bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of nutrient sensing nuclear hormone receptors promotes weight loss through appetite suppression in mice
Authors: Perreault M. , Will S. , Panza D. , Gareski T. , Harding K. , Kubasiak D. , Jalenak M. , Gartrell K. , Wang S. , Bollag G. , Artis D. R. , Ibrahim P. N. , Womack P. , Lin J. J. , Saiah E. , Mansour T. S. , Vlasuk G. P. , Erbe D. V. , Tobin J. F. 
Published: September 2009

Aim: Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in glucose and lipid metabolism. Three isoforms of PPARs have been identified with different tissue distribution and biological functions. Although the pharmacology of each receptor is well studied, the physiological effect of simultaneous activation of PPARα, γ and δ is only starting to emerge. We sought to determine the biological effects of a novel PPAR pan activator and elucidate the physiological mechanisms involved. Methods:
Ob/ob, diet‐induced obese (DIO) or PPARα knockout mice were administered a novel agonist that activates all PPARs to various degrees to determine the effect on body weight, body composition, food intake and energy expenditure. In addition, serum parameters including glucose, insulin, triglycerides and ketone bodies as well as tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and skeletal muscle histopathology was also studied. Results: We report that simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist treatment increased lipid oxidation, although appetite suppression was mainly responsible for the weight loss. Agonist‐induced weight loss was completely absent in PPARα knockout mice suggesting that PPARα pharmacology was the major contributor to weight regulation in mice. Conclusions: Our work provides evidence that simultaneous activation of PPARα, γ and δ decreases body weight by regulating appetite. These effects of the pan agonist were completely absent in PPARα knockout mice, suggesting that PPARα pharmacology was the major contributor to weight loss.
Colestilan monotherapy significantly improves glycaemic control and LDL cholesterol levels in patients with type 2 diabetes: a randomized double‐blind placebo‐controlled study
Authors: Kondo K. , Kadowaki T. 
Published: September 2009

Aim: To evaluate the plasma glucose‐reducing activity and safety of colestilan, a bile acid sequestrant, in patients with type 2 diabetes. Methods: Patients with fasting plasma glucose (FPG) 7.2–11.1 mmol/l and HbA 1c≥7.0% were randomly allocated in double‐blind manner to receive colestilan or placebo therapy for 12 weeks. Results: A total of 183 patients entered the double‐blind treatment phase. At 12 weeks, colestilan significantly reduced HbA 1c and FPG vs. placebo by 0.9% and 1.2 mmol/l respectively (both p < 0.001). A significant (p < 0.001) 22.5% reduction of LDL cholesterol was also observed in the 172 patients evaluated (colestilan group: n = 86; placebo group: n = 86). However, no significant reduction of fasting insulin was observed (p = 0.087). No incidence of hypoglycaemia was reported in this study. Conclusion: Colestilan improved glycaemic control and reduced LDL cholesterol levels in patients with type 2 diabetes.
Outside Directors on Korean Boards: Governance and Institutions
Authors: Chizema Amon , Kim Jootae 
Published: September 2009

abstractDrawing on institutional theory, this study examines the factors that pressured Korean firms to appoint outside directors to their boards. While this practice could be considered to be a management innovation in Korea, in the Anglo‐American corporate governance system it has long been used as one of several mechanisms to mitigate agency costs between management and shareholders. As such, this response by Korean firms, following the 1997–98 currency crisis in Asia, could be seen as an example of corporate governance convergence on the Anglo‐American model, where higher levels of outside director representation on the board are the norm. We examine the antecedents of having a higher proportion of outside directors on Korean boards. Our findings indicate that larger firms that are under stricter control by the government have higher representation of outside directors on the board. We also find a positive and significant relationship between the proportion of outside directors and business group affiliation, poor prior firm performance, higher levels of debt and foreign ownership.
Suppression of APP‐containing vesicle trafficking and production of β‐amyloid by AID/DHHC‐12 protein
Authors: Mizumaru Chie , Saito Yuhki , Ishikawa Takao , Yoshida Tomohiro , Yamamoto Tohru , Nakaya Tadashi , Suzuki Toshiharu 
Published: September 2009

