effects have not been observed. Since the incidences of clinical improvement of sicca symptoms and adverse effects were comparable with the other studies reported from US or Europe, our treatment protocol using pilocarpine hydrochloride (9 mg/day) was considered as appropriate for Japanese SS patients.
9122105 Signs and symptoms in patients with salivary gland hypofunction. 1997 Feb Salivary gland hypofunction can have a devastating effect on oral health and may be an indicator of systemic disease such as Sjögren's syndrome. This prospective study investigates the oral and non-oral signs and symptoms in 120 patients with objective evidence of salivary gland hypofunction (ie, an unstimulated whole salivary flow of < 0.2 ml/min). Patients were questioned about symptoms associated with decreased oral function; non-oral symptoms were also noted. The underlying cause of salivary gland hypofunction was established on the basis of clinical and laboratory findings and further investigations. Eighty-five per cent of patients reported symptoms of decreased oral function in addition to oral dryness. Non-oral signs and symptoms were reported by 106 patients. Fifty-three per cent of patients were diagnosed as having Sjögren's syndrome. The prevalence of the following non-oral signs and symptoms were significantly higher in patients with Sjögren's syndrome, than in those without; a history of dry/irritated eyes, salivary gland swelling, dry skin and reduced lacrimal flow. Salivary gland hypofunction is associated with a wide range of oral and non-oral signs and symptoms. Several of these are of potential value as triggers for the clinician to identify patients with Sjögren's syndrome, and should serve to prompt referral for specialist investigation.
9028107 [Evaluation of conjunctival epithelial damage in dry eye]. 1997 Jan Using sulphorhodamine B, which is highly sensitive in detecting damaged ocular surface epithelium, we evaluated conjunctival epithelial damage in dry eye patients. The subjects were 99 eyes of 50 dry eye patients (41 eyes of 21 patients with Sjögren's syndrome and 58 eyes of 29 keratoconjunctivitis sicca patients without Sjögren's syndrome). We also investigated the relation between sulphorhodamine B and fluorescein staining in ocular surface epithelium. The conjunctival epithelial damage stained with sulphorhodamine B showed a high correlation with corneal epithelial damage stained with fluorescein. In addition, conjunctival damage in Sjögren's syndrome tended to be more severe than in patients without Sjögren's syndrome.
10555040 Regulation of synovial cell apoptosis by proteasome inhibitor. 1999 Nov OBJECTIVE: Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of synovial cells, and whether cytokines modulate this process. METHODS: Type B synovial cells (fibroblast-like synovial cells) were cultured with tumor necrosis factor alpha (TNF alpha) or transforming growth factor beta1 (TGFbeta1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of synovial cells was determined by Hoechst 33258 dye staining and 51Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2-related proteins, and X chromosome-linked inhibitor of apoptosis (XIAP) in synovial cells was examined by Western blot analysis. RESULTS: Apoptosis of cultured synovial cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of synovial cells with TNF alpha significantly augmented both the activation of caspases and the proportion of apoptosis in synovial cells induced by LLL-CHO, whereas TGFbeta1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in synovial cells may not be directly associated with the susceptibility of synovial cells to apoptosis by LLL-CHO. CONCLUSION: Apoptosis of synovial cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling synovial cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.
9600686 HTLV-I-associated myelopathy associated with multi-organ inflammatory disease: a case repo 1998 Apr 15 We report a 73-year-old man with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) complicated with multi-organ inflammatory disease, including Sjögren's syndrome, interstitial cystitis, and uveitis. The presence of HTLV-I proviral DNA in peripheral blood mononuclear cells (PBMC), cerebrospinal fluid, salivary gland, mucosa of urinary bladder, and aqueous humor was confirmed by polymerase chain reaction using HTLV-I pX region primer. Western blot analysis revealed the presence of anti-HTLV-I antibodies in serum, CSF, saliva, and urine, suggesting replication of HTLV-I in each tissue. A high load of HTLV-I proviral DNA (20 copies out of 100 PBMC) was present, associated with increased spontaneous proliferation of peripheral blood lymphocytes (24,747 cpm). Our results suggest that the high load of HTLV-I in patients with HAM may potentially induce systemic inflammation in several organs.
10686641 Central nervous system involvement in Sjögren's syndrome: evidence from neuropsychologica 1999 Dec OBJECTIVE: To investigate the clinical, neuropsychological and imaging manifestations of Sjögren's syndrome (SS), a chronic auto-immune disease with peripheral and central nervous system (CNS) involvement. DESIGN/METHODS: Fourteen female patients suffering from confirmed SS underwent within 2 weeks: neurological examination, immunological staging, brain MRI, brain 99m Tc-HMPAO SPECT, psychological evaluation and in-depth neuropsychological testing. RESULTS: All patients showed neuropsychological abnormalities. The cognitive symptoms were of the same type in all patients, mostly frontal lobe syndrome and memory problems. The neuropsychological involvement was not associated with other kinds of CNS involvement or MRI abnormalities, but accurately reflected HMPAO imaging results. CONCLUSIONS: The results of this study indicate that cognitive evaluation is the most sensitive clinical test to diagnose CNS involvement in patients with SS, and that CNS involvement in SS seems to be more frequent when systematically assessed by neuropsychological tests.
