bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferation and adhesion of periodontal ligament cells on synthetic biominerals
Authors: Hatakeyama J , Hatakeyama Y , Takahashi I , Suzuki O , Sasano Y
Published: December 2006

Objective:  Hydroxiapatite (HA) has been suggested as a useful biomaterial to support the regeneration of tissues. In this study, we investigated the adhesion of periodontal ligament (PDL) cells on octacalcium phosphate (OCP) and its hydrolyzed apatitic product (HL), which are known precursors of HA.

Methods:  Rat PDL cells were cultured on OCP or HL‐coated dishes. Cell proliferation and adhesion and mRNA expression of collagen I, fibronectin integrin subunits were examined. Cell adhesion inhibition assays were carried out by GRGDSPK (Gly‐Arg‐Gly‐Asp‐Ser‐Pro‐Lys).

Results:  In early culture period, the cell number of PDL cells was lower on OCP and HL than that on control without any coating. However, the cell number on OCP or HL caught up with control later period. mRNA expression level of collagen I and fibronectin on OCP and HL were similar among OCP HL and control, although they differed early in the culture period. Integrin subunits were expressed on both OCP and HL as well as on control. Cell adhesion was inhibited by RGD inhibitor peptide.

Conclusion:  Our findings indicated that rat PDL cells produce collagen I and fibronectin on OCP and HL, and then show increased cell numbers depending on adhesion to the matrices through integrins.
Reductive nitrosylation and peroxynitrite‐mediated oxidation of heme–hemopexin
Authors: Ascenzi Paolo , Bocedi Alessio , Antonini Giovanni , Bolognesi Martino , Fasano Mauro
Published: December 2006

Hemopexin (HPX), which serves as a scavenger and transporter of toxic plasma heme, has been postulated to play a key role in the homeostasis of NO. In fact, HPX–heme(II) reversibly binds NO and facilitates NO scavenging by O2. HPX–heme is formed by two four‐bladed β‐propeller domains. The heme is bound between the two β‐propeller domains, residues His213 and His266 coordinate the heme iron atom. HPX–heme displays structural features of heme‐proteins endowed with (pseudo‐)enzymatic activities. In this study, the kinetics of rabbit HPX–heme(III) reductive nitrosylation and peroxynitrite‐mediated oxidation of HPX–heme(II)–NO are reported. In the presence of excess NO, HPX–heme(III) is converted to HPX–heme(II)–NO by reductive nitrosylation. The second‐order rate constant for HPX–heme(III) reductive nitrosylation is (1.3 ± 0.1) × 101 m−1·s−1, at pH 7.0 and 10.0 °C. NO binding to HPX–heme(III) is rate limiting. In the absence and presence of CO2 (1.2 × 10−3 m), excess peroxynitrite reacts with HPX–heme(II)–NO (2.6 × 10−6 m) leading to HPX–heme(III) and NO, via the transient HPX–heme(III)–NO species. Values of the second‐order rate constant for HPX–heme(III)–NO formation are (8.6 ± 0.8) × 104 and (1.2 ± 0.2) × 106 m−1·s−1 in the absence and presence of CO2, respectively, at pH 7.0 and 10.0 °C. The CO2‐independent value of the first‐order rate constant for HPX–heme(III)–NO denitrosylation is (4.3 ± 0.4) × 10−1 s−1, at pH 7.0 and 10.0 °C. HPX–heme(III)–NO denitrosylation is rate limiting. HPX–heme(II)–NO appears to act as an efficient scavenger of peroxynitrite and of strong oxidants and nitrating species following the reaction of peroxynitrite with CO2 (e.g. ONOOC(O)O–, CO3–, and NO2).
The Induction of CYP1A2, CYP2D6 and CYP3A4 by Six Trade Herbal Products in Cultured Primary Human Hepatocytes
Authors: Hellum Bent H. , Hu Zhuohan , Nilsen Odd Georg
Published: December 2006

Abstract: The aim of this study was to evaluate thein vitroinductive potential of six commonly used trade herbal products on CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Herbal components were extracted from the trade products in a way that ensured a composition equal to that present in the original product. Primary human hepatocytes and specific CYP substrates were used. Classic inducers were used as positive controls and herbal extracts were added inin vivo‐relevant concentrations. Metabolites were determined by high performance liquid chromatography (HPLC). St. John's wort and common valerian were the strongest inducing herbs. In addition to induction of CYP3A4 by St. John's wort, common valerian andGinkgo bilobaincreased the activity of CYP3A4 and 2D6 and CYP1A2 and 2D6, respectively. A general inhibitory potential was observed for horse chestnut,Echinacea purpureaand common sage. St. John's wort inhibited CYP3A4 metabolism at the highest applied concentration. Horse chestnut might be a herb with high inhibition potentialsin vivoand should be explored further at lower concentrations. We show for the first time thatG. bilobamay exert opposite and biphasic effects on CYP1A2 and CYP2D6 metabolism. Induction of CYP1A2 and inhibition of CYP2D6 were found at low concentrations; the opposite was observed at high concentrations. CYP2D6 activity, regarded generally as non‐inducible, was increased by exposure to common valerian (linear to dose) andG. biloba (highest concentration). An allosteric activation is suggested. From the data obtained,G. biloba, common valerian and St. John's wort are suggested as candidates for clinically significant CYP interactionsin vivo.
Policies and Opportunities for Physical Activity in Middle School Environments
Authors: Young Deborah R. , Felton Gwen M. , Grieser Mira , Elder John P. , Johnson Carolyn , Lee Jung‐Sun , Kubik Martha Y.
Published: December 2006

Background:  This study examined physical activity opportunities and barriers at 36 geographically diverse middle schools participating in the Trial of Activity for Adolescent Girls.

