bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalent human coxsackie B‐5 virus infects porcine islet cells primarily using the coxsackie‐adenovirus receptor
Authors: Myers Suzanne E. , Brewer Laurie , Shaw Daniel P. , Greene Wallace H. , Love Brenda C. , Hering Bernhard , Brad Spiller O. , Kariuki Njenga M. 
Published: October 2004

Abstract:  Background:  We have previously demonstrated that transplanting porcine encephalomyocarditis virus (EMCV)‐infected porcine islet cells (PICs) results in transmission of the virus to recipient mice, which is manifested by acute fatal infection within 5 to 8 days. Here, we determined PIC susceptibility to a related and highly prevalent human picornavirus, coxsackie B‐5 virus (CVB‐5).Methods:  PICs were inoculated with CVB‐5 in vitro for up to 96 hours and infectivity, level of virus replication, and cellular function determined. Subsequently, monoclonal and polyclonal antibody blocking experiments were used to investigate the receptor CVB‐5 uses to enter PICs, and the ability of CVB‐5‐infected islets to reverse diabetes analyzed in mice.Results:  Adult pig islets inoculated with CVB‐5 in vitro showed a typical picornaviral replication cycle with a 2‐h lag phase followed by a 4‐h exponential phase during which the virus titer increased by 4 logs. However, CVB‐5 was less cytolytic to PICs than EMCV, resulting in a persistent productive infection lasting for up to 96 h, with minimal evidence of cell lysis. Double immunostaining confirmed the presence of CVB‐5 antigens in insulin‐producing islets. Infection of PICs in the presence of antibodies against human coxsackie‐adenovirus receptor (CAR) resulted in near complete blockage in production of infectious virus particles whereas blocking with anti‐porcine decay‐accelerating factor (DAF, also called CD55) or anti‐porcine membrane cofactor protein (MCP, also called CD46) only slightly decreased the number of infectious CVB‐5 particles produced. Immunofluoresence staining showed CAR and MCP expression on the islet surface, but not DAF. Transplanting CVB‐5‐infected PICs into diabetic C57BL/6 mice resulted in reversal of diabetes.Conclusion:  Although PICs are susceptible to human CVB‐5, the infection does not appear to affect xenograft function in vitro or in vivo in the short term.
Factors, fiction and endothelium‐derived hyperpolarizing factor
Authors: Sandow Shaun L 
Published: October 2004

Summary1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium‐dependent vasodilatory mechanism is characterized as the hyperpolarization‐mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so‐called endothelium‐derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact‐mediated mechanism.2. Most evidence supports the concept that ‘EDHF’ activity is dependent on contact‐mediated mechanisms. This involves the transfer of an endothelium‐derived electrical current, as an endothelium‐derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease.3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less‐than‐optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature.4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the reported heterogeneity in the nature and mechanism of action of EDH(F), the contribution of experimental design and technique to this heterogeneity will be examined.
Endothelin‐1‐mediated coronary vasoconstriction deteriorates myocardial depression in hearts isolated from lipopolysaccharide–treated rats: Interaction with nitric oxide
Authors: Tu Jie , Shan Qixian , Jin Hongfeng , Bourreau Jean‐Pierre , Xia Qiang 
Published: October 2004

