bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stuttering priapism complicating Warfarin therapy in a patient with protein C deficiency
Authors: ABU SHAM’A R. A. H. , KUFRI F. H. , YASSIN I. H. 
Published: August 2007

SummaryPriapism is a rare disorder defined as a persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation. There are two types of priapism; ischemic low‐flow type or non‐ischemic high flow, with differing etiologies. Priapism associated with thrombophilia is a well‐recognized entity. However, the pathogenesis of this association is not fully understood. We report a rare case of recurrent (stuttering) priapism in a patient with protein C deficiency while maintained on Warfarin therapy. This therapy was also complicated by Warfarin‐induced skin necrosis.
Very early onset of an acute myeloid leukemia in an adult patient with B‐cell lymphoblastic leukemia
Authors: SHIVAROV V. , STOIMENOV A. , GALABOVA I. , BALATZENKO G. , GUENOVA M. 
Published: August 2007

SummaryWe report on a case of a 30‐year‐old male with acute B‐lymphoblastic leukemia (B‐ALL) with immunophenotype CD19+, CD22+, CD20+, CD10+, with aberrant expression of CD13 and CD117, and IgH gene rearrangements. Three months after treatment with GMALL‐2003 and Ida/FLAG protocols bone marrow showed predominance of blasts with myeloid morphology and phenotype MPO+, CD13+, CD33+, CD64+, CD15+, CD56+, EVI‐1 gene overexpression and lack of IgH rearrangements. The case is the first report of a very early emergence of myeloid leukemia during the induction treatment for B‐ALL in an adult patient. Different pathogenetic mechanisms are discussed – clonal evolution or selection, lineage switch or development of a de novo or therapy‐induced leukemia.
Discovery of Novel DNA Gyrase Inhibitors by High-Throughput Virtual Screening
Authors: Ostrov David A. , Hernández Prada José A. , Corsino Patrick E. , Finton Kathryn A. , Le Nhan , Rowe Thomas C. 
Published: August 2007

ABSTRACT

The bacterial type II topoisomerases DNA gyrase and topoisomerase IV are validated targets for clinically useful quinolone antimicrobial drugs. A significant limitation to widely utilized quinolone inhibitors is the emergence of drug-resistant bacteria due to an altered DNA gyrase. To address this problem, we have used structure-based molecular docking to identify novel drug-like small molecules that target sites distinct from those targeted by quinolone inhibitors. A chemical ligand database containing approximately 140,000 small molecules (molecular weight, <500) was molecularly docked onto two sites of
Escherichia coli
DNA gyrase targeting (i) a previously unexplored structural pocket formed at the dimer interface of subunit A and (ii) a small region of the ATP binding pocket on subunit B overlapping the site targeted by coumarin and cyclothialidine drugs. This approach identified several small-molecule compounds that inhibited the DNA supercoiling activity of purified
E. coli
DNA gyrase. These compounds are structurally unrelated to previously identified gyrase inhibitors and represent potential scaffolds for the optimization of novel antibacterial agents that act on fluoroquinolone-resistant strains.
Optimization of the Dosage of Flucytosine in Combination with Amphotericin B for Disseminated Candidiasis: a Pharmacodynamic Rationale for Reduced Dosing
Authors: Hope William W. , Warn Peter A. , Sharp Andrew , Reed Paul , Keevil Brian , Louie Arnold , Walsh Thomas J. , Denning David W. , Drusano George L. 
Published: August 2007

ABSTRACT
Amphotericin B and flucytosine (5FC) have an additive effect when used for disseminated candidiasis. Here, we bridge the results of an experimental pharmacodynamic study to humans and demonstrate that a 5FC dosage of 25 mg/kg of body weight/day in four divided doses in combination with amphotericin B produces near-maximal effect.
Pseudomonas aeruginosa
May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream Infections
Authors: Hocquet Didier , Berthelot Philippe , Roussel-Delvallez Micheline , Favre Roger , Jeannot Katy , Bajolet Odile , Marty Nicole , Grattard Florence , Mariani-Kurkdjian Patricia , Bingen Edouard , Husson Marie-Odile , Couetdic Gérard , Plésiat Patrick 
Published: August 2007

