bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)
Authors: Galy Bruno , Ferring Dunja , Minana Belen , Bell Oliver , Janser Heinz G. , Muckenthaler Martina , Schümann Klaus , Hentze Matthias W. 
Published: June 2005

AbstractIron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism. We report that young adult Irp2-/- mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis. In comparison with wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit. Serum iron and transferrin saturation are unchanged, and hence microcytosis is not due to an overt decrease in systemic iron availability. The liver and duodenum are iron loaded, while the spleen is iron deficient, associated with a reduced expression of the iron exporter ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation. This study links a classic regulator of cellular iron metabolism to systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1. (Blood. 2005;106: 2580-2589)
Activated platelets induce Weibel-Palade–body secretion and leukocyte rolling in vivo: role of P-selectin
Authors: Dole Vandana S. , Bergmeier Wolfgang , Mitchell Heather A. , Eichenberger Sarah C. , Wagner Denisa D. 
Published: June 2005

AbstractThe presence of activated platelets and platelet-leukocyte aggregates in the circulation accompanies major surgical procedures and occurs in several chronic diseases. Recent findings that activated platelets contribute to the inflammatory disease atherosclerosis made us address the question whether activated platelets stimulate normal healthy endothelium. Infusion of activated platelets into young mice led to the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of activated P-selectin-/- platelets did not induce leukocyte rolling, indicating that platelet P-selectin was involved in the endothelial activation. The endothelial activation did not require platelet CD40L. Leukocyte rolling was mediated solely by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade bodies on infusion of activated platelets was indicated by both elevation of plasma VWF levels and by an increase in the in vivo staining of endothelial P-selectin. We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin–mediated leukocyte rolling.
Feature selection and classification for microarray data analysis: Evolutionary methods for identifying predictive genes
Authors: Jirapech-Umpai Thanyaluk , Aitken Stuart 
Published: June 2005

Abstract
Background
In the clinical context, samples assayed by microarray are often classified by cell line or tumour type and it is of interest to discover a set of genes that can be used as class predictors. The leukemia dataset of Golub et al. [1] and the NCI60 dataset of Ross et al. [2] present multiclass classification problems where three tumour types and nine cell lines respectively must be identified. We apply an evolutionary algorithm to identify the near-optimal set of predictive genes that classify the data. We also examine the initial gene selection step whereby the most informative genes are selected from the genes assayed.

Results
In the absence of feature selection, classification accuracy on the training data is typically good, but not replicated on the testing data. Gene selection using the RankGene software [3] is shown to significantly improve performance on the testing data. Further, we show that the choice of feature selection criteria can have a significant effect on accuracy. The evolutionary algorithm is shown to perform stably across the space of possible parameter settings – indicating the robustness of the approach. We assess performance using a low variance estimation technique, and present an analysis of the genes most often selected as predictors.

Conclusion
The computational methods we have developed perform robustly and accurately, and yield results in accord with clinical knowledge: A Z-score analysis of the genes most frequently selected identifies genes known to discriminate AML and Pre-T ALL leukemia. This study also confirms that significantly different sets of genes are found to be most discriminatory as the sample classes are refined.
Genome-wide structural and evolutionary analysis of the P450 monooxygenase genes (P450ome) in the white rot fungus Phanerochaete chrysosporium : Evidence for gene duplications and extensive gene clustering
Authors: Doddapaneni Harshavardhan , Chakraborty Ranajit , Yadav Jagjit S 
Published: June 2005

Abstract
Background
Phanerochaete chrysosporium, the model white rot basidiomycetous fungus, has the extraordinary ability to mineralize (to CO2) lignin and detoxify a variety of chemical pollutants. Its cytochrome P450 monooxygenases have recently been implied in several of these biotransformations. Our initial P450 cloning efforts in P. chrysosporium and its subsequent whole genome sequencing have revealed an extraordinary P450 repertoire ("P450ome") containing at least 150 P450 genes with yet unknown function. In order to understand the functional diversity and the evolutionary mechanisms and significance of these hemeproteins, here we report a genome-wide structural and evolutionary analysis of the P450ome of this fungus.

