bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for whole chromosome 6 loss and duplication of the remaining chromosome in acute lymphoblastic leukemia
Authors: McEvoy Christopher R.E. , Morley Alexander A. , Firgaira Frank A. 
Published: May 2003

AbstractHLA class I molecules serve the essential immunological function of presenting antigen to CD8+ T lymphocytes. Tumor cells may present tumor‐specific antigen to T cells via these molecules, but many tumors show a loss or down‐regulation of HLA class I expression and this may serve as an immune escape mechanism. Using a microsatellite marker‐based method, we have searched for loss of heterozygosity (LOH) mutations at 3 genomic regions implicated in HLA class I expression in a cohort of 56 acute lymphoblastic leukemia (ALL) samples. The regions analyzed consisted of the HLA class I heavy chain genes located within the MHC genomic region on chromosome arm 6p, the HLA class I light chain (beta‐2‐microglobulin, B2M) gene on chromosome arm 15q, and the putative HLA modifier of methylation gene (MEMO1) located on chromosome arm 1q. Results revealed low frequencies of B2M (2/55) and MEMO1 (5/42) LOH but a high frequency of MHC LOH (19/56) that was usually associated with whole chromosome 6 loss (13/19). Cytogenetic data were available for 30 samples, including nine of those that exhibited apparent whole chromosome 6 loss. No cases of chromosome 6 monosomy were observed. We propose that whole chromosome 6 loss with reduplication of the remaining chromosome is common in ALL and that it is driven by the presence of tumor‐inhibiting factors on chromosome arm 6p (the HLA loci) along with previously localized tumor‐suppressor genes on chromosome arm 6q. © 2003 Wiley‐Liss, Inc.
High‐resolution analysis of acquired genomic imbalances in bone marrow samples from chronic myeloid leukemia patients by use of multiple short DNA probes
Authors: Reid Alistair G. , Tarpey Patrick S. , Nacheva Ellie P. 
Published: May 2003

AbstractChronic myeloid leukemia (CML) is a biphasic hematopoietic malignancy associated with a single cytogenetic aberration, the Philadelphia translocation t(9;22)(q34;q11), resulting in the BCR‐ABL1 fusion oncogene. Molecular heterogeneity was recently demonstrated in the form of extensive deletion of chromosomes 9 and 22 material from the der(9)t(9;22) in 15% of CML patients. The deletions were associated with a worse disease prognosis. Further genetic heterogeneity is seen during the terminal blast crisis stage of CML, in the form of additional non‐random chromosome abnormalities. These include most frequently an extra copy of the Ph chromosome, trisomy 8, and isochromosome 17q. We used the genetic heterogeneity of CML as a framework to explore a new technique for high‐throughput assessment of locus copy number in malignancy. Multiplex amplifiable probe hybridization (MAPH) relies on the ability of numerous short (100–300 bp) DNA probes to be recovered quantitatively by use of a common primer pair after hybridization to genomic DNA. Derivative chromosome 9 deletions were successfully mapped in a CML cell line (MC3) and nine patient bone marrow samples by simultaneous hybridization of 10 MAPH probes. All results were confirmed by fluorescence in situ hybridization. MAPH was found to be informative in the presence of up to 50% of normal cells, thus establishing the sensitivity of the technique in clonal tumor cell populations. MAPH was performed effectively on DNA samples extracted from fresh or methanol/acetic acid–fixed clonal cell populations. Amplifications of BCR‐ABL1 were also detected and quantified in four CML cell lines by use of MAPH probes specific for ABL1 exon 11 and BCR exon 1. Our results demonstrate that MAPH is a reproducible high‐throughput method suitable for the assessment of genomic imbalances of multiple loci in tumor DNA samples with heterogeneous cell populations at a resolution of 100–300 bp. © 2003 Wiley‐Liss, Inc.
Genome‐wide amplification and allelotyping of sporadic pituitary adenomas identify novel regions of genetic loss
Authors: Simpson D. J. , Bicknell E. J. , Buch H. N. , Cutty S. J. , Clayton R. N. , Farrell W. E. 
Published: May 2003

