bluuebunny/crossref_metadata_2025_split huggingface dataset:
A reporting system for the assessment of chemotherapy toxicity
Authors: Sassi Graziella , Striano Barbara , Merlo Ugo A 
Published: July 2005

Purpose. Toxicity may distress patients and cause delay or a discontinuance of scheduled chemotherapies. A key issue is to create a reporting system in order to assess toxicities and also evaluate treatments. Methods. In the Oncology Unit 3000 intravenous chemotherapies are administered each year, mostly in the day hospital. In summer 2002, oncologists and pharmacists agreed to assess myelosuppression and gastrointestinal toxicity of grades 3 and 4. Pharmacists designed a form and a database in order to collect toxicity data for every patient. The oncologist records type and grade of toxicity (according to the NCI CTC) on the patient chart before chemotherapy commences. During the validation of computerized prescriptions the pharmacist collects data about possible toxicities of every grade. Results. From August-October 2002, 675 chemotherapies were administered. Seventy-two patients developed GI toxicity at various grades, nine of grade 3 and two of grade 4. Regimens with fluorouracil, carboplatin, cisplatin and oxaliplatin were highly involved in GI toxicity. Eighty-seven patients developed myelosuppression, two of grade 3 and 33 of grade 4. Regimens with epirubicin, cyclophosphamide, paclitaxel, cisplatin and carboplatin were highly involved in myelosuppression. After the first report, oncologists and pharmacists decided to stop collecting data in order to improve the reporting system and to plan regular meetings. Conclusions. A reliable reporting system is a valuable tool for oncologists to manage toxicity and to evaluate chemotherapy regimens. Assessing chemotherapy toxicity is a good opportunity for pharmacists to take part in preventing toxicity and reducing patient’s discomfort.
α1-Adrenergic Receptor Antagonists: Novel Therapy for Pituitary Adenomas
Authors: Fernando Manory A. , Heaney Anthony P. 
Published: July 2005

Abstract
Pituitary tumors are common and cause considerable morbidity due to local invasion and altered hormone secretion. Doxazosin (dox), a selective α1-adrenergic receptor antagonist, used to treat hypertension, also inhibits prostate cancer cell proliferation. We examined the effects of dox on murine and human pituitary tumor cell proliferation in vitro and in vivo. dox treatment inhibited proliferation of murine pituitary tumor cells, induced G0-G1 cell cycle arrest, and reduced phosphorylated retinoblastoma levels. In addition, increased annexin-fluorescein isothiocyanate immunoreactivity and cleaved caspase-3 levels, in keeping with dox-mediated apoptosis, were observed in the human and murine pituitary tumor cells, and dox administration to mice, harboring corticotroph tumors, decreased tumor growth and reduced plasma ACTH levels. dox-mediated antiproliferative and proapoptotic actions were not confined to α-adrenergic receptor-expressing pituitary tumor cells and were unaffected by cotreatment with the α-adrenergic receptor blocker, phenoxybenzamine. dox treatment led to reduced phosphorylated inhibitory κB (IκB)-α expression, and nuclear factor-κB transcription and decreased basal and TNFα-induced proopiomelanocortin transcriptional activation. These results demonstrate that the selective α1-adrenergic receptor antagonist dox inhibits pituitary tumor cell growth in vitro and in vivo by mechanisms that are in part independent of its α-adrenergic receptor-blocking actions and involve down-regulation of nuclear factor-κB signaling. dox is proposed as a possible novel medical therapy for pituitary tumors.
Challenges in Detecting the Abuse of Growth Hormone in Sport
Authors: McHugh Cathy M , Park Roderick T , Sönksen Peter H , Holt Richard IG 
Published: July 2005

Abstract
Background: Growth hormone (GH) is reputed to be in widespread use in the sporting arena as a performance-enhancing agent and is on the list of banned substances published by the World Anti-Doping Agency. The detection of GH abuse poses many challenges. Unlike many substances of abuse, such as synthetic anabolic steroids, GH is a naturally occurring substance; therefore, demonstration of exogenous administration must rely on detecting concentrations in excess of an established reference interval. The purpose of this review is to discuss the methodologies being developed to detect GH abuse.
Methods: We undertook a comprehensive search using multiple electronic databases and hand searches of reference lists of articles. The data for this review reflect our academic interests and experience through work on the GH-2000 and GH-2004 projects.
Results: Two approaches have been taken to detect GH abuse. The first is based on assessment of the effect of exogenous GH on pituitary GH isoforms, and the second is based on measurement of markers of GH action. The advantages of each approach and the difficulties encountered with each technique, as well as future concepts in detection, are discussed.
Conclusion: Although there are substantial challenges for the detection of GH, methodologies now exist to detect GH abuse with reasonable sensitivity and specificity.
Use of Protein:Creatinine Ratio Measurements on Random Urine Samples for Prediction of Significant Proteinuria: A Systematic Review
Authors: Price Christopher P , Newall Ronald G , Boyd James C 
Published: July 2005

