bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis of Ventricular Aneurysm and Other Severe Segmental Left Ventricular Dysfunction Consequent to a Myocardial Infarction in the Presence of Right Bundle Branch Block: ECG Correlates of a Positive Diagnosis Made via Echocardiography and/or Contrast Ventriculography
Authors: Madias John E. , Ashtiani Ramin , Agarwal Himanshu , Narayan Virenjan K. , Win Moethu , Sinha Anjan 
Published: January 2005

Background: A diagnostic ECG sign of a ventricular aneurysm (VA) consequent to a myocardial infarction (MI) in the presence of complete left bundle branch block was recently described, and consists of the presence of ST‐segment elevation (+ST), instead of the expected ST‐segment depression (−ST), in leads V4–6. Generally, complete right bundle branch block (RBBB) is associated with −ST in ECG leads V1–3. We hypothesized that stable +ST, instead of the expected −ST in leads V1–3 in patients with RBBB could be also diagnostic of a VA and other severe segmental left ventricular dysfunction (VA/SSD). Thus, this study was performed to explore the feasibility of using the ECG to diagnose a VA/SSD in the presence of RBBB, and to evaluate the determinants of such diagnosis. Methods: The frequency of +ST ≥1 mm in leads V1–3 was assessed in patients with RBBB, prior MI, and a VA/SSD diagnosed by echocardiography and/or contrast left cine‐ventriculography. The ECG correlates for a positive or negative diagnosis of a VA/SSD were explored. Results: Out of 4197 files of our cohort of the Cardiology Clinic, RBBB was detected in 175 patients. Of these, 28 had an old MI, and had a VA/SSD diagnosed by ≥1 of noninvasive and/or invasive non‐ECG tests. Twenty‐one of these 28 patients had stable +ST in ≥1 of leads V1–3 (Group 1), and 7 did not (Group 2). Thus, the sensitivity of this ECG criterion for the diagnosis of VA/SSD was 75%, and the specificity was 100% in this highly selective group. VA/SSD in the septal and anterior myocardial regions was more frequent in the patients of Group 1, than in the patients of Group 2 (P = 0.03 and 0.02, correspondingly). The number of myocardial territories involved with the VA/SSD, or the ejection fraction were not different in the two groups (P = 0.65 and 0.55, correspondingly). Conclusion: VA/SSD can be diagnosed in the presence of RBBB by the concordant to the QRS repolarization changes (+ST) in leads V1–3. Positivity of this ECG marker for VA/SSD correlates with involvement of the septal or anterior myocardial regions, and represents mechanistically a superimposition of primary repolarization alterations, overcoming the secondary such changes.
Assessment of the Stability of the Individual‐Based Correction of QT Interval for Heart Rate
Authors: Couderc Jean‐Philippe , Xiaojuan Xia , Zareba Wojciech , Moss Arthur J. 
Published: January 2005

Background: Modeling the relationship between QT intervals and previous R‐R values remains a challenge of modern quantitative electrocardiography. The technique based on an individual regression model computed from a set of QT–R‐R measurements is presented as a promising alternative. However, a large set of QT–R‐R measurements is not always available in clinical trials and there is no study that has investigated the minimum number of QT–R‐R measurements needed to obtain a reliable individual QT–R‐R model. In this study, we propose guidelines to ensure appropriate use of the regression technique for heart rate correction of QT intervals. Method: Holter recordings from 205 healthy subjects were included in the study. QT–R‐R relationships were modeled using both linear and parabolic regression techniques. Using a bootstrapping technique, we computed the stability of the individual correction models as a function of the number of measurements, the range of heart rate, and the variance of R‐R values. Results: The results show that the stability of QT–R‐R individual models was dependent on three factors: the number of measurements included in its design, the heart‐rate range used to design the model, and the T‐wave amplitude. Practically our results showed that a set of 400 QT–R‐R measurements with R‐R values ranging from 600 to 1000 ms ensure a stable and reliable individual correction model if the amplitude of the T wave is at least 0.3 mV. Reducing the range of heart rate or the number of measurements may significantly impact the correction model. Conclusion: We demonstrated that a large number of QT–R‐R measurements (∼400) is required to ensure reliable individual correction of QT intervals for heart rate.
Effect of Reperfusion on P‐Wave Duration and P‐Wave Dispersion in Acute Myocardial Infarction: Primary Angioplasty versus Thrombolytic Therapy
Authors: Akdemir Ramazan , Ozhan Hakan , Gunduz Huseyin , Tamer Ali , Yazici Mehmet , Erbilen Enver , Albayrak Sinan , Bulur Serkan , Uyan Cihangir 
Published: January 2005

