bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of quantitative shear wave MR‐elastography with mechanical compression tests
Authors: Hamhaber U. , Grieshaber F.A. , Nagel J.H. , Klose U.
Published: January 2003

The mechanical properties of in vivo soft tissue are generally determined by palpation, ultrasound measurements (US), and magnetic resonance elastography (MRE). While it has been shown that US and MRE are capable of quantitatively measuring soft tissue elasticity, there is still some uncertainty about the reliability of quantitative MRE measurements. For this reason it was decided to determine in vitro how MRE measurements correspond with other quantitative methods of measuring characteristic elasticity values. This article presents the results of experiments with tissue‐like agar–agar gel phantoms in which the wavelength of strain waves was measured by shear wave MR elastography and the resultant shear modulus was compared with results from mechanical compression tests with small gel specimens. The shear moduli of nine homogeneous gels with various agar–agar concentrations were investigated. The elasticity range of the gels covered the elasticity range of typical soft tissues. The systematic comparison between shear wave MRE and compression tests showed good agreement between the two measurement techniques. Magn Reson Med 49:71–77, 2003. © 2003 Wiley‐Liss, Inc.
Congenital myasthenic syndromes: Progress over the past decade
Authors: Engel Andrew G. , Ohno Kinji , Sine Steven M.
Published: January 2003

Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic basal lamina, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. A basal lamina CMS is caused by mutations in the collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase that prevent the tail subunit from associating with catalytic subunits or from becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in subunits of the acetylcholine receptor (AChR) that alter the kinetic properties or decrease the expression of AChR. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow‐ and fast‐channel syndromes, respectively. Most low‐expressor mutations reside in the AChR ϵ subunit and are partially compensated by residual expression of the fetal type γ subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane. Muscle Nerve 27: 4–25, 2003
Expression of matrix metalloproteinases, inhibitor, and acid phosphatase in muscles of immobilized hindlimbs of rats
Authors: Reznick Abraham Z. , Menashe Ofir , Bar‐Shai Marina , Coleman Raymond , Carmeli Eli
Published: January 2003

External fixation procedures of limb immobilization provide excellent experimental models to study mechanisms involved in muscle disuse atrophy and recovery. Female Wistar rats (7–8 months old) had their right hindlimbs immobilized by an external fixation procedure for 5, 10, 21, and 30 days. Muscle mass of the gastrocnemius and quadriceps muscles was reduced by 41–46% in comparison with contralateral nonimmobilized legs. Acid phosphatase activities were significantly increased after 21 and 30 days of hindlimb immobilization. Histochemical staining for acid phosphatase activities increased in myofibers after the external fixation and also in macrophages in the adjacent extracellular matrix. Matrix metalloproteinase (MMP‐2 and MMP‐9) activities assessed by gel zymography and also a tissue inhibitor of metalloproteinases (TIMP‐1) assessed by Western blot were elevated in the immobilized hindlimb muscles. Our study demonstrated that metalloproteinases are expressed relatively late after limb immobilization and appear to be responsible to a large degree for degradation of the extracellular matrix in experimental disuse atrophy. Muscle Nerve 27: 51–59, 2003
Are voluntary muscle activation deficits in older adults meaningful?
Authors: Stevens Jennifer E. , Stackhouse Scott K. , Binder‐Macleod Stuart A. , Snyder‐Mackler Lynn
Published: January 2003

The relationship between the central activation ratio (CAR) and contraction force is curvilinear, not linear as was previously believed. Voluntary quadriceps femoris muscle activation from previously collected data sets in 46 older adults (64–84 years) and 46 young adults (18–32 years) were therefore reexamined using a curvilinear model of the voluntary muscle activation–percent maximum voluntary force relationship. This method revealed lower voluntary muscle activation in older adults (0.868 ± 0.018) than younger subjects (0.978 ± 0.005). The mean difference between older and younger adults was 11%, which may be more meaningful than previous reports of 2–4% because it could explain the greater rate of strength loss as compared to loss of muscle mass as humans age. Muscle Nerve 27: 99–101, 2003
Effect of training on contractile and metabolic properties of wrist extensors in spinal cord–injured individuals
Authors: Hartkopp Andreas , Harridge Stephen D. R. , Mizuno Masao , Ratkevicius Aivaras , Quistorff Björn , Kjær Michael , Biering‐Sörensen Fin
Published: January 2003

Paretic human muscle rapidly loses strength and oxidative endurance, and electrical stimulation training may partly reverse this. We evaluated the effects of two training protocols on the contractile and metabolic properties of the wrist extensor in 12 C‐5/6 tetraplegic individuals. The wrist extensor muscles were stimulated for 30 min/day, 5 days/week, for 12 weeks, using either a high‐resistance (Hr) or a low‐resistance (Lr) protocol. Total work output was similar in both protocols. The nontrained arm was used as a control. Maximum voluntary torque increased in the Hr (P < 0.05) but not the Lr group. Electrically stimulated peak tetanic torque at 15 HZ, 30 HZ, and 50 HZ were unchanged in the Lr group and tended to increase only at 15 HZ (P < 0.1) in the Hr group. Resistance to fatigue, however, increased (P < 0.05) in both Hr (42%) and Lr (41%) groups. Muscle metabolism was evaluated by 31P nuclear magnetic resonance spectroscopy (31P‐NMRS) during and following a continuous 40‐s 10‐HZ contraction. In the Hr group the cost of contraction decreased by 38% (P < 0.05) and the half‐time of phosphocreatine (PCr) recovery was shortened by 52% (P < 0.05). Thus, long‐term electrically induced stimulation of the wrist extensor muscles in spinal cord injury (SCI) increases fatigue resistance independent of training pattern. However, only the Hr protocol increased muscle strength and was shown to improve muscle aerobic metabolism after training. Muscle Nerve 27: 72–80, 2003
Consensus criteria for the diagnosis of multifocal motor neuropathy
Authors: Olney Richard K. , Lewis Richard A. , Putnam Timothy D. , Campellone Joseph V.
Published: January 2003

