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ID PMID Title PublicationDate abstract
18504520 Classification of acetabular changes in osteoarthritis: a histological and radiological an 2008 Oct BACKGROUND: Aseptic acetabular loosening cannot be explained with a single theory and lots of studies deal with the influence of implant design and surgical technique on implant survival. Implant registers show the effect of demographic and patient-related parameters on acetabular loosening. There is little information about the influence of the acetabular bone quality on cup loosening. METHODS: In a prospective study, we investigated the first 122 consecutive routinely taken biopsies out of acetabular bone stock taken during primary total hip arthroplasty (THA) before reaming of the cup. Undecalcified bone samples should be classified in respect to architecture and vitality in different histological types. Four types were defined and the primary diagnosis and the severity of the preoperative radiological changes were correlated to this classification. RESULTS: A total number of 110 (90%) out of 122 biopsies could be classified to one specific type of biopsy, nine were not classifiable and three showed special entities [rheumatoid arthritis (RA) and coxitis]. Double examination showed a high intraobserver agreement (kappa 0.972). There was a correlation between the four defined types of bone biopsies and the radiological severity of osteoarthritis (P<0.0001) but not with the diagnosis (P=0.104). CONCLUSION: Histological changes during the development of osteoarthritis of the hip occur regularly, can be classified in four groups and are predictable from radiological changes on preoperative radiographs.
18466509 Conditional genotype analysis: detecting secondary disease loci in linkage disequilibrium 2007 A number of autoimmune and other diseases have well established HLA associations; in many cases there is strong evidence for the direct involvement of the HLA class II peptide-presenting antigens, e.g., HLA DR-DQ for type 1 diabetes (T1D) and HLA-DR for rheumatoid arthritis (RA). The involvement of additional HLA region genes in the disease process is implicated in these diseases. We have developed a model-free approach to detect these additional disease genes using genotype data; the conditional genotype method (CGM) and overall conditional genotype method (OCGM) use all patient and control data and do not require haplotype estimation. Genotypes at marker genes in the HLA region are stratified and their expected values are determined in a way that removes the effects of linkage disequilibrium (LD) with the peptide-presenting HLA genes directly involved in the disease. A statistic has been developed under the null hypothesis of no additional disease genes in the HLA region for the OCGM method and was applied to the Genetic Analysis Workshop 15 simulated data set of Problem 3, which mimics RA (answers were known). In addition to the primary effect of the HLA DR locus, the effects of the other two HLA region simulated genes involved in disease were detected (gene C, 0 cM from DR, increases RA risk only in women; and gene D, 5.12 cM from DR, rare allele increases RA risk five-fold). No false negatives were found. Power calculations were performed.
18466481 Two-stage study designs for analyzing disease-associated covariates: linkage thresholds an 2007 The incorporation of disease-associated covariates into studies aiming to identify susceptibility genes for complex human traits is a challenging problem. Accounting for such covariates in genetic linkage and association analyses may help reduce the genetic heterogeneity inherent in these complex phenotypes. For Genetic Analysis Workshop 15 (GAW15) Problem 3 simulated data, our goal was to compare the power of several two-stage study designs to identify rheumatoid arthritis-related genes on chromosome 9 (disease severity), 11 (IgM), and 18 (anti-cyclic citrinullated protein), with knowledge of the answers. Five study designs incorporating an initial linkage step, followed by a case-selection scheme and case-control association analysis by logistic regression, were considered. The linkage step was either qualitative-trait linkage analysis as implemented in MERLIN-nonparametric linkage (NPL), or quantitative-trait locus analysis as implemented in MERLIN-REGRESS. A set of cases representing either one case from each available family, one case per linked family (NPL >/= 0), or one case from each family identified by ordered-subset analysis was chosen for comparison with the full set of 2000 simulated controls. As expected, the performance of these study designs depended on the disease model used to generate the data, especially the simulated allele frequency difference between cases and controls. The quantitative trait loci analysis performed well in identifying these loci, and the power to identify disease-associated alleles was increased by using ordered-subset analysis as a case selection tool.
