bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Expression of Interferon (IFN) Regulatory Factors and IFN-Stimulated Genes at Early Times after West Nile Virus Infection of Mouse Embryo Fibroblasts
Authors: Scherbik Svetlana V. , Stockman Bronislava M. , Brinton Margo A. 
Published: September 2007

ABSTRACT
Although lineage I West Nile virus (WNV) strain Eg101 induced beta interferon (IFN-β) production as early as 12 h after infection in primary mouse embryo fibroblasts and did not inhibit the JAK-STAT signaling pathway, it was still able to replicate efficiently. To gain insights about possible viral countermeasures used by this virus to suppress the host response, the cell transcriptional profile and the kinetics of IFN regulatory factor (IRF) expression and activation were examined at early times after infection. By 12 h after WNV infection, the majority of the up-regulated genes were ones involved in IFN pathways. However, comparison of IFN-stimulated gene (ISG) expression levels in mock-infected, IFN-treated, and virus-infected cells indicated that WNV infection suppressed the up-regulation of a subset of ISGs, including genes involved in transcriptional regulation, apoptosis, and stress responses, prior to 24 h after infection. Analysis of mRNA and protein levels for representative genes indicated that suppression was at the transcriptional and posttranscriptional levels. Translocation of IRF-3 to the nucleus was observed beginning at 8 h, IRF-7 expression was detected by 12 h, but IRF-1 expression was not detected until 24 h after infection. Virus-induced gene suppression was sufficient to overcome the effect of exogenous IFN pretreatment for 1 h but not for 4 h prior to infection. These data indicate that WNV can selectively counteract the host response at early times after infection by previously unreported mechanisms.
Effects of Identity Minimization on Moloney Murine Leukemia Virus Template Recognition and Frequent Tertiary Template-Directed Insertions during Nonhomologous Recombination
Authors: Duggal Nisha K. , Goo Leslie , King Steven R. , Telesnitsky Alice 
Published: September 2007

ABSTRACT
Homology requirements for Moloney murine leukemia virus recombination were addressed in this study by monitoring titer defects observed when acceptor/donor template identity lengths were systematically reduced. Recombination acceptors with at least 16 contiguous bases of donor template identity were recognized as efficiently as longer acceptors. In contrast, a sharp 1-log titer drop was observed for an acceptor of only 15 bases long, with an additional 1-log titer decline for an 8-base acceptor and further decreases for shorter acceptors. Eighty-three independent nonhomologous recombination products were sequenced to examine recombination template selection in the absence of significant sequence identity. These replication products contained a total of 152 nonhomologous crossover junctions. Forced copy choice models predict that forced nonhomologous recombination should result in DNA synthesis to the donor template's 5′ end, followed by microidentity-guided acceptor template selection. However, only a single product displayed this structure. The majority of examined nonhomologous recombination products contained junction-associated sequence insertions. Most insertions resulted from the use of one or more tertiary templates, recognizable as discontiguous portions of viral or host RNA or minus-strand DNA. The donor/acceptor template microidentity evident at most crossovers reconfirmed the remarkable capability of the reverse transcription machinery to recognize short regions of sequence identity. These results demonstrate that recruitment of discontiguous host or viral sequences is a common way for retroviruses to resolve nonhomologous recombination junctions and provide experimental support for the role of splinting templates in the generation of retroviral insertions.
Hepatitis C Virus Infection Induces the Beta Interferon Signaling Pathway in Immortalized Human Hepatocytes
Authors: Kanda Tatsuo , Steele Robert , Ray Ranjit , Ray Ratna B. 
Published: September 2007

ABSTRACT
Beta interferon (IFN-β) expression is triggered by double-stranded RNA, a common intermediate in the replication of many viruses including hepatitis C virus (HCV). The recent development of cell culture-grown HCV allowed us to analyze the IFN signaling pathway following virus infection. In this study, we have examined the IFN-β signaling pathway following infection of immortalized human hepatocytes (IHH) with HCV genotype 1a (clone H77) or 2a (clone JFH1). We observed that IHH possesses a functional Toll-like receptor 3 pathway. HCV infection in IHH enhanced IFN-β and IFN-stimulated gene 56 (ISG56) promoter activities; however, poly(I-C)-induced IFN-β and ISG56 expression levels were modestly inhibited upon HCV infection. IHH infected with HCV (genotype 1a or 2a) exhibited various levels of translocation of IRF-3 into the nucleus. The upregulation of endogenous IFN-β and 2′,5′-oligoadenylate synthetase 1 mRNA expression was also observed in HCV-infected IHH. Subsequent studies suggested that HCV infection in IHH enhanced STAT1 and ISG56 protein expression. A functional antiviral response of HCV-infected IHH was observed by the growth-inhibitory role in vesicular stomatitis virus. Together, our results suggested that HCV infection in IHH induces the IFN signaling pathway, which corroborates observations from natural HCV infection in humans.
Inhibition of Human Immunodeficiency Virus Type 1 Concerted Integration by Strand Transfer Inhibitors Which Recognize a Transient Structural Intermediate
Authors: Pandey Krishan K. , Bera Sibes , Zahm Jacob , Vora Ajaykumar , Stillmock Kara , Hazuda Daria , Grandgenett Duane P. 
Published: September 2007

