bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice
Authors: Ishikawa Fumihiko , Yasukawa Masaki , Lyons Bonnie , Yoshida Shuro , Miyamoto Toshihiro , Yoshimoto Goichi , Watanabe Takeshi , Akashi Koichi , Shultz Leonard D. , Harada Mine 
Published: May 2005

AbstractHere we report that a new nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse line harboring a complete null mutation of the common cytokine receptor γ chain (NOD/SCID/interleukin 2 receptor [IL2r] γnull) efficiently supports development of functional human hemato-lymphopoiesis. Purified human (h) CD34+ or hCD34+hCD38– cord blood (CB) cells were transplanted into NOD/SCID/IL2rγnull newborns via a facial vein. In all recipients injected with 105 hCD34+ or 2 × 104 hCD34+hCD38– CB cells, human hematopoietic cells were reconstituted at approximately 70% of chimerisms. A high percentage of the human hematopoietic cell chimerism persisted for more than 24 weeks after transplantation, and hCD34+ bone marrow grafts of primary recipients could reconstitute hematopoiesis in secondary NOD/SCID/IL2rγnull recipients, suggesting that this system can support self-renewal of human hematopoietic stem cells. hCD34+hCD38– CB cells differentiated into mature blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, and lymphocytes. Differentiation into each lineage occurred via developmental intermediates such as common lymphoid progenitors and common myeloid progenitors, recapitulating the steady-state human hematopoiesis. B cells underwent normal class switching, and produced antigen-specific immunoglobulins (Igs). T cells displayed the human leukocyte antigen (HLA)–dependent cytotoxic function. Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, suggesting reconstitution of human mucosal immunity. Thus, the NOD/SCID/IL2rγnull newborn system might be an important experimental model to study the human hemato-lymphoid system.
T cell–mediated suppression of angiogenesis results in tumor protective immunity
Authors: Zhou He , Luo Yunping , Mizutani Masato , Mizutani Noriko , Reisfeld Ralph A. , Xiang Rong 
Published: May 2005

AbstractAntiangiogenic intervention is known to inhibit tumor growth and dissemination by attacking the tumor's vascular supply. Here, we report that this was achieved for the first time using an oral DNA minigene vaccine against murine vascular endothelial growth factor receptor 2 (FLK-1), a self-antigen overexpressed on proliferating endothelial cells in the tumor vasculature. Moreover, we identified the first H-2Db–restricted epitope, FLK400 (VILT-NPISM), specifically recognized by cytotoxic T lymphocytes (CTLs). Such CTLs were capable of killing FLK-1+ endothelial cells, resulting in suppression of angiogenesis and long-lived tumor protection. The specificity of this immune response was indicated because the DNA vaccine encoding the entire FLK-1 gene also induced a FLK400-specific CTL response. This minigene vaccine strategy provides a more flexible alternative to whole-gene vaccination and facilitates in-depth mechanism studies to tailor DNA vaccines for optimal T-cell activation and tumor protection.
Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia
Authors: Haining W. Nicholas , Neuberg Donna S. , Keczkemethy Heather L. , Evans John W. , Rivoli Stephen , Gelman Rebecca , Rosenblatt Howard M. , Shearer William T. , Guenaga Javier , Douek Daniel C. , Silverman Lewis B. , Sallan Stephen E. , Guinan Eva C. , Nadler Lee M. 
Published: May 2005

Abstract
Despite profound T-cell immunodeficiency, most patients treated with chemotherapy do not succumb to infection. The basis for residual protective immunity in lymphopenic patients is not known. We prospectively measured T-cell numbers, thymopoiesis, and T-cell memory in 73 children undergoing a 2-year chemotherapy regimen for acute lymphoblastic leukemia (ALL) and compared them to an age-matched cohort of 805 healthy children. Most patients had profound defects in CD4 and CD8 T-cell numbers at diagnosis that did not recover during the 2 years of therapy. Thymic output and the fraction of naive T cells were significantly lower than in healthy controls. However, the remaining T-cell compartment was enriched for antigen-experienced, memory T cells defined both by phenotype and by function. This relative sparing of T-cell memory may, in part, account for the maintenance of protective immunity in lymphopenic patients treated for ALL. Moreover, because the memory T-cell compartment is least affected by ALL and its treatment, strategies to induce immunity to pathogens or tumor antigens in cancer patients may be most successful if they seek to expand pre-existing memory T cells. (Blood. 2005; 106:1749-1754)
Phylogenetic reconstruction of ancestral character states for gene expression and mRNA splicing data
Authors: Rossnes Roald , Eidhammer Ingvar , Liberles David A 
Published: May 2005

Abstract
Background
As genomes evolve after speciation, gene content, coding sequence, gene expression, and splicing all diverge with time from ancestors with close relatives. A minimum evolution general method for continuous character analysis in a phylogenetic perspective is presented that allows for reconstruction of ancestral character states and for measuring along branch evolution.

Results
A software package for reconstruction of continuous character traits, like relative gene expression levels or alternative splice site usage data is presented and is available for download at http://www.rossnes.org/phyrex. This program was applied to a primate gene expression dataset to detect transcription factor binding sites that have undergone substitution, potentially having driven lineage-specific differences in gene expression.

