bluuebunny/crossref_metadata_2025 huggingface dataset:
RanBPM is an L1‐interacting protein that regulates L1‐mediated mitogen‐activated protein kinase activation
Authors: Cheng Ling , Lemmon Sandra , Lemmon Vance
Published: July 2005

A yeast two‐hybrid screen using the last 28 amino acids of the cytoplasmic domain of the neural cell adhesion molecule L1 identified RanBPM as an L1‐interacting protein. RanBPM associates with L1 in vivo and the N‐terminal region of RanBPM (N‐RanBPM), containing the SPRY domain, is sufficient for the interaction with L1 in a glutathione S‐transferase pull‐down assay. L1 antibody patching dramatically changes the subcellular localization of N‐RanBPM in transfected COS cells. Overexpression of N‐RanBPM in COS cells reduces L1‐triggered extracellular signal‐regulated kinase 1/2 activation by 50% and overexpression of N‐RanBPM in primary neurons inhibits L1‐mediated neurite outgrowth and branching. These data suggest that RanBPM is an adaptor protein that links L1 to the extracellular signal‐regulated kinase/MAPK pathway.
Treatment of YAC128 mice and their wild‐type littermates with cystamine does not lead to its accumulation in plasma or brain: implications for the treatment of Huntington disease
Authors: Pinto John T. , Van Raamsdonk Jeremy M. , Leavitt Blair R. , Hayden Michael R. , Jeitner Thomas M. , Thaler Howard T. , Krasnikov Boris F. , Cooper Arthur J. L.
Published: July 2005

Cystamine is beneficial to Huntington disease (HD) transgenic mice. To elucidate the mechanism, cystamine metabolites were determined in brain and plasma of cystamine‐treated mice. A major route for cystamine metabolism is thought to be: cystamine → cysteamine → hypotaurine → taurine. Here we describe an HPLC system with coulometric detection that can rapidly measure underivatized cystamine, cysteamine and hypotaurine, as well as cysteine and glutathione in the same deproteinized tissue sample. A method is also described for the coulometric estimation of taurine as its isoindole‐sulfonate derivative. Using this new methodology we showed that cystamine and cysteamine are undetectable (≤ 0.2 nmol/100 mg protein) in the brains of 3‐month‐old HD transgenic (YAC128) mice (or their wild‐type littermates) treated daily for 2 weeks with cystamine (225 mg/kg) in their drinking water. No significant changes were observed in brain glutathione and taurine but significant increases were observed in brain cysteine. Cystamine and cysteamine were not detected in the plasma of YAC128 mice treated daily with cystamine between the ages of 4 and 12 or 7 and 12 months. These findings suggest that cystamine is not directly involved in mitigating HD but that increased brain cysteine or uncharacterized sulfur metabolites may be responsible.
Neurotoxicity and behavioral deficits associated with Septin 5 accumulation in dopaminergic neurons
Authors: Son Jin H. , Kawamata Hibiki , Yoo Myung S. , Kim Dae J. , Lee Young K. , Kim SooYoul , Dawson Ted M. , Zhang Hui , Sulzer David , Yang Lichuan , Beal M. Flint , DeGiorgio Lorraine A. , Chun Hong S. , Baker Harriet , Peng Chu
Published: July 2005

Septin 5, a parkin substrate, is a vesicle‐ and membrane‐associated protein that plays a significant role in inhibiting exocytosis. The regulatory function of Septin 5 in dopaminergic (DAergic) neurons of substantia nigra (SN), maintained at relatively low levels, has not yet been delineated. As loss of function mutations of parkin are the principal cause of a familial Parkinson's disease, a prevailing hypothesis is that the loss of parkin activity results in accumulation of Septin 5 which confers neuron‐specific toxicity in SN‐DAergic neurons. In vitro and in vivo models were used to support this hypothesis. In our well‐characterized DAergic SN4741 cell model, acute accumulation of elevated levels of Septin 5, but not synphilin‐1 (another parkin substrate), resulted in cytotoxic cell death that was markedly reduced by parkin co‐transfection. A transgenic mouse model expressing a dominant negative parkin mutant accumulated moderate levels of Septin 5 in SN‐DAergic neurons. These mice acquired a progressive l‐DOPA responsive motor dysfunction that developed despite a 25% higher than normal level of striatal dopamine (DA) and no apparent loss of DAergic neurons. The phenotype of this animal, increased striatal dopamine and reduced motor function, was similar to that observed in parkin knockout animals, suggesting a common DAergic alteration. These data suggest that a threshold level of Septin 5 accumulation is required for DAergic cell loss and that l‐DOPA‐responsive motor deficits can occur even in the presence of elevated DA.
Evidence that gabapentin reduces neuropathic pain by inhibiting the spinal release of glutamate
Authors: Coderre Terence J. , Kumar Naresh , Lefebvre Celeste D. , Yu Jonathan S. C.
Published: July 2005