10434755 [A case of progressive systemic sclerosis complicated by idiopathic portal hypertension wi 1999 Jun A 44-year-old woman had been diagnosed with progressive systemic sclerosis (PSS) at the age of 39 years old and mild pancytopenia was noted at that time. At the age of 41 years symptoms of dry mouth appeared. In April 1997, anemia was in progress (Hb 5.8 g/dl) and severe esophageal varices were found by gastrointestinal fiber scope, and massive splenomegaly by abdominal CT. Serological examination was negative for hepatitis virus and for anti-mitochondrial antibody. In addition, Indocyanine Green test was normal and typical findings of liver cirrhosis were not demonstrated by CT scan. Also, the bone marrow result was normal. Therefore hypersplenism with idiopathic portal hypertension (IPH) was suggested and the patient was referred for splenectomy with the aim of improving the pancytopenia. The weight of the spleen was 2100 g and the pressure of the portal vein was measured at 390 mm H2O. The diagnosis of IPH was determined because pathologically there were no findings for liver cirrhosis. After splenectomy, pancytopenia was remarkably improved (Hb 9.6 g/dl). Consequently, this case was diagnosed as IPH complicated with PSS and Sjögren syndrome.
10071138 Tear fluid analysis in patients with primary Sjögren's syndrome using lectin probes. A co 1999 Feb PURPOSE: To study and compare the glycoprotein composition of tear fluid from patients with primary Sjögren's syndrome, patients with other connective tissue diseases and control individuals. METHODS: SDS polyacrylamide gel electrophoresis followed by Coomassie staining or Western blotting and overlaying with ten different lectins. RESULTS: The frequency of many glycoprotein bands discovered was significantly decreased in primary Sjögren's syndrome compared with controls and patients with other connective tissue diseases. The reduction was most pronounced in the 14-68 kDa molecular weight range. CONCLUSIONS: A decrease in the production rate and/or a change in the glycosylation pattern of the tear glycoproteins was found in patients with primary Sjögren's syndrome. The changes discovered, however, were not specific enough to be useful as a diagnostic test.
9465547 Estimated prevalence and incidence of adult Still's disease: findings by a nationwide epid 1997 Dec To estimate prevalence and incidence of adult Still's disease in Japan, and to describe the epidemiological features of the patients, a nationwide epidemiological survey was conducted in 1994. The study consisted of two questionnaires which were distributed to the heads of the relevant departments, randomly sampled, in hospitals throughout Japan. Following major epidemiological findings emerged from the study: (a) The total annual number of patients treated for adult Still's disease was estimated as 1,100 in 1993 in Japan. The estimated crude prevalence among those aged 16 years or older were calculated as 0.73 and 1.47 per 100,000 population for males and females, respectively, with the corresponding crude incidence rate of 0.22 and 0.34. (b) The sex ratio (female to male) of the reported patients was 2.1. This female predominance might be specific to Japan, though additional surveys in other countries will be warranted. The mean age of the patients was 38.1 years, and female patients tended to be older than male ones; 50% of the female patients aged 40 years or older, while so did only 28% of the male patients.
9412854 Adie's tonic pupil as a manifestation of Sjögren's syndrome. 1997 Oct We here report two cases of Adie's tonic pupil, associated with clinical sensory polyneuropathy and Sjögren's syndrome, in one of whom it actually heralded the onset of the syndrome. Electrophysiology studies indicated absent H reflexes but normal peripheral nerve conductions, thus suggesting an involvement of the dorsal roots or spinal ganglion that would be in line with previously published reports of dorsal ganglionitis as the primary neuropathological lesion in Sjögren's syndrome. We suggest that all cases of tonic pupils should be screened for polyneuropathy and Sjögren's syndrome.
11712688 The epidemiology and significance of autoimmune diseases in health care. 2001 Autoimmune diseases are conditions in which the immune system damages normal components of the individual. Some estimates indicate that more than 20% of the population suffer from one or another autoimmune disease. Ten key points are briefly reviewed in this article to emphasise the significance of autoimmune diseases in health care. These include, among others, the great variety and worldwide distribution of these conditions, the clinical importance of some of these diseases such as systemic lupus erythematosus, the antiphospholipid syndrome, Sjögren's syndrome or systemic sclerosis, or the relationship between autoimmunity and virus infections, atherosclerosis, malignancy and Psychiatry.