Conclusion
Systematic analysis of lineage-specific evolution is becoming the cornerstone of comparative genomics. New methods, like phyrex, extend the capabilities of comparative genomics by tracing the evolution of additional biomolecular processes.
Potential genetic modifiers of the cystic fibrosis intestinal inflammatory phenotype on mouse chromosomes 1, 9, and 10
Authors: Norkina Oxana , De Lisle Robert C 
Published: May 2005

AbstractBackgroundAlthough cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines ofCftrdeficient mice (CF mice: Cftrtm1Unc) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.ResultsCF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.ConclusionPotential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype.
A generally applicable validation scheme for the assessment of factors involved in reproducibility and quality of DNA-microarray data
Authors: van Hijum Sacha AFT , de Jong Anne , Baerends Richard JS , Karsens Harma A , Kramer Naomi E , Larsen Rasmus , den Hengst Chris D , Albers Casper J , Kok Jan , Kuipers Oscar P 
Published: May 2005

Abstract
Background
In research laboratories using DNA-microarrays, usually a number of researchers perform experiments, each generating possible sources of error. There is a need for a quick and robust method to assess data quality and sources of errors in DNA-microarray experiments. To this end, a novel and cost-effective validation scheme was devised, implemented, and employed.

Results
A number of validation experiments were performed on Lactococcus lactis IL1403 amplicon-based DNA-microarrays. Using the validation scheme and ANOVA, the factors contributing to the variance in normalized DNA-microarray data were estimated. Day-to-day as well as experimenter-dependent variances were shown to contribute strongly to the variance, while dye and culturing had a relatively modest contribution to the variance.

Conclusion
Even in cases where 90 % of the data were kept for analysis and the experiments were performed under challenging conditions (e.g. on different days), the CV was at an acceptable 25 %. Clustering experiments showed that trends can be reliably detected also from genes with very low expression levels. The validation scheme thus allows determining conditions that could be improved to yield even higher DNA-microarray data quality.
Age related clinical features of childhood Coeliac disease in Australia
Authors: Stone Monique L , Bohane Timothy D , Whitten Kylie E , Tobias Vivienne H , Day Andrew S 
Published: May 2005

Abstract

Background
To describe the presenting clinical features of coeliac disease in a single paediatric centre, and to determine if the presenting features vary with age.

Methods
A review was conducted of children who had been referred with clinical suspicion of coeliac disease to the paediatric gastroenterology department of a tertiary paediatric hospital in Sydney, Australia. Coeliac disease was defined using standard histological criteria. Medical records were reviewed retrospectively.

Results
Clinical data were available for 74 cases of proven coeliac disease. Only 9% of patients were less than 2 years of age at diagnosis. Pre-school children (age <5 years) presented with different symptoms to school children (age ≥ 5 years). The most common presenting features in younger children were diarrhoea, irritability and weight loss. However, in older children, abdominal pain was the most common presenting feature.

Conclusion
We found a significant difference in the clinical features of coeliac disease in pre-school compared to school age children.
Epidemiologic measures and policy formulation: lessons from potential outcomes
Authors: Greenland Sander 
Published: May 2005

AbstractThis paper provides a critique of the common practice in the health-policy literature of focusing on hypothetical outcome removal at the expense of intervention analysis. The paper begins with an introduction to measures of causal effects within the potential-outcomes framework, focusing on underlying conceptual models, definitions and drawbacks of special relevance to policy formulation based on epidemiologic data. It is argued that, for policy purposes, one should analyze intervention effects within a multivariate-outcome framework to capture the impact of major sources of morbidity and mortality. This framework can clarify what is captured and missed by summary measures of population health, and shows that the concept of summary measure can and should be extended to multidimensional indices.
Reducing perinatal mortality among Indigenous babies in Queensland: should the first priority be better primary health care or better access to hospital care during confinement?
Authors: Johnston Trisha , Coory Michael 
Published: May 2005

AbstractBackgroundThe perinatal mortality rate among Indigenous Australians is still double that of the rest of the community. The aim of our study was to estimate the extent to which increased risk of low birthweight and preterm birth among Indigenous babies in Queensland account for their continuing mortality excess. If a large proportion of excess deaths can be explained by the unfavourable birthweight and gestational age distribution of Indigenous babies, then that would suggest that priority should be given to implementing primary health care interventions to reduce the risk of low birthweight and preterm birth (eg, interventions to reduce maternal smoking or genitourinary infections). Conversely, if only a small proportion is explained by birthweight and gestational age, then other strategies might need to be considered such as improving access to high-quality hospital care around the time of confinement.MethodologyPopulation-based, descriptive study of perinatal mortality rates among Indigenous and non-Indigenous babies, in Queensland, stratified by birthweight and gestational age.ResultsIndigenous babies are twice as likely to die as their non-Indigenous counterparts (rate ratio1998–2002: 2.01; 95%ci 1.77, 2.28). However, within separate strata of birth weight and gestational age, Indigenous and non-Indigenous rates are similar. The Mantel-Haenszel rate ratio adjusted for birth weight and gestational age was 1.13 (0.99, 1.28). This means that most of the excess mortality in Indigenous babies is largely due to their unfavourable birth weight and gestational-age distributions. If Indigenous babies had the same birth weight and gestational age distribution as their non-Indigenous counterparts, then the relative disparity would be reduced by 87% and 20 fewer Indigenous babies would die in Queensland each year.ConclusionOur results suggest that Indigenous mothers at high risk of poor outcome (for example those Indigenous mothers in preterm labour) have good access to high quality medical care around the time of confinement. The main reason Indigenous babies have a high risk of death is because they are born too early and too small. Thus, to reduce the relative excess of deaths among Indigenous babies, priority should be given to primary health care initiatives aimed at reducing the prevalence of low birth weight and preterm birth.
Detection of the inhibitory neurotransmitter GABA in macrophages by magnetic resonance spectroscopy
Authors: Stuckey D J , Anthony D C , Lowe J P , Miller J , Palm W M , Styles P , Perry V H , Blamire A M , Sibson N R 
Published: May 2005

