bluuebunny/crossref_metadata_2025 huggingface dataset:
The Occurrence and Characterization of New Recombinant Isolates of PVY Displaying Shared Properties of PVYNW and PVYNTN
Authors: Chikh Ali M. , Maoka T. , Natsuaki K. T.
Published: June 2007

Isolates of Potato virus Y (PVY), collected in Syria, induced vein necrosis in tobacco but reacted to PVYO monoclonal antibody, and were therefore classified as PVYNW (or PVYN:O). The possible recombinant points within the genome were checked using a previously reported multiplex RT‐PCR. These isolates were categorized in two groups according to recombinant points. Isolates with one recombinant point at the HC‐Pro/P3, identical to previously reported PVYNW (or PVYN:O), were designated as group 1. However, the majority of Syrian PVY isolates showed two recombinant points at both HC‐Pro/P3 and 6K2/NIa, revealing a new genomic recombination pattern that had never been reported for PVYNW (or PVYN:O), hereafter referred to as group 2. Further characterizations showed that isolates of group 2 had an additional recombinant point at the N‐terminal of the coat protein gene (CP) of their genome. Based on the bioassay on tobacco, serological and molecular studies, these isolates showed shared characteristics of both PVYNW and the recombinant PVYNTN, making it difficult to include them in any of these variants. We propose them as new isolates of PVYN strain, and label them PVYSYR (SYR is from Syria, the country of origin).
The long‐term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura
Authors: Satake Masaaki , Nishikawa Jun , Fukagawa Yuki , Akashi Keiko , Okamoto Takeshi , Yoshida Tomoharu , Hirano Atsuyoshi , Maetani Noboru , Iida Youzou , Sakaida Isao
Published: June 2007

Background and Aim:  A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori‐positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period.

Method:  Thirty‐eight ITP patients who were examined for H. pylori infection were assessed. H. pylori‐positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long‐term effect of H. pylori eradication on platelet recovery in patients with H. pylori‐positive ITP.

Results:  Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 × 109/L to 129 × 109/L in 23 H. pylori‐eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 × 109/L (n = 10), 193 × 109/L (n = 9), 168 × 109/L (n = 7), and 243 × 109/L (n = 4) after a mean follow‐up of 25.8 months.

Conclusion:  Eradication therapy for H. pylori‐positive patients with ITP was effective and a favorable effect was maintained for long periods.
Correlation of hepatitis B core antigen and β‐catenin expression on hepatocytes in chronic hepatitis B virus infection: Relevance to the severity of liver damage and viral replication
Authors: Kim Chang Wook , Yoon Seung Kew , Jung Eun Sun , Jung Chan Kwon , Jang Jeong Won , Kim Min Soo , Lee So Yeon , Bae Si Hyun , Choi Jong Young , Choi Sang Wook , Han Nam Ik , Lee Chang Don
Published: June 2007

Background and Aims:  The topographical distribution of hepatitis B core antigen (HBcAg) is related to the pathogenesis of liver damage caused by hepatitis B virus (HBV) infection. β‐catenin plays an important role in both intracellular adhesion and Wnt signaling transduction pathways. This study investigated the intrahepatic expression of HBcAg and β‐catenin in chronic HBV infection, and correlated the results with the degree of liver damage and viral replication.

Method:  Liver sections from 73 patients with chronic HBV infection were examined immunohistochemically for HBcAg and β‐catenin.

Results:  The distribution of HBcAg could be classified into four types: only nucleus (C‐1), both nucleus and cytoplasm (C‐2), only cytoplasm (C‐3) and all negative for nucleus and cytoplasm (C‐4). Significant differences in serum aminotransferase level, HBV DNA and necroinflammatory score were observed among the different distribution types, and as the distribution of HBcAg changed from C‐1 to C‐4, fibrosis stage and hepatitis B e antigen (HBeAg) negative/anti‐HBe positive rate increased concurrently. The distribution of β‐catenin could be classified into two types: only membrane (B‐1) and membrane with nucleus or cytoplasm (B‐2). B‐2 showed higher serum aminotransferase level and necroinflammatory score than B‐1. Between B‐1 and B‐2, there was no significant difference in serum HBV DNA level or fibrosis stage.

Conclusions:  In chronic HBV infection, HBcAg distribution may change from C‐1 to C‐4 gradually, and in correlation with serum aminotransferase, and HBV DNA and HBeAg negative/anti‐HBe positive rate. Nuclear or cytoplasmic distribution of β‐catenin, compared with exclusive membranous distribution of β‐catenin, is related to active hepatitis, but not viral replication.
Prospective study of cardiac troponin I release in patients with upper gastrointestinal bleeding
Authors: Iser David M , Thompson Alexander J V , Sia Koon Ket , Yeomans Neville D , Chen Robert Y M
Published: June 2007

Background and Aim:  The rate of cardiac injury in upper gastrointestinal hemorrhage is unclear. The aims of this study were to determine prospectively the risk of cardiac troponin I release and associated adverse cardiac events in patients with acute upper gastrointestinal hemorrhage.

