bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Mapping of the Nucleoprotein of Ebola Virus
Authors: Watanabe Shinji , Noda Takeshi , Kawaoka Yoshihiro 
Published: March 2006

ABSTRACT

At 739 amino acids, the nucleoprotein (NP) of Ebola virus is the largest nucleoprotein of the nonsegmented negative-stranded RNA viruses, and like the NPs of other viruses, it plays a central role in virus replication. Huang et al. (Y. Huang, L. Xu, Y. Sun, and G. J. Nabel, Mol. Cell
10:
307-316, 2002) previously demonstrated that NP, together with the minor matrix protein VP24 and polymerase cofactor VP35, is necessary and sufficient for the formation of nucleocapsid-like structures that are morphologically indistinguishable from those seen in Ebola virus-infected cells. They further showed that NP is O glycosylated and sialylated and that these modifications are important for interaction between NP and VP35. However, little is known about the structure-function relationship of Ebola virus NP. Here, we examined the glycosylation of Ebola virus NP and further investigated its properties by generating deletion mutants to define the region(s) involved in NP-NP interaction (self-assembly), in the formation of nucleocapsid-like structures, and in the replication of the viral genome. We were unable to identify the types of glycosylation and sialylation, although we did confirm that Ebola virus NP was glycosylated. We also determined that the region from amino acids 1 to 450 is important for NP-NP interaction (self-assembly). We further demonstrated that these amino-terminal 450 residues and the following 150 residues are required for the formation of nucleocapsid-like structures and for viral genome replication. These data advance our understanding of the functional region(s) of Ebola virus NP, which in turn should improve our knowledge of the Ebola virus life cycle and its extreme pathogenicity.
Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus
Authors: Voisin Véronique , Barat Corinne , Hoang Trang , Rassart Eric 
Published: March 2006

ABSTRACTThe Graffi murine leukemia virus (MuLV) was isolated in 1954 by Arnold Graffi, who characterized it as a myeloid leukemia-inducing retrovirus. He and his team, however, soon observed the intriguing phenomenon of hematological diversification, which corresponded to a decrease of myeloid leukemias and an increase of other types of leukemias. Recently, we derived two different molecular clones corresponding to ecotropic nondefective genomes that were named GV-1.2 and GV-1.4. The induced leukemias were classified as myeloid based on morphological analysis of blood smears. In this study, we further characterized the two variants of the Graffi murine retrovirus, GV-1.2 and GV-1.4, in three different strains of mice. We show that the Graffi MuLV is a multipotent retrovirus capable of inducing both lymphoid (T- and B-cell) and nonlymphoid (myeloid, erythroid, megakaryocytic) leukemia. Many of these are very complex with concomitant expression of different hematopoietic lineages. Interestingly, a high percentage of megakaryocytic leukemias, a type of leukemia rarely observed with MuLVs, arise in the FVB/n strain of mice. The genetic backgrounds of the different strains of mice influence greatly the results. Furthermore, the enhancer region, different for GV-1.2 and GV-1.4, plays a pivotal role in the disease specificity: GV-1.2 induces more lymphoid leukemias, and GV-1.4 induces more nonlymphoid ones.
Alternative splicing factor ASF/SF2 is down regulated in inflamed muscle
Authors: Xiong Z , Shaibani A , Li Y-P , Yan Y , Zhang S , Yang Y , Yang F , Wang H , Yang X-F 
Published: March 2006

Background:In our recent studies, alternative splicing has been shown to have a major role in inflammation and autoimmune muscle diseases.Aim:To examine the novel hypothesis that the expression of an essential alternative splicing factor, alternative splicing factor 2 (ASF/SF2), is modulated in muscle inflammation.Methods:ASF/SF2 expression in muscle biopsy samples from eight patients with inflammatory myopathy and six non-myositic controls was determined by using western blot with anti-ASF/SF2 antibodies. To further elucidate the mechanism of reduced ASF/SF2 expression in inflamed muscle, differentiated C2C12 myotubes were stimulated with proinflammatory cytokine tumour necrosis factor α (TNFα), followed by western blot analysis of ASF/SF2 expression.Results:ASF/SF2 expression in the muscle biopsy samples from patients with inflammatory myopathy was found to be lower (mean of relative densitometric units 41.1 (2SD 20.7)) than that of the non-myositic controls (mean of relative densitometric units 76.7 (39.6); p<0.05). In addition to this, ASF/SF2 expression was seen to be significantly down regulated (sevenfold) in C2C12 myotubes compared with expression variations in the β-actin control (0.62-fold; mean 1.22 (0.40); p<0.05).Conclusion:Collectively, it is shown, for the first time, that alternative splicing factor ASF/SF2 is down regulated in autoimmune inflammatory myositis—potentially via a TNFα-mediated pathway. The development of (1) novel autoantigen isoform microarrays for disease diagnosis and prognosis; (2) novel autoantigen-tolerising treatments for autoimmune diseases; and (3) novel splicing-redirection treatments can be facilitated by the ongoing study of alternative splicing of autoantigen transcripts.
Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects
Authors: Undas Anetta , Brożek Jan , Jankowski Miłosz , Siudak Zbigniew , Szczeklik Andrew , Jakubowski Hieronim 
Published: March 2006

