bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men
Authors: Lundin K B , Giwercman Y L , Rylander L , Hagmar L , Giwercman A 
Published: July 2006

Background: The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population.
Methods: We investigated the impact of CAG and GGN repeats on male reproductive function, one by one and in interaction with each other, in 220 adolescent men from the general Swedish population. Physical examination and semen analysis, including accessory sex gland markers and measurement of reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy, were recorded. GGN and CAG repeat lengths were determined by sequencing.
Results: GGN<23 was associated with lower semen volume when compared to GGN=23 (mean difference −0.6 ml, P=0.02) and GGN>23 (mean difference −0.9 ml, P=0.002). Men with GGN<23, exposed to maternal smoking during pregnancy, had higher body mass index compared to men with other GGN lengths, no matter whether their mother had smoked or not during pregnancy (mean difference 4.8 kg/m2, P<0.001).
Conclusions: Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity. Body composition may be influenced by the combination of fetal exposure to maternal smoking and certain AR genotypes.
Detection of thyroid peroxidase mRNA and protein in orbital tissue
Authors: Lai Oi Fah , Zaiden Norazean , Goh Sui Sin , Mohamed Nur-Ezan , Seah Lay Leng , Fong Kee Siew , Estienne Valerie , Carayon Pierre , Ho Su Chin , Khoo Daphne H C 
Published: July 2006

Objective: We have previously reported that the absence of thyroid peroxidase antibodies (TPOAb) in Graves’ disease (GD) was associated with an increased risk of Graves’ ophthalmopathy (GO). This observation raised the possibility that TPOAb could act as a protective factor. However, the presence of thyroid peroxidase (TPO) in the orbit has not been previously reported. The aim of this study was to confirm or exclude the presence of orbital TPO.
Methods and design: Relative TPO mRNA expression from GO (n = 6) and normal (n = 5) orbital fat tissue was determined using real-time PCR technique. Orbital fat in the normal group from blepharoplasty represents extraconal (anterior) fat. mRNA expression in fibroblasts grown from these tissues before and after adipocyte differentiation was also documented. Finally, Western blotting was carried out to verify translation of TPO mRNA transcripts.
Results and discussion: TPO transcripts were detected in the orbital fat tissue obtained from normal and GO subjects using the real-time PCR technique. TPO expression was increased in GO compared to normal (N) tissues. However, TPO expression in cultured fibroblasts was similar in both groups and adipogenesis did not appear to alter TPO expression. Protein was detected by Western blot analysis using the TPO MAB 47 (mAb 47). The predicted 110-kDa band was detected in orbital fat as well as in orbital fibroblasts. Our results suggest the presence of TPO in GO and N orbital tissues. We hypothesise that immune responses directed against orbital TPO might play a role in modulating the clinical expression of GO.
The ACAA-insertion/deletion polymorphism at the 3′ UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance
Authors: Villuendas Gemma , Botella-Carretero José I , López-Bermejo Abel , Gubern Carme , Ricart Wifredo , Fernández-Real José Manuel , Millán José L San , Escobar-Morreale Héctor F 
Published: July 2006

Objective: The IGF-II receptor gene (IGFIIR) is located at chromosome 6q26, a region that harbors a genetic marker linked to insulin-resistant traits in Mexican–Americans. In the present study conducted in Spaniards, we tested a common polymorphism in IGFIIR for association with type 2 diabetes and insulin-resistant traits.
Design: Case–control association study.
Methods: One hundred and forty-five type 2 diabetic patients and 217 non-diabetic controls were genotyped for the ACAA-insertion/deletion polymorphism at the 3′ UTR of IGFIIR. Phenotyping included anthropometrics and a metabolic profile, including serum lipid levels and surrogate indexes of insulin resistance whenever possible.
Results: Diabetic patients were more frequently homozygous for the wild type 144 bp allele of IGFIIR compared with controls (diabetic patients 77.2%, controls 51.6%, P<0.001) suggesting a potential protective role against type 2 diabetes for the IGFIIR 140 bp variant. Carrying 140 bp alleles was associated with an odds ratio of having diabetes of 0.290 (95% confidence interval 0.109–0.770), and controls homozygous for the wild type 144 bp allele presented with lower insulin and triglyceride levels, which are proxies for insulin resistance.
Conclusions: The ACAA-insertion/deletion polymorphism at the 3′ UTR of IGFIIR is associated with type 2 diabetes and influences surrogate markers of insulin resistance in non-diabetic subjects.
Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte–dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18
Authors: Luzina Irina G. , Papadimitriou John C. , Anderson Richard , Pochetuhen Kerill , Atamas Sergei P. 
Published: July 2006

