bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of paediatric asthma
Authors: Grigg J
Published: September 2004

Paediatric asthma best practice not only includes prescribing the correct therapeutic mix based on consensus guidelines, but also reducing therapy once control has been achieved. Clinicians should also be aware that asthma in young children is a heterogeneous entity, and a beneficial response to bronchodilators and/or inhaled steroids is not inevitable. In general, preschool children and infants should not be prescribed inhaled corticosteroids above 200 μg beclometasone dipropionate equivalent twice a day, or regular oral steroids, or long acting β2-adrenoceptor agonists. New therapies such as anti-IgE antibodies are on the horizon, but these are unlikely to replace the established drug combinations. More likely is that the delivery of established drugs will become more convenient (for example, once a day inhaled corticosteroids, or season dependent prophylactic therapy).
Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation
Authors: Hurst J R , Wedzicha J A
Published: September 2004

Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions.
Rosa rugosa Attenuates Diabetic Oxidative Stress in Rats with Streptozotocin-Induced Diabetes
Authors: Cho Eun Ju , Yokozawa Takako , Kim Hyun Young , Shibahara Naotoshi , Park Jong Cheol
Published: September 2004

The effects of Rosa rugosa on diabetic oxidative stress were investigated using rats with streptozotocin (STZ)-induced diabetes. The diabetic rats showed less body weight gain and heavier kidney and liver weights than normal rats, while the oral administration of Rosa rugosa at a dose of 100 or 200 mg/kg body weight/day for 20 days attenuated the physiological changes induced by diabetes. In addition, administrating Rosa rugosa to diabetic rats resulted in significant and dose-dependent decreases in the serum glucose and glycosylated protein levels, implying that Rosa rugosa improves the abnormal glucose metabolism that leads to oxidative stress. Diabetic rats had higher serum levels of superoxide and nitrite/nitrate. However, the administration of Rosa rugosa dose-dependently reduced the over-production of radicals associated with diabetes, suggesting Rosa rugosa is a radical scavenger that would play a crucial role in protecting against diabetic oxidative stress. Rosa rugosa significantly and dose-dependently reduced thiobarbituric acid-reactive substance levels in serum, hepatic and renal mitochondria, implying that Rosa rugosa would alleviate the oxidative stress associated with diabetes by inhibiting lipid peroxidation. This study provides evidence that Rosa rugosa has potential as a treatment for diabetes through attenuating oxidative stress induced by the diabetic condition
Evaluation of Analgesic, Antipyretic Activity and Toxicity Study ofBryonia laciniosain Mice and Rats
Authors: Sivakumar T. , Perumal P. , Sambath Kumar R. , Vamsi M. L. M. , Gomathi P. , Mazumder U. K. , Gupta M.
Published: September 2004

Analgesic, antipyretic activity and toxicity study of the leaves of Bryonia laciniosa Linn. (Family: Cucurbitaceae) was evaluated in the standard animal models. The methanol extract of Bryonia laciniosa (MEBL) was evaluated by hot plate and acetic acid-induced writhing methods to assess analgesic activity. The antipyretic activity of the extract was also evaluated by normal body temperature and yeast-induced hyperpyrexia. The extract showed significant analgesic and antipyretic activity. The MEBL was further evaluated for toxicity at the doses of 125 and 250 mg/kg administered orally for 14 days in rats. At the end of experiments, the blood, liver function and kidney metabolism were observed. The hematological profile and different biochemical parameters such as SGOT, SGPT and ALP were estimated. The present study revealed that MEBL exhibited significant analgesic and antipyretic activity in the tested experimental animal models. The toxicity study indicates that the extract is not toxic at the tested doses.
Evaluation of the Radioprotective Action of Geriforte in Mice Exposed to Different Doses of γ-Radiation
Authors: Jagetia Ganesh Chandra , Baliga Manjeshwar Shrinath
Published: September 2004

The effect of 5, 10, 20, 40 and 80 mg/kg b. wt. of hydroalcoholic extract of geriforte (an Ayurvedic herbal medicine) administered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of γ-radiation. Treatment of mice with different doses of geriforte consecutively for 5 days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. A maximum protection was observed for 10 mg/kg geriforte, where a highest number of survivors were reported by 30 days post-irradiation and further experiments were carried out using this dose of geriforte. The mice were treated with 10 mg/kg b. wt. geriforte or double distilled water (DDW) and exposed to 7, 8, 9, 10 and 11 Gy of gamma radiation and observed for the induction of symptoms of radiation sickness and mortality up to 30 days post-irradiation. The geriforte treatment protected the mice against the GI death as well as bone marrow deaths and the dose reduction factor (DRF) was found to be 1.14. Toxicity study showed that geriforte was non-toxic up to a dose of 4250 mg/kg, where no drug-induced mortality was observed. The LD 50 dose of geriforte was found to be 4750 mg/kg b. wt. To understand the mechanism of action of geriforte, free radical scavenging activity of the drug was evaluated. Geriforte was found to scavenge • OH , O 2•- ABTS •+ and NO • in a dose-dependent manner. Our study demonstrates that geriforte is a good radioprotective agent and the optimum protective dose of 10 mg/kg was 1/475th of the LD 50 dose.
Clinical Assessment of Usefulness, Effectiveness and Safety ofJackyakamcho-tang (Shaoyaogancao-tang)on Muscle Spasm and Pain: A Case Series
Authors: Jung Woo Sang , Moon Sang Kwan , Park Seong Uk , Ko Chang Nam , Cho Ki Ho
Published: September 2004

