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ID PMID Title PublicationDate abstract
12204342 Reaction of the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate with human biofluids. 2002 Aug 15 Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), an oxidant was previously detected in the plasma of patients with renal failure and the synovial tissue of rheumatoid arthritis patients. This oxidant has been shown to react with DBNBS to give a 3-line electron paramagnetic resonance (EPR) spectrum, previously assigned to the DBNBS radical cation (DBNBS*(+). However, confusion has arisen as to whether this paramagnetic species is indeed DBNBS*(+) or, rather, the DBNBS sulfite radical adduct (DBNBS-SO(3)*(-)). In the present study, DBNBS*(+) (a(N)=1.32 mT) was distinguished from DBNBS-SO(3)*(-) (a(N)=1.32 mT with an additional splitting of a(H)=0.06 mT) by (a) using different EPR parameters, (b) determining the effect of addition of sulfite on the EPR spectrum resulting from the incubation of DBNBS with either human biofluids or the horseradish peroxidase (HRP)-hydrogen peroxide (H(2)O(2)) system, and (c) replacing DBNBS with its analogues (DBNBS-d(2,) DBNBS-15N and DBNBS-d(2)-15N) in the two systems.
12126640 Ccr2 regulates the level of MCP-1/CCL2 in vitro and at inflammatory sites and controls T c 2002 May 21 CCR2, and its principle ligand MCP-1/CCL2, have been well documented for their ability to induce monocyte infiltration and promote the pathogenesis of rheumatoid arthritis and atherosclerosis. In order to assess additional roles for CCR2, we inserted allogeneic implants into CCR2-/- and MCP-1-/- mice and characterized T cell responses and the regulatory role of CCR2 on MCP-1 expression. The results demonstrate a marked decrease in lymphocyte infiltration in both CCR2-/- and MCP-1-/- animals. In contrast, IL-12 and CTL function were only suppressed in CCR2-/- animals. Further, whereas MCP-1 was only transiently elevated in the inflammatory fluid of WT animals, levels were sustained within the implants (5000pg/ml; >8 days) and serum (243pg/ml) of CCR2-/- mice. Higher levels of MCP-1 were also observed in the culture supernatants of CCR2-/- macrophages as compared to WT cells despite no difference in mRNA levels. Evidence that MCP-1 levels are regulated by receptor binding and internalization was suggested by its rapid decline when added to WT macrophages at 37 degrees C but not 4 degrees C. These studies indicate that CCR2 plays an important role in regulating T cell responses and controlling the level of MCP-1 at inflammatory sites.
12013503 Regulation of human B cell function by sulfasalazine and its metabolites. 2002 Apr Although sulfasalazine is a well-known disease-modifying antirheumatic drug (DMARD), the mechanisms of its action remain unclear. Indeed, it remains uncertain whether sulfasalazine itself or one of its metabolites is responsible for the antirheumatic effects of sulfasalazine. Since one of the characteristic features of rheumatoid arthritis (RA) is chronic stimulation of B cells, we compared the effects of sulfasalazine and its metabolites on the in vitro function of human B cells. Ig production was induced from highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. Sulfasalazine suppressed the production of IgM and IgG at its pharmacologically attainable concentrations (1-10 microg/ml). Of the metabolites of sulfasalazine, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA), but not 4-acethyl SP, also significantly suppressed the production of IgM and IgG at their pharmacologically relevant concentrations. By contrast, any of sulfasalazine, SP, 5-ASA and 4-acethyl SP did not suppress the IFN-gamma production of immobilized anti-CD3 stimulated CD4+ T cells. These results indicate that sulfasalazine and its metabolites preferentially suppress the function of B cells, but not that of T cells, at their pharmacologically attainable concentrations. The data therefore suggest that not only sulfasalazine, but its metabolites, might contribute to the beneficial effects of sulfasalazine.