AbstractObjectiveLevels of CCL18 are elevated in patients with scleroderma lung disease and other fibrotic pulmonary diseases associated with T lymphocyte involvement. We sought to determine whether CCL18 alone can induce pulmonary T lymphocytic infiltration and fibrosis in mouse lungs.MethodsAn adenovirus vector was constructed and used for CCL18 delivery to mouse lungs in vivo. Immunohistochemical, flow cytometric, and enzyme‐linked immunosorbent assay analyses were used to assess the resulting changes.ResultsOverexpression of CCL18 led to massive perivascular and peribronchial infiltration of T lymphocytes. Although the expression of CCL18 peaked on day 7, the infiltration persisted up to day 64 after infection. The infiltrates were negative for proliferating cell nuclear antigen and TUNEL, suggesting the role of cell trafficking, rather than proliferation and apoptosis, in the infiltration dynamics. Patchy destruction of the alveolar architecture and collagen accumulation in association with the infiltrates were also noticed. These changes were infiltration‐dependent, rather than CCL18‐dependent, since treatment with antilymphocyte serum completely abrogated the CCL18‐induced changes. The infiltrates consisted almost exclusively of T lymphocytes that were minimally activated, with a minimal increase in the expression of CD69 and no changes in the expression of CD25, Fas, FasL, or CD40L. There was no increase in total pulmonary levels of profibrotic cytokines transforming growth factor β1 (TGFβ1) or interleukin‐13, although active TGFβ1 was present locally in association with the infiltrates and areas of distorted alveolar architecture. Prestimulation of primary T lymphocytes with CCL18 in vitro caused an up‐regulation of TGFβ1 and collagen production in T lymphocyte/fibroblast cocultures.ConclusionCCL18 promotes selective, long‐term pulmonary infiltration of T lymphocytes and infiltration‐dependent accumulation of collagen through a TGFβ1‐dependent mechanism.
Mortality in systemic lupus erythematosus
Authors: Bernatsky S. , Boivin J.‐F. , Joseph L. , Manzi S. , Ginzler E. , Gladman D. D. , Urowitz M. , Fortin P. R. , Petri M. , Barr S. , Gordon C. , Bae S.‐C. , Isenberg D. , Zoma A. , Aranow C. , Dooley M.‐A. , Nived O. , Sturfelt G. , Steinsson K. , Alarcón G. , Senécal J.‐L. , Zummer M. , Hanly J. , Ensworth S. , Pope J. , Edworthy S. , Rahman A. , Sibley J. , El‐Gabalawy H. , McCarthy T. , St. Pierre Y. , Clarke A. , Ramsey‐Goldman R. 
Published: July 2006

AbstractObjectiveTo examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled.MethodsOur sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar‐year periods were determined.ResultsThe overall SMR was 2.4 (95% confidence interval 2.3–2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non‐Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar‐year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001.ConclusionOur data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.
Anti–β2‐glycoprotein I antibodies in complex with β2‐glycoprotein I can activate platelets in a dysregulated manner via glycoprotein Ib‐IX‐V
Authors: Shi Tong , Giannakopoulos Bill , Yan Xiaokai , Yu Pei , Berndt Michael C. , Andrews Robert K. , Rivera Juan , Iverson G. Michael , Cockerill Keith A. , Linnik Matthew D. , Krilis Steven A. 
Published: July 2006