This study is a retrospective single case series. Two hundred and thirty-seven patients were treated with Jackyakamcho-tang (JKT) for relief of muscle spasm and pain; 81 of them were included in analysis. (The others were excluded because of insufficient medical records to confirm the diagnosis or assess the response.) There were 29 patients with nocturnal leg cramps, 28 with cervical spondylosis, 13 with thalamic pain and 11 with carpal tunnel syndrome, for which the effectiveness was assessed as 86.2%, 60.7%, 45.5% and 72.8%, respectively. Adverse effects (indigestion, diarrhea or edema) were seen in 11.1% of the total patients, but severe cases were only 3.7%. Taking the effectiveness and the safety into consideration, the usefulness was assessed as 86.2%, 57.1%, 53.9% and 72.8% for treating nocturnal leg cramps, cervical spondylosis, thalamic pain and carpal tunnel syndrome, respectively. In conclusion, we suggest that JKT is a useful herbal medicine with analgesic and anti-spasmodic effects.
Changes in Serum Tumor Necrosis Factor (TNF-α) with Kami-Shoyo-San Administration in Depressed Climacteric Patients
Authors: Ushiroyama Takahisa , Ikeda Atsushi , Sakuma Kou , Ueki Minoru
Published: September 2004

An herbal medicine (Kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-α in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-α levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered Kami-shoyo-san according to the definition of above Sho. In contrast, 55 patients who were different in Sho of Kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-α concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-α after 12 weeks of treatment, to 17.22 ± 6.13 pg/ml from a baseline level of 14.16 ± 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-α differed significantly between the Kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 ± 7.8% and -1.22 ± 0.25%, respectively, p <0.01), 8 weeks (19.7 ± 3.4% and -2.45 ± 0.86%, respectively, p <0.01), and 12 weeks (21.3 ± 5.4% and -6.81 ± 2.2%, respectively, p <0.001). We found in this study that Kami-shoyo-san, an herbal medicine, increased plasma TNF-α levels in depressed menopausal patients. Cytokines may play various roles in mood and emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.
Development of the Meridian-Visualizing System that Superimposes a Bio-signal upon a Body Image
Authors: Jeong Dong-Myong , Lee Yong-Heum , Lee Myeong Soo
Published: September 2004

The precise selection and the identification of acupuncture points are essential for the diagnosis and treatment of patients in Oriental medicine. In this study, we have developed a meridian identification system using Single-Power Alternating Current (SPAC), which discriminates between true acupoints and non-acupoints. The SPAC system is not affected by skin resistance or pressure and is more accurate than the existing meridian location system, which uses direct current (DC) excitation current. The accuracy of the meridian location is ensured with the SPAC system because it has the highest sensitivity and the lowest effect on the human body. A microprocessor is used to enhance reliability and increase the accuracy of the SPAC measurements. Current distribution is displayed using an image that overlays the measured skin current on the body image. The positions of the acupoints are then displayed on the body image. This method visualizes the meridian by measuring skin current with an improved electrode using the acupoint discrimination system. A computer display shows the transmitted current as a color related to the electrode position. We demonstrated that by changing the point of measurement on the skin and tracing the electrode on the screen, it is possible to visualize acupoints and meridian phenomena using the color display.
CORRELATION FUNCTIONS OF THE TRI-CRITICAL 3-STATE POTTS MODEL
Authors: BALASKA S. , DEMMOUCHE K.
Published: September 2004

We build the Z3 invariants fusion rules associated to the (D4,A6) conformal algebra. This algebra is known to describe the tri-critical Potts model. The 4-point correlation functions of critical fields are developed in the bootstrap approach, and on the other hand, they are written in terms of integral representation of the conformal blocks. By comparing both expressions, one can determine the structure constants of the operator algebra.
CALCULATION OF COUPLING CONSTANT gϕπγIN QCD SUM RULES
Authors: AYDIN C. , YILMAZ A. H.
Published: September 2004

The coupling constant of ϕ→π0γ decay is calculated using QCD sum rules. A comparison of our prediction on the coupling constant with the result obtained from analysis of the experimental data is performed.
EXCITED CHARMED MESONS: OBSERVATIONS, ANALYSES AND PUZZLES
Authors: COLANGELO P. , DE FAZIO F. , FERRANDES R.
Published: September 2004

We review the status of recently observed positive parity charmed resonances, both in the non-strange and strange sectors. We describe the experimental findings, the main theoretical analyses and the open problems deserving further investigations.
MORE ABOUT ALL CURRENT-ALGEBRAIC ORBIFOLDS
Authors: HALPERN M. B. , WANG J. E.
Published: September 2004