12007704 Evaluation of chemical constituents and free-radical scavenging activity of Swarnabhasma ( 2002 May From ancient times, Swarnabhasma (gold ash) has been used in several clinical manifestations including loss of memory, defective eyesight, infertility, overall body weakness and incidence of early aging. Swarnabhasma has been used by Ayurvedic physicians to treat different diseases like bronchial asthma, rheumatoid arthritis, diabetes mellitus, nervous disorders, etc. In the present investigation, Swarnabhasma was prepared after proper purification and calcination as per Ayurvedic pharmacy which consisted of Realger (As(2)S(2)), Lead oxide (Pb(3)O(4)), Pure gold (Au) and Latex of Calotropis gigantea. Qualitative analyses indicated that Swarnabhasma contained not only gold but also several microelements (Fe, Al, Cu, Zn, Co, Mg, Ca, As, Pb, etc.). Infrared spectroscopy showed that the material was free from any organic compound. The metal content in the bhasma was determined by atomic absorption spectrometry. Acute oral administration of Swarnabhasma showed no mortality in mice (up to 1 ml /20 g b.w. of Swarnabhasma suspension containing 1mg of drug). Chronic administration of Swarnabhasma also showed no toxicity as judged by SGPT, SGOT, serum creatinine and serum urea level and histological studies. In an experimental animal model, chronic Swarnabhasma-treated animals showed significantly increased superoxide dismutase and catalase activity, two enzymes that reduce free radical concentrations in the body.
11927653 T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and 2002 Apr Adhesion of leukocytes to the vascular endothelium is an early event in inflammation. Since cell-cell signaling may be an important stimulus for endothelial activation, we focused in this study on the role of contact-mediated activation by T lymphocytes of endothelial cells (EC). T lymphocytes were cultured with anti-CD3 monoclonal antibody or in the presence of a combination of TNF-alpha, interleukin (IL)-6, and IL-2, prior to fixation and coculture with human umbilical vein EC. Fixed, activated (anti-CD3- or cytokine-stimulated), but not unstimulated T cells, induced release of monocyte chemotactic protein-1, IL-8, and IL-6 by EC in a contact-dependent manner. Moreover, expression of tissue-factor antigen and activity was also significantly increased. Addition of anti-CD40 ligand antibody abolished T cell-induced activation of EC. Our data suggest that contact-mediated activation of EC by T cells, involving ligand:counter ligand interactions such as CD40:CD40 ligand, may represent a novel pathogenic mechanism of progression in inflammatory diseases such as atherosclerosis or rheumatoid arthritis.
11895154 Fatty acids and lymphocyte functions. 2002 Jan The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.
11773609 Free radicals in the physiological control of cell function. 2002 Jan At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish "redox homeostasis." Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman (J Gerontol 11: 298-300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
15209999 Role of gene E2f1 in susceptibility to bacterial adherence of oral streptococci to tooth s 2004 Aug Dental plaque is composed of a biofilm community of microorganisms on teeth that coats the oral cavity, including attaching to the teeth, and provides a protective reservoir for oral microbial pathogens, which are the primary cause of persistent and chronic infectious diseases. Oral streptococci are pioneering organisms that play an important role in biofilm formation on tooth surfaces as well as being primary causative agents of dental caries. The purpose of this study was to clarify the role of the E2f1 gene in susceptibility to dry mouth and bacterial adherence of oral streptococci to tooth surfaces in animal model experiments. A mutation of the E2f1 gene in mice is known to cause enhanced T-lymphocyte proliferation, leading to testicular atrophy, splenomegaly, salivary gland dysplasia, and other systemic and organ-specific autoimmunity. We found a decreased volume of saliva production and protein production rate, along with increased amylase activity, IgA concentration, and mucin 1 concentration in E2F-1(-/-) mice as compared with the control C57BL/6 mice. Further, we quantified the recolonization of oral streptococci in E2F-1(-/-) mice and found that a higher number of some oral streptococci were colonized on the teeth of these mice. In particular, following oral ingestion of 1% sucrose in water, the colonization of Streptococcus mutans increased in comparison with other streptococci. Our results suggest that the E2f1 gene may affect susceptibility for oral biofilm formation by streptococci in humans with dry mouth.
