bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological treatment of disruptive behavior in Smith–Magenis syndrome
Authors: Laje Gonzalo , Bernert Rebecca , Morse Rebecca , Pao Maryland , Smith Ann C.M.
Published: October 2010

Smith–Magenis syndrome (SMS) is a complex genetic syndrome caused by an interstitial deletion of chromosome 17p11.2. Children and adults with SMS appear to have unique neurobehavioral problems that include: sleep disturbance, self‐injurious and maladaptive behaviors, stereotypies, and sensory integration disorders. We gathered retrospective psychotropic use information from parents or other caregivers of 62 individuals with SMS who were asked about use of psychotropic medication from a list of commonly used psychiatric medications. For those drugs identified, respondents were asked to rate the experience with the particular medication using a likert‐type scale. Drugs were grouped into seven main categories: (1) stimulants; (2) antidepressants; (3) antipsychotics; (4) sleep aides; (5) mood stabilizers; (6) alpha 2 agonists; and (7) benzodiazepines. Relative frequencies, means and standard deviations pertaining to age and medication effect were derived for each medication category. Six of the seven medication categories examined showed no meaningful deviations from the “no change” score. The benzodiazepine group showed a mild detrimental effect. There were no gender differences in efficacy. Use of psychotropic medication started early in life (mean age 5 years), particularly with sleep aides. Although no medication category was identified as efficacious in SMS, all the categories reported herein may be considered as an option for brief symptomatic relief. Published 2010 Wiley‐Liss, Inc.
The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment
Authors: Morris Colleen A.
Published: October 2010

Williams syndrome (WS), caused by hemizygous deletion of 1.55–1.8 Mb of chromosome 7q11.23, has a recognizable behavior phenotype that is an important diagnostic sign. Individuals with WS are overly friendly, gregarious, empathetic, and loquacious, but have difficulty interpreting social cues and in making and keeping friends. The neurodevelopmental profile is characterized by overall intellectual disability, strength in concrete language, weakness in visuospatial construction, difficulties with sensory modulation, balance, and tool use, and problems with attention and anxiety. Structural and functional MRI studies demonstrate that gray matter deficiency in the intraparietal sulcus alters processing of spatial information in the dorsal stream (spatial) visual pathway, likely contributing to the visuospatial construction disability. Deficient regulation of the amygdala by the oribitofrontal cortex appears to underlie both the social disinhibition and the specific phobia common in WS. Continued study of cognition, behavior, neuroanatomy, and function in WS will continue to elucidate the neurogenetic underpinnings of human behavior. © 2010 Wiley‐Liss, Inc.
Ciprofloxacin prevents myelination delay in neonatal rats subjected to E. coli sepsis
Authors: Loron Gauthier , Olivier Paul , See Hélène , Le Saché Nolwenn , Angulo Leslie , Biran Valérie , Brunelle Nadège , Besson‐Lescure Bernadette , Kitzis Marie‐Dominique , Pansiot Julien , Bingen Edouard , Gressens Pierre , Bonacorsi Stéphane , Baud Olivier
Published: October 2010

Objective

Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti‐inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis.

Methods

We adapted an Escherichia coli sepsis model to 5‐day‐old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory‐induced brain damage compared with cefotaxime (CTX) (treatment of reference).

Results

Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX.

Interpretation

These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis‐induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation. ANN NEUROL 2011
HLA–DRB1*0407 and *1304 are risk factors for scleroderma renal crisis
Authors: Nguyen Binh , Mayes Maureen D. , Arnett Frank C. , del Junco Deborah , Reveille John D. , Gonzalez Emilio B. , Draeger Hilda T. , Perry Marilyn , Hendiani Amir , Anand Kiran K. , Assassi Shervin
Published: October 2010

Objective

To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc).

Methods

SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA.

Results

Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti–RNA polymerase III (anti–RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti–RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA–DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27–8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30–15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti–RNAP III, and ACAs, remained significantly associated with SRC in the final model.

Conclusion

The results of this study suggest that DRB1*0407 and *1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.
Role of innate immunity in a murine model of histidyl–transfer RNA synthetase (Jo‐1)–mediated myositis
Authors: Soejima Makoto , Kang Eun Ha , Gu Xinyan , Katsumata Yasuhiro , Clemens Paula R. , Ascherman Dana P.
Published: October 2010

Objective

Previous studies in humans and in animal models support a key role of histidyl–transfer RNA synthetase (HisRS; also known as Jo‐1) in the pathogenesis of idiopathic inflammatory myopathy. While most investigations have focused on the ability of HisRS to trigger adaptive immune responses, in vitro studies clearly indicate that HisRS possesses intrinsic chemokine‐like properties capable of activating the innate immune system. The purpose of this study was therefore to examine the ability of HisRS to direct innate immune responses in a murine model of myositis.