Recently a construction was given for the stress tensors of all sectors of the general current-algebraic orbifold A(H)/H, where A(H) is any current-algebraic conformal field theory with a finite symmetry group H. Here we extend and further analyze this construction to obtain the mode formulation of each sector of each orbifold A(H)/H, including the twisted current algebra, the Virasoro generators, the orbifold adjoint operation and the commutator of the Virasoro generators with the modes of the twisted currents. As applications, general expressions are obtained for the twisted current–current correlator and ground state conformal weight of each twisted sector of any permutation orbifold A(H)/H, H⊂SN. Systematics are also outlined for the orbifolds A(Lie h(H))/H of the (H and Lie h)-invariant conformal field theories, which include the general WZW orbifold and the general coset orbifold. Finally, two new large examples are worked out in further detail: the general SNpermutation orbifold A(SN)/SNand the general inner-automorphic orbifold A(H(d))/H(d).
D1 AND D5-BRANE ACTIONS IN AdSm×Sn
Authors: DAWSON P.
Published: September 2004

The κ-invariant and supersymmetric actions of D1 and D5-branes in AdS3×S3 are investigated, as well as the action of a D5-brane in an AdS5×S5 background. The action of a D5-brane lying totally in an AdS3×S3 background is found. Some progress was made towards finding the action for the D5-brane free to move in the whole AdS3×S3×T4 space, however the supersymmetric action found here is not κ-invariant and the reasons the method used did not find a κ-invariant solution are discussed.
D-PARTICLE RECOIL SPACE–TIMES AND "GLUEBALL" MASSES
Authors: MAVROMATOS NICK E. , WINSTANLEY ELIZABETH
Published: September 2004

We discuss the properties of matter in a D-dimensional anti-de Sitter-type space–time induced dynamically by the recoil of a very heavy D(irichlet)-particle defect embedded in it. The particular form of the recoil geometry, which from a world sheet view point follows from logarithmic conformal field theory deformations of the pertinent sigma-models, results in the presence of both infrared and ultraviolet (spatial) cutoffs. These are crucial in ensuring the presence of mass gaps in scalar matter propagating in the D-particle recoil space–time. The analogy of this problem with the Liouville-string approach to QCD, suggested earlier by John Ellis and one of the present authors, prompts us to identify the resulting scalar masses with those obtained in the supergravity approach based on the Maldacena's conjecture, but without the imposition of any supersymmetry in our case. Within reasonable numerical uncertainties, we observe that agreement is obtained between the two approaches for a particular value of the ratio of the two cutoffs of the recoil geometry. Notably, our approach does not suffer from the ambiguities of the supergravity approach as regards the validity of the comparison of the glueball masses computed there with those obtained in the continuum limit of lattice gauge theories.
SYMPLECTIC AND ORTHOGONAL LIE ALGEBRA TECHNOLOGY FOR BOSONIC AND FERMIONIC OSCILLATOR MODELS OF INTEGRABLE SYSTEMS
Authors: MACFARLANE A. J. , PFEIFFER HENDRYK , WAGNER F.
Published: September 2004

To provide tools, especially L-operators, for use in studies of rational Yang–Baxter algebras and quantum integrable models when the Lie algebras so (N)(bn, dn) or sp (2n)(cn) are the invariance algebras of their R matrices, this paper develops a presentation of these Lie algebras convenient for the context, and derives many properties of the matrices of their defining representations and of the ad-invariant tensors that enter their multiplication laws. Metaplectic-type representations of sp (2n) and so (N) on bosonic and on fermionic Fock spaces respectively are constructed. Concise general expressions (see (5.2) and (5.5) below) for their L-operators are obtained, and used to derive simple formulas for the T operators of the rational RTT algebra of the associated integral systems, thereby enabling their efficient treatment by means of the algebraic Bethe ansatz.
QUANTUM DILATONIC GRAVITY IN d=2,4 AND 5 DIMENSIONS
Authors: NOJIRI SHIN'ICHI , ODINTSOV SERGEI D.
Published: September 2004

We review (mainly) quantum effects in the theories where the gravity sector is described by metric and dilaton. The one-loop effective action for dilatonic gravity in two and four dimensions is evaluated. Renormalization group equations are constructed. The conformal anomaly and induced effective action for 2d and 4d dilaton coupled theories are found. It is applied to the study of quantum aspects of black hole thermodynamics, like calculation of Hawking radiation and quantum corrections to black hole parameters and investigation of quantum instability for such objects with multiple horizons. The use of the above effective action in the construction of nonsingular cosmological models in Einstein or Brans–Dicke (super)gravity and investigation of induced wormholes in supersymmetric Yang–Mills theory are given.