12815278 Identification of the primary caspase 3 cleavage site in alpha II-spectrin during apoptosi 2003 Aug Alpha II-spectrin is one of the major proteins responsible for maintaining the cytoskeletal integrity of the cell. The caspase 3-mediated cleavage of alpha II-spectrin during apoptotic cell death may play an important role in altering membrane stability and the formation of apoptotic bodies. In this study, we identified the primary caspase 3 cleavage site in alpha II-spectrin. We found that the transcriptional inhibitor, actinomycin D, induced caspase 3 activation and that caspase 3 activation is coincident with the cleavage of alpha II-spectrin protein at a primary cleavage site. Deletion analysis and site directed mutagenesis identified the primary cleavage site in alpha II spectrin at amino acid 1185 (DETD). The primary caspase 3 cleavage site in alpha II spectrin is conserved in immature and mature B cells. Our results indicate that alpha II-spectrin is initially cleaved at a caspase 3 consensus site and this primary event likely alters the structural conformation of the protein exposing subsequent cleavage sites and altering cytoskeletal integrity. Identification of the primary cleavage site for caspase 3 may help to elucidate the role of alpha II-spectrin in membrane stability and apoptosis as well as provide new insights into alpha II-spectrin autoantibody formation associated with the autoimmune disease, Sjögren's syndrome.
12415590 Undifferentiated connective tissue disease: analysis of 83 patients with a minimum followu 2002 Nov OBJECTIVE: Undifferentiated connective tissue disease (UCTD) refers to a cluster of systemic disorders characterized by a simple clinical and autoantibody profile. Previously, we had described a series of 91 patients with UCTD who were followed at our unit for a minimum period of one year; here we report the extended followup of these patients. METHODS: Of the original 91 patients, 8 were lost to followup; the remaining 83, with a minimum followup of 5 years, were included in our analysis. RESULTS: During the followup 18 patients developed systemic lupus erythematosus (SLE) and one developed Sjögren's syndrome within a mean period of 54 months after the onset of the disease (range 17-96 mo). On analysis the 18 patients with SLE showed a clinical profile similar to cohorts reported in the literature. In one patient the evolution to SLE occurred during puerperium, but no other triggering factors were observed in our series. The presence of anticardiolipin antibodies and of multiple antibody specificities was significantly correlated with the development of SLE (p < 0.05). CONCLUSION: This analysis confirms the findings of our one year followup study that UCTD comprises a distinct group of mild diseases and that the rate of evolution to defined connective tissue diseases is higher during the first years after its onset. Patients who maintain an undifferentiated profile during the followup seem to run a decreasing risk of developing a defined CTD.
15093850 Pilocarpine toxicity and the treatment of xerostomia. 2004 May Pilocarpine has been used as an ophthalmologic agent for decades; however, toxicity rarely has been reported in the medical literature. Oral pilocarpine tablets, as well as another muscarinic agent (cevimeline), have recently been approved for the treatment of dry mouth (xerostomia). We report a case of unintentional overdose of oral pilocarpine tablets that resulted in bradycardia, mild hypotension, and muscarinic symptoms in a patient with Sjogren's syndrome. The patient's symptoms were relieved with 0.5 mg intravenous atropine and she recovered uneventfully. The case is unique in that it is the first reported ingestion of oral pilocarpine tablets and the first dosing error reported for this indication. In addition, this case underscores the importance of communication between physician and patient and the resulting toxicity related to miscommunication.
12512895 Value of minor salivary gland biopsy in diagnosing Sjögren's syndrome. 2002 Oct OBJECTIVE: Minor salivary gland biopsy is suggested for diagnosing Sjögren's syndrome in patients with clinical signs of sicca syndrome. This biopsy is mainly examined on the basis of the semiquantitative morphologic criteria without taking into account the detection of characteristic myoepithelial sialadenitis (MESA). DESIGN: The role of minor salivary gland biopsy in the diagnosis of Sjögren's syndrome as a possible detection method for MESA was examined in a retrospective study. METHODS: Minor salivary gland biopsies were obtained from 32 patients between 1986 and 1996. Twenty-two patients fulfilled the criteria for primary and 10 patients for secondary Sjögren's syndrome based on the catalogue of the European Study Group on Diagnostic Criteria for Sjögren's Syndrome. The histopathologic assessment was based on the histomorphologic MESA criteria, that is, parenchymatrophy, interstitial lymphocytic cell infiltration, and myoepithelial cell islands. RESULTS: The histopathologic assessment revealed normal minor salivary glands in 37.5% of the cases and chronic sialadenitis in 59.4% of the patients. Only one female patient (3.1%) had changes characteristic of MESA. CONCLUSION: Minor salivary gland biospy is therefore an unsuitable method for detecting MESA if the pathomorphologic correlative of MESA is used to confirm the diagnosis of Sjögren's syndrome.