Methods:  From January to September 2003, we prospectively studied patients with documented hematemesis and melena referred to the gastroenterology unit in a tertiary teaching hospital in Melbourne, Australia. Serial assays for cardiac troponin I were performed at 0, 12 and 24 h. Serial creatine kinase levels and electrocardiographs were also performed. Clinical and biochemical data were collected. The primary endpoint was a troponin level >0.5 μg/L within 24 h of recruitment. Various clinical variables were then compared between the groups of patients with or without troponin rise.

Results:  A total of 156 patients were included in the study. The mean age was 67 years (range 19–96). There were 104 (67%) male patients. A troponin level of greater than 0.5 μg/L was found in 30/156 (19%); 126 (81%) patients had normal troponin levels. Age greater than 65 years, signs of hemodynamic instability at presentation, a recent history of cardiac disease, cardiovascular compromise following endoscopy, and re‐bleeding were associated with troponin release.

Conclusion:  Upper gastrointestinal bleeding is associated with a risk of cardiac injury of up to 19%. Troponin assay could be used to screen for cardiac damage, especially in elderly patients who present with hemodynamic instability.
Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular carcinoma
Authors: Wu Xiong‐Zhi , Xie Guang‐Ru , Chen Dan
Published: June 2007

Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance, and radioresistance of hepatocellular carcinoma (HCC); suppresses differentiation and apoptosis of HCC; and consequently leads to resistance of transarterial embolization (with or without chemotherapy). Because transarterial embolization contributes to angiogenesis via inducing hypoxia, therapy combined with transarterial embolization and antiangiogenic therapy provides a new strategy for the treatment of HCC. Unfortunately, hypoxia leads to the escape of HCC cells from transarterial embolization and antiangiogenic therapy. Thus combined therapy that induces and targets hypoxia may be of benefit to HCC patients. Because angiogenesis plays an important role in recurrence of HCC after resection, antiangiogenic therapy is beneficial to HCC patients following surgical resection of the tumor.
A single center experience of methotrexate in the treatment of Crohn's disease and ulcerative colitis: A case for subcutaneous administration
Authors: Nathan Debbie M , Iser John H , Gibson Peter R
Published: June 2007

Background and Aim:  Methotrexate (MTX) is used as a second‐line immunodulator in patients with inflammatory bowel disease when purine analogs are not tolerated or lack efficacy. High‐level evidence indicates efficacy for intramuscular administration in Crohn's disease, but there are few reports of experience with subcutaneous delivery. This study aimed to evaluate the response to and tolerance of MTX where subcutaneous administration was the preferred option.

Method:  The records of all patients treated with MTX were evaluated with regard to the dose, duration, response, and tolerance to MTX. Remission was defined as improvement in symptoms with no corticosteroid requirement for 3 months or ability to wean off steroids.

Results:  MTX was initiated in 45 patients with Crohn's disease and 23 ulcerative colitis (median age, 46 years; range, 20–80 years; 54% men) because of intolerance (69%) or resistance (31%) to purine analogues. MTX was initiated in 74% of patients in doses of 25 mg (33) or 20 mg (17), administered by subcutaneous self‐injection in 90% of subjects. Remission was achieved in 24 of 45 (53%) with Crohn's disease and 11 of 23 (48%) with ulcerative colitis. An additional four (9%) patients with Crohn's disease and three patients (13%) with ulcerative colitis demonstrated symptomatic improvement and/or ability to decrease corticosteroid dose. While nine patients ceased therapy and nine successfully reduced their doses due to intolerance, three of four patients had no adverse effects. Subcutaneous delivery was well accepted.

Conclusions:  Subcutaneously administered MTX exhibits apparent efficacy, acceptance, tolerance, and safety in patients with Crohn's disease or ulcerative colitis who are steroid‐dependent and where purine analogs have been ineffective or intolerable.
Pharmacological interventions in aging and age‐associated disorders
Authors: Kitani Kenichi
Published: June 2007

In the present study, past attempts using different pharmaceuticals and chemicals which were reported to prolong lifespans of animals are critically reviewed. Despite a large number of trials in animals and humans, the validity of supplementation of antioxidant vitamins such as vitamins A, E and C for improving human health remains unresolved at present. A recent approach using antioxidant mimetics called the EUK series which, despite an initial enthusiastically reported success in prolonging the lifespan of nematodes, remains again unsettled because of the failure in reproducing the initial success by follow‐up studies. α‐Phenyl‐tert‐butylnitrone and related nitrones were initially introduced as radical scavengers. Some of these (e.g. disodium 2,4‐disulfophenyl‐N‐tert‐butylnitrone) are at phase 3 clinical trials as an agent to treat cerebral stroke. This effect, however, appears at least in part to be related to signal transduction which makes these agents effective against cerebral stroke even when they are administered later than its onset. (–)Deprenyl is a monoamine oxidase‐B inhibitor and has some neuroprotective and anti‐apoptotic effects. The drug has also been shown to prolong the lifespans of at least four different animal species. The drug upregulates superoxide dismutase and catalase activities in selective brain regions of dopaminergic nature. These effects on antioxidant enzyme activities are suspected to be causally related to its effect on lifespans of animals. Future trials using these and other drugs are expected to open new doors for interventions in aging and age‐associated disorders in humans.
Correlation between each task of the Mini‐Mental State Examination and regional glucose hypometabolism in at‐rest Alzheimer's disease patients
Authors: Mishina Masahiro , Ishii Kenji , Kitamura Shin , Suzuki Masahiko , Kobayashi Shiro , Ishiwata Kiichi , Katayama Yasuo
Published: June 2007

