bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of PKR and RNase L in translational control and induction of apoptosis after Hepatitis C polyprotein expression from a Vaccinia virus recombinant
Authors: Gómez Carmen E , Vandermeeren Andrée Marie , García María Angel , Domingo-Gil Elena , Esteban Mariano 
Published: September 2005

Abstract

Background
Hepatitis C virus (HCV) infection is of growing concern in public health with around 350 million chronically infected individuals worldwide. Although the IFN-α/rivabirin is the only approved therapy with 10–30% clinical efficacy, the protective molecular mechanism involved during the treatment is still unknown. To analyze the effect of HCV polyprotein expression on the antiviral response of the host, we developed a novel vaccinia virus (VV)-based delivery system (VT7-HCV7.9) where structural and nonstructural (except part of NS5B) proteins of HCV ORF from genotype 1b are efficiently expressed and produced, and timely regulated in mammalian cell lines.

Results
Regulated transcript production and viral polypeptide processing was demonstrated in various cell lines infected with the recombinant VT7-HCV7.9, indicating that the cellular and viral proteolytic machineries are functional within these cells. The inducible expression of the HCV polyprotein by VV inhibits the synthesis of both host and viral proteins over the time and also induces apoptosis in HeLa and HepG2-infected cells. These effects occur accompanying with the phosphorylation of the translation initiation factor eIF-2α. In cells co-infected with VT7-HCV7.9 and a recombinant VV expressing the dominant negative eIF-2α-S51A mutant in the presence of the inductor isopropyl-thiogalactoside (IPTG), protein synthesis is rescued. The IFN-inducible protein kinase PKR is responsible for the translational block, as demonstrated with PKR-/- and PKR+/+ cell lines. However, apoptosis induced by VT7-HCV7.9 is mediated by the RNase L pathway, in a PKR-independent manner.

Conclusion
These findings demonstrate the antiviral relevance of the proteins induced by interferon, PKR and RNase L during expression from a VV recombinant of the HCV polyprotein in human cell lines. HCV polyprotein expression caused a severe cytopathological effect in human cells as a result of inhibition of protein synthesis and apoptosis induction, triggered by the activation of the IFN-induced enzymes PKR and RNase L systems. Thus, the virus-cell system described here highlights the relevance of the IFN system as a protective mechanism against HCV infection.
Protein Kinases Mediate Increment of the Phosphorylation of Cyclic AMP -Responsive Element Binding Protein in Spinal Cord of Rats following Capsaicin Injection
Authors: Wu Jing , Su Guangxiao , Ma Long , Zhang Xuan , Lei Yongzhong , Li Junfa , Lin Qing , Fang Li 
Published: September 2005

Background: Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. Results: We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. Conclusion: These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.
Circulating anions usually associated with the Krebs cycle in patients with metabolic acidosis
Authors: Forni Lui G , McKinnon William , Lord Gwyn A , Treacher David F , Peron Jean-Marie R , Hilton Philip J 
Published: September 2005

Abstract
Introduction
Acute metabolic acidosis of non-renal origin is usually a result of either lactic or ketoacidosis, both of which are associated with a high anion gap. There is increasing recognition, however, of a group of acidotic patients who have a large anion gap that is not explained by either keto- or lactic acidosis nor, in most cases, is inappropriate fluid resuscitation or ingestion of exogenous agents the cause.

Methods
Plasma ultrafiltrate from patients with diabetic ketoacidosis, lactic acidosis, acidosis of unknown cause, normal anion gap metabolic acidosis, or acidosis as a result of base loss were examined enzymatically for the presence of low molecular weight anions including citrate, isocitrate, α-ketoglutarate, succinate, malate and d-lactate. The results obtained from the study groups were compared with those obtained from control plasma from normal volunteers.

