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ID PMID Title PublicationDate abstract
21145154 Endoscopic treatment of salivary glands affected by autoimmune diseases. 2011 Feb PURPOSE: To asses the possibility of an endoscopic technique to diagnose, treat, and maintain the salivary glands in patients with Sjögren syndrome and systemic lupus erythematosus. PATIENTS AND METHODS: A total of 8 patients with Sjögren syndrome and 2 with systemic lupus erythematosus with affected salivary glands were included in the present study. The treatment approach included parotid sialoendoscopy with thorough rinsing, and Stenson's duct dilation using hydrostatic pressure and a high-pressure balloon. Hydrocortisone 100 mg was injected through direct vision into the duct. The study was exempt by the Barzilai Medical Center review board. RESULTS: The main diagnosis of the patients was chronic recurrent parotitis, with the exception of 1 patient, who presented with salivary stones. CONCLUSIONS: The pathologic features of the salivary glands resulting from Sjögren syndrome and systemic lupus erythematosus can be managed successfully using an endoscopic approach.
22170493 Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. 2012 Apr Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisms (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 × 10(-8), odds ratio (OR)=1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. We hypothesize that c-Rel, as a member of the Rel/NF-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NFκBIA.
21745420 Disturbance of cytokine networks in Sjögren's syndrome. 2011 Jul 6 The difficulty in predicting the consequences of interactions between different cytokine networks has increased with the expansion of the T helper (Th) cell universe and the discovery of numerous B lymphocyte-derived cytokines. Consequently, it is now difficult to conceptualize a straightforward view of the contribution of these disturbances to the pathogenesis of primary Sjögren's syndrome (SS). Th1 cells, which produce interferon-γ and IL-2, and Th17 cells, which make IL-17 and TNF-α, have been cast in the leading roles of the play. However, the complex role of T-cell subsets in SS is accentuated by the reciprocal effects of Th17 cells and regulatory T cells found in salivary glands of SS patients. Furthermore, B lymphocyte polarization into type-1 B effector (Be1) and Be2 cells and B-cell modulating factors of the TNF family, most notably the B-cell-activating factor (BAFF), and their prominent role in SS are additional complicating factors. Whereas Th17 cells orchestrate autoreactive germinal centers, local BAFF would repress the generation of Th17 cells. Such new insights into interconnected cytokines in primary SS may lead to new treatments for these patients.
22849322 Low number of memory B cells in the salivary glands of patients with primary Sjögren's sy 2012 Nov We have previously shown that patients with primary Sjögren's Syndrome (pSS) show a significant reduction of autoantigen specific CD27(+) memory B cells and an abnormally elevated level of autoantibody producing plasma cells in peripheral blood (PB) compared to controls. Because both memory B cells and plasma cells have been detected in salivary glands (SG) of pSS patients, we aimed to study the B cell pattern in SG biopsies. Double immunohistochemical staining of CD20 and CD27 was carried out on paraffin-embedded SG tissue from 10 pSS patients to distinguish CD20(+)/CD27(+) memory B cells, and identify the CD20(+) glandular B cell zones (BCZ). Given that plasma blasts and plasma cells are CD27(++) and CD20(- ), additional CD138 single staining of serial sections allowed the distinction of CD27(++)/CD138(- ) plasma blasts located within the BCZ from CD27(++)/CD138(+) plasma cells that were found mostly on the periphery of the BCZ and also observed interstitially. Both BCZ and the memory B cell populations were then quantified. Contrary to what has been reported earlier through immunoflourescent staining of memory B cells in SG tissue, we have shown that there is a low number of memory B cells located within the glandular BCZ. Plasma blasts and plasma cells, however, were more abundant in the SG. Together our findings suggest that these low numbers of memory B cells in both PB and SG of pSS patients may be the result of activation of these cells into plasma cells at the site of inflammation.
22736090 Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syn 2013 May OBJECTIVE: To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called 'IFN type I signature', in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). METHODS: Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. RESULTS: An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. CONCLUSIONS: The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity.
