bluuebunny/crossref_metadata_2025 huggingface dataset:
T2‐Weighted MRI Correlates with Long‐Term Histopathology, Neurology Scores, and Skilled Motor Behavior in a Rat Stroke Model
Authors: PALMER GENE C. , PEELING JAMES , CORBETT DALE , Del BIGIO MARC R. , HUDZIK THOMAS J.
Published: July 2010

Abstract:The intraluminal suture model of transient middle cerebral artery occlusion (MCAO) in the Sprague Dawley strain of rats characteristically results in an inconsistently sized brain lesion. The purpose of the investigation reported here was to determine whether there were strong point‐to‐point correlations between the degree of cortical lesion size, as assessedin vivousing T2‐weighted magnetic resonance imaging (MRI) and corresponding cortical lesion size using routine histopathological techniques. Moreover, we aimed to investigate if cortical lesion size as determined by these two modalities correlates with neurological and/or skilled motor deficits observed in individual animals. Baseline behavioral scores were obtained on the animals prior to receiving 60 min of transient MCAO. Following MCAO, animals were tested for 1–21 days for neurological deficits. T2‐weighted MRIs of the cortex were taken at two and seven days post‐MCAO. At 30 and 60 days the rats were retested for forelimb dexterity in the staircase test. Subsequently, the cortex was examined for histopathological damage. Indeed, there were highly significant correlations between lesion size determined by MRI and histopathology. The degree of cortical damage observed in the T2‐weighted MRI, as well as the size of the histopathological lesions were, in turn, highly correlated with the degrees of deficiencies observed in the composite neurological assessments and with the deficits involving skilled use of the contralateral forepaw (damaged side).
Remarkable Application of Serum EBV EBER‐1 in Monitoring Response of Nasopharyngeal Cancer Patients to Salvage Chemotherapy
Authors: NGAN ROGER K. C. , LAU W. H. , YIP TIMOTHY T. C. , CHO WILLIAM C. S. , CHENG W. W. , LIM C. K. P. , WAN K. K. , CHU E. , JOAB I. , GRUNEWALD V. , POON Y. F. , HO JOHN H. C.
Published: July 2010

Abstract: Nineteen consecutive patients with metastatic or recurrent nasopharyngeal cancer (NPC) receiving combination chemotherapy were monitored for EBV DNA in their serum. EBV DNA (EBER‐1) concentration in serum was measured before, during, and after chemotherapy. Thirteen patients had additional multiple prechemotherapy readings. There was a significant lead time from first detection of serum EBER‐1 to clinical recurrence in 62% of patients by a mean of 17.4 weeks (range: 8–74.5 weeks; mean = 28.2 weeks if confined to the 8 patients with significant lead time). The median EBER‐1 concentration was significantly higher in those with distant metastasis as compared to those with loco‐regional recurrence only (17,468 vs. 684 pg/mL serum; p= 0.046, Mann‐Whitney U test). Among the 13 patients who responded to chemotherapy, 4 exhibited clinical complete remission (CR) who were only found in the group with EBER‐1 DNA drop to background level, while the magnitude of EBER‐1 drop did not discriminate partial remission (PR) and stable disease (SD) patients clearly. Subsequent profile of EBER‐1 DNA showed concordance with clinical course of either continuous remission or later progression. EBER‐1 DNA in serum can become a useful adjunctive surrogate marker to monitor chemotherapeutic response in NPC patients with distant metastasis or advanced local recurrence.
Genetic Studies on the Role of Proteinases and Growth Factors in Atherosclerosis and Aneurysm Formation
Authors: LUTTUN A. , CARMELIET P.
Published: July 2010

Abstract: Expression analysis and epidemiologic studies have provided indirect evidence that proteinases and growth factors play a role in the development of atherosclerosis and complications such as aneurysm formation and plaque rupture. Studies using genetically altered mice have proven to be an elegant tool to study the causal involvement of these factors in atherogenesis and to gain insight into the underlying mechanisms. Recently, proteinases of the plasminogen and matrix metalloproteinase (MMP) systems as well as their inhibitors have received much attention, and these studies together have emphasized the complexity of their role in vascular disease. This overview summarizes the current knowledge on plasminogen activator inhibitor‐1 (PAI‐1) in the progression of atherosclerosis and the influence of MMPs in aneurysm formation. In addition, a possible role for Gas6, the product of growth arrest‐specific gene 6, in atherosclerotic lesion development is put into perspective.
Inflammation and Atherothrombosis
Authors: ROBBIE LINDA , LIBBY PETER
Published: July 2010

Abstract: An immune and inflammatory response involving endothelial and smooth muscle cells accompanies the accumulation of lipids and fibrous materials in atheromatous arteries. The inflammatory response involves not only the intrinsic cells of the artery wall, but also circulating leukocytes. Lymphocytes as well as macrophages participate importantly in this disease process. Plaque composition and vulnerability have emerged as more critical determinants of plaque rupture than the degree of lumenal stenosis. Thus, plaque biology has proven more important than gross morphology in determining the clinical consequences of the disease. Rupture of the atherosclerotic plaque, its thrombotic complications, and their sequelae have gained increased recognition as the proximate causes of disability and death due to related syndromes such as acute myocardial infarction. Arterial thromboses occur much more readily in arteries damaged or distorted by the atherosclerotic process. The consequences of a given plaque disruption and subsequent thrombus formation will depend on both “systemic” or fluid phase determinants and local “solid state” factors. The complex heterogeneous structure of thrombi includes fibrin, platelets, erythrocytes, and leukocytes. The local balance of proteases and inhibitors on the fibrin and cell surfaces will determine thrombus stability and persistence. Enhanced understanding of the processes involved in the development and progression of atherosclerosis and its complications will surely provide areas that can be targeted in the treatment of the disease.
The Effect of Selective Estrogen Receptor Modulators on Parameters of the Hypothalamic‐Pituitary‐Gonadal Axis
Authors: PLOUFFE LEO , SIDDHANTI SURESH
Published: July 2010