Gabapentin is an anticonvulsant that successfully treats many neuropathic pain syndromes, although the mechanism of its antihyperalgesic action remains elusive. This study aims to help delineate gabapentin's antihyperalgesic mechanisms. We assessed the effectiveness of gabapentin at decreasing mechanical and cold hypersensitivity induced in a rat model of neuropathic pain. Thus, we compared the effectiveness of pre‐ or post‐treatment with systemic or intrathecal (i.t.) gabapentin at reducing the development and maintenance of the neuropathic pain symptoms. Gabapentin successfully decreased mechanical and cold hypersensitivity, both as a pretreatment and post‐treatment. Furthermore, both i.t. and systemic administration of gabapentin were effective in reducing the behavioral hypersensitivity; however, the i.t. administration was superior to the systemic. We also examined gabapentin's effects at inhibiting hindpaw formalin‐induced release of excitatory amino acids (EAAs) in the spinal cord dorsal horn (SCDH) both in naïve rats and in rats with neuropathic pain. We present the first evidence that gabapentin reduces the formalin‐induced release of both glutamate and aspartate in SCDH. Furthermore, i.t. gabapentin reduces the enhanced noxious stimulus‐induced spinal release of glutamate seen in neuropathic rats. These data suggest that gabapentin reduces neuropathic pain symptoms by inhibiting the release of glutamate in the SCDH.
Prostaglandin H2‐derived adducts of proteins correlate with Alzheimer's disease severity
Authors: Zagol‐Ikapitte Irene , Masterson Tina S. , Amarnath V. , Montine Thomas J. , Andreasson Katrin I. , Boutaud Olivier , Oates John A.
Published: July 2005

The formation of cyclooxygenase‐derived lipid adducts of protein in brains of patients who had Alzheimer's disease has been investigated. The enzymatic product of the cyclooxygenases, prostaglandin H2, rearranges in part to highly reactive γ‐ketoaldehydes, levuglandin (LG) E2 and LGD2. These γ‐ketoaldehydes react with free amines on proteins to yield a covalent adduct. Utilizing analysis of the levuglandinyl‐lysine adducts by liquid chromatography‐tandem mass spectrometry, we now find that this post‐translational modification is increased significantly in the hippocampus in Alzheimer's disease. The magnitude of the increase correlates with the pathological evidence of severity.
Characterization of a novel D2‐like dopamine receptor with a truncated splice variant and a D1‐like dopamine receptor unique to invertebrates from Caenorhabditis elegans
Authors: Sugiura Mai , Fuke Satoshi , Suo Satoshi , Sasagawa Noboru , Van Tol Hubert H. M. , Ishiura Shoichi
Published: July 2005

We have cloned two novel Caenorhabditis elegans dopamine receptors, DOP‐3 and DOP‐4. DOP‐3 shows high sequence homology with other D2‐like dopamine receptors. As a result of alternative splicing, a truncated splice variant of DOP‐3, DOP‐3nf, was produced. Because of the in‐frame insertion of a stop codon in the third intracellular loop, DOP‐3nf lacks the sixth and seventh transmembrane domains that are found in the full‐length DOP‐3 receptor. Reporter gene assay showed that DOP‐3 attenuates forskolin‐stimulated cAMP formation in response to dopamine stimulation, whereas DOP‐3nf does not. When DOP‐3 was coexpressed with DOP‐3nf, the ability to inhibit forskolin‐stimulated cAMP formation was reduced. DOP‐4 shows high sequence homology with D1‐like dopamine receptors unique to invertebrates, which are distinct from mammalian D1‐like dopamine receptors. Reporter gene assay showed that DOP‐4 stimulates cAMP accumulation in response to dopamine stimulation. These two receptors provide new opportunities to understand dopaminergic signaling at the molecular level.
Ratzinger Is Right
Authors: GIRARD RENÉ
Published: July 2005

No sooner had John Paul II stepped across the threshold of Heaven than Cardinal Ratzinger, now elected Pope Benedict, declared the new mission of the Catholic Church would be to fight “the dictatorship of relativism.”

To explore this theme, NPQ spoke with René Girard, the famous anthropologist and author of the seminal study Violence and the Sacred. We then asked Pankaj Mishra, one of the most exciting new non‐fiction writers and author of An End to Suffering: The Buddha in the World, to respond.
Cost Efficiency for Alberta and Ontario Dairy Farms: An Interregional Comparison
Authors: Hailu Getu , Jeffrey Scott , Unterschultz James
Published: July 2005

In this study, two non‐homothetic translog stochastic meta‐frontier cost functions—with and without local concavity imposed—are estimated using a nonlinear maximum likelihood estimation procedure to compare the cost efficiency of Alberta and Ontario dairy farms for the period 1984–96. The resulting cost efficiency estimates are not very sensitive to whether or not curvature is imposed. In contrast, the properties of the cost and input demand functions (e.g., elasticities) are sensitive to imposition of local concavity during estimation. The implication is that if an inappropriate model that does not satisfy the properties required by the economic theory is used, the estimated input demand functions may not be reliable. Average cost efficiency for the pooled sample, with local concavity imposed, is approximately 89%. This suggests some potential for improved performance in the sector. The results also suggest that Ontario dairy farms may be more cost efficient than Alberta dairy farms, but the statistical evidence is inconclusive.
SINGLE INTERFACE GROWTH: FLUCTUATIONS AND THE CORRELATION LENGTH
Authors: HECHT I. , BE'ER A. , TAITELBAUM H.
Published: July 2005

