bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral Disinhibition and the Development of Early-Onset Addiction: Common and Specific Influences
Authors: Iacono William G. , Malone Stephen M. , McGue Matt
Published: February 2008

Research on substance use disorders is often compartmentalized, focused on understanding addiction to one substance or substance class at a time. Although this approach has contributed significantly to knowledge about addictions, early-onset substance use disorders appear to share common etiology with each other and with other disorders, traits, behaviors, and endophenotypes associated with behavioral disinhibition. We propose that a common genetic liability to behavioral disinhibition underlies the co-occurrence of these externalizing attributes. This liability is expressed in part through brain mechanisms related to cognitive control, impulsivity, and sensitivity to reward, all of which are maturing during adolescence. During this important transitional period, problem behaviors emerge, including the initiation of substance use. Exposure to various environmental risks further amplifies the risk associated with the common liability, increasing the likelihood of addiction generally. Specific environmental and genetic factors ultimately contribute to the differentiation among externalizing disorders.
Neuropsychological Rehabilitation
Authors: Wilson Barbara A.
Published: February 2008

Neuropsychological rehabilitation (NR) is concerned with the amelioration of cognitive, emotional, psychosocial, and behavioral deficits caused by an insult to the brain. Major changes in NR have occurred over the past decade or so. NR is now mostly centered on a goal-planning approach in a partnership of survivors of brain injury, their families, and professional staff who negotiate and select goals to be achieved. There is widespread recognition that cognition, emotion, and psychosocial functioning are interlinked, and all should be targeted in rehabilitation. This is the basis of the holistic approach. Technology is increasingly used to compensate for cognitive deficits, and some technological aids are discussed. Evidence for effective treatment of cognitive, emotional, and psychosocial difficulties is presented, models that have been most influential in NR are described, and the review concludes with guidelines for good practice.
Psychosocial and Biobehavioral Factors and Their Interplay in Coronary Heart Disease
Authors: Williams Redford B.
Published: February 2008

Recent epidemiological research has confirmed that psychosocial factors are associated with increased risk of developing coronary heart disease (CHD), a major cause of death and disability worldwide. This association is probably mediated by changes in health risk behaviors and neuroendocrine and autonomic functions that affect metabolic, hemostatic, inflammatory, and cardiovascular functions that are the proximal agents in CHD pathogenesis over time as well as the precipitation of acute disease events. Recent developments in genomics have now made it possible to begin the process of identifying specific genetic variants that act either independently or via moderation of the impact of exposures to stressful environmental situations to increase the expression of these health-damaging psychosocial factors and the accompanying behavioral and physiological changes that lead to disease. It will be possible ultimately to use the knowledge emerging from research on gene x environment interactions that affect expression of psychosocial risk factors, health risk behaviors, and biological changes inside the body to speed the development of a new field of prospective medicine—a field where instead of spending the majority of health care resources on the treatment of chronic diseases at the end of life, it will be possible to allocate more resources to develop, test, and implement earlier in the disease process cost-effective, proactive interventions that target persons at high risk.
Stress and the Hypothalamic Pituitary Adrenal Axis in the Developmental Course of Schizophrenia
Authors: Walker Elaine , Mittal Vijay , Tessner Kevin
Published: February 2008

Diathesis-stress models of schizophrenia and other psychotic disorders have dominated theorizing about etiology for over three decades. More recently, with advances in our understanding of the biological processes mediating the effects of stress, these models have incorporated mechanisms to account for the adverse impact of stress on brain function. This review examines recent scientific findings on the role of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary neural systems triggered by stress exposure, in the expression of vulnerability for schizophrenia. The results indicate that psychotic disorders are associated with elevated baseline and challenge-induced HPA activity, that antipsychotic medications reduce HPA activation, and that agents that augment stress hormone (cortisol) release exacerbate psychotic symptoms. The cumulative findings are discussed in light of a neural diathesis-stress model that postulates that cortisol has the potential to increase activity of dopamine pathways that have been implicated in schizophrenia and other psychotic disorders.
The Empirical Status of Psychodynamic Therapies
Authors: Connolly Gibbons Mary Beth , Crits-Christoph Paul , Hearon Bridget
Published: February 2008

The goal of the current review is to examine the evidence for the efficacy of dynamic psychotherapy, primarily focusing on studies that meet the rigorous criteria proposed by Chambless & Hollon (1998) . We examine whether any progress has been made over the past decade in evaluating the efficacy of dynamic psychotherapy using well-controlled randomized designs. Over the past decade, multiple studies have been published supporting the efficacy of dynamic psychotherapy for the treatment of specific mental disorders. Dynamic psychotherapy should now be included as a possibly efficacious treatment for panic disorder and borderline personality disorder, as well as the original designation of possibly efficacious in the treatment of opiate dependence. In the context of medication usage, dynamic psychotherapy should be considered efficacious in the treatment of major depressive disorder (MDD). Studies suggest that dynamic psychotherapy has great promise as a monotherapy for MDD and alcohol dependence and thus should be evaluated further.
HowSaccharomycesResponds to Nutrients
Authors: Zaman Shadia , Lippman Soyeon Im , Zhao Xin , Broach James R.
Published: February 2008

