bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence ofCYP2C19*18andCYP2C19*19Alleles on Omeprazole 5‐Hydroxylation:In vitroFunctional Analysis of Recombinant Enzymes Expressed inSaccharomyces cerevisiae
Authors: Hanioka Nobumitsu , Tsuneto Yumi , Saito Yoshiro , Maekawa Keiko , Sawada Jun‐ichi , Narimatsu Shizuo
Published: February 2008

Abstract: Omeprazole is one of the most widely used proton pump inhibitors for the treatment of gastric acid‐related disorders. The major metabolic pathway of omeprazole is 5‐hydroxylation, which is catalysed by CYP2C19. In this study, the effect ofCYP2C19*18andCYP2C19*19alleles on omeprazole 5‐hydroxylation was studied using recombinant CYP2C19 enzymes of wild‐type (CYP2C19.1B having Ile331Val) and variants (CYP2C19.18 having Arg329His/Ile331Val and CYP2C19.19 Ser51Gly/Ile331Val) expressed in yeast cells. TheKmvalue for omeprazole 5‐hydroxylation of CYP2C19.1B was 1.46 µM. TheKmvalue of CYP2C19.19 was significantly higher (1.5‐fold) than that of CYP2C19.1B.VmaxandVmax/Kmvalues for omeprazole 5‐hydroxylation of CYP2C19.1B on the basis of cytochrome P450 protein level were 8.09 pmol/min./pmol CYP and 5.45 µl/min./pmol CYP, respectively. TheVmaxvalue of CYP2C19.19 was significantly higher (1.8‐fold) than that of CYP2C19.1B, whereas theVmax/Kmvalue was comparable to that of CYP2C19.1B. In contrast,Km,VmaxandVmax/Kmvalues of CYP2C19.18 were similar to those of CYP2C19.1B. These results suggest thatCYP2C19*19allele decreases the affinity between CYP2C19 enzyme and the substrate in omeprazole metabolism.
Interleukin‐10 and interferon‐gamma gene polymorphisms in patients with nasopharyngeal carcinoma
Authors: Farhat K. , Hassen E. , Gabbouj S. , Bouaouina N. , Chouchane L.
Published: February 2008

Nasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin‐10 (IL‐10) is known to reduce the production of interferon‐gamma (IFN‐γ), we supposed that genetic differences in IL‐10 and IFN‐γ expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL‐10 and IFN‐γ with NPC. Different IL‐10 –1082 G/A and IFN‐γ+874 Τ/Α genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL‐10 and IFN‐γ polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL‐10 and IFN‐γ do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.
Characterization, expression and evolution analysis of Toll‐like receptor 1 gene in pufferfish (Tetraodon nigroviridis)
Authors: Wu X‐Y. , Xiang L‐X. , Huang L. , Jin Y. , Shao J‐Z.
Published: February 2008

The Toll‐like receptor (TLR) family is a pathogen‐associated molecular pattern recognition receptor family that plays key roles in the activation of innate immune system. As an important member of TLRs, TLR1 is involved in the recognition of triacylated lipoproteins and mycobacterial products by binding to TLR2 to form a heterodimer. Although partial sequences of TLR1 has been predicted in Fugu and Danio by bioinformatics, the molecular cloning and characterization of this gene in fish still remains largely unclear. Here we report the full‐length sequence of TLR1 gene in the pufferfish (Tetraodon nigroviridis), providing experimental evidence to its existence in fish. The cloned Tetraodon TLR1 (TnTLR1) cDNA exhibited 2587 bp in length and contains a 122‐bp 5′ untranslated region (UTR), a 2391‐bp open reading frame and a 74‐bp 3′ UTR. Expression of TLR1 transcripts in most selected tissues were detected at lower levels; however, the transcripts in spleen was markedly increased (threefold) after stimulation with lipopolysaccharide, indicating that TLR1 in fish may be involved in the inflammatory responses to bacterial endotoxin or Gram‐negative bacteria infection. Gene organization of TnTLR1 is similar to mammalian and avian, and a high degree of conservation of chromosome synteny exists between them. The protein sequence shares 33.7–77.3% identity with known TLR1 members. Phylogenetic analysis grouped TnTLR1 with other fish TLRs on a separated branch, excluded from mammalian and avian TLR1s. TnTLR1 with 796 amino acids has a calculated molecular mass of 90.69 kDa and a theoretical pI of 8.43. Structurally, TnTLR1 has a Toll/interleukin‐1 receptor (TIR) domain, a transmembrane domain and leucine‐rich repeat domain which are the hallmarks of TLR family. Phylogenetic analysis provided evidence that the TnTLR1 was very close to mammalian TLR1, TLR6 and TLR10 and seemed to be their common ancestor. This report of the full‐length TLR1 gene in Tetraodon will provide us further insights into the study of both function and evolution of fish TLRs as a whole.
Processing of Bulk Alumina Ceramics Using Laser Engineered Net Shaping
Authors: Balla Vamsi Krishna , Bose Susmita , Bandyopadhyay Amit
Published: February 2008