AbstractThe metabolism of amyloid β‐protein precursor (APP) is regulated by various cytoplasmic and/or membrane‐associated proteins, some of which are involved in the regulation of intracellular membrane trafficking. We found that a protein containing Asp–His–His–Cys (DHHC) domain, alcadein and APP interacting DHHC protein (AID)/DHHC‐12, strongly inhibited APP metabolism, including amyloid β‐protein (Aβ) generation. In cells expressing AID/DHHC‐12, APP was tethered in the Golgi, and APP‐containing vesicles disappeared from the cytoplasm. Although DHHC domain‐containing proteins are involved in protein palmitoylation, a AID/DHHC‐12 mutant of which the enzyme activity was impaired by replacing the DHHC sequence with Ala–Ala–His–Ser (AAHS) made no detectable difference in the generation and trafficking of APP‐containing vesicles in the cytoplasm or the metabolism of APP. Furthermore, the mutant AID/DHHC‐12 significantly increased non‐amyloidogenic α‐cleavage of APP along with activation of a disintegrin and metalloproteinase 17, a major α‐secretase, suggesting that protein palmitoylation involved in the regulation of α‐secretase activity. AID/DHHC‐12 can modify APP metabolism, including Aβ generation in multiple ways by regulating the generation and/or trafficking of APP‐containing vesicles from the Golgi and their entry into the late secretary pathway in an enzymatic activity‐independent manner, and the α‐cleavage of APP in the enzymatic activity‐dependent manner.
Vagus nerve stimulation might have a unique effect in reflex eating seizures
Authors: Cukiert Arthur , Mariani Pedro Paulo , Burattini Jose Augusto , Cukiert Cristine Mella , Forster Cassio , Baise Carla , Argentoni‐Baldochi Meire , Mello Valeria 
Published: September 2009

SummaryWe studied the effects of vagus nerve stimulation (VNS) on eating seizures, which theoretically would be triggered by neural activity and signaling from organs innervated by the vagus nerve. Three adult patients with daily nonreflex and reflex eating seizures were studied; one patient also had hot‐water seizures. One patient had bilateral polymicrogyria and two had normal magnetic resonance imaging (MRI) findings. All patients were submitted to VNS implantation and had at least 2 years of postimplantation follow‐up. Final stimulation parameters were 2.0–2.5 mA, 500 μs, and 30 Hz. Eating seizures decreased 70–95% and nonreflex seizures decreased 0–40% after VNS. There was no improvement in hot‐water seizures. VNS seems to be an especially useful treatment modality in patients with reflex eating seizures not amenable to resective surgery.
Adult‐onset drug‐refractory seizure disorder associated with anti–voltage‐gated potassium‐channel antibody
Authors: Barajas Ramon F. , Eric Collins D. , Cha Soonmee , Geschwind Michael D. 
Published: September 2009

SummaryVoltage‐gated potassium channels are widely expressed throughout the entire nervous system. These channels play a critical role in establishing the resting membrane potential and generation of neuronal action potentials. There is mounting evidence that autoantibodies reactive to neuronal cell surface antigens, such as voltage‐gated potassium channels, play a pathogenic role in a wide spectrum of central and peripheral nervous system disorders. We report a case of new‐onset drug‐refractory seizure disorder associated with the presence of high levels of serum anti–voltage‐gated potassium channel antibodies that responded only to immunotherapy. As demonstrated by this case report, anti–voltage‐gated potassium channel antibody associated drug‐refractory seizure disorder, although rare, should be considered in patients with unexplained adult‐onset seizure activity. Once the diagnosis has been established the initiation of immunotherapy should be undertaken without delay.
Xp22.3 genomic deletions involving the CDKL5 gene in girls with early onset epileptic encephalopathy
Authors: Mei Davide , Marini Carla , Novara Francesca , Bernardina Bernardo D. , Granata Tiziana , Fontana Elena , Parrini Elena , Ferrari Anna R. , Murgia Alessandra , Zuffardi Orsetta , Guerrini Renzo 
Published: September 2009