ABSTRACT

In this study, we systematically investigated the resistance mechanisms to β-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of
Pseudomonas aeruginosa
. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic
P. aeruginosa
strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that
P. aeruginosa
may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary β-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant
P. aeruginosa
may remain fully pathogenic.
Ehrlichia canis
gp200 Contains Dominant Species-Specific Antibody Epitopes in Terminal Acidic Domains
Authors: Nethery Kimberly A. , Doyle C. Kuyler , Zhang Xiaofeng , McBride Jere W. 
Published: August 2007

ABSTRACT

Species-specific antibody epitopes within several major immunoreactive protein orthologs of
Ehrlichia
species have recently been identified and molecularly characterized. In this study, dominant B-cell epitopes within the acidic (pI 5.35) ankyrin repeat-containing 200-kDa major immunoreactive protein (gp200) of
Ehrlichia canis
were defined. The
E. canis
gp200 gene (4,263 bp; 1,421 amino acids) was cloned and expressed as four (N-terminal, 1,107 bp; N-internal, 910 bp; C-internal, 1,000 bp; and C-terminal, 1,280 bp) overlapping recombinant proteins. The N-terminal, C-internal, and C-terminal polypeptides (369, 332, and 426 amino acids, respectively) were strongly recognized by antibody, and the major epitope(s) in these polypeptides was mapped to four polypeptide regions (40 to 70 amino acids). Smaller overlapping recombinant polypeptides (14 to 15 amino acids) spanning these regions identified five strongly immunoreactive species-specific epitopes that exhibited conformational dependence. The majority of the epitopes (four) were located in two strongly acidic (pI 4 to 4.9) domains in the distal N- and C-terminal regions of the protein flanking the centralized ankyrin domain-containing region. The amino acid content of the epitope-containing domains included a high proportion of strongly acidic amino acids (glutamate and aspartate), and these domains appear to have important biophysical properties that influence the antibody response to gp200.
Listeriolysin O Secreted byListeria monocytogenesinto the Host Cell Cytosol Is Degraded by the N-End Rule Pathway
Authors: Schnupf Pamela , Zhou Jianmin , Varshavsky Alexander , Portnoy Daniel A. 
Published: August 2007

ABSTRACTThe intracellular pathogenListeria monocytogenesescapes from a phagosomal compartment into the cytosol by secreting the pore-forming cytolysin listeriolysin O (LLO). During the proliferation ofL. monocytogenesbacteria in the mammalian cell cytosol, the secreted LLO is targeted for degradation by the ubiquitin system. We report here that LLO is a substrate of the ubiquitin-dependent N-end rule pathway, which recognizes LLO through its N-terminal Lys residue. Specifically, we demonstrated by reverse-genetic and pharmacological methods that LLO was targeted for degradation by the N-end rule pathway in reticulocyte extracts and mouse NIH 3T3 cells and after its secretion by intracellular bacteria into the mouse cell cytosol. Replacing the N-terminal Lys of LLO with a stabilizing residue such as Val increased the in vivo half-life of LLO but did not strongly affect the intracellular growth or virulence ofL. monocytogenes. Nevertheless, this replacement decreased the virulence ofL. monocytogenesby nearly twofold, suggesting that a destabilizing N-terminal residue of LLO may stem from positive selection during the evolution of this and related bacteria. A double mutant strain ofL. monocytogenesin which upregulated secretion of LLO was combined with a stabilizing N-terminal residue was severely toxic to infected mammalian cells, resulting in reduced intracellular growth of bacteria and an ∼100-fold-lower level of virulence. In summary, we showed that LLO is degraded by the N-end rule pathway and that the degradation of LLO can reduce the toxicity ofL. monocytogenesduring infection, a property of LLO that may have been selected for its positive effects on fitness during the evolution ofL. monocytogenes.
Risk of Bladder Cancer Associated with Family History of Cancer: Do Low-Penetrance Polymorphisms Account for the Increase in Risk?
Authors: Murta-Nascimento Cristiane , Silverman Debra T. , Kogevinas Manolis , García-Closas Montserrat , Rothman Nathaniel , Tardón Adonina , García-Closas Reina , Serra Consol , Carrato Alfredo , Villanueva Cristina , Dosemeci Mustafa , Real Francisco X. , Malats Núria 
Published: August 2007