Methods:  Principals, physical education and health education department heads, and program leaders were interviewed to assess policies and instructional practices that support physical activity.

Results:  Schools provided approximately 110 hours per year in physical education instruction. Approximately 20% of students walked or bicycled to school. Eighty‐three percent of schools offered interscholastic sports and 69% offered intramural sports. Most schools offered programs for girls, but on average, only 24 girls (∼5%) in the schools attended any programs. Only 25% of schools allowed after school free play. An overall score created to assess school environmental support for physical activity indicated that, on average, schools met 6.7 items of 10 items. Free/reduced lunch program participation versus not (p = .04), perceived priority of physical education instruction over coaching (p = .02), and safety for walking/bicycling to school (p = .02) predicted environmental support score.

Conclusions:  Schools have policies and practices that support physical activity, although unfavorable practices exist. Schools must work with community partners and officials to provide environments that optimally support physical activity, especially schools that serve low‐income students.
Oxygen exchange in muscle of young and old rats: muscle–vascular–pulmonary coupling
Authors: Poole David C. , Ferreira Leonardo F.
Published: December 2006

Sustained performance of muscular exercise is contingent upon increasing muscle O2 delivery (
; the product of blood flow and arterial O2 content, i.e.
) and utilization (
) rapidly at exercise onset and sustaining necessary conductive and diffusive O2 fluxes throughout exercise. A tight co‐ordination of pulmonary, cardiovascular and muscle system responses is therefore required to prevent muscle microvascular O2 pressures (PmvO2) from falling to levels that impair blood–muscle O2 exchange and/or impact metabolic control and reduce exercise tolerance. Microvascular O2 pressures are determined by the balance between
and
, and emerging evidence indicates that this balance is regulated differently across muscle fibre types and also in aged muscle. Moreover, disease states such as diabetes (type I and II) and chronic heart failure (CHF) also impact PmvO2. This brief review primarily examines evidence obtained in animals that ageing: (1) redistributes exercising
away from highly oxidative muscles and muscle fibres; (2) alters muscle capillary haemodynamics; and (3) reduces the O2 pressure head within the microcirculation (PmvO2) that serves to facilitate blood–muscle O2 transfer. In many respects, these alterations found in healthy ageing animals bear a striking resemblance to those present in some chronic diseases (e.g. diabetes, CHF) and may help explain the compromised exercise tolerance present in aged individuals. Putative mechanistic insights are explored within the context of current knowledge and future investigative approaches.
Human cerebral autoregulation before, during and after spaceflight
Authors: Iwasaki Ken‐ichi , Levine Benjamin D. , Zhang Rong , Zuckerman Julie H. , Pawelczyk James A. , Diedrich André , Ertl Andrew C. , Cox James F. , Cooke William H. , Giller Cole A. , Ray Chester A. , Lane Lynda D. , Buckey Jay C. , Baisch Friedhelm J. , Eckberg Dwain L. , Robertson David , Biaggioni Italo , Blomqvist C. Gunnar
Published: December 2006

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head‐down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts ∼72 and 23 days before, after 1 and 2 weeks in space (n= 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat‐by‐beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low‐ (0.02–0.07 Hz), low‐ (0.07–0.20 Hz) and high‐frequency (0.20–0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (±s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, −4 ± 3 cm s−1 after versus−14 ± 3 cm s−1 before, P= 0.001; and percentage, −8.0 ± 4.8% after versus−24.8 ± 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low‐frequency gain decreased significantly (P < 0.05) by 26, 23 and 27% after 1 and 2 weeks in space and on landing day, respectively, compared with preflight values, which is also consistent with improved autoregulation. We conclude that human cerebral autoregulation is preserved, and possibly even improved, by short‐duration spaceflight.
Mechanical load plays little role in contraction‐mediated glucose transport in mouse skeletal muscle
Authors: Sandström Marie E. , Zhang Shi‐Jin , Westerblad Håkan , Katz Abram
Published: December 2006

The factors responsible for control of glucose transport during exercise are not fully understood. We investigated the role of mechanical load in contraction‐mediated glucose transport in an isolated muscle preparation. Mouse extensor digitorum longus muscles were stimulated with repeated contractions for 10 min with or without N‐benzyl‐p‐toluene sulphonamide (BTS, an inhibitor of myosin II ATPase) to block crossbridge activity. BTS inhibited force production during repeated contraction to ∼5% of control. In contrast, BTS had little effect on glucose transport in the basal state (control = 0.55 ± 0.04; BTS = 0.47 ± 0.09 μmol (20 min)−1 ml−1) or after contraction (control = 2.27 ± 0.15; BTS = 2.10 ± 0.16 μmol (20 min)−1 ml−1). BTS did not significantly alter the contraction‐mediated changes in high‐energy phosphates, glutathione status (a measure of oxidant status) or AMP‐activated protein kinase activity. In conclusion, these data show that mechanical load plays little role in contraction‐mediated glucose transport. Instead, it is likely that the increased glucose transport during contraction is a consequence of the increase in myoplasmic Ca2+ and the subsequent alterations in metabolism, e.g. increased energy turnover and production of reactive oxygen species.
Voltage‐dependent calcium channels of dog basilar artery
Authors: Nikitina Elena , Zhang Zhen‐Du , Kawashima Ayako , Jahromi Babak S. , Bouryi Vitali A. , Takahashi Masataka , Xie An , Macdonald R. Loch
Published: December 2006