Background: Atrial fibrillation (AF) is a common arrhythmia occurring in about 10–20% of patients with acute myocardial infarction (AMI). P‐wave dispersion (PWd) and P‐wave duration (PWD) have been used to evaluate the discontinuous propagation of sinus impulse and the prolongation of atrial conduction time, respectively. This study was conducted to compare the effects of reperfusion either by thrombolytic therapy or primary angioplasty on P‐wave duration and dispersion in patients with acute anterior wall myocardial infarction. Methods: We have evaluated 72 consecutive patients retrospectively (24 women, 48 men; aged 58 ± 12 years) experiencing acute anterior wall myocardial infarction (AMI) for the first time. Patients were grouped according to the reperfusion therapy received (primary angioplasty (PTCA) versus thrombolytic therapy). Left atrial diameter and left ventricular ejection fraction (LVEF) were determined by echocardiography in all patients. Electrocardiography was recorded from all patients on admission and every day during hospitalization. Maximum (P max) and minimum (P min) P‐wave durations and P‐wave dispersions were calculated before and after the treatment. Results: There were not any significant differences between the groups regarding age, gender, left ventricular ejection fraction, left atrial diameter and volume, cardiovascular risk factors, and duration from symptom onset to treatment. P‐wave dispersions and P‐wave durations were significantly decreased after PTCA [Mean P max was 113 ± 11 ms before and 95 ± 17 ms after the treatment (P = 0.007)]. Mean PWd was 46 ± 12 ms before and 29 ± 10 ms after the treatment (P = 0.001). Also, P max and PWd were significantly lower in PTCA group (for P max 97 ± 22 ms vs 114 ± 16 ms and for PWd 31 ± 13 ms vs 55 ± 5 ms, respectively). Conclusions: Primary angioplasty reduces the incidence of AF by decreasing P max and P‐wave dispersion.
Exercise‐Induced Ventricular Arrhythmias and Cardiovascular Death
Authors: Beckerman James , Mathur Anima , Stahr Stephen , Myers Jonathan , Chun Sung , Froelicher Victor 
Published: January 2005

Background: Exercise‐induced ventricular arrhythmias (EIVA) are frequently observed during exercise testing. However, the clinical guidelines do not specify their significance and so we examined this issue in our population. Methods: A retrospective analysis of prospectively collected data was performed on 5754 consecutive male veterans referred for exercise testing at two university‐affiliated Veterans Affairs Medical Centers. Exercise test responses were recorded and cardiovascular mortality was assessed after a mean follow‐up of 6 ± 4 years. EIVA were defined as frequent premature ventricular complexes (PVCs) constituting more than 10% of all ventricular depolarizations during any 30‐second ECG recording, or a run of three or more consecutive PVCs during the exercise test or recovery. Results: EIVA occurred in 426 patients (7.4%). There were 550 (10.6%) cardiovascular deaths during follow‐up. Seventy two (17%) patients with EIVA died of cardiovascular causes, whereas 478 (9.0%) of patients without EIVA died of cardiovascular causes (P < 0.001). Patients with EIVA had a higher prevalence of cardiovascular disease, resting PVCs, resting ST depression, and ischemia during exercise than patients without EIVA. In a Cox hazards model adjusted for age, cardiovascular disease, exercise‐induced ischemia, ECG abnormalities, exercise capacity and risk factors, EIVA was significantly associated with time to cardiovascular death. The combination of both resting PVCs and EIVA was associated with the highest hazard ratio. Conclusions: EIVA are independent predictors of cardiovascular mortality after adjusting for other clinical and exercise test variables; combination with resting PVCs carries the highest risk.
Prognostic Value of Head‐Up Tilt Test with Intravenous Beta‐Blocker Administration in Assessing the Efficacy of Therapy in Patients with Vasovagal Syncope
Authors: Gielerak Grzegorz , Makowski Karol , Cholewa Marian 
Published: January 2005