Methods

Following intramuscular immunization with soluble HisRS in the absence of exogenous adjuvant, selected strains of mice were evaluated at different time points for histopathologic evidence of myositis. Enzyme‐linked immunosorbent assay–based assessment of autoantibody formation and carboxyfluorescein succinimidyl ester proliferation studies provided complementary measures of B cell and T cell responses triggered by HisRS immunization.

Results

Compared to appropriate control proteins, a murine HisRS fusion protein induced robust, statistically significant muscle inflammation in multiple congenic strains of C57BL/6 and NOD mice. Time course experiments revealed that this inflammatory response occurred as early as 7 days postimmunization and persisted for up to 7 weeks. Parallel immunization strategies in DO11.10/RAG‐2–/– and C3H/HeJ (TLR‐4–/–) mice indicated that the ability of murine HisRS to drive muscle inflammation was not dependent on B cell receptor or T cell receptor recognition and did not require Toll‐like receptor 4 signaling.

Conclusion

Collectively, the findings of these experiments support a model in which HisRS can trigger both innate and adaptive immune responses that culminate in severe muscle inflammation that is the hallmark of idiopathic inflammatory myopathy.
An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: A three‐month randomized, placebo‐controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents
Authors: Genovese Mark C. , Kavanaugh Arthur , Weinblatt Michael E. , Peterfy Charles , DiCarlo Julie , White Michael L. , O'Brien Maryann , Grossbard Elliott B. , Magilavy Daniel B.
Published: October 2010

Objective

To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies.

Methods

A total of 219 patients with active RA in whom treatment with biologic agents had failed were enrolled in a 3‐month multicenter, randomized, double‐blind, placebo‐controlled trial of R788. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at month 3. Secondary end points included changes in inflammation and damage, as assessed by magnetic resonance imaging (MRI), and changes in the Disease Activity Score.

Results

The ACR20 response in the R788 100 mg twice daily group was 38%, versus 37% in the placebo group, at month 3. No significant differences were achieved in the ACR20, ACR50, or ACR70 response levels at 3 months. There were differences between the groups from baseline to month 3 in the secondary end points C‐reactive protein (CRP) level and synovitis score on MRI. There were baseline differences in steroid use, prior biologic use, and synovitis score on MRI between the R788 group and the placebo group that may have affected the outcomes. A high placebo response rate was seen in this trial, and exploratory analysis suggested that this may in part have been driven by patients who entered the trial with an elevated erythrocyte sedimentation rate but normal CRP level.

Conclusion

Our findings indicate that there were no differences in the primary end point between the R788 and placebo groups. Differences were observed between the R788 and placebo groups in secondary end points, particularly in those patients who entered the study with an elevated CRP level.
Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment
Authors: Stamp Lisa K. , O'Donnell John L. , Zhang Mei , James Jill , Frampton Christopher , Barclay Murray L. , Chapman Peter T.
Published: October 2010

Objective

To determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance–based dose in patients with gout.

Methods

Patients with gout who had been receiving a stable dose of allopurinol for ≥1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.

Results

Ninety patients were enrolled. The mean age of the patients was 58.7 years (range 27–83 years), 87.9% were male, and 81.9% were of European ancestry. Forty‐five patients had a serum urate concentration of ≥0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level ≥0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/liter (72% versus 88.5%; P = 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.

Conclusion

Increasing the dose of allopurinol above the proposed creatinine clearance–based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.
Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum
Authors: Shimada K , Nara S , Esaki M , Sakamoto Y , Kosuge T , Hiraoka N
Published: October 2010

Background

Major hemihepatectomy for advanced gallbladder carcinoma remains controversial as it is associated with serious postoperative complications and poor prognosis.

Methods

All those who underwent extended right hemihepatectomy were identified from a database of patients with gallbladder carcinoma who had surgical resection between 1999 and 2009. The clinicopathological data for these patients were analysed retrospectively.

Results

A total of 126 patients underwent surgical resection, 35 of whom had extended right hemihepatectomy. There were no deaths, but 16 patients had complications. The mean(s.d.) duration of operation and blood loss were 564(206) min and 1472(1268) ml respectively. No blood transfusions were needed in 28 patients. Tumour stage (International Union Against Cancer, sixth edition) was IIA in four, IIB in four, III in 15 and IV in 12 patients. The overall 5-year survival rate was 17 per cent with a median survival of 2·2 years. Three patients survived more than 5 years. The presence of hepatic metastases and gallbladder carcinoma originating from the cystic duct were indicators of poor prognosis.

