bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 replication in cell lines harboring INI1/hSNF5 mutations
Authors: Sorin Masha , Yung Eric , Wu Xuhong , Kalpana Ganjam V 
Published: September 2006

Abstract

Background
INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication.

Results
We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate.

Conclusion
Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that presence of INI1 or some other host factor in virions and reverse transcription complexes may be important for early events of HIV-1 replication.
Regression analysis with categorized regression calibrated exposure: some interesting findings
Authors: Dalen Ingvild , Buonaccorsi John P , Laake Petter , Hjartåker Anette , Thoresen Magne 
Published: September 2006

Abstract
Background
Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile) scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis.

Methods
We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC).

Results
In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis.

Conclusion
Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a percentile scale. Relating back to the original scale of the exposure solves the problem. The conclusion regards all regression models.
SIV escape mutants in rhesus macaques vaccinated with NEF-derived lipopeptides and challenged with pathogenic SIVmac251
Authors: Villefroy Pascale , Letourneur Franck , Coutsinos Zoe , Mortara Lorenzo , Beyer Christian , Gras-Masse Helene , Guillet Jean-Gerard , Bourgault-Villada Isabelle 
Published: September 2006

AbstractBackgroundEmergence of viral variants that escape CTL control is a major hurdle in HIV vaccination unless such variants affect gene regions that are essential for virus replication. Vaccine-induced multispecific CTL could also be able to control viral variants replication. To explore these possibilities, we extensively characterized CTL responses following vaccination with an epitope-based lipopeptide vaccine and challenge with pathogenic SIVmac251. The viral sequences corresponding to the epitopes present in the vaccine as well as the viral loads were then determined in every macaque following SIV inoculation.ResultsIn most cases, the emergence of several viral variants or mutants within vaccine CTL epitopes after SIV challenge resulted in increased viral loads except for a single macaque, which showed a single escape viral variant within its 6 vaccine-induced CTL epitopes.ConclusionThese findings provide a better understanding of the evolution of CD8+ epitope variations after vaccination-induced CTL expansion and might provide new insight for the development of an effective HIV vaccine.
Circulating viral core and E1 antigen levels as supplemental markers for HCV Chronic hepatitis
Authors: El Awady Mostafa K , El Abd Yasmine S , Shoeb Hussein A , Tabll Ashraf A , Hosny AlaaElDin MS , El Shenawy Reem M , Atef Khaled , Bader El Din Noha G , Bahgat Mahmoud M 
Published: September 2006

AbstractThe performance of polyclonal monospecific rabbit anti-sera raised against synthetic peptides derived from conserved HCV sequences of genotype 4 was evaluated for efficient detection of viral core and E1 antigens in circulating immune complexes (ICs) precipitated from 65 serum samples of HCV patients. The infection was established in those patients by the presence of HCV RNA in their sera. A novel enzyme-linked immunosorbent assay (ELISA) was developed for the detection of HCV core and E1 antigen in serum samples. Western blot analyses were used to demonstrate the presence of the core and E1 target antigen in serum samples. The mean OD readings of both core and E1 antigens were significantly higher (P < 0.05) among the viremic patients when compared to controls. Also a significant positive correlation (P < 0.05, r = 0.98) between the values of both core and E1 was recorded. Western blot analysis based on monospecific antibodies against core and E1 recognized the 38-kDa and 88 -kDa bands respectively in the sera of all infected patients. No specific reaction was observed with the sera from uninfected individuals. Interestingly the results of core and E1 antigen levels displayed no positive correlation with the HCV copy number as measured by bDNA. Liver enzymes (ALT and AST) showed a moderate positive correlation (r = 0.44 and 0.47 respectively) with the viral core antigens level. The same trend holds true for E1 (r = 0.43 and 0.64 for ALT and AST respectively). HCV load in infected patients revealed extremely poor correlation with serum ALT and AST levels (r = 0.022 and 0.002 respectively). In conclusion we present a new combination of serological tools correlating with liver enzyme levels that could be utilized as supplemental tests to viral load testing. Also, a sensitive and specific immunoassay was developed for the detection of HCV core and E1 in human serum. This test can be applied for laboratory diagnosis of HCV infection.
Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay
Authors: Shaneyfelt Mark E , Burke Anna D , Graff Joel W , Jutila Mark A , Hardy Michele E 
Published: September 2006