We investigated the relationship between each task of the Mini‐Mental State Examination (MMSE) and regional glucose hypometabolism in patients with Alzheimer's disease (AD). We studied 38 patients with probable AD using 2‐18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography (FDG PET). The images were corrected for differences in FDG uptake by cerebellar normalization, and were spatially normalized into a standard stereotactic anatomical space using statistical parametric mapping (SPM). There was a positive correlation between FDG uptake and the MMSE subscores for temporal orientation in the bilateral temporal and frontal cortex, and cingulate gyrus; for spatial orientation in the left parietal cortex, bilateral frontal and temporal cortex, and cingulate gyrus; for attention and calculation in the left temporal and frontal cortex; for writing in the left temporal cortex; and for copying and drawing, the correlation was positive in the bilateral parietal and occipital cortex. The total MMSE score was positively correlated with FDG uptake in the left temporal and frontal lobe. Our study demonstrated that, in AD patients, the distribution of hypometabolism in the resting state was related to clinical symptoms and that MMSE scores reflected brain dysfunction in the left hemisphere. Correlation analysis using SPM and FDG PET is useful for the objective evaluation of cognitive tests and diagnostic scoring.
Investigation of visual disorders of subacute myelo‐optico‐neuropathy (SMON) patients 32 years after onset: Questionnaire‐based survey and ophthalmological examination
Authors: Yamanaka Katsumi , Tsuzuki Kinnichi , Ujihira Takatoshi , Inaba Shizuyo , Sobue Gen
Published: June 2007

An investigation of subacute myelo‐optico‐neuropathy (SMON) patients (20 male and 132 female, aged 31–93 years) was conducted in December 1998 using a self‐administered questionnaire. Following this survey, ophthalmological examinations were performed on 33 patients between 1998 and 2000. The questionnaire‐based survey revealed that the prevalence of patients with cataracts was 52.0%, and those with glaucoma was 9.4%. By dividing the patients into two groups, according to the levels of visual disturbances at the time of onset of SMON, we found that the prevalence of glaucoma was higher in the group with visual disturbances than in the group with normal vision. However, the prevalence of cataracts, optico‐neuritis and fundus hemorrhage was not considerably different between the two groups. Ophthalmological examinations (e.g. intraocular pressure test, visual field test, slit lamp microscopy test, funduscopic examination) revealed that 63.6% of patients had cataracts, and 12.1% had glaucoma (9.1% for normal tension glaucoma). The ophthalmological examination revealed that the prevalence of normal tension glaucoma in the SMON patients tended to be higher than in other surveys in the general population of Japan. SMON patients need follow‐up ophthalmological examinations, especially for glaucoma, on a nationwide scale.
Characteristics of syncopal falls in community‐living older people transported to an emergency department
Authors: Takeshita Jun , Hirose Nobuyoshi , Hori Shingo
Published: June 2007

In older people, falls are major reasons for transporting to emergency departments (ED). Falls are etiologically classified into syncopal falls and non‐syncopal ones. The aim of this study is to clarify the characteristics of syncopal falls in community‐living older people transported to ED. The retrospective chart review was performed on patients older than 65 years, transported to the ED of Keio University Hospital in Tokyo because of falls during a 12‐month period. Age, sex, blood pressure and pulse rate at the arrival to ED, episode of syncope, type of fall, sustained injury and medical problems were screened. We analyzed the differences between syncopal falls and non‐syncopal ones. Patients with syncopal falls were given blood tests, electrocardiograms, and standing tests for orthostatic hypotension. The number of syncopal falls was 33 (29.5%), and that of non‐syncopal ones was 79 (69.3%). Syncopal falls frequently occurred on same level compared with from one level to another (84.8% versus 9.1%). In patients with syncopal falls, the frequency of falling on the same level was significantly higher than that in patients with non‐syncopal falls (84.8% vs 60.8%). Patients with syncopal falls significantly sustained fewer fractures (12.1% vs 34.2%), and used more antihypertensive agents (45.5% vs 18.9%) than those with non‐syncopal ones, respectively. The 14 syncopal fall patients were given standing tests, and four patients presented orthostatic hypotension. In community‐living older people transported to ED, syncopal falls frequently occurred on the same level, and the patients with syncopal falls were found to have sustained fewer fractures and use more antihypertensive agents.
Association of a single nucleotide polymorphism in the steroid and xenobiotic receptor (SXR) gene (IVS1‐579A/G) with bone mineral density
Authors: Urano Tomohiko , Shiraki Masataka , Ouchi Yasuyoshi , Inoue Satoshi
Published: June 2007

