bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel DSPPmutation is associated with type II dentinogenesis Imperfecta in a chinese family
Authors: Zhang Xianqin , Chen Lanying , Liu Jingyu , Zhao Zhen , Qu Erjun , Wang Xiaotao , Chang Wei , Xu Chengqi , Wang Qing K , Liu Mugen 
Published: August 2007

Abstract

Background
Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) (types I and II) and dentinogenesis imperfecta (DGI) (types I, II, and III). Type II DGI is one of the most common tooth defects with an autosomal dominant mode of inheritance. One disease-causing gene, the dentin sialophosphoprotein (DSPP) gene, has been reported for type II DGI.

Methods
In this study, we characterized a four-generation Chinese family with type II DGI that consists of 18 living family members, including 8 affected individuals. Linkage analysis with polymorphic markers D4S1534 and D4S414 that span the DSPP gene showed that the family is linked to DSPP. All five exons and exon-intron boundaries of DSPP were sequenced in members of type II DGI family.

Results
Direct DNA sequence analysis identified a novel mutation (c.49C→T, p.Pro17Ser) in exon 1 of the DSPP gene. The mutation spot, the Pro17 residue, is the second amino acid of the mature DSP protein, and highly conserved during evolution. The mutation was identified in all affected individuals, but not in normal family members and 100 controls.

Conclusion
These results suggest that mutation p.Pro17Ser causes type II DGI in the Chinese family. This study identifies a novel mutation in the DSPP gene, and expands the spectrum of mutations that cause DGI.
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics
Authors: A-Elbasit Ishraga E , Alifrangis Michael , Khalil Insaf F , Bygbjerg Ib C , Masuadi Emad M , Elbashir Mustafa I , Giha Hayder A 
Published: August 2007

Abstract

Background
The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance.

Objective
To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance.

Method
Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA.

Results & conclusion
Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus.
Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression
Authors: Coiras Mayte , López-Huertas María Rosa , Rullas Joaquín , Mittelbrunn Maria , Alcamí José 
Published: August 2007

AbstractBackgroundIn HIV-infected T lymphocytes, NF-κB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-κB heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with IκB inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-κB and IκBα ratio. Actually, control of IκBα by cellular factors such as Murr-1 plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear IκBα in T cells after PMA activation. Now we attempt to determine the dynamics of NF-κB/IκBα nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD4+T lymphocytes.Results and conclusionWe show that the inhibition of the nuclear export by leptomycin B in resting CD4+T cells resulted in nuclear accumulation of both IκBα and p65/RelA, as well as formation of NF-κB/IκBα complexes. This proves the existence of a rapid shuttling of IκBα between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of IκBα in resting CD4+T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD4+T lymphocytes. On the other hand, basal NF-κB activity detected in resting CD4+T lymphocytes was related to low level HIV replication in these cells.
Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study
Authors: Junius Sara , Haustermans Karin , Bussels Barbara , Oyen Raymond , Vanstraelen Bianca , Depuydt Tom , Verstraete Jan , Joniau Steven , Van Poppel Hendrik 
Published: August 2007

Abstract

Background
To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC).

Methods
38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT.
Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria.
Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse.

Results
None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%.
Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales.
Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized.

Conclusion
This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion.
Regulation of VASP serine 157 phosphorylation in human neutrophils after stimulation by a chemoattractant
Authors: Eckert Rachael E , Jones Samuel L 
Published: August 2007

