bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential gene expression profiles in the venom gland/sac ofOrancistrocerus drewseni(Hymenoptera: Eumenidae)
Authors: Baek Ji Hyeong , Woo Tae Ha , Kim Chang Bae , Park Jong Hwa , Kim Hyojoong , Lee Seunghwan , Lee Si Hyeock
Published: May 2009

To determine differential gene expression profiles in the venom gland and sac (gland/sac) of a solitary hunting wasp species,Orancistrocerus drewseniSaussure (1857), a subtractive cDNA library was constructed by suppression subtractive hybridization. A total of 498 expressed sequence tags (EST) were clustered and assembled into 205 contigs (94 multiple sequences and 111 singletons). About 65% (134) of the contigs had matched BLASTx hits (E≤10−4). Among these, 115 contigs had similarity to proteins with assigned molecular function in the Gene Ontology database, and most of them (112 contigs, 83%) were homologous to genes from Hymenoptera, particularly toApis mellifera(98 contigs). The contigs encoding hyaluronidase and phospholipase A2, known to be main components of wasp venoms, were found in high frequencies (27 and 4%, respectively, as judged by the number of ESTs) in the gene ontology category of catalytic activity. Full‐length open reading frames of hyaluronidase and phospholipase A2 were characterized and their abundance in the venom gland/sac was confirmed by quantitative real‐time PCR. Several contigs encoding enzymes, including zinc‐metallopeptidases that are likely involved in the processing and activation of venomous proteins or peptides, were also identified from the library. Discovery of venom gland/sac‐specific genes should promote further studies on biologically active components in the venom ofO. drewseni. © 2009 Wiley Periodicals, Inc.
Synthesis and pp60c‐Src Tyrosine Kinase Inhibitory Activities of Novel Indole‐3‐Imine and Amine Derivatives Substituted at N1 and C5
Authors: Kiliç Zuhal , Isgör Yasemin G. , Ölgen Süreyya
Published: May 2009

A series of novel 1,3,5‐trisubstituted indole derivatives, namely, N‐benzyl 5‐phenyl indole‐3‐imine, N‐benzyl‐5‐(p‐fluorophenyl)indole‐3‐imine and their corresponding amine congeners, were designed and synthesized as pp60c‐Src tyrosine kinase inhibitors, and their inhibitory activities toward pp60c‐Src tyrosine kinase were evaluated by in‐vitro kinase assay. Pre‐screening at two doses of compounds against kinase target revealed that, except for the N‐benzyl‐5‐phenyl indole imine derivatives 7a–7d, all indole derivatives show the target inhibition at varying levels. Consequently, the compounds, 8c, 8f, 8g, and 8h, were selected for prescreening tests. The dose‐response curves for up to six concentrations (250 to 7.8 μM) of the active compounds were obtained by tyrosine kinase assay and the four‐parameter logistic analysis of these data resulted in the IC50s of 4.69, 74.79, 75.06, and 84.23 μM for compounds 8c, 8f, 8g, and 8h, respectively. Therefore, compound 8c, 1‐(1‐benzyl‐5‐phenyl‐1H‐indole‐3‐yl)‐N‐(4‐fluorobenzyl)methanamine·HCl, was the promising inhibitor for pp60c‐Src, followed by compounds 8g and 8h. Under the same conditions, compound 8f did not provide any reasonable inhibition pattern to be considered as active compound. Therefore, among all four active compounds, compound 8f was not found suitable for further analysis.
Development of a radiographic scoring tool for ankylosing spondylitis only based on bone formation: Addition of the thoracic spine improves sensitivity to change
Authors: Baraliakos X. , Listing J. , Rudwaleit M. , Sieper J. , Braun J.
Published: May 2009

Objective

The modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS) quantifies radiographic changes in the cervical spine (C‐spine) and the lumbar spine (L‐spine), but not in the thoracic spine (T‐spine). Our objective was to study the contribution of the lower part of the T‐spine to structural damage in patients with ankylosing spondylitis (AS).

Methods

Radiographs of 80 AS patients obtained at baseline and after 2 years were scored by 2 readers using the mSASSS. In addition, changes in the lower T‐spine (T10–T12) were quantified. On this basis, a new scoring tool was developed: the Radiographic Ankylosing Spondylitis Spinal Score (RASSS). The RASSS includes 2 changes: no scoring of erosions in order to confine the scoring to new bone formation, and no scoring of squaring in the C‐spine for anatomic and feasibility reasons.

Results

The mean ± SD change was 0.9 ± 2.5 units using the mSASSS and 1.6 ± 2.8 units using the RASSS (P < 0.001). Although the mSASSS identified new syndesmophytes in mean ± SD 1.4 ± 2.9 vertebral edges over 2 years, an additional 0.6 ± 1.2 vertebral edges were seen in the lower T‐spine. New syndesmophytes or ankylosis were found in 15 patients (21.4%; 95% confidence interval [95% CI] 13.1–32.4%) in the C‐spine/L‐spine and in 6 patients (8.6%; 95% CI 3.8–17.2%) in the T‐spine alone. The reliability of the RASSS and the agreement between readers was excellent.

Conclusion

The lower T‐spine improves the sensitivity to change of scoring radiographic progression in AS. The tool developed in this study, the RASSS, showed better face and content validity than the mSASSS and was proven to be superior in the quantification of new bone formation in AS.
Prolactin alters the mechanisms of B cell tolerance induction
Authors: Saha Subhrajit , Gonzalez Juana , Rosenfeld Gabriel , Keiser Harold , Peeva Elena
Published: May 2009

Objective

Autoimmune diseases predominantly affect women, suggesting that female sex hormones may play a role in the pathogenesis of such diseases. We have previously shown that persistent mild‐to‐moderate elevations in serum prolactin levels induce a break in self tolerance in mice with a BALB/c genetic background. The aim of this study was to evaluate the effects of hyperprolactinemia on the mechanisms of B cell tolerance induction.