22210656 Cryoglobulinaemia related to Sjogren's syndrome or HCV infection: differences based on the 2012 Apr OBJECTIVE: The relationship of cryoglobulinaemia with lymphoproliferation of mucosa-associated lymphoid tissue (MALT) as risk factors for lymphoma evolution in SS remains to be clarified. The different biologic background of SS-related cryoglobulinaemia as compared with cryoglobulinaemia linked to HCV infection was clarified by different clinical and biologic approaches. METHODS: B-cell clonal expansion was analysed in the bone marrow of 27 consecutive cases with primary SS and mixed cryoglobulinaemia, HCV unrelated, in comparison with 55 HCV-related patients with cryoglobulinaemic vasculitis (CV) without SS. The results were related to the possible occurrence and localization of B-cell lymphoma in the single case. Secondly, the prevalence of mixed cryoglobulinaemia was investigated in 41 unselected patients with primary SS showing either parotid myoepithelial sialadenitis (MESA) or a frank B-cell non-Hodgkin's lymphoma. Thirdly, the levels of serum cryoglobulins and RF were followed in one patient with primary SS, CV and parotid B-cell lymphoma of MALT after bilateral subtotal parotidectomy. RESULTS: A polyclonal pattern of B expansion in the bone marrow was significantly more frequent in SS-related (19/27 cases) than in HCV-related cryoglobulinaemia (19/55) (P = 0.003). Cryoglobulins were positive in a fraction of patients with SS and malignant lymphoma or with parotid MESA (13/18 and 7/23, respectively), whereas MALT involvement by the lymphoproliferative disorder was the rule. Finally, the levels of serum cryoglobulins and RF markedly decreased in the SS patient undergoing bilateral subtotal parotidectomy. CONCLUSION: Lymphoproliferation of MALT appears as the biologic background of cryoglobulinaemia in SS, differently from HCV-related cryoglobulinaemia.
21655359 Comparison of telomere length and association with progenitor cell markers in lacrimal gla 2011 PURPOSE: Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups. METHODS: Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues. The mean fluorescence intensity of telomere spots was automatically quantified by image analysis as relative telomere length in lacrimal gland epithelial cells. Immunostaining for p63, nucleostemin, ATP-binding cassette, sub-family G, member 2 (ABCG2), and nestin was also performed. RESULTS: Telomere intensity in the Sjögren syndrome group (6,785.0±455) was significantly lower than that in the non-Sjögren syndrome group (7,494.7±477; p=0.02). Among the samples from the non-Sjögren syndrome group, immunostaining revealed that p63 was expressed in 1-3 acinar cells in each acinar unit and continuously in the basal layer of duct cells. In contrast, in the Sjögren syndrome group, p63 and nucleostemin showed a lower level of expression. ABCG2 was expressed in acinar cells in both sjogren and non-Sjogren syndrome. CONCLUSIONS: The results of this study indicate that 1) telo-FISH is a viable method of assessing telomere length in lacrimal gland, and 2) telomere length in Sjögren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjögren syndrome.
21124091 IgG4-associated sialadenitis. 2011 Jan PURPOSE OF REVIEW: An enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review aims to address the numerous controversies that have arisen regarding inflammatory diseases of the salivary gland over the past two centuries and more specifically address the relevance of IgG4 in this setting. RECENT FINDINGS: A significant percentage of cases previously classified as Mikulicz disease, Küttner tumor, and orbital pseudotumor (idiopathic orbital inflammation) show elevated numbers of IgG4-positive plasma cells, and some of these cases also show elevated levels of serum IgG4. These data support the evolving concept of IgG4-associated sialadenitis/dacroadenitis. The disease presents with enlargement of one of more salivary gland(s) and/or lacrimal gland(s). Histologically this disease is characterized by a dense polyclonal lymphoplasmacytic infiltrate, and is frequently associated with germinal centers, fibrosis and obliterative phlebitis. IgG4-bearing plasma cells are virtually always present, as is an elevated ratio of IgG4 to IgG containing plasma cells. SUMMARY: IgG4-related sialadenitis belongs to the IgG4-related systemic disease spectrum and shows a swift response to immunosuppression.
21566407 [Successful treatment with rituximab in a patient with primary thymic MALT lymphoma compli 2011 Apr A 53-year-old female developed epigastric discomfort and back pain in 2007. Diagnostic imaging studies demonstrated a soft tissue tumor with heterogeneous enhancement in the anterior mediastinum and multiple nodules in the right lung. She underwent expanded thymectomy with subtotal resection of the right lung. The pathological diagnosis was primary thymic mucosa-associated lymphoid tissue (MALT) lymphoma. The patient complained of ocular discomfort, oral dryness and continuous nasal bleeding in 2007. Detailed examination led to a diagnosis of Sjögren syndrome and acquired von Willebrand syndrome. Rituximab treatment for residual disease achieved not only a reduction of the lung MALT lymphoma but also clinical and hematological remission of both syndromes. This is, to our knowledge, the first reported case of primary thymic MALT lymphoma accompanied by Sjögren and acquired von Willebrand syndromes.