Summary1. The aim of the present study was to evaluate the contribution of disturbance of coronary perfusion to myocardial depression in hearts isolated from lipopolysaccharide (LPS)‐treated rats and to investigate the involvement of endothelin (ET)‐1 and nitric oxide (NO).2. Rats were treated with LPS (10 mg/kg, i.p.) and, 4 h later, plasma ET‐1 concentrations were measured by radioimmunoassay and hearts were excised for perfusion at a constant perfusion flow. The selective ETA receptor antagonist BQ‐123, in the absence or presence of aminoguanidine, a specific inhibitor of inducible NO synthase, was given 15 min before LPS challenge. Coronary perfusion pressure (CPP) and measures of myocardial contractile function were recorded.3. In hearts isolated from LPS‐treated rats, there was a marked increase in CPP that was abolished by pretreatment with BQ‐123. In parallel, an increase in plasma ET‐1 concentrations was seen in these rats. Lipopolysaccharide also induced decreases in left ventricular developed pressure (LVDP), the product of LVDP and heart rate and maximal rate of rise/fall of left ventricular pressure (+/– dP/dtmax). Single treatment with BQ‐123 or aminoguanidine attenuated LPS‐induced myocardial depression. However, when these two drugs were given simultaneously, myocardial depression elicited by LPS was blocked significantly.4. Endothelin‐1‐mediated coronary vasoconstriction, together with NO, contributes to myocardial depression in hearts isolated from LPS‐treated rats.
Effects of caffeic acid phenethyl ester on glycerol‐induced acute renal failure in rats
Authors: Aydogdu Nurettin , Atmaca Gulizar , Yalcin Omer , Batcioglu Kadir , Kaymak Kadir 
Published: October 2004

Summary1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti‐oxidant, on the myoglobinuric ARF induced by intramusculer hypertonic glycerol injection.2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 µmol/kg, i.p.) was administered to group 3 rats. Forty‐eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia.3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated.4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA.5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.
Antinociception induced by stimulating the anterior pretectal nucleus in two models of pain in rats
Authors: Villarreal Cristiane F , Kina Vania Aparecida V , Prado Wiliam A 
Published: October 2004

Summary1. This study examined whether different parts of the rat anterior pretectal nucleus (APtN) may be involved in the spinal control of brief (tail flick test) or persistent (surgical incision of the plantar aspect of a hind paw) noxious inputs via activation of descending pathways.2. We have confirmed that stimulation of the dorsal APtN produces a strong antinociceptive effect in the tail flick test, as opposed to a very weak effect obtained from the ventral APtN. Stimulation at the ventral APtN was the most effective part of the nucleus against a persistent incisional pain.3. The incisional pain was significantly increased following injection of 1 or 2% lignocaine (0.25 µL) into the nucleus, but the effect was more intense after neural block of the ventral rather than the dorsal APtN. Injection of 2% lignocaine (0.10 µL) into the ventral, but not dorsal, APtN significantly increased the perception of the incisional pain.4. We conclude that the effect of stimulating the APtN depends on the site of stimulation and model of pain used. Sustained noxious stimuli activate pathways from the ventral APtN to reduce further noxious spinal inputs. The noxious stimulation produced during the tail flick test may be not enough to activate the same circuitry, but electrical stimulation at the dorsal APtN is very effective in inhibiting brief thermal noxious inputs at the spinal level.
Gene expression profiles in response to the activation of adrenoceptors in A7r5 aortic smooth muscle cells
Authors: Wang Yongyu , Hou Rong , Li Ping , Li Jinliang , Yan Jie , Yin Feng , Han Chide , Zhang Youyi 
Published: October 2004