Conclusion

Extended right hemihepatectomy for gallbladder cancer is safe and may contribute to long-term survival in selected patients.
Comparison of treatment and outcome information between a clinical trial and the National Cancer Data Repository
Authors:   CLASICC trialists, Morris E J A , Jordan C , Thomas J D , Cooper M , Brown J M , Thorpe H , Cameron D , Forman D , Jayne D , Quirke P
Published: October 2010

Background

Clinical trials are important but many factors limit their success, including the costs of long-term follow-up and participants often not being representative of the general population. The National Cancer Data Repository (NCDR) contains data about patients with cancer in England that may help overcome some of these problems. This study compared treatment and outcome information between the Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (CLASICC) trial and the NCDR.

Methods

Participants in the CLASICC trial were identified in the NCDR, and management and outcome data were compared. Data on all surgically treated English patients with colorectal cancer were extracted from the NCDR and compared with those of CLASICC participants.

Results

Survival and treatment data for those in the CLASICC trial were available in the NCDR for 98·9 and 95·8 per cent of patients respectively. There was agreement in operation type for 86·1 per cent of patients but surgical approach coding was poor, with only 58·4 per cent of laparoscopic procedures coded in the NCDR. There was no significant difference in survival calculated from either data set. Surgical information was available in the NCDR for 19 of 20 trial participants with missing data. The trial population was younger (P < 0·001), of better socioeconomic status (P = 0·001) and with earlier disease (P < 0·001) than the general surgically treated colorectal cancer population. Rectal cancer survival was similar, but 5-year survival after treatment of colonic cancer was significantly better in the trial than in the national data: 57·1 (95 per cent confidence interval 51·5 to 62·3) versus 49·8 (49·3 to 50·2) per cent respectively.

Conclusion

The National Cancer Data Repository demonstrates potential for informing clinical trials, but limitations prevent full intention-to-treat analyses.
Structure and Dynamic Features of an Intramolecular Frustrated Lewis Pair
Authors: Axenov Kirill V. , Mömming Cornelia M. , Kehr Gerald , Fröhlich Roland , Erker Gerhard
Published: October 2010

Di(mesityl)cyclohexenylphosphine undergoes hydroboration with Piers' borane [HB(C6F5)2] to yield the cyclohexylene‐anellated frustrated Lewis pair 5. This P/B pair splits H2 with the formation of the product 4 and adds to the CO double bond of phenyl isocyanate to yield 6. In the crystal, compound 5 features a puckered four‐membered heterocyclic core structure with a long PB bond (av. 2.197(5) Å). The activation energy of the PB cleavage of the frustrated Lewis pair 5 was determined by dynamic 19F NMR spectroscopy at ΔG≠(298 K)=12.1±0.3 kcal mol−1.
Pain management in intellectually disabled children: Assessment, treatment, and translational research
Authors: Valkenburg Abraham J. , van Dijk Monique , de Klein Annelies , van den Anker Johannes N. , Tibboel Dick
Published: October 2010

The primary focus of pain research in intellectually disabled individuals is still on pain assessment. Several observational pain assessment scales are available, each with its own characteristics, its own target group and its own validated use. Observational studies report differences in the treatment of intra‐ and postoperative pain of intellectually disabled children and almost all children with intellectual disability have comorbidities that need to be addressed. The scope of research has started to broaden. In this review we aim to answer the question: Can we integrate validated ways of pain assessment and postoperative pain treatment in intellectually disabled children to develop specific analgesic algorithms? Regrettably there is little knowledge on possible interaction effects and other relevant pharmacological issues. Possible genotype–phenotype associations related to pain in children with Down syndrome have several promises as six possible candidate genes are located on chromosome 21. In conclusion, the pain assessment tools for intellectually disabled children are there. We should now focus on tailoring the pain treatment. To this aim we need to perform pharmacokinetic and pharmacodynamic studies of analgesics and obtain information about the genotype–phenotype relationships for pain. This can lead to the development of specific analgesic algorithms. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:248–257.
Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature
Authors: Häßler Frank , Reis Olaf
Published: October 2010

The review presented here describes the state of the art of pharmacological treatment of aggression in subjects with mental retardation (MR) summing up results for both, children and adults. In general, psychopharmacological treatment of disruptive behavior in individuals with MR is similar to the treatment in subjects without MR. Compared to individuals without MR medication should “start lower and go slower.” For children and adults results were similar but were obtained by somewhat different medications. There is evidence for the conventional antipsychotic zuclopenthixol having positive effects on disruptive behavior. Most studies described the atypical antipsychotic risperidone to control severe self‐injurious behavior and other behavior problems in a variety of diagnoses. Anticonvulsants, antidepressants, and anxiolytic medications are reported as effective as well for the treatment of individuals with disruptive behavior. Aggression‐related behavior often gets treated with stimulants or with stimulants combined with atypical neuroleptics. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:265–272.
Amino acid‐induced gene expression profiling in clonal β‐cell line INS‐1E cells
Authors: Liu Zhenping , Luo Yonglun , Jeppesen Per Bendix , Gregersen Søren , Hermansen Kjeld
Published: October 2010

Background

There is abundant evidence that glucotoxicity and lipotoxicity contribute to impaired β‐cell function in type 2 diabetes. Interestingly, amino acid (AA) derangement is also a characteristic part of the diabetic state. The acute effects of AA on pancreatic β‐cell function have been widely explored; however, to our knowledge, the chronic effects of AA, e.g. proline (Pro), homocysteine (Hcy), and leucine (Leu), on pancreatic β‐cell function and integrity have not yet been studied. We aimed to investigate global alterations in β‐cell gene expression after long‐term exposure of clonal INS‐1E cells to elevated level of specific AA in vitro.

