Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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20641579 | (99m)Tc-Glucosamino-Asp-cyclo(Arg-Gly-Asp-D-Phe-Lys). | 2004 | Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of α(v)β(3) are being studied as antitumor and antiangiogenic agents, and the agonists of α(v)β(3) are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (inhibition concentration (IC(50)), 7–40 nM) but not to integrins α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM). Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). Jung et al. (13) reported the development of glucosamino (99m)Tc-D-c(RGDfK) that contains N-D-glucosamine as a sugar moiety for imaging α(v)β(3) receptors during tumor angiogenesis. | |
15158312 | [Auto-antibodies to anti-ENA SSA/RO (52 and 60 kDa): an auto-immunity laboratory's experie | 2004 Jun | PURPOSE: Anti-SSA/Ro and anti-SSB/La autoantibodies are frequently encountered in SLE or SGS where anti-SSA subtypes 52 and 60 kDa seems to be differently found in connection with the disease type: anti-SSA/Ro 60 kDa more frequently found in SLE and anti-SSA/Ro 52 kDa in SGS. We try to find if it was interesting in identifying these specificities for all anti-ENA screening. METHOD: The study included 162 patients' sera found anti-SSA 52 and/or anti-SSA 60 and/or anti-SSB positive among 1600 screening tests from the different hospital's services. We used two assays: first, dotblot (Innolia-Ana Update INGEN) as a screening test and second, an Elisa (ENA-LISA BMD) as confirmation. Thirty-eight control sera were found negative with dotblot. RESULTS: Only one subtype of anti-SSA (52 or 60 kD) or anti-SSB was found for 55 sera (44 anti-SSA 52, 10 anti-SSA 60, 1 anti-SSB) and 107 sera were found positive for two or more (73 anti-SSA 52 + 60 and 34 anti-SSA 52 or 60 with another anti-ENA). While anti-SSA 60 kDa alone or not was always positive with the Elisa test, neither anti-SSA 52 alone was anti-SSA Elisa's positive. Diseases associations results show a greater linking of anti-SSA 60 kDa with SLE, a frequent linking of combined reactivity anti-SSA 52/60 in SLE and SGS and a greater spreading of anti-SSA 52 kDa alone among pathological groups, showing an autoimmune disease's linking in 68%. Among SGS, 29% had only anti-SSA 52 kDa. CONCLUSION: We suggest screening specific tests for identifying anti-SSA/Ro 52 kDa reactivity which are missed by routine testing (tests using animal's antigens) and could represent an additional serum marker in Connective Tissue Diseases. | |
14697016 | Xerostomia: clinical aspects and treatment. | 2003 Dec | Xerostomia or dry mouth is a condition that is frequently encountered in dental practice. The most common cause is the use of certain systemic medications, which make the elderly at greater risk because they are usually more medicated. Other causes include high doses of radiation and certain diseases such as Sjogren's syndrome. Xerostomia is associated with difficulties in chewing, swallowing, tasting or speaking. This results in poor diet, malnutrition and decreased social interaction. Xerostomia can cause oral discomfort, especially for denture wearers. Patients are at increased risk of developing dental caries. A thorough intraoral and extra-oral clinical examination is important for diagnosis. Treatment may include the use of salivary substitutes (Biotene), salivary stimulants such as pilocarpine, ongoing dental care, caries prevention, a review of the current prescription drug regimen and possible elimination of drugs having anticholinergic effects. Because of the ageing population, and the concomitant increase in medicated individuals, dentists can expect to be presented with xerostomia in an increasing number of patients in the coming years and therefore should be familiar with its diagnosis and treatment. Therefore, the purpose of this review is to outline for clinicians the common aetiologies, clinical identification, and routine therapeutic modalities available for individuals with xerostomia. | |
12617251 | IGF-1 and insulin receptor expression in the minor salivary gland tissues of Sjögren's sy | 2003 Jan | OBJECTIVE: To investigate the expression of IGF-1 receptors and insulin receptors on the minor salivary gland (MSG) tissues of patients diagnosed with Sjögren's syndrome (SS) and normal salivary gland tissue surrounding mucoceles. SUBJECTS AND METHODS: Five MSG tissue sections from SS and seven from mucocele patients were stained immunohistochemically using antibody to IGF-1 receptor and insulin receptor in a horse radish peroxidase and DAB system. RESULTS: The expression of the insulin receptor was increased in the SS sections compared with controls, while the insulin-like growth factor-1 receptor was more intensely expressed in the controls. CONCLUSION: The presence of differential expression of receptors for IGF and insulin might suggest a possible role of these growth factors in the pathogenesis of SS. | |