Background: Although beta‐blockers are frequently used in order to prevent the recurrence of vasovagal syncope, the efficacy of this treatment is difficult to determine. Objectives: To determine if the result of a tilt test with an intravenously administered beta‐blocker can predict the long‐term efficacy of beta‐blockade. Methods: The study group consisted of 62 patients (29 females, mean age 32.8 ± 12.3 years and 33 males, mean age 35.9 ± 18.2 years) with at least two syncopal episodes during 6 months preceding the positive tilt test. After the baseline tilt test, propranolol (0.1 mg/kg BW) was administered intravenously and the tilt test was repeated. Beta‐blockade was considered effective if the subsequent tilt test proved negative (complete efficacy) or if the time until the occurrence of syncope at the subsequent tilt test was longer compared to the baseline test (partial efficacy). All the patients were put on continuous propranolol treatment and were followed up for a period of 1 year or until the time when syncope recurred. Results: Intravenously administered propranolol prevented (n = 33) or delayed (n = 18) the occurrence of syncope at the tilt test in 51 patients (82%), while it was found ineffective in the remaining 11 patients (18%). During the 8.6 ± 6.7 months (range 1–14) of the follow‐up period, the syncope recurred in 20 patients (32%), with 13 patients (25%) in the group where intravenously administered propranolol proved effective versus 7 patients (64%) for whom intravenously administered propranolol did not prevent syncope during the tilt test (P < 0.015). The survival analysis with respect to the recurrence of syncope revealed a significant correlation between the results of the tilt test with intravenously administered propranolol and the efficacy of the long‐term beta‐blocker therapy (P < 0.003). There were no significant differences with respect to the predictive value of the tilt test with propranolol between the patients showing complete and partial propranolol efficacy (ns), while significant differences were observed between these two groups on one hand and the patients in whom intravenously administered propranolol was found ineffective on the other (P < 0.04 and P < 0.002, respectively). Conclusions: Intravenous propranolol prevents tilt‐induced syncope in a significant percentage of patients. The results of the tilt tests combined with the administration of propranolol predict the efficacy of a continuous propranolol treatment. Both complete and partial propranolol efficacy at tilt test can successfully identify those patients who will benefit from continuous beta blockade.
Herpes Simplex Virus 1 Infection Activates the Endoplasmic Reticulum Resident Kinase PERK and Mediates eIF-2α Dephosphorylation by the γ
1
34.5 Protein
Authors: Cheng Guofeng , Feng Zongdi , He Bin 
Published: January 2005

ABSTRACT

The γ
1
34.5 protein of herpes simplex virus (HSV) plays a crucial role in virus infection. Although the double-stranded RNA-dependent protein kinase (PKR) is activated during HSV infection, the γ
1
34.5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF-2α. Here we show that HSV infection also induces phosphorylation of an endoplasmic reticulum (ER) resident kinase PERK, a hallmark of ER stress response. The virus-induced phosphorylation of PERK is blocked by cycloheximide but not by phosphonoacetic acid, suggesting that the accumulation of viral proteins in the ER is essential. Notably, the maximal phosphorylation of PERK is delayed in PKR
+/+
cells compared to that seen in PKR
−/−
cells. Further analysis indicates that hyperphosphorylation of eIF-2α caused by HSV is greater in PKR
+/+
cells than in PKR
−/−
cells. However, expression of the γ
1
34.5 protein suppresses the ER stress response caused by virus, dithiothreitol, and thapsigargin as measured by global protein synthesis. Interestingly, the expression of GADD34 stimulated by HSV infection parallels the status of eIF-2α phosphorylation. Together, these observations suggest that regulation of eIF-2α phosphorylation by the γ
1
34.5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection.
An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate
Authors: Ye Jianjiang , Shedd Duane , Miller George 
Published: January 2005

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV) can be driven into the lytic cycle in vitro by phorbol esters and sodium butyrate. This report begins to analyze the process by which butyrate activates the promoter of KSHV open reading frame 50 (ORF50), the key viral regulator of the KSHV latency to lytic cycle switch. A short fragment of the promoter, 134 nucleotides upstream of the translational start of ORF50, retained basal uninduced activity and conferred maximal responsiveness to sodium butyrate. The butyrate response element was mapped to a consensus Sp1-binding site. By means of electrophoretic mobility shift assays, both Sp1 and Sp3 were shown to form complexes in vitro with the ORF50 promoter at the Sp1 site. Butyrate induced the formation of a group of novel complexes, including several Sp3-containing complexes, one Sp1-containing complex, and several other complexes that were not identified with antibodies to Sp1 or Sp3. Formation of all butyrate-induced DNA-protein complexes was mediated by the consensus Sp1 site. In insect and mammalian cell lines, Sp1 significantly activated the ORF50 promoter linked to luciferase. Chromatin immunoprecipitation experiments in a PEL cell line showed that butyrate induced Sp1, CBP, and p300 binding to the ORF50 promoter in vivo in an on-off manner. The results suggest that induction of the KSHV lytic cycle by butyrate is mediated through interactions at the Sp1/Sp3 site located 103 to 112 nucleotides upstream of the translational initiation of ORF50 presumably by enhancing the binding of Sp1 to this site.
Reverse Genetics System for Porcine Enteric Calicivirus, a Prototype Sapovirus in the
Caliciviridae
Authors: Chang Kyeong-Ok , Sosnovtsev Stanislav S. , Belliot Gaël , Wang Qiuhong , Saif Linda J. , Green Kim Y. 
Published: January 2005

