bluuebunny/crossref_metadata_2025_split huggingface dataset:
New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK
Authors: Fujiwara Kyoko , Igarashi Jun , Irahara Natsumi , Kimura Makoto , Nagase Hiroki 
Published: June 2007

AbstractBackgroundA variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. FifteenSktsloci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistantMus spretusmice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.ResultsIn the present study, we found that wild-derived PWK mice developed no tumour by treatment with the two-stage skin carcinogenesis protocol. This phenotype is dominant resistant when crossed with the highly susceptible strain FVB. By analyzing the F1 backcross generation between PWK and FVB, we found empirical evidence of significant linkage at the new lociSkts-fp1on chromosome 4 and suggestive linkage on chromosomes 1, 3, 11, 12 and 14 for skin tumour susceptibility.Skts-fp1includes theSkts7interval, which was previously mapped by aMus spretusand NIH backcross. We also observed suggestive linkage on chromosomes 1 and 2 in the female population only, while suggestive linkage on chromosomes 14 and 15 only was observed in the male population. A significant genetic interaction was seen between markers ofD11Mit339andD16Mit14.ConclusionAnalysis of this new cross may facilitate the identification of genes responsible for mouse skin cancer susceptibility and may reveal their biological interactions.
Gibberellins and heterosis of plant height in wheat (Triticum aestivum L.)
Authors: Zhang Yi , Ni Zhongfu , Yao Yingyin , Nie Xiuling , Sun Qixin 
Published: June 2007

Abstract

Background
Heterosis in internode elongation and plant height are commonly observed in hybrid plants, and higher GAs contents were found to be correlated with the heterosis in plant height. However, the molecular basis for the increased internode elongation in hybrids is unknown.

Results
In this study, heterosis in plant height was determined in two wheat hybrids, and it was found that the increased elongation of the uppermost internode contributed mostly to the heterosis in plant height. Higher GA4 level was also observed in a wheat hybrid. By using the uppermost internode tissues of wheat, we examined expression patterns of genes participating in both GA biosynthesis and GA response pathways between a hybrid and its parental inbreds. Our results indicated that among the 18 genes analyzed, genes encoding enzymes that promote synthesis of bioactive GAs, and genes that act as positive components in the GA response pathways were up-regulated in hybrid, whereas genes encoding enzymes that deactivate bioactive GAs, and genes that act as negative components of GA response pathways were down-regulated in hybrid. Moreover, the putative wheat GA receptor gene TaGID1, and two GA responsive genes participating in internode elongation, GIP and XET, were also up-regulated in hybrid. A model for GA and heterosis in wheat plant height was proposed.

Conclusion
Our results provided molecular evidences not only for the higher GA levels and more active GA biosynthesis in hybrid, but also for the heterosis in plant height of wheat and possibly other cereal crops.
Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators
Authors: Yaklichkin Sergey , Vekker Alexander , Stayrook Steven , Lewis Mitchell , Kessler Daniel S 
Published: June 2007

AbstractBackgroundThe Fox gene family comprises a large and functionally diverse group offorkhead-related transcriptional regulators, many of which are essential for metazoan embryogenesis and physiology. Defining conserved functional domains that mediate the transcriptional activity of Fox proteins will contribute to a comprehensive understanding of the biological function of Fox family genes.ResultsSystematic analysis of 458 protein sequences of the metazoan Fox family was performed to identify the presence of the engrailed homology-1 motif (eh1), a motif known to mediate physical interaction with transcriptional corepressors of the TLE/Groucho family. Greater than 50% of Fox proteins contain sequences with high similarity to the eh1 motif, including ten of the nineteen Fox subclasses (A, B, C, D, E, G, H, I, L, and Q) and Fox proteins of early divergent species such as marine sponge. The eh1 motif is not detected in Fox proteins of the F, J, K, M, N, O, P, R and S subclasses, or in yeast Fox proteins. The eh1-like motifs are positioned C-terminal to the winged helix DNA-binding domain in all subclasses except for FoxG proteins, which have an N-terminal motif. Two similar eh1-like motifs are found in the zebrafish FoxQ1 and in FoxG proteins of sea urchin and amphioxus. The identification of eh1-like motifs by manual sequence alignment was validated by statistical analyses of the Swiss protein database, confirming a high frequency of occurrence of eh1-like sequences in Fox family proteins. Structural predictions suggest that the majority of identified eh1-like motifs are short α-helices, and wheel modeling revealed an amphipathicity that supports this secondary structure prediction.ConclusionA search for eh1 Groucho interaction motifs in the Fox gene family has identified eh1-like sequences in greater than 50% of Fox proteins. The results predict a physical and functional interaction of TLE/Groucho corepressors with many members of the Fox family of transcriptional regulators. Given the functional importance of the eh1 motif in transcriptional regulation, our annotation of this motif in the Fox gene family will facilitate further study of the diverse transcriptional and regulatory roles of Fox family proteins.
Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells
Authors: Li Jinghuan , Smyth Paul , Flavin Richard , Cahill Susanne , Denning Karen , Aherne Sinead , Guenther Simone M , O'Leary John J , Sheils Orla 
Published: June 2007