At this time, there are no widely accepted criteria for the diagnosis of multifocal motor neuropathy. Furthermore, there is insufficient empirical data to define clinical and laboratory features that may reliably separate certain lower motor neuron syndromes with overlapping features as distinct. The AAEM therefore developed five criteria through a formal consensus process that are described in this document to act as a guide for diagnosing multifocal motor neuropathy with a high level of confidence (definite multifocal motor neuropathy) or with a moderate level of confidence (probable motor neuropathy). In brief, the diagnosis requires clinical weakness without objective sensory loss or upper motor neuron signs in the distribution of two or more named nerves that is due to conduction block in two or more motor nerves outside of common entrapment sites. Furthermore, normal results are required for sensory nerve conduction studies. Muscle Nerve 27:117–121, 2003
Report: Some recent developments in network economics
Authors: Nagurney Anna
Published: January 2003

This report highlights some recent developments in Network Economics based on papers presented at the Computing in Economics and Finance (CEF 2002) Conference held in Aix en Provence, France.
Optimal rectangular partitions
Authors: Calheiros Felipe C. , Lucena Abilio , de Souza Cid C.
Published: January 2003

Assume that a rectangle R is given on the Euclidean plane together with a finite set P of points that are interior to R. A rectangular partition of R is a partition of the surface of R into smaller rectangles. The length of such a partition equals the sum of the lengths for the line segments that define it. The partition is said to be feasible if no point of P is interior to a partition rectangle. The Rectangular Partitioning Problem (RPP) seeks a feasible rectangular partition of R with the least length. Computational evidence from the literature indicates that RPPs with noncorectilinear points in P, denoted NCRPPs, are the hardest to solve to proven optimality. In this paper, some structural properties of optimal feasible NCRPP partitions are presented. These properties allow substantial reductions in problem input size to be carried out. Additionally, a stronger formulation of the problem is also made possible. Based on these ingredients, a hybrid Lagrangian Relaxation—Linear Programming Relaxation exact solution algorithm is proposed. Such an algorithm has proved capable of solving NCRPP instances more than twice as large as those found in the literature. © 2002 Wiley Periodicals, Inc.
Are calcium isotopes a reliable monitor of trophic level in marine settings?
Authors: Clementz M. T. , Holden P. , Koch P. L.
Published: February 2003

Recent research has shown that calcium isotopes are fractionated by metabolic processes, leading to a decrease in 44Ca/40Ca ratio with increasing trophic level. If so, calcium isotopes could provide information on trophic relationships within foodwebs millions of years older than what we have been able to study thus far with alternative methods (i.e., nitrogen isotopes (δ15N), Sr/Ca). To explore whether δ44Ca values provided marine trophic level information, we measured the δ44Ca composition of tooth enamel and bone from modern marine mammals representing a 2.5 order range in trophic level. Marine mammal enamel δ44Ca values clustered into two groups—mammals foraging on vegetation or invertebrates exhibited higher δ44Ca values than those foraging on fish or other marine mammals. We next examined whether this correlation was preserved in the fossil record by examining a 15 Ma marine fauna from southern California and observed that the relationship between δ44Ca values of specimens followed the same pattern as observed in modern faunas, but the mean δ44Ca values were significantly different from modern δ44Ca values for mammals of similar trophic level. We conclude that the relative spacing of δ44Ca values amongst fossil taxa can serve as a valuable tool for defining trophic level of extinct organisms and can provide critical information on relationships within ancient foodwebs. Copyright © 2003 John Wiley & Sons, Ltd.
Expression of the dietary isotope signal in the compound‐specific δ13C values of pig bone lipids and amino acids
Authors: Howland M. R. , Corr L. T. , Young S. M. M. , Jones V. , Jim S. , Van Der Merwe N. J. , Mitchell A. D. , Evershed R. P.
Published: February 2003

Pigs were raised on six isotopically controlled diets to examine the dietary macronutrients used in the synthesis of bulk bone biochemical components (apatite, collagen and lipids) and individual compounds (bone fatty acids, cholesterol and amino acids from collagen). δ13C values of apatite and bulk bone lipids reflected those of the whole diet, with Δ13Capatite‐wholediet = 10.2 ± 1.3‰ and Δ13Cbonelipids‐wholediet = −2.4 ± 0.7‰. A wide variation observed in the Δ13Ccollagen‐wholediet values (0.5 to 6.1‰) was hypothesized to reflect the relative importance of (i) the direct incorporation of essential amino acids, and (ii) the balance between direct incorporation and de novo synthesis of non‐essential amino acids. Linear regression (n = 6) was used to assess the relationship between the δ13C values of whole diet and bulk bone components and individual compounds. Whole diet δ13C values showed a strong correlation with those of bone cholesterol (R2 = 0.81) and non‐essential fatty acids (0.97 ≤ R2 ≤ 0.99). Not surprisingly, bone linoleic acid δ13C values correlated well with dietary linoleic acid (R2 = 0.95). Mass balance calculations using the δ13C values of single amino acids accurately predicted the δ13C value of whole collagen. The δ13C values of whole diet were well correlated with those of the non‐essential amino acids, alanine (R2 = 0.85) and glutamate (R2 = 0.96) in collagen. The essential amino acids leucine (Δ13Ccollagenleu‐dietleu = 0.5 ± 1.2‰) and phenylalanine (Δ13Ccollagenphe‐dietphe = −0.6 ± 0.6‰) showed little isotopic fractionation between diet and bone collagen. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of mixing conditions on the morphology and properties of polystyrene/polyethylene blends compatibilized with styrene–butadiene block copolymers
Authors: Fortelný I. , Hlavatá D. , Mikešová J. , Michálková D. , Potroková L. , Šloufová I.
Published: February 2003