Results
Our analysis showed that P. chrysosporium P450ome could be classified into 12 families and 23 sub-families and is characterized by the presence of multigene families. A genome-level structural analysis revealed 16 organizationally homogeneous and heterogeneous clusters of tandem P450 genes. Analysis of our cloned cDNAs revealed structurally conserved characteristics (intron numbers and locations, and functional domains) among members of the two representative multigene P450 families CYP63 and CYP505 (P450foxy). Considering the unusually complex structural features of the P450 genes in this genome, including microexons (2–10 aa) and frequent small introns (45–55 bp), alternative splicing, as experimentally observed for CYP63, may be a more widespread event in the P450ome of this fungus. Clan-level phylogenetic comparison revealed that P. chrysosporium P450 families fall under 11 fungal clans and the majority of these multigene families appear to have evolved locally in this genome from their respective progenitor genes, as a result of extensive gene duplications and rearrangements.

Conclusion
P. chrysosporium P450ome, the largest known todate among fungi, is characterized by tandem gene clusters and multigene families. This enormous P450 gene diversity has evolved by extensive gene duplications and intragenomic recombinations of the progenitor genes presumably to meet the exceptionally high metabolic demand of this biodegradative group of basidiomycetous fungi in ecological niches. In this context, alternative splicing appears to further contribute to the evolution of functional diversity of the P450ome in this fungus. The evolved P450 diversity is consistent with the known vast biotransformation potential of P. chrysosporium. The presented analysis will help design future P450 functional studies to understand the underlying mechanisms of secondary metabolism and oxidative biotransformation pathways in this model white rot fungus.
Haploinsufficiency for BRCA1is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes
Authors: Latimer Jean J , Rubinstein Wendy S , Johnson Jennifer M , Kanbour-Shakir Amal , Vogel Victor G , Grant Stephen G 
Published: June 2005

AbstractBackgroundScreening mammography has had a positive impact on breast cancer mortality but cannot detect all breast tumors. In a small study, we confirmed that low power magnetic resonance imaging (MRI) could identify mammographically undetectable tumors by applying it to a high risk population. Tumors detected by this new technology could have unique etiologies and/or presentations, and may represent an increasing proportion of clinical practice as new screening methods are validated and applied. A very important aspect of this etiology is genomic instability, which is associated with the loss of activity of the breast cancer-predisposing genesBRCA1andBRCA2. In sporadic breast cancer, however, there is evidence for the involvement of a different pathway of DNA repair, nucleotide excision repair (NER), which remediates lesions that cause a distortion of the DNA helix, including DNA cross-links.Case presentationWe describe a breast cancer patient with a mammographically undetectable stage I tumor identified in our MRI screening study. She was originally considered to be at high risk due to the familial occurrence of breast and other types of cancer, and after diagnosis was confirmed as a carrier of a Q1200X mutation in theBRCA1gene. In vitro analysis of her normal breast tissue showed no differences in growth rate or differentiation potential from disease-free controls. Analysis of cultured blood lymphocyte and breast epithelial cell samples with the unscheduled DNA synthesis (UDS) assay revealed no deficiency in NER.ConclusionAs new breast cancer screening methods become available and cost effective, patients such as this one will constitute an increasing proportion of the incident population, so it is important to determine whether they differ from current patients in any clinically important ways. Despite her status as aBRCA1mutation carrier, and her mammographically dense breast tissue, we did not find increased cell proliferation or deficient differentiation potential in breast epithelial cells from this patient which might have contributed to her cancer susceptibility. Although NER deficiency has been demonstrated repeatedly in blood samples from sporadic breast cancer patients, analysis of blood cultured lymphocytes and breast epithelial cells for this patient proves definitively that heterozygosity for inactivation ofBRCA1does not intrinsically confer this type of genetic instability. These data suggest that the mechanism of genomic instability driving the carcinogenic process may be fundamentally different in hereditary and sporadic breast cancer, resulting in different genotoxic susceptibilities, oncogene mutations, and a different molecular pathogenesis.
Seroprevalence and risk factors for toxoplasmainfection among pregnant women in Aydin province, Turkey
Authors: Ertug Sema , Okyay Pinar , Turkmen Munevver , Yuksel Hasan 
Published: June 2005