Application of rapid prototyping (RP) in ceramics manufacturing is motivated by advances in engineering ceramics where attaining complex shapes using traditional processing is difficult. Laser Engineered Net Shaping (LENS™), a commercial RP process, is used to fabricate dense, net‐shaped structures of α‐Al2O3. Shapes such as cylinder, cube, and gear have been fabricated successfully with 10–25 mm section sizes. As‐processed structures show anisotropy in mechanical properties with a high compressive strength normal to the build direction and columnar grains along the build direction. Heat treatment did not alter strength and anisotropy, but increased the grain size from 6 to 200 μm and hardness from 1550 to 1700 Hv.
Mapping Ligand–receptor Interfaces: Approaching the Resolution Limit of Benzophenone‐based Photoaffinity Scanning
Authors: Wittelsberger Angela , Mierke Dale F. , Rosenblatt Michael
Published: February 2008

Photoaffinity crosslinking has yielded important insights in the study of G protein‐coupled receptors and the mode of ligand binding. The most widely used photolabile moiety is p‐benzoylphenylalanine largely because of its reportedly high site specificity, reduced reactivity to water and light, photokinetics, and ease of incorporation into peptide ligands during synthesis. However, in the course of our studies directed at characterizing the binding of parathyroid hormone to its cognate G protein‐coupled receptor, we find that inherent properties of p‐benzoylphenylalanine, such as its size and conformational flexibility, limit the resulting resolution of the ligand–receptor structure. Here, we examine and define these limits.
Microcalorimetry: a response to challenges in modern biotechnology
Authors: Krell Tino
Published: February 2008

Almost any process in life is accompanied by heat changes which can be monitored by isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Both techniques are now established tools in fundamental research but over the last decade a clear tendency towards more problem‐driven applications is noted. This review aims at summarizing these problem‐oriented applications of microcalorimetry and the solutions both techniques can provide to problems in biotechnology. The biotechnological issues to which microcalorimetry has been successfully applied are as diverse as rational drug design, overcoming drug resistance, optimization of long‐term stability of proteins, estimation of the bioavailability of drugs, control of complex pharmaceutical products or the optimization of gene delivery efficiency. The main limitation of microcalorimetry, which is the relatively large amounts of sample necessary for analysis, is less important in the biotechnology sector which frequently uses large‐scale produced bulk products for analysis. The recently developed high‐throughput DSC and ITC microcalorimeters will additionally reduce the labour intensity of these techniques. Due to the precision of microcalorimetric analyses and the versatility of processes which can be studied, it is expected that ITC and DSC will soon be key technologies in biotechnological research.
Poly‐3‐hydroxyalkanoate synthases from Pseudomonas putida U: substrate specificity and ultrastructural studies
Authors: Arias Sagrario , Sandoval Angel , Arcos Mario , Cañedo Librada M. , Maestro Beatriz , Sanz Jesús M. , Naharro Germán , Luengo José M.
Published: February 2008

The substrate specificity of the two polymerases (PhaC1 and PhaC2) involved in the biosynthesis of medium‐chain‐length poly‐hydroxyalkanoates (mcl PHAs) in Pseudomonas putida U has been studied in vivo. For these kind of experiments, two recombinant strains derived from a genetically engineered mutant in which the whole pha locus had been deleted (P. putida U Δpha) were employed. These bacteria, which expresses only phaC1 (P. putida U Δpha pMC‐phaC1) or only phaC2 (P. putida U Δpha pMC‐phaC2), accumulated different PHAs in function of the precursor supplemented to the culture broth. Thus, the P. putida U Δpha pMC‐phaC1 strain was able to synthesize several aliphatic and aromatic PHAs when hexanoic, heptanoic, octanoic decanoic, 5‐phenylvaleric, 6‐phenylhexanoic, 7‐phenylheptanoic, 8‐phenyloctanoic or 9‐phenylnonanoic acid were used as precursors; the highest accumulation of polymers was observed when the precursor used were decanoic acid (aliphatic PHAs) or 6‐phenylhexanoic acid (aromatic PHAs). However, although it synthesizes similar aliphatic PHAs (the highest accumulation was observed when hexanoic acid was the precursor) the other recombinant strain (P. putida U Δpha pMC‐phaC2) only accumulated aromatic PHAs when the monomer to be polymerized was 3‐hydroxy‐5‐phenylvaleryl‐CoA. The possible influence of the putative three‐dimensional structures on the different catalytic behaviour of PhaC1 and PhaC2 is discussed.
Development of a LytE‐based high‐density surface display system in Bacillus subtilis
Authors: Chen Chyi‐Liang , Wu Sau‐Ching , Tjia Wai Mui , Wang Christopher L. C. , Lohka Manfred J. , Wong Sui‐Lam
Published: February 2008

The three N‐terminal, tandemly arranged LysM motifs from a Bacillus subtilis cell wall hydrolase, LytE, formed a cell wall‐binding module. This module, designated CWBMLytE, was demonstrated to have tight cell wall‐binding capability and could recognize two classes of cell wall binding sites with fivefold difference in affinity. The lower‐affinity sites were approximately three times more abundant. Fusion proteins with β‐lactamase attached to either the N‐ or C‐terminal end of CWBMLytE showed lower cell wall‐binding affinity. The number of the wall‐bound fusion proteins was less than that of CWBMLytE. These effects were less dramatic with CWBMLytE at the N‐terminal end of the fusion. Both CWBMLytE and β‐lactamase were essentially functional whether they were at the N‐ or C‐terminal end of the fusion. In the optimal case, 1.2 × 107 molecules could be displayed per cell. As cells overproducing CWBMLytE and its fusions formed filamentous cells (with an average of nine individual cells per filamentous cell), 1.1 × 108β‐lactamase molecules could be displayed per filamentous cell. Overproduced CWBMLytE and its fusions were distributed on the entire cell surface. Surface exposure and accessibility of these proteins were confirmed by immunofluorescence microscopy.
Microbial whole‐cell arrays
Authors: Elad Tal , Lee Jin Hyung , Belkin Shimshon , Gu Man Bock
Published: February 2008