AbstractThrough the use of a candidate gene approach, several previous studies have identified loss of heterozygosity (LOH) at putative tumor‐suppressor gene (TSG) loci in sporadic pituitary tumors. This study reports a genome‐wide allelotyping by use of 122 microsatellite markers in a large cohort of tumors, consisting of somatotrophinomas and non‐functioning adenomas. Samples were first subject to prior whole genome amplification by primer extension pre‐amplification (PEP) to circumvent limitations imposed by insufficient DNA for whole‐genome analysis with this number of microsatellite markers. The overall mean frequency of loss in invasive tumors was significantly higher than that in their non‐invasive counterparts (7 vs. 3% somatotrophinomas; 6 vs. 3% non‐functioning adenomas, respectively). Analysis of the mean frequency of LOH, across all markers to individual chromosomal arms, identified 13 chromosomal arms in somatotrophinomas and 10 in non‐functioning tumors, with LOH greater than the 99% upper confidence interval calculated for the rate of overall random allelic loss. In the majority of cases, these losses were more frequent in invasive tumors than in their non‐invasive counterparts, suggesting these to be markers of tumor progression. Other regions showed similar frequencies of LOH in both invasive and non‐invasive tumors, implying these to be early changes in pituitary tumorigenesis. This genome‐wide study also revealed chromosomal regions where losses were frequently associated with an individual marker, for example, chromosome arm 1q (LOH > 30%). In some cases, these losses were subtype‐specific and were found at a higher frequency in invasive tumors than in their non‐invasive counterparts. Identification of these regions of loss provides the first preliminary evidence for the location of novel putative TSGs involved in pituitary tumorigenesis that are, in some cases, subtype‐specific. This investigation provides an unbiased estimate of global aberrations in sporadic pituitary tumors as assessed by LOH analysis. The identification of multiple “hotspots” throughout the genome may be a reflection of an unstable chromatin structure that is susceptible to a deletion or epigenetic‐mediated gene‐silencing events. © 2003 Wiley‐Liss, Inc.
Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia
Authors: Steudel Christine , Wermke Martin , Schaich Markus , Schäkel Ulrike , Illmer Thomas , Ehninger Gerhard , Thiede Christian 
Published: May 2003

AbstractPartial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well‐defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT‐PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease‐free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease‐free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor. © 2003 Wiley‐Liss, Inc.
Differentiating pathogenic mutations from polymorphic alterations in the splice sites of BRCA1 and BRCA2
Authors: Claes Kathleen , Poppe Bruce , Machackova Eva , Coene Ilse , Foretova Lenka , De Paepe Anne , Messiaen Ludwine 
Published: May 2003

