bluuebunny/crossref_metadata_2025 huggingface dataset:
Methotrexate catabolism to 7‐hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation
Authors: Baggott Joseph E. , Morgan Sarah L.
Published: July 2009

Objective

To assess the catabolism of methotrexate (MTX) to 7‐hydroxy‐MTX (7‐OH‐MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism.

Methods

Urinary excretion of MTX and its catabolite, 7‐OH‐MTX, was measured in 2 24‐hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7‐OH‐MTX concentrations were determined by high‐performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7.

Results

Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7‐OH‐MTX, but folinic acid did not. Excretion of 7‐OH‐MTX (determined as a percentage of the dose of MTX or as mg 7‐OH‐MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7‐OH‐MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7‐OH‐MTX excretion (P = 0.03). Relatively high 7‐OH‐MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35).

Conclusion

Our findings of a non‐normal distribution of 7‐OH‐MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7‐OH‐MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7‐OH‐MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo.
Physical activity in women with arthritis: Examining perceived barriers and self‐regulatory efficacy to cope
Authors: Gyurcsik Nancy C. , Brawley Lawrence R. , Spink Kevin S. , Brittain Danielle R. , Fuller Daniel L. , Chad Karen
Published: July 2009

Objective

To examine whether the theory‐based social cognitions of perceived barrier frequency, barrier limitation, and self‐regulatory efficacy to cope were predictors of planned physical activity among adult women with arthritis. A secondary purpose was to identify and provide a phenomenologic description of the relevant barriers and coping strategies reported by study participants.

Methods

Eighty adult women (mean ± SD age 49.09 ± 12.89 years) with self‐reported doctor‐diagnosed arthritis participated in this observational study. Participants completed online survey measures of barriers to physical activity and, for each barrier, reported the frequency of occurrence and the extent of limitation. Measures of coping strategies for each barrier, efficacy to cope, and physical activity were also obtained.

Results

A multiple hierarchical regression analysis resulted in a model that significantly predicted physical activity (F[9,70] = 6.80, P < 0.01, adjusted R2 = 0.40). Barrier limitation (standardized β = −0.56) and efficacy (standardized β = 0.20) were significant independent predictors. Phenomenologic findings indicated that arthritis‐specific personal barriers (e.g., pain and fatigue due to arthritis) and arthritis‐specific coping strategies (e.g., activity modification) were more commonly reported than generic barriers and coping strategies.

Conclusion

Self‐regulatory efficacy to cope and relevant perceived physical activity barriers, which were primarily arthritis‐specific and moderately or more limiting to planned physical activity, were important social cognitive predictors of physical activity, a key nonpharmacologic arthritis treatment, among women with arthritis. Future research direction should examine potential moderators of the relationship between these predictors and physical activity, such as pain acceptance.
Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome
Authors: Yin Hong , Borghi Maria Orietta , Delgado‐Vega Angélica M. , Tincani Angela , Meroni Pier‐Luigi , Alarcón‐Riquelme Marta E.
Published: July 2009

Objective

Primary antiphospholipid syndrome (APS) is formally classified by the presence of antiphospholipid antibodies, recurrent thrombosis, and/or pregnancy morbidity in the absence of any underlying full‐blown systemic autoimmune disease. However, systemic manifestations in patients with primary APS have been recently reported, as has the presence of serologic markers in common with systemic lupus erythematosus (SLE). In spite of similarities between the 2 diseases, only a minority of cases of primary APS evolve into full‐blown SLE, even after a long followup period. The aim of this study was to investigate whether the analysis of SLE susceptibility genes may provide at least a partial explanation for such a discrepancy.

Methods

One hundred thirty‐three patients with primary APS classified according to the Sydney criteria and 468 healthy control subjects from the same geographic area were recruited. We genotyped 3 single‐nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (rs2736340).

Results

STAT4 and BLK displayed a strong genetic association with primary APS (for rs7574865, odds ratio [OR] 2.19, P = 5.17 × 10−7; for rs2736340, OR 2.06, P = 1.78 × 10−6), while a weak association with IRF5 and no association with BANK1 were observed.

