bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus
Authors: Van Greevenbroek M. M. J. , Vermeulen V. M. M‐J. , Feskens E. J. M. , Evelo C. T. , Kruijshoop M. , Hoebee B. , Van Der Kallen C. J. H. , De Bruin T. W. A. 
Published: March 2007

AbstractAims  Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose‐responsive gene in pancreatic B‐cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21‐1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM.Methods  The frequency distribution of a 3′ UTR single nucleotide polymorphism (SNP) in TXNIP was investigated in subjects with normal glucose tolerance (NGT; n = 379), impaired glucose tolerance (IGT; n = 228) and Type 2 DM (n = 230). Metabolic data were used to determine the effect of this SNP on parameters associated with lipid and glucose metabolism.Results  The frequency of the TXNIP variation did not differ between groups, but within the group of diabetic subjects, carriers of the TXNIP‐T variant had 1.6‐fold higher triglyceride concentrations (P = 0.015; n = 136) and a 5.5‐mmHg higher diastolic blood pressure (P = 0.02; n = 212) than homozygous carriers of the common C‐allele, whereas in non‐diabetic subjects fasting glucose was 0.26 mmol/l lower (P = 0.002; n = 478) in carriers of the T‐allele. Moreover, a significant interaction between plasma glucose concentrations and TXNIP polymorphism on plasma triglycerides was observed (P = 0.012; n = 544).Conclusion  This is the first report to implicate TXNIP in a human disorder of energy metabolism, Type 2 diabetes. The effect of TXNIP on triglycerides is influenced by plasma glucose concentrations, suggesting that the biological relevance of TXNIP variations may be particularly relevant in recurrent episodes of hyperglycaemia.
The metabolic syndrome and incidence of cardiovascular disease in non‐diabetic subjects—a population‐based study comparing three different definitions
Authors: Nilsson P. M. , Engström G. , Hedblad B. 
Published: March 2007

AbstractAims  Between 1998 and 2005, a number of definitions of the metabolic syndrome (MetS) have been proposed. The aim of this population‐based cohort study was to compare prevalence rates and the prediction of cardiovascular disease (CVD) using different definitions of MetS.Methods  A total of 5047 non‐diabetic subjects (66% women), from the city of Malmö, Sweden, were followed. The incidence of fatal and non‐fatal CVD (cardiac events, n = 176, and stroke, n = 171) was monitored over 11 years of follow‐up. MetS was defined in three different ways [by International Diabetes Federation (IDF), National Cholesterol Education Program—Adult Treatment Panel III (NCEP‐ATPIII), or European Group for the study of Insulin Resistance (EGIR) criteria] based on data on waist circumference, blood pressure, serum triglycerides, High‐density lipoprotein cholesterol and fasting blood glucose. The IDF definition identified 21.9% of the subjects having the MetS. Corresponding figures for the NCEP‐ATPIII and EGIR definitions were 20.7 and 18.8%, respectively.Results  After taking age, gender, low‐density lipoprotein cholesterol and lifestyle factors into account, the hazard ratio (HR) for CVD event according to the IDF, NCEP‐ATPIII and EGIR definitions were HR 1.11 (95% CI: 0.86–1.44), 1.59 (1.25–2.03) and 1.35 (1.05–1.74), respectively. The results were largely similar for cardiac and stroke events.Conclusions  The prevalence of Mets according to the IDF definition was higher in comparison with NCEP‐ATPIII and EGIR definitions, but the IDF definition was not superior to these definitions for prediction of CVD events. This was true for both genders and questions the usefulness of the current IDF criteria of MetS in a North‐European, Caucasian population. In addition, single risk factors such as smoking had an equal prediction as the metabolic syndrome.
High‐frequency QRS electrocardiogram
Authors: Trägårdh Elin , Schlegel Todd T. 
Published: March 2007

