Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18593340 Prevalence and pattern of cross-reacting antibodies to HIV in patients with tuberculosis. 2008 Jul In many countries, HIV testing among tuberculosis (TB) patients is recommended so that both infections are appropriately treated. Cross-reacting antibodies to HIV antigens have been reported for several conditions, including TB, leprosy, malaria, and rheumatoid arthritis. To study the pattern and prevalence of cross-reacting antibodies to HIV antigens, we examined sera from 153 HIV-negative TB patients and 40 healthy individuals in Chennai, south India. We also studied the differences in cross-reactivity of various HIV antigens using two different Western blot kits. Of the 153 samples studied, 80 were tested using HIV Western blot and 73 were tested using INNOLIA. Most patients in the study had concordantly negative ELISA and rapid tests, and no subject had a positive Western blot. However, seven TB patients had antibodies that cross-reacted with HIV antigens, giving rise to an indeterminate result. While p51/55 was the most frequently recognized antigen in the Western blot assay, antibodies to sgp120 was most frequently identified in INNOLIA. Sequence similarities between the two organisms could be responsible for eliciting cross-reacting antibodies, since a few related epitopes were identified in HIV and Mycobacterium. These findings could have potential implications for the development of diagnostics and vaccines.
18440188 Nonoperative management of unruptured visceral artery aneurysms: treatment by transcathete 2008 Jun PURPOSE: To describe our experiences with the treatment of visceral artery aneurysms (VAA) by transcatheter coil embolization and to propose indications for treating VAA by this method. METHODS: We treated 22 patients with VAA by coil embolization; 9 had splenic-, 7 renal-, 4 pancreaticoduodenal arcade-, and 2 proper hepatic artery aneurysms. All nine splenic artery aneurysms patients presented with chronic hepatitis-C; four had hepatocellular carcinoma. Of the seven renal artery aneurysms patients, four were hypertensive and three had rheumatoid arthritis. Both pancreaticoduodenal arcade artery aneurysms patients manifested severe stenosis of the celiac axis. Our transcatheter coil embolization procedure includes coil embolization and coil-packing of the aneurysmal sac, preserving the native arterial circulation. RESULTS: Transcatheter coil embolization with aneurysm packing was technically successful in 16 (72.7%) of the 22 patients and the native arterial circulation was preserved. Postprocedure angiograms confirmed complete disappearance of the VAA. In four of the nine splenic artery aneurysm patients, the native arterial circulation was not preserved. In one renal artery aneurysm patient, stenosis at the aneurysmal neck necessitated placement of a stent before transcatheter coil embolization. Magnetic resonance angiographs obtained during the follow-up period (mean 27 months) demonstrated complete thrombosis of the VAA in all 22 patients. Infarction occurred in one splenic- and two renal artery aneurysms patients; the latter developed flank pain and fever after the procedure. CONCLUSIONS: Transcatheter coil embolization is an effective alternative treatment for patients with saccular and proximal VAA. In particular, the isolation technique using coil embolization is advantageous in splenic artery aneurysm patients.
18312869 Pediatric obstructive sleep apnea and quality of life: a meta-analysis. 2008 Mar OBJECTIVE: 1) To assess the quality of life (QOL) in children with obstructive sleep apnea (OSA) compared with QOL of children with chronic medical conditions, and 2) To determine QOL in children with OSA after adenotonsillectomy in short- and long-term follow-up. DATA SOURCES/REVIEW METHODS: A literature review on QOL in pediatric OSA using the PubMed database. RESULTS: The literature search yielded 10 articles that satisfied inclusion and exclusion criteria. In three studies, the Child Health Questionnaire (CHQ) survey was used to compare 193 patients who had OSA with 93 children who had juvenile rheumatoid arthritis (JRA) and with 815 healthy children. Of 12 CHQ subscale scores for children with OSA, 8 scores were significantly lower (indicating a poorer QOL) than controls. Children with OSA scored 19.23 points lower than healthy children in the subscale of parental impact-emotional. Children with OSA had QOL scores that were similar to those of children with JRA. In seven publications, 369 children with OSA undergoing adenotonsillectomy were studied by using the OSA-18 QOL instrument. The total OSA-18 score and each of the domain scores showed significant improvement (P < 0.0001) after adenotonsillectomy. At long-term follow-up, QOL scores remained significantly improved. CONCLUSIONS: Pediatric OSA has a significant impact on QOL. QOL in pediatric OSA is similar to that of children with JRA. Large improvements in QOL occur after adenotonsillectomy, and these findings are maintained in the long-term. The literature lacks control studies on QOL in pediatric OSA.