Vitamin K2 plays an important role in the bone metabolism. The steroid and xenobiotic receptor (SXR) as a nuclear receptor activated by vitamin K2 as well as rifampicin could increase bone markers such as alkaline phosphatase in human osteoblastic cells. Thus, the SXR could mediate vitamin K2 signaling pathway in bone cells. Therefore, we analyzed expression of the SXR mRNA in human primary osteoblasts and chondrocytes. We also studied association of a single nucleotide polymorphism (SNP) in the SXR gene with bone mineral density (BMD). Expression levels of the SXR mRNA were analyzed during the culture course of human primary osteoblasts and chondrocytes. Association of a SNP in the SXR gene in intron 1 (IVS1‐579A>G) with BMD was examined in 294 healthy postmenopausal Japanese women. The SXR mRNA increased at day 5 and then decreased at day 10 in human primary osteoblasts. Its mRNA gradually increased in human primary chondrocytes until day 10. As an association study of a SNP in the SXR gene (IVS1‐579A/G), the subjects without the A allele (GG; n = 47) had significantly higher total BMD than the subjects bearing at least one A allele (AA + AG; n = 247) (Z score ± SD; 0.635 ± 1.031 versus 0.268 ± 1.061; P = 0.0298). The SXR mRNA was expressed and regulated in primary human osteoblasts and chondrocytes. A genetic variation at the SXR gene locus is associated with BMD, suggesting an involvement of the SXR gene in human bone metabolism.
The impact of surface integrity by hard turning versus grinding on rolling contact fatigue – Part I: Comparison of fatigue life and acoustic emission signals
Authors: WARREN A. W. , GUO Y. B.
Published: June 2007

Hard turning and grinding are finishing processes for the manufacture of precision components, such as bearings, gears and cams. However, the effects of distinct surface integrity by hard turning versus grinding on rolling contact life are poorly understood. Four representative surface types were prepared: as‐turned, as‐ground, turned and polished and ground and polished. Surface integrity was characterized by surface topography, microstructure and micro/nanohardness. Fatigue tests were performed with an acoustic emission sensor and the signal processing software. The surface topographies show that skewness of the as‐ground surface is much more negative than the as‐tuned one while other surface parameters are equivalent. The turned surface has a thicker strain hardened zone and a thinner thermal affected zone than those of the ground one. The ground surface has higher micro‐ and nanohardness on surface and in the subsurface than the turned one. The amplitude of acoustic emission signal is the most stable and sensitive signal to fatigue failure. The turned surface may have a longer life (> 84%) than the ground one with equivalent surface finish. The fatigue lives of the bearing assembly are nearly identical for the turned surface versus the polished surface and the turned polished surface versus the ground and polished surface. In addition, polishing may not necessarily improve fatigue life of the machined surface, but increase bearing assembly life as much as 40%.
Crossed cortico‐spinal motor control after capsular stroke
Authors: Braun Christoph , Staudt Martin , Schmitt Carmen , Preissl Hubert , Birbaumer Niels , Gerloff Christian
Published: June 2007

While it is widely accepted that multiple nonprimary motor areas such as the dorsal premotor cortex contribute to recovery from stroke, the contribution of the ipsilesional and contralesional primary motor cortex (M1) is controversial. It has been suggested that re‐instating ‘near normal’ activation patterns is a good strategy for recovery of function [Baron et al., (2004) Cerebrovasc. Dis., 18, 260–267; Ward & Cohen, (2004) Arch. Neurol., 61, 1844–1848]. The present study addressed this aspect of stroke recovery by combining transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) in a cross‐sectional design on nine patients with well‐recovered motor function 17.6 ± 5.5 months (mean ± SD) after subcortical stroke. While TMS was applied to probe the integrity of the cortico‐spinal tract (CST) at rest, MEG was used to test for recruitment of CST pathways during a motor challenge [cortico‐muscular coherence (CMC) in a precision grip task]. With both techniques, crossed cortico‐spinal connectivity could be demonstrated. A significant correlation (r = 0.85) of CMC magnitude and recovered muscle strength underlined the functional relevance of crossed CST integrity for successful recovery. In conclusion, at the descriptive level, crossed CST connectivity is a common finding in well‐recovered patients with capsular stroke. This renders it likely that maintaining or regaining use of crossed CST fibers is one way to achieve effective recovery.
GABAergic mechanisms in absence epilepsy: a computational model of absence epilepsy simulating spike and wave discharges after vigabatrin in WAG/Rij rats
Authors: Bouwman Brigitte M. , Suffczynski Piotr , Lopes da Silva Fernando H. , Maris Eric , Van Rijn Clementina M.
Published: June 2007

In this study, the effects of vigabatrin on spike‐and‐wave discharges (SWDs) were measured in WAG/Rij rats, an animal model of absence epilepsy. Vigabatrin was used with the aim of enhancing GABAergic neurotransmission, and in this way to investigate the role of this process in the properties of SWDs. The study was carried out both in the rat, in vivo, and also using a computational model, in order to test different mechanisms that may account for the changes in SWDs after vigabatrin. The model parameters, representing GABA levels, were changed according to the known, and assumed, mechanism of action of the drug. The results show that the computational model can most adequately simulate the data obtained in vivo on the assumption that the enhancement of GABAergic neurotransmission due to application of vigabatrin is most pronounced at the level of the thalamic relay nuclei (TC cells). Furthermore, vigabatrin was shown to affect both the SWD starting and stopping mechanisms, as reflected by hazard rates. Based on these results, we suggest that GABAergic neurotransmission in TC cells is actively involved in the SWD termination.
Altered cerebellar development in mice lacking pituitary adenylate cyclase‐activating polypeptide
Authors: Allais Aurélie , Burel Delphine , Isaac Emma R. , Gray Sarah L. , Basille Magali , Ravni Aurélia , Sherwood Nancy M. , Vaudry Hubert , Gonzalez Bruno J.
Published: June 2007