SummaryPurpose:  Mutations of the X‐linked gene cyclin‐dependent kinase‐like 5 (CDKL5) cause an X‐linked encephalopathy with early onset intractable epilepsy, including infantile spasms and other seizure types, and a Rett syndrome (RTT)–like phenotype. Very limited information is available on the frequency and phenotypic spectrum associated with CDKL5 deletions/duplications. We investigated the role of CDKL5 deletions/duplications in causing early onset intractable epilepsy of unknown etiology in girls.Methods:  We studied 49 girls with early onset intractable epilepsy, with or without infantile spasms, and developmental impairment, for whom no etiologic factors were obvious after clinical examination, brain magnetic resonance imaging (MRI) and expanded screening for inborn errors of metabolism. We performed CDKL5 gene mutation analysis in all and multiplex ligation dependent probe amplification assay (MLPA) in those who were mutation negative. Custom Array‐comparative genomic hybridization (CGH), breakpoint polymerase chain reaction (PCR) analysis, and X‐inactivation studies were performed in patients in whom MLPA uncovered a genomic alteration.Results:  We found CDKL5 mutations in 8.2% (4 of 49) of patients and genomic deletions in 8.2% (4 of 49). Overall, abnormalities of the CDKL5 gene accounted for 16.3% (8 of 49) of patients.Discussion:  CDKL5 gene deletions are an under‐ascertained cause of early onset intractable epilepsy in girls. Genetic testing of CDKL5, including both mutation and deletion/duplication analysis, should be considered in this clinical subgroup.
Mutations in LGI1 gene in Japanese families with autosomal dominant lateral temporal lobe epilepsy: The first report from Asian families
Authors: Kawamata Jun , Ikeda Akio , Fujita Youshi , Usui Keiko , Shimohama Shun , Takahashi Ryosuke 
Published: September 2009

SummaryAutosomal dominant lateral temporal lobe epilepsy (ADLTE) caused by LGI1 (leucine‐rich gene, glioma‐inactivated‐1) mutations is a rare familial epileptic syndrome characterized by the auditory ictal manifestation and rare nocturnal generalized seizures. We have examined the sequence of the LGI1 gene in four Japanese families with lateral temporal lobe epilepsy having characteristic auditory features, and identified one novel (1421G>A), and one reported (1418C>T) point mutation each in two families. These two mutations were 3 bp apart in the LGI1 gene and caused adjoining amino acid substitutions. The two families presented different clinical phenotypes and seizure control to drug treatment. These findings suggest that LGI1 mutations in Japanese ADLTE families may not be uncommon, and that diverse clinical phenotypes make adequate diagnosis of ADLTE difficult when only based on clinical information.
Education in donation coping strategies encourages individuals to give blood: further evaluation of a donor recruitment brochure
Authors: France Christopher R. , France Janis L. , Kowalsky Jennifer M. , Cornett Tanya L. 
Published: September 2009

BACKGROUND: This study extends our prior assessment of a blood donation recruitment brochure by assessing persistence of observed changes in attitudes toward donation as well as the effects that such changes have on the behavior of registering to give blood.STUDY DESIGN AND METHODS: Participants were randomly assigned to read 1) a study brochure addressing common donor concerns and suggesting specific coping strategies, 2) a blood center brochure, or 3) a control brochure on healthy eating and exercise. Measures of blood donation attitudes, donation‐related anxiety, confidence in ability to avert vasovagal reactions, and intentions to give blood in the near future were completed before and after reading the brochures and again approximately 1 week later. In addition, participants were given the opportunity to sign up for an upcoming blood drive immediately after reading the brochure.RESULTS: Relative to the control brochure, the study brochure was associated with improvements in donation attitude, anxiety, confidence, and intention, and all of these effects persisted at follow‐up. Further, participants who read the study brochure were more likely to volunteer to give blood, an effect that was mediated by enhanced confidence in their ability to avoid vasovagal reactions.CONCLUSIONS: Exposure to a brief educational brochure can enhance prospective donor confidence and increase the likelihood that they will volunteer to give blood.
Partial C antigen in sickle cell disease patients: clinical relevance and prevention of alloimmunization
Authors: Tournamille Christophe , Meunier‐Costes Natacha , Costes Bruno , Martret Jennifer , Barrault Aurélie , Gauthier Philippe , Galactéros Frédéric , Nzouékou Ruben , Bierling Philippe , Noizat‐Pirenne France 
Published: September 2009