The effect of mixing conditions on the morphology, molten‐state viscoelastic properties, and tensile impact strength of polystyrene/polyethylene (80/20) blends compatibilized with styrene–butadiene block copolymers containing various numbers and lengths of blocks was studied. Under all mixing conditions, an admixture of a styrene–butadiene block copolymer led to a finer phase structure and to an increase in the dynamic viscosity, storage modulus, and tensile impact strength. The effects were stronger for S–B diblock with a short styrene block than for S–B–S–B–S pentablock with long styrene blocks (where S represents styrene and B represents butadiene). For all blends mixed longer than 2 min, the mixing time had only a small effect on their morphology and properties. Surprisingly, the localization of S–B diblock copolymers was strongly dependent on the rate of mixing. The mixing rate had a nonnegligible effect on the viscoelastic properties of the compatibilized blends. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 609–622, 2003
Modelling alpine permafrost distribution based on energy‐balance data: a first step
Authors: Stocker‐Mittaz Catherine , Hoelzle Martin , Haeberli Wilfried
Published: January 2003

The computer model PERMEBAL (which stands for Permafrost and Energy Balance) simulates the persistence of snow cover and daily ground surface temperatures of snow‐free gridpoints. It was developed for high‐mountain conditions. The model describes different vertical energy fluxes at the surface. With meteorological and site‐specific input data, PERMEBAL delivers daily ground surface temperatures of snow‐free gridpoints. Special emphasis is given to simulation of snow‐cover development (snow fall, snow redistribution, snowmelt). The resulting ground surface temperature data are intended for use as input data for future ground heat flux simulations. The aim is to model ground thermal conditions and thus permafrost distribution. The model was applied to the Corvatsch‐Furtschellas area (16 km2, Engadin, eastern Switzerland). The results show that the area could be divided into three classes of mean annual sums of daily ground surface temperatures of snow‐free pixels, similar to ‘permafrost probable’, ‘permafrost possible’ and ‘permafrost improbable’ classifications used in earlier empirical permafrost distribution models. Copyright © 2002 John Wiley & Sons, Ltd.
Bone induction by BMP‐2 transduced stem cells derived from human fat
Authors: Dragoo Jason L. , Choi Joon Y. , Lieberman Jay R. , Huang Jerry , Zuk Patricia A. , Zhang Jeffery , Hedrick Marc H. , Benhaim Prosper
Published: February 2003

Purpose: We have isolated pluripotent mesenchymal progenitor cells in large numbers from liposuction aspirates (processed lipoaspirate cells or PLAs). This study examines the osteogenic potential of PLAs and bone marrow aspirate cells (BMAs), when exposed to either recombinant human bone morphogenetic protein (BMP)‐2 (rh‐BMP‐2) or adenovirus containing BMP‐2 cDNA (Ad‐BMP‐2).

Methods: Liposuction aspirates underwent proteolytic digestion to obtain PLAs. After exposure to exogenous rh‐BMP‐2 or Ad‐BMP‐2 for four or seven days, PLAs and BMAs were assessed by histochemistry, spectrophotometry and RT‐PCR. Western blotting and ELISA confirmed BMP gene transduction. Results were compared to osteoblasts and cells in osteogenic media only. PLA‐Ad‐BMP‐2 cells were seeded on matrices and implanted in the hind limbs of SCID mice.

Results: Analysis of quantified bone precursor assays including extracellular ALP histomorphometry, intracellular ALP spectrophotometry, and calcified extracellular matrix (von Kossa) histomorphometry revealed that PLAs treated with exogenous rh‐BMP‐2 or transduced with a BMP‐2 containing adenovirus (PLA‐Ad‐BMP‐2) produced more bone precursors than osteoblasts (p = 0.001). PLAs treated with exogenous rh‐BMP‐2 or PLA‐Ad‐BMP‐2 also produced more bone precursors than BMAs (p = 0.001), except for day 7 ALP histomorphometry (p = 0.343). ELISA confirmed successful BMP‐2 production by both progenitor cell groups transduced with Ad‐BMP‐2. H&E sections from collagen I matrices seeded with PLA‐Ad‐BMP‐2 cells confirmed bone formation at six weeks.