18252866 Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. 2008 Apr Pre-B cell colony-enhancing factor (PBEF), also known as visfatin, is a highly conserved, 52-kDa protein found in living species from bacteria to humans. Originally a curiosity identified serendipitously in microarray studies but having no obvious functional importance, PBEF has now been shown to exert three distinct activities of central importance to cellular energetics and innate immunity. Within the cell, PBEF functions as a nicotinamide phosphoribosyl transferase, the rate-limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. By virtue of this role, it can regulate cellular levels of NAD and so impact not only cellular energetics but also NAD-dependent enzymes such as sirtuins. Although it lacks a signal peptide, PBEF is released by a variety of cells, and elevated levels can be found in the systemic circulation of patients with a variety of inflammatory diseases. As an extracellular cytokine, PBEF can induce the cellular expression of inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6. Finally, PBEF has been shown to be an adipokine expressed by fat cells that exerts a number of insulin mimetic and antagonistic effects. PBEF expression is up-regulated in a variety of acute and chronic inflammatory diseases including sepsis, acute lung injury, rheumatoid arthritis, inflammatory bowel disease, and myocardial infarction and plays a key role in the persistence of inflammation through its capacity to inhibit neutrophil apoptosis. This review summarizes the admittedly incomplete body of emerging knowledge about a remarkable new mediator of innate immunity.
18194365 The functional R620W variant of the PTPN22 gene is associated with celiac disease. 2008 Mar The functional (R620W) variant of human PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been implicated in the risk to several autoimmune disorders, including type 1 diabetes, Graves' disease, rheumatoid arthritis and systemic lupus erythematosus. In an association study of this single nucleotide polymorphism with celiac disease (CD), comparison of 262 young diagnosis patients and 214 adult controls from Spain showed a higher frequency of the minor allele in the CD group (9.7% vs 5.6% in controls; P = 0.018), suggestive of an increased genetic risk to the disease (odds ratio = 1.82; 95% confidence interval 1.1-3.0). These results support the role of PTPN22 as a general autoimmunity locus involved in tolerance induction in the thymus.
18039017 Palmar erythema. 2007 Palmar erythema (PE), an often overlooked physical finding, is due to several physiologic or systemic pathologic states. PE can exist as a primary physiologic finding or as a secondary marker of systemic pathology. Primary or physiologic PE can be due to heredity, occurs in at least 30% of pregnant women as a result of associated alterations in the function of the skin and its microvasculature, or may be a diagnosis of exclusion (i.e. idiopathic PE). Secondary PE from systemic pathology encompasses a wide range of disease states. Twenty-three percent of patients with liver cirrhosis, from varying causes, can manifest PE as a result of abnormal serum estradiol levels. Patients with a rare neonatal liver disease such as Wilson disease and hereditary hemochromatosis may exhibit PE along with the other systemic manifestations of the genodermatoses. PE has been reported to occur in >60% of patients with rheumatoid arthritis and is associated with a favorable prognosis. Up to 18% of patients with thyrotoxicosis and 4.1% of patients with diabetes mellitus can have PE. This cutaneous manifestation of diabetes occurs more often than the more classic diseases such as necrobiosis lipoidica diabeticorum (0.6%). PE can be seen in early gestational syphilis and among patients with human T-lymphotrophic virus-1-associated myelopathy. Drug-induced PE with hepatic damage has been documented with use of amiodarone, gemfibrozil, and cholestyramine, while topiramate and albuterol (salbutamol) have been reported to cause PE in the setting of normal liver function. Fifteen percent of patients with both metastatic and primary brain neoplasms may have PE. Increased levels of angiogenic factors and estrogens from solid tumors have been postulated as the cause of PE in such cases. Erythema ab igne can mimic PE, and patients with atopic diathesis are more likely to have PE than matched control subjects. Smoking and chronic mercury poisoning are environmental causes of PE.No treatment of primary PE is indicated. If medication is the cause of PE, the drug responsible should be discontinued if possible. Identification of PE related to underlying disorders should be followed by treatment of the underlying condition. In light of the numerous etiologies of PE, this article reviews the current literature and provides a framework to help guide the clinician in determining the cause of PE in patients presenting with this finding.