Summary1. Vascular adrenoceptors play an important role in vascular physiology and pathophysiology, such as hypertension, atherosclerosis and restenosis after angioplasty. To define the changes in the ene expression in vascular smooth muscle cells in response to the activation of α1‐ or β‐adrenoceptors, a DNA microarray was used.2. First, the existence of α1‐ and β‐adrenoceptors in A7r5 aortic smooth muscle cells was confirmed by radioligand binding. Then, the inhibitory effects of phenylephrine (an α1‐adrenoceptor agonist) and isoproterenol (a β‐adrenoceptor agonist) on the proliferation of A7r5 cells were determined by [3H]‐thymidine incorporation.3. The A7r5 cells were treated with 10 µmol/L phenylephrine or 1 µmol/L isoproterenol for 24 h and changes in gene expression were detected with the DNA microarray. Only 14 and 20 genes were identified after treatment of cells with phenylephrine and isoproterenol, respectively, and most genes displayed decreased expression. The changed genes could be grouped into five major functional categories: cell signalling/communication, cell structure/motility, cell/organism defence, gene/protein expression and metabolism. The gene expression profile in response to the activation of α1‐adrenoceptors was very different from that following activation of β‐adrenoceptors. Interestingly, many phenylephrine‐responsive genes were associated with metabolism, whereas many isoproterenol‐responsive genes encoded cell signalling and structure proteins. This means that adrenoceptors may modulate multiple aspects of biological function in vascular smooth muscle cells.4. Collectively, the activation of both α1‐adrenoceptors (with phenylephrine) and β‐adrenoceptors (with isoproterenol) inhibited the proliferation of A7r5 cells, but microarray data revealed that the mechanisms may be different: the activation of α1‐adrenoceptors could induce the expression of metabolic genes, resulting in the inhibition of proliferation, whereas activation of β‐adrenoceptors altered the expression of genes that encoded cell signalling and structure proteins to inhibit cell proliferation.
T393C polymorphism of GNAS1 associated with the autonomic nervous system in young, healthy Japanese subjects
Authors: Yasuda Koichiro , Matsunaga Tetsuro , Moritani Toshio , Nishikino Mariko , Gu Ning , Yoshinaga Mariko , Nagasumi Kae , Yamamura Tsubasa , Aoki Norihiko , Tsuda Kinsuke 
Published: October 2004

Summary1. T393C polymorphism of the gene encoding the Gs‐protein α‐subunit (GNAS1) has been reported recently to be associated with hypertension in which dysfunctions of the autonomic nervous system (ANS) are closely involved. In the present study, the association of this polymorphism with ANS activity was investigated in young, healthy Japanese males.2. Four hundred and one subjects were genotyped for the T393C polymorphism of GNAS1 by polymerase chain reaction–restriction fragment length polymorphism. Autonomic nervous system activity during supine rest and when standing was assessed in 137 subjects by electrocardiogram R‐R interval power spectral analysis.3. One hundred and fifty‐four subjects (38.4%) were homozygous for the T allele (TT), 188 (46.9%) were heterozygous (TC) and 59 (14.7%) were homozygous for the C allele (CC). There were no significant differences as to genotype among the clinical characteristics investigated. In power spectral analysis of heart rate variability, the high‐frequency component and parasympathetic nervous system (PNS) index during supine rest were significantly lower in TT and TC carriers than in CC carriers. Furthermore, the increase in heart rate and the responsiveness of sympathetic nervous system index and PNS index to postural change from supine rest to standing were significantly lower in TT and TC carriers than in CC carriers.4. These observations suggest that the GNAS1 T393C polymorphism is associated with ANS activity in youth, so that it may be useful as a genetic marker for future pathogenesis of hypertension. Follow‐up studies are necessary to clarify the prevalence rates of hypertension among 393T allele carriers in the present study.
Interactions of tachykinin receptor antagonists with lipopolysaccharide‐induced airway inflammation in mice
Authors: Veron M , Guenon I , Nenan S , Emonds‐Alt X , Advenier C , Lagente V , Boichot E 
Published: October 2004

Summary1. Several observations suggest that tachykinins are involved in the pathogenesis of bronchopulmonary alterations. We have investigated the effect of antagonists for tachykinin NK1 (SR 140333), NK2 (SR 48968) or NK3 (SR 142801) receptors on inflammatory cell recruitment, tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 release and matrix metalloproteinase (MMP)‐9 activity in the bronchoalveolar lavage fluid (BALF) of mice exposed to lipopolysaccharide (LPS; 100 µg/mL aerosol for 30 min).2. Treatment of mice with a combination of SR 140333 and SR 48968 (10−6 mol/L, aerosol) significantly reduced the increase in the number of total cells and neutrophils and MMP‐9 activity in the BALF of mice 2.5 h after LPS exposure. Treatment with the NK3 antagonist SR 142801 (10−6 mol/L, aerosol) did not inhibit the influx of neutrophils, but markedly reduced the increase in TNF‐α and IL‐6 levels at 2.5 h and MMP‐9 activity at 20 h.3. These results show that the three tachykinin receptor antagonists may interfere with the development of airway inflammation, namely neutrophilia, TNF‐α release or MMP‐9 activity in the BALF of mice exposed to LPS and suggest that not only NK1 and NK2 receptors, but also NK3 receptors are involved in the modulation of the inflammatory response and airway remodelling.
Different roles of α1‐adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats
Authors: Zhang Yongzhen , Yan Jie , Chen Kai , Song Yao , Lu Zhizhen , Chen Mingzhe , Han Chide , Zhang Youyi 
Published: October 2004