Methods

Global gene expression profiling was performed to characterize genes differently modified by Pro, Hcy, and Leu, respectively, in INS‐1E cells.

Results

Gene expression profiling revealed significant changes in INS‐1E cell mRNAs involved in the control of several aspects of β‐cell function, e.g. epigenetic regulation of gene expression, metabolism, innate and adaptive immune responses, cellular signalling, protein synthesis, apoptosis, and cellular stress response.

After 72 h, INS‐1E cells were differentially regulated (≥1.5‐ or ≤ −1.5‐fold) by Pro (295 transcripts), Hcy (301 transcripts), and Leu (701 transcripts). It appears that Hcy effects changes opposite to those induced by Leu and/or Pro.

Conclusions

AA appears to participate in and to influence many physiological processes including those involved in cholesterol metabolism, immune responses, and oxidative phosphorylation. Whether such events promote the β‐cell dysfunction and the β‐cell failure in diabetes remains to be elucidated. Our data strongly indicate that AA elevation may take part in the progressive development of type 2 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.
Dynamic expression patterns of 6‐O endosulfatases during zebrafish development suggest a subfunctionalisation event for sulf2
Authors: Gorsi Bushra , Whelan Simon , Stringer Sally E.
Published: October 2010

The 6‐O‐endosulfatase enzymes (Sulfs) edit the final sulfation pattern and function of heparan sulfate (HS) by removal of 6‐O‐sulfate groups from the chain. To date, two mammalian sulf genes have been identified that regulate many signalling pathways during embryonic development. In zebrafish a sulf1 ortholog and duplicate copies of the mammalian sulf2 gene, sulf2a and sulf2, have been identified, which contain conserved motifs characteristic of vertebrate sulf genes. Zebrafish sulf1 and sulf2a are broadly expressed in the central nervous system (CNS) and non‐neuronal tissue including heart, somite boundaries, olfactory system, and otic vesicle, whereas sulf2 expression is almost entirely restricted to the CNS. The duplicate copies of sulf2 have distinct expression patterns, which together mirror that of mouse sulf2, suggesting duplication in the teleost lineage has been followed by subfunctionalisation, whereby both genes need to be preserved by selection to ensure the ancestral gene's expression profile and function is maintained. Developmental Dynamics 239:3312–3323, 2010. © 2010 Wiley‐Liss, Inc.
Simple and efficient transgenesis withI‐SceImeganuclease in the newt,Cynops pyrrhogaster
Authors: Casco‐Robles Martin Miguel , Yamada Shouta , Miura Tomoya , Chiba Chikafumi
Published: October 2010

Newts have been recognized as an ideal model for body‐parts regeneration after traumatic injury since the 18thcentury. However, molecular mechanisms underlying regeneration remain a mystery because of technical limitations. In the current study, to break this obstacle, we established a simple and efficient transgenic protocol for the newtCynops pyrrhogasterby adapting anI‐SceImicroinjection technique, as well as a two‐aquarium‐tank (TAT) system that allows us to constantly obtain fertilized eggs in the laboratory for transgenesis. Following our protocol, ∼20% of injected embryos would exhibit non‐mosaic widespread transgene expression and survive beyond metamorphosis. This anticipated success rate is about 10 times higher than that obtained by previous protocols, reaching a practical level. Therefore, our transgenic protocol in conjunction with the TAT‐system could provide a key technique to open the way to uncover the long mystery underlying body‐parts regeneration of newts. Developmental Dynamics 239:3275–3284, 2010. © 2010 Wiley‐Liss, Inc.
lef1 controls patterning and proliferation in the posterior lateral line system of zebrafish
Authors: Gamba Laurent , Cubedo Nicolas , Lutfalla Georges , Ghysen Alain , Dambly‐Chaudiere Christine
Published: October 2010