Conclusion

The presence of a strong genetic association with only a few SLE susceptibility genes and the absence of a more complex gene association may contribute to the lack of cases of full‐blown SLE developing in patients with primary APS, in spite of the clinical and serologic similarities between SLE and primary APS.
Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti–Mi‐2 autoantibodies in women
Authors: Love Lori A. , Weinberg Clarice R. , McConnaughey D. Robert , Oddis Chester V. , Medsger Thomas A. , Reveille John D. , Arnett Frank C. , Targoff Ira N. , Miller Frederick W.
Published: July 2009

Objective

Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi‐2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti–Mi‐2 autoantibodies in the US.

Methods

We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service.

Results

UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9–5.8) and with the proportion of patients expressing anti–Mi‐2 autoantibodies (OR 6.0, 95% CI 1.1–34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3–11.0 and OR 17.3, 95% CI 1.8–162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti–signal recognition particle autoantibodies.

Conclusion

This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies.
Abrogation of antibody‐induced arthritis in mice by a self‐activating viridin prodrug and association with impaired neutrophil and endothelial cell function
Authors: Stangenberg Lars , Ellson Chris , Cortez‐Retamozo Virna , Ortiz‐Lopez Adriana , Yuan Hushan , Blois Joseph , Smith Ralph A. , Yaffe Michael B. , Weissleder Ralph , Benoist Christophe , Mathis Diane , Josephson Lee , Mahmood Umar
Published: July 2009

Objective

To test a novel self‐activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3‐kinase inhibitor, in a model of antibody‐mediated inflammatory arthritis.

Methods

The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10‐day disease course (serum‐transfer arthritis). Protease activity was measured by a near‐infrared imaging approach using a cleavable cathepsin–selective probe. Further near‐infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil–endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay.

Results

SAV prevented ankle swelling in mice with serum‐transfer arthritis in a dose‐dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor α was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease‐laden vesicles, were decreased by SAV administration.

Conclusion

A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody‐induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions.
Value of anti–modified citrullinated vimentin and third‐generation anti–cyclic citrullinated peptide compared with second‐generation anti–cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis
Authors: van der Linden Michael P. M. , van der Woude Diane , Ioan‐Facsinay Andreea , Levarht E. W. Nivine , Stoeken‐Rijsbergen Gerrie , Huizinga Tom W. J. , Toes René E. M. , van der Helm‐van Mil Annette H. M.
Published: July 2009

Objective

Autoantibodies such as rheumatoid factor (RF) and anti–citrullinated protein autoantibodies (ACPAs) determined by testing with second‐generation anti–cyclic citrullinated peptide (anti–CCP‐2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third‐generation anti‐CCP (anti–CCP‐3) and anti–modified citrullinated vimentin (anti‐MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease‐modifying antirheumatic drug (DMARD)–free remission in RA.

Methods

Patients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD‐free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti–CCP‐2, anti–CCP‐3, anti‐MCV, and RF) and between combinations of these tests.

Results

Among the single tests performed in patients with UA, anti–CCP‐2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA‐positive and ACPA‐negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test.

Conclusion

For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA.
Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin‐17
Authors: Fransen Justin H. , Hilbrands Luuk B. , Ruben Jurjen , Stoffels Monique , Adema Gosse J. , van der Vlag Johan , Berden Jo H.
Published: July 2009

Objective

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting.

Methods

The uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC‐induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme‐linked immunosorbent assay.

Results

DCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin‐6 (IL‐6) and tumor necrosis factor α production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb–induced DC maturation was shown to be independent of Toll‐like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb‐matured DCs induced production of IL‐2, interferon‐γ, and, in particular, IL‐17, suggesting a Th1/Th17 response.

Conclusion

Apoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb–induced DC maturation represents an important driving force in the autoimmune response in SLE.
Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints
Authors: Schett Georg , Kiechl Stefan , Bonora Enzo , Zwerina Jochen , Mayr Agnes , Axmann Roland , Weger Siegfried , Oberhollenzer Friedrich , Lorenzini Rolando , Willeit Johann
Published: July 2009

Objective

Osteoarthritis (OA) is a leading cause of pain and physical disability in middle‐aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight.