Abstract
The relationship between family history of cancer in first-degree relatives and risk of bladder cancer was examined in the Spanish Bladder Cancer Study. Information on family history of cancer was obtained for 1,158 newly diagnosed bladder cancer cases and 1,244 controls included in 18 hospitals between 1998 and 2001. A total of 464 (40.1%) cases and 436 (35.1%) controls reported a family history of cancer in ≥1 relative [odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.11-1.59]; the OR was 1.23 (95% CI, 1.01-1.50) among those with only one relative affected and 1.67 (95% CI, 1.23-2.29) among those with ≥2 affected relatives (Ptrend = 0.0004). A greater risk of bladder cancer was observed among those diagnosed at age ≤45 years (OR, 2.67; 95% CI, 1.10-6.50) compared with those diagnosed over age 45 years (OR, 1.27; 95% CI, 1.06-1.52). The OR of bladder cancer among subjects reporting a family history of cancer of the bladder was 2.34 (95% CI, 0.95-5.77). Statistically significant associations emerged between bladder cancer risk and family history of cancer of the esophagus, lung, prostate, and brain. The OR of bladder cancer for those reporting family history of bladder cancer was 4.76 (95% CI, 1.25-18.09) among NAT2-slow acetylators and 1.17 (95% CI, 0.17-7.86) among NAT2-rapid/intermediate acetylators (Pinteraction = 0.609). Among individuals with GSTM1 null and present genotypes, the corresponding ORs were 2.91 (95% CI, 0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (Pinteraction = 0.712). Limitations of our study are small sample size in subgroup analyses, reliability of family history data, and possible residual confounding by shared environmental exposures. Overall, our findings support the hypothesis that genetic factors play a role in bladder cancer etiology. Whether these correspond to low-penetrance cancer-predisposing polymorphisms acting together and/or interacting with environmental factors warrants further research. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1595–600)
Modulation of Human Glutathione S-Transferases by Polyphenon E Intervention
Authors: Chow H.-H. Sherry , Hakim Iman A. , Vining Donna R. , Crowell James A. , Tome Margaret E. , Ranger-Moore James , Cordova Catherine A. , Mikhael Dalia M. , Briehl Margaret M. , Alberts David S. 
Published: August 2007

Abstract
Purpose: Green tea consumption has been associated with decreased risk of certain types of cancers in humans. Induction of detoxification enzymes has been suggested as one of the biochemical mechanisms responsible for the cancer-preventive effect of green tea. We conducted this clinical study to determine the effect of repeated green tea polyphenol administration on a major group of detoxification enzymes, glutathione S-transferases (GST).
Methods: A total of 42 healthy volunteers underwent a 4-week washout period by refraining from tea or tea-related products. At the end of the washout period, a fasting blood sample was collected, and plasma and lymphocytes were isolated for assessment of GST activity and level. Following the baseline evaluation, study participants underwent 4 weeks of green tea polyphenol intervention in the form of a standardized Polyphenon E preparation at a dose that contains 800 mg epigallocatechin gallate (EGCG) once a day. Polyphenon E was taken on an empty stomach to optimize the oral bioavailability of EGCG. Upon completion of the intervention, samples were collected for postintervention GST assessment.
Results: Four weeks of Polyphenon E intervention enhanced the GST activity in blood lymphocytes from 30.7 ± 12.2 to 35.1 ± 14.3 nmol/min/mg protein, P = 0.058. Analysis based on baseline activity showed that a statistically significant increase (80%, P = 0.004) in GST activity was observed in individuals with baseline activity in the lowest tertile, whereas a statistically significant decrease (20%, P = 0.02) in GST activity was observed in the highest tertile. In addition, Polyphenon E intervention significantly increased the GST-π level in blood lymphocytes from 2,252.9 ± 734.2 to 2,634.4 ± 1,138.3 ng/mg protein, P = 0.035. Analysis based on baseline level showed that this increase was only significant (P = 0.003) in individuals with baseline level in the lowest tertile, with a mean increase of 80%. Repeated Polyphenon E administration had minimal effects on lymphocyte GST-μ and plasma GST-α levels. There was a small but statistically significant decrease (8%, P = 0.003) in plasma GST-α levels in the highest tertile.
Conclusions: We conclude that 4 weeks of Polyphenon E administration resulted in differential effects on GST activity and level based on baseline enzyme activity/level, with GST activity and GST-π level increased significantly in individuals with low baseline enzyme activity/level. This suggests that green tea polyphenol intervention may enhance the detoxification of carcinogens in individuals with low baseline detoxification capacity. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1662–6)
Interleukin-10 Gene (IL10) Polymorphisms and Human Papillomavirus Clearance among Immunosuppressed Adolescents
Authors: Shrestha Sadeep , Wang Chengbin , Aissani Brahim , Wilson Craig M. , Tang Jianming , Kaslow Richard A. 
Published: August 2007