Results
In five patients with lactic acidosis, a significant increase in isocitrate (0.71 ± 0.35 mEq l-1), α-ketoglutarate (0.55 ± 0.35 mEq l-1), malate (0.59 ± 0.27 mEq l-1), and d-lactate (0.40 ± 0.51 mEq l-1) was observed. In 13 patients with diabetic ketoacidosis, significant increases in isocitrate (0.42 ± 0.35 mEq l-1), α-ketoglutarate (0.41 ± 0.16 mEq l-1), malate (0.23 ± 0.18 mEq l-1) and d-lactate (0.16 ± 0.07 mEq l-1) were seen. Neither citrate nor succinate levels were increased. Similar findings were also observed in a further five patients with high anion gap acidosis of unknown origin with increases in isocitrate (0.95 ± 0.88 mEq l-1), α-ketoglutarate (0.65 ± 0.20 mEq l-1), succinate (0.34 ± 0.13 mEq l-1), malate (0.49 ± 0.19 mEq l-1) and d-lactate (0.18 ± 0.14 mEq l-1) being observed but not in citrate concentration. In five patients with a normal anion gap acidosis, no increases were observed except a modest rise in d-lactate (0.17 ± 0.14 mEq l-1).

Conclusion
The levels of certain low molecular weight anions usually associated with intermediary metabolism were found to be significantly elevated in the plasma ultrafiltrate obtained from patients with metabolic acidosis. Our results suggest that these hitherto unmeasured anions may significantly contribute to the generation of the anion gap in patients with lactic acidosis and acidosis of unknown aetiology and may be underestimated in diabetic ketoacidosis. These anions are not significantly elevated in patients with normal anion gap acidosis.
Posttraumatic Stress Symptoms During Treatment in Parents of Children With Cancer
Authors: Kazak Anne E. , Boeving C. Alexandra , Alderfer Melissa A. , Hwang Wei-Ting , Reilly Anne 
Published: September 2005

Purpose The conceptualization of childhood cancer and its treatment as traumatic has gained increasing support in the growing literature on medically related posttraumatic stress. Posttraumatic stress symptoms (PTSS) such as intrusive thoughts, physiologic arousal, and avoidance have been documented in mothers and fathers of childhood cancer survivors. In this study we investigated the presence of PTSS in parents of children currently in treatment and their association with treatment intensity and length of time since diagnosis. Methods Mothers (N = 119) and fathers (N = 52) of children currently in treatment for a childhood malignancy completed questionnaire measures of PTSS. Outcomes on these measures were compared with a sample of parents of childhood cancer survivors from our hospital. Oncologist ratings of treatment intensity were obtained based on diagnosis, treatment modalities, and protocol number. Results All but one parent reported PTSS. Mean scores indicated moderate PTSS for both mothers and fathers. In families with two participating parents, nearly 80% had at least one parent with moderate-to-severe PTSS. There were minimal associations between PTSS and length of time since diagnosis. Conclusion PTSS are common among parents of children currently undergoing cancer treatment. Trauma-informed psychosocial interventions can be used to help patients and families, including normalizing the experience as potentially traumatic and using evidence-based interventions that are emerging to facilitate long-term well-being.
Cardiac Morbidity of Adjuvant Radiotherapy for Breast Cancer
Authors: Patt Debra A. , Goodwin James S. , Kuo Yong-Fang , Freeman Jean L. , Zhang Dong D. , Buchholz Thomas A. , Hortobagyi Gabriel N. , Giordano Sharon H. 
Published: September 2005

PurposeAdjuvant breast irradiation has been associated with an increase in cardiac mortality, because left-sided breast radiation can produce cardiac damage. The purpose of this study was to determine whether modern adjuvant radiotherapy is associated with increased risk of cardiac morbidity.Patients and MethodsData from the Surveillance, Epidemiology, and End Results–Medicare database were used for women who were diagnosed with nonmetastatic breast cancer from 1986 to 1993, had known disease laterality, underwent breast surgery, and received adjuvant radiotherapy. The Cox proportional-hazards model was used to compare patients with left- versus right-sided breast cancer for the end points of hospitalization with the following discharge diagnoses (International Classification of Diseases, 9th Revision codes): ischemic heart disease (410-414, 36.0, and 36.1), valvular heart disease (394-397, 424, 35), congestive heart failure (428, 402.01, 402.11, 402.91, and 425), and conduction abnormalities (426, 427, 37.7-37.8, and 37.94-37.99).ResultsEight thousand three hundred sixty-three patients had left-sided breast cancer, and 7,907 had right-sided breast cancer. Mean follow-up was 9.5 years (range, 0 to 15 years). There were no significant differences in patients with left- versus right-sided cancers for hospitalization for ischemic heart disease (9.9% v 9.7%), valvular heart disease (2.9% v 2.8%), conduction abnormalities (9.7% v 9.6%), or heart failure (9.7% v 9.7%). The adjusted hazard ratio for left- versus right-sided breast cancer was 1.05 (95% CI, 0.94 to 1.16) for ischemic heart disease, 1.07 (95% CI, 0.89 to 1.30) for valvular heart disease, 1.07 (95% CI, 0.96 to 1.19) for conduction abnormalities, and 1.05 (95% CI, 0.95 to 1.17) for heart failure.ConclusionWith up to 15 years of follow-up there were no significant differences in cardiac morbidity after radiation for left- versus right-sided breast cancer.
Surgical Management of Idiopathic Normal-pressure Hydrocephalus
Authors: Bergsneider Marvin , Black Peter McL. , Klinge Petra , Marmarou Anthony , Relkin Norman 
Published: September 2005