21212317 Salivary anti-Ro60 and anti-Ro52 antibody profiles to diagnose Sjogren's Syndrome. 2011 Apr Simple and non-invasive saliva-based diagnostics may be useful for the identification, understanding, and monitoring of autoimmune and infectious diseases. Previously, Luciferase Immunoprecipitation Systems (LIPS) were used for sensitive detection of patient serum autoantibodies in Sjögren's Syndrome (SjS), a chronic autoimmune disease affecting the salivary and lacrimal glands. Here we explored the ability of LIPS to diagnose SjS based on IgG autoantibodies in patient saliva. From LIPS testing, anti-Ro60 autoantibodies were detected in the saliva of 70% (19/27) of SjS patients with 96% specificity. Positive anti-Ro60 autoantibodies were also found in 70% of the matched serum samples (96% specificity). LIPS detected Ro52 autoantibodies in the saliva and serum of 67% of SjS patients with 100% specificity. Overall, the autoantibody titers in saliva were approximately 4000-fold lower by volume than serum, but still distinguished seropositive patients from controls. These results suggest that LIPS salivary-based testing for SjS autoantibodies is a practical alternative to serum and compatible with point-of-care testing.
23493837 Synthesis and Evaluation of Pyridinyltriazoles as Inhibitors of p38 MAP Kinase. 2012 Jul OBJECTIVE(S): Inhibitors of p38 MAP kinase are considered as suitable target in the treatment of inflammatory diseases such as rheumatoid arthritis and bowel inflammatory diseases. The development of 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles as inhibitors of p38 MAP kinase is described. These are analogues of 4- pyridinyl imidazole p38 MAP kinase inhibitor reported by Merck Research Laboratories, in which imidazole ring has been replaced with triazole. MATERIALS AND METHODS: Reaction of pyridine-4-carboxylic acid hydrazide 1 and arylisothiocyanate (2a, b) gave the intermediate thiourea derivative 3a, b (Figure 2). Refluxing of the latter in aqueous saturated sodium carbonate gave 1-aryl-5-mercapto-2-(4-pyridinyl) triazoles 4a, b. Treatment of 4a, b with alkyl iodide afforded the desired 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles (5a-d). P38 MAP kinase inhibitory activity of the synthesized compounds was evaluated in vitro by ELISA method and also by molecular docking. RESULTS: Compound 5c at 1 µM concentration and compound 5d at 1 µM and 10 µM significantly inhibited the p38 phosphorylation. These inhibitory effects are equal to those of standard compound SB202190 and no significant differences were observed. CONCLUSION: We demonstrated that both tested compounds have inhibitory effect on p38 MAP kinase and we did not find significant difference between their inhibitory effects and those of standard inhibitor SB202190.
24116274 WIN-34B May Have Analgesic and Anti-Inflammatory Effects by Reducing the Production of Pro 2012 Jan WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, PGE2, and MMP-13 in IL-1β-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of PGE2, NO, IL-1β, and TNF-α were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and PGE2 was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. IκB signaling pathways were inhibited by WIN-34B, and the migration of NF-κB into the nucleus was inhibited, which is consistent with the degradation of IκB-α. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.
23305365 Bacterial urease and its role in long-lasting human diseases. 2012 Dec Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. The presence of ureolytic activity is an important marker of a number of bacterial infections. Urease is also an immunogenic protein and is recognized by antibodies present in human sera. The presence of such antibodies is connected with progress of several long-lasting diseases, like rheumatoid arthritis, atherosclerosis or urinary tract infections. In bacterial ureases, motives with a sequence and/or structure similar to human proteins may occur. This phenomenon, known as molecular mimicry, leads to the appearance of autoantibodies, which take part in host molecules destruction. Detection of antibodies- binding motives (epitopes) in bacterial proteins is a complex process. However, organic chemistry tools, such as synthetic peptide libraries, are helpful in both, epitope mapping as well as in serologic investigations. In this review, we present a synthetic report on a molecular organization of bacterial ureases - genetic as well as structural. We characterize methods used in detecting urease and ureolytic activity, including techniques applied in disease diagnostic processes and in chemical synthesis of urease epitopes. The review also provides a summary of knowledge about a toxic effect of bacterial ureases on human body and about occurrence of anti-urease antibodies in long-lasting diseases.