17934212 PhosphoBlast, a computational tool for comparing phosphoprotein signatures among large dat 2008 Jan Identification of specific protein phosphorylation sites provides predicative signatures of cellular activity and specific disease states such as cancer, diabetes, Alzheimer disease, and rheumatoid arthritis. Recent progress in phosphopeptide isolation technology and tandem mass spectrometry has provided the means to identify thousands of phosphorylation sites from a single biological sample. These advances now make it possible to profile global changes in the phosphoproteome at an unprecedented level. However, although this technology is generating a wealth of information, there is currently no efficient means to identify phosphoprotein signatures shared among large phosphoprotein databases. Identification of common phosphoprotein signatures found in biologically relevant systems and their conservation throughout evolution would provide valuable insight into mechanisms of signal transduction and cell function. Here we describe the development of a computational program (PhosphoBlast) that can rapidly match thousands of phosphopeptides that share phosphorylation sites within and across species. PhosphoBlast analysis of several large phosphoprotein datasets from the literature revealed common phosphorylation signatures shared across diverse experimental platforms and species. Moreover PhosphoBlast is a powerful analysis tool to identify specific phosphosite mutations. Comparison of the mouse and human phosphoproteomes revealed more than 130 specific phosphoamino acid mutations, some of which are predicted to alter protein function. Further analysis revealed that known phosphorylated amino acids are more evolutionally conserved than the Ser/Thr/Tyr amino acids not known to be phosphorylated. Together our results demonstrate that PhosphoBlast is a versatile mining tool capable of identifying related phosphorylation signatures and phosphoamino acid mutations among complex proteomics datasets in a highly efficient and accurate manner. PhosphoBlast will aid in the informatics analysis of the phosphoproteome and the identification of phosphoprotein biomarkers of disease.
17708602 Duration of treatment with 5-aminosalicylic acid compounds. 2007 Aug 28 The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis, but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962, the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973, the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However, in 1985, a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.
17645766 'Danger' effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendri 2007 Sep Dendritic cell (DC) maturation may accelerate autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, and may contribute to accelerated atherosclerosis seen in these patients. The immune system responds to both exogenous and endogenous 'dangerous' signals that can induce dendritic cell maturation. We have found that autologous plasma contains danger signals that induce up-regulation of major histocompatibility complex (MHC) class II and co-stimulatory molecules in immature DCs (iDCs). The objective of this study was to determine whether low-density lipoprotein (LDL) and/or oxidized LDL (oxLDL) constitute danger signals, and to assess the effect of exposure to LDL and oxLDL following monocyte differentiation into iDCs in lipoprotein-deficient serum (LPDS). IDCs were generated in the presence of autologous plasma or LPDS. Expression of maturation and migration molecules was evaluated using flow cytometry, and morphology was assessed by light microscopy. Pro- or anti-apoptotic effect was determined using annexin V and propidium iodide binding. Phagocytosis of apoptotic cells was evaluated using autologous plasma or LPDS. LDL and oxLDL were clearly able to slightly up-regulate levels of HLA-DR and co-stimulatory molecule CD86. High oxLDL concentrations (50-100 microg/ml) were associated with expression of additional maturation molecules. Moreover, iDCs that were prepared in LPDS showed partial maturation following exposure to LDL and oxLDL, and improved tolerogenic apoptotic cell uptake. This study suggests that oxLDL, and to some extent LDL, are at least partly responsible for the iDC 'danger' response induced by autologous plasma.
17573384 Comparison of the human and canine cytokines IL-1(alpha/beta) and TNF-alpha to orthologous 2007 The cytokines interleukin-1 (IL-1alpha and IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) both play a major role in the initiation and regulation of inflammation and immunity responses. Polymorphisms within the gene sequences of these cytokines IL-1 and TNF-alpha have been proposed to play an important role in the pathogenesis of certain diseases. Affecting nearly every organ, various diseases, including some cancers, are described to be associated with an increased level of IL-1 and TNF-alpha proteins, for example, solid tumors, hematologic malignancies, malignant histiocytosis, autoimmune disorders, Alzheimer's disease, Parkinson's disease, sepsis, and rheumatoid arthritis. Regarding genetic backgrounds and pathways, numerous canine diseases show close similarities to their human counterparts. As a genetic model, the dog could be used to unravel the genetic mechanisms, for example, in particular the predispositions, the development, and progression of cancer and metabolic diseases. The identity comparison of gene and protein sequences of different species could be used to elucidate the structure and function of the genes and proteins by identifying the evolutionary conserved regions and domains. Herein we analyzed in detail the mRNA and protein structures and identities of the present known mammalian (human, canine, murine, rat, ovine, equine, feline, porcine, and bovine) TNF-alpha, IL-1alpha, and IL-1beta mRNAs and proteins. Additionally, based on the canine genome sequence, we derived in silico the complete mRNA structures of the IL-1alpha and IL-1beta mRNAs.