12167246 Diverse perturbations may alter the lacrimal acinar cell autoantigenic spectra. 2002 May Lacrimal gland acinar cell autoantigens in Sjögren's syndrome include both intracellular proteins and plasma membrane proteins, to which the immune system normally must be tolerant. Attention has largely focused on the roles apoptotic cell death may play in exposing sequestered autoantigens and novel surface epitopes. We hypothesize that perturbations of ongoing membrane traffic in intact, functioning cells may also increase autoantigen exposure. We review the vesicular traffic between acinar cell basal-lateral plasma membranes (blm) and endomembrane compartments, then describe experiments in which isolated acinar cells were stimulated with epidermal growth factor (EGF), lysed, and analyzed by sorbitol gradient centrifugation. Whereas the cholinergic agonist, carbachol, impairs traffic from the trans-Golgi network to prelysosomes, causing Golgi, secretory, and lysosomal proteins to reflux into domains of the trans-Golgi network that communicate with the blm and to accumulate in the blm, EGF specifically causes a 2.6-fold (P < 0.05) increase in the beta-hexosaminidase content of the blm fraction, apparently by impairing traffic from early endosomes to prelysosome. We, therefore, suggest that a variety of physiologic stimuli may alter the spectra of autoantigens acinar cells secrete to the interstitium, express in their blm, and present via MHC Class II molecules after proteolytic processing.
12040964 General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug 2002 A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.
15579729 Pulmonary manifestations of primary Sjogren's syndrome: a clinical, radiologic, and pathol 2005 Mar 15 RATIONALE: Clinicopathologic pulmonary manifestations associated with primary Sjogren's syndrome have yet to be reviewed in a large series since the recognition of nonspecific interstitial pneumonia (NSIP) as a distinct histologic pattern. OBJECTIVES: To determine clinical presentations, high-resolution computed tomographic (HRCT) and histologic findings of the lung disease associated with primary Sjogren's syndrome in the light of NSIP, and to analyze prognosis of the disease. METHODS: On the basis of 33 cases (31 surgical lung biopsies and 2 autopsies) collected consecutively from multiple centers, we have retrospectively evaluated clinical, radiologic, and pathologic manifestations of the disease. Prognostic factors were identified by univariate and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: We found that NSIP was the most frequently seen histologic pattern (20 of 33 cases [61%], 19 fibrosing and 1 cellular). Bronchiolar diseases and amyloid and malignant lymphoma were seen less frequently. HRCT-pathologic correlation resulted in a 94% positive predictive value of CT-NSIP pattern for pathologic diagnosis of NSIP, whereas the diagnostic value of HRCT was low (15%) with an HRCT pattern other than NSIP, data that may influence the decision to biopsy. The 5-year survival rate was 84% overall and 83% in patients with NSIP. Multivariate analysis on all patients showed that low Pa(O(2)) (p = 0.02) and presence of microscopic honeycombing (p = 0.04) were independently associated with survival. Patients with NSIP showed lower vital capacity (mean +/- SD: 68.5 +/- 16.6%pred) than patients without NSIP (92.5 +/- 18.6%pred; p < 0.001). CONCLUSION: Among a diversity of pulmonary lesions in primary Sjogren's syndrome, NSIP was the commonest histologic pattern and had a favorable prognosis.