18466479 Marker selection for whole-genome association studies with two-stage designs using dense s 2007 Large-scale genome-wide association studies are increasingly common, due in large part to recent advances in genotyping technology. Despite a dramatic drop in genotyping costs, it is still too expensive to genotype thousands of individuals for hundreds of thousands single-nucleotide polymorphisms (SNPs) for large-scale whole-genome association studies for many researchers. A two-stage design has been a promising alternative: in the first stage, only a small fraction of samples are genotyped and tested using a dense set of SNPs, and only a small subset of markers that show moderate associations with the disease will be genotyped in the second stage. In this report, I developed an approach to select and prioritize SNPs for association studies with a two-stage or multi-stage design. In the first stage, the method not only evaluates associations of SNPs with the disease of interest, it also explicitly explores correlations among SNPs. I applied the approach on the simulated Genetic Analysis Workshop 15 Problem 3 data sets, which have modeled the complex genetic architecture of rheumatoid arthritis. Results show that the method can greatly reduce the number of SNPs required in later stage(s) without sacrificing mapping precision.
18426758 [Endproducts and receptors of advanced glycation and lipoxidation (AGE, ALE, RAGE) and chr 2008 Apr 27 BACKGROUND: Chronic diseases as well as complications to acute and chronic disease are repeatedly associated with accumulation in the body of glycated and lipoxidated proteins and peptides. These molecules are strongly associated with activation of a specific receptor called RAGE and a long-lasting exaggerated level of inflammation in the body. METHODS: PubMed reports in excess of 5000 papers plus about 14000 articles about the related HbA 1c , most of them published in the last five years. Most of available abstracts have been read and circa 800 full papers studied in detail. RESULTS: RAGE, a member of the immunoglobulin superfamily of cell surface molecules and receptor for advanced glycation endproducts, functions as a master switch, induces sustained activation of NF-kappaB, suppresses a series of endogenous autoregulatory functions and converts long-lasting pro-inflammatory signals into sustained cellular dysfunction and disease. Its activation is associated with high levels of dysfunctioning proteins in body fluids and tissues, and strongly associated with a series of diseases from allergy and Alzheimer to rheumatoid arthritis and urogenital disorders. Heat-treatment, irradiation and ionisation of foods increase the content in foods of AGE/ALE. CONCLUSIONS: Some processed foods are much like tobacco smoking great contributors to accumulation of glycated and lipoxidated molecules in the tissues. Change of life style: avoidance of foods rich in deranged proteins and peptides and increased consumption of antioxidants, especially polyphenols counteracts such a development.
18231633 Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Delta-Prost 2008 Jan 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.
18186796 CCL5/RANTES chemokine gene promoter polymorphisms are not associated with atopic and nonat 2008 Feb CCL5/RANTES, a member of the C-C chemokine family, is a potent eosinophil, monocyte, basophile and lymphocyte chemo-attractant at the site of inflammation. Recent studies revealed that a functional mutation at the -403 position in the promoter may have significance for atopic dermatitis, bronchial asthma, sarcoidosis, rheumatoid arthritis and HIV infection, and others. Another polymorphism in the -28 position has been reported. Our objective was to investigate the possible influence of the CCL5/RANTES promoter polymorphisms in the different types of bronchial asthma. CCL5/RANTES genotyping was performed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) in 306 asthmatic patients with non-atopic (n = 145) and atopic (n = 161) asthma and 242 controls. The 81.9% of the atopic asthma patients for -403G/A had the G allele and the A allele frequency was 18%. Of the non-atopic asthma patients, the G allele frequency was 79.7% and the A allele was 20.3%. Concerning the -28C/G polymorphism, the frequency of the CCL5/RANTES -28G allele in our patients is 2.8%, which is similar to Spanish adult population. After comparing patients with asthma, atopic patients, non-atopic patients and control population, we found no significant deviation in the distribution of the alleles or genotypes of CCL5/RANTES promoter polymorphisms in any tested comparison. Therefore, human CCL5/RANTES gene promoter polymorphisms are not associated with the different types of bronchial asthma in Spanish population.