Yeast cells sense the amount and quality of external nutrients through multiple interconnected signaling networks, which allow them to adjust their metabolism, transcriptional profile and developmental program to adapt readily and appropriately to changing nutritional states. We present our current understanding of the nutritional sensing networks yeast cells rely on for perceiving the nutritional landscape, with particular emphasis on those sensitive to carbon and nitrogen sources. We describe the means by which these networks inform the cell's decision among the different developmental programs available to them—growth, quiescence, filamentous development, or meiosis/sporulation. We conclude that the highly interconnected signaling networks provide the cell with a highly nuanced view of the environment and that the cell can interpret that information through a sophisticated calculus to achieve optimum responses to any nutritional condition.
The Biochemistry of Somatic Hypermutation
Authors: Peled Jonathan U. , Kuang Fei Li , Iglesias-Ussel Maria D. , Roa Sergio , Kalis Susan L. , Goodman Myron F. , Scharff Matthew D.
Published: February 2008

Affinity maturation of the humoral response is mediated by somatic hypermutation of the immunoglobulin (Ig) genes and selection of higher-affinity B cell clones. Activation-induced cytidine deaminase (AID) is the first of a complex series of proteins that introduce these point mutations into variable regions of the Ig genes. AID deaminates deoxycytidine residues in single-stranded DNA to deoxyuridines, which are then processed by DNA replication, base excision repair (BER), or mismatch repair (MMR). In germinal center B cells, MMR, BER, and other factors are diverted from their normal roles in preserving genomic integrity to increase diversity within the Ig locus. Both AID and these components of an emerging error-prone mutasome are regulated on many levels by complex mechanisms that are only beginning to be elucidated.
T Cell Trafficking in Allergic Asthma: The Ins and Outs
Authors: Medoff Benjamin D. , Thomas Seddon Y. , Luster Andrew D.
Published: February 2008

T cells are critical mediators of the allergic airway inflammation seen in asthma. Pathogenic allergen-specific T cells are generated in regional lymph nodes and are then recruited into the airway by chemoattractants produced by the asthmatic lung. These recruited effector T cells and their products then mediate the cardinal features of asthma: airway eosinophilia, mucus hypersecretion, and airway hyperreactivity. There has been considerable progress in delineating the molecular mechanisms that control T cell trafficking into peripheral tissue, including the asthmatic lung. In this review, we summarize these advances and formulate them into a working model that proposes that T cell trafficking into and out of the allergic lung is controlled by several discrete regulatory pathways that involve the collaboration of innate and acquired immune cells.
Monocyte-Mediated Defense Against Microbial Pathogens
Authors: Serbina Natalya V. , Jia Ting , Hohl Tobias M. , Pamer Eric G.
Published: February 2008

Circulating blood monocytes supply peripheral tissues with macrophage and dendritic cell (DC) precursors and, in the setting of infection, also contribute directly to immune defense against microbial pathogens. In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations. Inflammatory monocytes respond rapidly to microbial stimuli by secreting cytokines and antimicrobial factors, express the CCR2 chemokine receptor, and traffic to sites of microbial infection in response to monocyte chemoattractant protein (MCP)-1 (CCL2) secretion. In murine models, CCR2-mediated monocyte recruitment is essential for defense against Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans infection, implicating inflammatory monocytes in defense against bacterial, protozoal, and fungal pathogens. Recent studies indicate that inflammatory monocyte recruitment to sites of infection is complex, involving CCR2-mediated emigration of monocytes from the bone marrow into the bloodstream, followed by trafficking into infected tissues. The in vivo mechanisms that promote chemokine secretion, monocyte differentiation and trafficking, and finally monocyte-mediated microbial killing remain active and important areas of investigation.
The Actin Cytoskeleton in T Cell Activation
Authors: Burkhardt Janis K. , Carrizosa Esteban , Shaffer Meredith H.
Published: February 2008

T cell cytoarchitecture differs dramatically depending on whether the cell is circulating within the bloodstream, migrating through tissues, or interacting with antigen-presenting cells. The transition between these states requires important signaling-dependent changes in actin cytoskeletal dynamics. Recently, analysis of actin-regulatory proteins associated with T cell activation has provided new insights into how T cells control actin dynamics in response to external stimuli and how actin facilitates downstream signaling events and effector functions. Among the actin-regulatory proteins that have been identified are nucleation-promoting factors such as WASp, WAVE2, and HS1; severing proteins such as cofilin; motor proteins such as myosin II; and linker proteins such as ezrin and moesin. We review the current literature on how signaling pathways leading from diverse cell surface receptors regulate the coordinated activity of these and other actin-regulatory proteins and how these proteins control T cell function.
The IRF Family Transcription Factors in Immunity and Oncogenesis
Authors: Tamura Tomohiko , Yanai Hideyuki , Savitsky David , Taniguchi Tadatsugu
Published: February 2008