5d dilatonic gravity (bosonic sector of compactified IIB supergravity) is discussed in connection with bulk/boundary (or AdS/CFT) correspondence. Running gauge coupling and quark–antiquark potential for boundary gauge theory at zero or nonzero temperature are calculated from d=5 dilatonic anti-de Sitter-like background solution which represents anti-de Sitter black hole for periodic time.
DEVIATION EQUATIONS OF SYNGE AND SCHILD OVER $({\bar L}_n,g)$-SPACES
Authors: MANOFF S.
Published: September 2004

The deviation equation of Synge and Schild has been investigated over differentiable manifolds with contravariant and covariant affine connections (whose components differ not only by sign) and metric [[Formula: see text]-spaces]. It is shown that the condition £ξu=0 for obtaining this equation is only a sufficient (but not necessary) condition. By means of a nonisotropic (nonnull) vector field u [g(u,u)=e≠0] and the metric hu, orthogonal to it, a projected deviation equation of Synge and Schild has been obtained for the orthogonal to u vector field ξ⊥ and its square L2=g(ξ⊥, ξ⊥). For a given nonisotropic, auto-parallel and normalized vector field u this equation could have some simple solutions.
THE FIELD EQUATION FROM NEWTON'S LAW OF MOTION AND THE ABSENCE OF MAGNETIC MONOPOLE
Authors: SINGH PARAMPREET , DADHICH NARESH
Published: September 2004

By requiring the linear differential operator in Newton's law of motion to be self adjoint, we obtain the field equation for the linear theory, which is the classical electrodynamics. In the process, we are also led to a fundamental universal chiral relation between electric and magnetic monopoles which implies that the two are related. Thus there could just exist only one kind of charge which is conventionally called electric.
INSTANTONS AND CHIRAL ANOMALY IN FUZZY PHYSICS
Authors: BALACHANDRAN A. P. , VAIDYA S.
Published: September 2004

In continuum physics, there are important topological aspects like instantons, θ-terms and the axial anomaly. Conventional lattice discretizations often have difficulties in treating one or the other of these aspects. In this paper, we develop discrete quantum field theories on fuzzy manifolds using noncommutative geometry. Basing ourselves on previous treatments of instantons and chiral fermions (without fermion doubling) on fuzzy spaces and especially fuzzy spheres, we present discrete representations of θ-terms and topological susceptibility for gauge theories and derive axial anomaly on the fuzzy sphere. Our gauge field action for four dimensions is bounded by a constant times the modulus of the instanton number as in the continuum.
A-DEPENDENCE OF Z-SCALING
Authors: TOKAREV M. V. , PANEBRATSEV Yu. A. , ZBOROVSKÝ I. , ŠKORO G. P.
Published: September 2004

The A-dependence of z-scaling in inclusive hadron production in pA collisions at high transverse momenta is studied. The concept of z-scaling based on the fundamental principles of Nature such as self-similarity, locality, scale relativity and fractality reflecting the general features of particle interactions is applied for the description of processes of hadron production in pA collisions. The scaling function ψ is expressed via the invariant cross-section Ed3σ/dq3 and the average multiplicity density dN/dη of particles produced at pseudorapidity η=0 in the corresponding nucleon–nucleon interaction. The independence of the function ψ(z) on the center-of-mass energy [Formula: see text] for particle production near 90° in the NN c.m. system for different nuclei from D up to Pb is shown. The scale transformation z→az, ψ→a-1ψ is used to determine the A-dependence of the transformation parameter a. Based on the properties of z-scaling the dependence of the cross-sections for the π±, K±, and [Formula: see text] hadrons produced in pA collisions on transverse momentum q⊥ in the central region (η=0) at RHIC energies is predicted.
TWO-DIMENSIONAL ANYONS AND THE TEMPERATURE DEPENDENCE OF COMMUTATOR ANOMALIES
Authors: ILIEVA NEVENA
Published: September 2004

The temperature dependence of commutator anomalies is discussed on the explicit example of particular (anyonic) field operators in two dimensions. The correlation functions obtained show that the effects of the nonzero temperature might manifest themselves not only globally but also locally.
GAUGE FIELDS, SCALARS, WARPED GEOMETRY, AND STRINGS
Authors: SILVERSTEIN EVA
Published: September 2004

We review results on several interesting phenomena in warped compactifications of M theory, as presented at Strings 2000. The behavior of gauge fields in dimensional reduction from d+1 to d dimensions in various backgrounds is explained from the point of view of the holographic duals (and a point raised in the question session at the conference is addressed). We summarize the role of additional fields (in particular scalar fields) in 5d warped geometries in making it possible for Poincare-invariant domain wall solutions to exist to a nontrivial order in a controlled approximation scheme without fine-tuning of parameters in the 5d action (and comment on the status of the singularities arising in the general relativistic description of these solutions). Finally, we discuss briefly the emergence of excitations of wrapped branes in warped geometries whose effective thickness, as measured along the Poincare slices in the geometry, grows as the energy increases.
VERTEX OPERATORS FOR THE SUPERMEMBRANE AND BACKGROUND FIELD MATRIX THEORY
Authors: PLEFKA JAN
Published: September 2004