Objective—Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a hypothesis that the clot permeability and its resistance to fibrinolysis is associated with plasma total Hcy (tHcy) in human subjects.Methods and Results—We studied healthy men not taking any medication (n=76), male patients with advanced coronary artery disease (CAD) taking low-dose aspirin (n=33), men with diabetes mellitus diagnosed recently (median hemoglobin A1c7.65%; n=16), and patients with isolated hypercholesterolemia (>7.0 mmol/L; n=15). We assessed clot permeability and turbidimetric lysis time as the determinants of fibrin clot structure. In a regression model, including age and fibrinogen, plasma tHcy was an independent predictor of clot permeation and fibrinolysis time in healthy subjects (R2=0.88,P<0.0001 andR2=0.54,P<0.0001, respectively). In CAD patients, tHcy and fibrinogen were stronger predictors of the permeation coefficient (R2=0.84;P<0.0001) than was fibrinogen alone (R2=0.66;P<0.0001), whereas tHcy was the only predictor of lysis time (R2=0.69;P<0.0001). Elevated tHcy levels observed after methionine load were not associated with any of the fibrin clot properties. In patients with diabetes or hypercholesterolemia, the influence of Hcy on permeation and, to a lesser extent, on the lysis time was obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels resulted in increased clot permeability (P=0.0002) and shorter lysis time (P<0.0001).Conclusions—Our results indicate that plasma tHcy predicts clot permeation and susceptibility to fibrinolysis in healthy men and CAD patients. Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy–thiolactone.
Control of Heart Rate Versus Rhythm in Rheumatic Atrial Fibrillation: A Randomized Study
Authors: Vora Amit , Karnad Dilip , Goyal Venkat , Naik Ajay , Gupta Anup , Lokhandwala Yas , Kulkarni Hema , Singh Bramah N. 
Published: March 2006

Background: Patients with rheumatic heart disease with atrial fibrillation incur significant morbidity and mortality. Which approach, ventricular rate control or maintenance of sinus rhythm, in this setting might be superior is not known. The role of amiodarone in this patient population for maintaining sinus rhythm has not been evaluated. Methods and Results: We prospectively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol in which rhythm control (group I), comprising 48 patients each with amiodarone (group Ia) and placebo (group Ib), were compared with each other and with patients in a ventricular rate control group (group II) in which the effects by diltiazem were determined (n = 48, open-label). Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6 ± 10.3 years, left atrial size, 4.7 ±0.6 cm; atrial fibrillation duration, 6.1 ± 5.4 years; and 72.9% had valvular interventions performed. At 1 year, 45 patients with sinus rhythm in group I compared with 48 in group II demonstrated an increase in exercise time (2.6 ± 1.9 vs. 0.6 ± 2.5 min, P = .001), improvement in New York Heart Association class of 1 or more ( P = .002), and improvement in the quality-of-life score of one or greater ( P = 0.01) with no difference in hospitalizations, systemic bleeds, or thromboembolism. Five patients died in group II; none died in group I ( P =.02). In group I, 73 of 87 (83.9%) patients converted to sinus rhythm and 45 of 86 (52.3%) patients maintained the rhythm at 1 year. Conversion rates were 38 of 43 (88.4%) with amiodarone versus 34 of 44 (77.3%) with placebo ( P = .49); the corresponding rate for maintaining sinus rhythm was 29 of 42 (69.1%) versus 16 of 44 (36.4%) ( P = .008). A larger number of electrical cardioversions were required in the placebo group (2.1 vs. 1.4, P = .011). Conclusions: Maintenance of sinus rhythm is superior to ventricular rate control in patients with rheumatic atrial fibrillation with respect to effects on exercise capacity, quality of life, morbidity, and possibly mortality. Sinus rhythm could be restored in most patients, and amiodarone was superior to placebo in the restoration and maintenance of sinus rhythm.
Continuous Light Exposure and Sympathectomy Suppress Circadian Rhythm of Blood Pressure in Rats
Authors: Briaud S. A. , Zhang B. L. , Sannajust F. 
Published: March 2006