Methods

Joint replacement surgery due to severe hip or knee OA was recorded over a 15‐year period in the prospective Bruneck cohort study. Demographic characteristics and lifestyle and biochemical variables, including the level of soluble vascular cell adhesion molecule 1 (VCAM‐1), were assessed at the 1990 baseline visit and tested as predictors of joint replacement surgery.

Results

Between 1990 and 2005, hip or knee joint replacement due to OA was performed in 60 subjects. VCAM‐1 level emerged as a highly significant predictor of the risk of joint replacement surgery. Intervention rates were 1.9, 4.2, and 10.1 per 1,000 person‐years in the first, second, and third tertiles, of the VCAM‐1 level, respectively. In multivariable logistic regression analysis, the adjusted relative risk of joint replacement surgery in the highest versus the lowest tertile group of VCAM‐1 level was 3.9 (95% confidence interval 1.7–8.7) (P < 0.001). Findings were robust in various sensitivity analyses and were consistent in subgroups. Addition of the VCAM‐1 level to a risk model already including age, sex, and body mass index resulted in significant gains in model discrimination (C statistic) and calibration and in more accurate risk classification of individual participants.

Conclusion

The level of soluble VCAM‐1 emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe OA. If our findings can be reproduced in other epidemiologic cohorts, they will assist in routine risk classification and will contribute to a better understanding of the etiology of OA.
Changes in surface markers of human mesenchymal stem cells during the chondrogenic differentiation and dedifferentiation processes in vitro
Authors: Lee Hyun Jung , Choi Byung Hyune , Min Byoung‐Hyun , Park So Ra
Published: July 2009

Objective

To investigate surface markers showing specific changes during the chondrogenic differentiation and dedifferentiation of human mesenchymal stem cells (MSCs).

Methods

Human MSCs from adult bone marrow were subjected to chondrogenic differentiation in 3‐dimensional (3‐D) alginate culture with or without transforming growth factor β3 (TGFβ3) for 2 weeks, followed by dedifferentiation in monolayer for 1 week. Surface antigens were selected from those previously reported to show changes in expression during dedifferentiation of human articular chondrocytes (HACs).

Results

Flow cytometry was used to identify 3 groups of surface antigens with differential expression patterns that were quite different from those previously reported on HACs. Two groups of antigens were expressed at high levels on human MSCs. The expression of the first group of antigens (CD44, CD58, CD81, CD90, CD105, and CD166) was decreased reversibly by the 3‐D alginate culture and irreversibly in the presence of TGFβ3, except for CD81, which showed reversible changes regardless of TGFβ3. The expression of the second group of antigens (CD49c, CD49e, and CD151) was decreased during chondrogenic differentiation only in the presence of TGFβ3. During all experimental stages, the expression of the third group of antigens (CD14, CD26, CD49f, CD54, CD106, CD119, and CD140a) was maintained at low levels (expressed on <30% of cells), although with some fluctuations.

Conclusion

We speculate that the second group of surface antigens could be negative markers for chondrogenic differentiation of human MSCs.
Fcγ receptor–dependent expansion of a hyperactive monocyte subset in lupus‐prone mice
Authors: Santiago‐Raber Marie‐Laure , Amano Hirofumi , Amano Eri , Baudino Lucie , Otani Masako , Lin Qingshun , Nimmerjahn Falk , Verbeek J. Sjef , Ravetch Jeffrey V. , Takasaki Yoshinari , Hirose Sachiko , Izui Shozo
Published: July 2009

Objective

Lupus‐prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr‐1– monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (FcγR) in the development of monocytosis and to characterize the functional phenotype of the Gr‐1– subset that accumulates in lupus‐prone mice bearing the NZB‐type defective Fcgr2b allele for the inhibitory FcγRIIB.

Methods

The development of monocytosis was analyzed in BXSB and anti‐IgG2a rheumatoid factor–transgenic C57BL/6 mice deficient in activating FcγR. Moreover, we assessed the expression levels of activating FcγR and inhibitory FcγRIIB on Gr‐1+ and Gr‐1– monocyte subsets in C57BL/6 mice bearing the C57BL/6‐type or the NZB‐type Fcgr2b allele.