AbstractPersistent infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer, and HPV clearance seems to be under host genetic influence. This study evaluated associations between three single nucleotide polymorphisms in the IL10 promoter and clearance of low- or high-risk HPV infection in a cohort of 226 largely HIV-1–infected African-American adolescent females. Among immunosuppressed individuals (HIV-1 seropositive and CD4+ ≤ 500), the GCC haplotype in the IL10 promoter was associated with reduced clearance of high-risk HPV16-like [relative hazard (RH), 0.46; 95% confidence interval (95% CI), 0.25-0.85; P = 0.01], HPV18-like (RH, 0.33; 95% CI, 0.16-0.67; P = 0.002), and any high-risk type (RH, 0.37; 95% CI, 0.20-0.68; P = 0.002) but not with low-risk HPV type (RH, 0.60; 95% CI, 0.29-1.25; P = 0.17). No associations were observed among immunocompetent individuals. The IL10 GCC haplotype has been associated with production of relatively high levels of interleukin (IL)-10, which could (a) inhibit cytokines such as IL-2, TNF-α, IL-4, IL-6, and IL-12 that are involved in the TH1-TH2 immunoregulation; (b) down-regulate expression of MHC class I and class II molecules; or (c) induce the transcription of early promoter of HPV, all potentially contributing to duration of HPV infection among immunosuppressed individuals. These results support the hypothesis that IL10 polymorphisms influence the clearance of infection with high-risk HPV types and warrant further studies of host genetic control of HPV pathogenesis and cervical cancer in the context of immunosuppression. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1626–32)
DNA Quantification of Whole Genome Amplified Samples for Genotyping on a Multiplexed Bead Array Platform
Authors: Hansen Helen M. , Wiemels Joseph L. , Wrensch Margaret , Wiencke John K. 
Published: August 2007

Abstract
Whole genome amplification (WGA) permits genotyping DNA samples of limited quantity, expanding the number of samples available for genetic epidemiology studies. WGA, however, produces various nucleic acid side products that may interfere with accurate DNA quantification and further analysis. Although quality control of whole genome amplified DNA (wgaDNA) before genotyping is essential to prevent failed or poor genotyping results, little information is available to choose the best method for wgaDNA quantification. Therefore, we quantified wgaDNA from 54 buccal or poor quality blood samples by four methods: UV absorbance, PicoGreen fluorescence calibrated with λ bacteriophage or calf thymus DNA, and absolute quantification by real-time PCR amplification of human-specific Alu Yd6. We then genotyped these wgaDNA samples and paired high-quality genomic DNA samples on a custom 384-plex Illumina Golden Gate Panel. Of the 54 paired samples, 39 gave high concordance (&gt;99%), whereas 7 had moderate concordance (&gt;90-99%) and 8 had poor concordance (≤90%) of wgaDNA and genomic DNA genotyping results. Quantitative PCR of Alu was the only wgaDNA quantification method to distinguish wgaDNA samples that gave high, moderate, or low concordance results (i.e., wgaDNA quantities in the high, moderate, and poor concordance groups ranged at 4.14-118.32, 0.29-2.19, and 0.01-0.27 ng/μL, respectively). Human-specific quantitative PCR is a highly useful guide for determining the suitability of wgaDNA before high-throughput single-nucleotide polymorphism analysis. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1686–90)
Maximizing the Benefits of Model-Based Period Analysis of Cancer Patient Survival
Authors: Brenner Hermann , Hakulinen Timo 
Published: August 2007