Conclusions: Liposuction aspirates contain PLAs that can be transfected with the BMP‐2 gene, with rapid induction into the osteoblast phenotype at a rate comparable to rh‐BMP‐2 and osteoblast groups. Transduced PLAs produce more bone precursors with faster onset of calcified extracellular matrix than transduced BMAs. PLAs may be an ideal source of mesenchyme‐lineage stem cells for gene therapy and tissue engineering. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Calculation of associative and Penning ionization of H and D by He(2 1S) and He(2 3S)
Authors: Hickman A. P. , Morgner H.
Published: February 2003

Associative and Penning ionization cross sections are calculated for collisions of H and D with He(2 1S) and He(2 3S) in the energy range 0.03–1.0 eV. Ab initio configuration–interaction potential curves V* and V+ for these systems are used. For the autoionization width Γ, the recent results of Hickman, Isaacson, and Miller for He(2 3S) -H are employed, and their calculations are extended to obtain the width for He(2 1S) –H. For the latter system, the calculated associative ionization fraction and the relative energy dependence of the total ionization cross section are in excellent agreement with the recent experiments of Fort, Laucagne, Pesnelle, and Watel. Comparison with the experiments of Morgner at thermal energies, and of Howard, Riola, Rundel, and Stebbings, and Neynaber and Magnuson at higher energies suggests that Γ (R) for He(2 3S) –H is fairly accurate, and that Γ (R) for He(2 1S) –H is low by about a factor of 2.
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o effective core potentials including relativistic effects. I. Formalism and applications to the Xe and Au atoms
Authors: Lee Yoon S. , Ermler Walter C. , Pitzer Kenneth S.
Published: February 2003

An effective core potential system has been developed for heavy atoms in which relativistic effects are included in the effective potentials (EP). The EP’s are based on numerical Dirac–Hartree–Fock calculations for atoms and on the Phillips–Kleinman transformation with other aspects similar to the treatments of Goddard and Melius and Kahn, Baybutt, and Truhlar. The EP’s may be written UEP=Σl Σj=*l−1/2*l+1/2 Σm=−jj UljEP(r) ‖ljm≳<ljm‖, where ‖ljm≳ is a two-component angular basis function that is a product of a two-component Pauli spinor and spherical harmonics. The numerical functions UljEP(r) are approximated as expansions in terms of Gaussian or exponential functions. The use of these EP’s enables one to use the jj-coupling scheme for subsequent applications in all-valence-electron calculations on heavy atoms and their molecules. A standard atomic SCF program has been modified to accommodate these EP’s and Gaussian and exponential basis sets having the proper j angular dependence. Energy levels for many atomic states of Xe and Au were calculated. The study of Xe excited states indicates that the spin–orbit splittings are reasonably approximated and that the numerical DHF calculations are adequately reproduced. Au has been treated as an atom with 1, 11, 17, 19, or 33 valence electrons to investigate the effects of redefinition of the core.
Rate measurements of reactions of helium metastable species at atmospheric pressures. II. He2 (2 3Σ+u) in pure afterglows
Authors: Myers G. , Cunningham A. J.
Published: February 2003

Using resonance absorption spectrometry the rates of the reactions He2(2 3Σ+u)+He2(2 3Σ+u) →products and He2(2 3Σ+u)+Ne→products have been measured in the afterglow period of electron beam excited discharge plasmas in helium at atmospheric pressures. The reported rate for the first reactions at (1.3±0.3)10−10 cm3 sec−1 is an order of magnitude lower than previously reported values. A value for the inverse transition probability of the 3 3Πg←2 3Σ+u electronic transition has also been established.
Millimeterwave spectroscopy of active laser plasmas; the excited vibrational states of HCN
Authors: De Lucia Frank C. , Helminger Paul A.
Published: February 2003

Millimeter and submillimeter microwave techniques have been used for the spectroscopic study of an HCN laser plasma. Forty-seven rotational transitions in 12 excited vibrational states have been observed. Numerous rotational, vibrational, and perturbation parameters have been calculated from these data. A discussion of experimental techniques is included.
Studies of luminescence efficiency of Eu2+ activated phosphors as a function of temperature and high pressure
Authors: Tyner C. E. , Drickamer H. G.
Published: February 2003

The effect of pressure and temperature on peak energy and shape, intensity, and luminescence lifetime of a series of alkaline earth compounds doped with Eu2+ has been measured. The results are analyzed in terms of a quantum mechanical single configuration coordinate model. The quenching of the luminescence cannot be explained in terms of a two state model. It is possible to postulate the presence of a third state which accounts for the quenching. The properties of this third state vary in a reasonable and internally consistent manner among the compounds.
Tumor Necrosis Factor-α Causes Accumulation of a Ubiquitinated Form of Hypoxia Inducible Factor-1α through a Nuclear Factor-κB-Dependent Pathway
Authors: Zhou Jie , Schmid Tobias , Brüne Bernhard
Published: February 2003

Hypoxia-inducible factor-1 (HIF-1) is a regulator of metabolic adaptation to hypoxia. It is now appreciated that HIF-1α accumulation is achieved under normoxic conditions by various factors, such as TNF-α. Here, it was our intention to gain insight into the signaling mechanisms used by TNF-α to stimulate HIF-1α. In tubular LLC-PK1or human embryonic kidney cells, TNF-α induced accumulation of HIF-1α protein but not HIF-1α mRNA. Blocking nuclear factor (NF)-κB with sulfasalazine or expression of an IκB superrepressor attenuated HIF-1α accumulation, whereas transfection of active p50/p65-NF-κB subunits mimicked a TNF-α response. Experiments with actinomycin D and cycloheximide also pointed to a transcriptional and translational process in facilitating the TNF-α response. Interestingly, and in contrast to established hypoxic signaling concepts, TNF-α elicited HIF-1α accumulation in a ubiquitinated form that still bound the von Hippel-Lindau (pVHL) protein. These data indicate that HIF-1α accumulation by TNF-α demands the NF-κB pathway, preserves ubiquitination of HIF-1α, and allows the HIF-1α-pVHL interaction.
Natural‐resource institutions and property rights in inland African fisheries
Authors: Béné C. , Neiland A. , Jolley T. , Ladu B. , Ovie S. , Sule O. , Baba M. , Belal E. , Mindjimba K. , Tiotsop F. , Dara L. , Zakara A. , Quensiere J.
Published: February 2003