Methods

Effects of prolactin on splenic B cell subsets were studied in female BALB/c mice. B cell receptor (BCR)–mediated apoptosis and proliferation of transitional B cells were analyzed by flow cytometry. Expression of apoptotic genes was examined by microarrays and real‐time polymerase chain reaction analysis. B cells coexpressing κ/λ light chains were assessed by flow cytometry and immunohistochemistry. Activation status of transitional type 3 (T3) B cells was evaluated by BCR‐induced calcium influx studies.

Results

BCR‐mediated apoptosis of the T1 B cell subset, a major checkpoint for negative selection of autoreactive specificities, was decreased in prolactin‐treated mice. Microarray studies indicated that this event may be mediated by the prolactin‐induced up‐regulation of the antiapoptotic gene interferon‐γ receptor type II and down‐regulation of the proapoptotic gene Trp63. Prolactin treatment also altered the amount of receptor editing, as indicated by the increased number of transitional B cells coexpressing κ/λ light chains. Additionally, hyperprolactinemia modified the level of B cell anergy by increasing the degree of BCR‐induced calcium influx in the T3 B cells.

Conclusion

Persistently elevated serum prolactin levels interfere with B cell tolerance induction by impairing BCR‐mediated clonal deletion, deregulating receptor editing, and decreasing the threshold for activation of anergic B cells, thereby promoting autoreactivity.
Improved endothelial function after endothelin receptor blockade in patients with systemic sclerosis
Authors: Cardillo Carmine , Schinzari Francesca , Melina Domenico , Mores Nadia , Bosello Silvia , Peluso Giusy , Zoli Angelo , Ferraccioli Gianfranco
Published: May 2009

Objective

Impaired endothelium‐dependent vasodilator function may contribute to vascular damage in patients with systemic sclerosis (SSc). This study was undertaken to investigate whether increased activity of the endothelin 1 (ET‐1) system plays a role in the occurrence of endothelial dysfunction in patients with SSc.

Methods

In 12 patients with SSc (6 with diffuse cutaneous SSc [dcSSc] and 6 with limited cutaneous SSc [lcSSc]), forearm blood flow responses to graded doses of acetylcholine (ACh) and sodium nitroprusside (SNP) given intraarterially were assessed by plethysmography, during infusion of saline and following selective blockade of ETA receptors with BQ‐123 (10 nmoles/minute).

Results

During saline infusion, the vasodilator response to ACh was blunted in patients with SSc as compared with that in healthy controls (P < 0.001), whereas the response to SNP was not different between groups (P = 0.27). The vasodilator effect of ETA receptor antagonism was higher in patients than in controls (P < 0.001), indicating enhanced ET‐1–mediated vasoconstriction in SSc. In patients, ETA receptor blockade resulted in a potentiation of the vasodilator response to ACh (P < 0.001 versus saline), but did not affect the response to SNP (P = 0.31). Notably, both the vasodilator effect of ETA receptor antagonism and the improvement in the responsiveness to ACh following BQ‐123 infusion were higher in patients with dcSSc than in those with lcSSc (P < 0.01).

Conclusion

ET‐1–dependent vasoconstrictor tone is increased predominantly in the subgroup of SSc patients with dcSSc, in whom acute blockade of ETA receptors was able to improve impaired endothelium‐dependent vasodilator function. Our results suggest novel vasculoprotective effects of ETA receptor antagonism and support further exploration of strategies that target the ET‐1 pathway in SSc.
Single‐center series and systematic review of randomized controlled trials of malignancies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis receiving anti–tumor necrosis factor α therapy: Is there a need for more comprehensive screening procedures?
Authors: Nannini Carlotta , Cantini Fabrizio , Niccoli Laura , CassarÀ Emanuele , Salvarani Carlo , Olivieri Ignazio , Lally Edward V.
Published: May 2009

Objective

To systematically review the occurrence of malignancies among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) treated with anti–tumor necrosis factor α (anti‐TNFα) therapy in randomized controlled trials (RCTs), and to report a retrospective personal case series evaluating the frequency of malignancies in patients with RA, PsA, and AS requiring anti‐TNF therapy selected with more comprehensive cancer screening procedures compared with patients screened according to previously published procedures.

Methods

The primary outcome was the report of frequency of malignancies in RCTs and the latency between the therapy introduction and the occurrence of the neoplasm. A total of 363 consecutive RA, PsA, and AS patients requiring anti‐TNF therapy from 2002 to 2006 observed at the Rheumatology Unit in Prato, Italy, underwent extensive cancer screening procedures. An historical controlled group of 73 patients treated between January 1999 and December 2001 underwent the screening procedures accepted for the RCT procedures.

Results

Thirty‐six RCTs were included for analysis. Malignancies occurred in 60 (0.75%) of 8,015 patients randomized to the active treatment arm and in 21 (0.52%) of 3,991 patients in the placebo arms (P = 0.15). In the personal retrospective case series, 1 study patient (0.27%) and 3 controls (4.1%) developed cancer over the followup period (P = 0.017). Mean ± SD followup duration was 40.9 ± 16.7 months in study patients and 50.6 ± 18.1 months in controls.