The coming of age of whole‐cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines – the whole‐cell array. In the present review, we highlight the state‐of‐the‐art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high‐performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis and – most importantly – enhanced long‐term maintenance of viability and activity on the fabricated biochips.
The Meaning of Employee Engagement
Authors: Macey William H. , Schneider Benjamin
Published: February 2008

The meaning of employee engagement is ambiguous among both academic researchers and among practitioners who use it in conversations with clients. We show that the term is used at different times to refer to psychological states, traits, and behaviors as well as their antecedents and outcomes. Drawing on diverse relevant literatures, we offer a series of propositions about (a) psychological state engagement; (b) behavioral engagement; and (c) trait engagement. In addition, we offer propositions regarding the effects of job attributes and leadership as main effects on state and behavioral engagement and as moderators of the relationships among the 3 facets of engagement. We conclude with thoughts about the measurement of the 3 facets of engagement and potential antecedents, especially measurement via employee surveys.
Where Have We Been, How Did We Get There, and Where Shall We Go?
Authors: Lance Charles E.
Published: February 2008

Commentators expressed a wide variety of views on my evaluation of the state of assessment center (AC) research and practice. In this response, I first trace the evolution of the construct validity paradox “urban legend.” Next, I consider the commentators’ comments as they relate to (a) my recommendation to abandon dimension-based ACs in lieu of task- or role-based structures (b) my recommendation to discontinue design fix attempts toward making ACs conform to multitrait–multimethod construct validity criteria, and (c) considerations of construct validity and validation evidence. Finally, I offer some directions for future AC research and practice.
Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice
Authors: Mironov S. L.
Published: February 2008

Respiration in vertebrates is generated by a compact network which is located in the lower brainstem but cellular mechanisms which underlie persistent oscillatory activity of the respiratory network are yet unknown. Using two‐photon imaging and patch‐clamp recordings in functional brainstem preparations of mice containing pre‐Bötzinger complex (preBötC), we examined the actions of metabotropic glutamate receptors (mGluR1/5) on the respiratory patterns. The agonist DHPG potentiated and antagonist LY367385 depressed respiration‐related activities. In the inspiratory neurons, we observed rhythmic activation of non‐selective channels which had a conductance of 24 pS. Their activity was enhanced with membrane depolarization and after elevation of calcium from the cytoplasmic side of the membrane. They were activated by a non‐hydrolysable PIP2 analogue and blocked by flufenamate, ATP4− and Gd3+. All these properties correspond well to those of TRPM4 channels. Calcium imaging of functional slices revealed rhythmic transients in small clusters of neurons present in a network. Calcium transients in the soma were preceded by the waves in dendrites which were dependent on mGluR activation. Initiation and propagation of waves required calcium influx and calcium release from internal stores. Calcium waves activated TPRM4‐like channels in the soma and promoted generation of inspiratory bursts. Simulations of activity of neurons communicated via dendritic calcium waves showed emerging activity within neuronal clusters and its synchronization between the clusters. The experimental and theoretical data provide a subcellular basis for a recently proposed group‐pacemaker hypothesis and describe a novel mechanism of rhythm generation in neuronal networks.
Corticotropin‐releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C‐dependent enhancement ofIh
Authors: Wanat M. J. , Hopf F. W. , Stuber G. D. , Phillips P. E. M. , Bonci A.
Published: February 2008

Stress induces the release of the peptide corticotropin‐releasing factor (CRF) into the ventral tegmental area (VTA), and also increases dopamine levels in brain regions receiving dense VTA input. Therefore, stress may activate the mesolimbic dopamine system in part through the actions of CRF in the VTA. Here, we explored the mechanism by which CRF affects VTA dopamine neuron firing. Using patch‐clamp recordings from brain slices we first determined that the presence ofIhis an excellent predictor of dopamine content in mice. We next showed that CRF dose‐dependently increased VTA dopamine neuron firing, which was prevented by antagonism of the CRF receptor‐1 (CRF‐R1), and was mimicked by CRF‐R1 agonists. Inhibition of the phospholipase C (PLC)–protein kinase C (PKC) signalling pathway, but not the cAMP–protein kinase A (PKA) signalling pathway, prevented the increase in dopamine neuron firing by CRF. Furthermore, the effect of CRF on VTA dopamine neurons was not attenuated by blockade ofIA,IK(Ca)orIKir, but was completely eliminated by inhibition ofIh. Although cAMP‐dependent modulation ofIhthrough changes in the voltage dependence of activation is well established, we surprisingly found that CRF, through a PKC‐dependent mechanism, enhancedIhindependent of changes in the voltage dependence of activation. Thus, our results demonstrated that CRF acted on the CRF‐R1 to stimulate the PLC–PKC signalling pathway, which in turn enhancedIhto increase VTA dopamine neuron firing. These findings provide a cellular mechanism of the interaction between CRF and dopamine, which can be involved in promoting the avoidance of threatening stimuli, the pursuit of appetitive behaviours, as well as various psychiatric conditions.
Retrotrapezoid nucleus and central chemoreception
Authors: Guyenet Patrice G. , Stornetta Ruth L. , Bayliss Douglas A.
Published: February 2008