The interferon regulatory factor (IRF) family, consisting of nine members in mammals, was identified in the late 1980s in the context of research into the type I interferon system. Subsequent studies over the past two decades have revealed the versatile and critical functions performed by this transcription factor family. Indeed, many IRF members play central roles in the cellular differentiation of hematopoietic cells and in the regulation of gene expression in response to pathogen-derived danger signals. In particular, the advances made in understanding the immunobiology of Toll-like and other pattern-recognition receptors have recently generated new momentum for the study of IRFs. Moreover, the role of several IRF family members in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.
Thymus Organogenesis
Authors: Rodewald Hans-Reimer
Published: February 2008

The epithelial architecture of the thymus fosters growth, differentiation, and T cell receptor repertoire selection of large numbers of immature T cells that continuously feed the mature peripheral T cell pool. Failure to build or to maintain a proper thymus structure can lead to defects ranging from immunodeficiency to autoimmunity. There has been long-standing interest in unraveling the cellular and molecular basis of thymus organogenesis. Earlier studies gave important morphological clues on thymus development. More recent cell biological and genetic approaches yielded new and conclusive insights regarding the germ layer origin of the epithelium and the composition of the medulla as a mosaic of clonally derived islets. The existence of epithelial progenitors common for cortex and medulla with the capacity for forming functional thymus after birth has been uncovered. In addition to the thymus in the chest, mice can have a cervical thymus that is small, but functional, and produces T cells only after birth. It will be important to elucidate the pathways from putative thymus stem cells to mature thymus epithelial cells, and the properties and regulation of these pathways from ontogeny to thymus involution.
Mechanisms of high-glucose/insulin-mediated desensitization of acute insulin-stimulated glucose transport and Akt activation
Authors: Robinson Katherine A. , Buse Maria G.
Published: February 2008

High-glucose/low-dose insulin-mediated insulin resistance of glucose transport was studied in 3T3-L1 adipocytes. In this model, proximal insulin signaling, including insulin receptor substrate (IRS)-1-bound phosphatidylinositol 3-kinase (PI 3-kinase) activation, is preserved, but insulin-stimulated protein kinase B (Akt) activation is markedly impaired. To assess a difference in acute insulin-stimulated production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5) P3], cells were labeled with [32P]orthophosphate, and glycerophosphoinositides were quantified by HPLC. Although basal PtdIns(3,4,5) P3was similar, insulin stimulated its production 33.6% more in controls ( P < 0.03) than in insulin-resistant cells. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein, a lipid phosphatase that dephosphorylates PtdIns(3,4,5) P3in the 3-position, was significantly and specifically increased in insulin-resistant cells. Treatment with rapamycin [a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1)] inhibited the increased PTEN expression and partially restored insulin-stimulated glucose transport and Akt activation to insulin-resistant cells. Acute insulin markedly stimulated Ser636/639phosphorylation of IRS-1; this was rapamycin inhibited but was significantly decreased in cells that had been preexposed to insulin, whereas total IRS-1 was unaffected. These findings were essentially paralleled by changes in the activation of p70 S6 kinase and S6-ribosomal protein. Overexpression of uncoupling protein-1 or manganese superoxide dismutase did not prevent the development of insulin-resistant glucose transport and impaired Akt activation in high-glucose/low-insulin-pretreated cells. The insulin resistance associated with glucotoxicity in our model reflects in part decreased availability of PtdIns(3,4,5) P3, which correlates with increased PTEN protein expression. Chronic activation of mTORC1 plays a role in stimulating PTEN expression and possibly in activation or induction of a phosphoprotein phosphatase. No evidence was found for a role for increased mitochondrial superoxide production in this model.
Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury
Authors: Yasuda Hideo , Leelahavanichkul Asada , Tsunoda Shinichiro , Dear James W. , Takahashi Yoshiyuki , Ito Shuichi , Hu Xuzhen , Zhou Hua , Doi Kent , Childs Richard , Klinman Dennis M. , Yuen Peter S. T. , Star Robert A.
Published: February 2008

Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and AKI in a clinically relevant polymicrobial sepsis mouse model, even when administered 6 h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-α and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development.
A Cost–Benefit Analysis of Neuronal Morphology
Authors: Wen Quan , Chklovskii Dmitri B.
Published: February 2008

Over hundreds of millions of years, evolution has optimized brain design to maximize its functionality while minimizing costs associated with building and maintenance. This observation suggests that one can use optimization theory to rationalize various features of brain design. Here, we attempt to explain the dimensions and branching structure of dendritic arbors by minimizing dendritic cost for given potential synaptic connectivity. Assuming only that dendritic cost increases with total dendritic length and path length from synapses to soma, we find that branching, planar, and compact dendritic arbors, such as those belonging to Purkinje cells in the cerebellum, are optimal. The theory predicts that adjacent Purkinje dendritic arbors should spatially segregate. In addition, we propose two explicit cost function expressions, falsifiable by measuring dendritic caliber near bifurcations.
Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+
Authors: Shin D. S. , Carlen P. L.
Published: February 2008