17560008 Modulation of T-effector function by imatinib at the level of cytokine secretion. 2007 Aug OBJECTIVE: Recently, evidence was provided, that the selective tyrosine kinase inhibitor imatinib mesylate (imatinib) has immunomodulatory or suppressive effects. However, the discussion about imatinib's influence on immune cells is still controversial. The aim of this study was to clarify the effect of imatinib on CD8+ and CD4+ T-cell effector functions. MATERIALS AND METHODS: For analyzing T-cell effector functions T-cell receptor-transgenic ovalbumin-specific CD8+ T cells and in vivo primed CD4+ Th1 cells were used. T-cell effector functions were analyzed on the level of antigen responsiveness by intracellular cytokine staining, by measuring cytokine secretion in an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent assay and by detecting cytotoxicity using the fluorescein-activated cell sorting-based fluorometric assessment of T-lymphocyte antigen-specific lysis assay. RESULTS: It was demonstrated that imatinib inhibits antigen-specific IFN-gamma secretion of both CD4+ and CD8+ T-effector cells at therapeutically relevant concentrations, while T cells remain responsive. The decrease of IFN-gamma production was not due to the loss of T-cell viability. Further, it was shown that the effector T cells are modulated rather than suppressed, because the cytolytic functions of CD8+ cytotoxic T cells were not altered. Residual cytolytic activity in the presence of imatinib was not due to FasL interaction. CONCLUSIONS: These experiments provide evidence for a therapeutically relevant modulation of T-cell effector functions by imatinib. This might open a possible applicability of imatinib in various autoimmune and inflammatory diseases, including multiple sclerosis and rheumatoid arthritis.
17539723 Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy. 2007 Jun Chronic diseases, such as periodontal disease (PD) and rheumatoid arthritis (RA), are characterized by a robust immune response resulting in unresolved inflammation. Inflammation is mediated by proinflammatory cytokines; recently, a novel subset of T-helper (Th) cells was identified that plays a crucial role in inflammation and autoimmune disease. This population secretes several proinflammatory cytokines, including the novel cytokine interleukin (IL)-17, and, hence, has been termed "Th17." Inflammatory cytokines are implicated in the progression of localized chronic infections, such as PD, and in serious systemic pathologies, such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease. IL-17 mediates inflammation through a receptor (IL-17R) composed of two subunits, IL-17RA and IL-17RC. Drugs that antagonize inflammatory cytokines are used therapeutically to downregulate immune-mediated pathology in conditions such as RA, although not all patients respond well to this approach. Therefore, identification of potential novel therapeutic targets, such as the IL-17 signaling complex, may be clinically relevant for mitigating inflammatory pathology. However, the manner in which such a therapeutic may influence the onset and progression of PD is poorly understood. Therapeutics that antagonize inflammatory cytokines ameliorate inflammation and bone loss and may have broader implications for individuals with systemic diseases in which inflammation and autoimmunity predominate.
17471245 Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: rationa 2007 May Advances in our understanding of the pathogenesis of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus have led to the emergence of immunoglobulin-based therapy as a major therapeutic force. Numerous monoclonal antibodies that target proinflammatory cytokines or their receptors (e.g. infliximab, adalimumab, tocilizumab, belimumab, HuMax-IL-15), and cell-surface or co-stimulatory molecules (e.g. rituximab) are either in clinical development or have been approved for clinical use. These antibodies are safe and effective in the long-term therapy of many rheumatic diseases. In addition, polyclonal immunoglobulins (intravenous immunoglobulin) obtained from pooled plasma from healthy blood donors are an effective therapeutic approach in certain rheumatic diseases. The mechanisms of action of monoclonal antibodies and intravenous immunoglobulin include cytolysis of target cells through complement or antibody-dependent cell-mediated cytotoxicity, induction of apoptosis of target cells, blockade of co-stimulatory molecules, and neutralization of pathogenic antibodies and soluble factors such as cytokines and their receptors, which ultimately lead to amelioration of the inflammatory process. The success of currently available therapeutic immunoglobulins has led to considerable interest in the identification of novel molecular therapeutic targets in rheumatic diseases.