The ‘distributed chemoreception theory’ attributes the central chemoreflex (the stimulation of breathing by CNS acidification) to the cumulative effects of pH on multiple classes of respiratory neurons as well as on their tonic sources of drive. Opinions differ as to how many classes of pH‐sensitive neurons contribute to the central chemoreflex but the number of candidates is high and growing fast. The ‘specialized chemoreceptor theory’, endorsed here, attributes the chemoreflex to a limited number of specialized neurons. These neurons (the central chemoreceptors) would drive a respiratory pattern generator that is not or minimally activated by acidification. In this review we first describe the properties of the retrotrapezoid nucleus (RTN) and argue that this nucleus may contain the most important central chemoreceptors. Next, we subject the assumptions that underlie the distributed chemoreception theory to a critical analysis. We propose several explanations for the apparent contradiction between the two competing theories of central chemoreception. We attribute much of the current controversy to premature extrapolations of the effects of acidification on neurons recorded in vitro (chemosensitivity) and to a semantic confusion between chemosensitivity and chemoreception (the mechanism by which CO2 or pH activates breathing in vivo).
Covariant Glacial-Interglacial Dust Fluxes in the Equatorial Pacific and Antarctica
Authors: Winckler Gisela , Anderson Robert F. , Fleisher Martin Q. , McGee David , Mahowald Natalie
Published: February 2008

Dust plays a critical role in Earth's climate system and serves as a natural source of iron and other micronutrients to remote regions of the ocean. We have generated records of dust deposition over the past 500,000 years at three sites spanning the breadth of the equatorial Pacific Ocean. Equatorial Pacific dust fluxes are highly correlated with global ice volume and with dust fluxes to Antarctica, which suggests that dust generation in interhemispheric source regions exhibited a common response to climate change over late-Pleistocene glacial cycles. Our results provide quantitative constraints on the variability of aeolian iron supply to the equatorial Pacific Ocean and, more generally, on the potential contribution of dust to past climate change and to related changes in biogeochemical cycles.
Protein Synthesis and Neurotrophin-Dependent Structural Plasticity of Single Dendritic Spines
Authors: Tanaka Jun-ichi , Horiike Yoshihiro , Matsuzaki Masanori , Miyazaki Takashi , Ellis-Davies Graham C. R. , Kasai Haruo
Published: February 2008

Long-term potentiation (LTP) at glutamatergic synapses is considered to underlie learning and memory and is associated with the enlargement of dendritic spines. Because the consolidation of memory and LTP require protein synthesis, it is important to clarify how protein synthesis affects spine enlargement. In rat brain slices, the repetitive pairing of postsynaptic spikes and two-photon uncaging of glutamate at single spines (a spike-timing protocol) produced both immediate and gradual phases of spine enlargement in CA1 pyramidal neurons. The gradual enlargement was strongly dependent on protein synthesis and brain-derived neurotrophic factor (BDNF) action, often associated with spine twitching, and was induced specifically at the spines that were immediately enlarged by the synaptic stimulation. Thus, this spike-timing protocol is an efficient trigger for BDNF secretion and induces protein synthesis–dependent long-term enlargement at the level of single spines.
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Authors: Sreedharan Jemeen , Blair Ian P. , Tripathi Vineeta B. , Hu Xun , Vance Caroline , Rogelj Boris , Ackerley Steven , Durnall Jennifer C. , Williams Kelly L. , Buratti Emanuele , Baralle Francisco , de Belleroche Jacqueline , Mitchell J. Douglas , Leigh P. Nigel , Al-Chalabi Ammar , Miller Christopher C. , Nicholson Garth , Shaw Christopher E.
Published: February 2008

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of
TARDBP
in sporadic and familial ALS cases.
TARDBPM337V
segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the
TARDBP
locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.
Acute pseudoaneurysm of the femoral artery after repeated trauma in full-contact karate practice: Figure 1
Authors: Doiz E , Garrido F , Conejero R , García P , Fernández E
Published: February 2008

Traumatic pseudoaneurysms of the deep femoral artery are only encountered infrequently in sports medical literature. We present the case of a male who, after practising full-contact karate, experienced pain and oedema in the right thigh. The ultrasound results and the arteriography showed the presence of a pseudoaneurysm in a branch of the deep femoral artery. Traumatic pseudoaneurysms of the deep femoral artery are normally secondary to endovascular interventions or to mycotic infections in injecting drug users. The majority appear asymptomatically as a pulsatile mass, although on occasions clinical signs of compression (pain, neurological or venous symptoms) may occur or, if the aneurysm bursts, hypovolemic shock.
Injury trends in sanctioned mixed martial arts competition: a 5-year review from 2002 to 2007
Authors: Ngai K M , Levy F , Hsu E B
Published: February 2008

Background:

Professional mixed martial arts (MMA) competition is a full-contact sport that has risen rapidly in popularity in recent years. However, there is limited information regarding the incidence of competition injuries after sanctioning by an athletic commission.