High-frequency stimulation (HFS) is used to treat a variety of neurological diseases, yet its underlying therapeutic action is not fully elucidated. Previously, we reported that HFS-induced elevation in [K+]e or bath perfusion of raised Ke+ depressed rat entopeduncular nucleus (EP) neuronal activity via an enhancement of an ionic conductance leading to marked depolarization. Herein, we show that the hyperpolarization-activated ( Ih) channel mediates the HFS- or K+-induced depression of EP neuronal activity. The perfusion of an Ih channel inhibitor, 50 μM ZD7288 or 2 mM CsCl, increased input resistance by 23.5 ± 7% (ZD7288) or 35 ± 10% (CsCl), hyperpolarized cells by 3.4 ± 1.7 mV (ZD7288) or 2.3 ± 0.9 mV (CsCl), and decreased spontaneous action potential (AP) frequency by 51.5 ± 12.5% (ZD7288) or 80 ± 13.5% (CsCl). The Ih sag was absent with either treatment, suggesting a block of Ih channel activity. Inhibition of the Ih channel prior to HFS or 6 mM K+ perfusion not only prevented the previously observed decrease in AP frequency, but increased neuronal activity. Under voltage-clamp conditions, Ih currents were enhanced in the presence of 6 mM K+. Calcium is also involved in the depression of EP neuronal activity, since its removal during raised Ke+ application prevented this attenuation and blocked the Ih sag. We conclude that the enhancement of Ih channel activity initiates the HFS- and K+-induced depression of EP neuronal activity. This mechanism could underlie the inhibitory effects of HFS used in deep brain stimulation in output basal ganglia nuclei.
Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension
Authors: Moreno-Vinasco Liliana , Gomberg-Maitland Mardi , Maitland Michael L. , Desai Ankit A. , Singleton Patrick A. , Sammani Saad , Sam Lee , Liu Yang , Husain Aliya N. , Lang Roberto M. , Ratain Mark J. , Lussier Yves A. , Garcia Joe G. N.
Published: February 2008

Pulmonary hypertension (PH) and cancer pathology share growth factor- and MAPK stress-mediated signaling pathways resulting in endothelial and smooth muscle cell dysfunction and angioproliferative vasculopathy. In this study, we assessed sorafenib, an antineoplastic agent and inhibitor of multiple kinases important in angiogenesis [VEGF receptor (VEGFR)-1–3, PDGF receptor (PDGFR)-β, Raf-1 kinase] as a potential PH therapy. Two PH rat models were used: a conventional hypoxia-induced PH model and an augmented PH model combining dual VEGFR-1 and -2 inhibition (SU-5416, single 20 mg/kg injection) with hypoxia. In addition to normoxia-exposed control animals, four groups were maintained at 10% inspired O2fraction for 3.5 wk (hypoxia/vehicle, hypoxia/SU-5416, hypoxia/sorafenib, and hypoxia/SU-5416/sorafenib). Compared with normoxic control animals, rats exposed to hypoxia/SU-5416 developed hemodynamic and histological evidence of severe PH while rats exposed to hypoxia alone displayed only mild elevations in hemodynamic values (pulmonary vascular and right ventricular pressures). Sorafenib treatment (daily gavage, 2.5 mg/kg) prevented hemodynamic changes and demonstrated dramatic attenuation of PH-associated vascular remodeling. Compared with normoxic control rats, expression profiling (Affymetrix platform) of lung RNA obtained from hypoxia [false discovery rate (FDR) 6.5%]- and hypoxia/SU-5416 (FDR 1.6%)-challenged rats yielded 1,019 and 465 differentially regulated genes (fold change >1.4), respectively. A novel molecular signature consisting of 38 differentially expressed genes between hypoxia/SU-5416 and hypoxia/SU-5416/sorafenib (FDR 6.7%) was validated by either real-time RT-PCR or immunoblotting. Finally, immunoblotting studies confirmed the upregulation of the MAPK cascade in both PH models, which was abolished by sorafenib. In summary, sorafenib represents a novel potential treatment for severe PH with the MAPK cascade a potential canonical target.
Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences
Authors: Haddad Georges E. , Saunders Lori J. , Crosby Seth D. , Carles Maria , del Monte Federica , King Kindra , Bristow Michael R. , Spinale Francis G. , Macgillivray Thomas E. , Semigran Marc J. , Dec G. William , Williams Steven A. , Hajjar Roger J. , Gwathmey Judith K.
Published: February 2008

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men.
Crystal structure determination of new compounds Li6MB3O9(M=Nd,Sm,Eu,Tm,Er)
Authors: Lou Y. F. , Wang W. Y. , Cai G. M. , Sun Y. P. , Wang C.
Published: February 2008

