Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 12531122 | The significance of saliva during sleep and the relevance of oromotor movements. | 2002 Jun | Saliva is an essential component of the oroesophageal milieu and allows for normal speech, taste, mastication, food bolus formation and swallowing. Saliva has important functions in protecting the hard and soft tissues of the oral cavity from acids and pathogenic microbes. A large number of people suffer either subjective or objective alterations in quantity and/or quality of their saliva that may be secondary to disease, medications, medical treatments or emotional events. Sleep-related xerostomia is a sensation of dry mouth associated with a report of either mouth and/or throat discomfort that induces awakenings for water intake. The prevalence of self-reported dry mouth complaint during sleep (associated with awakening and water intake) in a Canadian survey was estimated at 23%. The biological significance of decreased saliva during sleep is unknown and it is unclear how the oral cavity compensates for this period of relative dryness. The amount of saliva produced is greatest during the waking hours of the day and diminishes dramatically during sleep and may represent another process in the human body that displays a circadian rhythmicity. Salivary secretion during wakefulness is, in part, associated with oromotor activity involving the masticatory muscles. Rhythmic masticatory muscle activity and swallowing are non-disruptive events that occur during normal sleep. We hypothesize herein that lubrication from saliva is necessary during sleep to protect tissue integrity and health of oroesophageal structures. | |
| 12532188 | Bone marrow transplantation: a new strategy for intractable diseases. | 2002 Feb | Bone marrow transplantation is becoming a powerful strategy for the treatment of hematologic disorders (leukemia, aplastic anemia, etc.), congenital immunodeficiencies, metabolic disorders and also autoimmune diseases. Using various animal models for autoimmune diseases, we have previously found that allogeneic (not autologous) bone marrow transplantation can be used to treat autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, immune thrombocytic purpura, insulin-dependent diabetes mellitus, chronic glomerulonephritis and certain types of non-insulin-dependent diabetes mellitus. In contrast, we have found that the transplantation of T-cell-depleted bone marrow cells or partially purified hemopoietic stem cells from autoimmune-prone mice to normal mice leads to the induction of autoimmune diseases in the recipients. These findings have recently been confirmed even in humans; autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Crohn's disease were resolved after allogeneic bone marrow transplantation. However, there have recently been reports on the rapid recurrence or persistence of autoimmune diseases after autologous bone marrow transplantation. Conversely, the adoptive transfer of autoimmune diseases such as myasthenia gravis, insulin-dependent diabetes mellitus and Graves' disease by allogeneic bone marrow transplantation from donors to recipients has been reported. Owing to these findings, we have proposed that autoimmune diseases are "stem cell disorders." We have thus succeeded in treating autoimmune diseases in various autoimmune-prone mice, except MRL/lpr mice, by conventional bone marrow transplantation. The MRL/lpr mouse itself is radiosensitive (<8.5 Gy), while the abnormal hemopoietic stem cells of the MRL/lpr mouse are radioresistant (>8.5 Gy); conventional bone marrow transplantation (8.5 Gy plus bone marrow transplantation) has a transient effect on autoimmune diseases, which recur three months after the bone marrow transplantation. However, bone marrow transplantation plus bone grafts (to recruit donor stromal cells) completely prevents the recurrence of autoimmune diseases in MRL/lpr mice. Donor-derived stromal cells (including mesenchymal stem cells) thus seem to play a crucial role in successful allogeneic bone marrow transplantation, since there is a major histocompatibility complex restriction between hemopoietic stem cells and stromal cells. We have, however, found that the combination of bone marrow transplantation plus bone grafts has no effect on the treatment of autoimmune diseases in MRL/lpr mice, since MRL/lpr mice become more radiosensitive after the onset of lupus nephritis due to the development of uremic enterocolitis. To reduce the cytotoxic effect of radiation on the intestine, we carried out fractionated irradiation and devised a new strategy. We injected allogeneic whole bone marrow cells (including a small number [<3%] of T cells, hemopoietic stem cells and stromal cells) from donors directly into the intra-bone marrow of recipients so that donor-derived