Background: Although the 24-hour rhythm in blood pressure is well known, it is not clear how environmental light controls circadian cardiovascular and behavioral rhythms. Methods and Results: The prolonged exposure of Wistar rats to continuous light for 17 weeks, beginning at 5 weeks old, induced a complete suppression of their blood pressure, heart rate, spontaneous locomotor activity, and body temperature circadian rhythms. Daily subcutaneous melatonin injections at the theoretical onset of darkness for 21 days could not restore light-suppressed blood pressure circadian rhythm, whereas it partially synchronized heart rate and body temperature rhythms and it fully restored spontaneous locomotor activity rhythms, as measured by radiotelemetry. The transfer of these rats from constant light to a standard 12:12-hour light/dark photoperiod fully restored circadian rhythmicity within 2 to 5 days, although their 24-hour diastolic blood pressure remained elevated. Synchronized rats were then subjected to superior cervical ganglionectomy (SCGx) and 6-hydroxydopamine sympathectomy (SYMPx). SCGx plus SYMPx completely abolished the circadian rhythm in blood pressure and significantly reduced those in heart rate, spontaneous locomotor activity, and body temperature. Conclusions: We conclude that in Wistar rats exposed to continuous light, the light-induced increase in sympathetic outflow can suppress blood pressure circadian rhythm, and sustained cardiac wall stress can alter diastolic function at rest. Preserved inotropy in these conditions must result from an adaptative hypertrophic response of myocytes.
Intravenous Nicorandil Can Reduce QT Dispersion and Prevent Bradyarrhythmia During Percutaneous Transluminal Coronary Angioplasty of the Right Coronary Artery
Authors: Ueda Hiroyasu , Hayashi Tomoshige , Tsumura Kei , Yoshimaru Kiyomichi , Nakayama Yasunori , Yoshikawa Junichi 
Published: March 2006

Background: Nicorandil, a potassium channel opener, is used for the treatment of angina pectoris and has a pharmacologic preconditioning effect. This study evaluated whether intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery. Methods: A historical cohort study on the effect of nicorandil on QT dispersion and bradyarrhythmia was conducted. Fifty patients who underwent PTCA of the right coronary artery were enrolled. The patients were divided into a nicorandil (n = 25) group and control group (n = 25). Nicorandil was injected at 4 mg/h continuously 1 hour before PTCA in the nicorandil group. QT dispersion was measured at 1 hour before PTCA (baseline), immediately before PTCA, and 1 minute after the initiation of the first balloon inflation. Results: QT dispersion at 1 minute after the initiation of the first balloon inflation in the control group increased significantly (QT dispersion: 37.1 ± 17.8 msec and 21.7 ± 12.2 msec, respectively, P < .001 vs baseline in the control group), and this was larger than at 1 minute after the initiation of the first balloon inflation in the nicorandil group (QT dispersion: 37.1 ± 17.8 msec and 20.8 ± 9.4 msec, respectively, P < .001). By two-way repeated measures analysis of variance, there were significant interactions between the time factor and the grouping factor in QT dispersion ( P < .001). Bradyarrhythmia was observed in 6 patients in the control group, but none was observed in the nicorandil group. Conclusions: Intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during PTCA of the right coronary artery.
Effects of Low-Dose Atorvastatin on Vascular Responses in Patients Undergoing Percutaneous Coronary Intervention With Stenting
Authors: Bae Jang-Ho , Bassenge Eberhard , Kim Ki-Young , Synn Yi-Chul , Park ki-Rack , Schwemmer Michael 
Published: March 2006