AbstractBackgroundThe aims of the present study were to determine the prevalence of toxoplasmosis in pregnant women at first trimester of their pregnancy and to follow up the seroconversion for next two trimesters, and to identify the risk factors and possible contamination routes in Aydin province, Turkey.MethodThe sample size was calculated as 423 on a prevalence of 50%, d=0.05 at a confidence level of 95% with 10% addition. It was a cross-sectional study with multistage sampling. After a questionnaire applied to the pregnant women, anti-Toxoplasma IgG antibodies were studied with ELISA and IFA, values in conflict with DA test, where IgM antibodies were studied with ELISA and for borderline or positive values of IgM avidity test was used.ResultsThe mean age of 389 (92.9%) of pregnant women in the study was 24.28+/-4.56 years, the seroprevalence of anti-Toxoplasma IgG antibodies for toxoplasmosis was 30.1%. Seroprevalence was increased with age (p=0.001) and with drinking water consumption other than bottled water (p=0.042). No significant relations were observed between anti-Toxoplasma IgG antibodies and education level, being native or migrant, abortion history, consumption of meat, vegetable and milk/milk products, personal or kitchen hygiene habits, cat owning at home of the pregnant women. No IgM antibody was detected.ConclusionOne of every three pregnant women in Aydin was at risk of toxoplasmosis at the first trimester of their pregnancy. Increased seroprevalance with age was a predictable result because of increasing time of exposure. Increased seroprevalence with consumption of municipal and uncontrolled water (well/spring water) supplies was similar with latest epidemiological findings.
Infrared thermography fails to visualize stimulation-induced meridian-like structures
Authors: Litscher Gerhard 
Published: June 2005

Abstract

Background
According to Traditional Chinese Medicine (TCM) the vital energy flows through a system of channels also called meridians. Generally accepted proof for meridians cannot be considered as being given. Goal of this study was to examine whether possible stimulation-induced meridian-like structures, as recently described by other authors, can be visualized and objectified simultaneously at different infrared wavelength ranges.

Methods
The study analyses evidence for the existence of acupuncture-specific, meridian-like artifacts in 6 healthy volunteers (mean age ± SD 28.7 ± 3.7 years; range 25 – 35 years). Two infrared cameras at different wavelength ranges were used for thermographic control of possible stimulation effects (moxibustion-cigar, infrared warmth stimulation, needle and laserneedle stimulation). In addition to thermography, temperature and microcirculatory parameters were registered at a selected point using laser-Doppler flowmetry.

Results and Conclusion
After moxibustion (or infrared light stimulation) of the body at 2 – 5 μm and 7.5 – 13 μm ranges, different structures appear on thermographic images of the human body which are technical artifacts and which are not identical to what are known as meridians in all textbooks of TCM. Further scientific studies are required regarding the possible visualization of meridians.
Acquisition of rifabutin resistance by a rifampicin resistant mutant of Mycobacterium tuberculosis involves an unusual spectrum of mutations and elevated frequency
Authors: Anthony Richard M , Schuitema Anja RJ , Bergval Indra L , Brown Tim J , Oskam Linda , Klatser Paul R 
Published: June 2005