SummaryThe standard 12‐lead electrocardiogram (ECG) is one of the most commonly used methods for diagnosing heart disease. Standard ECG is not always optimal, however, and new ECG methods can provide additional information. Analysis of high‐frequency QRS components (HF‐QRS) has been shown to increase the diagnostic performance of the ECG. Several investigators have studied HF‐QRS in different cardiac conditions, including acute myocardial ischaemia and myocardial infarction, but more knowledge is needed about the characteristics of HF‐QRS before clinicians can use it as an adjunct to standard ECG.
The New Political System of Israel
Authors: Diskin Abraham 
Published: March 2007

During the 1990s the israeli political system faced a number of major upheavals on both the macro- and the micro-political levels. As a result many of its basic features changed considerably. Presently, it is more difficult to predict future political behaviour in Israel than ever before.One may point at the only successful no-confidence vote, which took place on 15 March 1990, as an event that symbolically initiated the new era. Yitzhak Shamir, the head of the Likud and the acting prime minister at the time, overcame the crisis, formed a new government, and continued to serve as prime minister. Yitzhak Rabin of the Labour Party took power following the 1992 elections. Shimon Peres of Labour succeeded Rabin as premier following Rabin's assassination in November 1995. Peres lost the 1996 elections to Likud's new leader, Benjamin Netanyahu. In the 1999 elections, Labour returned to power under the leadership of Prime Minister Ehud Barak.
Improving the Interpretation of Ictal Scalp EEG: BSS–CCA Algorithm for Muscle Artifact Removal
Authors: Vergult Anneleen , De Clercq Wim , Palmini André , Vanrumste Bart , Dupont Patrick , Van Huffel Sabine , Van Paesschen Wim 
Published: March 2007

Summary:  Purpose: To investigate the potential clinical relevance of a new algorithm to remove muscle artifacts in ictal scalp EEG. Methods: Thirty‐seven patients with refractory partial epilepsy with a well‐defined seizure onset zone based on full presurgical evaluation, including SISCOM but excluding ictal EEG findings, were included. One ictal EEG of each patient was presented to a clinical neurophysiologist who was blinded to all other data. Ictal EEGs were first rated after band‐pass filtering, then after elimination of muscle artifacts using a blind source separation–canonical correlation analysis technique (BSS–CCA). Degree of muscle artifact contamination, lateralization, localization, time and pattern of ictal EEG onset were compared between the two readings and validated against the other localizing information. Results: Muscle artifacts contaminated 97% of ictal EEGs, and interfered with the interpretation in 76%, more often in extratemporal than temporal lobe seizures. BSS–CCA significantly improved the sensitivity to localize the seizure onset from 62% to 81%, and performed best in ictal EEGs with moderate to severe muscle artifact contamination. In a significant number of the contaminated EEGs, BSS–CCA also led to an earlier identification of ictal EEG changes, and recognition of ictal EEG patterns that were hidden by muscle artifact. Conclusions: Muscle artifacts interfered with the interpretation in a majority of ictal EEGs. BSS–CCA reliably removed these muscle artifacts in a user‐friendly manner. BSS–CCA may have an important place in the interpretation of ictal EEGs during presurgical evaluation of patients with refractory partial epilepsy.
Unsuspected periventricular leukomalacia in children with strabismus: a case series
Authors: Muen Wisam J. , Saeed Muhammad U. , Kaleem Musa , Abernethy Laurence , Chandna Arvind 
Published: March 2007