15098610 Severe interstitial cystitis associated with Sjögren's syndrome. 2004 Mar A 53-year-old woman presented with oliguria, urinary frequency, abdominal pain and severe edema of the lower extremities. Her serum creatinine was 8.1 mg/dl. Computed tomographic and ultrasonographic studies showed a severely dilated urinary bladder, and bilateral hydroureteronephrosis. Examination of a urinary bladder biopsy specimen showed subepithelial edema and infiltration by lymphocytes and plasmacytes. However, the patient complainted of dry mouth and dry eyes. Ophthalmologically, the Schirmer test was positive. A biopsy of the minor salivary glands in the lip showed chronic sialoadenitis. A diagnosis of Sjögren's syndrome complicated by interstitial cystitis was made. Since she had been anuric, secondary to urinary obstruction, intermittent self-catheterization was started. Combination of corticosteroid and cyclosporin therapy was initiated. Spontaneous urination began, and gradually the patient's symptoms remitted. After 8 months of therapy, bladder capacity increased from 140 ml to 350 ml, and she voided approximately 1,200 ml by herself and 600 ml by catheterization daily. This case suggests that when severe interstitial cystitis is associated with Sjögren's syndrome, a therapeutic trial of corticosteroids and cyclosporin may be beneficial.
14727559 [Two distinct types of neuropathy associated with Sjögren's syndrome developed in one pat 2003 Sep A 62-year-old woman was admitted to our hospital because of muscle weakness and sensory disturbance in extremities. She showed weakness, muscle atrophy and sensory abnormality in four limbs with patchy distribution, suggesting involvement of multiple peripheral nerve trunks. Serum titers of anti-SS-A, SS-B, and antinuclear antibody were elevated. Sural nerve biopsy showed recanalization and lymphocytic infiltration in the epineural small vessels, suggesting the presence of vasculitis. She was diagnosed as having vasculitic neuropathy complicated with Sjögren's syndrome. Methylprednisolone pulse therapy followed by oral prednisolone was started and these symptoms gradually improved in one month. At age 63, she felt dysesthesia in the right lower limb and this sensory abnormality spreaded to upper limbs. Two years later, she was admitted again due to clumsiness of hands and gait disturbance. Neurological examination showed decreased vibration and position sense of lower limbs and limb ataxia in addition to dysesthesia. Electrophysiological studies demonstrated significant decrease in amplitude of sensory nerve action potentials and delayed somatosensory evoked potentials after N13, indicating impairment of dorsal root ganglions. She was treated with intravenous immunoglobulin (400 mg/kg, total 15 g/day) for 5 days. One week later, sensory ataxia was improved. It has been known that Sjögren's syndrome is often complicate with various types of neuropathies including vasculitic neuropathy and sensory neuropathy. Our patient developed these two different types of neuropathies which were dramatically improved after two different therapeutic regimens; indicating the importance to select a suitable treatment regimen in accordance with the mechanism of neuropathy associated with Sjögren's syndrome.
12184435 Is the relationship between spondyloarthropathy and Sjögren's syndrome in women coinciden 2002 Jun OBJECTIVE: To determine the prevalence of Sjogren's syndrome (SS) in women with spondyloarthropathy (SpA). METHODS: Forty-one women with SpA manifesting as inflammatory back pain and/or peripheral arthritis were diagnosed as having ankylosing spondylitis, undifferentiated spondyloarthropathy, psoriatic arthritis, or enteropathic arthropathy based on accepted criteria. A validated questionnaire was used to look for sicca symptoms in the SpA group and in 102 controls with degenerative rheumatic diseases. Women with SpA and sicca symptoms and/or positive antinuclear antibodies (ANA) were investigated for SS by minor salivary gland biopsy. In the SpA group, the following tests were done: HLA B27; HLA DR, DQ; ENA; and serology for CMV, EBV, HIV, hepatitis B, and hepatitis C. RESULTS: Thirteen women (31.7%) met European criteria for SS, compared to three (2.9%) of the controls. Of the 41 women with SpA, 16 (39%) were ANA-positive. ANA were detected in eight of the 16 (50%) patients with SS. HLA B27 was present in 11 of the 13 (84.6%) SS patients. HLA DR 04.04 and DQ 03.03 seemed more common in SS patients, but the difference was not statistically significant. CONCLUSION: SS was far more common in the women with SpA (31.7%) than in the controls (2.9%), suggesting that the SpA-SS association may not be coincidental.