New compounds Li6MB3O9(M=Nd,Sm,Eu,Tm,Er) were synthesized by solid-state reaction. The crystal structure of Li6NdB3O9was analyzed from both powder and single crystal X-ray diffraction data. The results obtained by powder diffraction analysis and Rietveld refinement area=7.2725(4) Å,b=16.6398(9) Å,c=6.7529(5) Å,β=105.398(8)°, and space groupP21/c, which agree with the results obtained by single crystal diffraction analysis:a=7.2712(4) Å,b=16.6268(9) Å,c=6.7484(4) Å,β=105.411(1)°, and space groupP21/c. This compound is isostructural with Li6YB3O9. Single crystal structure analysis showed that the fundamental building unit of these isostructural compounds comprises three isolated [BO3]3−triangles, one distorted [NdO8]13−triangulated dodecahedron, four distorted [LiO5]9−five-coordinated polyhedra, and two [LiO4]7−tetrahedron. An analysis of the infrared spectrum of Li6NdB3O9confirmed the presence of isolated [BO3]3−triangles in Li6NdB3O9. The remaining four Li6MB3O9(M=Nd, Sm, Eu, Tm, and Er) compounds were found to be isostructural with Li6NdB3O9. Their unit cell dimensions decrease with an increase in the atomic number of the rare-earth atoms. DTA and TGA measurements of Li6MB3O9(M=Nd, Sm, Eu, Tm, and Er) revealed that these borates congruently melt from 800 °C to 860 °C.
Rietveld refinement of the ranciéite structure using synchrotron powder diffraction data
Authors: Post Jeffrey E. , Heaney Peter J. , Ertl Andreas
Published: February 2008

Rietveld refinement using synchrotron powder X-ray diffraction data of the ranciéite, Ca0.19K0.01(Mn4+0.91◻0.09)O2⋅0.63H2O, crystal structure reveals significant differences from that reported previously. The interlayer H2O molecules occupy sites halfway between the Mn,O octahedral sheets. The Mn sites in the octahedral sheets have 10% vacancies, and the mean Mn–O distance indicates that all Mn is tetravalent (Mn4+). The interlayer Ca cations are located above and below the Mn vacancies and are octahedrally coordinated to three O2 atoms in the octahedral sheet and three H2O molecules in the interlayer.
Texture-tuned growth of CdTe thin films by closed-space sublimation technique
Authors: Fei Shang , Jian Ji-kang , Rong Wu , Yu-feng Zheng , Yan-fei Sun
Published: February 2008

CdTe thin films were grown on indium tin oxide glass substrates by a closed-space sublimation method using a resistor heater. Crystalline structure, morphology, and band gaps of the films were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and optical absorption, respectively. The XRD analysis showed that the textures of the films were found to depend on the rate of increase in the heating current. The CdTe thin film had an (111) texture when the heating current rate was 2.0 A/min. The SEM analysis revealed that the film is composed of polyhedral grains of microns size. However, the (111) texture of the CdTe thin film observed by XRD decreased with the appearance of (220), (311), (400), (331), (422), and (511) peaks of the fcc CdTe phase when the heating current rate increased to 4.5 A/min. The (111) texture disappeared when the heating current was increased immediately from 0 A to the target current of 70 A. SEM results revealed that the grains in the film are round and the grain size is smaller than 1 μm. Optical absorption analysis showed that there is no distinctive difference in the band gaps of the films.
Effect of the Portacaval Shunt on Reperfusion Injury after 65% Hepatectomy in Pigs
Authors: Farantos C. , Arkadopoulos N. , Theodoraki K. , Kostopanagiotou G. , Katis K. , Tzavara K. , Andreadou I. , Dimopoulou K. , Hatzoudi E. , Sidiropoulou T. , Skalkidis I. , Paphiti A. , Smyrniotis V.
Published: February 2008

Background: Portal flow diversion by portacaval shunts (PCS) has been shown to prevent primary graft nonfunction in liver transplantation using small-for-size grafts. In this study, we examine whether PCS can improve reperfusion injury after major hepatectomy in pigs. Materials and Methods: In 14 pigs, a partial PCS was constructed following 65% hepatectomy and 1 h of inflow ischemia. During 24 h of reperfusion, the shunt was either closed (group A, n = 7) or left open (group B, n = 7). Results: 24 h after reperfusion, group A had higher levels of alanine aminotransferase (70 ± 12 IU/l vs. 51 ± 5.9 IU/l; p < 0.05), alanine aminotransferase per gram of liver remnant (0.41 ± 0.07 IU/l/g vs. 0.21 ± 0.05 IU/l/g; p < 0.05), prothrombin time (24.1 ± 2.4 s vs. 14.3 ± 2.9 s; p < 0.05), international normalized ratio (2.11 ± 0.15 vs. 1.29 ± 0.28; p < 0.05), hepatocyte necrosis scores and percentages of nuclei stained for proliferating cell nuclear antigen (52.57 ± 8.9% vs. 36.71 ± 6%; p < 0.05) compared to group B. Conclusions: Partial portal flow diversion appears to attenuate reperfusion injury in a porcine model of major hepatectomy.
Clinical Benefit of Early Anticoagulation in Cardioembolic Stroke
Authors: Micheli Sara , Agnelli Giancarlo , Caso Valeria , Paciaroni Maurizio
Published: February 2008