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) integrase (IN) inserts the viral DNA genome into host chromosomes. Here, by native agarose gel electrophoresis, using recombinant IN with a blunt-ended viral DNA substrate, we identified the synaptic complex (SC), a transient early intermediate in the integration pathway. The SC consists of two donor ends juxtaposed by IN noncovalently. The DNA ends within the SC were minimally processed (∼15%). In a time-dependent manner, the SC associated with target DNA and progressed to the strand transfer complex (STC), the nucleoprotein product of concerted integration. In the STC, the two viral DNA ends are covalently attached to target and remain associated with IN. The diketo acid inhibitors and their analogs effectively inhibit HIV-1 replication by preventing integration in vivo. Strand transfer inhibitors L-870,810, L-870,812, and L-841,411, at low nM concentrations, effectively inhibited the concerted integration of viral DNA donor in vitro. The inhibitors, in a concentration-dependent manner, bound to IN within the SC and thereby blocked the docking onto target DNA, which thus prevented the formation of the STC. Although 3′-OH recessed donor efficiently formed the STC, reactions proceeding with this substrate exhibited marked resistance to the presence of inhibitor, requiring significantly higher concentrations for effective inhibition of all strand transfer products. These results suggest that binding of inhibitor to the SC occurs prior to, during, or immediately after 3′-OH processing. It follows that the IN-viral DNA complex is “trapped” by the strand transfer inhibitors via a transient intermediate within the cytoplasmic preintegration complex.
The self-archiving principle: a momentous trek
Authors: Singh Nishith K 
Published: September 2007

Abstract
In the existing scholarly publishing empire, authors give away their valued research work to various commercial journals, thereby restricting free accessibility to the published useful work. Triggered by the gargantuan promise of the internet, the self-archiving principle is a new and revolutionary concept which potentially lets all research work become freely available online. It involves deposition of research documents at a publicly accessible website, and its proponents see the initiative as a means to set entire author works free of all access and impact barriers. This review briefly discusses the allied concepts, the course and implications of the initiative.
Orthostatic hypotension: framework of the syndrome
Authors: Naschitz Jochanan E , Rosner Itzhak 
Published: September 2007

Abstract
According to the 1996 consensus definition, orthostatic hypotension (OH) is diagnosed when a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 min of standing is recorded. The elements of orthostatic blood pressure drop that are relevant to the definition of OH include magnitude of the drop, time to reach the blood pressure difference defined as OH, and reproducibility of the orthostatic blood pressure drop. In each of these elements, there exist issues that argue for modification of the presently accepted criteria of OH. Additional questions need to be addressed. Should one standard orthostatic test be applied to different patient populations or should tests be tailored to the patients' clinical circumstances? Are different OH thresholds relevant to various clinical settings, aetiologies of OH and comorbidity? Which test has the best predictive power of morbidity and mortality?
A national online survey of final year medical students' opinion on the General Medical Council's proposed reforms to the undergraduate medical assessment system
Authors: Khan Kamran Z , Sear John W 
Published: September 2007

Abstract

Background
The General Medical Council (GMC) is holding consultations in order to decide on the proposed changes to the undergraduate medical assessment. In the last round of consultation only eight medical students formally responded nationally.

Aim
To determine the views of a larger proportion of final year medical students across the country on the proposed changes to the undergraduate medical assessment.

Method
An online national survey of 10 medical schools, from which 401 responses from final year medical students were collected.

Results and discussion
The results indicate the medical students' views on the GMC's proposed changes to standardise the assessment system. The majority of the students were in favour of having a say in any changes to their future assessment. They agreed with the principle that there should be a consistency between assessments at different medical schools and currently their results did not represent preparedness to practice.
Heparin induced thrombocytopenia: diagnosis and management update
Authors: Ahmed I , Majeed A , Powell R 
Published: September 2007

Abstract
Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin. Despite thrombocytopenia, bleeding is rare; rather, HIT is strongly associated with thromboembolic complications involving both the arterial and venous systems. A number of laboratory tests are available to confirm the diagnosis; however, when HIT is clinically suspected, treatment should not be withheld pending the result. Fortunately, therapeutic strategies have been refined, and new and effective therapeutic agents are available. Treatment options are focused on inhibiting thrombin formation or direct thrombin inhibition. Warfarin should not be used until the platelet count has recovered.
The role of genetics in stroke
Authors: Francis John , Raghunathan Senthil , Khanna Pradeep 
Published: September 2007