BACKGROUND: Partial Rh antigens have been widely described in black individuals. Carriers are prone to immunization when exposed to the normal antigens. In sickle cell disease (SCD), patient alloimmunization is a major cause of transfusion failure. The potential of individuals with partial C antigen to make anti‐C has not been investigated. We sought partial C status and anti‐C production in a cohort of SCD patients with the C+ phenotype, to determine whether exposure to normal C antigen should be avoided.STUDY DESIGN AND METHODS: We constituted a cohort of 177 randomly selected SCD patients expressing C antigen. We screened for (C)ces and RN haplotypes, presumably associated with partial C antigen in Afro‐Caribbeans, and we recorded the number of transfused C+ red blood cell (RBC) units, immunization status, and extended phenotype.RESULTS: Forty‐nine patients carried abnormal C antigen, deduced from the presence of (C)ces and/or RN, not compensated by a normal RHC allele in trans. Among patients with partial C phenotype exposed repeatedly to C+ RBCs, 30% produced anti‐C. Two patients experienced hemolysis. In our hospital, with 22% of SCD patients expressing C, prevention of anti‐C immunization for all individuals with partial C antigen would require a 7% increase in the use of C– RBC units. These RBCs are already in short supply for SCD patients who are C–.CONCLUSION: This study demonstrates the need to detect partial C within C+ SCD patients and to prevent immunization. A larger number of Afro‐Caribbeans donors is needed to provide these patients with C– RBCs.
Aortic Elastic Properties of Patients with Neurocardiogenic Syncope
Authors: SUCU MURAT M. , DAVUTOGLU VEDAT , AKCAY MURAT , YIĞITER REMZI , AL BEHCET 
Published: September 2009

Objective: Neurocardiogenic syncope (NCS) is a common clinical problem; however, hemodynamic mechanism is not clearly understood. Aim of the present study was to investigate aortic elastic parameters of patients with NCS provoked by head‐up tilt test.
Material and Method: We conducted a prospective study of 40 cases referred to our institution for head‐up tilt testing. Group I constituted as 22 patients who developed mixed response and were enrolled for analysis. Hemodynamic data were compared with subjects of negative head‐up tilt test (Group II). Aorta‐diastolic and aorta‐systolic diameters, aortic strain, aortic distensibility, aortic elastic modulus, and aortic stiffness index were calculated from transthoracic echocardiographically derived diameters of thoracic aorta.
Results: Aortic distensibility (mean ± SD; 2.7 ± 1.2 cm2× dyn−1× 10−6 vs 4.0 ± 1.2 cm2× dyn−1× 10−6, P = 0,003) and aortic strain index (mean ± SD; 7.0 ± 1.8% vs 8.7 ± 2.9%, P = 0.042) were lower, and aortic stiffness index (mean ± SD; 27.6 ± 10.9 vs 20.9 ± 6.18, P = 0.035) and aortic elastic modulus (mean ± SD; 0.94 ± 0.7 cm2× dyn−1× 10−6 vs 0.49 ± 0.1 cm2× dyn−1× 10−6, P = 0.009) were higher in patients in Group I compared with those in Group II. There was no difference between two groups for following clinical variables: aorta‐diastolic and aorta‐systolic diameters, systolic and diastolic blood pressure, pulse pressure, E/A, weight, height, and body mass index.
Conclusions: Findings of this study have shown that elastic properties of aorta are impaired in patients with NCS. The data suggest that increase in aortic stiffness might be one of the determinants responsible for NCS. This proposal of novel link should be confirmed in further studies.
Influence of lipopolysaccharide and interleukin‐6 on RANKL and OPG expression and release in human periodontal ligament cells
Authors: KRAJEWSKI ANNA C. , BIESSEI JANINE , KUNZE MELANIE , MAERSCH Stephan , PERABO LUCA , NOACK MICHAEL J. 
Published: September 2009