Methods:

We conducted a retrospective cohort study to examine MMA injury patterns during a 5 year period after sanctioning in the state of Nevada. Data from all regulated MMA competitions during the study period from March 2002 to September 2007 (1270 fight exposures) was obtained. Injury odds ratios were calculated by conditional logistic regression on match outcome, age, weight, and fight experience, using a pair-matched case-control design (n = 464) and by multiple logistic regression on match outcome, age, fight experience, weight, combat minutes, and scheduled rounds.

Results:

During the 635 professional MMA matches, 300 of the 1270 athletes sustained documented injuries with an injury rate of 23.6 per 100 fight participations. Most common reported injuries were lacerations and upper limb injuries. Severe concussion rate was 15.4 per 1000 athlete exposures, or 3% of all matches. No deaths or critical sports-related injuries resulted from any of the regulated matches during the study period. Age, weight and fight experience did not statistically increase the likelihood of injuries after controlling for other covariates.

Conclusions:

Injury rates in regulated professional MMA competition are similar to other combat sports; the overall risk of critical sports-related injury seems to be low. Additional study is warranted to achieve a better understanding of injury trends and ways to further lower injury risk in MMA.
A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength
Authors: Myer Gregory , Brent Jensen , Ford Kevin , Hewett Timothy
Published: February 2008

Objectives:The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength.

Methods:Twenty-one (TMNT n=14: 15.4 ± 1.4 yrs, 170.5 ± 5.0 cm, 64.1 ± 8.5 kg; CTRL n =7: 16.0 ± 1.7 yrs, 173.4 ± 10.0 cm, 63.9 ± 5.3 kg; p>0.05) high school female volleyball players were recruited to participate in this study. Fourteen participated in TNMT protocol (2 X/wk) over a ten week period in addition to their standard off-season strength training (1X/wk). Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured prior to and after TNMT.

Results:A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% dominant leg: 46.6 ± 10.1 to 52.9 ± 11.4 ft-lbs and 17.1% in the non-dominant leg: 46.1 ± 10.4 to 54.0 ± 10.7 ft-lbs; p = 0.01). There was no difference in the control group in pre- versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p=0.57) or knee flexion (p=0.57) strength.

Conclusions:Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower extremity alignment and decrease loads resulting from increased trunk displacement during sports activities.
The Adventures of Sonic Hedgehog in Development and Repair. IV. Sonic hedgehog processing, secretion, and function in the stomach
Authors: Zavros Yana
Published: February 2008

Sonic hedgehog (Shh) is recognized as one of the main morphogens that regulates cell differentiation during early development of the stomach. In the adult stomach, Shh is expressed and secreted from the acid-producing parietal cells, where it is believed to play an essential role in gastric tissue homeostasis and normal differentiation of the epithelium. The present Themes article focuses on reviewing the literature and controversies surrounding the processing and secretion and the role of Shh in the adult stomach.
Functional evidence for purinergic inhibitory neuromuscular transmission in the mouse internal anal sphincter
Authors: McDonnell Bronagh , Hamilton Ross , Fong Miranda , Ward Sean M. , Keef Kathleen D.
Published: February 2008

The neurotransmitter(s) underlying nitric oxide synthase (NOS)-independent neural inhibition in the internal anal sphincter (IAS) is still uncertain. The present study investigated the role of purinergic transmission. Contractile and electrical responses to electrical field stimulation of nerves (0.1–5 Hz for 10–60 s) were recorded in strips of mouse IAS. A single stimulus generated a 28-mV fast inhibitory junction potential (IJP) and relaxation. The NOS inhibitor Nω-nitro-l-arginine (l-NNA) reduced the fast IJP duration by 20%. Repetitive stimulation at 2.5–5 Hz caused a more sustained IJP and sustained relaxation. l-NNA reduced relaxation at 1 Hz and the sustained IJP at 2.5–5 Hz. All other experiments were carried out in the presence of NOS blockade. IJPs and relaxation were significantly reduced by the P2 receptor antagonists 4-[[4-formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid (PPADS) (100 μM), by desensitization of P2Y receptors with adenosine 5′-[β-thio]diphosphate (ADP-βS) (10 μM), and by the selective P2Y1 receptor blocker 2′-deoxy- N6-methyl adenosine 3′,5′-diphosphate (MRS2179) (10 μM). Relaxation and IJPs were also significantly reduced by the K+ channel blocker apamin (1 μM). Removal of extracellular potassium (Ko) increased IJP amplitude to 205% of control, whereas return of Ko 30 min later hyperpolarized cells by 19 mV and reduced IJP amplitude to 50% of control. Exogenous ATP (3 mM) relaxed muscles in the presence of TTX (1 μM) and hyperpolarized cells by 15 mV. In conclusion, these data suggest that purinergic transmission significantly contributes to NOS-independent neural inhibition in the mouse IAS. P2Y1 receptors, as well as at least one other P2 receptor subtype, contribute to this pathway. Purinergic receptors activate apamin-sensitive K+ channels as well as other apamin-insensitive conductances leading to hyperpolarization and relaxation.
Moderate hypothermia increases the chance of spiral wave collision in favor of self-termination of ventricular tachycardia/fibrillation
Authors: Harada Masahide , Honjo Haruo , Yamazaki Masatoshi , Nakagawa Harumichi , Ishiguro Yuko S. , Okuno Yusuke , Ashihara Takashi , Sakuma Ichiro , Kamiya Kaichiro , Kodama Itsuo
Published: February 2008