Abstract:The SERMs currently in clinical practice or in late stages of clinical development have been studied primarily for their effects on the breast, cardiovascular, bone, and reproductive systems. The effect of SERMs on the hypothalamic‐pituitary‐gonadal (HPG) axis has not been the primary focus of the studies conducted thus far. However the effect of SERMs on the HPG axis and the associated regulation of endocrine parameters may play an important role in their overall clinical profile. In this review the effects of selected SERMs on the HPG axis in premenopausal women, postmenopausal women, and men are summarized.
Protein Glycation
Authors: Yim Moon B. , Yim Hyung‐Soon , Lee Cheolju , Kang Sa‐Ouk , Chock P. Boon
Published: July 2010

Abstract: In a glycation reaction, α‐dicarbonyl compounds such as deoxyglucosone, methylglyoxal, and glyoxal are more reactive than the parent sugars with respect to their ability to react with amino groups of proteins to form inter‐ and intramolecular cross‐links of proteins, stable end products called advanced Maillard products or advanced end products (AGEs). The AGEs, which are irreversibly formed, accumulate with aging, atherosclerosis, and diabetes mellitus, and are especially associated with long‐lived proteins such as collagens, lens crystallins, and nerve proteins. It was suggested that the formation of AGEs not only modifies protein properites but also induces biological damage in vivo. In this report, we summerize results obtained from our studies for (1) identifying the structure of the cross‐linked radical species formed in the model system—the reaction between α‐dicarbonyl methylglyoxal with amino acids, and (2) the reactivity of the radical center of the protein created by the similar reaction. These results indicate that glycation of protein generates active centers for catalyzing one‐electron oxidation‐reduction reactions. This active center, which exhibits enzyme‐like character, is suggested to be the cross‐linked Schiff‐based radical cation of the protein. It mimics the characteristics of the metal‐catalyzed oxidation system. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free redicals.
A Neuronal Model of a Global Workspace in Effortful Cognitive Tasks
Authors: DEHAENE STANISLAS , KERSZBERG MICHEL , CHANGEUX JEAN‐PIERRE
Published: July 2010

Abstract: A minimal hypothesis is proposed concerning the brain processes underlying effortful tasks. It distinguishes two main computational spaces: a unique global workspace composed of distributed and heavily interconnected neurons with long‐range axons, and a set of specialized and modular perceptual, motor, memory, evaluative, and attentional processors. Workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice. They selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously coactivated, forming discrete though variable spatio‐temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. We outline predictions for spatio‐temporal activation patterns during brain imaging, particularly about the contribution of dorsolateral prefrontal cortex and anterior cingulate to the workspace.
Neural Specializations for Tonal Processing
Authors: ZATORRE ROBERT J.
Published: July 2010

Abstract: The processing of pitch, a central aspect of music perception, is neurally dissociable from other perceptual functions. Studies using behavioral‐lesion techniques as well as brain imaging methods demonstrate that tonal processing recruits mechanisms in areas of the right auditory cortex. Specifically, the right primary auditory area appears to be crucial for fine‐grained representation of pitch information. Processing of pitch patterns, such as occurs in melodies, requires higher‐order cortical areas, and interactions with the frontal cortex. The latter are likely related to tonal working memory functions that are necessary for the on‐line maintenance and encoding of tonal patterns. One hypothesis that may explain why right‐hemisphere auditory cortices seem to be so important to tonal processing is that left auditory regions are better suited for rapidly changing broad‐band stimuli, such as speech, whereas the right auditory cortex may be specialized for slower narrow‐band stimuli, such as tonal patterns. Evidence favoring this hypothesis was obtained in a functional imaging study in which spectral and temporal parameters were varied independently. The hypothesis also receives support from structural studies of the auditory cortex, which indicate that spectral and temporal processing may depend on interhemispheric differences in grey/white matter distribution and other anatomical features.
Brain Imaging of Attention Deficit/Hyperactivity Disorder
Authors: GIEDD JAY N. , BLUMENTHAL JONATHAN , MOLLOY ELIZABETH , CASTELLANOS F. XAVIER
Published: July 2010

Abstract: Advances in imaging technology allow unprecedented access to the anatomy and physiology of the living, growing human brain. Anatomical imaging studies of individuals with attention deficit/hyperactivity disorder (ADHD) consistently point to involvement of the frontal lobes, basal ganglia, corpus callosum, and cerebellum. Imaging studies of brain physiology also support involvement of right frontal‐basal ganglia circuitry with a powerful modulatory influence from the cerebellum. Although not currently of diagnostic utility, further extension and refinement of these findings may offer hope for greater understanding of the core nature of ADHD and possible subtyping to inform treatment interventions.
Borderline Personality Disorder
Authors: Gunderson John G. , Ridolfi Maria E.
Published: July 2010