Growth behavior of interfaces is usually described by a power-law of the growth in time of the interface width. This general scaling picture is an average behavior description, which may not be valid when only a finite number of interfaces is considered. In this work we study theoretically and experimentally the growth behavior of single interfaces and show that the growth of the interface width always exhibits a non-monotonic, fluctuating behavior. We study numerically the Quenched-noise Kardar-Parisi-Zhang (QKPZ) equation, using different noise distributions, and show that this behavior results from competing mechanisms of normal growth and surface tension forces in this equation. We define a new measure of the interface width fluctuations and present a way to extract the correlation length of the interface from these fluctuations.
ESCAPE TIMES IN STOCK MARKETS
Authors: BONANNO G. , SPAGNOLO B.
Published: July 2005

We study the statistical properties of escape times for stock price returns in the Wall Street market. In particular we get the escape time distribution for real data from daily transactions and for three models: (i) the Wiener process with drift and a constant market volatility, (ii) Heston and (iii) GARCH models, where the volatility is a stochastic process. We find that the first model is unable to catch all the features of the escape time distribution of real data. Moreover, the Heston model describes the probability density function for both return and escape times better than the GARCH model.
THE OPEN BCS MODEL, ITS STOCHASTIC LIMIT AND SOME GENERALIZATIONS
Authors: BAGARELLO FABIO
Published: July 2005

In this paper we use the stochastic limit approach as a tool to discuss the open BCS model of low temperature superconductivity. We also briefly discuss the role of a second reservoir interacting with the first one (but not with the system) in the computation of the critical temperature corresponding to the transition from a normal to a superconducting phase.
EXPLORING DECISION STRATEGIES AND EVALUATIONS OF PERFORMANCE BY NETWORKED AND NON-NETWORKED SMALL U.S. BUSINESSES
Authors: MILLER NANCY J. , BESSER TERRY L.
Published: July 2005

A strategic network perspective established the theoretical foundation for exploring aspects of business management in 383 small businesses predominantly operating in small communities across the U.S. It was proposed that those owner/managers involved in formal voluntary organizations to promote business effectiveness would differ in their strategic decisions and evaluations of performance from businesses without such formal group affiliations. Business strategies assessed involved the emphasis placed on employees, customers, and community, and the effect of these three variables in explaining four elements of business performance. Networking businesses were found to place more emphasis on strategies dealing with employees, customers, and community than non-networking businesses. Final results suggested that network membership held a direct effect on business strategies, and that these strategies held varying direct effects on perceptions of business performance. Findings offer initial support for strategic network theory as well as practical information for small business owners considering network membership.
Indirect Interaction Webs: Herbivore-Induced Effects Through Trait Change in Plants
Authors: Ohgushi Takayuki
Published: July 2005

▪ Abstract  Although predation has a lethal effect on prey, mature terrestrial plants are rarely killed by herbivores, but herbivory can change plant allelochemistry, cell structure and growth, physiology, morphology, and phenology. This review explores the herbivore-induced indirect effects mediated by such plant responses following herbivory in terrestrial systems. Herbivore-induced indirect effects are ubiquitous in many plant–herbivore systems, and indirect interactions occur among temporally separated, spatially separated, and taxonomically distinct herbivore species. Unlike interspecific competition, herbivores can benefit each other through plant-mediated indirect effects. Herbivore-induced changes in plants occur at low levels of herbivory, which increases the likelihood of plant-mediated indirect interactions between herbivores. The herbivore-induced indirect effects result in interaction linkages, which alter species richness and abundance in arthropod communities. Such interaction linkages should be depicted using indirect interaction webs, which incorporate nontrophic, indirect links. The idea of interaction linkages by herbivore-induced indirect effects that shape community organization and biodiversity is an important revision of the traditional view of plant-based terrestrial food webs.
Connecting Mammalian Genome with Phenome by ENU Mouse Mutagenesis: Gene Combinations Specifying the Immune System
Authors: Papathanasiou Peter , Goodnow Christopher C.
Published: July 2005

The human and mouse genome sequences bring closer the goal of understanding how characteristics of adult mammalian physiology and pathology are encoded by DNA. Here we review the challenge of understanding how genes specify mammalian traits, with particular focus on the cells and behavior of the immune system. Summarized is the emerging experience, advantages, and limitations of using ethylnitrosourea (ENU) to modify the mouse genome and select informative variants by phenotypic screens, yielding two main conclusions. First, ENU-induced variation provides an eminently feasible route to understanding how the genome encodes important mammalian processes without any prior assumptions about genes, their chromosomal locations, or expression patterns. Second, ENU alleles match those arising by natural variation. By changing individual protein domains or splice products, these alleles reveal separate gene functions specified through protein combinations.
Human umbilical cord blood-derived cells differentiate into hepatocyte-like cells in the Fas-mediated liver injury model
Authors: Nonome Kazunobu , Li Xiao-Kang , Takahara Terumi , Kitazawa Yusuke , Funeshima Naoko , Yata Yutaka , Xue Feng , Kanayama Masami , Shinno Eiji , Kuwae Chieko , Saito Shigeru , Watanabe Akiharu , Sugiyama Toshiro
Published: July 2005