12406302 | Nitric oxide signalling in salivary glands. | 2002 Nov | Nitric oxide (NO) plays multiple roles in both intracellular and extracellular signalling mechanisms with implications for health and disease. This review focuses on the role of NO signalling in salivary secretion. Attention will be paid primarily to endogenous NO production in acinar cells resulting from specific receptor stimulation and to NO-regulated Ca2+ homeostasis. Due to the fact that NO readily crosses membranes by simple diffusion, endogenous NO may play a physiological role in processes as diverse as modifying the secretory output, controlling blood supply to the gland, modulating transmitter output from nerve endings, participating in the host defence barrier, and affecting growth and differentiation of surrounding tissue. Furthermore, the role of NO in the pathogenesis of human oral diseases will be considered. | |
12115220 | Etanercept in the treatment of adult patients with Still's disease. | 2002 May | OBJECTIVE: To evaluate the safety and efficacy of etanercept in the treatment of adult patients with Still's disease. METHODS: Twelve adult patients who met criteria for Still's disease and had active arthritis were enrolled in a 6-month open-label trial of etanercept given in biweekly doses of 25 mg. The mean disease duration at study entry was 10.7 years. All patients had been treated unsuccessfully with other disease-modifying antirheumatic drugs. Efficacy was evaluated according to American College of Rheumatology (ACR) improvement criteria, and adverse events were recorded. RESULTS: Ten patients successfully completed the study; 2 withdrew due to disease flare. In 4 patients, the dosage of etanercept was increased from 25 mg biweekly to 25 mg 3 times per week. Seven patients met ACR 20% response criteria. Of these 7 responders, 4 met ACR 50% response criteria and 2 met ACR 70% response criteria. Among the 3 patients with systemic features of Still's disease (fever and rash), improvement in these features was seen in 1; the arthritis did not improve in any of these 3 patients. Except in the 2 patients who withdrew due to disease flare (rash, fever, and arthritis), no other significant adverse events occurred. CONCLUSION: In this initial study of etanercept therapy for Still's disease in the adult, this treatment resulted in improvement in the arthritis and was well tolerated. Additional trials should be performed to elucidate the effects of tumor necrosis factor inhibitors in Still's disease. | |
11959762 | Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/S | 2002 May | OBJECTIVES: To investigate the clinical and immunogenetic aspects of antibody formation against Ro/SSA and La/SSB as well as their linear B cell epitopes in patients with primary Sjögren's syndrome (pSS) from different European countries. PATIENTS AND METHODS: Ninety patients with pSS from six European centres were studied. Serum samples from all patients were tested in a control laboratory for anti-Ro/SSA and anti-La/SSB autoantibodies by RNA precipitation assay and autoantibodies to the previously reported B cell linear epitopes of Ro 60 kDa (p169-190aa and p211-232aa) and La/SSB (p147-154aa, p291-302aa, p301-318aa, and p349-364aa). DNA from 88 patients was used for the determination of HLA-DRB1, -DQA1, and -DQB1 genotypes. Analysis of the results was performed in the 88 patients who were genotyped and tested also for antipeptide antibodies. RESULTS: Antibodies to B cell epitopes of Ro 60 kDa were detected at a low frequency (range 10-37%). In contrast, B cell epitopes of La/SSB were detected frequently (range 58-86%) among the anti-La/SSB positive sera. Autoantibodies to the La/SSB epitope, p349-364aa, were significantly positively associated with longer disease duration (p<0.05), recurrent or permanent parotid gland enlargement (p<0.005), and a higher proportion of non-exocrine manifestations (p<0.005), compared with patients without autoantibodies. The presence of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly associated with the presence of HLA-DRB1*03 and DQB1*02 (p=0.038 and p=0.034, respectively). This association was even more prominent and extended to HLA-DQA1*0501 when patients were stratified according the presence of autoantibodies to discrete La/SSB B cell epitopes in comparison with autoantibody negative patients (p<0.01). They were found also to be highly associated with the alleles HLA-DQB1*02 and HLA-DQA1*0501 as well as the presence of a shared amino acid motif in the region 59-69aa of DQB1 first domain (p<0.01, respectively). CONCLUSIONS: Autoantibodies against La/SSB, binding to four synthetic peptides, derived from the sequence of the La protein were identified with increased frequency in sera of patients with pSS. The formation of autoantibodies against B cell epitope analogues of La/SSB in European patients with pSS may be dependent on the presence of a permissive HLA-DQ heterodimer, most prominently represented by the HLA-DQA1*0501/DQB1*0201 heterodimer, suggesting that a model of HLA restricted presentation of La/SSB peptide determinants is crucial for the autoimmune response against La/SSB. | |