Abstract: Epidemiological and neurobiological perspectives about suicidality in borderline patients are described, highlighting how self‐destructive and seemingly suicidal acts are their “behavioral specialty.” Principles for management, including the need for a primary clinician to oversee safety, and the pros and cons of both “contracting for safety” and hospitalization are presented. Clinical material is used to illustrate an approach that involves minimal initiative to rescue by therapists, a readiness to comply with patients' wishes for protection (the principle of false submission), and very active interpretation. This approach is contrasted with those advocated by Linehan and Kernberg.
A Genetic Rat Model of Cholinergic Hypersensitivity: Implications for Chemical Intolerance, Chronic Fatigue, and Asthma
Authors: Overstreet David H. , Djuric Veljko
Published: July 2010

Abstract: The fact that only some individuals exposed to environmental chemicals develop chemical intolerance raises the possibility that genetic factors could be contributing factors. The present communication summarizes evidence from a genetic animal model of cholinergic supersensitivity that suggests that an abnormal cholinergic system could be one predisposing genetic factor. The Flinders Sensitive Line (FSL) rats were established by selective breeding for increased responses to an organophosphate. It was subsequently found that these FSL rats were also more sensitive to direct‐acting muscarinic agonists and had elevated muscarinic receptors compared to the selectively bred parallel group, the Flinders Resistant Line (FRL) rats, or randomly bred control rats. Increased sensitivity to cholinergic agents has also been observed in several human populations, including individuals suffering from chemical intolerance. Indeed, the FSL rats exhibit certain behavioral characteristics such as abnormal sleep, activity, and appetite that are similar to those reported in these human populations. In addition, the FSL rats have been reported to exhibit increased sensitivity to a variety of other chemical agents. Peripheral tissues, such as intestinal and airway smooth muscle, appear to be more sensitive to both cholinergic agonists and an antigen, ovalbumin. Hypothermia, a centrally mediated response, is more pronounced in the FSL rats after nicotine and alcohol, as well as agents that are selective for the dopaminergic and serotonergic systems. In some cases, the increased sensitivity has been detected in the absence of any changes in the receptors with which the drugs interact (dopamine receptors), while receptor changes have been seen in other cases (nicotine receptors). Therefore, there may be multiple mechanisms underlying the multiple chemical sensitivity‐chemical intolerance of the FSL rats. An elucidation of these mechanisms may provide useful clues to those involved in chemical intolerance in humans.
Cytokines and Chronic Fatigue Syndrome
Authors: Patarca Roberto
Published: July 2010

Abstract: Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS, with predominance of so‐called T‐helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T‐helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.
Down‐regulation of Receptor‐mediated Endocytosis Is Reponsible for Senescence‐associated Hyporesponsiveness
Authors: PARK SANG CHUL , PARK JEONG‐SOO , PARK WOONG‐YANG , CHO KYOUNG‐A , AHN JEONG SOO , JANG IK SOON
Published: July 2010

Human diploid fibroblasts (HDF) do not divide indefinitely and eventually lead to an arrest of cell division by a process termed cellular or replicative senescence. Irreversible growth arrest of senescent cells is strongly related to the attenuated response to growth factors. Recently, we reported that up‐regulation of caveolin in the senescent cells is responsible for the attenuated response to growth factors. Senescent cells did not phosphorylate Erk‐1/2 after EGF stimulation, whereas young cells did. In those senescent cells, we found an increased level of caveolin proteins and strong interactions between caveolin‐1 and EGFR. When we overexpressed caveolin‐1 in young HDF, the activation of Erk‐1/2 on EGF stimulation was significantly suppressed. These results suggest that the hyporesponsiveness of senescent fibroblasts to EGF stimulation might be due to the overexpression of caveolin. In addition, the clathrin‐dependent endocytosis system plays the more active and dominant role over the caveolae system. Therefore, we monitored the efficiency of clathrin‐dependent receptor‐mediated endocytosis in the senescent cells in order to elucidate the exact mode of the attenuated response to growth factors in the senescent cells. Using a transferrin‐uptake assay and Western blot analysis of endocytosis‐related proteins, we found a significant decrease of amphiphysin‐1 in human diploid fibroblasts of multipassages. By adjusting the level of amphiphysin, we could modulate the efficiency of receptor‐mediated endocytosis either in young or old cells toward growth factors: that is, a dominant negative mutant of amphiphysin‐1 blocked the endocytosis in the young cells, while microinjection of the gene resumed its activity in the old cells. Taken together, we conclude that the loss of endocytotic activity of senescent cells is directly related to the down‐regulation of amphiphysin‐1 and/or up‐regulation of caveolins. This opens a new field of functional recovery of the senescent cells simply through adjusting the receptor‐mediated endocytosis capacity.
Mitochondrial DNA Deletion Mutations and Sarcopenia
Authors: AIKEN JUDD , BUA ENTELA , CAO ZHENGJIN , LOPEZ MARISOL , WANAGAT JON , McKENZIE DEBBIE , McKIERNAN SUSAN
Published: July 2010