We derive the vertex operators that are expected to govern the emission of the massless d=11 supermultiplet from the supermembrane in the light cone gauge. Our results immediately imply the linear coupling of matrix theory to an arbitrary supergravity background to all orders in anticommuting coordinates. Finally we address the definition of n-point tree level and one-loop scattering amplitudes. The resulting 3-point tree level amplitudes turn out to agree with d=11 supergravity and are completely fixed by supersymmetry and the existence of a normalizable ground state.
THE SUPERGRAVITY BRANE-WORLD
Authors: LIU JAMES T.
Published: September 2004

We examine the Randall-Sundrum brane-world and demonstrate how it may be realized in terms of a doubled D3-brane configuration of type IIB theory. We further investigate the supersymmetry of the brane-world and show that, despite claims to the contrary, it is indeed compatible with supersymmetry. This result depends on having a higher dimensional origin for the model, which the type IIB realization provides.
ASPECTS OF COLLAPSING CYCLES
Authors: GREENE BRIAN R.
Published: September 2004

Much has been learned about string theory over the last few years by studying properties of cycles and branes in a given background geometry. Here we discuss three situations (quantum volume, attractor flows/D-brane stability, and dynamical topology change) in which cycles in a Calabi-Yau background evolve and/or degenerate in some manner, yielding various insights into aspects of quantum geometry.
COSMOLOGICAL BREAKING OF SUPERSYMMETRY?
Authors: BANKS T.
Published: September 2004

This is the text of my talk at the Strings 2000 Conference at the University of Michigan. It consists of three interlocking conjectures about the nature of SUSY breaking and the Cosmological Constant, as well as evidence from a toy model that demonstrates the validity of the claim that systems with a UV/IR connection can exhibit much larger SUSY breaking than local field theory.
MONOTONE INDEPENDENCE, COMB GRAPHS AND BOSE–EINSTEIN CONDENSATION
Authors: ACCARDI LUIGI , BEN GHORBAL ANIS , OBATA NOBUAKI
Published: September 2004

The adjacency matrix of a comb graph is decomposed into a sum of monotone independent random variables with respect to the vacuum state. The vacuum spectral distribution is shown to be asymptotically the arcsine law as a consequence of the monotone central limit theorem. As an example the comb lattice is studied with explicit calculation.
REDUCTION OF FREE INDEPENDENCE TO TENSOR INDEPENDENCE
Authors: LENCZEWSKI ROMUALD
Published: September 2004

In the hierarchy of freeness construction, free independence was reduced to tensor independence in the weak sense of convergence of moments. In this paper we show how to reduce free independence to tensor independence in the strong sense. We construct a suitable unital *-algebra of closed operators "affiliated" with a given unital *-algebra and call the associated closure "monotone". Then we prove that monotone closed operators of the form [Formula: see text] are free with respect to a tensor product state, where X(k) are tensor independent copies of a random variable X and (pk) is a sequence of orthogonal projections. For unital free *-algebras, we construct a monotone closed analog of a unital *-bialgebra called a "monotone closed quantum semigroup" which implements the additive free convolution, without using the concept of dual groups.
STOCHASTIC PROCESSES ON CLASSIFYING SPACES AND STRING STRUCTURES
Authors: LÉANDRE RÉMI
Published: September 2004

We give a stochastic analog of the construction of McLaughlin of the string bundle on the loop space by using tools of algebraic topology.
Keratinocyte growth factor induces Akt kinase activity and inhibits Fas-mediated apoptosis in A549 lung epithelial cells
Authors: Bao Shenying , Wang Yijie , Sweeney Patricia , Chaudhuri Alpana , Doseff Andrea I. , Marsh Clay B. , Knoell Daren L.
Published: September 2004

Acute respiratory distress syndrome (ARDS) is a syndrome characterized by the rapid influx of protein-rich edema fluid into the air spaces. The magnitude of alveolar epithelial cell injury is a key determinant of disease severity and an important predictor of patient outcome. The alveolar epithelium is positioned at the interface of the host response in the initiation, progression, and recovery phase of the disease. Keratinocyte growth factor (KGF) is a potent survival factor unique to the epithelium that promotes lung epithelial cell survival, accelerates wound closure, and reduces fibrosis. We therefore hypothesized that KGF preserves lung function by inhibiting apoptosis through activation of a signal transduction pathway responsible for cell survival. To test this hypothesis we determined that KGF inhibits death following Fas activation, a relevant apoptosis pathway, and then determined that cell survival is mediated through activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt kinase signal transduction pathway. We found that KGF induces a dose- and time-dependent increase in Akt kinase activity and that, as expected, activation of Akt via KGF is PI3K dependent. KGF inhibited Fas-induced apoptosis as measured by a reduction in apoptotic cells and caspase-3 activity. This investigation supports our original hypothesis that KGF protects the lung epithelium by inhibiting apoptosis and that protection occurs through activation of PI3K/Akt-mediated cell survival pathway. Our results are in agreement with other reports that identify the PI3K/Akt axis as a key intracellular pathway in the lung epithelium that may serve as a therapeutic target to preserve epithelial integrity during inflammation.
Exercise training increases electron and substrate shuttling proteins in muscle of overweight men and women with the metabolic syndrome
Authors: Hittel Dustin S. , Kraus William E. , Tanner Chuck J. , Houmard Joseph A. , Hoffman Eric P.
Published: September 2004