Although there exists a rich literature on fisheries traditional management systems in North and South America, Caribbean, Asia and Pacific islands, much less information is available on inland African fisheries. Presents the first regional‐scale survey of traditional management systems operated within the Lake Chad Basin. The survey focused on the status and organization of the local (de facto) management systems and their interactions with the modern (de jure) regulations. The results show that fishing activities within the whole Basin are still largely under the control of the traditional local authorities. The few open‐access fishing grounds are areas that traditional authorities have never controlled or water‐bodies that they have had to “give up” in recent times due to the presence of armed groups. These areas are also areas where illegal taxation systems operated by non‐legitimated governement agents have developed, essentially as a consequence of the remoteness and political instability of the whole Basin.
Finite element analysis of a three‐dimensional package
Authors: Zhong Zhaowei , Kiong Yip Peng
Published: February 2003

A three‐dimensional (3D) package consisting of a stack of three silicon chips was conceptually designed. A finite element simulation of this 3D package was conducted in order to compare the fatigue lives of the solder joints with those in a typical single flip chip package when subjected to a cyclic thermal loading. It was found that the proposed design of the 3D package was feasible in terms of its mechanical deformation response to the thermal cycle.
Organisation of sensitisation of hind limb withdrawal reflexes from acute noxious stimuli in the rabbit
Authors: Harris John , Clarke Rob W.
Published: January 2003

Spatial aspects of central sensitisation were investigated by studying the effects on three hind limb withdrawal reflexes of an acute noxious stimulus (20 % mustard oil) applied to a number of locations around the body in decerebrate and in anaesthetised rabbits. Reflex responses to electrical stimulation of the toes were recorded from the ankle flexor tibialis anterior (TA) and the knee flexor semitendinosus (ST), whereas responses to stimulation of the heel were recorded from the ankle extensor medial gastrocnemius (MG). In non‐spinalised, decerebrated, pentobarbitone‐sedated preparations, flexor reflexes were facilitated significantly from sites on the plantar surface of the ipsilateral foot but were either inhibited or unaffected by stimulation of sites away from this location. The heel–MG reflex was facilitated from the ipsilateral heel and was inhibited from a number of ipsilateral, contralateral and off‐limb sites. In decerebrated, spinalised, pentobarbitone‐sedated animals, mustard oil applied to any site on the ipsilateral hind limb enhanced both flexor reflexes, whereas the MG reflex was enhanced only after stimulation at the ipsilateral heel and was inhibited after stimulation of the toe tips or TA muscle. Mustard oil on the contralateral limb had no effect on any reflex. In rabbits anaesthetised with pentobarbitone and prepared with minimal surgical interference, the sensitisation fields for the heel–MG and toes–TA reflexes were very similar to those in non‐spinal decerebrates whereas that for toes–ST was more like the pattern observed in spinalised animals. In no preparation was sensitisation or inhibition of reflexes related to the degree of motoneurone activity generated in direct response to the sensitising stimulus. This study provides for the first time a complete description of the sensitisation fields for reflexes to individual muscles. Descending controls had a marked effect on the area from which sensitisation of flexor reflexes could be obtained, as the sensitisation fields for the flexor reflexes evoked from the toes were larger in spinalised compared to decerebrated, non‐spinalised animals. The intermediate sizes of sensitisation fields in anaesthetised animals suggests that the area of these fields can be dynamically controlled from the brain. On the other hand, the sensitisation field for the heel–MG reflex varied little between preparations and appears to be a function of spinal neurones.
Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice
Authors: Massion P. B. , Balligand J.‐L.
Published: January 2003

The modulatory role of endothelial nitric oxide synthase (eNOS) on heart contraction, relaxation and rate is examined in light of recent studies using genetic deletion or overexpression in mice under specific conditions. Unstressed eNOS‐/‐ hearts in basal conditions exhibit a normal inotropic and lusitropic function, with either decreased or unchanged heart rate. Under stimulation with catecholamines, eNOS‐/‐ mice predominantly show a potentiation in their β‐adrenergic inotropic and lusitropic responsiveness. A similar phenotype is observed in β3‐adrenoceptor deficient mice, pointing to a key role of this receptor subtype for eNOS coupling. The effect of eNOS on the muscarinic cholinergic modulation of cardiac function probably operates in conjunction with other NO‐independent mechanisms, the persistence of which may explain the apparent dispensability of this isoform for the effect of acetylcholine in some eNOS‐/‐ mouse strains. eNOS‐/‐ hearts submitted to short term ischaemia‐reperfusion exhibit variable alterations in systolic and diastolic function and infarct size, while those submitted to myocardial infarction present a worsened ventricular remodelling, increased 1 month mortality and loss of benefit from ACE inhibitor or angiotensin II type I receptor antagonist therapy. Although non‐conditional eNOS gene deletion may engender phenotypic adaptations (e.g. ventricular hypertrophy resulting from chronic hypertension, or upregulation of the other NOS isoforms) potentially confounding the interpretation of comparative studies, the use of eNOS‐/‐ mice has undoubtedly advanced (and will probably continue to improve) our understanding of the complex role of eNOS (in conjunction with the other NOSs) in the regulation of cardiac function. The challenge is now to confirm the emerging paradigms in human cardiac physiology and hopefully translate them into therapy.
Regulation of cardiac excitation–contraction coupling by action potential repolarization: role of the transient outward potassium current (Ito)
Authors: Sah Rajan , Ramirez Rafael J. , Oudit Gavin Y. , Gidrewicz Dominica , Trivieri Maria G. , Zobel Carsten , Backx Peter H.
Published: January 2003