Conclusion

The results of RCTs and our data showing 26% of malignancies occurring within 12 weeks from enrollment suggest the need for a revision of current cancer screening procedures in RCTs and in clinical practice.
The effectiveness of Tai Chi for chronic musculoskeletal pain conditions: A systematic review and meta‐analysis
Authors: Hall Amanda , Maher Chris , Latimer Jane , Ferreira Manuela
Published: May 2009

Objective

To determine whether Tai Chi improves pain, disability, physical performance, and/or health‐related quality of life (HRQOL) in people with chronic musculoskeletal pain.

Methods

Eight databases were searched for randomized controlled trials (RCTs). Two independent reviewers rated trial quality and extracted trial data. Effect sizes and 95% confidence intervals were calculated for individual trials, and pooled effect sizes were calculated using a random‐effects model.

Results

Seven RCTs were selected for inclusion in the review. Of these, 6 studied people with chronic arthritis and 1 studied people with chronic tension headaches. The trials were typically small and of low methodologic quality. The pooled effect size for arthritic populations on a 0–100 scale was 10.1 (range 6.3–13.9) points for pain reduction, and was 9.6 (range 5.2–14.0) points for disability reduction. Additionally, physical performance and HRQOL outcomes favored the Tai Chi intervention, but of these outcomes, only the level of tension and satisfaction with general health were statistically significant.

Conclusion

The available data on the effect of Tai Chi are sparse and derived principally from low‐quality studies. These data suggest that Tai Chi has a small positive effect on pain and disability in people with arthritis. The extent to which it benefits other forms of musculoskeletal pain is unclear.
Expression and modulation of ghrelin O‐acyltransferase in cultured chondrocytes
Authors: Gómez Rodolfo , Lago Francisca , Gómez‐Reino Juan J. , Dieguez Carlos , Gualillo Oreste
Published: May 2009

Objective

To use reverse transcription–polymerase chain reaction to detect ghrelin O‐acyltransferase (GOAT) transcripts in both murine and human chondrocytes, to evaluate the effect of pharmacologic in vitro treatments with lipopolysaccharide (LPS), growth hormone, ghrelin, and dexamethasone on GOAT messenger RNA (mRNA) expression, and to study the GOAT mRNA profile during chondrocyte differentiation.

Methods

Murine and human GOAT and ghrelin mRNA levels were determined by the SYBR Green–based quantitative real‐time polymerase chain reaction method.

Results

GOAT mRNA was expressed in murine cartilage explants as well as in the cultured murine chondrogenic ATDC‐5 cell line. GOAT was also expressed in human immortalized chondrocyte cell lines and in human cultured primary chondrocytes. In addition, GOAT mRNA expression in differentiating ATDC‐5 cells was lower at the early stage of differentiation (days 3–7), whereas GOAT mRNA levels increased progressively at the late stages. Finally, among the drugs and hormones tested, only LPS was able to strongly decrease GOAT mRNA expression.

Conclusion

These data indicate that chondrocytes are equipped with biochemical machinery for the synthesis of acylated ghrelin and suggest a novel role of the ghrelin axis in prehypertrophic and hypertrophic chondrocyte differentiation during endochondral ossification.
The three‐year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France
Authors: Hachulla Eric , de Groote Pascal , Gressin Virginie , Sibilia Jean , Diot Elisabeth , Carpentier Patrick , Mouthon Luc , Hatron Pierre‐Yves , Jego Patrick , Allanore Yannick , Tiev Kiet Phong , Agard Christian , Cosnes Anne , Cirstea Daniela , Constans Joël , Farge Dominique , Viallard Jean‐François , Harle Jean‐Robert , Patat Frédéric , Imbert Bernard , Kahan André , Cabane Jean , Clerson Pierre , Guillevin Loïc , Humbert Marc
Published: May 2009

Objective

An algorithm for the detection of pulmonary arterial hypertension (PAH), based on the presence of dyspnea and the findings of Doppler echocardiographic evaluation of the velocity of tricuspid regurgitation (VTR) and right‐sided heart catheterization (RHC), which was applied in a large multicenter systemic sclerosis (SSc) population, estimated the prevalence of PAH to be 7.85%. The aim of this observational study was to investigate the incidence of PAH and pulmonary hypertension (PH) during a 3‐year followup of patients from the same cohort (the ItinérAIR‐Sclérodermie Study).

Methods

Patients with SSc and without evidence of PAH underwent evaluation for dyspnea and VTR at study entry and during subsequent visits. Patients in whom PAH was suspected because of a VTR of 2.8–3.0 meters/second and unexplained dyspnea or a VTR of >3.0 meters/second underwent RHC to confirm the diagnosis.

Results

A total of 384 patients were followed up for a mean ± SD of 41.03 ± 5.66 months (median 40.92 months). At baseline, 86.7% of the patients were women, and the mean ± SD age of the patients was 53.1 ± 12.0 years. The mean ± SD duration of SSc at study entry was 8.7 ± 7.6 years. After RHC, PAH was diagnosed in 8 patients, postcapillary PH in 8 patients, and PH associated with severe pulmonary fibrosis in 2 patients. The incidence of PAH was estimated to be 0.61 cases per 100 patient‐years. Two patients who exhibited a mean pulmonary artery pressure of 20–25 mm Hg at baseline subsequently developed PAH.