Human umbilical cord blood (HUCB) contains stem/progenitor cells, which can differentiate into a variety of cell types. In this study, we investigated whether HUCB cells differentiate into hepatocytes in vitro and in vivo. We also examined whether CD34 could be the selection marker of stem cells for hepatocytes. HUCB cells were obtained from normal full-term deliveries, and CD34+/−cells were further separated. For in vitro study, HUCB cells were cultured for 4 wk, and expressions of liver-specific genes were examined. For the in vivo study, nonobese diabetic/severe combined immunodeficient mice were subjected to liver injury by a Fas ligand-carried adenoviral vector or only radiated. Mice were treated simultaneously with or without cell transplantation of HUCB, CD34+, or CD34−cells. After 4 wk, human-specific gene/protein expression was examined. In the in vitro study, human liver-specific genes were positive after 7 days of culture. The immunofluorescent study showed positive staining of α-fetoprotein, cytokeratin 19, and albumin in round-shaped cells. In the in vivo study, immunohistochemical analysis showed human albumin-positive, hepatocyte-specific antigen-positive cells in mouse livers of the Fas ligand/transplantation group. Fluorescence in situ hybridization analysis using the human Y chromosome also showed positive signals. However, no difference between transplanted cell types was detected. In contrast, immunopositive cells were not detected in the irradiated/transplantation group. The RT-PCR result also showed human hepatocyte-specific gene expressions only in the Fas ligand/transplantation group. HUCB cells differentiated into hepatocyte-like cells in the mouse liver, and liver injury was essential during this process. The differences between CD34+and CD34−cells were not observed in human hepatocyte-specific expression.
PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage
Authors: Hsieh Ya-Ching , Yang Shaolong , Choudhry Mashkoor A. , Yu Huang-Ping , Rue Loring W. , Bland Kirby I. , Chaudry Irshad H.
Published: July 2005

Flutamide, an androgen receptor antagonist, is thought to improve cardiovascular function by blocking the androgen receptor after trauma-hemorrhage (T-H). Although 17β-estradiol (E2) and flutamide improve cardiac function after T-H, whether E2 and flutamide produce their salutary effect via the same or a different mechanism is unknown. We hypothesized that E2 and flutamide mediate their effects via estrogen receptor (ER)-mediated upregulation of peroxisome proliferator-activated receptor coactivator 1 (PGC-1). PGC-1, a key regulator of cardiac mitochondrial function, induces mitochondrial genes by activating transcription factors such as nuclear respiratory factor 2 (NRF-2), which regulates mitochondrial proteins [i.e., mitochondrial transcription factor A (Tfam), cytochrome- c oxidase subunit IV, and β-ATP synthase]. Adult male rats underwent T-H [5-cm midline incision and hemorrhage (blood pressure = 40 mmHg for ∼90 min)] and resuscitation. At the onset of resuscitation, rats received vehicle, flutamide (25 mg/kg), or E2 (50 μg/kg). Another group received the ER antagonist ICI-182780 (3 mg/kg) with or without flutamide. Flutamide or E2 administration after T-H restored depressed cardiac function. Moreover, E2 and flutamide normalized expression of cardiac PGC-1, NRF-2, Tfam, cytochrome- c oxidase subunit IV, and the mitochondrial DNA-encoded gene cytochrome- c oxidase subunit I and β-ATP synthase, mitochondrial ATP, and cytochrome- c oxidase activity. However, if the ER antagonist ICI-182780 was administered with flutamide, flutamide-mediated PGC-1 upregulation was totally abolished. These results indicate that E2 and flutamide upregulate PGC-1 via the ER. Thus PGC-1 upregulation appears to be the common mechanism by which E2 and flutamide mediate their salutary effects on cardiac function after T-H.
Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise
Authors: Miller Jordan D. , Pegelow David F. , Jacques Anthony J. , Dempsey Jerome A.
Published: July 2005

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Q̇fv) and net Q̇fv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/“rib cage” (ΔPab <2 cmH2O) or diaphragmatic (ΔPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Q̇fv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Q̇fv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Q̇fv relative to nonloaded conditions (net retrograde flow = −9 ± 12% and −4 ± 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Q̇fv, such that >90% of all anterograde Q̇fv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Q̇fv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Q̇fv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.
Reduction of Temporomandibular Joint Pain after Treatment with a Combination of Methotrexate and Infliximab Is Associated with Changes in Synovial Fluid and Plasma Cytokines in Rheumatoid Arthritis
Authors: Kopp Sigvard , Alstergren Per , Ernestam Sofia , Nordahl Silvi , Morin Pär , Bratt Johan
Published: July 2005