Results

We observed monocytosis with expansion of the Gr‐1– subset in anti‐IgG2a–transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti‐IgG2a–transgenic C57BL/6 mice deficient in activating FcγR. The Gr‐1– subset that accumulated in lupus‐prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory FcγRIIB, due to the presence of the NZB‐type Fcgr2b allele, but high levels of activating FcγRIV. This was in contrast to high levels of FcγRIIB expression and no FcγRIV expression on the Gr‐1+ subset.

Conclusion

Our results demonstrated a critical role of activating FcγR in the development of monocytosis and in the expansion of a Gr‐1–FcγRIIBlowFcγRIV+ hyperactive monocyte subset in lupus‐prone mice. Our findings further highlight the importance of the NZB‐type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells.
Determinants of self‐reported health status in a population‐based sample of persons with radiographic knee osteoarthritis
Authors: Reichmann William M. , Katz Jeffrey N. , Kessler Courtenay L. , Jordan Joanne M. , Losina Elena
Published: July 2009

Objective

Knee osteoarthritis (OA) is highly prevalent and disabling. Patients with radiographic knee OA may experience pain and functional impairment, which can diminish their health status. Our objective was to determine factors associated with self‐reported health status in a national population‐based sample with radiographic knee OA.

Methods

Our sample included all of the Third National Health and Nutrition Examination Survey (NHANES‐III) participants who underwent a knee radiograph and were found to have radiographic OA (defined as Kellgren/Lawrence grade 2 or higher). Self‐reported health status was determined by asking the participant to rate their overall health as excellent, very good, good, fair, or poor. Self‐reported health status was analyzed as an ordinal variable using cumulative logit regression, as a dichotomous variable (excellent/very good/good versus fair/poor) using logistic regression, and as a continuous variable after transformation using linear regression.

Results

A total of 1,021 (42%) of NHANES‐III participants with a knee radiograph were included in this analysis. The multivariable analyses were performed on 1,009 (99%) of the eligible participants with complete data. We found that nonwhite race, lower income, more comorbidities, and greater functional limitation were associated with worse self‐reported health status in all 3 multivariable analyses.

Conclusion

This study has quantified the role of clinical, radiographic, and socioeconomic factors associated with self‐reported health status in a population‐based sample of patients with knee OA. Self‐reported health status in patients with knee OA was associated with functional status and comorbidity.
Pena‐Shokeir phenotype (Fetal akinesia deformation sequence) revisited
Authors: Hall Judith G.
Published: July 2009

BACKGROUND: Pena and Shokeir described the phenotype of two sisters in 1974, and subsequently their features have become recognized as a sequence of deformational changes related to decreased or absent fetal movement (fetal akinesia deformation sequence [FADS]), because of the work of Moessinger (1983). METHODS: Identification of reported cases by searching Online Mendelian Inheritance in Man, Medlines, the London Dysmorphology Database, and the references found in these articles. These case reports were reviewed, tabulated, and summarized. RESULTS: It is now possible to recognize at least 20 familial types of Pena‐Shokeir phenotype (PSP), based on the differences found in the reports of the natural history and pathology found at fetal and newborn autopsy. In addition, characteristic changes in the central nervous system seen with embryonic/fetal vascular compromise have been recognized in many reported cases. Most of the reported cases of PSP/FADS related to vascular compromise are sporadic, but familial cases have also been reported. CONCLUSION: Lack of fetal movement (fetal akinesia) in humans produces a recognizable sequence of deformations. Many developmental processes must be accomplished for fetal movement to be normal, and for extra‐uterine life to be sustainable. Prenatal diagnosis is possible through real‐time ultrasound studies as early as 12 weeks. Most reported cases die in utero, at birth, or in the newborn period. Advances in embryo/fetus pathology have led to the recognition of the many familial subtypes, allowing improved genetic counseling and early recognition in subsequent pregnancies. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Extremely low frequency pulsed electromagnetic field designed for antinociception does not affect microvascular responsiveness to the vasodilator acetylcholine
Authors: McKay Julia C. , Corbacio Michael , Tyml Karel , Prato Frank S. , Thomas Alex W.
Published: July 2009