Previous studies have demonstrated that pituitary adenylate cyclase‐activating polypeptide (PACAP) exerts trophic effects during neurodevelopment. In particular, the occurrence of PACAP and its receptors in the cerebellum during pre‐ and postnatal periods suggests that it could play a crucial role in ontogenesis of this structure. To test this hypothesis, we compared the histogenesis of cerebellar cortex in wild‐type and PACAP‐knockout (PACAP–/–) mice at postnatal days (P)4 and 7. Morphometric analysis of PACAP–/–mice revealed a significant reduction in the thickness of the external granule cell layer at P4 and of the internal granule cell layer at P7. Expression of nestin, a neural precursor marker, and synaptophysin, a mature neuronal marker, was quantified by real‐time PCR and Western blot. No modification of nestin expression was noticed between wild‐type and PACAP–/–mice, but a substantial decrease in synaptophysin expression was observed in PACAP–/–mice at P4 and P7. Immunohistochemistry revealed a reduction in synaptophysin labelling in the molecular and internal granule cell layers of PACAP–/–mice at P7. Caspase‐3 activation was significantly increased in PACAP–/–mice at P4 and P7. Autoradiographic studies revealed no difference in PACAP binding site distributions and PACAP was effective at stimulating cAMP production in both wild‐type and PACAP–/–cultured granule cells. This study demonstrates that disruption of the PACAP gene induces alteration of the immature cerebellum. Neuronal differentiation of granule cells was delayed whereas cell death that naturally occurs during ontogeny was increased in PACAP–/–mice. These data provide the first evidence of a physiological role for PACAP during cerebellar development.
Insulin‐like growth factor‐1‐dependent maintenance of neuronal metabolism through the phosphatidylinositol 3‐kinase–Akt pathway is inhibited by C2‐ceramide in CAD cells
Authors: Arboleda Gonzalo , Huang Tze‐Jen , Waters Catherine , Verkhratsky Alex , Fernyhough Paul , Gibson Rosemary M.
Published: June 2007

Ceramide is a lipid second‐messenger generated in response to stimuli associated with neurodegeneration that induces apoptosis, a mechanism underlying neuronal death in Parkinson's disease. We tested the hypothesis that insulin‐like growth factor‐1 (IGF‐1) could mediate a metabolic response in CAD cells, a dopaminergic cell line of mesencephalic origin that differentiate into a neuronal‐like phenotype upon serum removal, extend processes resembling neurites, synthesize abundant dopamine and noradrenaline and express the catecholaminergic biosynthetic enzymes tyrosine hydroxylase and dopamine β‐hydroxylase, and that this process was phosphatidylinositol 3‐kinase (PI 3‐K)–Akt‐dependent and could be inhibited by C2‐ceramide. The metabolic response was evaluated as real‐time changes in extracellular acidification rate (ECAR) using microphysiometry. The IGF‐1‐induced ECAR response was associated with increased glycolysis, determined by increased NAD(P)H reduction, elevated hexokinase activity and Akt phosphorylation. C2‐ceramide inhibited all these changes in a dose‐dependent manner, and was specific, as it was not induced by the inactive C2‐ceramide analogue C2‐dihydroceramide. Inhibition of the upstream kinase, PI 3‐K, also inhibited Akt phosphorylation and the metabolic response to IGF‐1, similar to C2‐ceramide. Decreased mitochondrial membrane potential occurred after loss of Akt phosphorylation. These results show that IGF‐1 can rapidly modulate neuronal metabolism through PI 3‐K–Akt and that early metabolic inhibition induced by C2‐ceramide involves blockade of the PI 3‐K–Akt pathway, and may compromise the first step of glycolysis. This may represent a new early event in the C2‐ceramide‐induced cell death pathway that could coordinate subsequent changes in mitochondria and commitment of neurons to apoptosis.
Striatal dopaminergic activity (FDOPA‐PET) associated with cognitive items of a depression scale (MADRS) in Parkinson's disease
Authors: Koerts Janneke , Leenders Klaus L. , Koning Marthe , Portman Axel T. , Van Beilen Marije
Published: June 2007

Motor symptoms form the hallmark of Parkinson's disease (PD), although other features such as depression are often present. Currently‐used depression rating scales measure affective and somatic symptoms. These somatic symptoms of depression can also be core PD symptoms, suggesting an overlap of symptoms between depression and PD. Using in vivo radiotracer methods, striatal dopaminergic dysfunction is found in both PD and depression. This study investigates to what extent the overlapping symptoms of depression and PD are associated with the striatal dopaminergic dysfunction typical of PD. Symptoms of depression were assessed in 23 PD patients who did not have major depression according to the Montgomery–Åsberg depression rating scale (MADRS; cut‐off < 18) and according to a trained psychologist who interviewed all patients. The striatal dopaminergic activity of patients was assessed with FDOPA‐PET. Dopaminergic activity of the putamen and caudate nucleus was associated with MADRS total score and specifically with the symptom ‘Concentration difficulties’. These results suggest that the typical striatal dopaminergic dysfunction of PD can cause symptoms that can also be categorized as symptoms of depression. In particular, cognitive symptoms measured with a depression rating scale may be based on the dopaminergic dysfunction of the striatum in PD patients.
THE SECOND NOEL BUTLIN LECTURE: LABOUR‐INTENSIVE INDUSTRIALISATION IN GLOBAL HISTORY
Authors: Sugihara Kaoru
Published: June 2007