The aims were to investigate the effect of intravenous infusions of the tumor necrosis factor-α (TNF-α) antibody infliximab on symptoms and signs of temporomandibular joint (TMJ) involvement in relation to effects on synovial fluid and plasma proinflammatory TNF-α, interleukin-1β (IL-1β) and interleukin-6 as well as antiinflam matory soluble TNF receptor II (TNF-sRII), interleukin-1 receptor antagonist (IL-1ra), soluble IL-1 receptor II (IL-1sRII) and interleukin-10 (IL-10) in patients with active rheumatoid arthritis (RA). Nineteen patients with TMJ involvement taking methotrexate were included in the study. TMJ and general joint pain intensity as well as pain on mandibular movements, tenderness to digital palpation, pressure pain threshold and maximum mouth-opening capacity were assessed in a clinical examination. The effect of infliximab was assessed after 2 and 14 or 22 weeks. TMJ synovial fluid and venous blood were collected for cytokine analysis at all occasions while determination of erythrocyte sedimentation rate and C-reactive protein were performed at baseline and at long-term follow-up only. Reduction of TMJ pain was associated with raised levels of synovial fluid TNF-sRII and IL-1sRII as well as raised plasma levels of IL-1ra and IL-10. Decreased erythrocyte sedimentation rate was associated with decreased tenderness to digital palpation. Reduced general joint pain intensity was associated with reduced plasma levels of IL-6 and C-reactive protein. In conclusion, systemic treatment with a combination of infliximab and methotrexate reduces TMJ pain in RA in association with an increase in anti-inflammatory cytokines and receptors in synovial fluid and plasma.
Anatomically Based Modelling of the Human Skull and Jaw
Authors: van Essen N.L. , Anderson I.A. , Hunter P.J. , Carman J. , Clarke R.D. , Pullan A.J.
Published: July 2005

We present here an anatomically based model of the human masticatory system that provides a framework for simulating the complex chewing process. The initial motivation for creating this model was the desire to have a computational model of the human jaw that can be used to simulate the action of simple bites, and to calculate the stresses and forces on the teeth that are involved. The model created also provides a platform that can be used to investigate other features of the masticatory system. To construct this global model, individual models of the bones of the skull and jaw were created from generic data sets. Geometric models of the muscles of mastication were also created and attached to the appropriate bones. To complete this initial model, representations of the crowns of the teeth were created and a basic model of the temporomandibular joint (TMJ) was included. The finite element method was used to solve for the stresses and strains created by the loading conditions during a clenching simulation involving the mandible bone. The model presented here is also discussed in relation to a model of the entire musculo-skeletal system being developed as part of the Physiome Project.
Modeling of Temporomandibular Joint Function Using MRI and Jaw-Tracking Technologies – Mechanics
Authors: Gallo Luigi M.
Published: July 2005

The study of mechanics of the temporomandibular joint (TMJ) is important because its dysfunction and breakdown could be, at least partially, of mechanical origin. The incongruity of the articular surfaces of the TMJ is compensated by a fibrocartilaginous articular disc. Its dislocation and failure seem to be closely related to the development of osteoarthritis of the TMJ. The analysis of mandibular kinematics permits the detection and assessment of irregularities of TMJ function due to internal obstacles such as a displaced articular disc. Furthermore, the measurement of the dynamic relationship between the articular surfaces of the TMJ is useful to determine the strains undergone by the disc that if too high might compromise its integrity. The development of our research in TMJ mechanics has evolved from the acquisition of the traces of single mandibular points to an accurate and compact description of mandibular motion, in which the mechanical advantage of jaw muscles, and forces and torques acting on the jaw are considered as well. The combination of three-dimensional software models of TMJ anatomies obtained from MRI and jaw tracking with six degrees of freedom permits a subject-specific dynamic analysis of the intra-articular space, providing insight into individual disc deformation during function and TMJ loading. Studies performed with this system indicate that both TMJs are loaded during chewing, the balancing more so than the working joint. In fact, during chewing, the intra-articular distance is smaller for hard than for soft food, on closing than on opening, on the balancing than on the working side. This last finding is confirmed by static biting experiments, in which the condyle-fossa distance decreases more on the side contralateral to the bite force, depending on its magnitude. Also studies on the dynamics of compression areas indicate that plowing can occur through the disc during function, especially mediolaterally, due to stress field translation. This effect might contribute to cartilage wear and fatigue also because the disc is weaker mediolaterally. Further data indicate that the lateral area of the disc is mostly exposed to a higher mechanical energy density. This will be more intensively investigated using finite element method.
Why Look in the Brain for Answers to Temporomandibular Disorder Pain?
Authors: Sarlani Eleni , Greenspan Joel D.
Published: July 2005