Abstract
Background: Proteinuria is recognized as an independent risk factor for cardiovascular and renal disease and as a predictor of end organ damage. The reference test, a 24-h urine protein estimation, is known to be unreliable. A random urine protein:creatinine ratio has been shown to correlate with a 24-h estimation, but it is not clear whether it can be used to reliably predict the presence of significant proteinuria.
Methods: We performed a systematic review of the literature on measurement of the protein:creatinine ratio on a random urine compared with the respective 24-h protein excretion. Likelihood ratios were used to determine the ability of a random urine protein:creatinine ratio to predict the presence or absence of proteinuria.
Results: Data were extracted from 16 studies investigating proteinuria in several settings; patient groups studied were primarily those with preeclampsia or renal disease. Sensitivities and specificities for the tests ranged between 69% and 96% and 41% and 97%, respectively, whereas the positive and negative predictive values ranged between 46% and 95% and 45% and 98%, respectively. The positive likelihood ratios ranged between 1.8 and 16.5, and the negative likelihood ratios between 0.06 and 0.35. The cumulative negative likelihood ratio for 10 studies on proteinuria in preeclampsia was 0.14 (95% confidence interval, 0.09–0.24).
Conclusion: The protein:creatinine ratio on a random urine specimen provides evidence to “rule out” the presence of significant proteinuria as defined by a 24-h urine excretion measurement.
Clinical Restenosis after Coronary Stent Implantation Is Associated with the Heme Oxygenase-1 Gene Promoter Polymorphism and the Heme Oxygenase-1 +99G/C Variant
Authors: Gulesserian Talin , Wenzel Catharina , Endler Georg , Sunder-Plassmann Raute , Marsik Claudia , Mannhalter Christine , Iordanova Nelly , Gyöngyösi Mariann , Wojta Johann , Mustafa Stefan , Wagner Oswald , Huber Kurt 
Published: July 2005

AbstractBackground: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation.Methods: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography.Results: Carriers of the long allele of the HO-1 gene promoter (&gt;29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR) = 1.9; 95% confidence interval (95% CI), 1.0–3.4; P = 0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR = 3.4; 95% CI, 1.2–9.1; P = 0.017) in nonsmokers than in smokers (OR = 2.0; 95% CI, 0.7–5.2; P = 0.18).Conclusions: The long allele of the HO-1 gene promoter (&gt;29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the &gt;29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.
Separation of β2-Transferrin by Denaturing Gel Electrophoresis to Detect Cerebrospinal Fluid in Ear and Nasal Fluids
Authors: Görögh Tibor , Rudolph Pierre , Meyer Jens Eduard , Werner Jochen A , Lippert Burkard M , Maune Steffen 
Published: July 2005

AbstractBackground: Cerebrospinal fluid (CSF) leakage is a critical condition with a substantial risk of meningitis. We investigated the use of transferrin isoform analysis as a diagnostic marker for detection of CSF leakage in fluid samples.Methods: We analyzed 241 samples from patients with CSF leakage, most commonly presenting as otorrhea or rhinorrhea, by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent Western blotting and immunostaining for transferrin. Tears, saliva, nasal fluid, and ear secretions (20 samples each) were analyzed in parallel, and normal human serum served as a control in each experiment. We compared the minimum volume of added CSF that could be detected in secretions by our assay with the minimum volume detected by the prostaglandin-D synthase (β-trace) test. CSF was admixed with blood in different proportions to determine the influence of blood contamination on the transferrin pattern.Results: In all CSF samples, β1- and β2-transferrin were present in nearly equal amounts. In tears and ear secretions, β2-transferrin migrated in the gel in the same manner as in CSF, but its concentration was noticeably lower than that of β1-transferrin, a difference that allowed a clear distinction from the transferrin pattern of CSF. In saliva, both transferrin isoforms were also present but could be distinguished from those of other fluids by electrophoretic migration pattern rather than relative concentrations. With the β-trace test, a minimum of 5 μL of CSF was needed for detection, whereas our β2-transferrin assay yielded a signal of comparable intensity with a minimum of 2 μL of CSF.Conclusion: Analysis of the transferrin microheterogeneity pattern by SDS-PAGE for the identification of CSF leakage is a highly sensitive and specific method that merits consideration as a routine technique.
Genomewide Scan for Anal Atresia in Swine Identifies Linkage and Association With a Chromosome Region onSus scrofaChromosome 1
Authors: Wiedemann Sabine , Fries Ruedi , Thaller Georg 
Published: July 2005