Background: The primary endpoint of this study was to evaluate the effects of low-dose atorvastatin on carotid intima-media thickness (IMT) and endothelial function, and the secondary endpoint comprised restenosis and target lesion revascularization (TLR) in patients undergoing percutaneous coronary intervention (PCI) with stenting for the treatment of coronary artery disease. Methods: Two hundred five consecutive patients (mean age, 60 years) undergoing PCI were prospectively randomized to usual therapy (control group, n = 100) or to 10 mg of atorvastatin daily plus usual therapy (statin group, n = 105). Carotid IMT, endothelial function (flow-mediated dilatation [FMD] of the brachial artery), and coronary angiograms were taken before the study and 6 months after randomization. The 6-month follow-up measurements of the above factors were obtained in 83 patients (83%) of the control group and in 97 patients (92%) of the statin group. Results: No significant differences were noted in the baseline clinical and angiographic findings in either group. FMD was significantly improved during the 6 months in the statin group (4.38% ± 1.7% vs 4.85% ± 1.6%, P = .003), but did not change in the control group. Carotid IMT did not show any significant changes at 6 months in either group. There was a trend in favor of statin in terms of restenosis rate (26.8% vs 36.1%, P = .177) and TLR rate (18.6% vs 25.3%, P = .274). The changes of FMD were significantly correlated with the changes of total cholesterol and the changes of low-density lipoprotein, respectively ( r= -0.336, P = .009, and r = -0.310, P = .046). Conclusion: Low-dose atorvastatin reduces endothelial dysfunction as measured by FMD, which coincides with the beneficial effects on lipid profiles, and can decrease restenosis and TLR rate in patients undergoing PCI with stenting.
Vascular Effects of Natriuretic Peptides in Healthy Men
Authors: Komarek Marius , Bernheim Alain , Schindler Ruth , Steden Renate , Kiowski Wolfgang , Rocca Hans Peter Brunner-La 
Published: March 2006

Background: Most effects of atrial (ANP) and B-type natriuretic peptide (BNP) result from stimulation of the guanylyl-cyclase type A receptor. Chronic elevation causes hyporesponsiveness to ANP, whereas BNP effects tend to be preserved, implying an additional pathway of action. We, therefore, investigated the hemodynamic effects of co-infusion of ANP, BNP, and, as a positive control acting on type B receptor, C-type natriuretic peptide (CNP). Furthermore, vascular responses to short and prolonged infusions were compared to investigate rapid hyporesponsiveness of guanylyl-cyclase type A receptor. Methods: In 11 healthy volunteers, arterial response to continuous intra-arterial infusion of ANP (60 pmol/100 mL forearm tissue volume [FAV]/min) was assessed by venous occlusion plethysmography. Then, co-infusion of a similar dose of ANP, BNP, or CNP was administered in randomized order. Each infusion phase was followed by a washout period. Then, ANP was restarted, followed by co-infusion of one of the natriuretic peptides not yet infused. After a further washout period, ANP was restarted, followed by co-infusion of the natriuretic peptide not yet co-infused. In 6 subjects, infusion time was adjusted to plasma half-lives (5 times), and in the other 5 subjects, infusion time was 5 minutes. Results: ANP alone caused the expected vasodilation from 2.7 ± 0.3 mL/min/100 mL FAV to 6.0 ± 0.9 mL/min/100 mL FAV ( P < .004). This response remained unchanged in the group that received short-term infusions (6.2 ± 0.8 mL/min/100 mL FAV to 6.6 ± 1.1 mL/min/100mL FAV) but was reduced over time in the group receiving longer-term infusions (6.5 ± 1.2 mL/min/100 mL FAV to 4.5 ± 0.7 mL/min/100mL FAV, P < .05; difference between groups P < .05). Co-infusions of ANP, BNP, and CNP caused minor additional vasodilation (mean 0.8 ± 0.2 mL/min/100ml FAV, P < .01), which did not differ between the different co-infused natriuretic peptides. Conclusion: Our data provide evidence for rapid desensitization of the guanylyl-cyclase type A receptor in humans, but do not support the presence of a BNP-specific receptor.
Monocyte Chemoattractant Protein 1-Induced Monocyte Infiltration Produces Angiogenesis but Not Arteriogenesis in Chronically Infarcted Myocardium
Authors: Schwarz Ernst R. , Meven Dennis A. , Sulemanjee Nasir Z. , Kersting Philipp H. , Tussing Tanja , Skobel Erik C. , Hanrath Peter , Uretsky Barry F. 
Published: March 2006