hemopoietic cells including stromal cells could effectively accumulate in the bone marrow. All the MRL/lpr mice survived more than one year (>60 weeks after birth) without the recurrence of autoimmune diseases, and immunological functions were completely restored even when the radiation dose was reduced to 5 Gy x 2. These findings suggest that intra-bone marrow injection-bone marrow transplantation can be used to treat intractable autoimmune diseases under reduced radiation doses without using any immunosuppressants.Intra-bone marrow injection-bone marrow transplantation seems to be the best strategy for allogeneic bone marrow transplantation: 1) no graft-versus-host disease develops even if T cells are not depleted from the bone marrow; 2) no graft failure occurs even if the dose of radiation as the conditioning for bone marrow transplantation is reduced to 5 Gy x 2; 3) hemopoietic recovery is rapid; and 4) T-cell functions are completely restored even in donor-recipient combinations across the major histocompatibility complex barriers. Using cynomolgus monkeys, we have recently established a new method (the "perfusion method") for collecting bone marrow cells from the long bones (femur, humerus, etc.) without peripheral blood contamination. This method has various advantages: 1) no graft-versus-host disease develops even in cynomolgus monkeys, since the percentage of T cells in the bone marrow cells collected is less than 3%; 2) a large number of bone marrow cells can be collected quickly and safely; and 3) the bone marrow cells collected contain stromal cells including mesenchymal stem cells. We therefore believe that this method (intra-bone marrow injection-bone marrow transplantation in conjunction with the perfusion method) will become a powerful new strategy for not only allogeneic bone marrow transplantation but also organ transplantation in conjunction with bone marrow transplantation. Furthermore, this method could become a valuable strategy in regeneration therapy for injured organs and tissues (myocardial infarction, cerebral infarction, Alzheimer's disease, etc.), since it can efficiently reconstitute the recipient with both donor-derived hemopoietic stem cells and mesenchymal stem cells. | |
| 12225893 | Nitric oxide synthase I and VIP-activated signaling are affected in salivary glands of NOD | 2002 Sep | The autoimmune sialadenitis developed by non-obese diabetic (NOD) mice is considered a suitable model to study the ethiopathogenic mechanisms leading to sicca symptoms in Sjögren's syndrome (SS). Evidence supporting a neural rather than immune origin of the secretory dysfunction has been provided. As both nitric oxide and vasoactive intestinal peptide (VIP) are common messengers to nervous and immune systems mediating secretory and inflammatory responses, we examined nitric oxide synthase (NOS) activity with special focus on VIP-mediated effects in salivary glands of NOD mice. We found a decreased NOS activity and expression in major salivary glands of NOD mice with respect to control mice. In addition, there was a deficient VIP-activated signaling associated with a reduced saliva and amylase secretion in response to VIP. Our results support the hypothesis of an impaired balance of neuroimmune interactions in salivary glands as early events to take place in the progressive loss of secretory function of NOD mice. | |
| 11876766 | CD40 on salivary gland epithelial cells: high constitutive expression by cultured cells fr | 2002 Feb | CD40 has been identified in an expanding list of haematopoietic and non-haematopoietic cells and has received an increased interest based on its role in a variety of cell-mediated responses and its potential to participate in the pathogenesis of chronic inflammatory disorders. Sjögren's syndrome (SS) is an autoimmune exocrinopathy, which is characterized by chronic lymphocytic infiltration of exocrine glands and aberrant activation of epithelial tissues. We studied the expression of CD40 protein in cultured non-neoplastic salivary gland epithelial cell (SGEC) lines as well as in minor SG biopsies obtained from 17 SS patients and 12 controls. Immunocytochemical and flow cytometric analyses had revealed the occurrence of constitutively expressed CD40 molecules on the surface of long-term cultured SGEC lines, which could be further induced by interferon-gamma (IFN-gamma) and IL-1beta cytokines, but not tumour necrosis factor-alpha (TNF-alpha), IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IFN-alpha. Triggering of SGEC through CD40 enhanced the surface expression of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1)/CD54, but not MHC class I and class II (HLA-DR) molecules. Spontaneous CD40 expression was significantly higher in SGEC lines derived from SS patients, compared with controls (P < 0.001), which is suggestive of their intrinsically activated status. In SG biopsies, CD40 was constitutively expressed by lymphocytes, ductal epithelial cells and endothelial cells but not by other glandular cell types, such as acinar cells, myoepithelial cells and fibroblasts. In addition, CD40L staining was also detected in 30--50% of the infiltrating lymphocytes in the biopsies of SS patients. Our findings indicate the immunoregulatory potential of SGEC and lend further support to a model of intrinsic activation in salivary epithelia in SS, whereby these cells actively participate in the induction and maintenance of lymphocytic infiltrates of patients. | |