Conclusion

The estimated incidence of PAH among patients with SSc was 0.61 cases per 100 patient‐years. The high incidence of postcapillary PH highlights the value of RHC in investigating suspected PAH.
Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort
Authors: Pons‐Estel Guillermo J. , Alarcón Graciela S. , McGwin Gerald , Danila Maria I. , Zhang Jie , Bastian Holly M. , Reveille John D. , Vilá Luis M.
Published: May 2009

Objective

To assess whether hydroxychloroquine can delay renal damage development in lupus nephritis patients.

Methods

Lupus nephritis patients (n = 256) from the LUpus in MInorities, NAture versus nurture study (n = 635), a multiethnic cohort of African Americans, Hispanics, and Caucasians, age ≥16 years with disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined using the Systemic Lupus International Collaborating Clinics Damage Index (≥1 of the following lasting at least 6 months: estimated/measured glomerular filtration rate <50%, 24‐hour proteinuria ≥3.5 gm and/or end‐stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n = 53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potential confounders. Kaplan‐Meier survival curves based on hydroxychloroquine intake or the World Health Organization (WHO) class glomerulonephritis were also derived.

Results

Sixty‐three (31.0%) of the 203 patients included developed renal damage over a mean ± SD disease duration of 5.2 ± 3.5 years. The most frequent renal damage domain item was proteinuria. Patients who received hydroxychloroquine (79.3%) exhibited a lower frequency of WHO class IV glomerulonephritis, had lower disease activity, and received lower glucocorticoid doses than those who did not take hydroxychloroquine. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (hazard ratio [HR] 0.12, 95% confidence interval [95% CI] 0.02–0.97, P = 0.0464) and reduced (HR 0.29, 95% CI 0.13–0.68, P = 0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in those who did not take hydroxychloroquine and those classified as WHO class IV glomerulonephritis (P < 0.0001).

Conclusion

After adjusting for possible confounding factors, the protective effect of hydroxychloroquine in retarding renal damage occurrence in systemic lupus erythematosus is still evident.
Long‐term medical costs and resource utilization in systemic lupus erythematosus and lupus nephritis: A five‐year analysis of a large medicaid population
Authors: Li Tracy , Carls Ginger Smith , Panopalis Pantelis , Wang Sara , Gibson Teresa B. , Goetzel Ron Z.
Published: May 2009

Objective

To estimate the long‐term direct medical costs and health care utilization for patients with systemic lupus erythematosus (SLE) and a subset of SLE patients with nephritis.

Methods

Patients with newly active SLE were found in the MarketScan Medicaid Database (1999–2005), which includes all inpatient, outpatient, emergency department, and pharmaceutical claims for more than 10 million Medicaid beneficiaries. The date a patient became newly active was defined as the earliest observed SLE diagnosis code, with a 6‐month clean period prior to the diagnosis. This method identified 2,298 patients with a consecutive followup of 5 years. A reference group of patients without SLE was constructed using propensity score matching. Nephritis was assessed based on diagnosis and procedure codes involving the kidney.

Results

Mean annual medical costs for SLE patients totaled $16,089 at year 1, which is significantly greater (by $6,831) than that for reference patients. Costs decreased slightly at year 2 but then increased yearly at an average rate of 16% through year 5, to $23,860. SLE patients without nephritis (n = 1,809) had costs $967–3,756 higher than the reference patients. SLE patients with nephritis (n = 489) had costs $13,228–34,907 greater than the reference group. Inpatient visits for the nephritis subgroup were 0.6–1.0 per capita, which are approximately twice the rate for all SLE patients and 3 to 4 times higher than the reference group.

Conclusion

SLE is a costly condition to treat. Medical expenses incurred by SLE patients increase steadily over time, particularly for patients with nephritis.
Elevated serum interferon‐α activity in juvenile dermatomyositis: Associations with disease activity at diagnosis and after thirty‐six months of therapy
Authors: Niewold Timothy B. , Kariuki Silvia N. , Morgan Gabrielle A. , Shrestha Sheela , Pachman Lauren M.
Published: May 2009

Objective

Interferon‐α (IFNα) has been implicated in the pathogenesis of juvenile dermatomyositis (DM). The aim of this study was to examine serum IFNα activity in a cohort of children with juvenile DM to determine relationships between IFNα and indicators of disease activity and severity.

Methods

Thirty‐nine children with definite/probable juvenile DM were included in the study. Serum samples were obtained at the time of diagnosis from 18 untreated patients with juvenile DM. Second samples from 11 of these patients were obtained at 24 months, while they were receiving treatment, and third samples were obtained from 7 of these patients at 36 months. The remaining 21 children were studied 36 months after their initial diagnosis. Serum IFNα activity was measured using a functional reporter cell assay.

Results

Patients with juvenile DM had higher serum IFNα activity than both pediatric and adult healthy control subjects. In untreated patients, serum IFNα activity was positively correlated with serum muscle enzyme levels (P < 0.05 for creatine kinase, aspartate aminotransferase, and aldolase) and inversely correlated with the duration of untreated disease (P = 0.017). The tumor necrosis factor α −308A allele was associated with higher serum IFNα levels only in untreated patients (P = 0.030). At 36 months, serum IFNα levels were inversely correlated with muscle enzyme levels in those patients still requiring therapy and with the skin Disease Activity Score in those patients who had completed therapy (P = 0.002).