The embryonic development of the posterior lateral line of zebrafish involves the migration from head to tail of a primordium comprising approximately 100 cells, and the deposition at regular intervals of presumptive mechanosensory organs (neuromasts). Migration depends on the presence of chemokine SDF1 along the pathway, and on the asymmetrical distribution of chemokine receptors CXCR4 and CXCR7 in the primordium. Primordium polarization depends on Wnt signaling in the leading region. Here, we examine the role of a major effector of Wnt signaling, lef1, in this system. We show that, although its inactivation has no overt effect on the expression of cxcr4b and cxcr7b, lef1 contributes to their control. We also show that cell proliferation, which ensures constant primordium size despite successive rounds of cell deposition, is reduced upon lef1 inactivation. Because of this defect, the primordium runs short of cells and vanishes before the line has been completed. We conclude that lef1‐mediated Wnt signaling is involved in various aspects of primordium migration, although part of this implication is masked by a high level of developmental redundancy. Developmental Dynamics 239:3163–3171, 2010. © 2010 Wiley‐Liss, Inc.
Carbohydrate recognition and complement activation by rat ficolin‐B
Authors: Girija Umakhanth Venkatraman , Mitchell Daniel A. , Roscher Silke , Wallis Russell
Published: October 2010

Ficolins are innate immune components that bind to PAMPs and structures on apoptotic cells. Humans produce two serum forms (L‐ and H‐ficolin) and a leukocyte‐associated form (M‐ficolin), whereas rodents and most other mammals produce ficolins‐A and ‐B, orthologues of L‐ and M‐ficolin, respectively. All three human ficolins, together with mouse and rat ficolin‐A, associate with mannan‐binding lectin‐associated serine proteases (MASPs) and activate the lectin pathway of complement on PAMPs. By contrast, mouse ficolin‐B does not bind MASPs and cannot activate complement. Because of these striking differences together with the lack of functional information for other ficolin‐B orthologues, we have characterized rat ficolin‐B, and compared its physical and biochemical properties with its serum counterpart. The data show that both rat ficolins have archetypal structures consisting of oligomers of a trimeric subunit. Ficolin‐B recognized mainly sialyated sugars, characteristic of exogenous and endogenous ligands, whereas ficolin‐A had a surprisingly narrow specificity, binding strongly to only one of 320 structures tested: an N‐acetylated trisaccharide. Surprisingly, rat ficolin‐B activated MASP‐2 comparable to ficolin‐A. Mutagenesis data reveal that lack of activity in mouse ficolin‐B is probably caused by a single amino acid change in the putative MASP‐binding site that blocks the ficolin‐MASP interaction.
Efficient Treg depletion induces T‐cell infiltration and rejection of large tumors
Authors: Li Xingrui , Kostareli Efterpi , Suffner Janine , Garbi Natalio , Hämmerling Günter J.
Published: October 2010

There are a number of factors that hamper immunotherapy of cancer. For example, tumors exhibit an aberrant vasculature that appears to form a barrier against T‐cell infiltration. Another major obstacle is created by Treg. So far, conventional depletion of Treg with anti‐CD25 antibodies, which eliminate only 70% of Treg, has failed to significantly reduce the growth of established tumors. Using Foxp3.LuciDTR‐4 mice, we show here that 90–95% Treg depletion resulted in complete regression of large established tumors, whereas 70% depletion was ineffective. The extensive Treg depletion induced a number of processes that are critical for tumor rejection, including activation of tumor‐specific CD8+ T cells and enhanced infiltration of these cells into the tumor. The precise mechanism of enhanced infiltration is not known, but normalization of the tumor vasculature is assumed to assist infiltration. Indeed, we observed that 90% Treg depletion caused normalization of the tumor vasculature as indicated by a reduction in leakiness and the number of dilated vessels. These results suggest that for clinical immunotherapy of cancer, it would be desirable to have reagents that allow high‐level depletion of Treg, which, in conjunction with treatment modalities such as vaccination, may concomitantly increase T‐cell activation and infiltration.
Synthesis and Structure of Trisilane‐1,3‐diyl ansa Half‐Sandwich Complexes of Group 6 Metals
Authors: Braunschweig Holger , Dörfler Rainer , Hammond Kai , Mies Jan , Radacki Krzysztof
Published: October 2010

We present the synthesis and characterization of the firsttrisila‐bridged ansa half‐sandwich complexes of Group 6 transition metals in a one‐step synthesis from dilithiatedprecursors Li[M(η5‐C5H4Li)(CO)3] (M = W, Mo) by use ofstoichiometric amounts of Si3Me6Cl2 under dilute conditions. Variation of the reaction conditions leads to dinuclear trisila‐bridged half‐sandwich complexes, which were also characterized.
Optimization of oil extraction from locust bean using response surface methodology
Authors: Akinoso Rahman , Raji Akeem Olayemi
Published: October 2010

Optimization of oil extraction from locust beans (Parkia biglobosa) using central composite rotatable design of RSM was carried out. Independent variables were roasting temperature (90, 100, 110, 120, 130°C) and roasting duration (5, 10 15, 20, 25 min), while the responses were oil yield (OY), free fatty acid (FFA), color (CO), stability, anisidine value (AV), and specific gravity (SG). Data obtained from this study were analyzed using ANOVA and regression analysis. OY, FFA, CO, oil stability, AV, and SG of the oil ranged between (19.0–22.5%), (0.65–3.1%), (37.9–199.9 mg/L), (3.6–6.4%), (11.4–59.9 mg/L), (0.7–0.9), respectively. Roasting conditions significantly influenced all dependent variables at p<0.05. Coefficients of determination (R2) of the generated models ranged from 0.49 to 0.98. Optimum roasting condition was 108°C for 10 min. This gave 22.3% OY, 1.7% FFA, 54.9 mg/L CO, 4.1% stability, 16.5 mg/L AV, and 0.9 SG. Desirability of 0.8 was obtained for optimum conditions.