Temporomandibular disorder (TMD) patients often exhibit widespread clinical pain, as well as greater sensitivity to experimental pain than pain-free controls, suggesting a role of central pathophysiologic mechanisms in TMD. Moreover, TMD is more prevalent among women, which may be related to the higher sensitivity of women to experimental pain. Women also exhibit greater temporal summation of heat pain compared to men. Temporal summation, the increase in pain intensity upon repetitive noxious stimulation of constant intensity, at a high frequency is centrally mediated. Thus, greater temporal summation in women indicates that their central nociceptive processing is upregulated compared to men. Recent studies in our research center sought further evidence for upregulation of central nociceptive processing in females compared to males and in TMD patients compared to healthy controls, assessing group differences in temporal summation of mechanically evoked pain, and aftersensations following repetitive noxious stimulation. Sixteen series of 10 repetitive, sharp, mechanical stimuli were applied to the fingers of 25 female TMD patients, 25 healthy women, and 25 healthy men, with a computer-controlled small probe. All subjects rated the pain intensity or the unpleasantness evoked by the 1st, 5th and 10th stimulus in the series, and the aftersensations 15 s and 1 min after the last stimulus on visual-analog scales. TMD patients exhibited greater temporal summation of pain and unpleasantness, stronger aftersensations, and more frequent painful aftersensations than controls. Healthy females showed greater temporal summation of pain intensity and unpleasantness, higher intensity and unpleasantness of aftersensations, and more frequent painful aftersensations than males. Greater temporal summation of pain and aftersensations from digital stimulation of TMD patients than controls suggest a generalized hyperexcitability of the central nociceptive system in this patient group. Such hyperexcitability may contribute to the development and/or maintenance of chronic TMD pain. Moreover, greater temporal summation of pain and aftersensations in healthy females than males indicate that their central processing of nociceptive input may be more easily upregulated into pathological hyperexcitability, possibly accounting for the predominance of TMD among women.
Multilevel and Continuous Pleural Fluid pH Likelihood Ratios for Draining Parapneumonic Effusions
Authors: Heffner John E. , Heffner John N. , Brown Lee K.
Published: July 2005

Background: Although clinical practice guidelines endorse the use of pleural fluid pH to select patients with parapneumonic effusions for pleural drainage, no studies have reported likelihood ratios for pleural fluid pH. Objectives: We derived and tested the value of continuous likelihood ratios for selecting pneumonia patients for pleural drainage. Methods: Patient level pleural fluid pH results were obtained from a registry of primary studies that assessed the discriminative properties of pH. Multilevel likelihood ratios were calculated for four pH intervals. Continuous likelihood ratios were derived from logistic regression using discrete pH values. Binary, multilevel and continuous likelihood ratios were compared to evaluate the statistical (χ2) and clinical advantages of continuous likelihood ratios. Results: Hundred and ninety-seven pleural fluid pH results were retrieved from published reports and categorized into four pH ordinal intervals. Multilevel likelihood ratios ranged from a low of 0.13 (95% CI, 0.04–0.41) for pH values >7.40 to a high of 15.80 (95% CI, 7.04–35.45) for pH values ≤7.00. Logistic regression derived the following equation for continuous likelihood ratios: exp[–7.168(measured pH – 7.207)]. Continuous likelihood ratios offered more diagnostic information both statistically (p < 0.005) and clinically compared with binary and multilevel likelihood ratios. Conclusions: Analysis of a patient registry allows the derivation of an exponential equation that calculates continuous likelihood ratios for discrete pleural fluid pH values. Continuous likelihood ratios provide more clinically and statistically significant information compared with binary and multilevel likelihood ratios for calculating posttest probabilities of the need to drain parapneumonic effusions.
Response to Empirical Anti-Tuberculosis Treatment in Patients with Sputum Smear-Negative Presumptive Pulmonary Tuberculosis
Authors: Lee Chang-Hoon , Kim Woo Jin , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Shim Young-Soo , Yim Jae-Joon
Published: July 2005

Background: In many cases, physicians initiate anti-tuberculosis (TB) treatment based only on symptoms or radiographic findings without confirmation of pulmonary TB by acid-fast bacilli (AFB) smear. It has not been well known which clinical characteristics could be used as predictors for positive culture or real TB in patients with sputum smear-negative presumptive pulmonary TB. Objective: We tried to elucidate treatment outcomes in patients with sputum smear-negative presumptive pulmonary TB and to find predictors of positive culture results. Methods: We reviewed data of the patients who had been treated as presumptive TB with negative AFB smear on the basis of clinical and radiographic features from December 1998 to December 2000 at a university hospital in Korea. We reviewed medical records and radiographs of patients and analyzed possible predictors for positive culture. Results: One hundred and one patients were enrolled. Among them, pulmonary TB was confirmed by culture in 32 patients (31%). Thirty-one (96.9%) out of 32 culture-positive patients showed clinical or radiographic improvement as did 50 (72.5%) out of 69 culture-negative patients. The predictor for a positive culture result is the presence of patchy consolidation in an initial radiograph (p = 0.025; OR 2.89; 95% CI 1.14–7.28). Conclusions: The empirical anti-TB treatment in patients with sputum smear-negative presumptive pulmonary TB was effective and adequate, especially presented with patchy consolidation in initial chest radiographs in Korea.
Psychotherapy Improves Compliance with Tuberculosis Treatment
Authors: Janmeja A.K. , Das S.K. , Bhargava R. , Chavan B.S.
Published: July 2005