Electrophysiological and molecular characteristics of voltage‐dependent calcium (Ca2+) channels were studied using whole‐cell patch clamp, polymerase chain reaction and Western blotting in smooth muscle cells freshly isolated from dog basilar artery. Inward currents evoked by depolarizing steps from a holding potential of –50 or –90 mV in 10 mm barium consisted of low‐ (LVA) and high‐voltage activated (HVA) components. LVA current comprised more than half of total current in 24 (12%) of 203 cells and less than 10% of total current in 52 (26%) cells. The remaining cells (127 cells, 62%) had LVA currents between one tenth and one half of total current. LVA current was rapidly inactivating, slowly deactivating, inhibited by high doses of nimodipine and mibefradil (> 0.3 μm), not affected by ω‐agatoxin GVIA (γ100 nm), ω‐conotoxin IVA (1 μm) or SNX‐482 (200 nm) and probably carried by T‐type Ca2+ channels based on the presence of messenger ribonucleic acid (mRNA) and protein for Cav3.1 and Cav3.3α1 subunits of these channels. LVA currents exhibited window current with a maximum of 13% of the LVA current at –37.4 mV. HVA current was slowly inactivating and rapidly deactivating. It was inhibited by nimodipine (IC50= 0.018 μm), mibefradil (IC50= 0.39 μm) and ω‐conotoxin IV (1 μm). Smooth muscle cells also contained mRNA and protein for L‐ (Cav1.2 and Cav1.3), N‐ (Cav2.2) and T‐type (Cav3.1 and Cav3.3) α1 Ca2+ channel subunits. Confocal microscopy showed Cav1.2 and Cav1.3 (L‐type), Cav2.2 (N‐type) and Cav3.1 and Cav3.3 (T‐type) protein in smooth muscle cells. Relaxation of intact arteries under isometric tension in vitro to nimodipine (1 μm) and mibefradil (1 μm) but not to ω‐agatoxin GVIA (100 nm), ω‐conotoxin IVA (1 μm) or SNX‐482 (1 μm) confirmed the functional significance of L‐ and T‐type voltage‐dependent Ca2+ channel subtypes but not N‐type. These results show that dog basilar artery smooth muscle cells express functional voltage‐dependent Ca2+ channels of multiple types.
DYNAMICAL CASIMIR EFFECT IN A KICKED BOX
Authors: SORGE FRANCESCO
Published: December 2006

We investigate the Dynamical Casimir Effect (DCE) in the case of a scalar field enclosed in a box which undergoes a phase of strong acceleration (a kick) during its motion. Following a general-relativistic approach, we describe the acceleration field as a time-dependent space–time metric in the frame of a comoving, noninertial observer. Assuming a nonrelativistic motion of the box, we perturbatively solve the Klein–Gordon equation for the matter field, evaluating the β-Bogolubov coefficients, related to the particle creation. We show that, after the kick, a (small) number of created quanta is found inside the box. The resulting spectrum carries, in principle, information about the details of the box acceleration phase. The present approach can serve to shed light on the close relationship between DCE and Unruh–Hawking effect.
THE INTENSITY CORRELATION TIME OF A SINGLE-MODE LASER DRIVEN BY BOTH COLORED PUMP NOISE WITH SIGNAL MODULATION AND QUANTUM NOISE WITH CROSS-CORRELATION BETWEEN ITS REAL AND IMAGINARY PARTS
Authors: CHENG QING-HUA , XU DA-HAI , CAO LI , WU DA-JIN
Published: December 2006

Using linear approximation method, we calculate the intensity correlation time of a single-mode laser driven by both colored pump noise with signal modulation and quantum noise with cross-correlation between its real and imaginary parts, and analyze the influence of the signal, noise and its cross-correlation form on the statistical fluctuation of the laser system. We detect that the "color" of pump noise is an important factor that affects the statistical fluctuation of the laser system. When the colored pump noise is short time correlation, within a determinate parameter range, the intensity correlation time can be prolonged, and the statistical fluctuation of the laser system can be restrained by increasing the amplitude of modulation signal. The specific frequency of input signal will result in intensity correlation time to appear maximum, and the statistical fluctuation of the laser system is least here. When the colored pump noise is long time correlation, within a determinate parameter range, the intensity correlation time can be also prolonged by increasing the frequency of modulation signal and decreasing its amplitude, and the statistical fluctuation of the laser system will decrease. In particular, when the intensity of quantum noise increases and the cross-correlation between its real and imaginary parts enhance, the intensity correlation time will prolong, and the statistical fluctuation of the laser system is restrained.
ONE-STEP GENERATION OF GREENBERGER–HORNE–ZEILINGER STATES IN SUPERCONDUCTING QUANTUM INTERFERENCE DEVICES VIA RAMAN INTERACTION
Authors: ZHAN ZHI-MING
Published: December 2006