Aerobic conditioned muscle shows increased oxidative metabolism or glucose relative to untrained muscle at a given absolute exercise intensity. The studies of a targeted risk reduction intervention through defined exercise (STRRIDE) study is an aerobic exercise intervention in men and women with features of metabolic syndrome (Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, and Slentz CA, Med Sci Sports Exerc 33: 1774–1784, 2001), with four muscle biopsies taken during training and detraining time points. Here, we expanded a previous study (Hittel DS, Kraus WE, and Hoffman EP, J Physiol 548: 401–410, 2003) and used mRNA profiling to investigate gene transcripts associated with energy and substrate metabolism in STRRIDE participants. We found coordinate regulation of key metabolic enzymes with aerobic training in metabolic syndrome (aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-α1). All were also quickly downregulated by detraining, although the induction was not an acute response to activity. Protein and enzymatic assays were used to validate mRNA induction with aerobic training and loss with detraining (96 h to 2 wk) in 10 male and 10 female STRRIDE subjects. We propose that training coordinately increases the levels of aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-α1subunit, increasing glucose metabolism in muscle by liberating pyruvate for oxidative metabolism and, therefore, limiting lactate efflux. Serial measurement of fasting plasma lactate from 62 subjects from the same exercise group demonstrated a significant decrease of circulating lactate with training. We also found evidence for sex-specific molecular remodeling of muscle with ubiquinol-cytochrome c reductase core protein II, a component of mitochondrial respiratory complex III, which showed an increase after training that was specific to women. These biochemical adaptations complement existing molecular models for improved glucose tolerance with exercise intervention in prediabetic individuals.
ACL deficiency impairs the vasoconstrictive efficacy of neuropeptide Y and phenylephrine in articular tissues: a laser speckle perfusion imaging study
Authors: Miller Daniel , Forrester Kevin , Leonard Catherine , Salo Paul , Bray Robert C.
Published: September 2004

Sympathetic-derived neuropeptide Y (NPY) helps regulate inflammatory responses in injury and disease, is a vasoconstrictor, and stimulates angiogenesis. Rupture of the anterior cruciate ligament (ACL) is a common clinical presentation that results in tissue inflammation, hyperemia, and angiogenesis in the intact medial collateral ligament (MCL). This study is the first to examine the vasoregulatory role of NPY in ACL-deficient knee joints by using the newly developed technique of laser speckle perfusion imaging (LSPI). MCL blood flow was measured in two groups of adult rabbits: unoperated control ( n = 6), and 6-wk ACL transected ( n = 5). Under anesthesia, the MCL was surgically exposed and tissue blood flow was imaged at high resolution using LSPI. NPY was applied to the MCL vasculature in topical boluses of 100 μl (dose range 10−14 to 10−9 mol), and the α-adrenoceptor agonist phenylephrine was applied in doses of 10−14, 10−10, and 10−7 mol. In control rabbits, topical administration of NPY or phenylephrine produced dose-dependent vasopressor responses (maximal effect at 10−9 mol NPY and 10−7 mol phenylephrine). In ACL-transected knees, there was little or no vasoconstrictive response to NPY at any dose. The response to phenylephrine was significantly reduced compared with control ligaments. Possible causes of the reduced vasoconstrictive response to NPY in the MCL after 6 wk of ACL deficiency include development of tolerance to the peptide due to a prolonged increase in sympathetic nerve activity or change in the distribution or functionality of the NPY Y1 receptors. Chronic ACL deficiency leads to profound and protracted hyperemia in associated articular tissues. Abrogation of a vasoconstrictor response to both NPY and phenylephrine in the MCL indicates that ACL deficiency induces major changes in the vascular physiological homeostasis.
Age and regional specificity of peak limb vascular conductance in men
Authors: Proctor David N. , Le Khoi U. , Ridout Samuel J.
Published: September 2004