Conclusion

Serum IFNα activity was associated with higher serum levels of muscle‐derived enzymes and a shorter duration of untreated disease in patients with newly diagnosed juvenile DM and was inversely correlated with measures of chronic disease activity at 36 months postdiagnosis. These data suggest that IFNα could play a role in disease initiation in juvenile DM.
Neutralization of interferon‐α/β–inducible genes and downstream effect in a phase I trial of an anti–interferon‐α monoclonal antibody in systemic lupus erythematosus
Authors: Yao Yihong , Richman Laura , Higgs Brandon W. , Morehouse Christopher A. , de los Reyes Melissa , Brohawn Philip , Zhang Jianliang , White Barbara , Coyle Anthony J. , Kiener Peter A. , Jallal Bahija
Published: May 2009

Objective

Type I interferons (IFNs) play an important role in the pathogenesis of systemic lupus erythematosus (SLE). This phase Ia trial was undertaken to evaluate the safety, pharmacokinetics, and immunogenicity of anti‐IFNα monoclonal antibody (mAb) therapy in SLE. During the trial, we also examined whether overexpression of an IFNα/β‐inducible gene signature in whole blood could serve as a pharmacodynamic biomarker to evaluate IFNα neutralization and investigated downstream effects of neutralizing IFNα on BAFF and other key signaling pathways, i.e., granulocyte–macrophage colony‐stimulating factor (GM‐CSF), interleukin‐10 (IL‐10), tumor necrosis factor α (TNFα), and IL‐1β, in SLE.

Methods

Affymetrix Human Genome U133 Plus 2.0 microarrays were used to profile whole blood and lesional skin of patients receiving standard therapy for mild to moderate SLE. Selected IFNα/β‐inducible proteins were analyzed by immunohistochemistry.

Results

With the study treatment, we observed anti‐IFNα mAb–specific and dose‐dependent inhibition of overexpression of IFNα/β‐inducible genes in whole blood and skin lesions from SLE patients, at both the transcript and the protein levels. In SLE patients with overexpression of messenger RNA for BAFF, TNFα, IL‐10, IL‐1β, GM‐CSF, and their respective inducible gene signatures in whole blood and/or skin lesions, we observed a general trend toward suppression of the expression of these genes and/or gene signatures upon treatment with anti‐IFNα mAb.

Conclusion

IFNα/β‐inducible gene signatures in whole blood are effective pharmacodynamic biomarkers to evaluate anti‐IFNα mAb therapy in SLE. Anti‐IFNα mAb can neutralize overexpression of IFNα/β‐inducible genes in whole blood and lesional skin from SLE patients and has profound effects on signaling pathways that may be downstream of IFNα in SLE.
Association of a functional polymorphism in the IRF5 region with systemic sclerosis in a Japanese population
Authors: Ito Ikue , Kawaguchi Yasushi , Kawasaki Aya , Hasegawa Minoru , Ohashi Jun , Hikami Koki , Kawamoto Manabu , Fujimoto Manabu , Takehara Kazuhiko , Sato Shinichi , Hara Masako , Tsuchiya Naoyuki
Published: May 2009

Objective

Interferon regulatory factor 5, an established susceptibility factor for systemic lupus erythematosus (SLE), plays a role in type I interferon and proinflammatory cytokine induction. A recent study showed association of a functional single‐nucleotide polymorphism (SNP) in intron 1 of IRF5, rs2004640, with systemic sclerosis (SSc) in a European French population. We undertook the present study to determine whether IRF5 polymorphisms are also associated with a predisposition to SSc in Japanese.

Methods

A case–control association study was performed for rs2004640 as well as for rs10954213 and rs2280714, all of which were previously reported to be associated with SLE, in 281 SSc patients and 477 healthy controls. Patients with SSc complicated by SLE or Sjögren's syndrome were excluded. Association of the rs2280714 genotype with messenger RNA (mRNA) levels of IRF5 and adjacently located transportin 3 (TNPO3) was examined using the GENEVAR database.

Results

All 3 SNPs were significantly associated with SSc, with the rs2280714 A allele having the strongest association (allele frequency P = 0.0012, odds ratio 1.42 [95% confidence interval 1.15–1.75]). Association was preferentially observed in subsets of patients with diffuse cutaneous SSc (dcSSc) and anti–topoisomerase I antibody positivity. Conditional analysis revealed that rs2280714 could account for most of the association of these SNPs, while an additional contribution of rs2004640 was also suggested for dcSSc. The genotype of rs2280714 was strongly associated with IRF5 mRNA expression, while only marginal association was detected with TNPO3 mRNA expression.

Conclusion

Association of IRF5 with SSc was replicated in a Japanese population. Whether the causal SNP is different among populations requires further investigation.
The promise and challenges of microalgal‐derived biofuels
Authors: Pienkos Philip T. , Darzins Al
Published: May 2009

Microalgae offer great promise to contribute a significant portion of the renewable fuels that will be required by the Renewable Fuels Standard described in the 2007 Energy Independence and Security Act of the United States. Algal biofuels would be based mainly on the high lipid content of the algal cell and thus would be an ideal feedstock for high energy density transportation fuels, such as biodiesel as well as green diesel, green jet fuel and green gasoline. A comprehensive research and development program for the development of algal biofuels was initiated by the US Department of Energy (DoE) more than 30 years ago, and although great progress was made, the program was discontinued in 1996, because of decreasing federal budgets and low petroleum costs. Interest in algal biofuels has been growing recently due to increased concern over peak oil, energy security, greenhouse gas emissions, and the potential for other biofuel feedstocks to compete for limited agricultural resources. The high productivity of algae suggests that much of the US transportation fuel needs can be met by algal biofuels at a production cost competitive with the cost of petroleum seen during the early part of 2008. Development of algal biomass production technology, however, remains in its infancy. This perspective provides a brief overview of past algal research sponsored by the DoE, the potential of microalgal biofuels and a discussion of the technical and economic barriers that need to be overcome before production of microalgal‐derived diesel‐fuel substitutes can become a large‐scale commercial reality. Published in 2009 by John Wiley & Sons, Ltd.
Short‐term exposure to mobile phone base station signals does not affect cognitive functioning or physiological measures in individuals who report sensitivity to electromagnetic fields and controls
Authors: Eltiti Stacy , Wallace Denise , Ridgewell Anna , Zougkou Konstantina , Russo Riccardo , Sepulveda Francisco , Fox Elaine
Published: May 2009