AbstractAnal atresia is a rare and severe disorder in swine occurring with an incidence of 0.1–1.0%. A whole-genome scan based on affected half-sibs was performed to identify susceptibility loci for anal atresia. The analysis included 27 families with a total of 95 animals and 65 affected piglets among them. Animals were genotyped for 126 microsatellite markers distributed across the 18 autosomal porcine chromosomes and the X chromosome, covering an estimated 2080 cM. Single-point and multipoint nonparametric linkage scores were calculated using the computer package ALLEGRO 1.0. Significant linkage results were obtained for chromosomes 1, 3, and 12. Markers on these chromosomes and additionally on chromosomes for which candidate genes have been postulated in previous studies were subjected to the transmission disequilibrium test (TDT). The test statistic exceeded the genomewide significance level for adjacent markers SW1621 (P = 7 × 10−7) and SW1902 (P = 3 × 10−3) on chromosome 1, supporting the results of the linkage analysis. A specific haplotype associated with anal atresia that could prove useful for selection against the disorder was revealed. Suggestive linkage and association were also found for markers S0081 on chromosome 9 and SW957 on chromosome 12.
Multiple Signatures of Positive Selection Downstream of Notch on the X Chromosome in Drosophila melanogaster
Authors: DuMont Vanessa Bauer , Aquadro Charles F 
Published: July 2005

Abstract
To identify genomic regions affected by the rapid fixation of beneficial mutations (selective sweeps), we performed a scan of microsatellite variability across the Notch locus region of Drosophila melanogaster. Nine microsatellites spanning 60 kb of the X chromosome were surveyed for variation in one African and three non-African populations of this species. The microsatellites identified an ∼14-kb window for which we observed relatively low levels of variability and/or a skew in the frequency spectrum toward rare alleles, patterns predicted at regions linked to a selective sweep. DNA sequence polymorphism data were subsequently collected within this 14-kb region for three of the D. melanogaster populations. The sequence data strongly support the initial microsatellite findings; in the non-African populations there is evidence of a recent selective sweep downstream of the Notch locus near or within the open reading frames CG18508 and Fcp3C. In addition, we observe a significant McDonald-Kreitman test result suggesting too many amino acid fixations species wide, presumably due to positive selection, at the unannotated open reading frame CG18508. Thus, we observe within this small genomic region evidence for both recent (skew toward rare alleles in non-African populations) and recurring (amino acid evolution at CG18508) episodes of positive selection.
Evidence of a Major Gene From Bayesian Segregation Analyses of Liability to Osteochondral Diseases in Pigs
Authors: Kadarmideen Haja N , Janss Luc L G 
Published: July 2005

AbstractBayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384–37.81), compared to the polygenic variance ($\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\sigma}}_{\mathrm{u}}^{2}\) \end{document}$). Consequently, heritabilities for a mixed inheritance (range 0.65–0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38–0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on $\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\sigma}}_{\mathrm{u}}^{2}\) \end{document}$, showed significant improvement in marginal distributions and accuracy of parameters. MITM with a “reduced polygenic model” for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an “individual polygenic model.” In all cases, “shrinkage estimators” for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans.
Segmental Structure of the Brassica napus Genome Based on Comparative Analysis With Arabidopsis thaliana
Authors: Parkin Isobel A P , Gulden Sigrun M , Sharpe Andrew G , Lukens Lewis , Trick Martin , Osborn Thomas C , Lydiate Derek J 
Published: July 2005

Abstract
Over 1000 genetically linked RFLP loci in Brassica napus were mapped to homologous positions in the Arabidopsis genome on the basis of sequence similarity. Blocks of genetically linked loci in B. napus frequently corresponded to physically linked markers in Arabidopsis. This comparative analysis allowed the identification of a minimum of 21 conserved genomic units within the Arabidopsis genome, which can be duplicated and rearranged to generate the present-day B. napus genome. The conserved regions extended over lengths as great as 50 cM in the B. napus genetic map, equivalent to ∼9 Mb of contiguous sequence in the Arabidopsis genome. There was also evidence for conservation of chromosome landmarks, particularly centromeric regions, between the two species. The observed segmental structure of the Brassica genome strongly suggests that the extant Brassica diploid species evolved from a hexaploid ancestor. The comparative map assists in exploiting the Arabidopsis genomic sequence for marker and candidate gene identification within the larger, intractable genomes of the Brassica polyploids.
Quantitative Trait Locus Analysis of Longitudinal Quantitative Trait Data in Complex Pedigrees
Authors: Macgregor Stuart , Knott Sara A , White Ian , Visscher Peter M 
Published: July 2005