Background: Nonvalvular atrial fibrillation is the most common source of cardiac embolism with a high reported risk of stroke and a high stroke-related mortality. A common clinical dilemma in patients with acute stroke is whether the detection of one of the major cardiac sources of emboli requires an early anticoagulation to reduce early stroke recurrence and mortality. Methods: In this review, we report on the results of clinical trials that have investigated the efficacy of early treatment for acute cardioembolic stroke. Results: Large clinical trials demonstrate that there is no evidence supporting the administration of heparin in patients with acute ischemic stroke within 48 h from stroke onset. Conclusions: The results of recent studies showing an advantage of the very early administration of heparin (<3 h from stroke onset) should encourage clinicians to perform further trials on the efficacy of an early administration of heparin in acute cardioembolic stroke.
Prediction of Progressive Motor Deficits in Patients with Deep Subcortical Infarction
Authors: Kim Soo Kyoung , Song Pamela , Hong Ji Man , Pak Chang-Yun , Chung Chin-Sang , Lee Kwang Ho , Kim Gyeong-Moon
Published: February 2008

Background and Purpose: Early motor deterioration (EMD) in deep subcortical infarction is usually associated with long-term functional disability. In this study, we investigated the clinical characteristics, biochemical markers and MRI variables in patients with deep subcortical infarction to identify the predictors of progressive motor deficits. Methods: A total of 167 consecutive patients with deep subcortical infarction in the anterior circulation were included. All of the patients must have motor deficit as one of the presented symptoms. EMD was defined as a modified National Institutes of Health Stroke Scale (mNIHSS) motor score of ≧1 during the first week of symptom onset. The patients were assessed with clinical findings such as stroke risk factors, blood pressure on admission, laboratory variables and radiological findings; lesion characteristics on MRI, stenosis or occlusion in the relevant parental artery on MRA and diffusion/perfusion mismatch. Results: Twenty-three (13.8%) of the 167 patients revealed EMD. The independent factors related to the EMD in multiple regression analysis were initial high systolic blood pressure (OR = 1.035, 95% CI = 1.007–1.063; p = 0.013) and lesion involvement in the posterolateral striatum (OR = 15.98; 95% CI = 1.842–138.534; p = 0.012); however, the other clinical and radiological factors were not related. Conclusions: The involvement of the posterolateral striatum appears to be an important predictor for EMD. It can be explained by (1) the lateral lenticulostriate artery (LSA), which supplies the posterolateral striatum vulnerable to ischemic damage due to the lack of collateral vessels, and (2) the posterolateral division of the striatum may be susceptible to progressive motor deficit because of anatomic proximity to the corticospinal tract in the same LSA territory. Further research should include precise anatomical and functional study to determine the relationship between the posterolateral striatum and corticospinal tract in predicting progressive motor deficit.
Carotid and Transcranial Color-Coded Duplex Ultrasonography for the Diagnosis of Dural Arteriovenous Fistulas
Authors: Duan Yun You , Zhou Xiao Yan , Liu Xi , Gao Guo Dong , Zhao Zhen Wei , Hou Wei Hua , Cao Tie Sheng
Published: February 2008

Background and Purpose: Dural arteriovenous fistulas (DAVF) can affect a variety of cerebral venous structures and can present at various clinical stages. This study was designed to introduce the characteristic manifestation of DAVF detected with both carotid and transcranial color-coded duplex ultrasonography (CDUS) and to evaluate the diagnostic value of CDUS in DAVF. Methods: Nineteen patients with DAVF confirmed by cerebral angiography were studied with CDUS. The sonogram and spectrum of the affected area were observed. Hemodynamic parameters such as peak systolic velocity, end-diastolic velocity, mean velocity and resistance index (RI) were measured and recorded in the feeding artery, draining vein and extracranial artery. All results were compared with cerebral angiography. Fifty healthy volunteers were enrolled as a control group. Related hemodynamic changes were compared between the patients and normal controls. Results: The blood flow of fistulas presented as an irregular mosaic color bolus with a clear boundary detected with CDUS. Blood flow imaging of fistulas was abnormal in 12 cases and absent in 7 cases. The detection rate was 63% (12/19). Fifty-three main feeding arteries (73.6%) were detected by ultrasonography. All the venous drainages through the transverse sinus and superior ophthalmic vein were detected, while the ones through the superior sagittal sinus and cortical vein were not. There was a significant difference in average diameter, flow velocity and RI of the occipital artery and superficial temporal artery between the patients and normal controls (p < 0.05). Conclusions: CDUS could indicate DAVF by analyzing both imaging results of the diseased region and hemodynamic changes of the relative vasculature. It is a promising technique for the diagnosis and follow-up study of DAVF.
Aphasia during the Acute Phase in Ischemic Stroke
Authors: Inatomi Y. , Yonehara T. , Omiya S. , Hashimoto Y. , Hirano T. , Uchino M.
Published: February 2008