This manuscript summarizes our studies on mitochondrial DNA and enzymatic abnormalities that accumulate, with age, in skeletal muscle. Specific quadricep muscles, rectus femoris in the rat and vastus lateralis in the rhesus monkey, were used in these studies. These muscles exhibit considerable sarcopenia, the loss of muscle mass with age. The focal accumulation of mtDNA deletion mutations and enzymatic abnormalities in aged skeletal muscle necessitates a histologic approach in which every muscle fiber is examined for electron transport system (ETS) enzyme activity along its length. These studies demonstrate that ETS abnormalities accumulate to high levels within small regions of aged muscle fibers. Concomitant with the ETS abnormalities, we observe intrafiber atrophy and, in many cases, fiber breakage. Laser capture microdissection facilitates analysis of individual fibers from histologic sections and demonstrates a tight association between mtDNA deletion mutations and the ETS abnormalities. On the basis of these results, we propose a molecular basis for skeletal muscle fiber loss with age, a process beginning with the mtDNA deletion event and culminating with muscle fiber breakage and loss.
Molecular Mimicry in Type 1 Diabetes
Authors: ROEP B. O. , HIEMSTRA H. S. , SCHLOOT N. C. , DE VRIES R. R. P. , CHAUDHURI A. , BEHAN P. O. , DRIJFHOUT J. W.
Published: July 2010

Abstract: Type 1 diabetes is caused by a T cell‐mediated autoimmune destruction of the pancreatic beta cells. Molecular mimicry between viral pathogens and beta cell protein has been a popular theory to explain loss of tolerance in type 1 diabetes. However, functional data in support of this hypothesis have been lacking, presumably because the homologies were defined on the basis of linear similarities in peptide sequences, which ignores the criteria of HLA versus T cell receptor contact residues in peptide epitopes required for T cell recognition. We applied a HLA‐binding dedicated peptide microarray analysis using autoreactive T cell clones specific for the autoantigen GAD65 to determine the algorithm of T cell recognition by this given T cell clone. The subsequent database search identified a 100% fit with cytomegalovirus peptide, which was subsequently shown to be recognized by these clonal T cells. However, T cell clones reactive with linear homologies previously described as putative candidates for T cell cross‐reactivity between GAD65 and Coxsackie virus peptide were unable to recognize the homologous counterparts.
Biological Selection Criteria for Radical Prostatectomy
Authors: MUZZONIGRO GIOVANNI , GALOSI ANDREA B.
Published: July 2010

Abstract: Tumors clinically confined to the prostate gland (T1‐2) are heterogeneous with respect to pathological staging and outcome after definitive radical surgery (radical prostatectomy). The preoperative prognostic factors that could predict pathological stage and outcome of individual patients with clinically localized prostate cancer are reviewed. New preoperative factors have been identified by histological analysis of needle biopsy prostate specimens in addition to Gleason grading score, serum markers (PSA), and clinical staging. These factors are related to tumor volume, zonal origin of the tumor, and spread into the gland and surrounding tissues. Other biological factors are identified by molecular and immunohistochemical analysis (neuroendocrine differentiation, DNA content, microvessel density, and perineural invasion). Biomolecular factors can also be assessed preoperatively on serum samples (free/total PSA ratio, PSA RT‐PCR). Although only a few of these factors have a role in predicting treatment failure and/or disease recurrence, the neural network analysis seems to be the most important tool for identifying patients with more aggressive disease. A combination of these new factors, also using neural networks, could be relevant in the preoperative management of patients with prostate cancer to identify those with confined disease and to select those suitable for a “nerve sparing radical prostatectomy” to preserve sexual function and to achieve definitive cancer control.
Neurotoxicity of Diethylpropion
Authors: GALVAN‐ARZATE SONIA , SANTAMARIA ABEL
Published: July 2010

Abstract: The effects of diethylpropion (DEP), an amphetamine derivative and a well‐known anorectic agent, on different neurochemical and behavioral markers of toxicity in rats were evaluated. Animals received a daily dose of DEP (5 mg/kg po) for 15 days, and all tests were performed 24 hours after the last DEP administration. As neurochemical markers, the brain regional levels of some amino acids, such as aspartate (Asp), glutamate (Glu), gamma‐aminobutyric acid (GABA), and glutamine (Gln), as well as the brain regional rates of lipid peroxidation as a current index of oxidative stress were measured. As behavioral markers, the actions of DEP on both mercaptopropionic acid (MPA)‐induced seizures and kainic acid (KA)‐induced wet‐dog body shakes were explored to investigate whether DEP induces behavioral sensitization to the effects of agents affecting the central activity of neuroactive amino acids. Treatment with DEP produced significant changes in the levels of Asp in the hypothalamus (Ht) and cortex (Cx); Glu in the Ht, Cx, midbrain (Mb), and striatum (S); and Gln in the Cx. The regional levels of GABA remain unchanged. Lipid peroxidation was increased in the hippocampus (Hc), Mb, and S. Also, latency to the first seizure induced by MPA (1.2 mmol/kg ip) and the total number of wet‐dog body shakes induced by KA (10 mg/kg ip) were significantly affected by DEP treatment. These findings suggest that low doses of DEP may affect different neurochemical substrates, inducing changes in neuroactive amino acids along the brain regions, probably involving dopamine release. Consequently, behavioral changes could be the result of excitotoxic events related to excessive Glu or lack of an inhibitory process. Also, DEP is thought to involve free radical formation and oxidative stress as potential features of its regional pattern of neurotoxicity, as evidenced by lipid peroxidation.
Morphological and Biochemical Evidence that Apomorphine Rescues Striatal Dopamine Terminals and Prevents Methamphetamine Toxicity
Authors: BATTAGLIA G. , GESI M. , LENZI P. , BUSCETI C. L. , SOLDANI P. , ORZI F. , RAMPELLO L. , NICOLETTI F. , RUGGIERI S. , FORNAI F.
Published: July 2010