AbstractBackgroundMutations in a small region of therpoBgene are responsible for most rifamycin resistance inMycobacterium tuberculosis. In this study we have sequentially generated resistant strains to first rifampicin and then rifabutin. Portions of therpoBgene were sequenced from 131 randomly selected mutants. Second round selection resulted in a changed frequency of specific mutations.MethodsMycobacterium tuberculosis(strain Mtb72) rifamycin resistant mutants were selectedin vitrowith either rifampicin or rifabutin. One mutant R190 (rpoBS522L) selected with rifampicin had a rifampicin MIC of 32 μg/ml but remained sensitive to rifabutin (MIC<0.8 μg/ml). This mutant was subjected to a second round of selection with rifabutin.ResultsAll 105 first round resistant mutants derived from the parent strain (Mtb72) screened acquired mutations within the 81 bprpoBhotspot. When the rifampicin resistant but rifabutin sensitive S522L mutant was subjected to a second round of selection, single additionalrpoBmutations were identified in 24 (92%) of 26 second round mutants studied, but 14 (54%) of these strains contained mutations outside the 81 bp hotspot (codons 144, 146, 148, 505). Additionally, spontaneous rifabutin resistant mutants were produced at >10 times the frequency by the S522L mutant than the parent strain.ConclusionFirst round selection of mutation S522L with rifampicin increased the frequency and changed the spectrum of mutations identified after selection with rifabutin.
Long term remission of metastatic placental site trophoblastic tumor (PSTT): Case report and review of literature
Authors: Behtash Nadereh , Ghaemmaghami Fatemeh , Hasanzadeh Malihe 
Published: June 2005

Abstract

Background
Placental site trophoblastic tumor (PSTT) is a rare and unique form of gestational trophoblastic disease (GTD). This tumor represents a neoplastic transformation of intermediate trophoblastic cells. We document a case of long term remission in a patient with metastatic PSTT.

Case presentaion
A 27-year-old patient with metastatic PSTT was treated with combination therapy (chemotherapy and surgery). Patient is alive after 10 years without any evidence of recurrence. Literature on PSTT was searched using Medline and cross references, and pertinent articles were reviewed.

Conclusion
With surgery and chemotherapy it is possible to achieve long-term remission in metastatic PSTT. Only a handful of previously reported cases with prolonged remission had been treated with the described combined chemotherapy and surgical approach. We suggest that this approach may be recommended for metastatic PSTT.
Second language acquisition and first language loss in adult early bilinguals: exploring some differences and similarities
Authors: Montrul Silvina 
Published: June 2005

This study compares the linguistic knowledge of adult second language (L2) learners, who learned the L2 after puberty, with the potentially ‘eroded’ first language (L1) grammars of adult early bilinguals who were exposed to the target language since birth and learned the other language simultaneously, or early in childhood (before age 5). I make two main claims: (1) that the L1 grammar of bilinguals at a given stabilized state (probably endstate) resembles the incomplete (either developing or stabilized) grammars typical of intermediate and advanced stages in L2 acquisition; and (2) that despite similar patterns of performance, when language proficiency is factored in, early bilinguals are better than the L2 learners, probably due to exposure to primary linguistic input early in childhood. I offer empirical evidence from an experimental study testing knowledge of the syntax and semantics of unaccusativity in Spanish, conducted with English-speaking L2 learners and English-dominant Spanish heritage speakers living in the USA. I consider recent treatments of unaccusativity and language attrition within the generative framework (Sorace, 1999; 2000a; 2000b), that offer a unifying account of the formal parallels observed between these two populations I discuss how input, use and age may explain differences and similarities in the linguistic attainment of the two groups.
Objective Response to Chemotherapy As a Potential Surrogate End Point of Survival in Metastatic Breast Cancer Patients
Authors: Bruzzi Paolo , Del Mastro Lucia , Sormani Maria P. , Bastholt Lars , Danova Marco , Focan Christian , Fountzilas George , Paul James , Rosso Riccardo , Venturini Marco 
Published: June 2005

Purpose To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer. Patients and Methods We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy. Results The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months). Conclusion These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.
Avascular Necrosis of Femoral and/or Humeral Heads in Multiple Myeloma: Results of a Prospective Study of Patients Treated With Dexamethasone-Based Regimens and High-Dose Chemotherapy
Authors: Talamo Giampaolo , Angtuaco Edgardo , Walker Ronald C. , Dong Li , Miceli Marisa H. , Zangari Maurizio , Tricot Guido , Barlogie Bart , Anaissie Elias 
Published: June 2005

PurposeTo assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.Patients and MethodsA total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.ResultsWith a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.ConclusionAVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.