Practical applications: Generally, African locust bean is fermented to give condiment. It has not been used for commercial oil production despite its richness in oil, but soybean with a similar oil content of about 18–20% has been used both for condiment and commercial oil production. Research into the potential of locust bean as a source of edible oil is desirable. Roasting is among pre‐treatment methods employed in vegetable oil industry. Information on degree of influence of these parameters on quantity and quality of oil recovered oil from African locust benefits both entrepreneur and researchers. Also, the developed mathematical expression for OY, FFA, CO, oil stability, AV, and SG, as influenced by roasting temperature and duration is an effective tool in predicting these parameters. The research output has both immediate and potential application.
Effects of Orlistat on white adipose tissue (WAT) in the γ‐irradiated mouse model
Authors: Roh Changhyun , Choi Nam‐Hee , Park Hae‐Ran , Jung Uhee , Jo Sung Kee
Published: October 2010

In this study, we showed that γ‐irradiation could trigger biological response like the fat accumulation of gonadal white adipose tissue (gWAT) in mice. The irradiated animal can be used as a useful model for evaluation of anti‐obesity drugs. To induce the fat accumulation by γ‐irradiation, 2‐months‐old female C57BL/6 mice were irradiated at 5 Gy and further raised for 6 months. Subsequently, the mice were i.p. injected daily with Orlistat (25 mg/kg) or vehicle for 3 wk and analyzed for the adipose tissue weight and serum triglyceride and T‐cholesterol levels. The abdominal WAT of the γ‐irradiated mice weighed an average of 3.9/100 g body weight, 1.7‐fold higher than what was seen in normal mice (2.3/100 g body weight), indicating that γ‐irradiation induced the fat accumulation in the adipose tissue. However, the administration of Orlistat, a well‐known anti‐obesity agent, significantly reduced the adipose tissue weight to 1.7/100 g body weight in irradiated mice. In addition, in these Orlistat‐treated mice, a significant reduction of serum triglyceride and T‐cholesterol was observed up to 14% and 27%, respectively.
Reaction of Baylis–Hillman Adducts with Fluorinated Silanes
Authors: Zemtsov Artem A. , Levin Vitalij V. , Dilman Alexander D. , Struchkova Marina I. , Belyakov Pavel A. , Tartakovsky Vladimir A. , Hu Jinbo
Published: October 2010

Reactions of acylated Baylis–Hillman adducts bearing nitrile, ester, or ketone groups with C6F5‐substituted silicon reagents MenSi(C6F5)4–n (n = 1–3) have been studied. The reactions are initiated by Bu4NOAc (5 mol‐%) in MeCN or DMF under mild conditions and afford products of allylic substitution of the acetoxy group by the C6F5 carbanion in good yields. Predominant or exclusive formation of one geometrical isomer was observed in all cases (Z for nitriles, E for esters and ketones). For substrates containing carbonyl groups, nucleophilic attack of the C6F5 carbanion chemoselectively occurred at the C=C bond. Reactions of acylated Baylis–Hillman adducts with Me3SiCF3 were found to be inefficient, as the CF3 carbanion had the propensity to attack the C=O bond of substrates with ester or ketone substituents.
The Use of a Single Derivative in the Configurational Assignment of Ketone Cyanohydrins
Authors: Louzao Iria , Seco José M. , Quiñoá Emilio , Riguera Ricardo
Published: October 2010

The absolute stereochemistry of ketone cyanohydrins can be easily determined by preparing a single MPA derivative. The comparison of two NMR spectra at different temperatures allows the assignment by just paying attention to the evolution of the cyanohydrin chemical shifts. The special case of α‐aryl‐substituted cyanohydrins is also described.
Purified silk fibroin‐L‐asparaginase bioconjugates show increased thermostability and resistance to trypsin digestion
Authors: Wang Bochu , Cao Yang
Published: October 2010