Abstract.Purpose:  We report a case series of seven patients who presented with strabismus and no apparent known neurological deficit.Methods:  A retrospective review of notes was performed on all patients presenting at the Royal Liverpool Children's Hospital (Alder Hey) with strabismus, in whom subsequent investigation revealed the presence of periventricular leukomalacia (PVL).Results:  All seven patients presented with esotropia. One patient also had dissociated vertical deviation. A history of premature birth was elicited in six cases; however, one patient had been born at 42 weeks. Apparently uncomplicated routine surgery produced unexpectedly poor results.Conclusions:  Patients with undiagnosed PVL may present to the ophthalmologist with strabismus and no other apparent neurological abnormality. Where it is suspected that the patient may have suffered a significant hypoxic‐ischaemic event, the ophthalmologist should have a low threshold for investigating with magnetic resonance imaging, particularly if the patient shows unexpected outcomes following appropriate treatment. Patients and parents should be counselled on possible suboptimal results prior to the offer of surgical correction of strabismus.
Simultaneous Quantification of Epstein-Barr Virus, Cytomegalovirus, and Human Herpesvirus 6 DNA in Samples from Transplant Recipients by Multiplex Real-Time PCR Assay
Authors: Wada Kaoru , Kubota Naomi , Ito Yoshinori , Yagasaki Hiroshi , Kato Koji , Yoshikawa Tetsushi , Ono Yasuyuki , Ando Hisami , Fujimoto Yasuhiro , Kiuchi Tetsuya , Kojima Seiji , Nishiyama Yukihiro , Kimura Hiroshi 
Published: March 2007

ABSTRACT
We developed a multiplex real-time PCR assay using 6-carboxyfluorescein, 6-carboxy-4′,5′-dichloro-2′,7′-dimethoxyfluorescein, and carbocyanine 5-labeled probes to simultaneously quantify Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) DNA. When previously tested and stored DNA samples were examined, results of the multiplex real-time PCR assay were as sensitive and specific as those of a single real-time PCR assay. The multiplex assay was used to quantify the EBV, CMV, and HHV-6 DNA in 46 transplant recipients. A total of 303 whole-blood and plasma specimens were collected and analyzed. According to the results of the multiplex assay, the detection rates for viral DNA in whole blood and plasma were 23.8% and 5.9% for EBV, 11.2% and 5.3% for CMV, and 12.5% and 2.0% for HHV-6, respectively. All forms of viral DNA were detected more frequently in whole blood than in plasma. During the symptomatic period, EBV DNA was detected in all whole-blood specimens but not in all plasma specimens. Furthermore, the EBV DNA load in whole blood was higher during the symptomatic period than during the asymptomatic period, whereas the EBV DNA load in plasma was similar for both periods. These results demonstrate that whole blood is more suitable for the quantification of EBV DNA in transplant patients. However, a cutoff value with clinical relevance still needs to be determined.
Clinical and Virological Characteristics of Hepatitis B Virus Subgenotypes Ba, C1, and C2 in China
Authors: Wang Zhanhui , Tanaka Yasuhito , Huang Yuehua , Kurbanov Fuat , Chen Jinjun , Zeng Guobing , Zhou Bin , Mizokami Masashi , Hou Jinlin 
Published: March 2007

ABSTRACT
Hepatitis B virus (HBV) subgenotypes Ba, C1 (Cs), and C2 (Ce) are the most prevalent HBV variants in China. To investigate the virological characteristics of these subgenotypes and their clinical implications, we enrolled a cohort of 211 patients in the Guangdong Province of China, including 132 with chronic hepatitis B virus infection (CH), 32 with liver cirrhosis (LC), and 47 with hepatocellular carcinoma (HCC) according to clinical examination, liver function test, and ultrasonograph results. Overall, HBV Ba was found in 51.2% (108/211), HBV C1 in 33.6% (71/211), and HBV C2 in 15.2% (32/211) of the cases. The distribution of HBV genotype C was greater among patients in the LC and HCC groups than among patients in the CH group, while the distribution of HBV genotype B was greater among the CH patients than among the LC and HCC patients. No significant differences in clinical features were found among patients with HBV Ba, C1, and C2. Virologically, HBV C1 had the strongest association with the A1762T G1764A double mutation, while the mutation at position 1896 resulting in A (1896A) was uncommon. In contrast, HBV Ba had the highest frequency of 1896A but the lowest of A1762T G1764A, and HBV C2 had intermediate frequencies of these mutations. Mutations of 1653T and 1753V were specifically associated with HBV C2 and C1, respectively. Multivariate analyses showed that the 1653T, 1753V, and A1762T G1764A mutations and patient age significantly increased the risk of HCC development. In conclusion, HBV Ba, C1, and C2 have different mutation patterns in the enhancer II/core promoter/precore region. Therefore, genotyping and detecting the 1653T and 1753V mutations, in addition to the A1762T G1764A double mutation, might have important clinical implications as predictive risk factors for hepatocarcinogenesis.
Infectivity Determinants of the Hepatitis B Virus Pre-S Domain Are Confined to the N-Terminal 75 Amino Acid Residues
Authors: Blanchet Matthieu , Sureau Camille 
Published: March 2007