Recent research into periodontal disease pathology focuses on the role of receptor activator of nuclear factor‐κB ligand (RANKL) and osteoprotegerin (OPG) in periodontal bone destruction processes. RANKL regulates the differentiation of osteoclast by binding to its specific receptor RANK, while OPG inhibits the differentiation of osteoclasts by binding RANKL and therefore preventing RANKL to bind RANK. The aim of the present study was to investigate the influence of Porphyromonas gingivalis lipopolysaccharide (LPS) and interleukin‐6 (IL‐6) on RANKL and OPG expression and release in periodontal ligament (PDL) cells. Human PDL cells were stimulated for 48 h with purified P. gingivalis LPS and IL‐6. OPG and sRANKL release were assessed by using enzyme‐linked immunosorbent assay technique. OPG and RANKL expression was quantitatively measured by using the real‐time PCR technique. Whereas P. gingivalis LPS induced sRANKL release, expression was only slightly increased, IL‐6 did not show an effect on RANKL expression or release. In conclusion the data demonstrate that stimulation of PDL cells with P. gingivalis LPS leads to an increased release of sRANKL, rather than increased RANKL expression. Through this action, P. gingivalis LPS may exert its biological effect on osteoclast formation and bone resorption.
In vivo assessment of the effect of an adhesive for complete dentures on colonisation of Candida species
Authors: Oliveira Mario C. S. , Oliveira Viviane M. B. , Vieira Alex C. , Rambob Isabel 
Published: September 2009

doi: 10.1111/j.1741‐2358.2009.00345.x

In vivo assessment of the effect of an adhesive for complete dentures on colonisation of Candida species Objective:  Denture adhesives have long been recognised by denture wearers as a useful adjunct to denture retention and stability. The objective of the present study was to evaluate, in vivo, the effect of a denture adhesive on oral quantities of Candida species by determination of absolute counts of colony‐forming units (CFU) per ml of saliva of individuals who use this denture adhesive for a period of 14 days.Materials and methods:  Twenty‐four individuals were randomised in two equal groups of 12 (test and control), with the individuals of the test group using the adhesive for 14 days. Samples of saliva were collected from all individuals on days 0 (initial), 7 and 14. Aliquots of saliva were diluted and plated in duplicate on Sabouraud dextrose agar with chloramphenicol and incubated for 37°C for 48 h, the CFU/ml were counted in the individuals of each group and the data of each group were compared at the different time periods and analysed statistically by the non‐parametric Mann‐Whitney U‐test (α ≤ 5%).Results:  There were no statistically significant differences between the test and control groups during the test periods.Conclusion:  Within of the limitations of this study, the data suggested that the denture adhesive tested did not significantly alter the oral microbiota during the 14‐day trial period.
Brain Neurons Express Ornithine Decarboxylase‐Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease
Authors: Mäkitie Laura T. , Kanerva Kristiina , Polvikoski Tuomo , Paetau Anders , Andersson Leif C. 
Published: September 2009

AbstractPolyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward‐rectifier K+‐channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate‐limiting enzyme of polyamine synthesis. Elevated levels of ODC activity and polyamines are detected in various brain disorders including stroke and Alzheimer's disease (AD).We originally reported a novel brain‐ and testis‐specific AZIN, called AZIN2, the distribution of which we have now studied in normal and diseased human brain by in situ hybridization and immunohistochemistry. We found the highest accumulation of AZIN2 in a pearl‐on‐the‐string‐like distribution along the axons in both the white and gray matter. AZIN2 was also detected in a vesicle‐like distribution in the somas of selected cortical pyramidal neurons. Double‐immunofluorescence staining revealed co‐localization of AZIN2 and N‐methyl D‐aspartate‐type glutamate receptors (NMDARs) in pyramidal neurons of the cortex. Moreover, we found accumulation of AZIN2 in brains affected by AD, but not by other neurodegenerative disorders (CADASIL or Lewy body disease). ODC activity is mostly linked to cell proliferation, whereas its regulation by AZIN2 in post‐mitotically differentiated neurons of the brain apparently serves different purposes. The subcellular distribution of AZIN2 suggests a role in vesicular trafficking.