ABSTRACT

A porcine enteric calicivirus (PEC), strain Cowden in the genus
Sapovirus
of the
Caliciviridae
family, can be propagated in a porcine kidney continuous cell line (LLC-PK) in the presence of bile acids in the cell culture medium. A full-length cDNA copy of the Cowden PEC genome was cloned into a plasmid vector directly downstream from the T7 RNA polymerase promoter, and capped RNA transcripts derived from this clone were infectious when transfected into LLC-PK cells. The recovery of PEC after transfection of RNA transcripts was dependent on the presence of bile acids, consistent with our recent identification of a bile acid-mediated signaling pathway required for PEC replication (Chang et al., Proc. Natl. Acad. Sci. USA
101:
8733-8788, 2004). Recovery of virus was verified by detection of PEC antigen in transfected cells by immunofluorescence and enzyme-linked immunosorbent assays, direct observation of recovered viral particles by electron microscopy, and partial sequence analysis of their genomes (first 1,070 nucleotides) to differentiate them from tissue culture-adapted parental virus. The recovered virus retained its ability to infect piglets when administered by the oral route and showed an attenuated phenotype similar to that of the tissue culture-adapted parental virus. This reverse genetics system for PEC provides a new tool to study the molecular basis of replication and pathogenesis for caliciviruses associated with diarrheal disease.
The Phosphorylation Status of the Serine-Rich Region of the Human Cytomegalovirus 86-Kilodalton Major Immediate-Early Protein IE2/IEP86 Affects Temporal Viral Gene Expression
Authors: Barrasa M. Inmaculada , Harel Noam Y. , Alwine James C. 
Published: January 2005

ABSTRACT
The 86-kDa major immediate-early protein (IE2/IEP86) of human cytomegalovirus (HCMV) contains a serine-rich region (amino acids 258 to 275) with several consensus casein kinase II (CKII) sites. We performed extensive mutational analysis of this region, changing serines to alternating alanines and glycines. Mutation of the serines between amino acids 266 and 275 eliminated in vitro phosphorylation by CKII. In vitro CKII phosphorylation of the serines between amino acids 266 and 269 or between amino acids 271 and 275 inhibited the ability of IE2/IEP86 to bind to TATA-binding protein. Correspondingly, nonphosphorylatable mutants in these regions showed increased activation of specific HCMV gene promoters in transfection studies. Viruses containing mutations of the serines throughout the entire region (amino acids 258 to 275) or the second half (amino acids 266 to 275) of the region showed delayed expression of all viral proteins tested and, correspondingly, delayed growth compared to wild-type HCMV. Mutation of the serines in the first half of the serine-rich region (amino acids 258 to 264) or between amino acids 266 and 269 propagated very slowly and has not been further studied. In contrast, mutation of the serines between amino acids 271 and 275 resulted in accelerated virus growth and accelerated temporal expression of viral proteins. These results suggest that the serine-rich region is structurally complex, possibly affecting multiple functions of IE2/IEP86. The data show that the phosphorylation state of the serine-rich region, particularly between amino acids 271 and 275, modulates the temporal expression of viral genes.
Mutual Interference between Genomic RNA Replication and Subgenomic mRNA Transcription in Brome Mosaic Virus
Authors: Grdzelishvili Valery Z. , Garcia-Ruiz Hernan , Watanabe Tokiko , Ahlquist Paul 
Published: January 2005