18092266 Increased titres of anti-nuclear antibodies do not predict the development of associated d 2007 Nov OBJECTIVE: To determine whether patients with elevated anti-nuclear antibodies (ANA), absent extractable nuclear antigen (ENA) reactivity, and no definite associated disease develop an ANA-associated disease (AAD). METHODS: Patients with ANA titres of at least 1:320 and no ENA reactivity were identified by searching the database of our laboratory serving a tertiary care university hospital between 1998 and 2002. Medical records of this index time point were reviewed to exclude patients with active AAD at screening. Case patients were contacted by questionnaire between 2004 and 2005 and invited for a clinical visit to ascertain the individual disease status. RESULTS: Seventy-six patients were evaluated after a median follow-up of 32 months. An AAD was diagnosed in eight patients: connective tissue disease (CTD) in three, autoimmune hepatitis in two, rheumatoid arthritis in one, encephalomyelitis disseminate in one, and lymphoma in one. The only predictive factor associated with the development of AAD was the suspicion of an autoimmune disease by the treating physician at the initial evaluation. In the absence of initial suspicion for an autoimmune disease, only two out of 54 patients developed AAD, whereas six out of 22 patients with initial disease suspicion developed a defined AAD. CONCLUSION: In the absence of a clinical suspicion, elevated ANA titres have a low positive predictive value of 4% for developing AAD for the upcoming 3 years.
18070214 Assessment of health state utilities of controlled and uncontrolled psoriasis and atopic e 2008 Feb BACKGROUND: Health utilities are used to express relevant trade-offs for resource allocation. The absence of valid and generalizable utilities for atopic eczema (AE) and psoriasis limits the validity of previous cost-utility analyses. OBJECTIVES: (i) To assess health utilities of standardized scenarios of controlled and uncontrolled AE and psoriasis in participants from the general population and in patients using the time trade-off (TTO) method; (ii) to test the association of the utilities obtained with demographic and patient characteristics; and (iii) to compare these utilities with other health economic outcomes [utilities assessed on visual analogue scale (VAS), willingness to pay (WTP)]. METHODS: A single-centre study conducted in 2006 at the Department of Dermatology, Dresden, Germany. Standardized interactive computer-assisted interviews in a random sample from the general population (n=139), and patients with AE (n=58) and psoriasis (n=62). Information on health states included characteristic clinical pictures and a short text explaining aetiology, signs, symptoms and quality of life impact. RESULTS: In participants from the general population median utilities (TTO) of controlled and uncontrolled AE were 0.97 and 0.64, respectively. For psoriasis the corresponding utilities were 0.93 and 0.56. Utilities were independent of sex and socioeconomic position, and tended to be lower in patients with psoriasis. Correlations between TTO, VAS and WTP responses were weak. CONCLUSIONS: To avoid uncontrolled psoriasis or eczema participants chose an approximately 40% shorter life expectancy. This indicates that severe chronic inflammatory skin diseases may be considered as severe as angina pectoris, chronic anxiety, rheumatoid arthritis, multiple sclerosis or regional oesophageal cancer. The different economic outcomes assessed are not interchangeable.
18059136 Bee venom stimulates human melanocyte proliferation, melanogenesis, dendricity and migrati 2007 Oct 31 Pigmentation may result from melanocyte proliferation, melanogenesis, migration or increases in dendricity. Recently, it has been reported that secreted phospholipase A(2)(sPLA(2)) known as a component of bee venom (BV), stimulates melanocyte dendricity and pigmentation. BV has been used clinically to control rheumatoid arthritis and to ameliorate pain via its anti-inflammatory and antinociceptive properties. Moreover, after treatment with BV, pigmentation around the injection sites was occasionally observed and the pigmentation lasted a few months. However, no study has been done about the effect of BV on melanocytes. Thus, in the present study, we examined the effect of BV on the proliferation, melanogenesis, dendricity and migration in normal human melanocytes and its signal transduction. BV increased the number of melanocytes dose and time dependently through PKA, ERK, and PI3K/Akt activation. The level of cAMP was also increased by BV treatment. Moreover, BV induced melanogenesis through increased tyrosinase expression. Furthermore, BV induced melanocyte dendricity and migration through PLA(2) activation. Overall, in this study, we demonstrated that BV may have an effect on the melanocyte proliferation, melanogenesis, dendricity and migration through complex signaling pathways in vitro, responsible for the pigmentation. Thus, our study suggests a possibility that BV may be developed as a therapeutic drug for inducing repigmentation in vitiligo skin.