| 15483550 | Monarthritis of the pediatric knee joint: differential diagnosis after a thorn injury. | 2004 Oct | Foreign-body injury of the juvenile knee is frequently seen in the outpatient department. Arthroscopy is the most important diagnostic and therapeutic procedure along with radiographic examination in a case of typical history and clinical symptoms. In this case, an intra-articular thorn in a juvenile knee was not diagnosed at arthroscopy despite typical injury. Five months later, the boy developed knee pain and joint swelling. Bacterial infection of the knee and rheumatoid causes were excluded by serologic blood analysis several times at the children's hospital. Magnetic resonance imaging of the knee revealed an intra-articular foreign body. At a second arthroscopy, the thorn was removed and a hypertrophic plica with dependent cartilage damage of the medial femoral condyle was resected. At follow-up after 4 weeks, the boy was free of pain and swelling. After the first arthroscopy, persistent knee swelling and pain had to be taken as a hint of an intra-articular irritation. All arthroscopic surgeons should do a complete diagnostic examination of the affected joint in case of a foreign-body injury. | |
| 15457459 | Effective treatment of a mouse model of Sjögren's syndrome with eyedrop administration of | 2004 Sep | OBJECTIVE: To determine whether eyedrop administration of an anti-CD4 monoclonal antibody (mAb) is effective in the treatment of Sjögren's syndrome (SS) using a mouse model of the disease. METHODS: The anti-CD4 mAb was administered daily into the eyes of mice with SS from ages 4 to 8 weeks or ages 10 to 12 weeks. During treatment, tear volume was monitored and after final treatment, histologic features of the lacrimal and salivary glands, the phenotypes and function of T cells, and serum titers of anti-alpha-fodrin antibody were examined. RESULTS: Eyedrop administration of anti-CD4 mAb before the onset of SS prevented the autoimmune pathology seen in the lacrimal glands but not that in the salivary glands. Furthermore, eyedrop administration of anti-CD4 mAb after the development of SS inhibited mononuclear cell infiltration and the destruction of parenchyma only in the lacrimal glands. Eyedrop administration of anti-CD4 mAb suppressed the local activation of CD4+ T cells rather than deleting CD4+ T cells, which reduced the expansion of pathologic CD4+ T cells against alpha-fodrin. CONCLUSION: These results demonstrate the remarkable efficacy of anti-CD4 mAb eyedrops in the treatment of SS eye symptoms, which illustrates a new antibody-based therapeutic strategy for patients with eye problems caused by SS as well as other diseases. | |
| 12548436 | Intra-erythrocyte deposition of growth hormone in rheumatic diseases. | 2003 Jan | Standard radioimmunoassay was employed to quantify matched basal intra-erythrocyte growth hormone (GH) and serum GH levels from patients with osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH), gout, and Sjögren's syndrome and in a group of normal volunteers (control group). Basal intra-erythrocyte GH concentration was significantly higher ( P<0.05) than serum GH concentration in blood samples from patients with osteoarthritis and DISH but not from those with gout or Sjögren's syndrome. Regression analysis determined that basal serum GH levels did not correlate with age. While intra-erythrocyte GH levels exceeded serum GH levels in osteoarthritis and DISH, intra-erythrocyte GH was not a strong predictor of serum GH levels in osteoarthritis, DISH, or in the control group. | |