12022353 Change in final diagnosis on second evaluation of labial minor salivary gland biopsies. 2002 May OBJECTIVE: We evaluated the diagnostic accuracy of labial salivary gland specimens from a group of patients with symptoms or signs of dry mouth and/or dry eyes referred for assessment of possible Sjögren's syndrome (SS). METHODS: Fifty-eight individuals (52 women, 6 men; median age 54.5 yrs, range 19-90) had previously undergone one (n = 58) or 2 (n = 2) labial salivary gland biopsies, serologic studies, and objective tests for dry eyes and/or dry mouth to diagnose possible SS. Patients were referred to our institution for a second opinion regarding diagnosis and/or management of SS. All biopsy specimens underwent blinded review to measure aggregate glandular area, identify lymphocytic foci, and calculate focus scores that might verify the submitted diagnoses. Results were classified according to accepted histologic criteria: chronic sialadenitis, focal lymphocytic sialadenitis, indeterminate, insufficient tissue for diagnosis, and within normal limits. Institutional sources of submitted diagnoses included university hospitals (n = 26), university affiliates (n = 9), community hospitals (n = 18), commercial laboratories (n = 6), and a governmental agency (n = 1). RESULTS: Upon reexamination, 32 of 60 accessions (53%) sustained a revision of the initial diagnosis. Application of the focus scoring system combined with clinical features to reveal 12 hitherto undocumented cases of SS and refuted the diagnosis of SS in 8 instances. The principal reason for inaccurate initial interpretation was failure to apply the focus scoring system in 58 of 60 instances. Median diagnostic delay for the 12 SS cases was 302 days (range 55-2821). CONCLUSION: It is possible that widespread cross-institutional failure to apply the focus scoring system in the interpretation of labial salivary gland biopsies may delay the recognition and/or treatment of SS.
12165360 Effects of dietary omega3 and omega6 lipids and vitamin E on chemokine levels in autoimmun 2002 Aug Elevated levels of chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), and Macrophage Inflammatory Protein-1beta (MIP-1beta) have been found in rheumatoid arthritis (RA) and juvenile arthritis (JA), and they may be associated with the pathogenesis of these diseases. These chemokines are implicated in the migration of specific leukocytes into the joints. Omega-3 (omega3) fatty acid rich-fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study was designed to understand the effects of dietary lipids (omega-6 and omega-3 fatty acids) and vitamin E on the production of chemokines in autoimmune-prone MRL/lpr (a mouse model for RA) and congenic control MRL/++ mice. The MRL mice were fed for 4.5 months omega-6 and omega-3 diets that varied in lipid sources (corn oil; CO and fish oil; FO) and vitamin E levels (269 I.U./kg and 694 I.U./kg diet). Spleen cells were isolated and cultured aseptically in the presence of PHA for 48 h at 37 degrees C and the levels of chemokines (RANTES, JE/MCP-1 and MIP-1alpha) were determined in the cell-free supernatants. The levels of RANTES and JE/MCP-1 were significantly higher in MRL/lpr mice compared to MRL/++ mice. The FO had differential effect on RANTES and MCP-1 production by spleen cells. The production of RANTES and JE/MCP-1 by spleen cells in mice fed the FO diets was significantly lower than in mice fed the CO diets (p < 0.0001). The levels of vitamin E did not affect the production of RANTES and JE/MCP-1. The levels of vitamin E had a significant effect on MIP-1alpha as the spleen cells of mice fed diets containing 694 IU/kg diet of vitamin E produced significantly higher levels of MIP-1alpha compared to the group of mice fed the diets containing 269 IU of vitamin E (p < 0.0001). The data obtained from this study in MRL/lpr and MRL/++ mice suggest that FO diets containing omega-3 fatty acids are beneficial in decreasing the levels of certain pro-inflammatory chemokines (RANTES and MCP-1) thereby delaying the onset of and severity of autoimmune symptoms in MRL/lpr mouse model.