Abstract:Apomorphine, given by a single injection, repeated injections, or by continuous infusion, was tested for neuroprotective effects in mice administered methamphetamine orN‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in order to induce striatal dopamine (DA) depletion. In the first part of the study, the DA agonist (R)‐apomorphine was administered at various doses (1, 5, and 10 mg/kg), 15 min before methamphetamine (5 mg/kg × 3, 2 h apart). Mice were sacrificed 5 days later. In the second part, apomorphine was administered either continuously by subcutaneous minipump (cumulative daily dose of 0.5, 1, and 3.15 mg/kg), or as single, repeated daily injections (up to 5 mg/kg) starting 40 hafteran acute administration of MPTP (30 mg/kg). Mice were sacrificed at different time intervals (up to 1 month) following MPTP injection. In all the animals, the integrity of striatal DA terminals was evaluated by measuring striatal DA levels and TH immunohistochemistry. Apomorphine dose‐dependently prevented methamphetamine toxicity. These effects were neither due to a decrease in the amount of striatal methamphetamine nor to the hypothermia, and they were not reversed by the DA antagonist haloperidol. Moreover, chronic, continuous (but not pulsatile) administration of apomorphine rescued damaged striatal dopaminergic terminals. These findings confirm a protective effect of apomorphine that also consists of a neurorescue of damaged striatal DA terminals. This suggests a new hypothesis about the long‐term benefits observed during continuous apomorphine administration in Parkinson's disease patients.
Tissue‐Specific Modes of Na/Ca Exchanger Regulation
Authors: HRYSHKO LARRY V.
Published: July 2010

Abstract: Ionic regulation of Na+/Ca2+ exchange describes the secondary modulating effects exerted on exchange activity by the transport substrates Na+ and Ca2+. These effects have been extensively characterized for the cardiac Na+/Ca2+ exchanger, NCX1.1, primarily by the giant excised patch‐clamp technique. Moreover, several studies have provided functional evidence for ionic regulation of Na+/Ca2+ exchange activity in intact cellular systems. Through structure‐function analyses, important protein domains involved in these regulatory processes have been identified. However, despite major progress in characterizing ionic regulation at the functional and molecular levels, the physiological importance of these processes remains unknown. In this study, we have examined Na+/Ca2+ exchange activity for three members of the NCX1 family, namely NCX1.1, NCX1.3, and NCX1.4. These exchangers were expressed in Xenopus laevis oocytes and were characterized using the giant excised patch‐clamp technique. We show that these three splice variants exhibit considerable differences in the kinetic features of their ionic regulatory profiles. Information of this type is beginning to provide insight into the physiological basis for tissue‐specific expression of alternatively spliced Na+/Ca2+ exchangers.
Results of Long‐Term Experimental Studies on the Carcinogenicity of Methyl Alcohol and Ethyl Alcohol in Rats
Authors: SOFFRITTI MORANDO , BELPOGGI FIORELLA , CEVOLANI DANIELA , GUARINO MARINA , PADOVANI MICHELA , MALTONI CESARE
Published: July 2010

Abstract: Methyl alcohol was administered in drinking water supplied ad libitum at doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female Sprague‐Dawley rats 8 weeks old at the start of the experiment. Animals were kept under observation until spontaneous death. Ethyl alcohol was administered by ingestion in drinking water at a concentration of 10% or 0% supplied ad libitum to groups of male and female Sprague‐Dawley rats; breeders and offspring were included in the experiment. Treatment started at 39 weeks of age (breeders), 7 days before mating, or from embryo life (offspring) and lasted until their spontaneous death. Under tested experimental conditions, methyl alcohol and ethyl alcohol were demonstrated to be carcinogenic for various organs and tissues. They must also be considered multipotential carcinogenic agents. In addition to causing other tumors, ethyl alcohol induced malignant tumors of the oral cavity, tongue, and lips. These sites have been shown to be target organs in man by epidemiologic studies.
Structural and Functional Abnormalities of the Amygdala in Schizophrenia
Authors: LAWRIE STEPHEN M. , WHALLEY HEATHER C. , JOB DOMINIC E. , JOHNSTONE EVE C.
Published: July 2010