AbstractVasodilator-stimulated phosphoprotein (VASP) is a cAMP-dependent protein kinase A (PKA) substrate, which links cellular signaling to cytoskeletal organization and cellular movement. VASP is phosphorylated by PKA on serine 157 (Ser 157), which is required for VASP function in platelet adhesion and fibroblast motility. Our hypothesis is that PKA regulates neutrophil migration through VASP Ser 157 phosphorylation. The objective of this study was to characterize VASP Ser 157 phosphorylation in chemoattractant-stimulated neutrophils. fMLF, IL-8, leukotriene B4, or platelet-activating factor stimulation resulted in an initial increase in VASP Ser 157 phosphorylation, which was maximal by 30 s and was followed by a return to baseline Ser 157 phosphorylation by 10 min. In contrast, stimulation with the nonchemoattractant, proinflammatory cytokine TNF-α did not affect Ser 157 phosphorylation. The kinetics of fMLF-induced VASP Ser 157 phosphorylation levels closely matched the kinetics of the fold-change in F-actin levels in fMLF-stimulated neutrophils. fMLF-induced Ser 157 phosphorylation was abolished by pretreatment with the PKA inhibitor H89 and the adenylyl cyclase inhibitor SQ22536. In contrast, fMLF-induced Ser 157 phosphorylation was unaffected by the PKC inhibitors calphostin and staurosporine, the PKG inhibitors Rp-8-pCPT-cGMP and KT5823, and the calmodulin-dependent protein kinase II inhibitor KN-62. Inhibition of adhesion with EDTA or the anti-β2-integrin antibody IB4 did not alter fMLF-induced VASP phosphorylation or dephosphorylation. These data show that chemoattractant stimulation of human neutrophils induces a rapid and transient PKA-dependent VASP Ser 157 phosphorylation. Adhesion does not appear to be an important regulator of the state of VASP Ser 157 phosphorylation in chemoattractant-stimulated neutrophils.
Store-operated calcium entry mediates intracellular alkalinization, ERK1/2, and Akt/PKB phosphorylation in bovine neutrophils
Authors: Sandoval Alvaro J , Riquelme Jeanette P , Carretta María D , Hancke Juan L , Hidalgo María A , Burgos Rafael A 
Published: August 2007

AbstractNeutrophil’s responses to G protein-coupled chemoattractants are highly dependent on store-operated calcium (Ca2+) entry (SOCE). Platelet-activating factor (PAF), a primary chemoattractant, simultaneously increases cytosolic-free Ca2+, intracellular pH (pHi), ERK1/2, and Akt/protein kinase B (PKB) phosphorylation. In this study, we looked at the efficacy of several putative SOCE inhibitors and whether SOCE mediates intracellular alkalinization, ERK1/2, and Akt/PKB phosphorylation in bovine neutrophils. We demonstrated that the absence of external Ca2+ and the presence of EGTA reduced the intracellular alkalinization and ERK1/2 phosphorylation induced by PAF, apparently via SOCE influx inhibition. Next, we tested the efficacy of several putative SOCE inhibitors such as 2-aminoethoxydiphenyl borate (2-APB), capsaicin, flufenamic acid, 1-{β-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl}-1H-imidazole hydrochloride (SK&F 96365), and N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP2) on Ca2+ entry induced by PAF or thapsigargin. 2-APB was the most potent SOCE inhibitor, followed by capsaicin and flufenamic acid. Conversely, SK&F 96365 reduced an intracellular calcium ([Ca2+]i) peak but SOCE partially. BTP2 did not show an inhibitory effect on [Ca2+]i following PAF stimuli. 2-APB strongly reduced the pHi recovery, whereas the effect of flufenamic acid and SK&F 96365 was partial. Capsaicin and BTP2 did not affect the pHi changes induced by PAF. Finally, we observed that 2-APB reduced the ERK1/2 and Akt phosphorylation completely, whereas the inhibition with flufenamic acid was partial. The results suggest that 2-APB is the most potent SOCE inhibitor and support a key role of SOCE in pH alkalinization and PI-3K–ERK1/2 pathway control. Finally, 2-APB could be an important tool to characterize Ca2+ signaling in neutrophils.
CD31 delays phagocyte membrane repolarization to promote efficient binding of apoptotic cells
Authors: Vernon-Wilson Elizabeth F , Auradé Frédéric , Tian Lijun , Rowe Iain C M , Shipston Michael J , Savill John , Brown Simon B 
Published: August 2007