Because of methodological variation in previous studies, age-associated changes in peak limb vascular conductance (VCpeak; a functional index of arterial structure) and its determinants remain poorly defined. The objectives of this study were to describe and compare age-associated changes in peak forearm and calf conductance across a broad age range and to identify physiological characteristics that are predictive of variation in limb-specific VCpeak. Peak conductance (plethysmographic flow/brachial mean arterial pressure) of the forearm (forearm VCpeak) and calf (calf VCpeak) after 10 min of arterial occlusion was measured twice in 68 healthy, normally active men aged 20–79 yr. Aerobic capacity (cycle peak oxygen consumption), arterial health (ankle-brachial index, pulse wave velocity), and limb-specific measures of muscle mass (dual-energy X-ray absorptiometry) and isometric strength (grip, plantar flexion) were also assessed. The relative decline in forearm VCpeak with age (−6.6% per decade; P < 0.001) was greater than the decline in calf VCpeak (−3.4% per decade; P = 0.004). Limb VCpeak per kilogram of muscle declined with age in the forearm (−3.8% per decade; P = 0.004) but not in the calf ( P = 0.35). Age, V̇o2 peak, and regional muscle mass were significant predictors of peak conductance in both limbs; however, these predictors explained considerably less variance in the calf than in the forearm. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in men, but the magnitude of this effect is reduced in the calf relative to the forearm. This could reflect regional differences in habitual muscle use with aging in normally active men.
Tendon elongation influences the amplitude of interpolated doublets in the assessment of activation in elderly men
Authors: Morse Christopher I. , Thom Jeanette M. , Birch Karen M. , Narici Marco V.
Published: September 2004

This study investigated the influence of tendon elongation (TE) on postcontraction doublet (PCD) torque in the assessment of activation in the plantar flexors of nine elderly men (EM, age 73.7 ± 3.6 yr) and nine young men (YM, age 24.7 ± 4.7 yr). Plantar flexion maximal voluntary contractions (MVC) and activation were assessed at ankle joint angles of −20° (dorsiflexion), 0°, and 20° (plantar flexion). Across the ankle joint angles tested, compared with YM, the EM had a 36–49% lower plantar flexion MVC ( P < 0.01), TE was greater by 25–31% ( P < 0.01), and electromechanical delay was 65–108% greater ( P < 0.01). Activation (PCD torque to interpolated doublet torque) was 15% lower in EM compared with YM at −20° ( P < 0.05), but no different at 0 and 20°. In the EM, PCD torque relative to MVC torque was significantly lower at 20° compared with 0° ( P < 0.05). Electromechanical delay was positively correlated with TE ( R2 = 0.489, P < 0.01). In conclusion, this investigation demonstrates that, although a negative association exists between TE and PCD torque, the consequence of a greater TE on the estimation of activation in EM is negligible. This is due to a greater influence of ankle joint angle on the occlusion of a superimposed doublet, which counteracts the lesser influence of joint angle on TE and PCD torque. However, a greater TE in EM was found to significantly increase electromechanical delay, which is expected to influence the time needed for postural readjustments.
Mucociliary and long-term particle clearance in the airways of healthy nonsmoker subjects
Authors: Möller Winfried , Häußinger Karl , Winkler-Heil Renate , Stahlhofen Willi , Meyer Thomas , Hofmann Werner , Heyder Joachim
Published: September 2004

Spherical monodisperse ferromagnetic iron oxide particles of 1.9-μm geometric and 4.2-μm aerodynamic diameter were inhaled by 13 healthy nonsmoking subjects using the shallow bolus technique. The bolus width was 100 ml, and the penetration front depth was 150 ± 27 ml. The mean flow rate during inhalation and exhalation was 250 ml/s. The Fowler dead space and the phase 1 dead space of the airways were 282 ± 49 and 164 ± 34 ml, respectively. Deposition was below 20% without breath holding and 51 ± 8% after an 8-s breath-holding time. We attempted to confine the bolus deposition to the bronchial airways by limiting the bolus front depth to the phase 1 dead space volume. Particle retention was measured by the magnetopneumographic method over a period of 9 mo. Particle clearance from the airways showed a fast and a slow phase; 49 ± 9% followed the fast phase with a mean half-time of 3.0 ± 1.6 h and characterized the mucociliary clearance. The remaining fraction was cleared slowly with a half-time of 109 ± 78 days. The slow clearance phase was comparable to clearance measurements from the lung periphery of healthy nonsmokers, which allowed macrophage-dependent clearance mechanisms of the slow cleared fraction to be taken into account. Despite the fact that part of the slowly cleared particles may originate from peripheral deposition, the data demonstrate that mucociliary clearance does not remove all particles deposited in the airways and that a significant fraction undergoes long-term retention mechanisms, the origin of which is still under discussion.
Abnormalities of Interstitial Cells of Cajal in Dominant Megacolon Mice
Authors: Tam Wing Yip , Yip Fung Ping , Chan Wood Yee
Published: September 2004