| 15379867 | Abnormal cell-specific expressions of certain protein kinase C isoenzymes in peripheral mo | 2004 Oct | We have studied the expressions of various protein kinase C (PKC) isoenzymes in T cells and monocytes from patients with systemic lupus erythematosus (SLE), in comparison to those of healthy controls and patients with other immunological disorders. As measured by Western blotting, the levels of PKCbeta, delta, eta, epsilon, theta and zeta (but not of PKCalpha) significantly decreased in T cells of SLE patients. In monocytes, however, we observed marked suppressions only in the expressions of PKCdelta, epsilon and zeta but not in the expressions of other PKC isoforms. In vivo corticosteroid application, as well as in vitro steroid treatment of monocytes, elevated the expressions of most isoforms close to normal values; however, the decreased levels of PKCtheta and zeta were not affected by steroid application. These alterations were characteristic to SLE because we could not detect any changes in the PKC levels in mononuclear cells of primary Sjögren's syndrome and mixed connective tissue disease patients. These results suggest that impaired PKC isoenzyme pattern may exist in the T cells and monocytes of SLE patients. Furthermore, the clinically efficient glucocorticoid application in SLE can increase the expression of some members of PKC system. | |
| 12784417 | Canadian Rheumatology Association Consensus on the use of anti-tumor necrosis factor-alpha | 2003 Jun | Spondyloarthritis (SpA) represents a group of related arthritides characterized by their association with HLA-B27 and the development of sacroiliitis and enthesitis. Functional impairment, disability, and loss of quality of life may resemble that observed in rheumatoid arthritis. The SpA Research Consortium of Canada (SPARCC) is an informal association of rheumatologist members of the Canadian Rheumatology Association (CRA) with a special interest in therapeutics and outcomes research in SpA. Recent experience with anti-tumor necrosis factor-a (anti-TNF-a) directed therapies prompted a consensus-based evaluation of the evidence supporting their efficacy, safety, and appropriate use in SpA. We evaluated the clinical evidence in support of anti-TNF-a directed therapies in SpA. Medline was searched using appropriate keywords. Abstracts of the 1999-2002 annual meetings of the American College of Rheumatology and the European Congress of Rheumatology were extracted and admitted if sufficient detail was available to determine the level of evidence. Recommendations were based on randomized placebo-controlled trials (Level A evidence) and clinical studies without randomization (Level B evidence). Where the scientific literature was incomplete, recommendations reflected the consensus of SPARCC members (Level C evidence). Following development of an original draft document, consensus for revisions was achieved among members of SPARCC. The document was then posted on the CRA website prior to its final revision. The following recommendations have been endorsed by the Therapeutics Committee of the CRA: Infliximab and etanercept are indicated for reduction of signs and symptoms of moderate to severely active SpA in patients who have had an inadequate response to maximal doses of > or = 2 nonsteroidal antiinflammatory drugs (NSAID) over a 3-month period of observation; and either sulfasalazine or methotrexate is indicated in those with predominantly active peripheral arthritis. Current evidence supports their use as monotherapy (level of evidence A) for at least one year. NSAID and/or second line therapy with either sulfasalazine or methotrexate can be continued concomitantly. There is no evidence addressing potential advantages or disadvantages of combining methotrexate with anti-TNF therapy for SpA. Recommended doses for adults are: infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter; etanercept 25 mg subcutaneously twice weekly. No therapy has been shown to slow progression of axial disease in SpA, and prognostic factors for determining response to therapy remain to be determined. It is the position of the CRA that all therapeutic options should be equally available according to the best judgments of the treating physician and the informed decision of the patient. | |
| 14530197 | Sulfatides: targets for anti-phospholipid antibodies. | 2003 Oct 28 | BACKGROUND: Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. METHODS AND RESULTS: Beta2-glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound beta2-glycoprotein I. CONCLUSIONS: These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome. | |
| 12223516 | Interferon-gamma stimulates the expression of galectin-9 in cultured human endothelial cel | 2002 Sep | Galectin-9 is a member of the galectin family and has been identified as an eosinophil chemoattractant produced by activated T lymphocytes. Vascular endothelial cells play an important role in the initial step of eosinophil recruitment and activation in immune and inflammatory responses. We have addressed the stimulation of galectin-9 expression in endothelial cells. Galectin-9 was detected in membrane and cytosolic fractions of human umbilical vein endothelial cells stimulated with interferon-gamma (IFN-gamma). IFN-gamma also enhanced the adhesion of human eosinophilic leukemia-1 cells to endothelial monolayers, and it was inhibited by the presence of lactose. Interleukin-4, which induces eotaxin expression, did not affect the expression of galectin-9. The in situ endothelium from patients with inflammatory diseases was found to express galectin-9. IFN-gamma-induced production of galectin-9 by endothelial cells may play an important role in immune responses by regulating interactions between the vascular wall and eosinophils. | |
