bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global reduction of the epigenetic H3K79 methylation mark and increased chromosomal instability in CALM-AF10–positive leukemias
Authors: Lin Yi-Hui , Kakadia Purvi M. , Chen Ying , Li Ya-Qiang , Deshpande Aniruddha J. , Buske Christian , Zhang Kang-Ling , Zhang Yi , Xu Guo-Liang , Bohlander Stefan K. 
Published: May 2009

Abstract
Chromosomal translocations generating fusion proteins are frequently found in human leukemias. The fusion proteins play an important role in leukemogenesis by subverting the function of one or both partner proteins. The leukemogenic CALM-AF10 fusion protein is capable of interacting with the histone H3 lysine 79 (H3K79)–specific methyltransferase hDOT1L through the fused AF10 moiety. This interaction leads to local H3K79 hypermethylation on Hoxa5 loci, which up-regulates the expression of Hoxa5 and contributes to leukemogenesis. However, the long latency of leukemogenesis of CALM-AF10 transgenic mice suggests that the direct effects of fusion oncogene are not sufficient for the induction of leukemia. In this study, we show that the CALM-AF10 fusion protein can also greatly reduce global H3K79 methylation in both human and murine leukemic cells by disrupting the AF10-mediated association of hDOT1L with chromatin. Cells with reduced H3K79 methylation are more sensitive to γ-irradiation and display increased chromosomal instability. Consistently, leukemia patients harboring CALM-AF10 fusion have more secondary chromosomal aberrations. These findings suggest that chromosomal instability associated with global epigenetic alteration contributes to malignant transformation in certain leukemias, and that leukemias with this type of epigenetic alteration might benefit from treatment regimens containing DNA-damaging agents. This study is registered with www.clinicaltrials.gov as NCT00266136.
Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network
Authors: Alousi Amin M. , Weisdorf Daniel J. , Logan Brent R. , Bolaños-Meade Javier , Carter Shelly , DiFronzo Nancy , Pasquini Marcelo , Goldstein Steven C. , Ho Vincent T. , Hayes-Lattin Brandon , Wingard John R. , Horowitz Mary M. , Levine John E. 
Published: May 2009

Abstract
Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www.clinicaltrials.gov as NCT00224874.
Quadriceps muscle strength in scoliosis
Authors: Swallow E. B. , Barreiro E. , Gosker H. , Sathyapala S. A. , Sanchez F. , Hopkinson N. S. , Moxham J. , Schols A. , Gea J. , Polkey M. I. 
Published: May 2009

Quadriceps muscle weakness is an important component of chronic obstructive pulmonary disease (COPD). We hypothesised that quadriceps weakness would also be a feature of restrictive lung disease due to scoliosis.We studied 10 patients with severe scoliosis (median (interquartile range (IQR)) forced expiratory volume in 1 s (FEV1)35.3 (11)% predicted), 10 patients with severe COPD (FEV126.5 (9.0)% pred) and 10 healthy age-matched adults. We measured quadriceps strength, exercise capacity and analysed quadriceps muscle biopsies for myosin heavy-chain (MyHC) isoform expression and the presence of oxidative stress.Both groups exhibited quadriceps weakness with median (IQR) maximal voluntary contraction force being 46.0 (17.0) kg, 21.5 (21.0) kg and 31.5 (11.0) kg, respectively (p = 0.02 and 0.04, respectively, for each patient group against controls). Oxidative stress was significantly greater in the quadriceps of both restrictive and COPD patients. The scoliosis patients exhibited a decrease in the proportion of MyHC type I compared with controls; median (IQR) 35.3 (18.5)% compared with 47.7 (9.3)%, p = 0.028. The scoliosis patients also showed an increase in MyHC IIx (26.3 (15.5)% compared with 11.3 (13.0)%, p = 0.01.Quadriceps weakness is a feature of severe scoliosis; the similarities between patients with scoliosis and patients with COPD suggest a common aetiology to quadriceps weakness in both conditions.
Systematic identification of transcription factors associated with patient survival in cancers
Authors: Cheng Chao , Li Lei M , Alves Pedro , Gerstein Mark 
Published: May 2009

AbstractBackgroundAberrant activation or expression of transcription factors has been implicated in the tumorigenesis of various types of cancer. In spite of the prevalent application of microarray experiments for profiling gene expression in cancer samples, they provide limited information regarding the activities of transcription factors. However, the association between transcription factors and cancers is largely dependent on the transcription regulatory activities rather than mRNA expression levels.ResultsIn this paper, we propose a computational approach that integrates microarray expression data with the transcription factor binding site information to systematically identify transcription factors associated with patient survival given a specific cancer type. This approach was applied to two gene expression data sets for breast cancer and acute myeloid leukemia. We found that two transcription factor families, the steroid nuclear receptor family and the ATF/CREB family, are significantly correlated with the survival of patients with breast cancer; and that a transcription factor named T-cell acute lymphocytic leukemia 1 is significantly correlated with acute myeloid leukemia patient survival.ConclusionOur analysis identifies transcription factors associating with patient survival and provides insight into the regulatory mechanism underlying the breast cancer and leukemia. The transcription factors identified by our method are biologically meaningful and consistent with prior knowledge. As an insightful tool, this approach can also be applied to other microarray cancer data sets to help researchers better understand the intricate relationship between transcription factors and diseases.
Genes within the serotonergic system are differentially expressed in human brain
Authors: Sugden Karen , Tichopad Ales , Khan Nadeem , Craig Ian W , D'Souza Ursula M 
Published: May 2009