17979642 Voltammetric determination of sinomenine in biological fluid using a glassy carbon electro 2007 Aug Polycysteic acid based electrochemical oxidation of L-cysteine (CySH) and carbon nanotubes (CNTs) formed a composite thin film material at a glassy carbon electrode (GCE) that was used a novel modifier for electroanalytical determination of sinomenine which is used for rheumatoid arthritis treatment. The determination of sinomenine at the composite modified electrode was studied by differential pulse voltammetry (DPV). The peak current obtained at + 0.632 V (vs SCE) from DPV was linearly dependent on the sinomenine concentration in the range of 1.0 x 10(-7) to 6.0 x 10(-5) M in a B-R buffer solution (0.04 M, pH 1.81) with a correlation coefficient of 0.998. The detection limit (S/N = 3) was 5.0 x 10(-8) M. The electrochemical reaction mechanism of sinomenine was also discussed. This new method was then applied to the high-throughput determination of sinomenine in human serum samples with satisfactory results. This polycysteic acid/CNTs composite film may be considered to be a promising, low-cost, durable, and biocompatible material for the modification of sensors in applications to pharmaceutical and biomedical analysis.
17924176 Structural changes in lymphocytes membrane of Chernobyl clean-up workers from Latvia. 2007 Nov ABM (3-aminobenzanthrrone derivative) developed at the Riga Technical University, Riga, Latvia) has been previously shown as a potential probe for determination of the immune state of patients with different pathologies . The fist study (using probe ABM) of peripheral blood mononuclear cells (PBMC) membranes of 97 Chernobyl clean-up workers from Latvia was conducted in 1997. Now we repeatedly examine the same (n = 54) individuals in dynamics. ABM spectral parameters in PBMC suspension, fluorescence anisotropy and blood plasma albumin characteristics were recorded. In 1997 screening showed 5 different patterns of fluorescence spectra, from which in 2007 we obtained only two. These patterns of spectra had never been previously seen in healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc., examined by us. Patterns of ABM fluorescence spectra are associated with membrane anisotropy and conformational changes of blood plasma albumin. We observed that in dynamics 1997-2007 the lipid compartment of the membrane became more fluid while the lipid-protein interface became more rigid. The use of probe ANS and albumin auto-fluorescence allowed show conformational alterations in Chernobyl clean-up workers blood plasma. It is necessary to note that all investigated parameters significantly differ in observed groups of patients. These findings reinforce our understanding that that the cell membrane is a significant biological target of radiation. The role of the membrane in the expression and course of cell damage after radiation exposure must be considered. So ten years dynamic of PBMC membrane characteristics by ABM (spectral shift and anisotropy indexes) in Chernobyl clean-up workers reveal progressive trend toward certain resemblance with those of chronic B-cell lymphoid leukemia.
17848087 Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and pro 2007 Sep Systemic lupus erythematosus (SLE) is an autoimmune disease involving deposition of immune complexes in normal tissues and the consequent accumulation of immune cells and tissue injury. Activated macrophages are thought to contribute to disease pathogenesis by releasing inflammatory mediators that both cause direct tissue damage and attract other immune cells that augment inflammation. Previous studies in animal models of rheumatoid arthritis have shown that activated macrophages express a folate receptor that can be targeted with folate-linked haptens, leading to (1) marking of the activated macrophages with highly immunogenic haptens, (2) recognition of the marked cells by Fc receptor-expressing immune cells, and (3) destruction of the antibody-coated macrophages by the body's own immune system. Here we demonstrate that the same folate-hapten-targeted immunotherapy can greatly suppress symptoms of SLE in two animal models of the disease, resulting in reduced immune complex deposition, diminished damage to normal tissues, and prolonged animal survival.