AbstractMacrophages are key components of the inflammatory response to tissue injury, but their activities can exacerbate neuropathology. High-resolution magnetic resonance spectroscopy was used to identify metabolite levels in perchloric acid extracts of cultured cells of the RAW 264.7 murine macrophage line under resting and lipopolysaccharide-activated conditions. Over 25 metabolites were identified including γ-aminobutyric acid (GABA), an inhibitory neurotransmitter not previously reported to be present in macrophages. The presence of GABA was also demonstrated in extracts of human peripheral blood monocyte-derived macrophages. This finding suggests that there may be communication between damaged central nervous system (CNS) tissue and recruited macrophages and resident microglia, which could help orchestrate the immune response. On activation, lactate, glutamine, glutamate, and taurine levels were elevated significantly, and GABA and alanine were reduced significantly. Strong resonances from glutathione, evident in the macrophage two-dimensional 1H spectrum, suggest that this may have potential as a noninvasive marker of macrophages recruited to the CNS, as it is only present at low levels in normal brain. Alternatively, a specific combination of spectroscopic changes, such as lactate, alanine, glutathione, and polyamines, may prove to be the most accurate means of detecting macrophage recruitment to the CNS.
Childhood Cancer Survival Trends in Europe: A EUROCARE Working Group Study
Authors: Gatta Gemma , Capocaccia Riccardo , Stiller Charles , Kaatsch Peter , Berrino Franco , Terenziani Monica ,   the EUROCARE Working Group
Published: May 2005

Purpose EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe. Patients and Methods Survival in 44,129 children diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated. Results For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms’ tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt’s lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year. Conclusion These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase.
Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Detected by Clonotypic Polymerase Chain Reaction Despite Continuous Pathologic Remission Induced by Involved-Field Radiotherapy
Authors: Noy Ariela , Yahalom Joachim , Zaretsky Leah , Brett Ian , Zelenetz Andrew D. 
Published: May 2005

Purpose Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is indolent and often associated with Helicobacter pylori bacterial infection. H pylori–independent MALT develops either in the absence of the bacteria or persists after bacterial eradication. We have previously demonstrated long-term pathologic remission after involved-field radiotherapy therapy (IFRT). We determined molecular remission status by clonotypic polymerase chain reaction (PCR). Patients and Methods Twenty-four consecutive patients with stage I to IIE gastric MALT lymphoma who obtained a pathologic remission after IFRT alone were evaluated. All had at least two follow-up endoscopic gastroduodenal biopsies at Memorial Sloan-Kettering Cancer Center. IFRT median dose was 30 Gy (range, 28.5 to 43.5 Gy). Post-treatment biopsies were subjected to semi-nested clonotypic PCR. Results All patients obtained a complete response based on routine immunohistochemical pathologic analysis of random post-treatment gastric biopsies. Median follow-up from completion of IFRT was 63 months (range, 19 to 117 months). Event-free survival was 96%; 23 of 34 patients remained in clinical and pathologic complete remission. Baseline DNA extraction yielded 17 clone-specific primer pairs. At the first follow-up test, 14 of 17 pairs were PCR positive. Eight remained persistently positive; and one was persistently negative. Others were intermittently positive. Conclusion Despite sustained biopsy-proven remissions for as long as 117 months after radiation, the vast majority of patients remain positive by clonotypic PCR. This suggests that the malignant clone is present but missing either an internal or external signal essential to the cancer phenotype. One possibility is that radiation eradicates the polyclonal H pylori–specific T cells eliminating critical local factors necessary for proliferation of the monoclonal B cells.
Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator
Authors: Iwasaki Toshiharu , Koibuchi Noriyuki , Chin William W. 
Published: May 2005

AbstractWe previously cloned and characterized a novel RNA-binding motif-containing coactivator, named coactivator activator (CoAA), as a thyroid hormone receptor-binding protein-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical with synovial sarcoma translocation (SYT)-interacting protein. Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C terminus compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues, such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. Glutathione-S-transferase pull-down studies showed that SYT binds to the C-terminus of CoAA, but not to the coactivator modulator. Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, COS-1, and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA, to interact with the histone acetyltransferase complex.