15640780 | Appropriate utilization of semi-quantitative analysis in salivary scintigraphy. | 2004 Dec | AIM: The purpose of this case-control study was to determine whether semi-quantitative indices derived from salivary time-activity curves (TACs) are useful in the diagnosis and management of xerostomia. METHODS: Twenty-six healthy volunteers and 83 consecutive patients with xerostomia, including a subset of 40 patients with Sjogren's syndrome, underwent sequential salivary scintigraphy (SSS). Semi-quantitative analysis of the TACs was performed, deriving six different indices, previously cited in the literature, for each patient. These reflected trapping and uptake, stimulated excretion, or stimulated and unstimulated oral radioactivity. The indices were the percentage uptake, uptake ratios, maximum accumulation, pre-stimulatory oral radioactivity index, post-stimulatory oral radioactivity index and ejection fraction. RESULTS: Reduced parotid activity relative to submandibular activity, expressed as the P : S ratio, was able to distinguish abnormal from normal salivary function, and a parotid ejection fraction of greater than 50% also indicated normal parotid function. The other parameters showed no statistically significant difference between controls and patients. Individual variation in all indices served to widen the reference limits obtained from controls to the extent that they overlapped with those from the xerostomic population. CONCLUSIONS: This finding, together with previous work indicating that uptake parameters are only sensitive to differences exceeding 25% of the gland mass, the possibility that xerostomia may result from qualitative as well as quantitative changes in saliva and the probability that immune factors decrease neurosecretory circuits without affecting acinar mass, suggest that those indices derived from salivary TACs that directly reflect trapping and uptake are not useful in the detection of salivary gland disease. | |
15334476 | Detection of anti-type 3 muscarinic acetylcholine receptor autoantibodies in the sera of S | 2004 Aug | OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune disease affecting primarily the salivary and lacrimal glands, leading to dry mouth and dry eyes. Recent studies have suggested that autoantibodies reactive with the type 3 muscarinic acetylcholine receptors (M3Rs) expressed on salivary and lacrimal gland cells may be highly specific for SS. To test this hypothesis, we constructed a cell line expressing the human M3R gene in order to screen for anti-M3R autoantibodies in sera from SS patients. METHODS: Complementary DNA encoding the open-reading frame (ORF) of the human M3R gene was amplified, ligated into the pcDNA5/FRT/V5-His-TOPO TA vector, and then used to transform Escherichia coli bacteria. Plasmid DNA containing the M3R ORF with the correct orientation was transfected into Flp-In Chinese hamster ovary (CHO) cells using Flp recombinase-mediated site-specific recombination. An M3R-transfected CHO cell line, selected and propagated in hygromycin, was used to detect anti-M3R autoantibodies in SS patient and healthy control sera by flow cytometry. RESULTS: Testing of sera for the presence of anti-M3R autoantibodies bound to CHO-transfected cells revealed the presence of anti-M3R autoantibodies in SS patients (9 of 11) but not in healthy controls (0 of 11). Although the anti-M3R autoantibodies detected in patient sera were of multiple isotypes, the most consistently detected were IgG1, IgG3, and IgA. CONCLUSION: Using a newly constructed cell line expressing human M3R, anti-M3R autoantibodies were easily detected in sera from SS patients. These autoantibodies were skewed toward the IgG1, IgG3, and IgA isotypes, probably recognizing a tertiary epitope created by extracellular domains of the receptor protein. Anti-M3R autoantibodies represent a highly promising clinical marker for the identification of SS. | |
15334433 | Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndro | 2004 Aug 15 | OBJECTIVE: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). METHODS: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). RESULTS: Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. CONCLUSION: DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown. | |