AbstractAbout 4% of all BRCA1 and BRCA2 alterations reported to the Breast Information Core database are splice site variants. Only a limited number of them have been studied at the RNA level. By BRCA1 and BRCA2 mutation analysis of breast/ovarian cancer families, we identified two novel and eight previously reported potential splice site mutations, never characterized at the cDNA level before. RT‐PCR was performed to determine whether these variants disrupted correct splicing. To ensure efficient detection of transcripts containing premature termination codons, a nonsense‐mediated mRNA decay inhibitor was added to the lymphoblastoid cell lines of the patients before RNA extraction. We found that BRCA1 IVS3+3A>C, 4304G>A (in the last codon of exon 12), and IVS19+2delT and BRCA2 IVS6+1G>A, IVS23−2A>G, and IVS24+1G>A lead to aberrant transcripts in lymphocytes. Therefore, they were considered to be true pathogenic mutations, predisposing carriers to cancers of the hereditary breast/ovarian cancer syndrome. BRCA2 IVS24−16T>C is a frequent polymorphism in linkage disequilibrium, with a polymorphic stop codon in exon 27, K3326X. BRCA1 IVS2−14C>T and BRCA2 IVS9−5insT and IVS25+9A>C represent rare variants, not disrupting normal splicing in blood lymphocytes. However, some of the alterations may act differently, qualitatively and/or quantitatively, in breast or ovarian tissues. The data provided in this paper allowed more accurate risk estimation of patients and relatives carrying the mutations described herein and have facilitated genetic counseling. Furthermore, our study is important for a better understanding of splicing mechanisms and revealed new patterns of alternative splicing in BRCA1 and BRCA2. © 2003 Wiley‐Liss, Inc.
SOCS1 methylation in patients with newly diagnosed acute myeloid leukemia
Authors: Chen Chien‐Yuan , Tsay Woei , Tang Jih‐Luh , Shen Hwei‐Ling , Lin Shu‐Wha , Huang Sheng‐Yi , Yao Ming , Chen Yao‐Chang , Shen Ming‐Ching , Wang Chiu‐Hwa , Tien Hwei‐Fang 
Published: May 2003

AbstractThe proliferation and differentiation of hematopoietic precursor cells depend on various cytokines. The suppressor of cytokine signaling‐1 (SOCS1) down‐regulates Janus kinases/signal transducers and activators of transcription (JAK/STAT) pathway activity and inhibits the biological effects of cytokines. SOCS1 has been shown to have tumor‐suppressor activity, and methylation of this gene, resulting in transcriptional silencing, has been found in 65% of hepatocellular carcinoma and has been suggested to play an important role in the development of the cancer. The methylation status of the SOCS1 gene in acute myeloid leukemia (AML) has not been reported before. In this study, we analyzed SOCS1 methylation in 89 patients with newly diagnosed AML and correlated the result with immunophenotypes, cytogenetics, clinical features, and treatment outcome. SOCS1 methylation was found in the leukemic cells from 53 patients (60%). Thirteen (76%) of the 17 patients with t(15;17) had SOCS1 methylation, whereas this gene was methylated in only one (11%) of the nine patients with t(8;21). The frequencies of SOCS1 methylation among various cytogenetic subgroups differed significantly (P = 0.014). Other clinical and laboratory parameters and the disease‐free survival and overall survival were similar between patients with and without SOCS1 methylation. In conclusion, SOCS1 methylation occurs in more than half of AML cases, correlates with cytogenetic abnormalities, and may play an important role in the development of subsets of AML. © 2003 Wiley‐Liss, Inc.
Insertion of MLL sequences into chromosome band 5q31 results in an MLL‐AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemia
Authors: Deveney Ramona , Chervinsky David S. , Jani‐Sait Sheila N. , Grossi Mauro , Aplan Peter D. 
Published: May 2003

AbstractMLL gene rearrangements leading to production of MLL fusion proteins are commonly detected in infant leukemia patients; the most common MLL fusion associated with infant leukemia is the MLL‐AF4 fusion. A single case of chromosomal rearrangement leading to production of an MLL fusion with AF5Q31, a gene structurally similar to AF4, has been detected recently in the malignant cells of an infant leukemia patient. We have identified a second case of MLL‐AF5Q31 fusion, arising from an insertion of MLL sequences into chromosome 5, also in an infant leukemia patient. Because MLL and AF5Q31 are transcribed in opposite orientations, a simple balanced chromosomal translocation cannot produce a fusion protein, and complex chromosomal rearrangements such as insertions and inversions are required to produce an MLL‐AF5Q31 fusion protein. This report demonstrates that chromosomal insertion of MLL sequences is a rare but recurrent abnormality associated with infant leukemia. © 2003 Wiley‐Liss, Inc.
Haploinsufficiency and reduced expression of genes localized to the 8p chromosomal region in human prostate tumors
Authors: Chaib Hassan , MacDonald James W. , Vessella Robert L. , Washburn Joseph G. , Quinn Janna E. , Odman Austin , Rubin Mark A. , Macoska Jill A. 
Published: May 2003