In cardiac arrest due to ventricular fibrillation (VF), moderate hypothermia (MH, 33°C) has been shown to improve defibrillation success compared with normothermia (NR, 37°C) and severe hypothermia (SH, 30°C). The underlying mechanisms remain unclear. We hypothesized that MH might prevent reentrant excitations rotating around functional obstacles (rotors) that are responsible for the genesis of VF. In two-dimensional Langendorff-perfused rabbit hearts prepared by cryoablation ( n = 13), action potential signals were recorded by a high-resolution optical mapping system. During basic stimulation (2.5–5.0 Hz), MH and SH caused significant prolongation of action potential duration and significant reduction of conduction velocity. Wavelength was unchanged at MH, whereas it was shortened significantly at SH at higher stimulation frequencies (4.0–5.0 Hz). The duration of direct current stimulation-induced ventricular tachycardia (VT)/VF was reduced dramatically at MH compared with NR and SH. The spiral wave (SW) excitations documented during VT at NR were by and large organized, whereas those during VT/VF at MH and SH were characterized by disorganization with frequent breakup. Phase maps during VT/VF at MH showed a higher incidence of SW collision (mutual annihilation or exit from the anatomical boundaries), which caused a temporal disappearance of phase singularity points (PS-0), compared with that at NR and SH. There was an inverse relation between PS-0 period in the observation area and VT/VF duration. MH data points were located in a longer PS-0 period and a shorter VT/VF duration zone compared with SH. MH causes a modification of SW dynamics, leading to an increase in the chance of SW collision in favor of self-termination of VT/VF.
An increase of late sodium current induces delayed afterdepolarizations and sustained triggered activity in atrial myocytes
Authors: Song Yejia , Shryock John C. , Belardinelli Luiz
Published: February 2008

This study determined the role of a slowly inactivating component of sodium current ( INa), late INa, to induce delayed afterdepolarizations (DADs) and triggered activity. We hypothesized that an increase of late INa may induce not only early afterdepolarizations (EADs), but also intracellular calcium overload and DADs. Guinea pig atrial myocytes were studied using the whole cell patch-clamp technique. Anemone toxin II (ATX-II) (5–10 nmol/l) was used to enhance late INa. Ranolazine (10 μmol/l) and TTX (2 μmol/l) were applied to block ATX-II-induced late INa. ATX-II prolonged action potential duration and induced EADs. In the continuous presence of ATX-II, following the appearance of EADs, both DADs and sustained triggered activity occurred. Triggered activity was abolished and DADs were reduced by either ranolazine or TTX. Consistent with induction of DADs, ATX-II induced the transient inward current ( ITI). The amplitude of ITI was significantly reduced by ranolazine. ATX-II induced only EADs, but no DADs, in the presence of the sodium-calcium exchange inhibitor KB-R7943 or the sarcoplasmic reticulum calcium release channel inhibitor ryanodine, or when the calcium chelator EGTA or BAPTA was included in the pipette solution. In conclusion, an increase of late INa, in addition to inducing EADs, can cause cellular calcium overload and induce DADs and sustained triggered activity in atrial myocytes. The data reveal that an increase of late INa is a novel mechanism for initiation of atrial arrhythmic activity.
The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells
Authors: Brown Sean G. , Gallacher Michael , Olver Richard E. , Wilson Stuart M.
Published: February 2008

Analysis of membrane currents recorded from hormone-deprived H441 cells showed that the membrane potential ( Vm) in single cells (approximately −80 mV) was unaffected by lowering [Na+]o or [Cl−]o, indicating that cellular Na+ and Cl− conductances ( GNa and GCl, respectively) are negligible. Although insulin (20 nM, ∼24 h) and dexamethasone (0.2 μM, ∼24 h) both depolarized Vm by ∼20 mV, the response to insulin reflected a rise in GCl mediated via phosphatidylinositol 3-kinase (PI3K) whereas dexamethasone acted by inducing a serum- and glucocorticoid-regulated kinase 1 (SGK1)-dependent rise in GNa. Although insulin stimulation/PI3K-P110α expression did not directly increase GNa, these maneuvers augmented the dexamethasone-induced conductance. The glucocorticoid/SGK1-induced GNa in single cells discriminated poorly between Na+ and K+ ( PNa/ PK ∼0.6), was insensitive to amiloride (1 mM), but was partially blocked by LaCl3 (La3+; 1 mM, ∼80%), pimozide (0.1 mM, ∼40%), and dichlorobenzamil (15 μM, ∼15%). Cells growing as small groups, on the other hand, expressed an amiloride-sensitive (10 μM), selective GNa that displayed the same pattern of hormonal regulation as the nonselective conductance in single cells. These data therefore 1) confirm that H441 cells can express selective or nonselective GNa ( 14 , 48 ), 2) show that these conductances are both induced by glucocorticoids/SGK1 and subject to PI3K-dependent regulation, and 3) establish that cell-cell contact is vitally important to the development of Na+ selectivity and amiloride sensitivity.
Double Colorectal Cancer Only Diagnosed by Computed Tomographic Colonography
Authors: Nagata Koichi , Endo Shungo , Tatsukawa Kishiko , Kudo Shin-ei
Published: February 2008