Abstract: Schizophrenia is characterized by delusions and hallucinations, which tend to respond to treatment with dopamine receptor blockers, and a loss of motivation and affect, which do not. Structural magnetic resonance imaging (sMRI) has convincingly demonstrated reduced volumes of the amygdala‐hippocampal complex (AHC) and other limbic and paralimbic structures, on both manual tracing and automated analyses. The Edinburgh High‐Risk Study (EHRS) of initially healthy adolescents with at least two affected relatives has found that AHC volumes are reduced pre‐morbidly but not to schizophrenic levels, suggesting that further volume reductions may be associated with the onset of schizophrenia. AHC volumes appear to be genetically mediated in families with a dominant pattern of transmission, whereas prefrontal lobe and basal ganglia volumes are related to genetic liability to schizophrenia in the generality of high‐risk subjects. Temporal lobe volumes may fall as psychotic symptoms develop, in the context of drug abuse and stress. Neuropsychological testing has also demonstrated pre‐morbid impairments and symptom‐related deterioration. More detailed analyses of the temporal lobe changes on sMRI and fronto‐temporal dysconnectivity on fMRI are in progress. These findings are discussed with reference to other indications of pre‐morbid developmental disturbance in our high‐risk subjects, animal models of schizophrenia, and reliable findings from neuropathological, neuropsychological, and functional imaging studies of patients with schizophrenia.
Neuroprotection by NGF in the PC12 In Vitro OGD Model
Authors: TABAKMAN RINAT , JIANG HAO , SHAHAR IRIS , ARIEN‐ZAKAY HADAR , LEVINE ROBERT A. , LAZAROVICI PHILIP
Published: July 2010

Abstract: Neurodegenerative disorders and chronic disability due to stroke in the brain or spinal cord afflict a large sector of the population. To investigate the mechanism involved in ischemic stroke and to develop neuroprotective drugs/therapies, in vivo and in vitro, pharmacological models are needed. To investigate the cellular and molecular neuroprotective mechanisms of nerve growth factor (NGF), a member of the nervous system neurotrophin family of growth factors, under ischemia, we used an oxygen‐glucose‐deprivation (OGD) device and pheochromocytoma PC12 cells exposed to a paradigm of ischemic insult. Pretreatment of the cultures with 50 ng/mL of NGF, 18 h prior to OGD insult, conferred 30% of neuroprotection. Time‐course experiments showed marked activation of the ERK, JNK, and p‐38 MAPK isoforms during the OGD phase, but not during OGD reperfusion. Pretreatment of the cultures with 50 ng/mL of NGF, 18 h prior to OGD insult, resulted in 50% attenuation of OGD‐induced activation of JNK 1, and 20% and 50% attenuation of OGD‐induced activation of p‐38 α and β, respectively. The effect of NGF on gene expression in the PC12 ischemic model using Affymatrix Rat DNA‐Microarray technology indicates that only 6% of the genes are differentially regulated (induced/suppressed) by OGD insult and/or NGF. These findings support the notion that pretreatment with NGF confers neuroprotection from OGD insult, a phenomenon coincidentally related to differential inhibition of MAPK stress kinase isoforms and differential gene expression. This ischemic model may be useful to investigate molecular mechanisms of OGD‐induced neurotoxicity and NGF‐induced neuroprotection, and to generate novel therapeutic concepts for stroke treatment.
Chronic Exposure to Nitrous Oxide Increases [3H]MK801 Binding in the Cerebral Cortex, but Not in the Hippocampus of Adult Mice
Authors: SOMMER NATASCHA , ROMANO CARMELO , JEVTOVIC‐TODOROVIC VESNA
Published: July 2010

Abstract:Chronic exposure of adult mice to inhalational anesthetic nitrous oxide (N2O) results in anesthetic tolerance. N2O is an NMDA (N‐methyl‐d‐aspartate) antagonist. It has been demonstrated that chronic administration of members of the NMDA antagonist class of drugs (e.g., MK801) causes upregulation of NMDA receptors in certain brain regions that could, at least in part, explain the development of tolerance. We sought to determine whether the anesthetic tolerance resulting from chronic exposure to N2O reflects changes in the number and/or distribution of NMDA receptors. We exposed mice to either a 50‐ or 75‐vol% N2O atmosphere continuously for 1 or 2 weeks and performed binding studies with [3H]MK801 and NR1 antibodies. Binding studies revealed a significant (P< 0.05) increase in [3H]MK801 binding in the cerebral cortex after 2 weeks of N2O (50‐ and 75‐vol%) exposure. Immunocytochemical binding of NR1 antibodies in selected brain regions showed no changes in distribution pattern. The timing of this increase in [3H]MK801 binding correlates with the time period required for development of tolerance.
Oxidative stress caused by mitochondrial calcium overload
Authors: Peng Tsung‐I , Jou Mei‐Jie
Published: July 2010

Mitochondrial oxidative stress has been reported as the result of respiratory complex anomalies, genetic defects, or insufficient oxygen or glucose supply. Although Ca2+ has no direct effect on respiratory chain function or oxidation/reduction process, mitochondrial Ca2+ overload can lead to reactive oxygen species (ROS) increase. Even though Ca2+ is well known for its role as crucial second messenger in modulating many cellular physiological functions, Ca2+ overload is detrimental to mitochondrial function and may present as an important cause of mitochondrial ROS generation. Possible mechanisms include Ca2+ stimulated increase of metabolic rate, Ca2+ stimulated nitric oxide production, Ca2+ induced cytochrome c dissociation, Ca2+ induced cardiolipin peroxidation, Ca2+ induced mitochondrial permeability transition pore opening with release of cytochrome c and GSH‐antioxidative enzymes, and Ca2+‐calmodulin dependent protein kinases activation. Different mechanisms may exist under different mitochondrial preparations (isolated mitochondria vs. mitochondria in intact cells), tissue sources, animal species, or inhibitors used. Furthermore, mitochondrial ROS rise can modulate Ca2+ dynamics and augment Ca2+ surge. The reciprocal interactions between Ca2+ induced ROS increase and ROS modulated Ca2+ upsurge may cause a feedforward, self‐amplified loop createing cellular damage far beyond direct Ca2+ induced damage.
On the Concept of «Psychopathy« and the Treatment of so called «Psychopaths«.
Authors: Kinberg Olof
Published: July 2010