AbstractCytogenetic and molecular studies have suggested that deletion or rearrangement of sequences that map to the short arm of chromosome 8 may be permissive for tumorigenesis in several organ systems, and in human prostate tumors in particular. In this study, we hypothesized that genes deleted for one copy and localized to the 8p chromosomal region may be transcriptionally down‐regulated or ablated in affected human prostate tumor tissues. To test this hypothesis, we used cDNA microarray analysis to determine the transcriptional profiles for 259 transcribed sequences mapping to the 8p chromosomal region for seven human prostate tumor xenografts, completely characterized for numerical and structural alterations on chromosome 8, and five normal human prostate tissues. These experiments identified 33 genes differentially expressed between normal and malignant prostate tissues, the majority of which (28/33, 85%) were transcriptionally down‐regulated in malignant compared to normal human prostate tissues. These findings, that haploinsufficiency and transcriptional down‐regulation for genes mapping to 8p are largely coincident in human prostate tumors, should provide a powerful tool for the identification of tumor‐suppressor genes associated with human prostate cancer initiation and progression. © 2003 Wiley‐Liss, Inc.
Estimation of the determinants of household health care expenditures in Nepal with controls for endogenous illness and provider choice
Authors: Rous Jeffrey J. , Hotchkiss David R. 
Published: May 2003

AbstractThis paper uses the Nepal Living Standards Survey, a nationally representative sample of households from 1996, to investigate the determinants of household out‐of‐pocket health expenditures. The analysis uses a multi‐equation joint estimation to control for endogeneity of sickness and provider choice. The results of this analysis indicate several interesting findings. First, common unobserved factors were found to be statistically significant determinants of illness, choice of provider, and health expenditures, and may cause bias to parameter estimates if not controlled. Second, the income elasticity is estimated to be 1.10, with income having both a direct effect on health expenditure, and an indirect effect through likelihood of illness and the type of provider that is chosen. Third, housing and sanitary conditions were found to have a substantial effect on illness, and as a result, out‐of‐pocket health care expenditures. Fourth, despite the fact that urban, ill individuals who seek care are more likely to utilize care in more expensive settings, average health care expenditure among the urban sample was found to be substantially lower than among the rural sample, partly due to a lower likelihood of reporting illnesses and injuries and of using any type of health care provider. Copyright © 2002 John Wiley & Sons, Ltd.
The person trade‐off method and the transitivity principle: an example from preferences over age weighting
Authors: Dolan Paul , Tsuchiya Aki 
Published: May 2003

AbstractThe person trade‐off (PTO) is increasingly being used to elicit preferences in health. This paper explores the measurement properties of the PTO method in the context of a study about how members of the public prioritise between patients of different ages. In particular, it considers whether PTO responses satisfy the transitivity principle; that is, whether one PTO response can be inferred from two other PTO responses. The results suggest that very few responses to PTO questions satisfy cardinal transitivity condition. However, this study has produced results that suggest that cardinal transitivity will hold, on average, when respondents who fail to satisfy the ordinal transitivity condition have been excluded from the analysis. This suggests that future PTO studies should build in checks for ordinal transitivity. Copyright © 2002 John Wiley & Sons, Ltd.
The labour market for nursing: a review of the labour supply literature
Authors: Antonazzo Emanuela , Scott Anthony , Skatun Diane , Elliott Robert. F. 
Published: May 2003