17432820 Inhibition of angiogenesis by the antifungal drug itraconazole. 2007 Apr 24 Angiogenesis, the formation of new blood vessels, is implicated in a number of important human diseases, including cancer, diabetic retinopathy, and rheumatoid arthritis. To identify clinically useful angiogenesis inhibitors, we assembled and screened a library of mostly Food and Drug Administration-approved drugs for inhibitors of human endothelial cell proliferation. One of the most promising and unexpected hits was itraconazole, a known antifungal drug. Itraconazole inhibits endothelial cell cycle progression at the G1 phase in vitro and blocks vascular endothelial growth factor/basic fibroblast growth factor-dependent angiogenesis in vivo. In attempts to delineate the mechanism of action of itraconazole, we found that human lanosterol 14alpha-demethylase (14DM) is essential for endothelial cell proliferation and may partially mediate the inhibition of endothelial cells by itraconazole. Together, these findings suggest that itraconazole has the potential to serve as an antiangiogenic drug and that lanosterol 14DM is a promising new target for discovering new angiogenesis inhibitors.
17424975 Clinical evaluation of the effect of attenuation correction technique on 18F-fluoride PET 2007 Feb OBJECTIVE: The purpose of this study is to evaluate effect of attenuation correction technique on 18F-fluoride positron emission tomography (PET). METHODS: We performed PET scans after the injection of 185 MBq 18F-fluoride on 32 patients from October 20th, 2004 to April 13th, 2005. We calculated bone-to-muscle ratios for the images with and without attenuation correction. We placed regions of interest (ROIs) on normal bone accumulation in 22 patients. The exclusion criteria were bone metastasis, Paget's disease, and rheumatoid arthritis. Several regions were chosen for ROI placement: skull, cervical vertebra, mandible, scapula, thoracic vertebra, rib, humerus, lumbar vertebra, radius, ulna, pelvis, femoral head, femoral shaft, tibia, and fibula. The count ratios of normal bones to gluteus muscle were calculated as bone-to-muscle ratios. The count ratios of abnormal skeletal lesions to gluteus muscles were calculated as bone-to-muscle ratios, while the count ratios of abnormal skeletal lesions to normal bones were calculated as bone-to-bone ratios. RESULTS: PET images without attenuation correction showed significantly higher mean bone-to-muscle ratios than those with attenuation correction (p < 0.05) for all normal bones except the femoral head and lumbar vertebrae. For abnormal bones, bone-to-muscle ratios without attenuation correction were significantly higher than those with attenuation correction (p < 0.005). The same statistical significance was found for bone-to-bone ratios (p < 0.005). CONCLUSIONS: The attenuation correction technique is not necessary to conduct the visual interpretation of 18F-fluoride PET images. The bone-to-muscle ratio analysis without attenuation correction may be of use to differentiate malignant from benign disease processes.
17407218 Measurement of antinuclear antibodies by multiplex immunoassay: a prospective, multicenter 2007 May OBJECTIVE: We conducted a prospective, multicenter evaluation of autoantibody testing by multiplex immunoassay in patients with known or suspected connective tissue diseases (CTD). We evaluated agreement between multiplex immunoassay and enzyme immunoassay (EIA) and assessed the diagnostic utility of autoantibody profiles. METHODS: Samples from 908 patients with suspected CTD seen in rheumatology clinics were collected prospectively at 3 tertiary care centers. Diagnoses were established according to recognized classification criteria. Tests for autoantibodies were obtained by multiplex immunoassay and by EIA. The results of the multiplex immunoassay were analyzed using a previously validated interpretative algorithm, MDSS (Medical Decision Support Software), that suggests possible disease associations based on the pattern of results for the autoantibodies. RESULTS: The median patient age was 49.7 years; 83% were female. The most common diagnoses were rheumatoid arthritis in 352 patients and systemic lupus erythematosus (SLE) in 332 patients. Agreement between multiplex and EIA testing ranged from a high of 99% (95% CI 98% to 100%) for Jo-1 to a low of 79% (95% CI 76% to 82%) for antinuclear antibodies. The MDSS algorithm suggested an appropriate disease association in 75% to 100% of patients with SLE. The results varied depending on the disease and the autoantibodies present. CONCLUSION: These results suggest that patterns of autoantibodies detected by multiplex immunoassay testing, when analyzed by an interpretative algorithm, are useful in the evaluation of patients with CTD in situations of high disease prevalence. Further testing is necessary to determine its utility in settings of low disease prevalence.