ABSTRACT

Replication by many positive-strand RNA viruses includes genomic RNA amplification and subgenomic mRNA (sgRNA) transcription. For brome mosaic virus (BMV), both processes occur in virus-induced, membrane-associated compartments, require BMV replication factors 1a and 2a, and use negative-strand RNA3 as a template for genomic RNA3 and sgRNA syntheses. To begin elucidating their relations, we examined the interaction of RNA3 replication and sgRNA transcription in
Saccharomyces cerevisiae
expressing 1a and 2a, which support the full RNA3 replication cycle. Blocking sgRNA transcription stimulated RNA3 replication by up to 350%, implying that sgRNA transcription inhibits RNA3 replication. Such inhibition was independent of the sgRNA-encoded coat protein and operated in
cis
. We further found that sgRNA transcription inhibited RNA3 replication at a step or steps after negative-strand RNA3 synthesis, implying competition with positive-strand RNA3 synthesis for negative-strand RNA3 templates, viral replication factors, or common host components. Consistent with this, sgRNA transcription was stimulated by up to 400% when mutations inhibiting positive-strand RNA3 synthesis were introduced into the RNA3 5′-untranslated region. Thus, BMV subgenomic and genomic RNA syntheses mutually interfered with each other, apparently by competition for one or more common factors. In plant protoplasts replicating all three BMV genomic RNAs, mutations blocking sgRNA transcription often had lesser effects on RNA3 accumulation, possibly because RNA3 also competed with RNA1 and RNA2 replication templates and because any increase in RNA3 replication at the expense of RNA1 and RNA2 would be self-limited by decreased 1a and 2a expression from RNA1 and RNA2.
Probing Sequence Variation in the Receptor-Targeting Domain of Feline Leukemia Virus Envelope Proteins with Peptide Display Libraries
Authors: Bupp Keith , Sarangi Anindita , Roth Monica J. 
Published: January 2005

ABSTRACT

Determinants of cellular tropism and receptor targeting lie within a short peptide in the Vr1 region of the envelope (Env) proteins of feline leukemia virus (FeLV) subgroups A and C. Libraries of FeLV Env proteins with random amino acid substitutions in the peptide were screened for their ability to deliver a marker gene to D17 and AH927 cells. Screening on D17 canine cells yielded D17-specific Env proteins that used the FeLV-C receptor. Screening on AH927 cells yielded Env proteins with a broader host range, with maximal titers on AH927 cells and similar or lower titers on other cells. These Env proteins used an unidentified non-FeLV receptor for entry. The A5 isolate obtained from the AH927 screen was readily concentrated to yield titers of 10
5
on human PC-3 prostate tumor cells. The sequence divergence observed among targeting peptides of library-selected Env proteins was greater than that found in parental FeLV isolates. Substitution analyses of a conserved R in the middle of the targeting peptide held constant during screening indicated that maximal titers were obtained only when R was present in both a D17 selected isolate and an AH927 selected isolate. The ability to isolate Env proteins with unique tropisms dependent on the cells on which the library is screened has direct implications for targeting gene delivery vectors.
Hepatitis C Virus (HCV) Constitutively Activates STAT-3 via Oxidative Stress: Role of STAT-3 in HCV Replication
Authors: Waris Gulam , Turkson James , Hassanein Tarek , Siddiqui Aleem 
Published: January 2005

ABSTRACT

The hepatitis C virus (HCV) causes chronic hepatitis, which often results in liver cirrhosis and hepatocellular carcinoma. We have previously shown that HCV nonstructural proteins induce activation of STAT-3 via oxidative stress and Ca
2+
signaling (G. Gong, G. Waris, R. Tanveer, and A. Siddiqui, Proc. Natl. Acad. Sci. USA
98:
9599-9604, 2001). In this study, we focus on the signaling pathway leading to STAT-3 activation in response to oxidative stress induced by HCV translation and replication activities. Here, we demonstrate the constitutive activation of STAT-3 in HCV replicon-expressing cells. The HCV-induced STAT-3 activation was inhibited in the presence of antioxidant (pyrrolidine dithiocarbamate) and Ca
2+
chelators (BAPTA-AM and TMB-8). Previous studies have shown that maximum STAT-3 transactivation requires Ser727 phosphorylation in addition to tyrosine phosphorylation. Using a series of inhibitors and dominant negative mutants, we show that HCV-induced activation of STAT-3 is mediated by oxidative stress and influenced by the activation of cellular kinases, including p38 mitogen-activated protein kinase, JNK, JAK-2, and Src. Our results also suggest a potential role of STAT-3 in HCV RNA replication. We also observed the constitutive activation of STAT-3 in the liver biopsy of an HCV-infected patient. These studies provide an insight into the mechanisms by which HCV induces intracellular events relevant to liver pathogenesis associated with the viral infection.