The cardiac action potential (AP) is critical for initiating and coordinating myocyte contraction. In particular, the early repolarization period of the AP (phase 1) strongly influences the time course and magnitude of the whole‐cell intracellular Ca2+ transient by modulating trans‐sarcolemmal Ca2+ influx through L‐type Ca2+ channels (ICa,L) and Na‐Ca exchangers (ICa,NCX). The transient outward potassium current (Ito) has kinetic properties that make it especially effective in modulating the trajectory of phase 1 repolarization and thereby cardiac excitation‐contraction coupling (ECC). The magnitude of Ito varies greatly during cardiac development, between different regions of the heart, and is invariably reduced as a result of heart disease, leading to corresponding variations in ECC. In this article, we review evidence supporting a modulatory role of Ito in ECC through its influence on ICa,L, and possibly ICa,NCX. We also discuss differential effects of Ito on ECC between different species, between different regions of the heart and in heart disease.
Effects of continuous positive airway pressure on upper airway inspiratory dynamics in awake patients with sleep‐disordered breathing
Authors: Vérin E. , Similowski T. , Sériès F.
Published: January 2003

Continuous positive airway pressure (CPAP) is the main treatment of the obstructive sleep apnoea syndrome (OSAS). We assessed its effects on the upper airway (UA) dynamics in response to bilateral anterior magnetic phrenic nerve stimulation (BAMPS) in 17 awake untreated OSAS patients (15 males; 52 ± 7 years) whose effective CPAP (Peff) had been determined beforehand by a conventional titration sleep study. All twitch‐related inspirations were flow‐limited, flow first rising to a maximum (V̇Imax), then decreasing to a minimum (V̇Imin), and then increasing again (M‐shaped pattern). Up to V̇Imin, the relationship between driving pressure (Pd) and flow (V̇) could adequately be fitted to a polynomial regression model (V̇=k1Pd+k2Pd2; r2= 0.71‐0.98, P < 0.0001). At atmospheric pressure V̇Imax was 700 ± 377 ml s−1, V̇Imin was 458 ± 306 ml s−1, k1 was 154.5 ± 63.9 ml s−1 (cmH2O)−1, and k2 was 10.7 ± 7.3 ml s−1 (cmH2O)−1. CPAP significantly increased V̇Imax and V̇Imin (peak values 1007 ± 332 ml and 837 ± 264 ml s−1, respectively) as well as k1 and k2 (peak values 300.9 ± 178.2 ml s−1 (cmH2O)−1 and 55.2 ± 65.3 ml s−1 (cmH2O)−1, respectively). With increasing CPAP, k1/k2 increased up to a peak value before decreasing. We defined as Peff,stim the CPAP value corresponding to the highest k1/k2 value. Peff,stim was correlated with Peff (Peff= 7.0 ± 2.0; Peff,stim= 6.4 ± 2.6 cmH2O; r= 0.886; 95 % CI 0.696‐0.960, P < 0.001). We conclude that CPAP improves UA dynamics in OSAS and that the therapeutic CPAP to apply can be predicted during wakefulness using BAMPS.
Intracellular sodium changes during the speract response and the acrosome reaction in sea urchin sperm
Authors: Rodríguez Esmeralda , Darszon Alberto
Published: January 2003

The sperm‐activating peptide speract and fucose‐sulphate glycoconjugate (FSG) are sea urchin egg‐envelope components that modulate sperm ion permeability. They influence motility and induce acrosomal reaction (AR), respectively. A fluorescent Na+‐sensitive dye (Na+‐binding benzofuran isophthalate, SBFI) was used to determine how these egg envelope components influence sperm Na+ permeability. [Ca2+]i and pHi were also measured to correlate their changes in response to speract and FSG with those observed in [Na+]i. SBFI determinations indicate that the resting [Na+]i is 20 ± 8 mm in sea urchin sperm. Saturating levels of speract increased [Na+]i by ≈15 mm, while similar levels of FSG caused a further elevation of ≈30 mm. The kinetics of the [Na+]i, [Ca2+]i and pHi changes induced by saturating levels of speract were faster than those induced by FSG. Both egg ligands appeared to activate more than one Na+ transport system. Nifedipine, Ni2+ and TEA+ inhibited the ionic changes and the AR induced by FSG but, importantly, did not alter those caused by speract. Thus, there are differences in some of the ionic transport mechanisms that operate in the speract and FSG responses. ZD2788, a blocker of hyperpolarization and cyclic‐nucleotide‐gated (HCN) channels such as SpHCN present in sea urchin sperm, did not decrease the speract‐induced [Na+]i increase, but slowed its kinetics. Therefore, SpHCN does not play a major role in the uptake of Na+ triggered by this decapeptide. KB‐R7943, an inhibitor of Na+/Ca2+ exchangers, decreased the resting [Na+]i and did not change significantly the speract‐induced [Ca2+]i increase, but slowed its recovery.
Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system
Authors: de la Rosa Diego Alvarez , Krueger Stefan R. , Kolar Annette , Shao Deren , Fitzsimonds Reiko Maki , Canessa Cecilia M.
Published: January 2003