Background: Monocyte chemoattractant protein 1 (MCP-1) stimulates the invasion of monocytes into ischemic tissue with concomitant adhesion to endothelial cells. Monocyte stimulation has been shown to be involved in the induction of arteriogenesis, which is the development of functional arterioles resulting in improvement of perfusion. However, angiogenesis (newly developed capillaries contribute to improved tissue perfusion) in several models has not resulted in any improvement in blood flow.Objective: The effects of MCP-1 on potential angiogenesis and arteriogenesis as well as changes in left ventricular function were tested in a chronic infarct model in rat hearts.Methods: Anesthetized rats were subjected to open-chest ligation of the left coronary artery with subsequent myocardial infarction. After 6 weeks, animals were randomized to receive either MCP-1 (3 µL in 0.15 mL NaCl, group 1, n = 9) or saline (0.15 mL, group 2, n = 9), which was injected into the myocardium at the border zones of the infarcts. For assessment of left ventricular dimensions and global cardiac function, transthoracic two-dimensional echocardiography was performed at baseline, 6 weeks after myocardial infarction, and 4 weeks after MCP-1 or saline injection, by use of a 12-MHz pediatric transducer. For light microscopic analysis, myocardial tissue was stained with Elastica-van-Giesson and von Willebrand factor for blood vessels and endothelial cells, respectively. In a subset of animals, hearts were excised 24 hours after MCP-1 administration (n = 4) or saline administration (n = 4) for assessment of monocyte infiltration by immunohistologic staining of the CD31 antigen.Results: Left ventricular dimensions and ejection fraction changed after coronary occlusion (from 60.4% ± 2.85% to 24.8% ± 5.01% ejection fraction in group 1, and from 58.4% ±2.06% to 26.3% ± 4.3% ejection fraction in group 2 at 6 weeks, P < .005) without any further change 4 weeks after treatment (ejection fraction in group 1, 26.3% ± 2.7%, ejection fraction in group 2, 25.0% ± 5.18%). The MCP-1 group resulted in 390.6 ± 10.36 endothelial cells compared with 285.2 ± 13.56 in group 2 ( P < .005) at the injection site. Monocyte infiltration was observed at the MCP-1 injection site with an increase in capillary growth (angiogenesis). However, there was no difference in the number of arteriolar structures between animals treated with MCP-1 and saline animals (group 1, 19.0 ± 1.52 vs group 2,16.4 ± 0.68, P > .05).Conclusion: A single intramyocardial injection of MCP-1 into the infarct border zone resulted in neo-angiogenesis and monocyte infiltration but not arteriogenesis in the rat heart. There was no functional change of chronically infarcted myocardium in the present model.
Effect of Flaxseed Consumption on Blood Pressure, Serum Lipids, Hemopoietic System and Liver and Kidney Enzymes in Healthy Humans
Authors: Stuglin Carlo , Prasad Kailash 
Published: March 2006

Background: Effects of flaxseed on serum lipids have been studied in humans, but the results are variable. Flaxseed is ineffective in lowering blood pressure in rats. Its effect on blood pressure in humans is not known. It is also not known if long-term use of flaxseed in humans has deleterious effects on the hemopoietic system, serum glucose, and renal and kidney function. We investigated the effect of short-term use of flaxseed in humans on arterial pressure and serum lipids (triglycerides, total cholesterol; high-, low-, and very-low-densitylipoprotein cholesterol [HDL-C, LDL-C, VLDL-C], hemopoietic system (red blood cells, neutrophils, hemoglobin) and the various biochemical parameters, such as serum protein, albumin, total bilirubin, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, related to hepatic and renal function, and serum glucose. Methods: Fifteen healthy men, aged 22 to 47 years, consumed three muffins daily containing 32.7 g of total flaxseed for 4 weeks, in addition to their normal daily diet. Blood pressure and blood samples for various biochemical measurements were collected before and after 4 weeks of flaxseed diet. Results: Blood pressures, heart rate, hemoglobin, and counts of red blood cells, white blood cells, and neutrophils remained unaltered after flaxseed diet. Serum total cholesterol, HDLC, LDL-C, and VLDL-C remained unchanged, but serum triglycerides levels were elevated. Serum total bilirubin, aspartate aminotransferase, alkaline phosphatase, protein, albumin, glucose, and urea remained unaltered, but serum levels of creatinine decreased. Conclusion: These results suggest that 4 weeks use of flaxseed does not have deleterious effects on the hemopoietic system or renal and hepatic function and does not lower blood pressure and serum lipids. However, the level of serum triglyceride level was elevated.