Abstract

Background
Serotonin is an important neurotransmitter with wide-ranging functions throughout the central nervous system. There is strong evidence to suggest that regulation of serotonergic gene expression might be related to genetic variability, and several studies have focused on understanding the functional effects of specific polymorphisms within these genes on expression levels. However, the combination of genotype together with gender and brain region could have an overall effect on gene expression. In this study, we report expression patterns of five serotonergic genes (TPH1, TPH2, 5-HT2A, 5-HT2C, 5-HTT) in seven different human post-mortem brain regions (superior frontal gyrus, superior temporal gyrus, striatum, cerebellum, hippocampus, midbrain and thalamus) using TaqMan™ real-time quantitative PCR. In addition, the effect of genotype and gender on their expression levels was determined.

Results
The data revealed that mRNA from the five genes investigated was detected in all brain regions and showed an overall significant difference in expression levels. Furthermore, the expression of 5-HT2C, 5-HT2A and TPH2 was found to be significantly different between the various brain regions. However, neither gender nor genotype showed significant effects on the expression levels of any of the genes assayed. Interestingly, TPH1 and TPH2 were expressed in all brain regions similarly except for within the striatum and cerebellum, where TPH1 was expressed at a significantly higher level than TPH2.

Conclusion
The effect of brain region has a greater influence on serotonergic gene expression than either genotype or gender. These data add to the growing body of evidence that effects of functional polymorphisms on gene expression in vitro are not observed ex vivo, and provide information that will aid in the design of expression studies of the serotonergic gene system within human post-mortem brain.
Both SEPT2 and MLL are down-regulated in MLL-SEPT2therapy-related myeloid neoplasia
Authors: Cerveira Nuno , Santos Joana , Bizarro Susana , Costa Vera , Ribeiro Franclim R , Lisboa Susana , Correia Cecília , Torres Lurdes , Vieira Joana , Snijder Simone , Mariz José M , Norton Lucília , Mellink Clemens H , Buijs Arjan , Teixeira Manuel R 
Published: May 2009

Abstract

Background
A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in MLL-related leukemia. Recently, we have established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described in the literature.

Methods
Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: CBFB-MYH11 (n = 13), PML-RARA (n = 12); RUNX1-RUNX1T1 (n = 12), normal karyotype (n = 11), and MLL gene fusions other than MLL-SEPT2 (n = 10). We also studied all three MLL-SEPT2 myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient.

Results
When compared with normal controls, we found a 12.8-fold reduction of wild-type SEPT2 and MLL-SEPT2 combined expression in cases with the MLL-SEPT2 gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type MLL and MLL-SEPT2 combined expression (p = 0.028). The down-regulation of SEPT2 in MLL-SEPT2 myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other MLL gene fusions). In addition, MLL expression was also down-regulated in the group of MLL fusions other than MLL-SEPT2, when compared with the normal control group (p = 0.023)

Conclusion
We found a significant down-regulation of both SEPT2 and MLL in MLL-SEPT2 myeloid neoplasias. In addition, we also found that MLL is under-expressed in AML patients with MLL fusions other than MLL-SEPT2.
Kinetic and Thermodynamic Characterization of Dihydrotestosterone-Induced Conformational Perturbations in Androgen Receptor Ligand-Binding Domain
Authors: Jasuja Ravi , Ulloor Jagadish , Yengo Christopher M. , Choong Karen , Istomin Andrei Y. , Livesay Dennis R. , Jacobs Donald J. , Swerdloff Ronald S. , Mikšovská Jaroslava , Larsen Randy W. , Bhasin Shalender 
Published: May 2009