23076162 IL-33: a potential therapeutic target in autoimmune diseases. 2012 Dec Interleukin 33 (IL-33) is a newly described member of the IL-1 superfamily of cytokines. Through activation of the ST2 receptor, which is widely expressed particularly by helper T 2 cells and mast cells, IL-33 is involved in T-cell-mediated immune responses. Many previous studies have demonstrated that IL-33 may have a pleiotropic function in different diseases, and it could represent a novel target for the treatment of a range of diseases. Recent works have explored the role of IL-33 in chronic autoimmune diseases, such as systemic sclerosis, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. These results indicate that IL-33 may contribute to the pathogenesis of chronic autoimmune diseases. Hence, in this review, we discuss the biological features of IL-33 and summarize recent advances on the role of IL-33 in the pathogenesis and treatment of autoimmune diseases.
23071896 Non-antibacterial tetracycline formulations: clinical applications in dentistry and medici 2012 In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years' duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.
23057144 Sixteen years' result of posterior-stabilized TKA. 2012 Jul Total knee arthroplasty (TKA) had been reported to have excellent result; however, most of the publications reported either mixed cruciate retaining and posterior-stabilized prostheses or mixed patient groups of rheumatoid arthritis and primary osteoarthritis. The long-term result of posterior-stabilized TKA in primary osteoarthritis has rarely reported. From 1994 to 2001, the survival of 179 posterior-stabilized TKAs (Insall-Burstein II, Zimmer, Warsaw, IN) in 146 patients with primary osteoarthritis was studied. The survival using revision surgery for aseptic loosening as end point and the potential prognostic factors (gender, age <65 years old, activity level, body mass index) were studied. The 10 and 16.4 years survival using revision surgery for aseptic loosening as end point were 97.7 and 94.8%, respectively. Seven knees were revised for aseptic loosening with mechanical failure rate of 3.9%. No significant prognostic factor for the long-term survival of posterior-stabilized TKA was identified. The long-term survival of the posterior-stabilized TKA was comparable with cruciate retaining and mobile bearing TKA in primary osteoarthritis.
22991859 [Asymptomatic classical hereditary xanthinuria type 1]. 2012 Jun We report on a girl who was diagnosed with classical hereditary xanthinuria due to an incidental finding of extremely low Levels of uric acid in the blood. The girl is compLetely asymptomatic. Hereditary xanthinuria is a rare autosomal recessive disease that usually causes early urolithiasis but may cause rheumatoid arthritis-like disease and even be associated with defects in the formation of bone, hair and teeth. In Israel it has mostly been described in patients of Bedouin origin. Throughout the world, only about 150 cases have been described; about two thirds of these patients were asymptomatic. Since the clinical presentation and age of symptom appearance are diverse, the case raises questions as to the required follow-up of these patients and as to whether a low oxalate diet should be initiated.
22951134 [Summary of the multidisciplinary guideline on cardiovascular risk management (revision 20 2012 The decision whether to treat individuals not previously known to have cardiovascular disease is based on a new risk table in which Dutch research data on morbidity have been incorporated. An explanation of the roles of additional risk factors ignored in the cardiovascular risk function, such as a sedentary lifestyle and a high BMI, is provided. A method for estimating the cardiovascular risk in patients with diabetes mellitus and rheumatoid arthritis has been developed. New recommendations concerning the measurement of blood pressure at home and in the ambulatory setting have been formulated. The recommendations for the choice of antihypertensive drugs have been revised. The recommendations on handling therapy-resistant hypertension are provided. Recommendations for choosing statins based on a current cost-effectiveness analysis are provided.
22941885 An integrated approach in the diagnosis of smoking-related interstitial lung diseases. 2012 Sep 1 Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.
22659733 The development and function of follicular helper T cells in immune responses. 2012 Sep Follicular helper T cells (Tfh) have been referred as a lineage that provides a help for B cells to proliferate and undergo antibody affinity maturation in the germinal center. Evidence has supported that Tfh subset development, like other lineages, is dependent on microenvironment where a particular transcriptional program is initiated. It has been shown that Bcl-6 and IL-21 act as master regulators for the development and function of Tfh cells. Tfh dysregulation is involved in the development of autoimmune pathologies, such as systemic lupus erythematosus, rheumatoid arthritis and other autoimmune diseases. The present review highlights the recent advances in the field of Tfh cells and focus on their development and function.