Abstract
There is currently considerable interest in genetic analysis of quantitative traits such as blood pressure and body mass index. Despite the fact that these traits change throughout life they are commonly analyzed only at a single time point. The genetic basis of such traits can be better understood by collecting and effectively analyzing longitudinal data. Analyses of these data are complicated by the need to incorporate information from complex pedigree structures and genetic markers. We propose conducting longitudinal quantitative trait locus (QTL) analyses on such data sets by using a flexible random regression estimation technique. The relationship between genetic effects at different ages is efficiently modeled using covariance functions (CFs). Using simulated data we show that the change in genetic effects over time can be well characterized using CFs and that including parameters to model the change in effect with age can provide substantial increases in power to detect QTL compared with repeated measure or univariate techniques. The asymptotic distributions of the methods used are investigated and methods for overcoming the practical difficulties in fitting CFs are discussed. The CF-based techniques should allow efficient multivariate analyses of many data sets in human and natural population genetics.
Blocked Recombination Along the Mating-Type Chromosomes of Neurospora tetrasperma Involves Both Structural Heterozygosity and Autosomal Genes
Authors: Jacobson David J 
Published: July 2005

Abstract
The Neurospora tetrasperma mating-type chromosomes have been shown to be structurally heterozygous by reciprocal introgression of these chromosomes between N. tetrasperma and N. crassa. This structural heterozygosity correlates with both a previously described recombination block and cytologically visible unpaired chromosomes at pachytene. Genes on the autosomes are also implicated in blocking recombination.
Discrepancies Between Recombination Frequencies and Physical Distances in Aspergillus nidulans: Implications for Gene Identification
Authors: Espeso Eduardo A , Cobeño Laura , Arst Herbert N 
Published: July 2005

Abstract
A rapid route to gene molecular identification involves using recombination frequencies in locating mutational sequence changes. We describe a case where the recombination frequency is deceptively low, probably reflecting centromere proximity. Recombination frequencies are greatly reduced near the centromeres on the right arms of chromosomes III and IV of Aspergillus nidulans.
Regulation of Histone Deposition Proteins Asf1/Hir1 by Multiple DNA Damage Checkpoint Kinases in Saccharomyces cerevisiae
Authors: Sharp Judith A , Rizki Gizem , Kaufman Paul D 
Published: July 2005

Abstract
CAF-1, Hir proteins, and Asf1 are histone H3/H4 binding proteins important for chromatin-mediated transcriptional silencing. We explored genetic and physical interactions between these proteins and S-phase/DNA damage checkpoint kinases in the budding yeast Saccharomyces cerevisiae. Although cells lacking checkpoint kinase Mec1 do not display defects in telomeric gene silencing, silencing was dramatically reduced in cells lacking both Mec1 and the Cac1 subunit of CAF-1. Silencing was restored in cac1Δ and cac1Δ mec1Δ cells upon deletion of Rad53, the kinase downstream of Mec1. Restoration of silencing to cac1Δ cells required both Hir1 and Asf1, suggesting that Mec1 counteracts functional sequestration of the Asf1/Hir1 complex by Rad53. Consistent with this idea, the degree of suppression of silencing defects by rad53 alleles correlated with effects on Asf1 binding. Furthermore, deletion of the Dun1 kinase, a downstream target of Rad53, also suppressed the silencing defects of cac1Δ cells and reduced the levels of Asf1 associated with Rad53 in vivo. Loss of Mec1 and Rad53 did not alter telomere lengths or Asf1 protein levels, nuclear localization, or chromosome association. We conclude that the Mec1 and Dun1 checkpoint kinases regulate the Asf1-Rad53 interaction and therefore affect the activity of the Asf1/Hir complex in vivo.
Rmr6 Maintains Meiotic Inheritance of Paramutant States in Zea mays
Authors: Hollick Jay B , Kermicle Jerry L , Parkinson Susan E 
Published: July 2005

Abstract
Paramutation generates heritable changes affecting regulation of specific alleles found at several Zea mays (maize) loci that encode transcriptional regulators of anthocyanin biosynthetic genes. Although the direction and extent of paramutation is influenced by poorly understood allelic interactions occurring in diploid sporophytes, two required to maintain repression loci (rmr1 and rmr2), as well as mediator of paramutation1 (mop1), affect this process at the purple plant1 (pl1) locus. Here we show that the rmr6 locus is required for faithful transmission of weakly expressed paramutant states previously established at both pl1 and red1 (r1) loci. Transcriptional repression occurring at both pl1 and booster1 (b1) loci as a result of paramutation also requires Rmr6 action. Reversions to highly expressed, nonparamutant states at both r1 and pl1 occur in plants homozygous for rmr6 mutations. Pedigree analysis of reverted pl1 alleles reveals variable latent susceptibilities to spontaneous paramutation in future generations, suggesting a quantitative nature of Rmr6-based alterations. Genetic tests demonstrate that Rmr6 encodes a common component required for establishing paramutations at diverse maize loci. Our analyses at pl1 and r1 suggest that this establishment requires Rmr6-dependent somatic maintenance of meiotically heritable epigenetic marks.