Summary:

The organization of the treatment of mentally diseased ab‐normal or defective people should be carried out on the follow‐ing lines.
The Concept of Randomness
Authors: RESCHER NICHOLAS.
Published: July 2010

Though there be no such thing as chance in the world, our ignorance of the real causes of any event begets a like species of belief or opinion.
Parts and Partitions
Authors: HUMBERSTONE LLOYD
Published: July 2010

Abstract: We use some ideas of David Lewis firom modal metaphysics ‐ in particular the concept of duplication and the Principle of Recombination—together with Lewis's theory of subject matters as partitions of the set of worlds, to illuminate the perennially elusive topic of logical subtraction, systematic theorising about which is in dire need of a non‐standard notion of logical independence. A paradigm case of the desired notion emerges as the kind of independence which obtains between statements which are in Lewis's sense ‘entirely about’ mereologically disjoint spatial regions.
Critical study: Recent work on Frege
Authors: Stjernberg Fredrik
Published: July 2010

Book reviewed in this article:

GILEAD BAR‐ELLI, The Sense of Reference. Internationality in Frege, W. de Gruyter, BerliaNew York

MICHAEL BEANEY, Frege: Making Sense, Duckworth, London
Proof, Reliability, and Mathematical Knowledge*
Authors: PERESSINI ANTHONY
Published: July 2010

Abstract With respect to the confirmation of mathematical propositions, proof possesses an epistemological authority unmatched by other means of confirmation. This paper is an investigation into why this is the case. I make use of an analysis drawn from an early reliability perspective on knowledge to help make sense of mathematical proofs singular epistemological status.
Intelligent Design: neither scientific nor religious*
Authors: CLARKE DAVID
Published: July 2010

Abstract: The debate between creationism and evolution remains vigorous after 80 years. The philosophical arguments against creationism have changed little but they now confront a more nimble opponent ‐ Intelligent Design (ID). This paper examines the main tenets of ID ‐ its appeals to information theory, entropy, specified complexity and essen‐tialism ‐ through an extended critique of William A. Dembski's The Design Revolution. In addition, the philosophy of Wittgenstein exposes ID's inherent scientism.
The Concept of tolerance
Authors: HANSSON ANDERS
Published: July 2010

Abstract: Several writers have improved our understanding of the concept of tolerance, but still there are problems that must be solved. This article, therefore, sets out to explicate the concept of tolerance by exploring some formal aspects and some of its basic parts. The article defines the ‘conditions’ of the concept, emphasizes an important distinction between ‘tolerance’ and ‘toleration’, discuss the nature of the reasons to object to items (the ‘scope’ of tolerance), and the reasoning and rationality of tolerant agents. The aim is to sketch a consistent view of the concept of tolerance, from which a ‘theory of tolerance’ ‐ or a defence of tolerance ‐ could be developed.
Action Explanations Are Not Inherently Normative
Authors: GRÜNE‐YANOFF TILL
Published: July 2010

“Though this be madness, yet there is method in't.”

Hamlet, act II, scene ii

Abstract:  Inherent normativity is the claim that intentional action explanations necessarily have to comply with normatively understood rationality constraints on the ascribed propositional attitudes. This paper argues against inherent normativity in three steps. First, it presents three examples of actions successfully explained with propositional attitudes, where the ascribed attitudes violate relevant rationality constraints. Second, it argues that the inference rules that systematise propositional attitudes are qualitatively different from rationality constraints both in their justification and their recipients. Third, it rejects additional conditions on propositional attitudes, which purport to necessitate a normative commitment. Thus, inherent normativity is rejected; and with it the claim that intentional action explanations differ substantially from other explanations because they are inherently normative.
No New Miracles, Same Old Tricks
Authors: BUSCH JACOB
Published: July 2010

Abstract: Laudan (1984) distinguishes between two senses of success for scientific theories: (i) that a particular theory is successful, and (ii) that the methods for picking out approximately true theories are successful. These two senses of success are reflected in two different ways that the no miracles argument for scientific realism (NMA) may be set out. First, I set out a (traditional) version of NMA that considers the success of particular theories. I then consider a more recent formulation of NMA (Psillos, 1999). This version of NMA is aimed at making us believe that our methods for picking out approximately true theories are reliable. I shall argue that the success of the latter argument is dependent on the success of the first. Therefore, even though Psillos presents a new formulation of NMA, the evidential support for it is no stronger than the evidential support for the original version.
Frege's Theory of Sense and Reference: Some Exegetical Notes1
Authors: KRIPKE SAUL A.
Published: July 2010