East Asian industrialisation has shown that modern industry has occurred across different cultures under a variety of factor‐endowment conditions. The global history of the diffusion of industrialisation over the past two centuries suggests two distinct routes. The first is the ‘Western path’ associated with capital‐ and energy‐intensive industry. The second path to creating a modern industrial economy is the ‘East Asian path’ based on labour‐intensive industrialisation that has built on quality labour resources cultivated in the traditional sector. This was the path followed by Japan from the nineteenth century and by many other countries in Asia during the twentieth century.
Tax Competition Reconsidered
Authors: DHILLON AMRITA , WOODERS MYRNA , ZISSIMOS BEN
Published: June 2007

In a classic model of tax competition, this paper shows that the level of public good provision and taxation in a decentralized equilibrium can be efficient or inefficient with either too much or too little public good provision. The key is whether there exists a unilateral incentive to deviate from the efficient state and, if so, whether this entails raising or lowering taxes. A priori, there is no reason to suppose the incentive is in either one direction or the other.
Modification of neutrophil adhesion to human endothelial cell line in acute ischemic stroke by dipyridamole and candesartan
Authors: Hallevi H. , Hazan‐Halevy I. , Paran E.
Published: June 2007

Ischemic stroke is a leading cause of disability. Inflammation of the vessel wall following neutrophil adhesion to vascular endothelium may contribute to ischemic damage. We studied the effect of a platelet inhibitor and an angiotensin II receptor antagonist: alone or in combination, on the adhesion of neutrophils to endothelial cell line in stroke patients. Neutrophils were collected from 12 patients with ischemic stroke within 48 h. Six patients with previous stroke and six healthy volunteers served as control. Neutrophils were incubated with dipyridamole, candesartan or both and allowed to adhere to human endothelial cell line (ECV‐304). Adhesion and expression of adhesion molecules (AM) were determined using fluorescence‐activated cell‐sorting (FACS). Dipyridamole and the combination of dipyridamole and candesartan inhibited significantly the adhesion of neutrophils from ischemic stroke patients as compared to controls with a prominent additive effect. No inhibition was seen in the control groups. These drugs also reduced significantly the expression of the AM Mac‐1. Both candesartan and dipyridamole inhibited the adhesion of neutrophils to vascular endothelium in ischemic stroke patients but not in chronic stroke patients or healthy persons. This effect may be related to specific downregulation of Mac‐1 by these drugs or other intracellular events.
Persistence of the Common Hartnup Disease D173N Allele in Populations of European Origin
Authors: Azmanov Dimitar N. , Rodgers Helen , Auray‐Blais Christiane , Giguère Robert , Bailey Charles , Bröer Stefan , Rasko John E. J. , Cavanaugh Juleen A.
Published: June 2007

Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids.
Optical bioluminescence imaging of human ES cell progeny in the rodent CNS
Authors: Bradbury Michelle S. , Panagiotakos Georgia , Chan Bill K. , Tomishima Mark , Zanzonico Pat , Vider Jelena , Ponomarev Vladimir , Studer Lorenz , Tabar Viviane
Published: June 2007

Pre‐clinical efforts of grafting human embryonic stem cell (hESC)‐derived neural precursors have been hampered by problems ranging from graft rejection to overgrowth and tumor formation. The ability to detect such potential complications sensitively and reliably in clinically relevant contexts will rest upon the implementation of suitable non‐invasive imaging technologies for continuously probing graft survival, proliferation, and migration. Neural precursors were transduced ex vivo using a lentiviral‐mediated gene delivery system expressing firefly d‐luciferase, under the control of a cytomegalovirus promoter. Transduced cells revealed no loss of cellular morphology, proliferative capacity, or neural phenotype in vitro. As a novel approach to monitoring the fate of human grafts within the living brain, we adapted optical bioluminescence imaging to assess long‐term graft viability in immunodeficient mouse models transplanted with genetically engineered human neural precursor cells. We additionally applied this technology to immunocompetent models for detecting and characterizing the time course of graft rejection. Using this strategy, we define statistically relevant imaging criteria that can predict graft rejection or overgrowth. In conclusion, our data suggest that optical bioluminescence imaging can serve as an essential tool for the development of hESC‐based grafting strategies in the CNS.
Systemically delivered Erythropoietin transiently enhances adult hippocampal neurogenesis
Authors: Ransome Mark I. , Turnley Ann M.
Published: June 2007