We put forward a fast scheme for one-step generation of maximally entangled Greenberger–Horne–Zeilinger (GHZ) states by superconducting quantum interference devices (SQUIDs) in cavity via Raman interaction. The scheme only requires a quantized cavity field and classical microwave pulses. One of the key advantages of our Raman-interaction scheme is that an improvement of overcoming decoherence for the preparation of the desired GHZ states can be achieved.
ROBUST REPRESENTATION OF 3D FACES FOR RECOGNITION
Authors: BELÉN MORENO A. , SÁNCHEZ ÁNGEL , FRÍAS-MARTÍNEZ ENRIQUE
Published: December 2006

Automatic face recognition is becoming increasingly important due to the security applications derived from it. Although the facial recognition problem has focused on 2D images, recently, due to the proliferation of 3D scanning hardware, 3D face recognition has become a feasible application. This 3D approach does not need any color information. In this way, it has the following main advantages in comparison to more traditional 2D approaches: (1) being robust under lighting variations and (2) providing more relevant information. In this paper we present a new 3D facial model based on the curvature properties of the surface. Our system is able to detect the subset of the characteristics of the face with higher discrimination power from a large set. The robustness of the model is tested by comparing recognition rates using both controlled and noncontrolled environments regarding facial expressions and facial rotations. The difference between the recognition rates of the two environments of only 5% proves that the model has a high degree of robustness against pose and facial expressions. We consider that this robustness is enough to implement facial recognition applications, which can achieve up to 91% correct recognition rate. A publish 3D face database containing face rotations and expressions has been created to achieve the recognition experiments.
RUNWAY DETECTING AND TRACKING OF AN UNMANNED AERIAL LANDING VEHICLE BASED ON VISION
Authors: WANG HONGQUN , PENG JIAXIONG , LI LINGLING
Published: December 2006

When a monocular vision-based unmanned aerial vehicle (UAV) is flown to the final approach to intercept the glide slope, the position and orientation of the airport runway in the image must be detected accurately for a host of suitable procedures to be followed. The approaching marking on the runway is showed as some white spots of high intensity as well as the complicated backgrounds. In our paper, we use pin-hole perspective principle, the constraint condition of the rectangle in inertial space, the front shot constraint condition of the target, as well as the clustering algorithm to identify the runway and output its position and orientation in image space. The results of the experiments show that by this algorithm, even from a place far away from the runway with marks being unclear, effective detection is possible. After all, single-frame detection errors exist, so we extend the basic runway-detection algorithm to the runway tracking. A full filtering strategy using particle filter can guard against potentially catastrophic results and improve the detection rate. Apparently, the whole algorithm of our paper can be treated as a special vision sensor for landing equipment of UAV.
FAST NUMERICAL INTEGRATION FOR SIMULATION OF STRUCTURED POPULATION EQUATIONS
Authors: FISCHER T. , LOGASHENKO D. , KIRKILIONIS M. , WITTUM G.
Published: December 2006

In this paper, we consider the fast computation of integral terms arising in simulations of structured populations modeled by integro-differential equations. This is of enormous relevance for demographic studies in which populations are structured by a large number of variables (often called i-states) like age, gender, income etc. This holds equally for applications in ecology and biotechnology. In this paper we will concentrate on an example describing microbial growth. For this class of problems we apply the panel clustering method that has str almost linear complexity for many integral kernels that are of interest in the field of biology. We further present the primitive function method as an improved version of the panel clustering for the case that the kernel function is non-smooth on hypersurfaces. We compare these methods with a conventional numerical integration algorithm, all used in-side standard discretization schemes for the complete system of integro-differential equations.
OPTIMAL CONTROL OF CRYSTALLIZATION PROCESSES
Authors: GÖTZ THOMAS , PINNAU RENE , STRUCKMEIER JENS
Published: December 2006

In this paper an optimal control problem for polymer crystallization is investigated. The crystallization is described by a non-isothermal Avrami–Kolmogorov model and the temperature at the boundary of the domain serves as control variable. The cost functional takes into account the spatial variation of the crystallinity and the final degree of crystallization. This results in a boundary control problem for a parabolic equation coupled with two ordinary differential equations, which is treated by an adjoint variable approach. We prove the existence and uniqueness of solutions to the state system as well as the existence of a minimizer for the cost functional under consideration. The adjoint system is derived and we use a steepest descent algorithm to solve the problem numerically. Numerical simulations illustrate the applicability and performance of the optimization algorithm.
Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney
Authors: Piotrkowski Barbara , Fraga Cesar G. , de Cavanagh Elena M. V.
Published: December 2006

The renal and cardiac benefits of renin-angiotensin system (RAS) inhibition in hypertension exceed those attributable to blood pressure reduction, and seem to involve mitochondrial function changes. To investigate whether mitochondrial changes associated with RAS inhibition are related to changes in nitric oxide (NO) metabolism, four groups of male Wistar rats were treated during 2 wk with a RAS inhibitor, enalapril (10 mg·kg−1·day−1; Enal), or a NO synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME) (1 mg·kg−1·day−1), or both (Enal+l-NAME), or were untreated (control). Blood pressure and body weight were lower in Enal than in control. Electron transfer through complexes I to III and cytochrome oxidase activity were significantly lower, and uncoupling protein-2 content was significantly higher in kidney mitochondria isolated from Enal than in those from control. All of these changes were prevented by l-NAME cotreatment and were accompanied by a higher production/bioavailability of kidney NO. l-NAME abolished mitochondrial NOS activity but failed to inhibit extra-mitochondrial kidney NOS, underscoring the relevance of mitochondrial NO in those effects of enalapril that were suppressed by l-NAME cotreatment. In Enal, kidney mitochondria H2O2production rate and MnSOD activity were significantly lower than in control, and these effects were not prevented by l-NAME cotreatment. These findings may clarify the role of NO in the interactions between RAS and mitochondrial metabolism and can help to unravel the mechanisms involved in renal protection by RAS inhibitors.
A kinetic model of bone marrow neutrophil production that characterizes late phenotypic maturation
Authors: Orr Yishay , Wilson David P. , Taylor Jude M. , Bannon Paul G. , Geczy Carolyn , Davenport Miles P. , Kritharides Leonard
Published: December 2006

Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic maturation time and releasing younger neutrophils; however, the kinetics of this change in maturation time remains unknown. We propose a kinetic model that examines the rate of change in neutrophil average age at exit from the bone marrow during active mobilization to quantify this response and use this model to examine the temporal profile of late neutrophil phenotypic maturation. Total and CD10−/CD16lowcirculating neutrophils were quantified in cardiac surgery patients during extracorporeal circulation (ECC). Net growth in the circulating neutrophil pool occurred during the procedural (0.04 ± 0.02 × 109·l−1·min−1), warming (0.14 ± 0.02 × 109·l−1·min−1), and weaning (0.12 ± 0.06 × 109·l−1·min−1) phases of ECC. When applied to our differential equation mathematical model, these results predict that neutrophil average age at exit from the bone marrow decreased continually during ECC, resulting in average neutrophil release 8.44 ± 2.20 h earlier during the weaning phase than at the beginning of ECC sampling. Modeling of concurrent changes in CD10−/CD16lowneutrophil numbers indicates that CD10 expression is directly related to neutrophil mean age and predicts that the proportion of mobilizable postmitotic neutrophils that are CD10+increases from 64 to 81% during these sampled 8.4 h of maturation.
Optimal electrode placement for noninvasive electrical stimulation of human abdominal muscles
Authors: Lim Julianne , Gorman Robert B. , Saboisky Julian P. , Gandevia Simon C. , Butler Jane E.
Published: December 2006

Abdominal muscles are the most important expiratory muscles for coughing. Spinal cord-injured patients have respiratory complications because of abdominal muscle weakness and paralysis and impaired ability to cough. We aimed to determine the optimal positioning of stimulating electrodes on the trunk for the noninvasive electrical activation of the abdominal muscles. In six healthy subjects, we compared twitch pressures produced by a single electrical pulse through surface electrodes placed either posterolaterally or anteriorly on the trunk with twitch pressures produced by magnetic stimulation of nerve roots at the T10level. A gastroesophageal catheter measured gastric pressure (Pga) and esophageal pressure (Pes). Twitches were recorded at increasing stimulus intensities at functional residual capacity (FRC) in the seated posture. The maximal intensity used was also delivered at total lung capacity (TLC). At FRC, twitch pressures were greatest with electrical stimulation posterolaterally and magnetic stimulation at T10and smallest at the anterior site (Pga, 30 ± 3 and 33 ± 6 cmH2O vs. 12 ± 3 cmH2O; Pes 8 ± 2 and 11 ± 3 cmH2O vs. 5 ± 1 cmH2O; means ± SE). At TLC, twitch pressures were larger. The values for posterolateral electrical stimulation were comparable to those evoked by thoracic magnetic stimulation. The posterolateral stimulation site is the optimal site for generating gastric and esophageal twitch pressures with electrical stimulation.
Transcriptional Repression of HepaticCytochrome P450 3A4Gene in the Presence of Cancer
Authors: Charles Kellie A. , Rivory Laurent P. , Brown Sandie L. , Liddle Christopher , Clarke Stephen J. , Robertson Graham R.
Published: December 2006

Purpose: Many chemotherapeutic drugs have an inherent lack of safety due to interindividual variability of hepatic cytochrome P450 (CYP) 3A4 drug metabolism. This reduction in CYP3A4 in cancer patients is possibly mediated by cytokines associated with tumor-derived inflammation. We sought to examine this link by using an explant sarcoma in a novel transgenic mouse model of human CYP3A4 regulation.

Experimental Design: Engelbreth-Holm-Swarm sarcoma cells were injected into the hindlimb of transgenic CYP3A4/lacZ mice. Hepatic expression of the human CYP3A4 transgene was analyzed by direct measurement of the reporter gene product, β-galactosidase enzyme activity. Hepatic expression of murine Cyp3a was analyzed at the mRNA, protein, and function levels. The acute phase response was assessed by examining cytokines [interleukin-6 (IL-6) and tumor necrosis factor] in serum, liver, or tumor as well as hepatic expression of serum amyloid protein P.

Results: Engelbreth-Holm-Swarm sarcoma elicited an acute phase response that coincided with down-regulation of the human CYP3A4 transgene in the liver as well as the mouse orthologue Cyp3a11. The reduction of murine hepatic Cyp3a gene expression in tumor-bearing mice resulted in decreased Cyp3a protein expression and consequently a significant reduction in Cyp3a-mediated metabolism of midazolam. Circulating IL-6 was elevated and IL-6 protein was only detected in tumor tissue but not in hepatic tissue.