A 225 µT, extremely low frequency, pulsed electromagnetic field (PEMF) that was designed for the induction of antinociception, was tested for its effectiveness to influence blood flow within the skeletal microvasculature of a male Sprague–Dawley rat model (n = 103). Acetylcholine (0.1, 1.0, or 10 mM) was used to perturb normal blood flow and to delineate differential effects of the PEMF, based on degree of vessel dilation. After both 30 and 60 min of PEMF exposure, we report no effects on peak perfusion response to acetylcholine (with only 0.2% of the group difference attributed to exposure). Spectral analysis of blood flow data was generated to obtain information related to myogenic activity (0.15–0.40 Hz), respiratory rate (0.4–2.0 Hz), and heart rate (2.0–7.0 Hz), including the peak frequency within each of the three frequency regions identified above, peak power, full width at half maximum (FWHM), and mean within band. No significant effects due to exposure were observed on myogenic activity of examined blood vessels, or on heart rate parameters. Anesthesia‐induced respiratory depression was, however, significantly reduced following PEMF exposure compared to shams (although exposure only accounted for 9.4% of the group difference). This set of data suggest that there are no significant acute physiological effects of 225 µT PEMF after 30 and 60 min of exposure on peak blood flow, heart rate, and myogenic activity, but perhaps a small attenuation effect on anesthetic‐induced respiratory depression. Bioelectromagnetics 31:64–76, 2010. © 2009 Wiley‐Liss, Inc.
Evolutionary formation of new protein folds is linked to metallic cofactor recruitment
Authors: Ji Hong‐Fang , Chen Lei , Jiang Ying‐Ying , Zhang Hong‐Yu
Published: July 2009

To explore whether the generation of new protein folds could be linked to metallic cofactor recruitment, we identified the oldest examples of folds for manganese, iron, zinc, and copper proteins by analyzing their fold‐domain mapping patterns. We discovered that the generation of these folds was tightly coupled to corresponding metals. We found that the emerging order for these folds, i.e., manganese and iron protein folds appeared earlier than zinc and copper counterparts, coincides with the putative bioavailability of the corresponding metals in the ancient anoxic ocean. Therefore, we conclude that metallic cofactors, like organic cofactors, play an evolutionary role in the formation of new protein folds. This link could be explained by the emergence of protein structures with novel folds that could fulfill the new protein functions introduced by the metallic cofactors. These findings not only have important implications for understanding the evolutionary mechanisms of protein architectures, but also provide a further interpretation for the evolutionary story of superoxide dismutases.
Pannexins, distant relatives of the connexin family with specific cellular functions?
Authors: D'hondt Catheleyne , Ponsaerts Raf , De Smedt Humbert , Bultynck Geert , Himpens Bernard
Published: July 2009

Intercellular communication (IC) is mediated by gap junctions (GJs) and hemichannels, which consist of proteins. This has been particularly well documented for the connexin (Cx) family. Initially, Cxs were thought to be the only proteins capable of GJ formation in vertebrates. About 10 years ago, however, a new GJ‐forming protein family related to invertebrate innexins (Inxs) was discovered in vertebrates, and named the pannexin (Panx) family. Panxs, which are structurally similar to Cxs, but evolutionarily distinct, have been shown to be co‐expressed with Cxs in vertebrates. Both protein families show distinct properties and have their own particular function. Identification of the mechanisms that control Panx channel gating is a major challenge for future work. In this review, we focus on the specific properties and role of Panxs in normal and pathological conditions.
Expanding roles for AMP‐activated protein kinase in neuronal survival and autophagy
Authors: Poels Jeroen , Spasić Miloš R. , Callaerts Patrick , Norga Koenraad K.
Published: July 2009

AMP‐activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti‐diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted.
Trans‐splicing of organelle introns – a detour to continuous RNAs
Authors: Glanz Stephanie , Kück Ulrich
Published: July 2009