Erythropoietin is a primary regulator of erythropoiesis in the hematopoietic system. More recently erythropoietin has been shown to play a role in neurogenesis and provide neurotrophic support to injured CNS tissue. Here the effects of large systemic doses of erythropoietin on basal levels of adult hippocampal neurogenesis in mice were examined. A 7‐day period of recombinant human erythropoietin (rhEPO) administration increased the number of bromodeoxyuridine [BrdU(+)] cells in the sub‐granular zone (SGZ) by 30%. Analysis of cell phenotype revealed an increase in mitotically active doublecortin(+) neuronal progenitor cells and glial fibrillary acidic protein(+) SGZ radial astrocytes/stem cells but not mature S100β(+) astrocytes. These effects appeared to be mediated, in part, by mitogen‐activated protein kinase signaling and potentially regulated by suppressor of cytokine signaling‐3. Hippocampal levels of phosphorylated extracellular signal‐related kinase 42/44 and suppressor of cytokine signaling‐3 were increased 2–6 h after a single systemic rhEPO injection. However, rhEPO had no observed effect on the long‐term survival of new born cells in the SGZ, with similar numbers of BrdU(+) cells and BrdU(+)/NeuN(+) co‐labeled cells after 4 weeks. Therefore, systemically delivered rhEPO transiently increased adult hippocampal neurogenesis without any apparent long‐term effects.
Inter‐annual variation in provisioning behaviour of Southern Rockhopper Penguins Eudyptes chrysocome chrysocome at Staten Island, Argentina
Authors: RAYA REY ANDREA , TRATHAN PHIL , SCHIAVINI ADRIAN
Published: June 2007

Understanding the relationship between reproductive performance and food availability requires knowledge about many different variables, including such factors as the length of incubation shifts, provisioning rates and patterns, as well as how variability in these factors affects reproductive output. To examine some of the most important aspects of parental investment, we studied the provisioning behaviour and patterns of adult Southern Rockhopper Penguins Eudyptes chrysocome chrysocome breeding at Staten Island, Argentina. We investigated foraging trip duration, provisioning rates and chick survival using adult foraging patterns. Our results show that Rockhopper Penguins had clear sex‐specific differences in their provisioning behaviour. Females provision chicks throughout chick rearing. By contrast, males provision chicks only during the crèche stage and at a slightly lower rate than females during this period. Foraging trips increased in length as the breeding season progressed. Rockhopper Penguins from Staten Island performed longer trips throughout the breeding season than do other species of Eudyptes at several other locations. Our results also show differences in parental investment between years that were related to differences in chick survival. We suggest that this was most likely to be related to female rather than male foraging behaviour as only females showed inter‐annual differences in their provisioning rates.
Hemodialysis at Home Series Editors: Bertrand L. Jaber and John Moran: Effects of Home Hemodialysis on Health‐Related Quality of Life Measures
Authors: Finkelstein Fredric O. , Finkelstein Susan H. , Wuerth Diane , Shirani Shirin , Troidle Laura
Published: June 2007

In recent years, there has been an increased interest in performing hemodialysis (HD) more frequently than thrice weekly, particularly in the home setting. This interest has been stimulated by some studies that have indicated significant benefits to performing more frequent HD on various medical and quality of life outcome measures. However, only a few studies using varying quality of life instruments have critically examined the impact of frequent HD on the quality of life of patients. Although not consistent across studies, results suggest a positive impact of more frequent HD on patients’ quality of life. It is hoped that the results of two landmark studies, now in progress (the Frequent Hemodialysis Network trial and the FREEDOM study), will provide more insight into the impact of more frequent HD on quality of life.
Fellows’ Forum in Dialysis :edited by Mark A. Perazella: Nontuberculous Mycobacterial Peritonitis in Peritoneal Dialysis Patients
Authors: Rho Mira , Bia Frank , Brewster Ursula C.
Published: June 2007

While nontuberculous mycobacterial peritonitis is uncommon among peritoneal dialysis (PD) patients, these infections have serious consequences. They present a significant diagnostic and therapeutic challenge for clinicians. Diagnosis can be delayed due to the slow growth rate of some mycobacterial species. These organisms can also be overlooked when adequate culture media are not used in the microbiological evaluation process. The choice of antimicrobial therapy depends upon isolation and speciation of the infecting Mycobacterium species, and prompt catheter removal is essential. Because serious intra‐abdominal complications may follow infection, identifying patient risk factors for nontuberculous mycobacterial peritonitis and initiating prompt diagnosis and treatment are essential. We report three cases of peritonitis associated with Mycobacterium chelonae and Mycobacterium gordonae, each with a unique presentation, and discuss the appropriate diagnosis and treatment strategies for the management of PD‐associated mycobacterial infections.
Beneficial Effects of Aldosterone Blockade in Heart Failure
Authors: Muhammad Khalid , Ventura Hector O. , Stapleton Dwight D. , Smart Frank W.
Published: June 2007

The authors describe the use of spironolactone, an aldosterone receptor blocker, in a patient with heart failure refractory to conventional therapy. The clinical importance of this case is that not only does spironolactone improve symptoms, but its use also improves survival in patients with severe heart failure. Clinicians should be aware that this therapy has to be added to the medical armamentarium for patients with severe heart failure. In addition, it is important to point out that the use of the aldosterone receptor blockers and their beneficial effects in morbidity and mortality in heart failure has helped to understand more clearly the relationship between aldosterone and its importance in the pathophysiology of heart failure.
Bridging Patients to Cardiac Transplantation
Authors: Higginbotham Michael B. , Russell Stuart D. , Mehra Mandeep R. , Ventura Hector O.
Published: June 2007