Abstract

Background
Archival formalin-fixed paraffin-embedded (FFPE) tissues have limited utility in applications involving analysis of gene expression due to mRNA degradation and modification during fixation and processing. This study analyzed 160 miRNAs in paired snap frozen and FFPE cells to investigate if miRNAs may be successfully detected in archival specimens.

Results
Our results show that miRNA extracted from FFPE blocks was successfully amplified using Q-RT-PCR. The levels of expression of miRNA detected in total RNA extracted from FFPE were higher than that extracted from snap frozen cells when the quantity of total RNA was identical. This phenomenon is most likely explained by the fact that larger numbers of FFPE cells were required to generate equivalent quantities of total RNA than their snap frozen counterparts.

Conclusion
We hypothesise that methylol cross-links between RNA and protein which occur during tissue processing inhibit the yield of total RNA. However, small RNA molecules appear to be less affected by this process and are recovered more easily in the extraction process. In general miRNAs demonstrated reliable expression levels in FFPE compared with snap frozen paired samples, suggesting these molecules might prove to be robust targets amenable to detection in archival material in the molecular pathology setting.
Farber disease: clinical presentation, pathogenesis and a new approach to treatment
Authors: Ehlert Karoline , Frosch Michael , Fehse Natalja , Zander Axel , Roth Johannes , Vormoor Josef 
Published: June 2007

Abstract

Background
Farber Disease is an autosomal-recessively inherited, lysosomal storage disorder caused by acid ceramidase deficiency and associated with distinct clinical phenotypes. Children with significant neurological involvement usually die early in infancy, whereas patients without or only mild neurological findings suffer from progressive joint deformation and contractures, subcutaneous nodules, inflammatory, periarticular granulomas, a hoarse voice and finally respiratory insufficiency caused by granuloma formation in the respiratory tract and interstitial pneumonitis leading to death in the third or fourth decade of live. As the inflammatory component of this disorder is caused by some kind of leukocyte dysregulation, allogeneic hematopoietic stem cell transplantation can restore a healthy immune system and thus may provide a curative option in Farber Disease patients without neurological involvement. Previous stem cell transplantations in two children with severe neurological involvement had resulted in a disappointing outcome, as both patients died of progressive deterioration of their neurological status. As a consequence, stem cell transplantation does not appear to be able to abolish or even reduce the neurotoxic effects of the abundant ceramide storage in the brain.

Methods
After myeloablative, busulfan-based preparative regimens, four Farber Disease patients without neurological involvement received an allogeneic hematopoietic stem cell transplantation from related and unrelated donors. Stem cell source was BM in three patients and PBSC in one patient; GvHD-prophylaxis consisted of CsA and short course MTX.

Results and discussion
In all patients, HSCT resulted in almost complete resolution of granulomas and joint contractures, considerable improvement of mobility and joint motility without relevant therapy-related morbidities. All patients are alive and well at this point with stabile donor cell chimerism and without evidence of chronic GvHD or other late sequelae of stem cell transplantation.

Conclusion
Allogeneic hematopoietic stem cell transplantation provides a promising approach for Farber Disease patients without neurological involvement.
Tau phosphorylation by GSK-3β promotes tangle-like filament morphology
Authors: Rankin Carolyn A , Sun Qian , Gamblin Truman C 
Published: June 2007

Abstract

Background
Neurofibrillary tangles (NFTs) are intraneuronal aggregates associated with several neurodegenerative diseases including Alzheimer's disease. These abnormal accumulations are primarily comprised of fibrils of the microtubule-associated protein tau. During the progression of NFT formation, disperse and non-interacting tau fibrils become stable aggregates of tightly packed and intertwined filaments. Although the molecular mechanisms responsible for the conversion of disperse tau filaments into tangles of filaments are not known, it is believed that some of the associated changes in tau observed in Alzheimer's disease, such as phosphorylation, truncation, ubiquitination, glycosylation or nitration, may play a role.