| 15207789 | Adult Still's disease reflects a Th2 rather than a Th1 cytokine profile. | 2004 Jul | Adult Still's disease (ASD) is a chronic multisystemic disease. Extraordinarily high serum levels of IL-18 in ASD patients have been described, whereas the mechanism remains to be clarified. This study aimed to evaluate proinflammatory cytokines and to consider their pathological roles. In patients with rheumatic diseases (n = 151), blood samples were taken at the active phase and the serum levels of IL-18 and other proinflammatory cytokines were measured by ELISA. The extra-high levels of IL-18 were confirmed selectively in ASD patients (n = 10). In the active phase of ASD patients, the levels of IL-6 were elevated accordingly, but IL-1beta and TNF-alpha were undetectable. As to Th1-Th2 cytokines, the levels of IL-4 and IL-13, but not INF-gamma, IL-12, or IL-2, were elevated in all ASD patients examined. Moreover, the serum levels of IL-18 showed a good correlation with those of IL-4, suggesting that ASD reflects a Th2 rather than a Th1 cytokine profile. | |
| 15039641 | Histopathological and immunohistochemical analysis of lymphoid follicles in labial salivar | 2004 Apr | BACKGROUND: Ectopic lymphoid follicles are considered morphological indices of local chronic antigen stimulation. The objective of this study was to present a detailed histopathological and immunohistochemical analysis of ectopic lymphoid follicles in salivary glands in Sjögren's syndrome (SS), compared to lymphoid follicles in lymph nodes. MATERIAL/METHODS: Samples of labial salivary glands from 37 patients with primary and 57 with secondary SS were examined by histopathology and immunohistochemical methods with monoclonal antibodies (DAKO) to identify follicular dendritic cells, T and B lymphocytes, immunoglobulins and class II MHC HIA DPQR. Lymph nodes from 2 patients with primary SS were also examined for the same markers. RESULTS: Focal inflammatory infiltrations in labial salivary glands in 64.9% of primary and 23.1-49.6% secondary SS were found to morphologically mimic lymphoid follicles in various stages of development. Secondary ectopic lymphoid follicles resemble the histological structure and immunohistochemistry of germinal centers in lymphoid follicles in reactive lymph nodes due to the large number of centrally located B cells (CD20+), reticular pattern of dendritic cells (CD21+) and T helper/inducer cells (CD4+). The centers of secondary ectopic lymphoid follicles contain deposits of IgG and IgM. CONCLUSIONS: Ectopic lymphoid follicles quite often present in labial salivary gland in SS show structural and immunohistochemical features typical for lymphoid tissue. These ectopic follicles are the place of immune complex trapping, antigen presentation on dendritic cells and initiation of autoimmunologic response. This finding seems be very important for better understanding of the pathogenesis and diagnosis of SS as an autoimmunlogical disorder. | |
| 12472667 | CD40, CD154, Bax and Bcl-2 expression in Sjögren's syndrome salivary glands: a putative a | 2002 Dec | Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by chronic lymphocytic infiltration and decreased secretion in the salivary glands (SGs). For some time, apoptosis has been suggested to constitute the major mechanism for acinar epithelial destruction during the effector phases; however, this is still controversial. We have recently demonstrated that despite the expression of Fas and FasL, the incidence of apoptosis is not increased in SS patients compared with control individuals. Our aim was therefore to further evaluate the expression of the pro- and anti-apoptotic Bax and Bcl-2 proteins. CD40 and CD154 expression was also investigated, as CD40 ligation has been suggested to protect cells from Fas-mediated apoptosis. Immunohistochemical staining was performed on SG tissue from primary and secondary SS patients, a group of patients with non-SS-related degenerative changes as well as on healthy control individuals. The frequency of stained cells in the foci of infiltrating mononuclear cells (IMCs) and in the acinar and ductal epithelium was determined. We found the expression of Bcl-2 but rarely Bax in SS SG IMCs. Bcl-2 in epithelial cells was sparse, while Bax expression occurred frequently and with no significant difference between the patient groups. CD40 and CD154 expression was high among SS IMCs, while CD40 levels were slightly decreased in SS epithelium compared with controls. Elevated CD154 expression was found in SS epithelium, being significantly increased in the ducts. In conclusion, our study further supports the hypothesis about apoptosis resistance among SS focal IMCs and suggests a putative protective role of CD40 ligation in SS SG epithelium. | |