AbstractBackgroundThere is widespread interest in the use of innate immune modulators as a defense strategy against infectious pathogens. Using rotavirus as a model system, we developed a cell-based, moderate-throughput screening (MTS) assay to identify compounds that reduce rotavirus infectivity in vitro, toward a long-term goal of discovering immunomodulatory agents that enhance innate responses to viral infection.ResultsA natural product library consisting of 280 compounds was screened in the assay and 15 compounds that significantly reduced infectivity without cytotoxicity were identified. Time course analysis of four compounds with previously characterized effects on inflammatory gene expression inhibited replication with pre-treatment times as minimal as 2 hours. Two of these four compounds, α-mangostin and 18-β-glycyrrhetinic acid, activated NFκB and induced IL-8 secretion. The assay is adaptable to other virus systems, and amenable to full automation and adaptation to a high-throughput format.ConclusionIdentification of several compounds with known effects on inflammatory and antiviral gene expression that confer resistance to rotavirus infection in vitro suggests the assay is an appropriate platform for discovery of compounds with potential to amplify innate antiviral responses.
Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery
Authors: Seiler CM , Fröhlich BE , Veit JA , Gazyakan E , Wente MN , Wollermann C , Deckert A , Witte S , Victor N , Buchler MW , Knaebel HP 
Published: September 2006

Abstract

Background
Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT.

Methods/design
CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers.

Discussion
As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice.
Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature
Authors: Putnik Kurt , Stadler Peter , Schäfer Christof , Koelbl Oliver 
Published: September 2006

Abstract

Background
Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's wort).

Case report
A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward.

Conclusion
Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative drugs because patients tend to conceal such medication as harmless.
TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells
Authors: Ando Takashi , Ichikawa Jiro , Wako Masanori , Hatsushika Kyosuke , Watanabe Yoshiyuki , Sakuma Michitomo , Tasaka Kachio , Ogawa Hideoki , Hamada Yoshiki , Yagita Hideo , Nakao Atsuhito 
Published: September 2006

AbstractTumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of the TNF family, is a multifunctional cytokine that regulates cell growth, migration, and survival principally through a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14). However, its physiological roles in bone are largely unknown. We herein report various effects of TWEAK on mouse osteoblastic MC3T3-E1 cells. MC3T3-E1 cells expressed Fn14 and produced RANTES (regulated upon activation, healthy T cell expressed and secreted) upon TWEAK stimulation through PI3K-Akt, but not nuclear factor-κB (NF-κB), pathway. In addition, TWEAK inhibited bone morphogenetic protein (BMP)-2-induced expression of osteoblast differentiation markers such as alkaline phosphatase through mitogen-activated protein kinase (MAPK) Erk pathway. Furthermore, TWEAK upregulated RANKL (receptor activation of NF-κB ligand) expression through MAPK Erk pathway in MC3T3-E1 cells. All these effects of TWEAK on MC3T3-E1 cells were abolished by mouse Fn14-Fc chimera. We also found significant TWEAK mRNA or protein expression in osteoblast – and osteoclast-lineage cell lines or the mouse bone tissue, respectively. Finally, we showed that human osteoblasts expressed Fn14 and induced RANTES and RANKL upon TWEAK stimulation. Collectively, TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in MC3T3-E1 cells. TWEAK may thus be a novel cytokine that regulates several aspects of osteoblast function.
The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins
Authors: Adachi Jun , Kumar Chanchal , Zhang Yanling , Olsen Jesper V , Mann Matthias 
Published: September 2006

Abstract
Background
Urine is a desirable material for the diagnosis and classification of diseases because of the convenience of its collection in large amounts; however, all of the urinary proteome catalogs currently being generated have limitations in their depth and confidence of identification. Our laboratory has developed methods for the in-depth characterization of body fluids; these involve a linear ion trap-Fourier transform (LTQ-FT) and a linear ion trap-orbitrap (LTQ-Orbitrap) mass spectrometer. Here we applied these methods to the analysis of the human urinary proteome.

Results
We employed one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and reverse phase high-performance liquid chromatography for protein separation and fractionation. Fractionated proteins were digested in-gel or in-solution, and digests were analyzed with the LTQ-FT and LTQ-Orbitrap at parts per million accuracy and with two consecutive stages of mass spectrometric fragmentation. We identified 1543 proteins in urine obtained from ten healthy donors, while essentially eliminating false-positive identifications. Surprisingly, nearly half of the annotated proteins were membrane proteins according to Gene Ontology (GO) analysis. Furthermore, extracellular, lysosomal, and plasma membrane proteins were enriched in the urine compared with all GO entries. Plasma membrane proteins are probably present in urine by secretion in exosomes.