AbstractHomophilic ligation of CD31, a member of the Ig superfamily of adhesion receptors, promotes macrophage clearance of apoptotic leukocytes by a mechanism hitherto not described. In studying CD31-dependent regulation of β1-integrin binding of fibronectin-coated Latex™ beads, we discovered a role for the voltage-gated potassium channel ether-à-go-go-related gene (ERG) as a downstream effector of CD31 signaling. ERG was identified by tandem mass spectrometry as a 140-kDa protein, which was selectively modified with biotin following the targeted delivery of a biotin-transfer reagent to CD31 using Fab fragments of an anti-CD31 mAb. Similar results were obtained with macrophages but not K562 cells, expressing a truncated cytoplasmic tail of CD31, which failed to regulate bead binding. Colocalization of CD31 with ERG was confirmed by immunofluorescence for K562 cells and macrophages. We now demonstrate that the resting membrane potential of macrophages is depolarized on contact with apoptotic cells and that CD31 inhibits the ERG current, which would otherwise function to repolarize. Sustained depolarization favored the firm binding of phagocytic targets, a prerequisite for efficient engulfment. Our results identify ERG as a downstream effector of CD31 in the regulation of integrin-dependent binding of apoptotic cells by macrophages.
Statins and the Risk of Colorectal Cancer: A Meta-Analysis of 18 Studies Involving More Than 1.5 Million Patients
Authors: Bonovas Stefanos , Filioussi Kalitsa , Flordellis Christodoulos S. , Sitaras Nikolaos M. 
Published: August 2007

Purpose Statins have been suggested to prevent colorectal cancer. Several epidemiologic studies have evaluated this association, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods A comprehensive search for studies published up to December 2006 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates with 95% CIs were calculated using the fixed- and random-effects models. Results Eighteen studies involving more than 1.5 million participants contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of colorectal cancer either among RCTs (RR = 0.95; 95% CI, 0.80 to 1.13; n = 6) or among cohort studies (RR = 0.96; 95% CI, 0.84 to 1.11; n = 3). However, statin use was associated with a modest reduction in the risk of colorectal cancer among case-control studies (RR = 0.91; 95% CI, 0.87 to 0.96; n = 9). Low evidence of publication bias or heterogeneity was found. Conclusion Our meta-analysis results do not support the hypothesis that statins strongly reduce the risk of colorectal cancer, when taken for management of hypercholesterolemia. However, we cannot rule out a modest reduction in risk or an effect associated with higher doses of statins.
Irinotecan Fluorouracil Plus Leucovorin Is Not Superior to Fluorouracil Plus Leucovorin Alone As Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803
Authors: Saltz Leonard B. , Niedzwiecki Donna , Hollis Donna , Goldberg Richard M. , Hantel Alexander , Thomas James P. , Fields Anthony L.A. , Mayer Robert J. 
Published: August 2007

Purpose Randomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer. Methods A total of 1,264 patients were randomly assigned to receive either standard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV. The primary end points of the study were overall survival (OS) and disease-free survival (DFS). Results Treatment arms were well-balanced for patient characteristics and prognostic variables. There were no differences in either DFS or OS between the two treatment arms. Toxicity, including lethal toxicity, was significantly higher on the CPT-11 plus FU plus LV arm. Conclusion The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease, but did increase both lethal and nonlethal toxicity. This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment, and it reinforces the need for randomized controlled adjuvant studies.
Statistical Power of Negative Randomized Controlled Trials Presented at American Society for Clinical Oncology Annual Meetings
Authors: Bedard Philippe L. , Krzyzanowska Monika K. , Pintilie Melania , Tannock Ian F. 
Published: August 2007