In eukaryotes, RNA trans‐splicing is an important RNA‐processing form for the end‐to‐end ligation of primary transcripts that are derived from separately transcribed exons. So far, three different categories of RNA trans‐splicing have been found in organisms as diverse as algae to man. Here, we review one of these categories: the trans‐splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. Trans‐spliced exons can be predicted from DNA sequences derived from a large number of sequenced organelle genomes. Further molecular genetic analysis of mutants has unravelled proteins, some of which being part of high‐molecular‐weight complexes that promote the splicing process. Based on data derived from the alga Chlamydomonas reinhardtii, a model is provided which defines the composition of an organelle spliceosome. This will have a general relevance for understanding the function of RNA‐processing machineries in eukaryotic organelles.
Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer
Authors: Lujan J , Valero G , Hernandez Q , Sanchez A , Frutos M D , Parrilla P
Published: July 2009

Background

The laparoscopic treatment of rectal cancer is controversial. This study compared surgical outcomes after laparoscopic and open approaches for mid and low rectal cancers.

Methods

Some 204 patients with mid and low rectal adenocarcinomas were allocated randomly to open (103) or laparoscopic (101) surgery. The surgical team was the same for both procedures. Most patients had stage II or III disease, and received neoadjuvant therapy with oral capecitabine and 50–54 Gy external beam radiotherapy.

Results

Sphincter-preserving surgery was performed in 78·6 and 76·2 per cent of patients in the open and laparoscopic groups respectively. Blood loss was significantly greater for open surgery (P < 0·001) and operating time was significantly greater for laparoscopic surgery (P = 0·020), and return to diet and hospital stay were longer for open surgery. Complication rates, and involvement of circumferential and radial margins were similar for both procedures, but the number of isolated lymph nodes was greater in the laparoscopic group (mean 13·63 versus 11·57; P = 0·026). There were no differences in local recurrence, disease-free or overall survival.

Conclusion

Laparoscopic surgery for rectal cancer has a similar complication rate to open surgery, with less blood loss, rapid intestinal recovery, shorter hospital stay, and no compromise of oncological outcomes. Registration number: NCT00782457 (http://www.clinicaltrials.gov).
Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer
Authors: Yoshikawa T , Sasako M , Yamamoto S , Sano T , Imamura H , Fujitani K , Oshita H , Ito S , Kawashima Y , Fukushima N
Published: July 2009

Background

Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma.

Methods

Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m2 on days 1 and 15) and cisplatin (80 mg/m2 on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death.

Results

The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14·6 months and the 3-year survival rate 27 per cent.

Conclusion

This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.
Systematic review of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis
Authors: Petrov M S , Savides T J
Published: July 2009

Background

Endoscopic ultrasonography (EUS) has emerged as an accurate diagnostic alternative to endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to perform a systematic review of all randomized controlled trials of EUS-guided ERCP versus ERCP alone in patients with suspected choledocholithiasis.

Methods

The search for eligible studies was carried out using the MEDLINE, Cochrane Central Register of Controlled Trials, and Science Citation Index electronic databases. Meta-analysis was conducted using a random-effects model.

Results

Four trials containing 213 patients randomized to EUS-guided ERCP and 210 to ERCP alone were selected. In the EUS-guided ERCP group, ERCP was avoided in 143 patients (67·1 per cent) when EUS did not detect choledocholithiasis. The use of EUS significantly reduced the risk of overall complications (relative risk 0·35 (95 per cent confidence interval (c.i.) 0·20 to 0·62); P < 0·001) and post-ERCP acute pancreatitis (relative risk 0·21 (95 per cent c.i. 0·06 to 0·83); P = 0·030).

Conclusion

By performing EUS first, ERCP may be safely avoided in two-thirds of patients with common bile duct stones. Application of EUS in the selection of patients for therapeutic ERCP significantly reduces the complication rate.
Childhood risk factors for offending before first psychiatric admission for people with schizophrenia: a case–control study of high security hospital admissions
Authors: Jones Roland M. , Van den Bree Marianne , Ferriter Michael , Taylor Pamela J.
Published: July 2009

Background

People with schizophrenia who offend do not constitute a homogenous population. Pre‐illness characteristics may distinguish groups.

Aims

To test for differences in prevalence of childhood risk factors for offending between serious offenders with schizophrenia who had started offending before their first ever psychiatric admission (pre‐admission offenders) and those who had started after it (post‐admission offenders). Our hypothesis was that such adverse childhood factors would be more prevalent in the pre‐admission offenders.