Individuals who report sensitivity to electromagnetic fields often report cognitive impairments that they believe are due to exposure to mobile phone technology. Previous research in this area has revealed mixed results, however, with the majority of research only testing control individuals. Two studies using control and self‐reported sensitive participants found inconsistent effects of mobile phone base stations on cognitive functioning. The aim of the present study was to clarify whether short‐term (50 min) exposure at 10 mW/m2 to typical Global System for Mobile Communication (GSM) and Universal Mobile Telecommunications System (UMTS) base station signals affects attention, memory, and physiological endpoints in sensitive and control participants. Data from 44 sensitive and 44 matched‐control participants who performed the digit symbol substitution task (DSST), digit span task (DS), and a mental arithmetic task (MA), while being exposed to GSM, UMTS, and sham signals under double‐blind conditions were analyzed. Overall, cognitive functioning was not affected by short‐term exposure to either GSM or UMTS signals in the current study. Nor did exposure affect the physiological measurements of blood volume pulse (BVP), heart rate (HR), and skin conductance (SC) that were taken while participants performed the cognitive tasks. Bioelectromagnetics 30:556–563, 2009. © 2009 Wiley‐Liss, Inc.
Effects of W‐CDMA 1950 MHz EMF emitted by mobile phones on regional cerebral blood flow in humans
Authors: Mizuno Yoko , Moriguchi Yoshiya , Hikage Takashi , Terao Yasuo , Ohnishi Takashi , Nojima Toshio , Ugawa Yoshikazu
Published: May 2009

Use of the third generation mobile phone system is increasing worldwide. This is the first study to investigate the effects of the third generation system on regional cerebral blood flow (rCBF) in humans. We compared effects of the electromagnetic field (EMF) emitted from the Wideband Code Division Multiple Access (W‐CDMA) cellular system versus sham control exposure on rCBF in humans. Nine healthy male volunteers participated in this study. Positron emission tomography (PET) scans were obtained before, during, and after unilateral 30 min EMF exposure. The subtraction analysis revealed no significant rCBF changes caused by the EMF conditions compared with the sham exposure, suggesting that EMF emitted by a third generation mobile phone does not affect rCBF in humans. Bioelectromagnetics 30:536–544, 2009. © 2009 Wiley‐Liss, Inc.
Electromagnetic fields and epidemiology: An overview inspired by the fourth course at the International School of Bioelectromagnetics
Authors: Schüz Joachim , Lagorio Susanna , Bersani Ferdinando
Published: May 2009

The fourth course at the International School of Bioelectromagnetics addressed various aspects of the epidemiology of exposure to electromagnetic fields (EMF). In this overview, inspired by the lectures and the discussions among participants, we summarize current knowledge on exposure to EMF and disease risk, with emphasis on studies of use of mobile phones and brain tumours and exposure to power lines and childhood leukaemia. Sources of bias and error hamper straightforward conclusions in some areas and, in order to move forward, improvements in study design and exposure assessment are necessary. The scientific evidence available to date on possible long‐term effects from exposure to ELF and RF fields is not strong enough to revise current protection limits based on the known acute effects of such exposures. Precautionary measures may be considered to reduce ELF exposure of children or exposure to RF during mobile phone use, keeping in mind that it is unclear whether they involve any preventive benefit. Possible health effects from mobile phone use in adults and in children should be investigated further by prospective epidemiological studies with improved exposure assessment and brain tumour incidence rates should be monitored. Further studies on the relation between childhood leukaemia and ELF magnetic fields would be worthwhile if they focus on heavily exposed groups and attempt to minimize possible selection bias. In conclusion, epidemiological studies conducted with appropriate diligence can play a key role in finding the answers. Bioelectromagnetics 30:511–524, 2009. © 2009 Wiley‐Liss, Inc.
Improving TNF as a cancer therapeutic: Tailor‐made TNF fusion proteins with conserved antitumor activity and reduced systemic side effects
Authors: Gerspach Jeannette , Pfizenmaier Klaus , Wajant Harald
Published: May 2009

Tumor necrosis factor (TNF) is highly pleiotropic cytokine regulating diverse cellular processes such as proliferation, cell migration, angiogenesis, differentiation, apoptosis, necrosis, but also survival. Because of its name‐giving tumor necrosis‐inducing capabilities, TNF has attracted attention very early for antitumor therapy. Although TNF is in clinical use for treatment of soft tissue sarcoma in isolated limb perfusion, its broad use in tumor therapy is prevented so far by its strong systemic proinflammatory effects. Nevertheless, over the past decade, a variety of tailor‐made TNF variants have been developed with the aim to reduce TNFs systemic activity without losing its antitumoral effects. Here, we review the progress made toward improving the efficacy of TNF by genetic engineering, tumor targeting, and introduction of prodrug concepts. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Mathematical modeling of elution curves for a protein mixture in ion exchange chromatography applied to high protein concentration
Authors: Orellana C.A. , Shene C. , Asenjo J.A.
Published: May 2009