AbstractObjectiveResults of previous studies suggest that anti–β2‐glycoprotein I (anti‐β2GPI) antibodies in complex with β2GPI activate platelets in a dysregulated manner, potentially contributing to the prothrombotic tendency associated with the antiphospholipid syndrome (APS). We undertook this study to investigate the possible contribution of the GPIb‐IX‐V receptor to platelet activation mediated by the anti‐β2GPI antibody–β2GPI complex.MethodsIn vitro methods were used in the present study. The interaction between β2GPI and the GPIbα subunit of the GPIb‐IX‐V receptor was delineated using direct binding and competitive inhibition assays. The interaction between the anti‐β2GPI antibody–β2GPI complex and platelets was studied using a novel method in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by two methods; one involved measuring thromboxane B2 production and the other involved assessment of the activation of the phosphatidylinositol 3‐kinase/Akt/glycogen synthase kinase 3β intracellular signaling pathway. The contribution of the GPIbα receptor to platelet activation induced by the anti‐β2GPI antibody–β2GPI complex was assessed by observing the influence of 2 anti‐GPIbα antibodies (AK2 and SZ2) directed against distinct epitopes.ResultsThis study showed that β2GPI could bind to the GPIbα receptor. The anti‐β2GPI antibody–β2GPI complex was able to activate platelets, and this effect was inhibited by anti‐GPIbα antibody directed against epitope Leu‐36–Gln‐59, but not by anti‐GPIbα antibody directed against residues Tyr‐276–Glu‐282.ConclusionOur findings show that inappropriate platelet activation by the anti‐β2GPI antibody–β2GPI complex via the GPIbα receptor may contribute to the prothrombotic tendency associated with APS.
Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritis
Authors: Kong S. Y. , Stabler T. V. , Criscione L. G. , Elliott A. L. , Jordan J. M. , Kraus V. B. 
Published: July 2006

AbstractObjectiveTo evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee.MethodsTwenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS‐5D4), aggrecan neoepitope (CS846), high‐sensitivity C‐reactive protein (hsCRP), osteocalcin, transforming growth factor β1 (TGFβ1), and type II collagen (CII)–related epitopes (neoepitope from cleavage of CII [C2C], carboxy‐terminus of three‐quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy‐propeptide [CPII] in serum, and C‐terminal telopeptides of CII [CTX‐II] and C2C in urine).ResultsLevels of serum HA, COMP, KS‐5D4, and TGFβ1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX‐II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS‐5D4, TGFβ1, and urinary CTX‐II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3).ConclusionOur study results suggest that serum and urine sampling for HA, COMP, KS‐5D4, TGFβ1, CPII, urinary CTX‐II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort.
Rates of serious infection, including site‐specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti–tumor necrosis factor therapy: Results from the British Society for Rheumatology Biologics Register
Authors: Dixon W. G. , Watson K. , Lunt M. , Hyrich K. L. , Silman A. J. , Symmons D. P. M. 
Published: July 2006

AbstractObjectiveTo determine whether the rate of serious infection is higher in anti–tumor necrosis factor (anti‐TNF)–treated rheumatoid arthritis (RA) patients compared with RA patients treated with traditional disease‐modifying antirheumatic drugs (DMARDs).MethodsThis was a national prospective observational study of 7,664 anti‐TNF–treated and 1,354 DMARD‐treated patients with severe RA from the British Society for Rheumatology Biologics Register. All serious infections, stratified by site and organism, were included in the analysis.ResultsBetween December 2001 and September 2005, there were 525 serious infections in the anti‐TNF–treated cohort and 56 in the comparison cohort (9,868 and 1,352 person‐years of followup, respectively). The incidence rate ratio (IRR), adjusted for baseline risk, for the anti‐TNF–treated cohort compared with the comparison cohort was 1.03 (95% confidence interval 0.68–1.57). However, the frequency of serious skin and soft tissue infections was increased in anti‐TNF–treated patients, with an adjusted IRR of 4.28 (95% confidence interval 1.06–17.17). There was no difference in infection risk between the 3 main anti‐TNF drugs. Nineteen serious bacterial intracellular infections occurred, exclusively in patients in the anti‐TNF–treated cohort.ConclusionIn patients with active RA, anti‐TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment, after adjustment for baseline risk. In contrast, the rate of serious skin and soft tissue infections was increased, suggesting an important physiologic role of TNF in host defense in the skin and soft tissues beyond that in other tissues.
Urinary neutrophil gelatinase–associated lipocalin as a biomarker of nephritis in childhood‐onset systemic lupus erythematosus
Authors: Brunner Hermine I. , Mueller Michelle , Rutherford Cynthia , Passo Murray H. , Witte David , Grom Alexei , Mishra Jaya , Devarajan Prasad 
Published: July 2006