Conclusion
Our analysis provides a high-confidence set of proteins present in human urinary proteome and provides a useful reference for comparing datasets obtained using different methodologies. The urinary proteome is unexpectedly complex and may prove useful in biomarker discovery in the future.
The role of cytokines in hepatocellular carcinoma
Authors: Budhu Anuradha , Wang Xin Wei 
Published: September 2006

Abstract
Hepatocellular carcinoma (HCC) is a frequent malignancy worldwide with a high rate of metastasis. The hepatitis B and C viruses are considered major etiological factors associated with the development of HCC, particularly as a result of their induction of chronic inflammation. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including HCC. Specifically, this review aims to cover evidence for the potential roles of cytokines, an important component of the immune system, in promoting HCC carcinogenesis and progression. A global summary of cytokine levels, functions, polymorphisms, and therapies with regard to HCC is presented. In particular, the role of proinflammatory Th1 and anti-inflammatory Th2 cytokine imbalances in the microenvironment of HCC patients with metastasis and the possible clinical significance of these findings are addressed. Overall, multiple studies, spanning many decades, have begun to elucidate the important role of cytokines in HCC.
MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4)
Authors: Visintin Alberto , Halmen Kristen A , Khan Naseema , Monks Brian G , Golenbock Douglas T , Lien Egil 
Published: September 2006

Abstract
The cell surface receptor complex formed by TLR4 and myeloid differentiation 2 (MD-2) is engaged when cells are exposed to LPS. Recent studies suggested that surface localization of functional mouse TLR4 (mTLR4) depends on the simultaneous expression of MD-2. As we did not observe a similar requirement, we conducted a comparative study of human TLR4 and mTLR4 surface expression in immune cells derived from the MD-2 knockout mouse and LPS-responsive cell lines and in cells that ectopically express TLR4. Our results indicate that in the human and mouse models, neither TLR4 function nor TLR4 surface targeting requires MD-2 coexpression. Accordingly, we report on one human cell line, which constitutively expresses functional TLR4 on the cell surface in the absence of MD-2 expression.
Procedural Sedation in the Community Emergency Department: Initial Results of the ProSCED Registry
Authors: Sacchetti Alfred , Senula Gary , Strickland James , Dubin Reva 
Published: September 2006

Abstract Objectives Procedural sedation and analgesia (PSA) has been well profiled in experimental studies in university emergency departments. Extrapolation of these practices into the community hospital setting is not well established. This report describes community hospital practices and outcomes in a multicenter PSA registry. Methods The Procedural Sedation in the Community Emergency Department (ProSCED) registry is a prospective observational database composed of consecutive emergency physician–directed procedural sedation cases in community hospitals. Registered procedures described by 15 categorical data fields are collected at the time of the patient encounter and entered into a secure Internet‐housed database. Results A total of 1,028 procedural sedations were performed on 980 patients at 14 study sites. The most common specified procedures performed included shoulder relocation (392), hip relocation (102), elbow relocation (70), upper extremity fracture care (69), lower extremity fracture care (66), and facial laceration repair (67). Complications of any description occurred in 42 cases (4.1%), with no patient's disposition changed secondary to a complication. Patients' ages ranged from 1 month to 95 years, with a median age of 31 years. Of procedures attempted, 982 (95.5%) were successfully completed, 21 cases (2.0%) were adequately sedated but unable to have their procedure completed, and 21 cases (2.0%) were believed to be inadequately sedated. Medication use included midazolam in 423 cases (41.1%), propofol in 253 (24.6%), fentanyl in 253 (24.6%), etomidate in 241 (23.4%), and ketamine in 145 (14.1%), as well as several others. Cases using either ketamine or propofol exhibited the fewest complications, while those using fentanyl, hydromorphone, or midazolam demonstrated the highest complication rates. Conclusions Community emergency physicians deliver safe and effective PSA over a wide variety of ages and procedures while using a broad selection of agents.
The Effects of Ambulance Diversion: A Comprehensive Review
Authors: Pham Julius Cuong , Patel Ronak , Millin Michael G. , Kirsch Thomas Dean , Chanmugam Arjun 
Published: September 2006

ObjectivesTo review the current literature on the effects of ambulance diversion (AD).MethodsThe authors performed a systematic review of AD and its effects. PubMed, EMBASE, the Cochrane database, societal meeting abstracts, and references from relevant articles were searched. All articles were screened for relevance to AD.ResultsThe authors examined 600 citations and reviewed the 107 articles relevant to AD. AD is a common occurrence that is increasing in frequency. AD is associated with periods of emergency department (ED) crowding (Mondays, mid‐afternoon to early evening, influenza season, and when hospitals are at capacity). Interventions that redesign the AD process or that provide additional hospital or ED resources reduce diversion frequency. AD is associated with increased patient transport times and time to thrombolytics but not with mortality. AD is associated with loss of estimated hospital revenues. Short of anecdotal or case reports, no studies measured the effect of AD on ED crowding, morbidity, patient and provider satisfaction, or EMS resource utilization.ConclusionsDespite its common use, there is a relative paucity of studies on the effects of AD. Further research into these effects should be performed so that we may understand the role of AD in the health system.