Protein elution curves in ion exchange chromatography (IEC) were simulated with a rate model. Three pure proteins and their mixture were used (α‐lactalbumin, BSA, and conalbumin) under different operational conditions. The anionic matrix Q‐Sepharose FF was used packed in a 1 mL column. A high protein concentration (37.5 mg/mL of total protein injected into the column) was used in order to extend the utility of the model. Mass transfer parameters were calculated using empiric correlations, where the axial dispersion was negligible (Pe > 300) and the mass transfer was controlled by the intraparticle diffusion (Bi > 10). The model assumes a modulator–eluite relationship were the equilibrium constant of the Langmuir isotherm was a function of salt concentration. Adsorption kinetic parameters were estimated from experimental data. The parameters for pure proteins were determined, and elution curves for changes in flow rate, ionic strength gradient, concentration, and sample size were predicted by the model. Then the kinetic parameters of the mixture were determined under the same operational conditions and some of the parameters had to be modified to take into account effects such as protein–protein interactions, competition, and displacement. Experimental elution curves obtained for changes in operational conditions such as flow rate and ionic strength gradient were simulated by the rate model for the protein mixture with a relative error in retention time of visible peaks <5%. IEC operational conditions and the peak fraction collection can be selected using a cost function of the production process which considers yield, purity, concentration, and process time that are obtained from simulations. Operational conditions that gave the minimum cost were selected. Simulations allows to diminish experimental time and cost. Biotechnol. Bioeng. 2009; 104: 572–581 © 2009 Wiley Periodicals, Inc.
Fungal pretreatment of lignocellulose by Phanerochaete chrysosporium to produce ethanol from rice straw
Authors: Bak Jin Seop , Ko Ja Kyong , Choi In‐Geol , Park Yong‐Cheol , Seo Jin‐Ho , Kim Kyoung Heon
Published: May 2009

Phanerochaete chrysosporium is a wood‐rot fungus that is capable of degrading lignin via its lignolytic system. In this study, an environmentally friendly fungal pretreatment process that produces less inhibitory substances than conventional methods was developed using P. chrysosporium and then evaluated by various analytical methods. To maximize the production of manganese peroxidase, which is the primary lignin‐degrading enzyme, culture medium was optimized using response surface methodologies including the Plackett–Burman design and the Box–Behnken design. Fermentation of 100 g of rice straw feedstock containing 35.7 g of glucan (mainly in the form of cellulose) by cultivation with P. chrysosporium for 15 days in the media optimized by response surface methodology was resulted in a yield of 29.0 g of glucan that had an enzymatic digestibility of 64.9% of the theoretical maximum glucose yield. In addition, scanning electronic microscopy, confocal laser scanning microscopy, and X‐ray diffractometry revealed significant microstructural changes, fungal growth, and a reduction of the crystallinity index in the pretreated rice straw, respectively. When the fungal‐pretreated rice straw was used as a substrate for ethanol production in simultaneous saccharification and fermentation (SSF) for 24 h, the ethanol concentration, production yield and the productivity were 9.49 g/L, 58.2% of the theoretical maximum, and 0.40 g/L/h, respectively. Based on these experimental data, if 100 g of rice straw are subjected to fungal pretreatment and SSF, 9.9 g of ethanol can be produced after 96 h, which is 62.7% of the theoretical maximum ethanol yield. Biotechnol. Bioeng. 2009; 104: 471–482 © 2009 Wiley Periodicals, Inc.
Incarviditone: A Novel Cytotoxic Benzofuranone Dimer from Incarvillea delavayiBureau et Franchet
Authors: Chen Yu‐Qi , Shen Yun‐Heng , Su Yong‐Qing , Kong Ling‐Yi , Zhang Wei‐Dong
Published: May 2009

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A novel benzofuranone dimer, named incarviditone (1), along with known rengyolone (2), was isolated from Incarvillea delavayi Bureau et Franchet. The structure of the new compound was elucidated on the basis of spectroscopic methods, especially 2D‐NMR and MS analyses. Compound 1 is the first example of a benzofuranone dimer connected by a CC bond, which presents a new C‐skeleton. The cytotoxicities of compounds 1 and 2 were evaluated against the cell lines A549, LOVO, HL‐60, 6T‐CEM, and HepG2. Incarviditone (1) exhibited cytotoxicity only against HL‐60 and 6T‐CEM cell lines with IC50 values of 14.8 and 22.2 μg/ml, respectively, while rengyolone (2) was more active against all cell lines with IC50 values between 6.7 and 20.2 μg/ml.
Anti‐Inflammatory and Anticancer Activity of Ergoflavin Isolated from an Endophytic Fungus
Authors: Deshmukh Sunil Kumar , Mishra Prabhu Dutt , Kulkarni‐Almeida Asha , Verekar Shilpa , Sahoo Manas Ranjan , Periyasamy Giridharan , Goswami Hitesh , Khanna Amit , Balakrishnan Arun , Vishwakarma Ram
Published: May 2009

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Biodiversity is a major resource for identification of new molecules with specific therapeutic activities. To identify such an active resource, high throughput screening (HTS) of the extracts prepared from such diversity are examined on specific functional assays. Based on such HTS studies and bioactivity‐based fractionation, we have isolated ergoflavin, a pigment from an endophytic fungus, growing on the leaves of an Indian medicinal plantMimosops elengi(bakul). We report here the isolation, structure elucidation, and biological properties of this compound, which showed good anti‐inflammatory and anticancer activities.
4‐Aryl‐Substituted 2,5‐Dimethoxyphenethylamines: Synthesis and Serotonin 5‐HT2AReceptor Affinities
Authors: Trachsel Daniel , Nichols David E. , Kidd Stephanie , Hadorn Marcel , Baumberger Franz
Published: May 2009