Method

Retrospective interview and records case–control study of all first high security hospital admissions diagnosed with schizophrenia in England 1972–2000. Risk factors were identified by multivariate logistic regression.

Results

853 patients were pre‐ and 741 post‐admission offenders. Our hypothesis was confirmed in that factors associated with pre‐admission offending were paternal criminal convictions, larger family size, and younger age at first use of illicit drugs, on first smoking cigarettes, and at maternal separation. There were differences too in pre‐high security hospital treatment: pre‐admission offenders had been younger at first court appearance and had more criminal justice system disposals, post‐admission offenders were younger at first ever psychiatric hospital admission and more often hospitalized.

Conclusions

While early offending among people with schizophrenia may delay treatment, making the distinction between pre‐admission and post‐admission offending may be useful in understanding the aetiology of the offending, and establishment of such a history may help in targeting interventions supplementary to treatment specific for the psychosis. Copyright © 2009 John Wiley & Sons, Ltd.
Consideration of the blood supply of the ileocecal segment in valve preserving right hemicolectomy
Authors: Fernando E.D.P.S. , Deen K.I.
Published: July 2009

The ileocecal valve (ICV) is known to control the flow of chyme and to prevent bacterial colonization of the small intestine. Preservation of this segment during right hemicolectomy is likely to prevent loss of its function. This study aimed at evaluating the arterial supply of the ICV to help preserve the valve during right hemicolectomy. Fifty‐four fresh human cadavers (37 male, 17female; median age: 54 years, range: 18–90 years) were studied after relatives gave written, informed consent. At postmortem, 20 cm of terminal ileum with the ileocecal segment and up to 20 cm of ascending colon were removed en bloc with its mesentery and blood supply. The ileocolic artery was cannulated and injected with 10 ml of water‐soluble red dye under pressure. The arterial supply was dissected to demonstrate a pattern. In all, the ICV was supplied by the ileocolic artery, a branch of the superior mesenteric, which divided into an anterior and a posterior cecal artery. A marginal branch of the right colic was noted to contribute to ICV blood supply in only two (4%). Furthermore, study of the anastomosis at the ICV showed that the anterior cecal artery was present in all (100%), posterior cecal in 48 (89%), and recurrent ileal artery in 53 (98%). A rich anastomosis between vessels at the ICV; small “windows,” short tributaries, were seen in 38 (70%), whereas a poor anastomotic network at the ICV; large “windows,” long tributaries, between these vessels were seen in 12 (22%). In four (8%), we were unable to clearly determine between rich and poor anastomotic networks. Other variants included, absent posterior cecal artery in six (11%) and absent recurrent ileal artery in one (2%). The ICV has a predictable blood supply in the majority of patients. Preservation of the anterior cecal artery would ensure a vascularized ICV in right hemicolectomy. Clin. Anat. 22:712–715, 2009. © 2009 Wiley‐Liss, Inc.
Protective mechanisms of the common fibular nerve in and around the fibular tunnel: A new concept
Authors: El Gharbawy Ramadan M. , Skandalakis Lee J. , Skandalakis John E.
Published: July 2009

The most frequent site at which the common fibular nerve is affected by compression, trauma, traction, masses, and surgery is within and around the fibular tunnel. The aim of this study was to determine whether there were protective mechanisms at this site that guard against compression of the nerve. Twenty‐six lower limbs of 13 preserved adult cadavers (11 males and two females) were used. Proximal to the entrance of the tunnel, three anatomical configurations seemed to afford the required protection for the nerve: reinforcement of the deep fascia; tethering of the common fibular nerve to both the tendon of the biceps femoris and the reinforced fascia; and the particular arrangement of the deep fascia, fibular head, and soleus and gastrocnemius muscles. At the entrance of the tunnel, contraction of the first segment of fibularis longus muscle could afford the required protection. In the tunnel, contraction of the second and third segments of fibularis longus muscle could guard against compression of the nerve. The tough fascia on the surface of fibularis longus muscle and the fascial band within it, which have long been accused of compression of the nerve, may actually be elements of the protective mechanisms. We conclude that there are innate, anatomical protective mechanisms which should be taken into consideration when decompressing the common fibular nerve. To preserve these mechanisms whenever possible, the technique should be planned and varied according to the underlying etiology. Clin. Anat. 22:738–746, 2009. © 2009 Wiley‐Liss, Inc.
An integrated VR–GIS navigation platform for city/region simulation
Authors: Ma Chunyong , Chen Ge , Han Yong , Qi Yongyang , Chen Yong
Published: July 2009