Objectives: We investigated the incidence, clinical characteristics, outcome and factors associated with aphasia and early improvement in acute ischemic stroke. Methods: We consecutively studied 855 patients with acute ischemic stroke who were admitted to our hospital within 48 h after onset and who were not comatose on admission. Assessment of aphasia was performed on admission (day 0) and day 10. We examined the incidence, severity, and subtypes of aphasia, and compared the clinical background of patients with and without aphasia on admission, and also those with and without early improvement by day 10. In addition, we investigated the independent factors associated with the presence of aphasia on admission and with early improvement. Results: Of the 855 patients, 130 (15.2%) had aphasia on admission. The National Institutes of Health Stroke Scale (NIHSS) on admission (OR 1.21; 95% CI 1.17–1.26) was a significant and independent factor associated with the presence of aphasia on admission. Early improvement was seen in 56 of 121 aphasic patients (46.3%) who were still alive on day 10. A history of hypercholesterolemia (OR 3.27; 95% CI 1.14–9.39) was a significant and independent factor associated with early improvement in aphasia during the acute phase and NIHSS on admission (OR 0.95; 95% CI 0.90–0.99) was marginally significant. Conclusion: It is difficult to predict the outcome of aphasia within the first few days after the onset of ischemic stroke.
Telemedically Provided Stroke Expertise beyond Normal Working Hours
Authors: Vatankhah Bijan , Schenkel Johannes , Fürst Andrea , Haberl Roman L. , Audebert Heinrich J.
Published: February 2008

Background: State-of-the-art stroke management requires neurological expertise for the recognition of complex cerebrovascular syndromes or stroke-mimicking symptoms and initiation of proven acute therapies. Many community hospitals struggle to fulfill these premises particularly at evening/nighttimes or weekends. Telemedicine can improve that situation by offering rapid access to neurological expertise, but it has not been shown to what extent it is used beyond working times. Methods: The Telemedical Project for Integrated Stroke Care is a telemedical network of 2 stroke centers and 12 regional general hospitals with newly established stroke wards in Bavaria. This analysis comprises all teleconsultations from 1st February 2003 to 15th December 2006. The consultations were prospectively documented and categorized according to predefined indications and direct impact on clinical decisions. The teleconsultations were analyzed concerning whether they were requested during regular working time or during off-time (at evening/nighttimes or weekends). Results: A total of 10,239 teleconsultations were carried out in 8,326 patients. The 6,679 patients with cerebrovascular diagnosis comprised 51% of all admitted stroke cases between 2003 and 2006. During off-time 6,306 consultations (62%) were requested; 1,598 teleconsultations yielded nonstroke diagnoses, with 68% beyond working hours. Of all presented stroke patients 567 (8.5%) received systemic thrombolysis, with 58% off-time. Interhospital transports were initiated in 1,050 patients (10.5% of all), mainly for specific diagnostic workup or interventional treatments. Sixty percent of these transfers were launched off-time. Conclusions: The majority of teleconsultations were requested beyond normal working times and a significant proportion had an immediate impact on clinical decisions.
Thrombolytic Toxicity: Blood Brain Barrier Disruption in Human Ischemic Stroke
Authors: Kidwell Chelsea S. , Latour Larry , Saver Jeffrey L. , Alger Jeffry R. , Starkman Sidney , Duckwiler Gary , Jahan Reza , Vinuela Fernando , Kang Dong-Wha , Warach Steven
Published: February 2008

Background: In experimental models of cerebral ischemia, thrombolytic drugs have been demonstrated to have a number of neurovascular toxic effects including blood brain barrier disruption. Early barrier opening caused by focal cerebral ischemia in human stroke can be assessed by the presence of gadolinium enhancement of cerebrospinal fluid, termed ‘Hyperintense Acute Injury Marker’ (HARM). Methods: In a retrospective analysis, the frequency of HARM was studied in 140 patients, 38 receiving intra-arterial thrombolytics, 18 undergoing mechanical embolectomy, 24 receiving intravenous tissue plasminogen activator and 60 patients receiving no acute intervention. Results: HARM was found in 66% of patients undergoing intra-arterial thrombolysis and 50% of patients receiving intravenous tissue plasminogen activator, compared to 28% of patients undergoing mechanical embolectomy and 30% of patients receiving no acute therapy (p = 0.002). Both thrombolytic therapy (p = 0.001) and age (p = 0.001) were independent predictors of HARM. HARM was an independent predictor of hemorrhagic transformation (p = 0.007). Conclusions: This is the first study in humans providing supportive evidence of the neurovascular toxic effects of thrombolytics and suggests that HARM may be used as a biomarker of blood brain barrier disruption in future research of acute stroke therapies.
Acute Neurolupus Manifested by Seizures Is Associated with High Frequency of Abnormal Cerebral Blood Flow Velocities
Authors: Baizabal-Carvallo José Fidel , Cantú-Brito Carlos , García-Ramos Guillermo
Published: February 2008