The acid‐sensitive ion channel ASIC1 is a proton‐gated ion channel from the mammalian nervous system. Its expression in sensory neurons and activation by low extracellular pH suggest that ASIC is involved in transmitting nociceptive impulses produced by the acidification caused by injury or inflammation. However, ASIC1 expression is not restricted to sensory neurons. To understand the functional role of ASIC1 in the CNS we investigated its expression and subcellular distribution therein. In particular, we examined the presence of ASIC1 in domains where the local pH may drop sufficiently to activate ASIC1 under physiological conditions. Immunostaining with specific antibodies revealed broad expression of ASIC1 in many areas of the adult rat brain including the cerebral cortex, hippocampus and cerebellum. Within cells, ASIC1 was found predominantly throughout the soma and along the branches of axons and dendrites. ASIC1 was not enriched in the microdomains where pH may reach low values, such as in synaptic vesicles or synaptic membranes. Pre‐ or postsynaptic ASIC1 was not gated by synaptic activity in cultured hippocampal neurons. Blockage or desensitization of ASIC1 with amiloride or pH 6.7, respectively, did not modify postsynaptic currents. Finally, the ontogeny of ASIC1 in mouse brain revealed constant levels of expression of ASIC1 protein from embryonic day 12 to the postnatal period, indicating an early and almost constant level of expression of ASIC1 during brain development.
The time course and direction of lower limb vascular conductance changes during voluntary and electrically evoked isometric exercise of the contralateral calf muscle in man
Authors: Fisher James P. , White Michael J.
Published: January 2003

This study aimed to clarify the direction and timing of the change of non‐active lower limb vascular conductance at the onset of contralateral limb isometric exercise and to examine the mechanisms controlling this change. Fifteen human subjects performed 2 min of electrically evoked (Stim) or voluntary (Vol) ischaemic isometric calf plantar flexor exercise at 30 % maximum voluntary contraction (MVC). Blood pressure (BP) and heart rate were continuously recorded and blood flow in the non‐active contralateral lower limb was recorded at 15 s intervals. In subsets of subjects the presence of inadvertent muscle contraction was monitored by calf muscle EMG and the effects of the sensation of electrical stimulation without muscle contraction (sham) were investigated. After 10‐15 s conductance had increased significantly (P < 0.05) in Vol and Stim by a mean of 15 and 12 %, respectively, whilst BP was unchanged. Following this initial increase conductance decreased progressively during Stim and Vol whilst blood pressure rose. No EMG activity was seen during either protocol. In the sham stimulation experiments where no contraction was evoked the conductance change at the onset of stimulation replicated that seen during Stim exercise. Increases in conductance were independent of central command and muscle force generation, were not activated in anticipation of exercise but could be activated secondarily to peripheral sensations associated with expected exercise. The explanation for our results might involve sympathetic withdrawal related to mental stress; however, a central pathway, which directly activates a vasodilator mechanism in passive calf muscle, remains a possibility.
Enhanced neuronal nitric oxide synthase expression is central to cardiac vagal phenotype in exercise‐trained mice
Authors: Danson E. J. F , Paterson D. J.
Published: January 2003

We investigated whether enhanced cardiac vagal responsiveness elicited by exercise training is dependent on neuronal nitric oxide synthase (NOS‐1), since the NO‐cGMP pathway facilitates acetylcholine release. Isolated atria with intact right vagal innervation were taken from male mice (18‐22 weeks old) after a period of 10 weeks voluntary wheel‐running (+EX, n= 27; peaked 9.8 ± 0.6 km day−1 at 5 weeks), and from mice housed in cages without wheels (‐EX, n= 27). Immunostaining of whole atria for NOS‐1 identified intrinsic neurones, all of which co‐localized with choline acetyltransferase‐positive ganglia. Western blot analysis confirmed that NOS‐1 protein level was significantly greater in +EX compared to ‐EX atria (P < 0.05, unpaired t test). Basal heart rates (HR) were slower in +EX than in ‐EX atria (322 ± 6 versus 360 ± 7 beats min−1; P < 0.05, unpaired t test) However, in +EX atria, HR responses to vagal stimulation (VNS, 3 and 5 Hz) were significantly enhanced compared to ‐EX atria (3 Hz, +EX: −76 ± 8 beats min−1versus ‐EX: −62 ± 7 beats min−1; 5 Hz, +EX: −106 ± 4 beats min−1versus ‐EX: −93 ± 3 beats min−1; P < 0.01, unpaired t test). Inhibition of NOS‐1 with vinyl‐l‐N‐5‐(1‐imino‐3‐butenyl)‐l‐ornithine (l‐VNIO, 100 μm) or soluble guanylyl cyclase with 1H‐[1, 2, 4]oxadiazolo[4, 3‐a]quinoxalin‐1‐one (ODQ, 10 μm) abolished the difference in HR responses to VNS between +EX and ‐EX atria, and effects of l‐VNIO were reversed by excess l‐arginine (1 mm; P < 0.01, ANOVA). There were no differences between the HR responses to the bath‐applied acetylcholine analogue carbamylcholine chloride in +EX and ‐EX atria (IC50 concentrations were 5.9 ± 0.4 μm (‐EX) and 5.7 ± 0.4 μm (+EX)), suggesting that the changes in vagal responsiveness resulted from presynaptic facilitation of neurotransmission. In conclusion, NOS‐1 appears to be a key protein in generating the cardiac vagal gain of function elicited by exercise training.
Expansion of Human T-Cell Leukemia Virus Type 1 (HTLV-1) Reservoir in Orally Infected Rats: Inverse Correlation with HTLV-1-Specific Cellular Immune Response
Authors: Hasegawa Atsuhiko , Ohashi Takashi , Hanabuchi Shino , Kato Hirotomo , Takemura Fumiyo , Masuda Takao , Kannagi Mari
Published: February 2003