17357298 Antimitotic activity of high affinity ligands for peripheral benzodiazepine receptor (PBR) 2006 PURPOSE: Overexpression of PBR has been found in several tumor types including ovarian, colon, breast adenocarcinomas, esophageal cancer. There is evidence suggesting that PBR ligands regulate cell proliferation. However, their action is probably cell-type specific. We decided to evaluate mitotic activity of PBR ligands in some normal and neoplastic cell lines. MATERIAL AND METHODS: The cells were maintained according to standard procedures. Ligand binding assay was performed in cell extract using PK-11195 or Ro-54864 and [N-methyl-3H] Ro-54864 or [N-methyl-3H] PK-11195. Cell proliferation was evaluated using 5-[3H]-thymidine assay. Western Immunoblot assay was conducted using polyclonal anti-PBR antibody. RESULTS: We have found that, macrophages evoked strong binding of both Ro-54864 and PK-11195. This phenomenon was accompanied by drastic decrease in the cell divisions. Similar effect was found only in the case of non-estrogen-dependent breast cancer cells MDA-MB 231. It suggest that PBR-ligand mediated inhibition of mitogenesis may represent a new anticancer strategy in non-estrogen-dependent breast cancer. In respect to macrophages inhibition of the cell division by both PBR ligands may have implication in modulation of inflammatory response. It has been postulated that PBR ligands may have anti-inflammatory activity in rheumatoid arthritis. The presence of peripheral benzodiazepine receptors in chondrocytes, T cells, macrophages and mesenchymal cells suggest that peripheral benzodiazepine receptor ligands may interfere with the cytokine network and thus modulate inflammatory response. CONCLUSIONS: The data suggest that PBR-ligand mediated inhibition of DNA synthesis in non-estrogen dependent breast cancer cells and in macrophages may represent a new therapeutic approach of breast anti-cancer and anti-inflammatory therapy.
17261875 The association of C-reactive protein with an oxidative metabolite of LDL and its implicat 2007 Apr C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.
17257802 Uncommon leg ulcers in the lower extremity. 2007 Mar OBJECTIVE: To determine the prevalence of uncommon ulcers, unrelated to venous or arterial etiology, in patients presenting to vascular clinics. METHODS: This was a multicenter prospective study of consecutive patients presenting with lower extremity ulceration. The settings were university hospital outpatient centers and venous clinics. A total of 799 limbs in 710 patients with leg ulcers were evaluated. Patients with venous ulcer disease and with evidence of arterial disease with an ankle-brachial index less than 0.7 were excluded from the study. Out of 710 patients, 17 patients with a total of 21 limbs fit the criteria for inclusion. All limbs included in this study underwent physical examination, ankle-brachial index measurements, duplex ultrasonography, and skin biopsies. RESULTS: The mean age of patients with uncommon ulcers was 65.6 years, and the mean duration was 5.5 years. A total of 2.1% of all leg ulcers seen were due to uncommon etiology unrelated to venous or arterial pathology. Most of these ulcers were located in the medial lower calf (n = 19). In six patients with ulcers, the histology did not reveal any specific cause; five had a neoplasia, three had chronic inflammation, two had sickle cell disease, two had vasculitis, one had rheumatoid arthritis, one had pyoderma gangrenosum, and one had ulcer due to hydroxyurea. CONCLUSIONS: The prevalence of leg ulcers unrelated to arterial and venous disease that presented with signs and symptoms of chronic venous disease was 2.1%. Their etiology is variable, most often including vasculitis, neoplasia, metabolic disorders, infection, and other rare causes. Early identification of uncommon ulcers may facilitate timely and appropriate management.
17222220 Elevated serum BAFF levels in patients with localized scleroderma in contrast to other org 2007 Feb Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.