Abstract

OBJECTIVE:
To develop evidence-based guidelines for surgical management of idiopathic normal-pressure hydrocephalus (INPH). Compared with the diagnostic phase, the surgical management of INPH has received less scientific attention. The quality of much of the literature concerning the surgical management has been limited by many factors. These include retrospective analysis, small patient numbers, analysis of a mixed NPH population, and sometimes a lack of detail as to what type of shunt system was used. Many earlier studies predated our current understanding of the hydrodynamics of cerebrospinal fluid shunts, and therefore, the conclusions drawn may no longer be valid.

METHODS:
A MEDLINE and PubMed search from 1966 to the present was conducted using the following key terms: normal-pressure hydrocephalus and idiopathic adult-onset hydrocephalus. Only English-language literature in peer-reviewed journals was reviewed. The search was further limited to articles that described the method of treatment and outcome selectively for INPH patients. Finally, only studies that included 20 or more INPH patients were considered with respect to formulating the recommendations in these Guidelines (27 articles).

RESULTS:
For practical reasons, it is important to identify probable shunt responders diagnosed with INPH. If the patient is an acceptable candidate for anesthesia, then an INPH-specific risk-benefit analysis should be determined. In general, patients exhibiting negligible symptoms may not be suitable candidates for surgical management, given the known risks and complications associated with shunting INPH. The choice of valve type and setting should be based on empirical reasoning and a basic understanding of shunt hydrodynamics. The most conservative choice is a valve incorporating an antisiphon device, with the understanding that underdrainage (despite a low opening pressure) may occur in a small percentage of patients because of the antisiphon device. On the basis of retrospective studies, the use of an adjustable valve seems to be beneficial in the management of INPH.

CONCLUSION:
The treatment of INPH should not be considered lightly, given the seriousness of the potential complications. Within these limitations and the available evidence, guidelines for surgical management were developed.
Development of Guidelines for Idiopathic Normal-pressure Hydrocephalus: Introduction
Authors: Marmarou Anthony , Bergsneider Marvin , Relkin Norman , Klinge Petra , Black Peter McL. 
Published: September 2005

Abstract

OBJECTIVE:
There are no currently accepted evidence-based guidelines for the diagnosis and management of the normal-pressure hydrocephalus (NPH) patient. As a result, an independent study group was assembled to address this issue and determine the feasibility of developing standardized guidelines, which would be acceptable in the United States and abroad and would be based on the available scientific evidence. The guidelines were to encompass value of clinical presentation, value of supplementary diagnostic tests, surgical management, and outcome assessment.

METHODS:
Initially, a series of 10 questions were formulated in the areas of pathophysiology, diagnosis, and treatment to obtain a consensus by panels of experts (see Acknowledgments) assembled in San Antonio, TX, in September 2000. This workshop provided significant insight into the difficulties in developing NPH guidelines, and a consensus was reached as to those questions involving expert opinion. Subsequently, evidentiary tables were developed on the basis of the available evidence. Only those studies with 20 or more idiopathic NPH (INPH) patients were included.

RESULTS:
Sensitivity, specificity, and positive and negative predictive values for INPH diagnostic criteria were assessed, and guidelines were developed on the basis of the available evidence. Recommendations for classification of INPH and additional studies were documented.