Abstract
Period analysis has been shown to provide more up-to-date estimates of cancer survival than traditional methods of survival analysis. There is, however, a tradeoff between up-to-dateness and precision of period survival estimates: increasing up-to-dateness by restricting the analysis to a relatively short period, such as the most recent calendar year, goes along with loss of precision. Recently, a model-based approach was proposed, in which more precise period survival estimates for the most recent year can be obtained through modeling of survival trends within a recent 5-year period. We assess possibilities to extend the time window used for modeling to come up with even more precise, but equally accurate and up-to-date estimates of prognosis. Empirical evaluation using data from the Finnish Cancer Registry shows that extension of the time window to about 10 years provides, in most cases, as accurate results as using a 5-year time window (whereas further extension may lead to considerably less accurate results in some cases). Using 10-year time windows for modeling, SEs of survival estimates can be approximately halved compared with conventional period survival estimates for the most recent calendar year. Furthermore, we present a modification of the modeling approach, which allows extension to 10-year time windows to be achieved without the need to include additional cohorts of patients diagnosed longer time ago and which provides similarly accurate survival estimates at comparable levels of precision in most cases. Our analyses indicate opportunities to further maximize benefits of model-based period analysis of cancer survival. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1675–81)
A Method of Producing Carcinoma in Upper Aerodigestive Tree and Esophagus of the Syrian Golden Hamster Using Wounding and Instillation of N-Methylnitrosourea
Authors: Estensen Richard D. , Anderson W. Robert , Galbraith Arthur R. , Hartle Donna E. , Jordan Margaret M. , Ondrey Frank G. , Wattenberg Lee W. 
Published: August 2007

Abstract
Details of a method for producing carcinoma of the aerodigestive tree of the Syrian golden hamster and the use of this model to evaluate putative agents for chemoprevention of these carcinomas are described. The method produces a majority of squamous carcinomas of the trachea and glottis that follow squamous metaplasia of respiratory epithelium. In addition, seen are adenocarcinomas arising in glands of the respiratory tree. Squamous carcinomas of the digestive epithelium arise in primary squamous epithelium. These tumors of digestive epithelium have a growth pattern that differs from that of the respiratory epithelium in that they grow and invade without filling the epithelial layer with tumor cells.(Cancer Epidemiol Biomarkers Prev 2007;16(8):1644–50) (Cancer Epidemiol Biomarkers Prev 2007;16(8):1644–50)
Whole-Genome Amplification of Oral Rinse Self-Collected DNA in a Population-Based Case-Control Study of Breast Cancer
Authors: Liang Xueying , Trentham-Dietz Amy , Titus-Ernstoff Linda , Newcomb Polly A. , Welch Rober A. , Hutchinson Amy A. , Hampton John M. , Sutcliffe Cara B. , Haines Jonathan L. , Egan Kathleen M. 
Published: August 2007

Abstract
The availability of large amounts of genomic DNA (gDNA) is the limiting factor for many of the molecular biology assays in genetic epidemiologic studies. Whole-genome amplification using multiple displacement amplification is used to amplify a representative sample of gDNA from small amounts of gDNA to optimize gDNA yield. We collected oral rinse DNA samples through the mail from 3,377 women enrolled in a population-based U.S. breast cancer case-control study and did whole-genome amplification by multiple displacement amplification. Genotyping was done for 66 single nucleotide polymorphisms (SNP) in 18 candidate susceptibility genes using amplified DNA with genomic replicates included for quality control. The concordance rates (percentages of agreement) in 95 quality control replicates of gDNA and amplified DNA for 66 SNPs ranged from 88% to 100% (median, 97%). The average allelic error rate was 0.9%. However, in further analyses based on the full control series (n = 1,492), &gt;60% of the SNPs failed tests for Hardy-Weinberg equilibrium (P &lt; 0.05), with evidence of heterozygote loss in the great majority. Even eliminating the 9% of samples with lower quality or input DNA, tests for Hardy-Weinberg equilibrium indicated persistent allele bias in nearly a third of the SNPs. Whole-genome amplification may introduce substantial allele amplification bias in gDNA collected using a common protocol in population-based epidemiologic studies. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1610–4)