Conclusions: The current study provides a mechanistic link between cancer-associated inflammation and impaired drug metabolism in vivo. Targeted therapy to reduce inflammation may provide improved clinical benefit for chemotherapy drugs metabolized by hepatic CYP3A4 by improving their pharmacokinetic profile.
HER2-Specific T-Cell Immune Responses in Patients Vaccinated with Truncated HER2 Protein Complexed with Nanogels of Cholesteryl Pullulan
Authors: Kitano Shigehisa , Kageyama Shinichi , Nagata Yasuhiro , Miyahara Yoshihiro , Hiasa Atsunori , Naota Hiroaki , Okumura Satoshi , Imai Hiroshi , Shiraishi Taizo , Masuya Masahiro , Nishikawa Masakatsu , Sunamoto Junzo , Akiyoshi Kazunari , Kanematsu Takashi , Scott Andrew M. , Murphy Roger , Hoffman Eric W. , Old Lloyd J. , Shiku Hiroshi
Published: December 2006

Purpose: We developed a complex of tumor antigen protein with a novel nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of the vaccine and HER2-specific T-cell immune responses measured by the newly developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin-stimulated CD4+ T cells in HLA-A2402-positive patients with therapy-refractory HER2-expressing cancers.

Experimental Design: Nine patients with various types of solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300 μg of CHP-HER2 vaccine for three times followed by booster doses. HER2-specific T-cell responses were evaluated by enzyme-linked immunospot assay by targeting autologous phytohemagglutinin-stimulated CD4+ T cells transduced with 146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for MHC class I and class II that might exist in the sequence of the vaccine protein.

Results: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1 transient skin reaction at the sites of vaccination. HER2-specific CD8+ and/or CD4+ T-cell immune responses were detected in five patients who received four to eight vaccinations, among whom both T-cell responses were detected in these patients. In four patients with CD8+ T-cell responses, two patients reacted to previously identified HER263-71 peptide and the other two reacted only to 146HER2 mRNA-transduced cells.

Conclusions: CHP-HER2 vaccine was safe and induced HER2-specific CD8+ and/or CD4+ T-cell immune responses.
Nuclear Factor-κB p65 Inhibits Mitogen-Activated Protein Kinase Signaling Pathway in Radioresistant Breast Cancer Cells
Authors: Ahmed Kazi M. , Dong Shaozhong , Fan Ming , Li Jian Jian
Published: December 2006

The molecular mechanism by which tumor cells increase their resistance to therapeutic radiation remains to be elucidated. We have previously reported that activation of nuclear factor-κB (NF-κB) is causally associated with the enhanced cell survival of MCF+FIR cells derived from breast cancer MCF-7 cells after chronic exposure to fractionated ionizing radiation. The aim of the present study was to reveal the context of NF-κB pathways in the adaptive radioresistance. Using cell lines isolated from MCF+FIR populations, we found that the elevated NF-κB activity was correlated with enhanced clonogenic survival, and increased NF-κB subunit p65 levels were associated with a decrease in phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK in all radioresistant MCF+FIR cell lines. Further irradiation with 30 fractions of radiation also inhibited MEK/ERK phosphorylation in paired cell lines of MCF+FIR and parental MCF-7 cells. Activation of ataxia-telangiectasia mutated (ATM) protein, a sensor to radiation-induced DNA damage, was elevated with increased interaction with NF-κB subunits p65 and p50. The interaction between p65 and MEK was also enhanced in the presence of activated ATM. In contrast, both interaction and nuclear translocation of p65/ERK were reduced. Inhibition of NF-κB by overexpression of mutant IκB increased ERK phosphorylation. In addition, MEK/ERK inhibitor (PD98059) reduced the interaction between p65 and ERK. Taken together, these results suggest that NF-κB inhibits ERK activation to enhance cell survival during the development of tumor adaptive radioresistance. (Mol Cancer Res 2006;4(12):945–55)
The Phosphotransferase System of Corynebacterium glutamicum: Features of Sugar Transport and Carbon Regulation
Authors: Moon Min-Woo , Park Sun-Yang , Choi Soo-Keun , Lee Jung-Kee
Published: December 2006

In this review, we describe the phosphotransferase system (PTS) of Corynebacterium glutamicum and discuss genes for putative global carbon regulation associated with the PTS. C. glutamicum ATCC 13032 has PTS genes encoding the general phosphotransferases enzyme I, HPr and four enzyme II permeases, specific for glucose, fructose, sucrose and one yet unknown substrate. C. gluamicum has a peculiar sugar transport system involving fructose efflux after hydrolyzing sucrose transported via sucrose EII. Also, in addition to their primary PTS, fructose and glucose are each transported by a second transporter, glucose EII and a non-PTS permease, respectively. Interestingly, C. glutamicum does not show any preference for glucose, and thus co-metabolizes glucose with other sugars or organic acids. Studies on PTS-mediated sugar uptake and its related regulation in C. glutamicum are important because the production yield of lysine and cell growth are dependent on the PTS sugars used as substrates for fermentation. In many bacteria, the PTS is also involved in several regulatory processes. However, the detailed molecular mechanism of global carbon regulation associated with the PTS in this organism has not yet been revealed.
A Glucose Kinase from Mycobacterium smegmatis
Authors: Pimentel-Schmitt Elisângela F. , Thomae Andreas W. , Amon Johannes , Klieber Michael A. , Roth Heide-Marie , Muller Yves A. , Jahreis Knut , Burkovski Andreas , Titgemeyer Fritz
Published: December 2006