CONCLUSION:
The development of the guidelines was made difficult because systematic studies of INPH and patient numbers were few. It was decided to maintain the classification of NPH into two major categories, INPH and those of known cause (secondary NPH). Many studies “mixed” these classifications, and as a result, they could not be used in the evidentiary tables. Despite these problems, evidence-based guidelines were developed, and it is hoped that they will be useful in guiding clinical management of the INPH patient.
A Patient with a Resistant Major Depression Disorder Treated with Deep Brain Stimulation in the Inferior Thalamic Peduncle
Authors: Jiménez Fiacro , Velasco Francisco , Salin-Pascual Rafael , Hernández José A. , Velasco Marcos , Criales José L. , Nicolini Humberto 
Published: September 2005

ABSTRACTOBJECTIVE AND IMPORTANCE:The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD).CLINICAL PRESENTATION:This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient's symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD.INTERVENTION:The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20.CONCLUSION:Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.
Prediction of Prolonged Postprocedural Hypotension after Carotid Artery Stenting
Authors: Nonaka Tadashi , Oka Shinichi , Miyata Kei , Mikami Takeshi , Koyanagi Izumi , Houkin Kiyohiro , Yoshifuji Kazuhisa , Imaizumi Toshio 
Published: September 2005

ABSTRACT

OBJECTIVE:
Stent placement for the treatment of carotid artery stenosis may cause hemodynamic instability that induces ischemic complications for patients with bilateral carotid lesions. We carried out this study to define predictors of persistent hypotension after carotid stenting.

METHODS:
Thirty-three lesions in 31 consecutive patients (mean age, 69.2 ± 8.6 yr) who underwent stent deployment for carotid stenosis were studied. Fourteen lesions were treated with Easy Wall stents (Boston Scientific, Tokyo, Japan) and 19 lesions were treated with Smart stents (Johnson & Johnson, Warren, NJ). We reviewed preoperative angiograms and ultrasonograms of the carotid artery and analyzed the predictive factors of postprocedural prolonged hypotension (systolic blood pressure &lt;90 mm Hg and periods &gt;3 h).

RESULTS:
Postprocedural hypotension was observed in 14 lesions (42.4%), of which medical treatment was necessary in seven (21.2%). A distance between carotid bifurcation and maximum stenotic lesion (≤10 mm; P = 0.0028) and type of stenosis (eccentric; P = 0.0287) on angiogram and fibrous plaque morphological features (P = 0.0008) and calcifications at carotid bifurcation (P = 0.0004) on ultrasonograms were determined to be independent risk factors of postprocedural hypotension. We introduced a scoring system for predicting prolonged hypotension that included factors such as the distance from carotid bifurcation to maximum stenotic lesion (≤10 mm), type of stenosis (eccentric), plaque morphological features (echogenic), and calcification at carotid bifurcation. The score was determined by adding one point for each of these factors. Three points or more on this score strongly suggested a high risk of prolonged hypotension.

CONCLUSION:
Our scoring system, which includes angiographic and ultrasonographic findings, may be a good index for the prediction of prolonged hypotension after carotid stenting and may contribute to the reduction of periprocedural ischemic events.
Reconstruction of Anterior Iliac Crest after Bone Graft Harvest Decreases Pain: A Randomized, Controlled Clinical Trial
Authors: Resnick Daniel K. 
Published: September 2005

ABSTRACT

OBJECTIVE:
A substantial number of patients report persistent pain after graft harvest from the anterior iliac crest. There have been several retrospective case series published that suggest that iliac crest reconstruction using a variety of techniques may decrease graft site pain. This study, a randomized, controlled clinical trial at a university hospital, tested the hypothesis that reconstruction of the iliac crest will reduce graft harvest site pain.

METHODS:
A randomized, controlled clinical trial using the McGill Pain Inventory as the primary outcome measure was performed to evaluate the effect of anterior iliac crest reconstruction after graft harvest. Thirty patients who were treated with anterior cervical discectomy and fusion or cervical corpectomy and fusion with autologous iliac crest graft were randomized to one of two groups. Patients in Group 1 were treated with reconstruction of the iliac crest with commercially available tricalcium phosphate bone void filler after graft harvest. Patients in Group 2 were treated without graft site reconstruction. Graft site pain was assessed immediately after surgery, 6 weeks after surgery, and 3 months after surgery.

RESULTS:
Treatment groups were well matched with regard to patient age, sex, and smoking history. Although patients in each group reported persistent pain 6 weeks and 3 months after graft harvest, patients in the reconstruction group reported significantly less severe pain at 6 weeks and tended to have less pain at 3 months after surgery.

CONCLUSION:
Reconstruction of the iliac crest with tricalcium phosphate bone void filler significantly decreases the severity of postoperative pain 6 weeks after surgery.