Interstitial cells of Cajal (ICCs) in the gastrointestinal tract are a group of cells interacting with enteric neurons and smooth muscle cells. They serve as mediators of neurotransmission and pacemakers of the peristaltic movement of the gut. Previous investigations on patients with Hirschsprung’s disease and mice with aganglionic megacolon showed contrasting results on the relationship between the abnormalities of ICCs and enteric neurons. In order to ascertain whether the development of ICCs is also perturbed in the aganglionic segment of the gut, we used Dominant megacolon (Dom) mice as an animal model and an antibody specific to c-kit (a tyrosine kinase receptor expressed in ICCs) to examine the spatial distribution of ICCs in the developing and adult colon. Our results showed that in the wild-type adult colon, ICCs were bipolar in shape in the smooth muscle layer and dense networks of ICCs were observed in the myenteric and deep muscular plexuses, whereas in the aganglionic colon of Dom heterozygous mice, no ICCs could be found in the smooth muscle layer and disrupted patterns of ICC networks were observed in the myenteric and deep muscular plexuses. On 14.5 days of development, the levels of expression of c-kit and its ligand (stem cell factor) were similar in the wild-type, heterozygous and homozygous Dom embryos. However, by 18.5 days, the numbers of ICCs were greatly reduced in the myenteric and submucosal plexuses of the terminal colon of the heterozygous embryos comparing with the wild-type counterparts. Based on our results, we postulate that the abnormal development of ICCs may disrupt the neurotransmission and pacemaker activity of the gut, leading to interrupted peristalsis.
Amifostine Stimulates the Formation of Hematopoietic Bone Marrow Progenitors from B-Cell Chronic Lymphocytic Leukemia
Authors: Tsatalas Costas , Spanoudakis Emmanuel , Pantelidou Despoina , Margaritis Dimitris , Kotsianidis Ioannis , Chalkia Panagiota , Tripsianis Gregory , Basdiara Ioanna , Kartasis Zafiris , Karakolios Apostolos , Bourikas George
Published: September 2004

Amifostine is a phosphorylated aminothiol that not only protects hematopoietic progenitor cells from chemotherapy and radiotherapy, but also stimulates normal hematopoiesis. The effect of amifostine on the in vitro growth of hematopoietic progenitors derived from B-cell chronic lymphocytic leukemia(B-CLL) was investigated. The colony-forming units (CFU)-granulocyte macrophage (CFU-GM), the burst-forming units-erythroid (BFU-E) and the CFU-granulocyte erythroid macrophage megakaryocytes (CFU-GEMM) increased 38, 20 and 100%, respectively, after the incubation with amifostine. There was no statistical difference in the in vitro progenitor growth of patients grouped according to their disease stage, bone marrow lymphocytic infiltration or therapy. Our data indicate that apart from cytoprotection the parallel use of amifostine and chemotherapy in patients with B-CLL could enhance bone marrow recovery.
Eosinophilic Gastroenteritis or Eosinophilic Chloroma?
Authors: Julia A. , Nomdedeu J.F.
Published: September 2004

Granulocytic sarcoma of the small intestine preceding or as the presenting feature of acute myelogenous leukemia with chromosome 16 abnormalities has been observed in at least 4 patients. We report the case of a patient initially diagnosed with eosinophilic gastroenteritis, responding to corticosteroid treatment for 21 months and eventually transforming into an acute myelogenous leukemia with eosinophilia (M4Eo variant).
Transient Pancytopenia Preceding T Lineage Acute Lymphoblastic Leukemia
Authors: Zhao Hui , Zhang Li , Zhu Xiaofan , Chen Yumei , Zou Yao , Zhang Lei , Yang Renchi , Han Zhong Chao
Published: September 2004

Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL) is a rare occurrence usually affecting children with subsequent development of B lineage ALL. We report a case of pre-ALL characterized by a T cell immunophenotype and abnormal karyotype t (11; 14) (q10; q10). The patient achieved a transient complete remission after initial therapy, but relapsed within a few months and died of leukemic encephalopathy. To the best of our knowledge, this is the first report of T lineage pre-ALL.
Sensory Systems in Amphioxus: A Window on the Ancestral Chordate Condition
Authors: Lacalli Thurston C.
Published: September 2004

Amphioxus has an assortment of cells and organs for sensing light and mechanical stimuli. Vertebrate counterparts of these structures are not always apparent, and a strong case can be made for homology in only a few instances. For example, amphioxus has anatomically simple but plausible homologs of both the pineal and paired eyes of vertebrates. Placodal and neural crest derivatives are, however, more problematic: the evidence for an olfactory system in amphioxus is only circumstantial and, despite the variety of secondary sensory cell types that occur on the body surface in amphioxus, none are obvious homologs of vertebrate taste buds, neuromasts or acoustic hair cells. A useful perspective can nevertheless be gained by examining differences in amphioxus and vertebrate development, specifically how each specifies and positions sensory precursors, controls their proliferation, and deploys them through the body. The much larger size of vertebrate embryos and the need to cope developmentally with increased scale and cell numbers may account for some key vertebrate innovations, including placodes and neural crest. The presence or absence of specific structural adaptations, like the latter, is therefore less useful for judging homology between amphioxus and vertebrates than shared features of specific cell types. It is also clear that the duration of embryogenesis in vertebrates has been significantly extended in comparison with ancestral chordates so as to incorporate events that would originally have occurred during the post-embryonic growth period, including events of neurogenesis. Consequently, no scenario for the origin of vertebrates can be considered complete unless it deals explicitly with the whole of the life history and changes to it.
Keeping Sensory Cells and Evolving Neurons to Connect Them to the Brain: Molecular Conservation and Novelties in Vertebrate Ear Development
Authors: Fritzsch B. , Beisel K.W.
Published: September 2004

The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an ‘organ’ system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.