Purpose To investigate the prevalence of underpowered randomized controlled trials (RCTs) presented at American Society of Clinical Oncology (ASCO) annual meetings. Methods We surveyed all two-arm phase III RCTs presented at ASCO annual meetings from 1995 to 2003 for which negative results were obtained. Post hoc calculations were performed using a power of 80% and an α level of .05 (two sided) to determine sample sizes required to detect small, medium, and large effect sizes. For studies reporting a proportion or time-to-event as primary end point, effect size was expressed as an odds ratio (OR) or hazard ratio (HR), respectively, with a small effect size defined as OR/HR ≥ 1.3, medium effect size defined as OR/HR ≥ 1.5, and large effect size defined as OR/HR ≥ 2.0. Logistic regression was used to identify factors associated with lack of statistical power. Results Of 423 negative RCTs for which post hoc sample size calculations could be performed, 45 (10.6%), 138 (32.6%), and 233 (55.1%) had adequate sample size to detect small, medium, and large effect sizes, respectively. Only 35 negative RCTs (7.1%) reported a reason for inadequate sample size. In a multivariable model, studies that were presented at oral sessions (P = .0038), multicenter studies supported by a cooperative group (P < .0001), and studies with time to event as primary outcome (P < .0001) were more likely to have adequate sample size. Conclusion More than half of negative RCTs presented at ASCO annual meetings do not have an adequate sample to detect a medium-size treatment effect.
Attitudes Toward Research Participation and Investigator Conflicts of Interest Among Advanced Cancer Patients Participating in Early Phase Clinical Trials
Authors: Gray Stacy W. , Hlubocky Fay J. , Ratain Mark J. , Daugherty Christopher K. 
Published: August 2007

Purpose Although both financial and intrinsic conflicts of interest can exist throughout the drug development process, little is known about how advanced cancer patients enrolled onto early phase clinical trials perceive investigator conflicts of interests. Patients and Methods We interviewed 102 advanced cancer patients enrolled onto phase I clinical trials using a standardized survey that addressed multiple issues related to conflicts of interest and research participation. Results Fifty-five percent of patients would not be concerned if physicians involved in running a clinical trial had financial conflicts of interest, whereas 65% of patients would be concerned if physicians involved in running a trial had intrinsic conflicts of interest. Most patients reported that potential conflicts of interest should be disclosed to patients on research trials (52% for financial conflicts of interest and 61% for more intrinsic conflicts of interest). Most patients would be willing to participate in trials after learning conflict of interest information (63%). Younger patients expressed more concern regarding financial conflict of interest than older patients (odds ratio, 6.22; 95% CI, 1.41 to 27.24). Conclusion Patients with advanced cancer are equally, if not more, concerned about traditional intrinsic conflicts of interest as compared with financial conflicts of interest. Patients generally believed that conflict of interest information should be disclosed to research participants. The fact that younger patients expressed more concern about financial conflicts of interest may have the potential to influence clinical trial participation rates. The actual impact of conflict of interest disclosure to research subjects needs to be evaluated more carefully.
Impact on physician workload and revenue following the creation of a specialty vein clinic within an academic vascular practice
Authors: Passman M A , Dattilo J B , Guzman R J , Naslund T C 
Published: August 2007

Objective: To evaluate the impact of creating a new specialty vein clinic within an academic-based vascular practice on clinical volume, physician workload and financial parameters. Methods: All patients evaluated and treated for varicose vein related problems within an academic vascular surgery practice were identified from institutional billing databases. Data were stratified according to the time period prior to establishing a vein clinic (PRE-VC) (1999–2001) and after creation of a vein clinic (POST-VC) (2002–2004). Clinical volume, physician workload and financial parameters were evaluated. Comparisons were made between vein (VEIN) and overall vascular (VASC) practice trends. Results: Comparison of clinical volume, physician workload and financial parameters in both the clinic and operative settings showed larger and more rapid expansion of the VEIN practice than VASC practice between PRE-VC and POST-VC time periods (VEIN vs. VASC growth, respectively: new patient clinic volume +162 vs. +18%; clinic relative value units (RVUs) +131 vs. +1%, clinic revenue +201 vs. +44%; procedure volume +348 vs. +19%; procedure RVUs +129 vs. +11%; procedure revenue +93 vs. +10%). Comparing the beginning of PRE-VC to the end of POST-VC time periods, an increasing trend was also present for the percentage of VEIN practice accounting for the total VASC practice (%VEIN PRE-VC to POST-VC, respectively: new patient clinic volume 11.6–30.2%; clinic RVUs 3.2–48.2%; clinic revenue 17.6–31.2%; procedure volume 3.1–14.3%; procedure RVUs 2.8–9.8%; procedure revenue 3.3–11.7%). Conclusion: Establishing a specialty vein clinic within an academic vascular practice can lead to a rapid expansion of clinical volume with associated increase in physician workload and reimbursement at a rate greater than that for the overall vascular practice.