Background: Systemic lupus erythematosus may present with a wide variety of neurological manifestations, which could be related to the presence of vasculopathy and microembolic signals (MES). Objectives: We aimed to determine the prevalence of MES and altered blood flow velocities (BFVs) by transcranial Doppler (TCD) in patients with acute neuropsychiatric lupus erythematosus (NPLE). Methods: Fifteen consecutive patients with acute NPLE (cases) and 30 patients with systemic lupus erythematosus but without acute NPLE (controls) underwent TCD testing for comparison purposes. Results: We found higher mean BFVs in cases compared with controls in the left (100 vs. 73.5 cm/s, p = 0.018) and in the right (96 vs. 70 cm/s, p = 0.013) middle cerebral arteries. The proportion of MES in both groups was the same (13%). Abnormal TCDs were more frequent in patients with acute NPLE, 67 versus 17% (p = 0.001), and occurred more often in patients who presented seizures. Conclusions: The frequency of MES was the same in both groups; however, patients with seizures due to acute NPLE usually present with higher BFVs than controls. This could be a marker of diffuse acute cerebral vasculopathy.
Aspirin Responsiveness in Acute Brain Ischaemia: Association with Stroke Severity and Clinical Outcome
Authors: Schwammenthal Y. , Tsabari R. , Shenkman B. , Schwartz R. , Matetzky S. , Lubetsky A. , Orion D. , Israeli-Korn S. , Chapman J. , Savion N. , Varon D. , Tanne D.
Published: February 2008

Purpose: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. Methods: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. Results: Among 105 patients (mean age 63 ± 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8–34.9), 3.1 for lack of early clinical improvement (95% CI 1.1–8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4–30.4). Less robust trends were observed with the Impact-R. Conclusions: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies.
Effect of Phospholipase C Blockade on Cerebral Vasospasm
Authors: Jadhav Vikram D. , Jabre Anthony , Lee Tony Jer-Fu
Published: February 2008

Background: Delayed cerebral ischemia due to cerebral vasospasm remains a major cause of morbidity and mortality following subarachnoid hemorrhage. Oxyhemoglobin (OxyHb) and vasoconstrictor prostanoids have been suggested as putative spasmogens. We have previously reported a synergistic vasoconstrictive action between thromboxane A2 (TXA2) and OxyHb. In the present study we examine the effect of neomycin, a phospholipase C inhibitor, on the cerebral vasoconstriction induced by TXA2 and OxyHb. Methods: Using an in vitrotissue bath method, we assess the effect of neomycin in a concentration-dependent manner, on isolated porcine basilar arteries constricted by U-46619 (TXA2 analogue) and OxyHb. Results: The functional synergism between TXA2 and OxyHb, leading to significant cerebral vasoconstriction, is attenuated in a dose-dependent manner by neomycin. Conclusion: Blockade of phospholipase C may provide an alternative strategy in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm.
Changes in Speaking Fundamental Frequency Characteristics with Aging
Authors: Nishio Masaki , Niimi Seiji
Published: February 2008

Changes in speaking fundamental frequency (SFF) associated with aging were studied in a total of 374 healthy normal speakers (187 males and 187 females) from adolescent to older age groups. Participants were asked to read a sample passage aloud, and acoustic analysis was performed. The main results were as follows: (1) Males exhibited no significant trend for SFF changes in aging. However, a slight increase was observed in participants aged 70 years or older. (2) Females in their 30s and 40s showed obviously lower frequencies than those in their 20s. Across all age groups, including the 80s, SFF tended to decrease markedly in association with aging. (3) The degree of SFF change in association with aging was much larger in females than in males. In addition, reference intervals (mean ± 1.96 SD) obtained for males and females in each age group are considered useful for clinical detection of abnormalities of SFF, as well as for detection of laryngeal diseases causing SFF abnormality.
Diagnostik der taktil-kinästhetischen Wahrnehmung bei Vorschulkindern: ein Methodenvergleich
Authors: Colmant Clarissa , Eysholdt Ulrich , Rosanowski Frank
Published: February 2008

Tactile-kinesthetic perception (TKP) is the processing, arrangement, evaluation, and integration of sensations, which are transmitted via both surface and depth sensibility. In the phoniatric field TKP is of special importance for speech development. In this study, two German diagnostic test procedures for the assessment of TKP, i.e. the ‘Diagnostischer Elternfragebogen zur taktil-kinästhetischen Responsivität’ (DEF-TK) and the ‘Göttinger Entwicklungstest der taktil-kinästhetischen Wahrnehmung’ (TAKIWA), were evaluated in 30 preschool children. The DEF-TK could not be analyzed in 14/30 of the children because of too many unobservable (not missing) items. This result does not correspond with data presented in the test manual but with results obtained in a former study of the reporting group. Three quarters of the children showed abnormal tactile-kinesthetic features in their DEF-TK, whereas in the TAKIWA test, a quarter of the children were found to have abnormal TKP. The DEF-TK questionnaire is not suited for clinical purposes. The nosologic and prognostic value of the TAKIWA has to be investigated in the future.