Adult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type 1 (HTLV-1)-infected individuals. Although the critical risk factor for ATL development is not clear, it has been noted that ATL is incidentally associated with mother-to-child infection, elevated proviral loads, and weakness in HTLV-1-specific T-cell immune responses. In the present study, using a rat system, we investigated the relationships among the following conditions: primary HTLV-1 infection, a persistent HTLV-1 load, and host HTLV-1-specific immunity. We found that the persistent HTLV-1 load in orally infected rats was significantly greater than that in intraperitoneally infected rats. Even after inoculation with only 50 infected cells, a persistent viral load built up to considerable levels in some orally infected rats but not in intraperitoneally infected rats. In contrast, HTLV-1-specific cellular immune responses were markedly impaired in orally infected rats. As a result, a persistent viral load was inversely correlated with levels of virus-specific T-cell responses in these rats. Otherwise very weak HTLV-1-specific cellular immune responses in orally infected rats were markedly augmented after subcutaneous reimmunization with infected syngeneic rat cells. These findings suggest that HTLV-1-specific immune unresponsiveness associated with oral HTLV-1 infection may be a potential risk factor for development of ATL, allowing expansion of the infected cell reservoir in vivo, but could be overcome with immunological strategies.
Entry of Herpes Simplex Virus Type 1 into Primary Sensory Neurons In Vitro Is Mediated by Nectin-1/HveC
Authors: Richart Sarah M. , Simpson Scott A. , Krummenacher Claude , Whitbeck J. Charles , Pizer Lewis I. , Cohen Gary H. , Eisenberg Roselyn J. , Wilcox Christine L.
Published: February 2003

Primary cultures of rat and mouse sensory neurons were used to study the entry of herpes simplex virus type 1 (HSV-1). Soluble, truncated nectin-1 but not HveA prevented viral entry. Antibodies against nectin-1 also blocked infection of rat neurons. These results indicate that nectin-1 is the primary receptor for HSV-1 infection of sensory neurons.
Elucidating TOR Signaling and Rapamycin Action: Lessons from
Saccharomyces cerevisiae
Authors: Crespo José L. , Hall Michael N.
Published: January 2003

TOR (target of rapamycin) is a phosphatidylinositol kinase-related protein kinase that controls cell growth in response to nutrients. Rapamycin is an immunosuppressive and anticancer drug that acts by inhibiting TOR. The modes of action of TOR and rapamycin are remarkably conserved from S. cerevisiae to humans. The current understanding of TOR and rapamycin is derived largely from studies with S. cerevisiae. In this review, we discuss the contributions made by S. cerevisiae to understanding rapamycin action and TOR function.
Helicobacter pylori
Interactions with Host Serum and Extracellular Matrix Proteins: Potential Role in the Infectious Process
Authors: Dubreuil J. Daniel , Giudice Giuseppe Del , Rappuoli Rino
Published: January 2003

Helicobacter pylori, a gram-negative spiral-shaped bacterium, specifically colonizes the stomachs of humans. Once established in this harsh ecological niche, it remains there virtually for the entire life of the host. To date, numerous virulence factors responsible for gastric colonization, survival, and tissue damage have been described for this bacterium. Nevertheless, a critical feature of H. pylori is its ability to establish a long-lasting infection. In fact, although good humoral (against many bacterial proteins) and cellular responses are observed, most infected persons are unable to eradicate the infection. A large body of evidence has shown that the interaction between H. pylori and the host is very complex. In addition to the effect of virulence factors on colonization and persistence, binding of specialized bacterial proteins, known as receptins, to certain host molecules (ligands) could explain the success of H. pylori as a chronically persisting pathogen. Some of the reported interactions are of high affinity, as revealed by their calculated dissociation constant. This review examines the binding of host proteins (serum and extracellular matrix proteins) to H. pylori and considers the significance of these interactions in the infectious process. A more thorough understanding of the kinetics of these receptin interactions could provide a new approach to preventing deeper tissue invasion in H. pylori infections and could represent an alternative to antibiotic treatment.
Critical review of unstable angina and non-ST elevation myocardial infarction
Authors: Sheridan P J , Crossman D C
Published: January 2003

Within the coronary vasculature the progression of a stable atherosclerotic plaque into a vulnerable and ultimately unstable lesion leads to a cascade of events culminating in the clinical presentation of unstable angina or acute myocardial infarction. In recent years studies have provided new insights in to the pathology and natural history, stimulating advances in diagnosis, treatment, and management. The review discusses the progress made including the role of inflammation, cardiac biomarkers, antiplatelet therapy, and percutaneous intervention. Current issues of debate and future directions are also addressed.
Monitoring hormone replacement therapy by biochemical markers of bone metabolism in menopausal women
Authors: Dogan E , Posaci C
Published: January 2003

Biochemical markers of bone metabolism are divided into two groups: formation and resorption markers. Bone turnover is a dynamic process, which increases in postmenopausal period. Hormone replacement therapy (HRT) can diminish this increased bone turnover. Biochemical markers reflect acute changes in bone metabolism. Therefore, they may be very useful for the prediction of subsequent bone mineral density changes after HRT in menopausal women. Both oral and transdermal routes of HRT are efficacious in decreasing the levels of biochemical markers. However, markers do not replace bone mineral density measurement. Collagen type I cross linked N-telopeptide, collagen type I cross linked C-telopeptide, and osteocalcin are the most promising markers.