Potential recipients of heart transplants have the most advanced form of congestive heart failure, in which standard therapy fails to maintain clinical stability. In the absence of guidelines derived from evidence obtained in clinical trials, caring for these patients becomes a challenge. A successful approach requires the proper coordination of surgical and nonsurgical strategies, including revascularization and valvular surgery as well as mechanical ventricular support and medical strategies. Intensive medical therapy is the most commonly used approach for prolonged bridging to transplantation. Although carefully individualized regimens are necessary to achieve desired goals, most centers adopt a fairly standardized approach involving vasodilators, diuretics, and inotropic support. Bridging patients with cardiac decompensation to transplantation presents a major therapeutic challenge. Appropriate strategies will maximize patients' chances that the bridge from decompensation to transplantation remains intact.
Cardiac Resynchronization for Heart Failure: Present Status
Authors: Auricchio Angelo , Spinelli Julio
Published: June 2007

Ventricular dysfunction is a hallmark of heart failure, and is often linked to ventricular dilatation and ventricular conduction delays. Recent studies have demonstrated that systolic function can be improved in patients with left bundle branch block by pre‐exciting the site of late activation, usually the left ventricular free wall. Furthermore, it has been recently reported that this improvement is associated with a decrease in myocardial oxygen consumption. We hypothesize that the pre‐excitation of the region covered by the blocked bundle acts as an “electrical bypass,” resynchronizing the contraction of the septum and the left ventricular free wall. In addition, optimization of the electronic atrioventricular delay allows the simultaneous resynchronization of the atrioventricular contractions, and minimization of diastolic mitral regurgitation. Systolic mitral regurgitation may also be reduced by removing the geometric distortion introduced by the Left Bundle Branch Block. The recently reported positive outcome of the PATH‐CHF I controlled trial reinforces that the positive acute and chronic results that have been reported up to now may translate into long‐term clinical benefit for patients with heart failure and conduction defects. Larger studies are needed to confirm these initial results and to establish the impact of this new therapeutic modality on morbidity and mortality.
ACE Inhibitors and Anemia in Congestive Heart Failure
Authors: Sica Domenic A.
Published: June 2007

The use of angiotensin‐converting enzyme inhibitors can be accompanied by a number of adverse events, including cough, angioedema, and hyperkalemia, as well as a peculiar form of functional renal insufficiency. Other, less obvious side effects accompany ACE inhibitor use, such as a reduction in red blood cell production. This feature of ACE inhibitor use may be employed to good effect, as in the management of post‐transplant erythrocytosis. Alternatively, the suppressive effect of ACE inhibitors on red blood cell production may intensify the anemia of chronic renal failure and/or congestive heart failure. The untreated congestive heart failure patient typically has an increased red blood cell mass as a consequence of increased erythropoietin levels, with the latter governed by congestive heart failure‐related renal hypoxia. This is not expressed as an increase in hemoglobin concentration because of the increase in plasma volume that marks advanced congestive heart failure. ACE inhibitor therapy can be expected to both reduce plasma volume and decrease red blood cell production. As a result, the hemoglobin concentration changes very little in the ACE inhibitor‐treated congestive heart failure patient and usually falls in the low normal range. Recently, erythropoietin has been employed to good effect in congestive heart failure patients with borderline anemia.
Antibiotic and Infection Tracking in Minnesota Long‐Term Care Facilities
Authors: O'Fallon Erin , Harper Jane , Shaw Shelly , Lynfield Ruth
Published: June 2007

OBJECTIVES: To describe current systems used to track infections, antibiotic use, and antibiotic‐resistant infections in Minnesota long‐term care facilities (LTCFs).

DESIGN: Self‐administered multiple‐choice survey assessing the methods, frequency, content, and dissemination of information used to track infections and antibiotic use.

SETTING: Licensed Minnesota LTCFs providing skilled nursing care to geriatric residents as of June 2005.

PARTICIPANTS: Surveys addressed to the director of nursing at 393 eligible LTCFs.

MEASUREMENTS: Responses to survey questions, assessed by percentage of all responders. Of the 345 surveys returned, the majority had a system to track infections (94.1%), antibiotics prescribed (80.6%), and antibioticresistant infections (86.2%). Most facilities used only a nonelectronic format to track antibiotic use (73.4%) and antibiotic‐resistant infections (72.4%). Respondents collected information on antibiotic susceptibility results from cultures of blood (49.0%), urine (53.0%), sputum (50.0%), or wounds (50.0%). One third of attending clinicians were routinely informed of trends in facility antibiotic use. In 42% of facilities, less than 5 hours per month of paid time for an infection control practitioner was provided. Two‐thirds of responders (64.2%) described their systems as not or somewhat effective at optimizing appropriate antibiotic use in their facilities.

CONCLUSION: Most facilities in Minnesota have a system in place to track infections, antibiotic use, and antibiotic resistance. These systems may not collect or disseminate information effectively enough to identify or address the development of antibiotic resistance. Paid infection control practitioner time is limited.