Frege's theory of indirect contexts and the shift of sense and reference in these contexts has puzzled many. What can the hierarchy of indirect senses, doubly indirect senses, and so on, be? Donald Davidson gave a well‐known ‘unlearnability’ argument against Frege's theory. The present paper argues that the key to Frege's theory lies in the fact that whenever a reference is specified (even though many senses determine a single reference), it is specified in a particular way, so that giving a reference implies giving a sense; and that one must be ‘acquainted’ with the sense. It is argued that an indirect sense must be ‘immediately revelatory’ of its reference. General principles for Frege's doctrine of sense and reference are sated, for both direct and indirect quotation, to be understood iteratively. I also discuss Frege's doctrine of tensed and first person statements in the light of my analysis. The views of various other authors are examined. The conclusion is to ascribe to Frege an implicit doctrine of acquaintance similar to that of Russell.
Local Union Leadership Orientation and Union Democracy*
Authors: Won George
Published: July 2010

Cette ktude pr6sente une alternative au concept du systPme de dew partis pour le maintient d' un ordre democratique dans les organizations dites volontaires. On a présupposé que, en l'absence de conflit institutionalisé les orientations de rôle de militants qui se dedient des rôles de leaders determinent le caractère politique de l'organization.

On a choisi les délégués Aune convention constitutionelle des United Auto Workers (Syndicat des Travailleurs de 1'Automobile). On a supposé que les facteurs qui conditionnent un ordre democratique sont (i) l'orientation des valeurs des delbgues, (ii) l'evaluation du syndicat comme organization d6mocratique par les délégukés (iii)la perception par les dhgués du comportement politique des membres et de l'attitude de ceux‐ci envers le direction du syndicat. Les resultats suggerent qu' il y a chez ces degues un fort attachement aux valeurs democratiques. En plus, l'evaluation du syndicat par les delegubs et leur perception de l'attitude et du comportement des membres sont des influences determinantes qui renforcent leur attachement B un syst6me democratique de direction.
Eskimo Education, Danish and Canadian: A Comparison*
Authors: Hobart C. W. , Brant C. S.
Published: July 2010

Les auteurs comparent les facilityés d'enseignement mises à la disposition des Esquimaux du Groënland et de ceux de l'Arctique occidental canadien. La comparaison est faite d'une perspective historique et aussi du point de vue du fonctionnement eontemporain des deux systèmes d'éducation. La langue utilisée dans l'enseignement, les antécédents, la formation et les rôles de l'instituteur, le contenu des programmes, l'internat et l'externat sont l'objet d'une analyse. Cette analyse recherche les conséquences de ces facteurs sur l'adaptation socio‐culturelle des éléves et de la population des deux régions.
Who Were The “Laurentian Iroquois”?
Authors: Trigger Bruce G.
Published: July 2010

On a exprimé des opinions diverses sur l'identité des Indiens que Cartier a observés le long du Saint‐Laurent pendant la première moitié du XVIe siécle. II est certain que cétait des Iroquois, mais les opinions diffèrent quant à leur lien avec des groupes iroquois connus subséquemment. Le matériel archéologique découvert établit un lien étroit entre les Hochelagas (groupe de Montréal) et le groupe historique Onontagué Onneiout; une approche linguistique suggère, par ailleurs, que les Stadaconés (groupe de Québec) formaient un groupe distinct parmi les Iroquois connus au XVIIe siècle. Des recherches supplémentaires sont requises afin de voir si les données archéologiques s'appliquent aussi aux Stadaconés et, d'autre part, les données linguistiques, aux Hochelagas.
Conjugal Patterns in Ghana*
Authors: Pool D. I.
Published: July 2010

L'étude des types d'unions conjugales est de grande importance en sociologie et en démographic. Dans une communication dont la portée est surtout démographique, l'auteur examine les types d'alliances en tant que sources de relations sexuelles, lesquelles affectent les taux de natalité dans une société où l'on ne pratique pas le contrôle des naissances. L'enquête porte sur tous les types d'alliances et l'on y met surtout en lumiète l'écart entre les deux types les plus répandus: le mariage coutumier et l'union ne s'appuyant que sur le consentement des partenaires. On y décrit le tau de chaque type d'union, les façons de mettre fin à une alliance et la polygamie. L'auteur établit une association entre le type d'alliance, d'une part, et différents taux de natalité et différentes attitudes à l'endroit de la taille de la famille, d'autre part.
Blood Pressure Changes among Male Navaho Migrants to an Urban Environment
Authors: Alfred Braxton M.
Published: July 2010

Des donnees comparatives sur la pression sanguine systolique et diastolique des Navahos de sexe masculin furent recueillies avant et apres leur emigration d'un milieu rural a un centre urbain. Les deux mesures furent significativement plus elevees apres l'emigration. Quelques facteurs causaux tels que le changement d'altitude, l'ingestion de gras satures et l'age furent elimines. D'un maniere pro‐visoire, on conclut que des facteurs associes a l'emigration, tels qu'un changement dans les habitudes de repos, la pollution de l'air ainsi que la separation de la parente sont a l'origine de ces changements physiologiques.

Comparative data on systolic and diastolic blood pressures were obtained on male Navahos before and after migration from a rural to an urban environment. Both measures were significantly higher after migration. Various possible causes ‐ such as change in altitude, saturated fat intake, and age ‐ are eliminated. It is tentatively concluded that altered rest patterns, urban pollution, and separation from kin, i.e., things specific to the act of migration, are causally implicated.