This paper introduces a virtual city oriented VR–GIS platform which synthesizes several latest information technologies including virtual reality, 3D geographical information system, remote sensing, and multi‐dimensional visualization. The platform is a seamless integration of VR functions and GIS analysis methods, which can be used to organize and present massive spatial data. It also supplies 3D spatial analysis functions, 3D visualization for spatial process and natural simulation, and serves as an engine platform for digital city. Copyright © 2009 John Wiley & Sons, Ltd.
Enantioselective Nitroso‐Diels–Alder Reaction and Its Application for the Synthesis of (−)‐Peracetylated Conduramine A‐1
Authors: Jana Chandan Kumar , Grimme Stefan , Studer Armido
Published: July 2009

CuI‐catalyzed enantioselective nitroso‐Diels–Alder reactions (NDA reactions) of 2‐nitrosopyridine with various dienes are presented. The [CuPF6(MeCN)4]/Walphos‐CF3 catalyst system is best suited to catalyze the NDA reaction of various dienes by using 2‐nitrosopyridine as a dienophile. In most of the cases studied, cycloadducts are obtained in quantitative yield with very good to excellent enantioselectivities. Based on DFT calculations, a model to explain the stereochemical outcome of the NDA reaction is presented. Finally, an efficient short synthesis of (−)‐peracetylated conduramine A‐1 by applying the enantioselective NDA reaction as a key step is described.
ChemInform Abstract: Cadmium‐Auride AIICdxAu2‐x (AII: Ca, Sr) — Synthesis, Crystal Structure, Chemical Bonding.
Authors: Harms Wiebke , Duerr Ines , Roehr Caroline
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Vanadium Octacyanoniobate‐Based Magnet with a Curie Temperature of 138 K.
Authors: Kosaka Wataru , Imoto Kenta , Tsunobuchi Yoshihide , Ohkoshi Shin‐ichi
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Sol—Gel Synthesis and Electrochemical Properties of CuV2O6 Cathode Material.
Authors: Cao Jun‐qi , Wang Xian‐you , Tang Anping , Wang Xin , Wang Ying , Wu Wen
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Citrate—Oxide Method to Prepare SrBi4Ti4O15 Powders and Ceramics.
Authors: Xu Zhijun , Chu Ruiqing , Hao Jigong , Li Guorong , Yin Qingrui
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Preparation, Characterization, Impedance and Thermal Expansion Studies of Mn0.5MSb(PO4)3 (M: Al, Fe and Cr).
Authors: Anantharamulu Navulla , Rao K. Koteswara , Vithal M. , Prasad G.
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: The Lanthanoid Osmium Gallides Er2Os3Ga10 and Tm2Os3Ga10 with Yb2Ru3Ga10‐Type Structure.
Authors: Jeitschko Wolfgang , Schlueter Martin
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Hydrocarbamoylation of Unsaturated Bonds by Nickel/Lewis‐Acid Catalysis.
Authors: Nakao Yoshiaki , Idei Hiroaki , Kanyiva Kyalo Stephen , Hiyama Tamejiro
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: A Convenient, One‐Step Synthesis of Benzyl (Ar) Ureas of the Type ArCH2NHCONHR from Ar and R1OCH2NHCONHR via Ureidoalkylation.
Authors: Meece F. Alex , Jayasinghe Champika , Histand Gary , Burns Dennis H.
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Ruthenium‐Mediated Oxidation under Buffered Conditions: A Simple and Useful Protocol for the Synthesis of Norbornyl α‐Diketones with Acid Sensitive Functionalities.
Authors: Khan Faiz Ahmed , Sudheer Ch.
Published: July 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.