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A series of novel ligands for the serotonin 5‐HT2A/Creceptor subtype bearing the 2‐phenylethylamine pharmacophore was synthesized and assayed for its 5‐HT2Areceptor binding affinity. As the 4′‐aryl‐substituted 2‐(2,5‐dimethoxyphenyl)ethylamines were previously unknown, an initial series of twelve compounds was chosen to obtain initial insight into their structure–activity relationships. The 4′‐aryl moiety was introduced in moderate‐to‐high yield by a Pd‐catalyzedSuzukireaction of twelve arylboronic acids withN‐Boc‐protected 2‐(2,5‐dimethoxy‐4‐iodophenyl)ethylamine (8).N‐Boc Deprotection then afforded the novel 2‐phenylethylamines5a–5l. Additionally, biphenyl compound6lacking the 5′‐MeO substituent was prepared, starting from 2‐methoxy‐4‐hydroxybenzaldehyde. Except for5l, all of the compounds proved to be antagonists with generally low affinity at the rat 5‐HT2Areceptor. Substituents are generally not well tolerated on the 4′‐aryl moiety, except in the 4″‐position. Indeed, the relatively high affinity of the 4″‐butyl‐, 4″‐phenyl‐, and 4′‐naphthyl‐substituted compounds5i, 5k, and5e, respectively (Ki=32, 33, and 41nM, resp.), attests a rather remarkable tolerance for bulk in this location.
Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods
Authors: Gumral Nurhan , Nazıroglu Mustafa , Ongel Kurtulus , Beydilli Emine Dasdibi , Ozguner Fehmi , Sutcu Recep , Calıskan Sadettin , Akkaya Ahmet
Published: May 2009

An imbalance between oxidative stress and antioxidative capacity may play an important role in the development and progression of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). We carried out a study to assess the systemic oxidant–antioxidant status during the exacerbation and the stable period in patients with BA and COPD. A total of 33 patients, 16 with BA and 17 with COPD were included in the study. During the exacerbation and the stable periods, levels of malondialdehyde (MDA), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), glutathione reductase (GRd), and catalase (CAT) in erythrocytes and serum melatonin concentrations were investigated. Blood counts, respiratory functions, and blood gases of the patients were also performed. During an exacerbation period of BA, despite the decreases in GSH‐Px, GRd and melatonin levels, MDA and CAT levels, and the white blood cell count, the percentage of eosinophils were significantly higher than in the stable period. Also, it was found that FEV1/L (where FEV1 is the forced expiratory volume in 1 s), FVC/L (where FVC is forced vital capacity), PEF/L/s (where PEF is peak expiratory flow), pO2 (where pO2 is oxygen pressure) levels increased during the stable period in patients with BA. MDA and SOD values were higher in the exacerbation period than in the stable period although GSH‐Px, GRd, melatonin, pH, and pO2 values were lower in the exacerbation period than in the stable period. The blood counts and the respiratory function tests did not change between the exacerbation and the stable period of patients with COPD significantly. In conclusion, we observed that oxidative stress in the exacerbation period of patients with BA and COPD increased whereas the antioxidant enzymes and melatonin values reduced. The episodes of BA or COPD might be associated with elevated levels of oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.
Thermoregulated Microemulsions by Cyclodextrin Sequestration: A New Approach to Efficient Catalyst Recovery
Authors: Leclercq Loïc , Lacour Matthieu , Sanon Samantha H. , Schmitzer Andreea R.
Published: May 2009

The combination of imidazolium surfactants with α‐cyclodextrins (CDs, in green) was used as a control element in the thermoregulated aqueous olefin hydroformylation. The self‐assembly of the imidazolium surfactants (red) favors the micellization process at high temperatures, whereas at lower temperatures the complexation of the surfactant monomers into the α‐CDs is favored.

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A Unified Strategy for the Stereospecific Construction of Propionates and Acetate–Propionates Relying on a Directed Allylic Substitution
Authors: Reiss Tomislav , Breit Bernhard
Published: May 2009

Flexible friends: A new strategy that relies on o‐DPPB‐directed allylic substitution has been implemented for the flexible and stereospecific construction of major polyketide and isoprenoid structural elements (see scheme; o‐DPPB=ortho‐diphenylphosphanyl benzoate; PG=protecting group).

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ChemInform Abstract: Ionothermal Synthesis of Tailor‐Made LiFePO4 Powders for Li‐Ion Battery Applications.
Authors: Recham N. , Dupont L. , Courty M. , Djellab K. , Larcher D. , Armand M. , Tarascon J.‐M.
Published: May 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: Hydrothermal Synthesis, Characterization, and Photocatalytic Properties of Zn2SnO4.
Authors: Fu Xianliang , Wang Xuxu , Long Jinlin , Ding Zhengxin , Yan Tingjiang , Zhang Guoying , Zhang Zhizhong , Lin Huaxiang , Fu Xianzhi
Published: May 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: Sn3I8·2(18‐crown‐6): A Mixed‐Valent Tin‐Crown‐Ether Complex.
Authors: Wolff Michael , Harmening Thomas , Poettgen Rainer , Feldmann Claus
Published: May 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: Enantioselective α‐Hydrazination of α‐Fluoro‐β‐ketoesters Catalyzed by Chiral Nickel Complexes.
Authors: Mang Joo Yang , Kwon Dae Gil , Kim Dae Young
Published: May 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.