15182268 | Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vascu | 2004 Jun | OBJECTIVE: The association of pulmonary fibrosis (PF) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitides has not been well documented. The aim of this study was to assess the clinicopathological characteristics of PF in patients who tested positive for MPO-ANCA. METHODOLOGY: In this study, 31 patients (17 males and 14 females; mean age, 69 years) diagnosed as having PF with positive MPO-ANCA levels ranging from 10 to 840 EU with a mean of 112.5 EU, were evaluated clinicopathologically. RESULTS: Among 31 patients with PF, 22 had underlying systemic diseases such as collagen vascular diseases, while nine had unknown aetiology. Evidence of glomerulonephritis was demonstrated in 14 patients. The clinical features were a history of dry cough and/or fine crackles in all 31 patients. Chest CT scans showed honeycombing in the lung bases in 26 patients. The histopathological features of the diseased lung tissues in all 11 autopsied cases were compatible with the usual interstitial pneumonia (UIP) pattern. Vasculitis was confirmed in bronchial arteries and/or pulmonary arterioles in five patients. The mortality was as high as 13 of the 31 patients. The causes of death were: deterioration of PF in five (two of whom were associated with pulmonary haemorrhage), lung cancer in two, pneumonia in four, and digestive tract bleeding in two. The survival rates in PF with MPO-ANCA-negative collagen vascular diseases, cryptogenic fibrosing alveolitis (CFA), and PF with positive MPO-ANCA, were compared. The 5-year survival rate in PF with positive MPO-ANCA was worse than in PF with MPO-ANCA-negative collagen vascular diseases and was the same for CFA. CONCLUSION: Although there was no correlation between MPO-ANCA titres and the activity of PF, this study demonstrated that the presence of positive MPO-ANCA was an unfavorable prognostic factor in patients with PF. | |
15174222 | Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary gl | 2004 May | The pathogenesis of Sjögren's syndrome (SS) is poorly understood. In this study we used an in-house mouse spleen cDNA microarray to analyse genes in spleens from MRL/lpr (an SS mouse model) mice. We have previously demonstrated that GRAP genes were up-regulated in salivary glands of the same mice. The microarray analysis showed that seven out of 2304 genes were highly expressed in spleens from the MRL/lpr mice, one of which was the GRAP gene. In other words, the GRAP gene is highly expressed in the salivary glands and spleen of MRL/lpr mice. We also carried out immunohistochemical studies. Mouse and human Grb-2-related adaptor protein (GRAP) antigens were expressed on ductal cells and infiltrating lymphocytes in salivary glands of MRL/lpr mice and SS patients, but only weakly in controls (MRL/+ mice and individuals with salivary cysts). These results suggest that the GRAP gene might have a role in the pathogenesis of SS. | |
12765482 | Levels of BAFF in serum in primary biliary cirrhosis and autoimmune diabetes. | 2002 Dec | Levels of the B-cell activating cytokine BAFF are increased in serum in various autoimmune disease, and particularly Sjögren's syndrome in which there is evident B-lymphocyte proliferation. Studies in two autoimmune disease in which B-cell proliferation is less evident, primary biliary cirrhosis (PBC), and adult-onset Type 1 diabetes, showed serum levels of BAFF to be mostly in the normal range. A single raised level among eight sera tested in one patient studied with autoimmune hepatitis (AH) coincided with a relapse of the disease. Increased levels of BAFF in human sera, indexing a potent antigenic drive on B-cell production and survival in some autoimmune diseases, may mark only particular stages in the evolution of such diseases. | |
12711377 | Electrolytes in stimulated whole saliva in individuals with hyposalivation of different or | 2003 May | There are reasons to believe that changes in the secretion rate of saliva as well as changes in its protein and electrolyte composition promote the growth of micro-organisms associated with oral disorders. Knowledge of the electrolytes in the saliva of those with hyposalivation might therefore be of value in designing oral health-promoting measures. In this study, electrolytes in stimulated whole saliva were analysed in individuals with hyposalivation due to radiation therapy in the head and neck region (RT group), primary Sjögren's syndrome (pSS group), neuroleptic treatment (Neuro group), and to medication or of unknown origin (Unknown group). The bicarbonate concentration was significantly lower in all four hyposalivation groups compared with controls. The bicarbonate concentration, which in normal conditions is positively correlated with the salivary secretion rate, was lower in the Neuro group than in the RT and Sjögren's groups despite a stimulated secretion rate about twice as high. Furthermore, the Neuro group had the highest phosphate concentration. The RT and Sjögren's groups tended to have increased sodium concentrations. For potassium and calcium, the RT group had significantly higher concentrations than the other hyposalivation groups and the controls. The substantial increase in calcium and decrease in bicarbonate suggest that the function of the parotid glands is more affected than that of the other salivary glands. The results also indicate a contribution of plasma to the electrolyte concentrations determined in whole saliva in the RT and Sjögren's groups. In conclusion, in individuals with hyposalivation the concentrations of electrolytes in stimulated whole saliva seem to be more related to the reason for the hyposalivation than to the salivary secretion rate. | |