Summary1. Three different α1‐adrenoceptor subtypes, designated α1A, α1B and α1D, have been cloned and identified pharmacologically in cardiomyocytes. In vitro studies have suggested that α1‐adrenoceptors play an important role in facilitating cardiac hypertrophy. However, it remains controversial as to which subtype of α1‐adrenoceptors is involved in this response. In the present study, we investigated the different role of each α1‐adrenoceptor subtype in mediating cardiomyocyte protein synthesis, which is a most important characteristic of cardiac hypertrophy in cultured neonatal rat cardiomyocytes.2. Cardiomyocyte hypertrophy was monitored by the following characteristic phenotypic changes: (i) an increase in protein synthesis; (ii) an increase in total protein content; and (iii) an increase in cardiomyocyte size.3. The role of each α1‐adrenoceptor subtype in mediating cardiomyocyte protein synthesis was investigated by the effect of specific α1‐adrenoceptor subtype‐selective antagonists on noradrenaline‐induced [3H]‐leucine incorporation. In addition, pKB values for α1‐adrenoceptor subtype‐selective antagonists were calculated and compared with the corresponding pKi values to further identify their effects.4. Activation of α1‐adrenoceptors by phenylephrine or noradrenaline in the presence of propranolol significantly increased [3H]‐leucine incorporation, protein content and cell size.5. Pre‐incubating cardiomyocytes with 5‐methyl‐urapidil, RS 17053 or WB 4101 significantly inhibited noradrenaline‐induced [3H]‐leucine incorporation. However, there was no effect when cardiomyocytes were pre‐incubated with BMY 7378. The correlation coefficients between pKB values for α1‐adrenoceptor subtype‐selective antagonists and pKi values obtained from cloned α1A‐, α1B‐ or α1D‐adrenoceptors were 0.92 (P < 0.01), 0.66 (P > 0.05) and 0.24 (P > 0.05), respectively.6. Our results suggest that the α1‐adrenoceptor is dominantly responsible for adrenergic hypertrophy of cultured cardiomyocytes in neonatal rats. The efficiency in mediating cardiomyocyte protein synthesis is α1A > α1B ≫ α1D.
Management of hepatitis C virus genotype 4
Authors: ABDO AYMAN A , LEE SAMUEL S 
Published: October 2004

AbstractHepatitis C virus (HCV) genotype 4 is predominantly found in the Middle East and North Africa. Because most of the large randomized controlled trials of antiviral therapy for chronic hepatitis C were conducted in North America and Europe, little is known about management of patients with this particular genotype. Based on the available data, sustained virological response rates to interferon‐based therapies appear to be intermediate between the relatively resistant HCV genotype 1 and the readily responsive genotypes 2 and 3. Several large prospective studies of pegylated interferon plus ribavirin combination therapy, the current gold‐standard treatment, have recently been completed and will be reviewed.© 2004 Blackwell Publishing Asia Pty Ltd
Molecular epidemiologic analysis of hepatitis C virus infection in injecting drug users with acute hepatitis C in Japan
Authors: SATOH YASUHIRO , HINO KEISUKE , KATO TAKANOBU , MIZOKAMI MASASHI , YAMASHITA SATOYOSHI , NAKAMURA HIROKI , OKITA KIWAMU 
Published: October 2004