AbstractObjectiveRenal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase–associated lipocalin (NGAL) is a high‐quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis.MethodsA cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood‐onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double‐blind, cross‐sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme‐linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls.ResultsNGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood‐onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r ≥ 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood‐onset SLE patients with biopsy‐proven nephritis.ConclusionUrinary NGAL is a promising potential biomarker of childhood‐onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes.
Change in joint space width: Hyaline articular cartilage loss or alteration in meniscus?
Authors: Hunter D. J. , Zhang Y. Q. , Tu X. , LaValley M. , Niu J. B. , Amin S. , Guermazi A. , Genant H. , Gale D. , Felson D. T. 
Published: July 2006

AbstractObjectiveTo explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space.MethodsThe Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30‐month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight‐bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0–3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross‐sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables.ResultsWe evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m2). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space.ConclusionThe meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.
Anti–N‐methyl‐D‐aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus
Authors: Lapteva Larissa , Nowak Miroslawa , Yarboro Cheryl H. , Takada Kazuki , Roebuck‐Spencer Tresa , Weickert Thomas , Bleiberg Joseph , Rosenstein Donald , Pao Maryland , Patronas Nicholas , Steele Sonya , Manzano Melissa , van der Veen Jan Willem C. , Lipsky Peter E. , Marenco Stefano , Wesley Robert , Volpe Bruce , Diamond Betty , Illei Gabor G. 
Published: July 2006

AbstractObjectiveTo assess the association of cognitive dysfunction and depression with serum antibodies to N‐methyl‐D‐aspartate (NMDA) receptor (anti‐NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE).MethodsSixty patients underwent neurocognitive assessment, evaluation for depression with the Beck Depression Inventory II (BDI‐II) and psychiatric interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM‐IV] criteria), brain magnetic resonance imaging, and proton magnetic resonance spectroscopy imaging (1H‐MRSI). Cognition was assessed in 5 domains: memory, attention/executive, visuospatial, motor, and psychomotor, and adjusted to each individual's best level of prior cognitive functioning estimated from the reading subtest of the Wide Range Achievement Test–3 (WRAT‐3). Serum anti‐NR2 antibodies were measured by enzyme‐linked immunosorbent assay using a pentapeptide from the human NMDA receptor.ResultsCognitive dysfunction was found in 28 of 60 patients (mild in 8, moderate in 20) before adjustment for WRAT‐3 and in 35 of 60 patients (mild in 15, moderate in 11, and severe in 9) after adjustment for WRAT‐3. The changes were most pronounced in the memory and visuospatial domains. There was no significant association between anti‐NR2 antibody levels and cognition. On 1H‐MRSI, patients with moderate or severe cognitive dysfunction had significantly higher choline:creatine ratios in the dorsolateral prefrontal cortex and the white matter, compared with patients with mild or absent cognitive dysfunction. Anti‐NR2 antibodies were significantly correlated with BDI scores; patients with BDI‐II scores of ≥14 had higher serum levels of anti‐NR2 antibodies (P = 0.005, 95% confidence interval 0.83, 4.31), and there was a trend toward higher anti‐NR2 antibody levels among patients who fulfilled the DSM‐IV criteria for major depression.ConclusionSerum anti‐NR2 antibodies are associated with depressive mood but not with cognitive dysfunction in SLE at a given time point. Larger longitudinal studies are needed to address the possible association between anti‐NR2 antibodies and depression in SLE.