14690138 | Analysis of B-cell clonality in the hepatic tissue of patients with Sjögren's syndrome. | 2003 | OBJECTIVE: We investigated the incidence of B-cell clonality in the minor salivary gland and liver (extra-glandular lesion) of patients with Sjögren's syndrome (SS). We also compared B-cell clonality in the minor salivary gland and liver in the same individuals, and compared its incidence among patients with various liver diseases, such as primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH). METHODS: A minor salivary gland biopsy was performed on 35 patients with SS (30 patients with primary SS, and five patients with secondary SS). A liver biopsy was performed on nine patients with SS associated with bile duct lesions, two patients with PBC, one patient with AIH, one patient with drug-induced liver dysfunction, and three patients with viral hepatitis. DNA was extracted from each tissue sample and then subjected to Polymerase Chain Reaction (PCR). B-cell clonality was analysed by assessing the rearrangement of the immunoglobulin heavy chain (IgH) gene by PCR. RESULTS: B-cell clonality was confirmed in the minor salivary gland biopsy sample in 23 of the 35 patients (65.7%), and in the liver biopsy sample (non-exocrine organ involvement) in seven of the nine patients (77.8%). The presence or absence of B-cell clonality was investigated in both the minor salivary gland and liver in seven patients, but B-cell clonality was confirmed in both tissues in only one patient, and the pattern of clonality in the minor salivary gland differed from that in the liver. B-cell clonality was detected in the liver of the PBC and AIH patients. CONCLUSION: B-cell clonality is a phenomenon that is observed frequently in SS lesions in the salivary glands and liver. The appearance of B-cell clonality was shown to be attributable to antigen-driven clonal expansion. | |
12812666 | [Expression of chemokine in the labial glands of patients with Sjogren's syndrome]. | 2003 Feb 10 | OBJECTIVE: To investigate the expression of chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein 1alpha (MIP-1alpha) in the labial glands of patients with Sjogren's syndrome (SS) and discuss their involvement in SS etiopathology. METHODS: Immunohistochemistry was used to examine the expression of RANTES and MIP-1alpha in the specimens of labial gland of 14 cases of primary SS, 7 cases of secondary SS (sSS), and 8 cases of controls, including maxillofacial injury and lip cyst. RESULTS: The expression rate of RANTES was 86% (12/14) in the pSS group and 71% (10/14) in the sSS group, and was 0 in the control group (P < 0.01). The expression rate of MIP-1alpha was 86% (5/7) in the pSS group, 71% (5/7) in the sSS group, and 25% (2/8) in the control group (P > 0.05). The RANTES and MIP-1alpha were expressed in the cytoplasm of ductal epithelium and part of infiltrated lymphocytes. The positive expression of RANTES was more evident than that of MIP-1alpha. CONCLUSION: RANTES and MIP-1alpha may attract the circulating lymphocytes towards inflammation site of labial gland so as play a crucial role in the pathogenesis of SS etiopathology. | |
12588452 | Oral microbiota associated with hyposalivation of different origins. | 2003 Feb | We analysed and compared the oral microbial flora in four groups with hyposalivation caused by radiation therapy (RT), primary Sjögren's syndrome (pSS), medication or unknown factors (Unknown), or neuroleptic treatment (Neuro). A control group with normal salivary secretion was also included. The subjects included were 54 +/- 8 years old and had 25 +/- 4 teeth. We analysed their microflora in rinsing samples using a cultivation technique. A marked increase in Lactobacillus spp. and Candida albicans was characteristic of the RT group. In the pSS group, 85% of subjects had high numbers of mutans streptococci despite good oral hygiene, frequent dental visits and fluoride use. The Unknown group had an oral flora similar to that of the controls. In the Neuro group, with a stimulated secretion rate similar to that of the Unknown group, the numbers of aciduric and acidogenic microorganisms were close to those in the pSS group. The results indicate that changes in the oral microflora associated with hyposalivation are related to the reason for the hyposalivation rather than to the magnitude of the decrease in the salivary secretion rate. | |