| 15724389 | Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren | 2004 | Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS. | |
| 12640289 | Extrahepatic manifestations of hepatitis C infection. | 2003 Mar | Hepatitis C virus (HCV) affects 1.8% of the American population, and approximately 38% of patients with HCV will manifest symptoms of at least 1 extrahepatic manifestation during the illness. Renal disease, neuropathy, lymphoma, and Sjögren syndrome with or without mixed cryoglobulinemia are all strongly associated with HCV infection. Porphyria cutanea tarda and diabetes have also been linked to HCV. Most extrahepatic manifestations of chronic HCV infection are immunological, and the chronic infection seems to be necessary for their development. The molecular study of the unique way in which the HCV virus interacts with the human immune system is beginning to provide plausible explanations of the pathogenic role of HCV in some of these syndromes, but many pathogenetic links remain completely obscure. | |
| 15475440 | A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor in patien | 2004 Oct 1 | PURPOSE: Tumor necrosis factor (TNF) alpha is a key player in the tumor microenvironment and is involved in the pathogenesis of breast cancer. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biological activity, and therapeutic efficacy of Etanercept in metastatic breast cancer. EXPERIMENTAL DESIGN: We initiated a Phase II, nonrandomized, open-labeled study in patients with progressive metastatic breast cancer refractory to conventional therapy (Phase I toxicity data were available in patients with rheumatoid arthritis). Etanercept was administered subcutaneously at a dose of 25 mg twice weekly until disease progression. RESULTS: Sixteen patients were recruited [median age 53 years (range, 34 to 74)]. A total of 141.6 weeks of therapy was administered (median of 8.1 weeks). Seven patients received > or =12 weeks of therapy. The most common side effects were injection site reactions (6), fatigue (5), loss of appetite (2), nausea (1), headache (1), and dizziness (1). Brief period of disease stabilization was seen in 1 patient lasting for 16.4 weeks. Immunoreactive TNF-alpha was elevated within 24 hours of therapy and persisted until the end of treatment (days 7, 28, 56, and 84). Phytohemagglutinin stimulates the production of interleukin-6 and CCL2 in peripheral blood cells, and the ability of Etanercept to modulate this response was assessed in a cytokine release assay. A consistent decrease in interleukin-6 and CCL2 level was seen compared with pretreatment values in serial blood samples (days 1, 7, 28, 56, and 84). CONCLUSIONS: Our study shows the safety and biological activity of Etanercept in breast cancer and provides data to assess pharmacodynamic endpoints of different schedules of Etanercept and combinations with chemotherapy or other biological therapies. | |
| 12591005 | Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. | 2003 Mar | The anti-inflammatory effects of both n-3 and n-6 polyunsaturated fatty acids (PUFA) have been demonstrated in vitro and in many disease states, in particular in the treatment of rheumatoid arthritis. The benefit of n-3 PUFA supplementation has been documented in animal models of periodontal inflammation and a trend towards reduced inflammation has been seen in human experimental gingivitis. The purpose of this study was to examine the potential anti-inflammatory effects of PUFA supplementation, by administration of fish oil as a source of the n-3 PUFA, eicosapentaenoic acid, and borage oil as a source of the n-6 PUFA, gamma-linolenic acid (GLA), to adults with periodontitis. Thirty adult human subjects with periodontitis were administered either fish oil 3000 mg daily; borage oil 3000 mg daily; fish oil 1500 and borage oil 1500 mg daily, or placebo. The modified gingival index, the plaque index (PI), periodontal probing depths and beta-glucuronidase levels in gingival crevicular fluid were measured at baseline and after 12 weeks of treatment. Improvement in gingival inflammation was observed in subjects treated with borage oil (P<0.016), with a trend apparent in subjects treated with fish oil or a combination of PUFA. There was no statistically significant improvement in PI, although a trend was apparent in those receiving borage oil. Improvement in probing depth was seen in those subjects treated with either fish oil alone or borage oil alone, but statistical significance was only seen for the comparison of borage oil and placebo (P<0.044). No change was seen in gingival crevicular fluid (GCF) beta-glucuronidase levels. The use of borage oil supplementation, a source of the n-6 PUFA, GLA, can have beneficial effects on periodontal inflammation. n-6 PUFA supplementation seemed to offer more impressive results than either n-3 PUFA supplementation or the combination of lower doses of the two supplements. Additional studies will be necessary to more fully assess the potential of these agents to favorably affect periodontal inflammation. | |