Abstract
Stroke is a leading cause of death and disability in developed countries. While both modifiable and non-modifiable risk factors are acknowledged, studies have shown that these may account for just 50% of stroke risk and that other factors, including genetic ones, may be important. Over recent years family history, twin and candidate gene studies have supported this and various mendelian stroke syndromes have now been identified in humans. This article provides an up-to-date summary of the common single gene disorders associated with stroke as a principle manifestation, including their genetic basis, pathogenesis, presentation and suggested management. Often these disorders present with stroke at a young age; this article provides a practical approach to the management and investigation of a young stroke patient.
A cross sectional survey of secondary prevention measures in patients with peripheral arterial disease in primary care
Authors: Dunkley Alison , Stone Margaret , Sayers Robert , Farooqi Azhar , Khunti Kamlesh 
Published: September 2007

Abstract

Background
The National Service Framework for coronary heart disease (CHD) defines standards for the secondary prevention of cardiovascular disease in at risk individuals, including those with peripheral arterial disease (PAD).

Aim
To assess current standards of secondary prevention and health monitoring in patients with PAD following a vascular procedure, and additionally compare care in patients with and without diagnosed CHD.

Methods
Indicators for this cross sectional survey were identified from national recommendations and evidence. A retrospective review was conducted of general practitioner records, for patients who were treated in hospital for PAD.

Results
Data were collected for 103 patients from 42 practices. Overall, prescribing was well achieved for antiplatelets but poor for statins. Standards of assessment of blood pressure, smoking status, and smoking cessation advice were high. However, approximately only half of the patients received advice about exercise or had their body mass index checked. Furthermore, for all indicators, standards of care for patients who additionally had a diagnosis of CHD were better than for patients without CHD.

Conclusion
The cross sectional survey suggested the treatment received by some patients with established PAD is substandard. There is considerable potential to increase secondary prevention of CHD in patients with PAD disease in primary care.
Effect of pioglitazone and its combination with statins in coronary artery disease patients with hyperinsulinemia
Authors: Mehta Anita , Shah Urmil , Parikh Keyur , Chag Milan , Baxi Hemang , Chandarana Anish , Naik Ajay , Naik Asha , Shah Kanan , Goyal Ramesh 
Published: September 2007

The objective of the study was to demonstrate the effect of pioglitazone and pioglitazone in combination with statin on East Indian patients with hyperinsulinemia and hyperlipidemia. It was a randomized, placebo-controlled, double-blind study with a parallel-group design comprising 83 patients. Patients of either sex with cardiac complications, including hyperlipidemia and (or) diabetes mellitus with or without hyperinsulinemia, were enrolled. Patients over 70 years of age, with renal or hepatic failure, or with severe diabetes mellitus (total glucose >400 mg/dL) were excluded from the study. Enrolled patients were randomly assigned to 4 groups that received placebo, pioglitazone, atorvastatin, or both. Blood samples were collected before and after treatment for analysis of serum glucose, insulin, lipid profile, apolipoprotein (apo) A1, apo B, and fibrinogen. Data were compared with that of patients with normal insulin or hyperinsulinemia. The patients with hyperinsulinemia receiving only pioglitazone showed a significant decrease in insulin levels compared with those with normal insulin levels. These patients also showed a significant increase in HDL levels. However, no significant change was observed in patients treated with both atorvastatin and pioglitazone. Pioglitazone was also found to increase significantly the apo A1 levels in patients with hyperinsulinemia, but there was no significant increase in patients given both atorvastatin and pioglitazone. Our data suggests that pioglitazone should be given preferably to the patients with hyperinsulinemia and statin should not be coadministered.
Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat-fed rats
Authors: Manjunatha H. , Srinivasan K. 
Published: September 2007

The beneficial hypolipidemic and antioxidant influences of the dietary spice compounds curcumin and capsaicin were evaluated. Curcumin, capsaicin, or their combination were included in the diet of high-(30%)-fat-fed rats for 8 weeks. Dietary high-fat-induced hypertriglyceridemia was countered by dietary curcumin, capsaicin, or their combination by 12%–20%. Curcumin, capsaicin, and their combination also produced a slight decrease in serum total cholesterol in these animals. Serum α-tocopherol content was increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats. Serum total thiol content in high-fat-fed animals and serum ascorbic acid in normal animals was elevated by the combination of curcumin and capsaicin. Hepatic glutathione was increased by curcumin, capsaicin, or their combination in normal animals. Hepatic glutathione and α-tocopherol were increased, whereas lipid peroxide level was reduced by dietary curcumin and combination of curcumin and capsaicin in high-fat-fed animals. Serum glutathione peroxidase and glutathione transferase in high-fat-fed rats were generally higher as a result of dietary curcumin, capsaicin, and the combination of curcumin and capsaicin. Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals. The additive effect of the 2 bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential. However, the effectiveness of the combination was higher in a few instances.
Anticonvulsant effect of A1but not A2Aadenosine receptors of piriform cortex in amygdala-kindled rats
Authors: Rezvani Mohammad Ebrahim , Mirnajafi-Zadeh Javad , Fathollahi Yaghoub , Palizvan Mohammad Reza 
Published: September 2007