Results
We have investigated the effects of tau phosphorylation by glycogen synthase kinase-3β (GSK-3β) on tau filaments in an in vitro model system. We have found that phosphorylation by GSK-3β is sufficient to cause tau filaments to coalesce into tangle-like aggregates similar to those isolated from Alzheimer's disease brain.

Conclusion
These results suggest that phosphorylation of tau by GSK-3β promotes formation of tangle-like filament morphology. The in vitro cell-free experiments described here provide a new model system to study mechanisms of NFT development. Although the severity of dementia has been found to correlate with the presence of NFTs, there is some question as to the identity of the neurotoxic agents involved. This model system will be beneficial in identifying intermediates or side reaction products that might be neurotoxic.
Cost-effectiveness of first-v.second-generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy
Authors: Davies Linda M. , Lewis Shôn , Jones Peter B. , Barnes Thomas R. E. , Gaughran Fiona , Hayhurst Karen , Markwick Alison , Lloyd Helen 
Published: June 2007

BackgroundThere are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life.AimsTo determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia.MethodCost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice.ResultsConventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective.ConclusionsThe primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.
Brain opioid receptor binding in early abstinence from opioid dependence
Authors: Williams Tim M. , Daglish Mark R. C. , Lingford-Hughes Anne , Taylor Lindsay G. , Hammers Alexander , Brooks David J. , Grasby Paul , Myles Judith S. , Nutt David J. 
Published: June 2007

BackgroundAlthough opioid receptor function in humans is clearly reduced during opioid dependence, what happens to the receptor in early abstinence is not understood.AimsThis study sought to examine changes in opioid receptor availability in early abstinence from opioid dependence.MethodTen people with opioid dependence who had completed inpatient detoxification and 20 healthy controls underwent [11C]-diprenorphine positron emission tomography. Clinical variables were assessed with structured questionnaires. Opioid receptor binding was characterised as the volume of distribution of [11C]-diprenorphine using a template of predefined brain volumes and an exploratory voxel-by-voxel analysis.ResultsCompared with controls, participants with opioid dependence had increased [11C]-diprenorphine binding in the whole brain and in 15 of the 21 a priori regions studied.ConclusionsThis study suggests that opioid receptor binding is increased throughout the brain in early abstinence from dependent opioid use. These data complement the findings in cocaine and alcohol dependence.
Metabolic disease and cardiovascular risk in people treated with antipsychotics in the community
Authors: Mackin Paul , Bishop David , Watkinson Helen , Gallagher Peter , Ferrier I. Nicol 
Published: June 2007

BackgroundPrevalence of physical comorbidity in severe mental illness is a significant public health concern, but comparative data in people with diagnoses other than schizophrenia are sparse.AimsTo investigate the prevalence of metabolic disease and cardiovascular risk in people with severe mental illness treated with antipsychotics in the community.MethodsCase – control study of 90 people treated with antipsychotics in the community and 92 age- and gender-matched controls. The prevalence of metabolic syndrome and 10-year cardiovascular risk were calculated.ResultsPeople on antipsychotics had a significantly worse metabolic profile than controls (F=6.583, d.f. = 15,161, P<0.0001). Moreover, metabolic syndrome was more prevalent (OR=3.68, 95% CI 1.71–7.93, P=0.001), as was cardiovascular risk across a number of outcomes. These results are consistent across diagnostic groups.ConclusionsPeople with severe mental illness treated with antipsychotics have excess metabolic dysfunction and heightened risk for cardiovascular disease.
Theory of mind in schizophrenia
Authors: Sprong Mirjam , Schothorst Patricia , Vos Ellen , Hox Joop , Van Engeland Herman 
Published: June 2007

BackgroundMentalising impairment (an impaired ability to think about people in terms of their mental states) has frequently been associated with schizophrenia.AimsTo assess the magnitude of the deficit and analyse associated factors.MethodTwenty-nine studies of mentalising in schizophrenia (combined n = 1518), published between January 1993 and May 2006, were included to estimate overall effect size. Study descriptors predicted to influence effect size were analysed using weighted regression-analysis techniques. Separate analyses were performed for symptom subgroups and task types.ResultsThe estimated overall effect size was large and statistically significant (d= –1.255, P < 0.001) and was not significantly affected by sample characteristics. All symptom subgroups showed significant mentalising impairment, but participants with symptoms of disorganisation were significantly more impaired than the other subgroups (P<0.01).ConclusionsThis meta-analysis showed significant and stable mentalising impairment in schizophrenia. The finding that patients in remission are also impaired favours the notion that mentalising impairment represents a possible trait marker of schizophrenia.
Implementing evidence-based supported employment
Authors: Rinaldi Miles , Perkins Rachel 
Published: June 2007