Bioconjugation protocols have been recently used to improve the therapeutic properties of the anti‐leukemic enzyme L‐asparaginase. In this study, we study the variation of reaction factors, such as mass ratio, pH value, reaction temperature and time, and the concentration of cross‐linker, in the modification reaction of L‐asparaginase with silk fibroins. The optimum reaction parameters were obtained as follows: pH 7.0, mass ratio of silk fibroin to L‐asparaginase 5:1, reaction time 8 h, and temperature 4°C. The rate of ε‐amino group modification was 57.88% and the recovery of modified L‐asparaginase was 66.58% under these reaction conditions. We isolated and purified the silk‐L‐asparaginase conjugates with two consecutive chromatography steps: anion‐exchange (XK 16×20, Q Sepharose FF) and gel filtration (Tricorn 10×600, Sephcryl S‐300 HR) chromatography. Finally, the stabilities of the enzymes were investigated. The results showed that modified L‐asparaginase had a higher thermostability and higher resistance to trypsin digestion.
Laryngeal cancer in Egypt: Quality of life measurement with different treatment modalities
Authors: Hamid Ossama A. , El Fiky Lobna M. , Medani Medani M. , AbdelHady Ayman , Ali Hanan H.
Published: October 2010

Background

Quality of life (QOL) reflects the need to assess the patient's overall sense of well‐being. A nonrandomized, prospective longitudinal study was conducted to evaluate QOL in Egyptian patients treated for laryngeal cancer.

Methods

In all, 60 newly diagnosed patients with laryngeal cancer were divided into 3 groups: surgical resection, radiotherapy, and combined therapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC‐QLQ) were administered to the patients at 4 points: prior to treatment, during active treatment, and at 3 and 6 months after completion of treatment.

Results

All pretreatment scales were worse in the combined therapy group. The functional scales reached their lowest levels in all groups during active treatment. Radiotherapy group scales showed persistent slow recovery. There was striking prevalence of the financial difficulties score in all groups.

Conclusion

QOL measurement provides information to guide clinical decision making in patients treated for laryngeal carcinoma. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Outcome of transoral laser microsurgery for T2‐T3 tumors growing in the laryngeal anterior commissure
Authors: Blanch José‐Luis , Vilaseca Isabel , Caballero Miguel , Moragas Miguel , Berenguer Joan , Bernal‐Sprekelsen Manuel
Published: October 2010

Background

To evaluate the outcomes of transoral laser microsurgery (TLM) in the treatment of T2 to T3 laryngeal carcinomas growing in the laryngeal anterior commissure.

Methods

This study was a retrospective analysis of 107 patients. Overall survival, disease‐specific survival, and laryngectomy‐free survival were analyzed. Technical difficulties, postoperative complications, influence of the learning curve, and the number of surgeries were evaluated.

Results

Five‐year overall survival, disease‐specific survival, and laryngectomy‐free survival were 71%, 79.5%, and 71.4%, respectively. The probability of tumor relapse was related to the status of the margins (p = .01) and to surgical experience (p = .02), but not to tumor exposure (p = .78) or pT category (p = .36). Disease‐specific survival differed significantly between the group of patients treated in the early period of surgical experience and those treated in the advanced period of surgical experience (71% vs 94%; p = .02)

Conclusion

TLM is a useful treatment for T2 to T3 laryngeal carcinomas growing in the laryngeal anterior commissure when it is performed under an advanced learning curve. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Interactional quality depicted in infant and toddler videos: where are the interactions?
Authors: Fenstermacher Susan K. , Barr Rachel , Brey Elizabeth , Pempek Tiffany A. , Ryan Maureen , Calvert Sandra L. , Shwery Clay E. , Linebarger Deborah
Published: October 2010

This study examined the social–emotional content and the quality of social interactions depicted in a sample of 58 DVDs marketed towards infants and toddlers. Infant‐directed videos rarely used social interactions between caregiver and child or between peers to present content. Even when videos explicitly targeted social–emotional content, correlations between educational claims and the actual content of the videos were modest at best. Similarly, other domain content (e.g. language skills) that is best learned through high‐quality social interactions was typically depicted without social interactions. The results suggest that producers of infant‐directed media are not applying developmental principles or research evidence in ways that take full advantage of developmentally appropriate interaction strategies to present their content. Copyright © 2010 John Wiley & Sons, Ltd.
Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors
Authors: Lorke Dietrich E. , Hasan Mohamed Y. , Nurulain Syed M. , Shafiullah Mohamed , Kuča Kamil , Petroianu Georg A.
Published: October 2010

Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors before exposure to organophosphorus compounds (OPCs) can reduce OPC‐induced mortality. Pyridostigmine is the only FDA‐approved substance for such use. The AChE‐inhibitory activity of known AChE inhibitors was quantified in vitro and their in vivo mortality‐reducing efficacy was compared, when given prophylactically before the exposure to the OPC diisopropylfluorophosphate (DFP). The IC50 was measured in vitro for the known AChE inhibitors pyridostigmine, physostigmine, ranitidine, tiapride, tacrine, 7‐methoxytacrine, amiloride, metoclopramide, methylene blue and the experimental oxime K‐27. Their in vivo efficacy, when given as pretreatment, to protect rats from DFP‐induced mortality was quantified by determining the relative risk of death (RR) by Cox analysis, with RR = 1 for animals given only DFP, but no pretreatment. Physostigmine was the strongest in vitro AChE‐inhibitor (IC50 = 0.012 µ m), followed by 7‐methoxytacrine, tacrine, pyridostigmine and methylene blue. Ranitidine (IC50 = 2.5 µ m), metoclopramide and amiloride were in the mid‐range. Tiapride (IC50 = 256 µ m) and K‐27 (IC50 = 414 µ m) only weakly inhibited RBC AChE activity. Best in vivo protection from DFP‐induced mortality was achieved when physostigmine (RR = 0.02) or tacrine (RR = 0.05) was given before DFP exposure, which was significantly superior to the pretreatment with all other tested compounds, except K‐27 (RR = 0.18). The mortality‐reducing effect of pyridostigmine, ranitidine and 7‐methoxytacrine was inferior, but still significant. Tiapride, methylene blue, metoclopramide and amiloride did not significantly improve DFP‐induced mortality. K‐27 may be a more efficacious alternative to pyridostigmine, when passage into the brain precludes administration of physostigmine or tacrine. Copyright © 2010 John Wiley & Sons, Ltd.
Continuous ethanol fermentation in a closed‐circulating system using an immobilized cell coupled with PDMS membrane pervaporation
Authors: Ding Wen‐Wu , Wu Yun‐Tao , Tang Xiao‐Yu , Yuan Lin , Xiao Ze‐Yi
Published: October 2010

BACKGROUND: A closed‐circulating system for ethanol fermentation was constructed by coupling a cell‐immobilized bed fermentor with pervaporation using a composite PDMS membrane. A continuous fermentation experiment was carried out for about 250 h in the system at 28 °C.

RESULTS: The cell density in the immobilized bed was up to 1.76 × 1010 cells g−1 gel. The ethanol concentration in the broth was maintained at about 43 g L−1. The glucose utilization and ethanol productivity were 23.26 g L−1 h−1 and 9.6 g L−1 h−1, respectively. The total flux and the ethanol flux through the membrane pervaporation unit varied in the range 300–690 g m−2 h−1 and 61–190 g m−2 h−1, respectively. The average ethanol concentration in the permeate was 23.1% (wt%). The carbon recovery efficiency was 86.8% (wt%), determined by calculating the carbon balance kinetics. The effect of ethanol concentration in the broth on the ethanol productivity was analyzed by modeling product formation kinetics of the system.

CONCLUSIONS: Compared with the traditional free cell fermentation system and packed bed fermentation system, the closed‐circulating system has the promising features of higher glucose utilization and ethanol productivity, and cleaner production. Copyright © 2010 Society of Chemical Industry
Electricity generation from molasses wastewater by an anaerobic baffled stacking microbial fuel cell
Authors: Zhong Chen , Zhang Baogang , Kong Lingcai , Xue An , Ni Jinren
Published: October 2010

BACKGROUND: The conventional treatment of molasses wastewater has many disadvantages including intensive energy requirements, excessive chemicals consumption and large quantities of waste generation. The microbial fuel cell (MFC) is a promising technology for power generation along with wastewater treatment. However, low power output and high construction costs limit the scale‐up and field implementation of MFCs. In this study, a novel anaerobic baffled stacking microbial fuel cell (ABSMFC) composed of four units was constructed and used to treat molasses wastewater.

RESULTS: The ABSMFC was operated at three different organic loading rates (OLRs) and the highest average power density of 115.5 ± 2.7 mW m−2 was achieved for the four units at an OLR of 3.20 kg COD m−3 d−1. Accordingly, 50–70% of total COD removal efficiency was accomplished. Power generation was further improved in terms of voltage or current by connecting units in series or parallel. The low voltage loss (8.1%) during series connection resulted from low parasitic current of adjacent units.

CONCLUSION: The ABSMFC is effective for molasses wastewater treatment. It can promote current or voltage output and minimize energy loss during series connection. This is a promising scalable architecture and can be combined with other existing wastewater treatment technologies. Copyright © 2010 Society of Chemical Industry
A rare association between mitral valve fibroelastoma and myxomatous disease with severe mitral regurgitation
Authors: Sisu Roxana Cristina , Lanzillo Guido , Benea Diana Crina , Cerin Gheorghe , Vinereanu Dragos
Published: October 2010

We report a rare case of association between mitral valve fibroelastoma and myxomatous disease in a patient with long history of asymptomatic myxomatous disease and progressive severe mitral regurgitation. The tumor was an intraoperative transesophageal echocardiographic finding and was confirmed during surgery. The differential diagnosis of the echocardiographic image was infective endocarditis. © Wiley Periodicals, Inc. J Clin Ultrasound, 2011.