12539025 | A pilot study to test the efficacy of oral administration of interferon-alpha lozenges to | 2003 Jan | BACKGROUND: Complications from Sjögren's syndrome-induced xerostomia may cause a significant disruption in daily routines such as speech and eating habits. In addition, the reduction in salivary output may lead to increased incidence of caries, oral ulcers, sialadenitis, periodontal problems, and Candida infections. Interferon-alpha has been suggested as an effective drug therapy to increase salivary output. OBJECTIVE: The objective was to test the efficacy of interferon-alpha lozenges in relieving the symptoms of dry mouth and dry eyes when administered orally to patients with Sjögren's syndrome in double-blind placebo-controlled and open-label trials. STUDY DESIGN: Twelve patients with a diagnosis of primary Sjögren's syndrome were provided an Institutional Review Board-approved, written informed-consent form. During the double-blind placebo-controlled study they were randomized to receive 150 IU of interferon-alpha (8 patients) or placebo (4 patients) for 24 weeks with 6-week reevaluations. Five patients who received interferon-alpha in the double-blind placebo-controlled trial were treated in an open-label study for another 24 weeks. Whole saliva was measured during each visit, and symptoms were assessed by questionnaires and visual analog scales. The Wilcoxon signed rank test was used to detect significant changes for each variable. RESULTS: The results indicated that, by the end of 24 weeks, patients who received interferon-alpha had a statistically significant improvement in unstimulated salivary flow rate (P < .05), and statistically significant changes were observed in the median ocular dryness visual analog scale (P < .05) and oral dryness visual analog scale (P < .05). No significant changes were observed among the placebo patients. By the end of 48 weeks, medicated patients had better results than they had at the end of the double-blind placebo-controlled study and showed improvements in whole stimulated salivary flow rate, conditions of throat, and swallowing dry food. CONCLUSION: Oral administration of 150 IU interferon-alpha 3 times a day for the patients with primary Sjögren's syndrome improved saliva production, relieved symptoms of xerostomia and xerophthalmia, and was well tolerated by the patients. | |
12416563 | An autopsy case of amebic meningoencephalitis. The first Japanese case caused by Balamuthi | 2002 Sep | We report here the first case of amebic meningoencephalitis caused by Balamuthia mandrillaris in a 78-year-old Japanese woman with Sjögren's syndrome. Fourteen days before her death, she presented with high fever and lost consciousness and later developed neck stiffness and abducens palsy. Computed tomography scans of the brain demonstrated multiple low-density areas throughout the brain. Neuropathologically, hemorrhagic and necrotic lesions with many amebic trophozoites were scattered in the brain and spinal cord. Granulomatous lesions were only rarely found. The amebas were identified as Balamuthia mandrillaris based on immunofluorescence assay. Clinicopathologically, our case was thought to be an intermediate between primary amebic meningoencephalitis due to Negleria fowleri and granulomatous amebic encephalitis due to Acanthameba species. Essentially, the case was one of an elderly person with suspected immunodeficiency with fulminant necrotic meningoencephalitis and scanty granulomatous lesions of 14 days course. | |
15472036 | Detection of anti-SSA antibodies by indirect immunofluorescence. | 2004 Dec | BACKGROUND: HEp-2 cells that overexpress the human 60-kDa SSA antigen have been used to improve sensitivity and specificity for the detection of anti-SSA antibodies by indirect immunofluorescence. We describe a survey on the detection of anti-SSA antibodies using a commercial substrate that overexpresses SSA. METHODS: The evaluation was done on 18 371 consecutive samples submitted to the laboratory for detection of anti-nuclear antibodies, from which 188 anti-SSA antibody-containing and clinically documented samples were obtained. The presence of anti-SSA antibodies produced a distinct bright speckled pattern with nucleolar staining in 10-20% of interphase cells. The identity of all anti-SSA antibodies was confirmed by dot-blot analysis. RESULTS: Samples containing anti-SSA antibodies were separated into three main groups: group I, distinctive SSA pattern and other nuclear staining (50%); group II, only the distinctive SSA pattern (29%); group III, nuclear staining but without the distinctive SSA pattern (21%). Anti-SSA antibodies with concurrent SSB antibodies were associated with group I, whereas anti-SSA antibodies with concurrent U(1)-RNP antibodies were associated with group III. Group I included mainly patients with Sjogren syndrome and systemic lupus erythematosus (SLE), whereas group III included patients with mixed connective tissue disease and SLE. Diseases not classically associated with the presence of anti-SSA antibodies were found in group II in >50% of the cases. CONCLUSIONS: SSA-positive individuals were identified in a population selected on the basis of HEp-2000 positivity. Our study highlights diseases associated with anti-SSA antibodies and associations between the presence of the distinctive SSA pattern on HEp-2000 and some clinical conditions. |