Background: Low treatment completion rate in tuberculosis (TB) patients is a major concern. Physicians have always been striving for better treatment adherence in such patients. The present study is one such attempt in this direction. Objectives: The study was aimed to evaluate the role of behavior modification by psychotherapy in improving compliance with short-course anti-TB chemotherapy in India. Methods: It was a prospective controlled trial involving patients with confirmed pulmonary and extrapulmonary TB enrolled in the National Tuberculosis Program. The intervention group underwent pretreatment psychological assessment followed by regular psychotherapy sessions. Results: The intervention group had a demographic profile comparable to that of the control group. The patients were mostly from low- and middle-income backgrounds from urban and semi-urban areas. They consistently showed poor knowledge about the nature of the disease, low motivation, and had considerable apprehensions. Following the sessions, the intervention group showed improved compliance compared with the control group, reflected in significantly higher treatment completion and cure rates. Conclusions: The study suggests that psychological intervention is effective in improving compliance with anti-TB treatment, and may reduce the incidence of treatment failure, relapse and drug resistance.
Survival Analyses of Patients with Thoracic Complications Secondary to Bronchial Carcinoma at the Time of Diagnosis
Authors: Bülbül Yılmaz , Oztuna Funda , Topba Murat , Ozlu Tevfik
Published: July 2005

Background: The impact on survival of thoracic complications secondary to bronchial carcinoma has not been clearly analyzed. Objectives: The purpose of this study was to assess the significance of these complications for the survival of lung cancer patients. Methods: All patients diagnosed at our center from March 2000 to January 2004 were analyzed to estimate survival among patients with or without thoracic complication. Any intrathoracic change or abnormality secondary to bronchial carcinoma such as atelectasis or pleural effusion was defined a thoracic complication. Survival was calculated using the Kaplan-Meier method, and the complications predicting survival were evaluated using Cox’s regression analysis. Results: Of the 182 eligible patients, 61.5% had at least one thoracic complication. The complications were atelectasis, pulmonary metastases, pleural effusion, laryngeal nerve involvement, vena cava superior syndrome and others. Specific survival times for each complication were not different, except in the case of atelectasis. Median survival was significantly longer in patients with atelectasis, as opposed to nonatelectatic patients. Survival times in patients with at least one complication were not different than those of patients without complication. However, median survival of patients with one of the complications, excluding atelectasis (since this was associated with improved survival), was 3 months shorter (p = 0.029). Cox’s regression analysis also predicted atelectasis for improved survival. Conclusion: Atelectasis, which was determined to be the most frequent thoracic complication, was identified as a favorable prognostic factor in patients with advanced stage lung cancer.
Respiratory Impedance following Bronchoscopic or Surgical Lung Volume Reduction for Emphysema
Authors: Ingenito Edward P. , Tsai Larry W. , Mentzer Steven J. , Jaklitsch Michael T. , Reilly John J. , Lutchen Kenneth , Mazan Melissa , Hoffman Andrew
Published: July 2005

Background: Bronchoscopic methods for achieving lung volume reduction (BLVR) are presently undergoing clinical trials, and will soon be clinically available. Understanding the differential effects of surgical volume reduction therapy (LVRS) and BLVR on lung and chest wall physiology will assist physicians in selecting an optimal approach for patients. Objectives: Determine whether LVRS adversely affects lung or chest wall physiology at 3-month follow-up relative to BLVR in an experimental model of sheep emphysema. Methods: Twelve mixed-breed sheep were treated with papain to produce experimental emphysema, and were divided into control, LVRS, and BLVR treatment groups. Lung and chest wall impedance was measured at 0, 5, and 10 cm H2O positive end-expiratory pressure at baseline and 3-month follow-up. Results: Emphysema was associated with increased airway resistance, decreased lung tissue resistance and elastance, and increased chest wall tissue resistance. Following treatment, equivalent increases in lung elastance occurred in the LVRS and BLVR groups compared to controls. LVRS did not adversely affect chest wall impedance despite causing extensive pleural scarring. Conclusions: (1) Experimental emphysema following prolonged papain exposure progresses after cessation of treatment. (2) BLVR and LVRS produced equivalent lung and chest wall impedance responses at 3-month follow-up. (3) LVRS did not adversely affect chest wall impedance despite being associated with extensive pleural scarring.
Interleukin-1 Gene Cluster Polymorphisms Are Associated with Nutritional Status and Inflammation in Patients with End-Stage Renal Disease
Authors: Maruyama Yukio , Nordfors Louise , Stenvinkel Peter , Heimbürger Olof , Bárány Peter , Pecoits-Filho Roberto , Axelsson Jonas , Hoff Catherine M. , Holmes Clifford J. , Schalling Martin , Lindholm Bengt
Published: July 2005