ABSTRACT
The N-terminal pre-S domain of the large hepatitis B virus (HBV) envelope protein plays a pivotal role at the initial step of the viral entry pathway. In the present study, the entire pre-S domain was mapped for infectivity determinants, following a reverse-genetics approach and using in vitro infection assays with hepatitis delta virus (HDV) or HBV particles. The results demonstrate that lesions created within the N-terminal 75 amino acids of the pre-S region abrogate infectivity, whereas mutations between amino acids 76 and 113, overlapping the matrix domain, had no effect. In contrast to the results of a recent study (L. Stoeckl, A. Funk, A. Kopitzki, B. Brandenburg, S. Oess, H. Will, H. Sirma, and E. Hildt, Proc. Natl. Acad. Sci. 103:6730-6734, 2006), the deletion of a cell membrane translocation motif (TLM) located between amino acids 148 and 161 at the C terminus of pre-S2 did not interfere with the infectivity of the resulting HDV or HBV mutants. Furthermore, a series of large deletions overlapping the pre-S2 domain were compatible with infectivity, although the efficiency of infection was reduced when the deletions extended to the pre-S1 domain. Overall, the results demonstrate that the activity of the pre-S domain at viral entry solely depends on the integrity of its first 75 amino acids and thus excludes any function of the matrix domain or TLM.
Identification of Hendra Virus G Glycoprotein Residues That Are Critical for Receptor Binding
Authors: Bishop Kimberly A. , Stantchev Tzanko S. , Hickey Andrew C. , Khetawat Dimple , Bossart Katharine N. , Krasnoperov Valery , Gill Parkash , Feng Yan Ru , Wang Lemin , Eaton Bryan T. , Wang Lin-Fa , Broder Christopher C. 
Published: March 2007

ABSTRACT
Hendra virus (HeV) is an emerging paramyxovirus capable of infecting and causing disease in a variety of mammalian species, including humans. The virus infects its host cells through the coordinated functions of its fusion (F) and attachment (G) glycoproteins, the latter of which is responsible for binding the virus receptors ephrinB2 and ephrinB3. In order to identify the receptor binding site, a panel of G glycoprotein constructs containing mutations was generated using an alanine-scanning mutagenesis strategy. Based on a predicted G structure, charged amino acids residing in regions that could be homologous to those in the measles virus H attachment glycoprotein known to be involved in its protein receptor interaction were targeted. Using a coprecipitation-based assay, seven single-amino-acid substitutions in HeV G were identified as having significantly impaired binding to both the ephrinB2 and ephrinB3 viral receptors: D257A, D260A, G439A, K443A, G449A, K465A, and D468A. The impairment of receptor interaction conferred a concomitant diminution in their abilities to promote membrane fusion when coexpressed with F. The G glycoprotein mutants were also recognized by three or more conformation-dependent monoclonal antibodies of a panel of five, were expressed on the cell surface, and retained their abilities to bind and coprecipitate F. Interestingly, some of these mutant G glycoproteins coprecipitated with F more efficiently than wild-type G. Taken together, these data provide strong biochemical and functional evidence that some of these residues could be part of a conformation-dependent, discontinuous, and overlapping ephrinB2 and -B3 binding domain within the HeV G glycoprotein.
Downregulation of an Astrocyte-Derived Inflammatory Protein, S100B, Reduces Vascular Inflammatory Responses in Brains Persistently Infected with Borna Disease Virus
Authors: Ohtaki Naohiro , Kamitani Wataru , Watanabe Yohei , Hayashi Yohei , Yanai Hideyuki , Ikuta Kazuyoshi , Tomonaga Keizo 
Published: March 2007