17785335 Comparison of three multiplex immunoassays for detection of antibodies to extractable nucl 2007 Aug We set out to determine the agreement of three multiplex immunoassays for the detection of autoantibodies involved in connective tissue disease using clinically defined sera. Usefulness of the immunoassays will be defined by correlation to disease state. Using the immunoassays from Inova Diagnostics, Biomedical Diagnostics (BMD), and AtheNA, reactivity, to Smith (Sm), ribonucleic protein (RNP), SSA (Ro), SSB (La), Scl-70, and dsDNA or chromatin, we tested 273 clinically defined sera consisting of 57 systemic lupus erythrematosus (SLE) sera, 69 rheumatoid arthritis (RA) sera, 47 sera defined as various other connective tissue diseases, and 100 normal donor sera. Samples were also tested for anti-nuclear antibody (ANA) oN HEp-2 cells by IFA for analysis of discrepant results. Inova, BMD, and AtheNA assays demonstrated 57%, 89%, and 80% concordance, respectively, in the 47 connective tissue disease sera. The BMD assay was the most sensitive in detecting Scl-70. The immunoassays did not correlate well in the 57 SLE-defined sera; however, each had a variety of antibodies positive for each serum. The AtheNA assay demonstrated the highest degree of nonspecificity. Inova, BMD, AtheNA, and the Inova ANA HEp-2 IFA demonstrated 97%, 98%, 97%, and 99% specificity, respectively, using normal sera. Thus, all three assays showed a 97% or better negative predictive value. Positive correlation varied from 83% to 98%. Antibodies in SLE sera did not compare well among the three immunoassays. Significant variation in specificity and sensitivity due to individual characteristics of each assay was demonstrated, with the BMD assay showing the highest correlation with clinical diagnosis.
17647199 Soluble CD30 serum level--an adequate marker for allograft rejection of solid organs? 2007 Nov The CD30 molecule, a 120 kDa cell surface glycoprotein, is a member of the tumor necrosis factor receptor (TNF-R) superfamily and was originally identified on the surface of Reed-Sternberg cells and anaplastic large cell lymphomas in Hodgkin's disease patients. In addition to lymphoproliferative disorders the expression of CD30 was found in both activated CD8+ and CD4+ Th2 cells which lead to the activation of B-cells and consequently to the inhibition of the Th1-type cellular immunity. The membrane-bound CD30 molecule can be proteolytically cleaved, thereby generating a soluble form (sCD30) of about 85 kDa. Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situations such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukaemia/lymphoma. In addition, it has recently been suggested that pre- or post-transplant levels of sCD30 represent a biomarker for graft rejection associated with an impaired outcome for transplanted patients. We here review (i) the current knowledge of the clinical significance of sCD30 serum levels for solid organ transplantations and (ii) our own novel data regarding inter- and intra-individual variations as well as time-dependent alterations of sCD30 levels in patients. (iii) Based on this information the implementation of sCD30 as predictive pre-transplant or post-transplant parameter for solid organ transplantation is critically discussed.
17550695 [High tibial dome osteotomy complications in genu varum patients]. 2007 Mar OBJECTIVE: To identify if pre-surgical risk factors or the surgical technique were associated with the complications of the osteotomy in genu varus patients. METHODOLOGY: A case-control study was conducted in patients that underwent Maquet proximal tibial osteotomy for treatment of genu varus between January and December 2003. The risk factors were the following: age 50 or more years old, comorbidity such as type 2 diabetes, hypertension, rheumatoid arthritis, overweight and obesity (BMI > or = 25 and > or = 30), duration of ischemia longer than 60 min and local pain. Cases were those who developed one or more complications. Descriptive and inferential statistical analyses were performed. RESULTS: One hundred and thirty-four patients were included, among which 53% had complications. None of the risk factors were statistically significant (p > 0.05). CONCLUSIONS: None of pre-surgical risk factors were associated with the complications of osteotomy; therefore, these could be attributable to the surgical technique. It is necessary to outweigh the temporary benefits of the tibial osteotomy versus the increase in the risk of complications when performing total knee arthroplasty.