Carbon metabolism and regulation is poorly understood in mycobacteria, a genus that includes some major pathogenic species like Mycobacterium tuberculosis and Mycobacterium leprae. Here, we report the identification of a glucose kinase from Mycobacterium smegmatis. This enzyme serves in glucose metabolism and global carbon catabolite repression in the related actinomycete Streptomyces coelicolor. The gene, msmeg1356 (glkA), was found by means of in silico screening. It was shown that it occurs in the same genetic context in all so far sequenced mycobacterial species, where it is located in a putative tricistronic operon together with a glycosyl hydrolase and a putative malonyl-CoA transacylase. Heterologous expression of glkA in an Escherichia coli glucose kinase mutant led to the restoration of glucose growth, which provided in vivo evidence for glucose kinase function. GlkAMsm was subsequently overproduced in order to study its enzymatic features. We found that it can form a dimer and that it efficiently phosphorylates glucose at the expense of ATP. The affinity constant for glucose was with 9 mM about eight times higher and the velocity was about tenfold slower when compared to the parallel measured glucose kinase of S. coelicolor. Both enzymes showed similar substrate specificity, which consists in an ATP-dependent phosphorylation of glucose and no, or very inefficient, phosphorylation of the glucose analogues 2-deoxyglucose and methyl α-glucoside. Hence, our data provide a basis for studying the role of mycobacterial glucose kinase in vivo to unravel possible catalytic and regulatory functions.
Regulation of Carbon Metabolism in the Mollicutes and Its Relation to Virulence
Authors: Halbedel Sven , Hames Claudine , Stülke Jörg
Published: December 2006

The mollicutes are cell wall-less bacteria that live in close association with their eukaryotic hosts. Their genomes are strongly reduced and so are their metabolic capabilities. A survey of the available genome sequences reveals that the mollicutes are capable of utilizing sugars as source of carbon and energy via glycolysis. The pentose phosphate pathway is incomplete in these bacteria, and genes encoding enzymes of the tricarboxylic acid cycle are absent from the genomes. Sugars are transported by the phosphotransferase system. As in related bacteria, the phosphotransferase system does also seem to play a regulatory role in the mollicutes as can be concluded from the functionality of the regulatory HPr kinase/phosphorylase. In Mycoplasma pneumoniae, the activity of HPr kinase is triggered in the presence of glycerol. This carbon source may be important for the mollicutes since it is available in epithelial tissues and its metabolism results in the formation of hydrogen peroxide, the major virulence factor of several mollicutes. In plant-pathogenic mollicutes such as Spiroplasma citri, the regulation of carbon metabolism is crucial in the adaptation to life in plant tissues or the insect vectors. Thus, carbon metabolism seems to be intimately linked to pathogenicity in the mollicutes.
Sex Differences in Frequency and Intensity in Reading and Voice Range Profiles for Taiwanese Adult Speakers
Authors: Hwa Chen Sheng
Published: December 2006

The purposes of the study were to (1) compare speaking frequency and speaking intensity between normal adult Taiwanese females and males, and (2) compare the physiological frequency and physiological intensity between normal adult Taiwanese females and males. Forty normal young Taiwanese females and 40 males were selected for study. The frequency and intensity variables in reading and in vocal range profiles were collected and analyzed. The independent t test was used to find a statistical significance between the female and male groups. In reading, the speaking fundamental frequency, the highest and lowest speaking ranges, and the maximum range of speaking fundamental frequency for the female group were significantly greater than those for the male group. In vocal range profiles, the lowest and highest frequencies, and the soft and loud voice for the female group were significantly greater than those for the male group. The maximum dynamic frequency range for the male group was significantly greater than that for the female group. The frequency and intensity ranges for both sexes in this study were greater than other findings for nontonal language speakers. The data may provide a voice assessment tool for Mandarin speakers in Taiwan and in other countries.
The Nasality Severity Index: An Objective Measure of Hypernasality Based on a Multiparameter Approach
Authors: van Lierde Kristiane M. , Wuyts Floris L. , Bonte Katrien , van Cauwenberge Paul
Published: December 2006

There is a need for an objective measure that describes normal resonance and resonance disorders. The current standard of practice has not led to mismanagement but a refined objective assessment protocol will benefit a more precise objective assessment of velopharyngeal disorders. The purpose of the present study is to construct a nasality severity index (NSI) that reflects the multidimensional nature of resonance. Objective and subjective assessment techniques were used to determine the nasalance, the nasality and aerodynamic capacities in 21 children with cleft palate and a control group of 25 children without cleft palate. Stepwise logistic regression was used to determine the optimal index. The NSI consists of a linear combination of 4 variables, where each variable has a different weight. The equation is: NSI = –60.69 – (3.24 × percent oral text) – (13.39 × Glätzel value /a/) + [0.244 × maximum duration time (seconds)] – (0.558 × % /a/) + (3.38 × percent oronasal text). NSI sensitivity is 88% and specificity is 95%. Daily clinical use of the NSI has shown it to be an efficient and practical tool to describe the presence of hypernasality. Three distinct follow-up cases are presented to illustrate the impact of a surgical technique, the use of a speech bulb and velopharyngeal biofeedback training on NSI. The implementation of the NSI may help clinicians to quantitatively assess the severity of nasality disorders beside the perceptual judgments.
SACRAL Syndrome: Spinal Dysraphism, Anogenital, Cutaneous, Renal and Urologic Anomalies, Associated with an Angioma of Lumbosacral Localization
Authors: Stockman Annelies , Boralevi F. , Taïeb Alain , Léauté-Labrèze Christine
Published: December 2006