ABSTRACT

Borna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca
2+
-binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM-1), as well as the infiltration of encephalitogenic T cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S100B in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection.
Hepatitis C Virus (HCV)-Specific CD8+Cells Produce Transforming Growth Factor β That Can Suppress HCV-Specific T-Cell Responses
Authors: Alatrakchi Nadia , Graham Camilla S. , van der Vliet Hans J. J. , Sherman Kenneth E. , Exley Mark A. , Koziel Margaret James 
Published: March 2007

ABSTRACTHepatitis C virus (HCV)-specific T-cell responses are rarely detected in peripheral blood, especially in the presence of human immunodeficiency virus (HIV) coinfection. Based on recent evidence that T-regulatory cells may be increased in chronic HCV, we hypothesized that functional blockade of regulatory cells could raise HCV-specific responses and might be differentially regulated in the setting of HIV coinfection. Three groups of subjects were studied: HCV monoinfected, HCV-HIV coinfected, and healthy controls. Frequencies of peripheral T cells specific for peptides derived from HCV core, HIV type 1 p24, and recall antigens were analyzed by gamma interferon (IFN-γ) enzyme-linked immunospot assay. HCV-specific T-cell responses were very weak in groups with HCV and HCV-HIV infections. Addition of blocking antibodies against transforming growth factor β1 (TGF-β1), -2, and -3 and interleukin-10 specifically increased the HCV-specific T-cell responses in both infected groups; however, this increase was attenuated in the group with HCV-HIV coinfection compared to HCV infection alone. No increase in recall antigen- or HIV-specific responses was observed. Flow cytometric sorter analysis demonstrated that regulatory-associated cytokines were produced by HCV-specific CD3+CD8+CD25−cells. Enhancement of the IFN-γ effect was observed for both CD4 and CD8 T cells and was mediated primarily by TGF-β1, -2, and -3 neutralization. In conclusion, blockade of TGF-β secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection.
Inhibition of Transcription of the Beta Interferon Gene by the Human Herpesvirus 6 Immediate-Early 1 Protein
Authors: Jaworska Joanna , Gravel Annie , Fink Karin , Grandvaux Nathalie , Flamand Louis 
Published: March 2007

ABSTRACTHuman herpesviruses (HHV) are stealth pathogens possessing several decoy or immune system evasion mechanisms favoring their persistence within the infected host. Of these viruses, HHV-6 is among the most successful human parasites, establishing lifelong infections in nearly 100% of individuals around the world. To better understand this host-pathogen relationship, we determined whether HHV-6 could interfere with the development of the innate antiviral response by affecting interferon (IFN) biosynthesis. Using inducible cell lines and transient transfection assays, we have identified the immediate-early 1 (IE1) protein as a potent inhibitor of IFN-β gene expression. IE1 proteins from both HHV-6 variants were capable of suppressing IFN-β gene induction. IE1 prevents IFN-β gene expression triggered by Sendai virus infection, double-stranded RNA (dsRNA) and dsDNA transfection, or the ectopic expression of IFN-β gene activators such as retinoic inducible gene I protein, mitochondrial antiviral signaling protein, TBK-1, IκB kinase ε (IKKε), and IFN regulatory factor 3 (IRF3). While the stability of IFN-β mRNA is not affected, IE1-expressing cells have reduced levels of dimerized IRF3 and nucleus-translocated IRF3 in response to activation by TBK-1 or IKKε. Using nuclear extracts and gel shift experiments, we could demonstrate that in the presence of IE1, IRF3 does not bind efficiently to the IFN-β promoter sequence. Overall, these results indicate that the IE1 protein of HHV-6, one of the first viral proteins synthesized upon viral entry, is a potent suppressor of IFN-β gene induction and likely contributes to favor the establishment of and successful infection of cells with this virus.