Background: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1β (IL-1β) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. Methods: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52 ± 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B –511C/T, –31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. Results: Wasting (SGA >1) was present in 31%, whereas inflammation (CRP ≧10 mg/l) was present in 36% of the patients. The male carriers of the –511T/T and –31C/C genotypes had a lower prevalence of wasting (p < 0.05), higher body mass index (BMI) (p < 0.05), and higher lean body mass (LBM) (p < 0.01). In a stepwise multiple regression model, age (p < 0.05), BMI (p < 0.01) and the IL-1B –511 genotype (p < 0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p < 0.05) and lower serum hsCRP (p < 0.05). The VNTR in IL-1RN was not associated with any markers. Conclusion: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.
Stroke Research in the Modern Era: Images versus Dogmas
Authors: Baron Jean-Claude
Published: July 2005

Recovery of function following ischaemic stroke is a fascinating clinical observation. It comprises several modes, e.g. spectacular recovery in a matter of hours or days and gradual recovery over months or even years. That a non-functioning neural system can regain its function, even partially so, is challenging because of the obvious therapeutic implications. Until the mid-70s, however, dogmas largely prevailed which underpinned the then nihilistic approach to stroke patients. Proving these dogmas wrong has been a major achievement of modern stroke research. Thanks particularly to physiological imaging, key observations from the basic neurosciences have translated into the clinical realm in ways immediately understandable to the clinician, allowing the emergence of pathophysiology-based management.
History of Blood Transfusion before 1990 Is a Risk Factor for Stroke and Cardiovascular Diseases: The Japan Collaborative Cohort Study (JACC Study)
Authors: Yamada Shigeki , Koizumi Akio , Iso Hiroyasu , Wada Yasuhiko , Watanabe Yoshiyuki , Date Chigusa , Yamamoto Akio , Kikuchi Shogo , Inaba Yutaka , Kondo Takaaki , Toyoshima Hideaki , Tamakoshi Akiko
Published: July 2005

Background: We have previously shown novel evidence that history of blood transfusion is a risk factor for mortality from subarachnoid hemorrhage. This study was conducted to assess history of transfusion as a risk factor for other hemorrhagic stroke or ischemic stroke and cardiovascular diseases. Study Design and Methods: A total of 88,312 Japanese participants (36,823 men and 51,489 women), aged 40–79 years, without history of stroke, heart disease or cancer, completed a questionnaire including history of transfusion under the JACC Study from 1988 to 1990. Participants were followed up annually until deceased, or when they moved away from the surveyed community, or at the end of 1999. The underlying causes of death were determined according to the International Classification of Diseases, 10th revision (ICD-10). Results: Total follow-up person-years were 871,437 (males 359,437, females 512,000). During this 10-year period, 309 died from intracerebral hemorrhage, 587 from ischemic stroke and 472 from coronary heart disease. The multivariate relative risks of a transfusion history were 2.16 (95% CI 1.42–3.27, p < 0.001) for intracerebral hemorrhage, 1.63 (95% CI 1.18–2.27, p = 0.004) for ischemic stroke and 1.66 (95% CI 1.17–2.36, p = 0.005) for coronary heart disease, after adjustment for conventional cardiovascular risk factors. Conclusion: A transfusion history was associated with increased mortality from stroke and coronary heart disease.
Cost-Effectiveness Analysis of Thrombolytic Treatment for Stroke
Authors: Mar Javier , Begiristain Jose Maria , Arrazola Arantza
Published: July 2005

Purpose: Thrombolysis is used to treat stroke patients based on the National Institute of Neurological Disorders and Stroke study and meta-analysis results. We present a cost-effectiveness analysis based on a probabilistic model of the use of thrombolytic therapy in stroke treatment. Methods: We surveyed patients who had had a stroke during their hospital stay and examined them again 1 year after release from the hospital to obtain data on costs and natural history. We then calculated utility weights using the European Quality of Life Questionnaire. When the model runs, 4,000 Monte Carlo simulations are undertaken in which each parameter value changes depending on its probability distribution. The results are expressed in terms of the cost-effectiveness plane and the cost-effectiveness acceptability curve. Results: We studied 435 patients, of whom 304 had had an ischemic stroke. One year later, 216 were still alive. The mean utility values were 0.22 for disabled patients and 0.77 for autonomous patients. The incremental cost-effectiveness ratio (ICER) obtained by means of the parameters was –19,000 EUR/quality-adjusted life year, reflecting a saving of 6,000 EUR and a health benefit for patients. The cost-effectiveness plane showed that thrombolysis was a dominant variable in 96.1% of simulations. In the acceptability curves, only 0.4 of simulations obtained an ICER higher than the societal threshold. Conclusions: Thrombolytic therapy seems to be a useful intervention because it is inexpensive and cost-effective. The key factor is the decreased rate of disability, which results in a better quality of life of the patient and lower costs.