In this study, the effect of A1and A2Aadenosine receptor activity of the piriform cortex (PC) on amygdala-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the amygdala. In fully kindled rats, N6-cyclohexyladenosine (CHA, a selective A1agonist), 8-cyclopentyl-1,3-dimethylxanthine (CPT, a selective A1antagonist), CGS21680 hydrochloride (CGS, a selective A2Aagonist), and ZM241385 (ZM, a selective A2Aantagonist) were microinjected bilaterally into the PC. Rats were stimulated 5 min post-drug microinjection and seizure parameters were measured. Results showed that intra-PC CHA (10 and 100 μmol/L) decreased the duration of both afterdischarge and stage 5 seizure and significantly increased the latency to stage 4 seizure. Intra-PC CPT increased afterdischarge and stage 5 seizure duration at the dose of 20 μmol/L. The anticonvulsant effect of CHA (100 μmol/L) was eliminated by CPT (10 μmol/L) pretreatment. On the other hand, neither intra-PC CGS nor ZM had a significant effect on kindled seizures. These results suggest that activity of A1, but not A2A, receptors of the PC have anticonvulsant effects on kindled seizures elicited from electrical stimulation of the amygdala.
The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep
Authors: Boyce Amanda C. , Gibson Karen J. , Wintour E. Marelyn , Koukoulas Irene , Gatford Kathryn L. , Owens Julie A. , Lumbers Eugenie R. 
Published: September 2007

We imposed a sustained reduction in glucose supply to late-gestation fetal sheep to see whether the reduction in glucose and insulin levels affected renal growth, renin expression and synthesis, and renal function. Maternal glucose concentrations were lowered to 1.7–1.9 mmol/L for 12–13 days by i.v. insulin infusion (n = 9, 121 days gestation, term = 150 days). Control ewes (n = 7) received vehicle. Maternal and fetal glucose concentrations were 40% and 31% lower than in controls (p < 0.001), respectively. Fetal plasma insulin levels fell 36% ± 7% by day 7 (p < 0.05); IGF-I levels were unchanged. Arterial PO2and pH increased and PCO2fell (p < 0.05). Renal function was largely unaffected. Longitudinal growth was 28% slower and spleen weights were 36% smaller (p < 0.05); body and kidney weights were not affected. Renal renin levels and renin, angiotensinogen, and angiotensin receptor mRNA levels were similar to those of controls. Plasma renin levels increased from 2.1 ± 0.6 to 7.6 ± 2.8 ng angiotensin I·mL–1·h–1(p = 0.01). Thus reductions in fetal glucose and insulin levels in late gestation that were sufficient to retard skeletal growth had no effect on kidney growth or function or the renal renin–angiotensin system, possibly because IGF-I levels were not reduced. There was, however, increased activity of the circulating renin–angiotensin system similar to that seen during insulin-induced hypoglycaemia.
Effect of artemether on pentobarbitone sleep and electrical activity in rats
Authors: Ejiofor Janet I. , Kwanashie Helen O. , Anuka Joseph A. 
Published: September 2007

Artemether (AM), a highly effective treatment for multidrug-resistant malaria and a component of artemisinin combination therapy, has been associated with some neurotoxicity following repeated high doses. This study was aimed at investigating the effect of AM on pentobarbitone sleep and electrical activities in rats. Wistar rats received AM i.p. at 3 dose levels: 1.5, 7.5, and 15 mg/kg, whereas control rats received 0.2 mL of the vehicle (3% v/v Tween 80). AM administered 20 min before pentobarbitone had no significant effect on the onset and duration of sleep. However, after a 7-day pretreatment, AM dose-dependently prolonged pentobarbitone sleep, as did chloramphenicol. Electroencephalogram and electromyogram recordings 20 min after pretreatment showed that AM (15 mg/kg) exhibited inhibitory activity similar to chlorpromazine as opposed to the excitatory effect of amphetamine. When pretreated for 7 days, rats receiving 1.5 mg/kg AM also showed inhibitory activity of the cortical centres, whereas desynchronization of the optic tectum and reticular formation was observed in rats pretreated with 7.5 and 15 mg/kg AM. The present data suggest that although the therapeutic equivalent dose of 1.5 mg/kg AM had no appreciable effects on pentobarbitone sleep but caused reduced electrical activity in rats, higher doses have more profound effects on both indices.