A 58-year-old woman presented to her physician with rectal bleeding and intermittent diarrhea. Optical colonoscopy revealed a bulky tumor which was diagnosed as rectal cancer. She was referred to our institution for further evaluation and treatment. Slim optical colonoscopy showed an obstructive cancer in the rectosigmoid junction and no information of the proximal side of the obstruction. The patient then underwent computed tomographic (CT) colonography for further evaluation of the proximal side. Three-dimensional endoluminal ‘fly-through’ images revealed another protruded lesion in the proximal side of the obstruction. Diagnosis of synchronous double cancer was made by CT colonography. This CT data was not only used to create three-dimensional images but also to decide on a preoperative clinical staging. Laparoscopy-assisted high anterior resection was performed and T3 rectal cancer and T1 sigmoid colon cancer were confirmed in the resected specimen. Follow-up optical colonoscopy revealed no other tumors. CT colonography has recently become a popular preoperative examination tool with significant improvement in quality of image due to a rapid progress in computer technology. CT colonography correctly showed synchronous double cancer in our case and provided crucial information for planning surgery. We recommend that CT colonography should be used for evaluating the proximal side of obstructive colorectal cancer.
Prohepcidin Levels in Refractory Anaemia Caused by Lead Poisoning
Authors: Arnold Jayantha , Busbridge Mark , Sangwaiya Arvind , Bhatkal Bharati , Paskaran Parth , Pal Arabinda , Geoghegan Frank , Kealey Terence
Published: February 2008

Recent research evidence suggests a central role for hepcidin in iron homeostasis. Hepcidin is a hormone synthesized in the liver. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. A 38-year-old female who presented with recurrent abdominal pain was found to have raised urinary porphyrins and a blood lead level of 779 µg/l. Her haemoglobin level was 8.3 g/dl. Her MCV was normal. Serum ferritin, B12 and folate were normal. Her serum prohepcidin level was 2,489 ng/ml (normal <450 ng/ml ). To our knowledge, this is the first report of raised prohepcidin levels in a patient with anaemia of chronic disease resulting from lead poisoning.
Morphology and Epidermal Thickness of Normal Skin Imaged by Optical Coherence Tomography
Authors: Mogensen Mette , Morsy Hanan A. , Thrane Lars , Jemec Gregor B.E.
Published: February 2008

Background: Optical coherence tomography (OCT) is an optical imaging technology with a potential in the non-invasive diagnosis of skin cancer. To identify skin pathologies using OCT, it is of prime importance to establish baseline morphological features of normal skin. Aims: The aim of this study is to describe normal skin morphology using OCT and polarization-sensitive OCT (PS-OCT), which is a way of representing birefringent tissue such as collagen in OCT images. Anatomical locations in 20 healthy volunteers were imaged, and epidermal thickness (ET) was measured and compared to age, gender and skin colour. Methods: OCT imaging is based on infrared light reflection/backscatter from tissue. PS-OCT detects birefringence of tissue. Imaging was performed in 12 skin regions. ET was calculated from the OCT images. Results: Normal skin has a layered structure. Layering is less pronounced in adults. In glabrous skin the stratum corneum is visible. Children had larger ET (p < 0.0001). Age had a negative correlation with ET (p < 0.05). No gender- or skin-type-related differences in ET were found. Conclusion: This study contributes to understanding OCT and PS-OCT images of normal skin and indicates that OCT can be used for both the qualitative and quantitative assessment of skin.
Efficacy in Patients with Dose Reduction in Combination Therapy of Peginterferon and Ribavirin for Chronic Hepatitis C
Authors: Arase Yasuji , Suzuki Fumitaka , Sezaki Hitomi , Kawamura Yusuke , Suzuki Yoshiyuki , Kobayashi Masahiro , Akuta Norio , Hosaka Tetsuya , Yatsuji Hiromi , Hirakawa Miharu , Kobayashi Mariko , Ikeda Kenji , Kumada Hiromitsu
Published: February 2008

Objective: The aim of this study was to elucidate efficacy after dose reduction in combination therapy of peginterferon and ribavirin for chronic hepatitis C. Methods: Inclusion criteria were hepatitis C virus (HCV) genotype 1b, serum HCV RNA level of ≧100 KIU/ml, dose reduction of peginterferon and/or ribavirin between the first 4 weeks and 20 weeks after the initiation of treatment. 164 patients were enrolled in this retrospective cohort study. Predictive factors for sustained viral response (SVR) after dose reduction were examined. Results: Out of the 146 patients treated with dose reduction, 57 had SVR. Multivariate analysis showed that SVR occurred when serum HCV RNA at the time of dose reduction was negative (p < 0.001) and total ribavirin dose was ≧100% of the anticipated total dose (p < 0.001). 57% (55/97) of patients with undetectable serum HCV RNA at the time of dose reduction had SVR. In contrast, only 4% (2/49) of patients with detectable serum HCV RNA at the time of dose reduction had SVR. Conclusions: On dose reduction of combination therapy for chronic hepatitis C, undetectable serum HCV RNA at the time of dose reduction and attainment of the total ribavirin dose of ≧100% enhance SVR.
Fasting and Caloric Restriction Increases mRNA Concentrations of Novel Organic Cation Transporter-2 and Carnitine Concentrations in Rat Tissues
Authors: Luci Sebastian , Hirche Frank , Eder Klaus
Published: February 2008