17531166 Protective effect of an aqueous extract of Harpagophytum procumbens upon Escherichia coli 2007 Apr 15 Regardless of its lethal effects upon Escherichia coli (E. coli) cultures trough the production of free radicals (FR), stannous chloride (SnCl2) remains to be the most used reducing agent on the production of technetium-99m radiopharmaceuticals, to obtain images on nuclear medicine. Moreover, authors have reported that vegetal extracts are able to protect Escherichia coli cultures against the cytotoxicity of this agent. Harpagophytum procumbens, also known as Devil's Claw, is a plant used in folk medicine, as an analgesic and anti-inflammatory in cases of joint and back pain, on the treatment of degenerative rheumatoid arthritis, osteoarthritis, kidney inflammation and heart diseases. The presence of this extract reduced the lesive effects of SnCl2 upon E. coli AB1157 (proficient in DNA repair), BW9091 (deficient in the xthA gene) and BH110 (deficient in the xthA, nfo and fpg genes) cultures, and the deficient strains (BW9091 e BH110) were more sensible to this SnCl2 action than the proficient one. The substances in the extract could be acting as: (i) chelator of the stannous ions, avoiding the generation of FR, (ii) FR scavenger, protecting the cells against the oxidation, and/or (iii) an oxidant compound acting upon the stannous ions, reducing the SnCl2 cytotoxicity.
17502099 The structure of chagasin in complex with a cysteine protease clarifies the binding mode a 2007 May Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds.
17475444 The effects of acute psychological stress on circulating inflammatory factors in humans: a 2007 Oct Stress influences circulating inflammatory markers, and these effects may mediate the influence of psychosocial factors on cardiovascular risk and other conditions such as psoriasis and rheumatoid arthritis. Inflammatory responses can be investigated under controlled experimental conditions in humans, and evidence is beginning to emerge showing that circulating inflammatory factors respond to acute psychological stress under laboratory conditions. However, research published to date has varied greatly in the composition of study groups, the timing of samples, assay methods, and the type of challenge imposed. The purpose of this review is to synthesize existing data using meta-analytic techniques. Thirty studies met inclusion criteria. Results showed robust effects for increased levels of circulating IL-6 (r=0.19, p=0.001) and IL-1beta (r=0.58, p<0.001) following acute stress, and marginal effects for CRP (r=0.12, p=0.088). The effects of stress on stimulated cytokine production were less consistent. Significant variation in the inflammatory response was also related to the health status of participants and the timing of post-stress samples. A number of psychobiological mechanisms may underlie responses, including stress-induced reductions in plasma volume, upregulation of synthesis, or enlargement of the cell pool contributing to synthesis. The acute stress-induced inflammatory response may have implications for future health, and has become an important topic of psychoneuroimmunological research.
17434468 Lineage tree analysis of immunoglobulin variable-region gene mutations in autoimmune disea 2006 Dec Autoimmune diseases show high diversity in the affected organs, clinical manifestations and disease dynamics. Yet they all share common features, such as the ectopic germinal centers found in many affected tissues. Lineage trees depict the diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. We previously developed an algorithm for quantifying the graphical properties of IGV gene lineage trees, allowing evaluation of the dynamical interplay between SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we apply this method to ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid Arthritis, and Sjögren's Syndrome, using data scaling to minimize the effects of the large variability due to methodological differences between groups. Autoimmune trees were found to be significantly larger relative to normal controls. In contrast, comparison of the measurements for tree branching indicated that similar selection pressure operates on autoimmune and normal control clones.