Aims and MethodWe evaluated the impact of implementing the individual placement and support (IPS) approach within eight community mental health teams (CMHTs) in two London boroughs. Demographic, clinical and vocational data were collected enabling a comparison of the number of people supported in work/education and individual client outcomes at 6 and 12 months.ResultsFollowing the integration of employment specialists there were significant increases in the number and proportion of clients engaged in mainstream work or educational activity at 6 months and 12 months. The employment specialists supported 38% in open employment at 6 months and 39% at 12 months.Clinical ImplicationsThe results support the use of IPS in clinical practice in CMHTs.
Impact of Psychotherapeutic Support for Patients With Gastrointestinal Cancer Undergoing Surgery: 10-Year Survival Results of a Randomized Trial
Authors: Küchler Thomas , Bestmann Beate , Rappat Stefanie , Henne-Bruns Doris , Wood-Dauphinee Sharon 
Published: June 2007

Purpose The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied. Patients and Methods A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices. Results Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer. Conclusion The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.
Single Versus Sequential High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Tumors: A Prospective Randomized Multicenter Trial of the German Testicular Cancer Study Group
Authors: Lorch Anja , Kollmannsberger Christian , Hartmann Joerg Thomas , Metzner Bernd , Schmidt-Wolf Ingo G.H. , Berdel Wolfgang E. , Weissinger Florian , Schleicher Jan , Egerer Gerlinde , Haas Antje , Schirren Rebekka , Beyer Jörg , Bokemeyer Carsten , Rick Oliver 
Published: June 2007

Purpose To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs). Patients and Methods Between November 1999 and November 2004, 230 patients were planned to be recruited in a prospective, randomized, multicenter trial comparing one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2, and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE; arm A) versus three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC; arm B). Results The study was stopped prematurely after recruitment of 216 patients as a result of excess treatment-related mortality in arm B. One hundred eleven (51%) of 216 patients were randomly assigned to sequential HDCT, and 105 (47%) of 216 patients were randomly assigned to single HDCT. Five (2%) of 216 patients had to be excluded because of non-GCT histologies at review. With a median follow-up time of 36 months, 109 (52%) of 211 patients were alive, and 91 (43%) of 211 patients were progression free. At 1 year, event-free, progression-free, and overall survival rates were 40%, 53%, and 80%, respectively, in arm A compared with 37%, 49%, and 61%, respectively, in arm B (P > .05 for all comparisons). Treatment-related deaths, mainly as a result of sepsis and cardiac toxicity, were less frequent in arm A (four of 108 patients, 4%) compared with arm B (16 of 103 patients, 16%; P < .01). Conclusion We found no difference in survival probabilities between single HDCT using CE and sequential HDCT using CEC. Sequential HDCT was better tolerated and resulted in fewer treatment-related deaths.
STAT3 Polymorphism Predicts Interferon-Alfa Response in Patients With Metastatic Renal Cell Carcinoma
Authors: Ito Noriyuki , Eto Masatoshi , Nakamura Eijiro , Takahashi Atsushi , Tsukamoto Taiji , Toma Hiroshi , Nakazawa Hayakazu , Hirao Yoshihiko , Uemura Hirotsugu , Kagawa Susumu , Kanayama Hiroomi , Nose Yoshiaki , Kinukawa Naoko , Nakamura Tsuyoshi , Jinnai Nobuyoshi , Seki Toyokazu , Takamatsu Masanobu , Masui Yoshihiro , Naito Seiji , Ogawa Osamu 
Published: June 2007

Purpose To clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-α) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-α immunotherapy. Patients and Methods We carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-α for MRCC. Results After adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-α. Linkage disequilibrium mapping revealed that the SNP in the 5′ region of STAT3, rs4796793, was the most significant predictor of IFN-α response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN-α by STAT3 suppression in an RCC cell line supported the results of the present association study. Conclusion The present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-α therapy in patients with MRCC. An efficient response marker for IFN-α needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.