Background: Recently, we have shown that activation of peroxisome proliferator-activated receptor (PPAR)-α by clofibrate leads to an upregulation of novel organic cation transporter (OCTN)-2, a carnitine transporter, and in turn increases the carnitine concentration in the liver of rats. In this study, we tested the hypothesis that fasting and caloric restriction, conditions under which PPARα activation also occurs, cause similar effects. Methods: Three groups of rats received the diet either ad libitum (control rats) or 10.5 g diet/day (70% of energy requirement for maintenance, E70 rats) or 6 g diet/day (40% of energy requirement for maintenance, E40 rats) for 10 days. A 4th group received the diet ad libitum for 9 days and was then fasted for 24 h (fasted rats). Results: Fasted and calorie-restricted rats had increased mRNA concentrations of acyl-CoA oxidase and carnitine palmitoyltransferase-1 in the liver, heart and kidneys compared to control rats (p < 0.05), indicative of activation of PPARα in these tissues. E70 rats had increased OCTN2 mRNA concentrations in liver (2.6-fold) and kidneys (1.5-fold) and increased total carnitine concentrations in these tissues compared to control rats. E40 rats had increased OCTN2 mRNA concentrations in the liver (3.3-fold), skeletal muscle (2.2-fold), heart (2.3-fold) and kidneys (3.5-fold) and increased total carnitine concentrations in these four tissues compared to control rats. Fasted rats had increased OCTN2 mRNA concentrations in the liver (4.0-fold), heart (2.1-fold) and kidneys (2.0-fold) and increased total carnitine concentrations in these three tissues (p < 0.05). Conclusion: The study shows that fasting and caloric restriction lead to an upregulation of OCTN2 in several tissues, probably mediated by activation of PPARα. Increased tissue carnitine concentrations in fasted and calorie-restricted rats might be at least in part due to increased uptake of carnitine by OCTN2.
Early Migration of Sacral Neural Crest Cells in Mouse Embryos
Authors: Dong M. , Wang X. , Chan A.K. , Burns A.J. , Chan W.Y.
Published: February 2008

Background: Neural crest cells (NCCs) are a group of multipotent embryonic cells which originate from the neural tube (developing central nervous system) and are capable of migrating to different locations within the embryo to form a variety of derivatives. In the avian, NCCs in the sacral region (sacral NCCs) have been shown to be able to give rise to neurons and glia of the hindgut. By using quail-chick chimeras, the complete migratory pathway of sacral NCCs from their origin to their final locations in the hindgut has been mapped. However, in mammals, information on sacral NCC migration is still scarce. Aims: In the present study, we used in situ cell labeling with wheat germ agglutinin gold conjugates or DiI as cell markers, whole embryo culture and histochemical staining to determine the early spatiotemporal migration of sacral NCCs in normal mouse embryos. Results and Conclusions: It was found that most of the sacral NCCs at the neuraxis caudal to the 24th somite (postumbilical level) started migration from the dorsal part of the neural tube at E9.5 and then migrated dorsoventrally in the pelvic mesenchyme between the neural tube and the somite. Many of the sacral NCCs resided in the region of the dorsal root ganglia on each side of the neural tube, while some of them continued to migrate dorsoventrally to reach the region around the dorsal aorta by E11.0. Hence, sacral NCCs enter the hindgut well after E11.0. Further studies will be carried out to find out the entire migratory pathway of sacral NCCs in the mouse prior to their entry to the hindgut.
Body Mass Index and Poststroke Mortality
Authors: Olsen Tom Skyhøj , Dehlendorff Christian , Petersen Hans Gregers , Andersen Klaus Kaae
Published: February 2008

Background: Obesity is an established cardiovascular risk factor. We studied the association between body mass index (BMI) and all-cause mortality after stroke. Methods: A registry started in 2001 with the aim to register all hospitalized stroke patients in Denmark now includes 21,884 patients in whom BMI was recorded. There are five BMI groups: underweight (BMI <18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese (BMI 30.0–34.9) and severely obese (BMI ≧35). All patients underwent an evaluation including stroke severity, computed tomography, and cardiovascular risk factors. Survival was followed up to 5 years after stroke (median 1.5 years). Independent predictors of death were identified by means of a survival model based on 13,242 individuals with a complete data set. Results: Compared to normal-weight patients, mortality was lower in overweight [hazard rate (HR) 0.73, 95% CI 0.66–0.81], obese (HR 0.84, 95% CI 0.73–0.98) and severely obese stroke patients (HR 0.84, 95% CI 0.64–1.10), while mortality was higher in underweight patients (HR 1.63, 95% CI 1.41–1.90). Conclusions: Poststroke mortality is inversely related to BMI: overweight and obese stroke patients have a lower poststroke mortality rate than normal-weight and underweight patients.