Background: Publications concerning perineal infantile hemangiomas are scarce, and comprise no large series. Objective: Studying clinical features of hemangiomas of the perineal area, complications and associated malformations. Methods: Retrospective analysis of all hemangiomas localized in the perineal area, encountered at the Children’s Hospital in Bordeaux from 1994. Results: Of 49 perineal hemangiomas (34 girls, 15 boys), 5 patients had accompanying malformation, mainly lipomyelomeningocele with tethered cord. The superficial hemangiomas were more represented in males and presented sooner than the nodular counterpart. The average rate of ulceration was 73%, ulcerations developed earlier in the superficial forms than their nodular counterparts (2 vs. 4 months). Conclusion: Superficial perineal hemangiomas are more often complicated by ulceration, and are associated with developmental anomalies. As a counterpart for the PHACE syndrome in facial hemangioma, we propose the acronym SACRAL for perineal hemangiomas: Spinal dysraphism, Anogenital anomalies, Cutaneous anomalies, Renal and urologic anomalies, associated with Angioma of Lumbosacral localization.
Correction of Sagittal Craniosynostosis Using a Novel Parietal Bone Fixation Technique: Results over a 10-Year Period
Authors: Sikorski Christian W. , Iteld Lawrence , McKinnon McKay , Yamini Bakhtiar , Frim David M.
Published: December 2006

Isolated sagittal synostosis is a common form of craniosynostosis affecting roughly 1 in 5,000 children at birth. This results in a scaphocephalic head shape with a characteristically elongated anterior-posterior dimension and narrowed biparietal diameter. We present our experience with the correction of scaphocephaly due to sagittal synostosis using cranial vault reconstruction with a novel form of parietal bone fixation in 21 patients over 10 years. The medial fixation results in a hinging effect whereby transverse brain growth at the squamoid suture is enhanced. This results in excellent cosmetic results that are immediate and durable without the need for postoperative molding helmets. Furthermore, the complications associated with this procedure are limited.
Endoscopic Third Ventriculostomy in Prepontine-Suprasellar Tuberculoma with Tuberculous Meningitis Hydrocephalus: A Case Report
Authors: Jha Deepak , Khatri Prakash , Choudhary Ajay , Sethi Rajeev , Kumar Sushil
Published: December 2006

We present a case of prepontine-suprasellar tuberculoma involving the premamillary region of the third ventricular floor, a site suitable to perform an endoscopic third ventriculostomy (ETV) stoma, managed endoscopically, and discuss our findings. A 5-year-old male child was admitted in an unconscious state with a history of gradually progressive symptoms of raised intracranial pressure and low-grade fever for the last 3 months. Head computed tomography showed thick enhancing basal exudates, a prepontine-suprasellar ring-enhancing lesion with consequent obstructive hydrocephalus. The child was subjected to urgent endoscopy which revealed multiple ependymal tubercles along with prepontine-suprasellar tuberculoma involving the premamillary region of the third ventricular floor. The tuberculoma was decompressed using a 5-french catheter, and ETV was performed. Postoperatively, the child improved clinicoradiologically on antitubercular chemotherapy and needed no further cerebrospinal fluid diversion surgery; he is under regular follow-up. We conclude that ETV may be attempted even in the presence of thick basal exudates and/or prepontine-suprasellar tuberculoma.
Pentasomy 49,XXXXY Associated with a Chiari Type 1 Malformation and Cervical Syrinx
Authors: Raven Ramin , Bingham Peter M. , Graupman Patrick
Published: December 2006

Pentasomy 49,XXXXY occurs in 1/85,000 newborn males. The origin of this particular form of aneuploidy is believed to be a result of consecutive nondisjunction events during maternal meiosis. Typical presentation consists of hypotonia, developmental delay, various dysmorphic features, and severe hypogenitalism. A 13-year-old with pentasomy 49,XXXXY and a Chiari type 1 malformation with an associated cervical syrinx is presented.
Unusual Presentation of Cervical Spinal Intramedullary Arachnoid Cyst in Childhood: Case Report and Review of the Literature
Authors: Guzel Aslan , Tatlı Mehmet , Yılmaz Fahri , Bavbek Murad
Published: December 2006

The authors report a 7-year-old girl who presented with progressive quadriparesis which had started a month before admission. Magnetic resonance imaging of the spine revealed an intramedullary cystic lesion extending from C2 to C4. After performing a C2–5 laminectomy, the cyst was drained and anatomically fenestrated with the subarachnoid space by a 1-cm vertical median myelotomy without using a stent. The histopathological findings revealed arachnoid cyst. In the first month after operation, the neurological deficits disappeared gradually, except for a slight left upper paresis. Cervical spinal intramedullary arachnoid cyst is extremely rare and should be considered in the differential diagnosis of intramedullary cystic lesions in childhood. Recovery is possible after subtotal excision and fenestration of the cyst to allow communication with the subarachnoid space even if neurological deficits are present for a long time.