AbstractBackground and Aim:  The aim of this study was to examine whether particular hepatitis C virus (HCV) subtypes are spreading among injecting drug users (IDUs) in Yamaguchi prefecture, on the south‐western tip of the island of Honshu in Japan, as found in European countries.Methods:  We prospectively enrolled acute hepatitis C patients from January 2001 to March 2003. E2 gene sequences of HCV isolates from IDUs with acute hepatitis C were phylogenetically compared to those from 30 chronic hepatitis C patients with the same HCV subtypes who had or did not have a history of intravenous drug use.Results:  Nine of 11 patients (82%) with acute hepatitis C were IDUs. The HCV subtypes were 2a in four and 2b in five, which contrasted with the high prevalence of subtype 1b in patients with chronic liver diseases in Japan. IDUs with acute hepatitis C (22.0 ± 2.4 years old) were significantly younger than those with chronic hepatitis C (49.5 ± 9.5 years old) for subtype 2a (P = 0.0005), but not for subtype 2b (25.6 ± 5.4 vs 28.1 ± 2.4 years old). Some HCV isolates of subtype 2b from IDUs with acute hepatitis C were phylogenetically related to those from IDUs with chronic hepatitis C. By contrast, there was no phylogenetic segregation of HCV in IDUs with subtype 2a. HCV isolates from non‐IDUs were genetically divergent from each other and those from IDUs, irrespective of the HCV subtype.Conclusion:  Hepatitis C virus of the non‐1b subtype, particularly subtype 2b, seemed to be transmitted between IDUs very recently in Yamaguchi prefecture, Japan.
Telomerase reverse transcriptase gene amplification in hepatocellular carcinoma
Authors: TAKUMA YOSHITAKA , NOUSO KAZUHIRO , KOBAYASHI YOSHIYUKI , NAKAMURA SHINICHIRO , TANAKA HIRONORI , MATSUMOTO EIJI , FUJIKAWA TATSUYA , SUZUKI MAYUMI , HANAFUSA TADASHI , SHIRATORI YASUSHI 
Published: October 2004

AbstractBackground and Aim:  Telomerase activation is essential for the immortality of cancer cells. The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, regulates telomerase activity in human cancers. Amplification of the hTERT gene, located at chromosome 5p, is thought to be a potential genetic event contributing to telomerase activation in sporadic tumors.Methods:  The amplification of the hTERT gene was examined in 46 surgically resected hepatocellular carcinomas (HCC) by real‐time polymerase chain reaction and the status was compared with the expression of hTERT mRNA and clinicopathological parameters.Results:  Amplified hTERT genes were found in 21.7% (10/46) of HCC. The incidence of amplified hTERT genes in poorly differentiated HCC (6/12, 50%) was significantly higher than that in highly to moderately differentiated HCC (4/34, 11.8%; P = 0.012). Tumor size in those cases with hTERT gene amplification was larger compared to those cases with no amplification (P = 0.047). Amplification of the hTERT gene was not observed in non‐cancerous tissues. The hTERT mRNA level did not correlate with the number of hTERT genes.Conclusions:  Based on these results, it is thought that hTERT gene amplification is a cancer‐specific event, and may furthermore contribute to the dedifferentiation and development of HCC. However, hTERT gene overexpression was rarely due to an increased hTERT gene copy number in HCC.© 2004 Blackwell Publishing Asia Pty Ltd
Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease
Authors: ALLEN KATRINA J , CHEAH DAPHNE MY , WRIGHT PAUL FA , GAZEAS SOPHIE , PETTIGREW‐BUCK NICOLE E , DEAL YOLANDA H , MERCER JULIAN FB , WILLIAMSON ROBERT 
Published: October 2004

AbstractBackground and Aim:  The toxic milk (tx) mouse is a non‐fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper‐transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.Methods:  Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4‐month‐old tx mice, which were then placed on various copper‐loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age‐matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.Results:  Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non‐repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.Conclusion:  Transplanted liver cells can proliferate and correct a non‐fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.