AbstractThe need to ensure adequate numbers of motivated health professionals is at the forefront of the modernisation of the UK NHS. The aim of this paper is to assess current understanding of the labour supply behaviour of nurses, and to propose an agenda for further research. In particular, the paper reviews American and British economics literature that focuses on empirical econometric studies based on the classical static labour supply model.American research could be classified into first generation, second generation and recent empirical evidence. Advances in methods mirror those in the general labour economics literature, and include the use of limited dependent variable models and the treatment of sample selection issues. However, there is considerable variation in results, which depends on the methods used, particularly on the effect of wages.Only one study was found that used UK data, although other studies examined the determinants of turnover, quit rates and job satisfaction. The agenda for further empirical research includes the analysis of discontinuities in the labour supply function, the relative importance of pecuniary and non‐pecuniary job characteristics, and the application of dynamic and family labour supply models to nursing research. Such research is crucial to the development of evidence‐based policies. Copyright © 2002 John Wiley & Sons, Ltd.
A preliminary investigation of the effects of restrictions on Medicaid funding for abortions on female STD rates
Authors: Sen Bisakha 
Published: May 2003

AbstractThere is evidence in the economics literature that restrictions on Medicaid funding for abortion reduces the demand for abortion. The unresolved question is whether such restrictions also increase safe sex (that is, pregnancy avoidance) behavior among women. This study explores that issue using state‐level gonorrhea rates among women for 1975–1995. The rationale is that sexual behavior that leads to greater risk of accidental pregnancies is likely to be highly correlated with sexual behavior leading to greater risk of STD infection. Since gonorrhea has an incubation period of about a week, and is transmitted almost exclusively through sexual intercourse, a change in sexual behavior should soon be followed by a change in gonorrhea rates. The study used a partial adjustment model with lagged‐dependent variables estimated using Arellano‐Bond's GMM method. Results fail to find any statistically significant evidence that Medicaid funding restrictions are effective in reducing gonorrhea rates. This finding is robust to a variety of alternate specifications and tests. This suggests that restrictions on Medicaid funding for abortion fail to promote safe sex behavior among women. Copyright © 2002 John Wiley & Sons, Ltd.
Conjoint analysis. The cost variable: an Achilles' heel?
Authors: Slothuus Skjoldborg Ulla , Gyrd‐Hansen Dorte 
Published: May 2003

AbstractThis paper seeks to enlighten the readers on the potential complexities involved in including cost variables in conjoint analysis, with the aim of emphasising that interpretation of implicit WTP values should be tackled with caution. To illustrate the potential pitfalls, a large data set from a recent Danish study is applied. The data consists of 1991 interviews in which participants are required to perform three discrete choice tasks regarding choice of hospitals, and three choice tasks involving health‐care systems in general. Model comparisons are performed which test the effect of (1) the cost range applied and (2) the effect of including a dummy variable to represent the utility associated with payment per se. A wider cost range including higher payments is associated with lower parameter weights associated with the payment variable, and thus increased WTP values. Including a dummy variable to explain utility associated with payment per se has significant effects on the model incurring some of the other variables to become insignificant, and others to change sign. Results suggest that inclusion of a two‐dimensional structure to explain the relationship between cost and utility may avoid erroneous conclusions and give rise to significant changes in implicit WTP estimates. Copyright © 2002 John Wiley & Sons, Ltd.
The efficiency of health production: re‐estimating the WHO panel data using parametric and non‐parametric approaches to provide additional information
Authors: Hollingsworth Bruce , Wildman John 
Published: May 2003

AbstractThe World Health Report 2000 focuses on the performance of health‐care systems around the globe. The report uses efficiency measurement techniques to create a league table of health‐care systems, highlighting good and bad performers. Efficiency is measured using panel data methods. This paper suggests that the WHO's estimation procedure is too narrow and that contextual information is hidden by the use of one method. This paper uses and validates a range of parametric and non‐parametric empirical methods to measure efficiency using the WHO data. The rankings obtained are compared to the WHO league table and we demonstrate that there are trends and movements of interest within the league tables. We recommend that the WHO broaden its range of techniques in order to reveal this hidden information. Copyright © 2002 John Wiley & Sons, Ltd.