| 17041399 | Prescription and tolerability of meloxicam in day-to-day practice: postmarketing observati | 2002 Dec | The goal of this study was to obtain data for prescription habits, tolerability for patients at high risk, and clinical effectiveness of meloxicam administered at 7.5 mg and 15 mg for various rheumatic diseases under real world prescribing conditions. This was a 3-month large-scale prospective observational cohort study in 4000 medical practices throughout Germany shortly after the introduction of meloxicam. To be eligible, patients had to have a diagnosis of acute or chronic active rheumatic disease for which nonsteroidal antiinflammatory drug (NSAID) therapy was required according to the prescribing information. In this study, 13,307 patients receiving meloxicam prescriptions (7.5 mg in 65% and 15 mg in 33%) were observed. The diagnoses of these patients included osteoarthritis (61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%), and other rheumatic conditions (28%). A substantial proportion of high risk patients were enrolled: 12% with a previous history of a perforation, ulceration, and bleeding (PUB), 24% with at least one concomitant cardiovascular disorder, and 26% receiving concomitant antihypertensive medication. Many of the patients (58%) had received NSAIDs before meloxicam, including patients with insufficient prior treatment effectiveness (43%) and those with NSAID-related adverse drug reactions (21%). In 85% and 94% of the patients, respectively, effectiveness and tolerability were rated as good or very good. Quality of life and daily functions improved in 64% to 84% of the patients. Only 0.8% of the patients reported gastrointestinal (GI) adverse drug reactions. Four uncomplicated cases of gastric ulceration, one serious perforated gastric ulcer, and one serious ileus complication were reported after incorrect use or overdosing of meloxicam. Treatment with the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam in doses of 7.5 mg and 15 mg resulted in meaningful treatment responses under real life conditions, despite inclusion of a substantial number of patients with insufficient effectiveness of previous use of non-COX-2 selective NSAIDs. All major GI toxicity (PUB) observed was owing to the fact that prescribing conditions were not respected appropriately. Despite a selection of high risk patients overall, GI, cardiovascular, and renal tolerability was favorable. | |
| 15766230 | Use of osteogenic protein-1 in spinal fusion: literature review and preliminary results in | 2002 Dec 15 | OBJECT: The safety and effectiveness of osteogenic protein (OP)-1 putty (recombinant human bone morphogenetic protein-7) in promoting fusion in complex spinal cases was studied in nine cases. METHODS: The authors prospectively evaluated nine patients requiring spinal fusion in whom there were medical risk factors that would inhibit osseous fusion. Intraoperatively the OP-1 putty mixed with autologous bone was placed at the fusion site. Outcome measurement instruments were used to provide information on patient demographics, comorbidities, and pain. The Short Form (SF)-36 questionnaire and Oswestry Disability Index (ODI) were administered pre- and postoperatively. All patients underwent routine radiography of the surgery site during follow-up examination. The age of the five women and four men ranged from 21 to 74 years (mean height 1.6 m, mean weight 76.7 kg). Risk factors included mucopolysaccharide syndrome, adrenal insufficiency, rheumatoid arthritis with chronic corticosteroid use, morbid obesity, and heavy smoking. Surgery, which consisted of five cervical and four lumbar procedures, including intradural surgery in three patients, was uneventful in all cases without perioperative complication. The follow-up period ranged from 1 to 15 months (mean 5.22 months). The ODI score changed from severe disability (mean 46.89) preoperatively to minimal and moderate disability (mean 34.56) postoperatively. The SF-36 survey showed overall improved mental and physical health scores. Fusion was present in all patients with greater than 3 months follow up. CONCLUSIONS: The OP-1 putty appears to be safe and effective in promoting spinal arthrodesis in patients in whom adverse medical risk factors exist. |