AbstractLigand-induced conformational perturbations in androgen receptor (AR) are important in coactivator recruitment and transactivation. However, molecular rearrangements in AR ligand-binding domain (AR-LBD) associated with agonist binding and their kinetic and thermodynamic parameters are poorly understood. We used steady-state second-derivative absorption and emission spectroscopy, pressure and temperature perturbations, and 4,4′-bis-anilinonaphthalene 8-sulfonate (bis-ANS) partitioning to determine the kinetics and thermodynamics of the conformational changes in AR-LBD after dihydrotestosterone (DHT) binding. In presence of DHT, the second-derivative absorption spectrum showed a red shift and a change in peak-to-peak distance. Emission intensity increased upon DHT binding, and center of spectral mass was blue shifted, denoting conformational changes resulting in more hydrophobic environment for tyrosines and tryptophans within a more compact DHT-bound receptor. In pressure perturbation calorimetry, DHT-induced energetic stabilization increased the Gibbs free energy of unfolding to 8.4 ± 1.3 kcal/mol from 3.5 ± 1.6 kcal/mol. Bis-ANS partitioning studies revealed that upon DHT binding, AR-LBD underwent biphasic rearrangement with a high activation energy (13.4 kcal/mol). An initial, molten globule-like burst phase (k ∼30 sec−1) with greater solvent accessibility was followed by rearrangement (k ∼0.01 sec−1), leading to a more compact conformation than apo-AR-LBD. Molecular simulations demonstrated unique sensitivity of tyrosine and tryptophan residues during pressure unfolding with rearrangement of residues in the coactivator recruitment surfaces distant from the ligand-binding pocket. In conclusion, DHT binding leads to energetic stabilization of AR-LBD domain and substantial rearrangement of residues distant from the ligand-binding pocket. DHT binding to AR-LBD involves biphasic receptor rearrangement including population of a molten globule-like intermediate state.
Tethering, recycling and activation of the epithelial sodium–proton exchanger, NHE3
Authors: Alexander R. Todd , Grinstein Sergio 
Published: May 2009

SUMMARYNHE3 is a sodium–proton exchanger expressed predominantly in the apical membrane of renal and intestinal epithelia, where it plays a key role in salt and fluid absorption and pH homeostasis. It performs these functions through the exchange of luminal sodium for cytosolic protons. Acute regulation of NHE3 function is mediated by altering the total number of exchangers in the plasma membrane as well as their individual activity. Traffic between endomembrane and plasmalemmal pools of NHE3 dictates the density of exchangers available at the cell surface. The activity of the plasmalemmal pool, however,is not fixed and can be altered by the association with modifier proteins, by post-translational alterations (such as cAMP-mediated phosphorylation) and possibly also via interaction with specific plasmalemmal phospholipids. Interestingly, association with cytoskeletal components affects both levels of regulation, tethering NHE3 molecules at the surface and altering their intrinsic activity. This paper reviews the role of proteins and lipids in the modulation of NHE3 function.
Cytomegalovirus-fertőzés terhességben
Authors: Pusztai Rozália 
Published: May 2009

Absztrakt
A várandós anyák primer és rekurrens humán cytomegalovirus- (HCMV-) fertőzéséhez
társulhat a magzat fertőzése. A HCMV a congenitalis fertőzések leggyakoribb
okozója, amelynek legsúlyosabb következményei a szellemi visszamaradottság,
progrediáló halláskárosodás, látászavarok. Az anya primer fertőzését követi
leggyakrabban a magzat fertőzése, és a magzat károsodásai rendszerint súlyosak.
Növekszik az anyai rekurrens fertőzések után jelentkező, különböző súlyosságú
tünetekkel járó congenitalis HCMV-fertőzések száma. Az aktív HCMV-fertőzéssel
komplikált terhességek gondozásában döntő szerepet játszik a praenatalis
diagnosztika. A congenitalis HCMV-fertőzés potenciálisan súlyos következményei
ellenére kevés adat áll rendelkezésünkre a HCMV vertikális terjedésének
antivirális gyógyszerrel történő megelőzésére, de a passzív immunizálással
biztató eredmények vannak. Vakcina hiányában is elkerülhető a várandós anyák
aktív HCMV-fertőzése, ha felhívjuk a figyelmet a fertőzés veszélyeire és
ismertetjük a fertőzés megelőzésének lehetőségeit.
The Relationship Between Remittances and Health Care Provision in Mexico
Authors: Frank Reanne , Palma-Coca Oswaldo , Rauda-Esquivel Juan , Olaiz-Fernández Gustavo , Díaz-Olavarrieta Claudia , Acevedo-García Dolores 
Published: May 2009

Objectives. We examined whether remittances sent from the United States to Mexico were used to access health care in Mexico. Methods. Data were from a 2006 survey of 2 localities in the municipal city of Tepoztlán, Morelos, Mexico. We used logistic regression to determine whether household remittance expenditure on health care was associated with type of health insurance coverage. Results. Individuals who lacked insurance coverage or who were covered by the Seguro Popular program were significantly more likely to reside in households that spend remittances on health care than were individuals covered by an employer-based insurance program. Conclusions. Improving the coverage and quality of care within Mexico's health care system will help ensure that remittances serve as a complement, and not a substitute, to formal access to care.
Health Disparities Among Mexican American Women Aged 15–44 Years: National Health and Nutrition Examination Survey, 1999–2004
Authors: Wingo Phyllis A. , Kulkarni Aniket , Borrud Lori G. , McDonald Jill A. , Villalobos Susie A. , Green Diane C. 
Published: May 2009

Objectives. We analyzed the health of Mexican American women aged 15 to 44 years, by generation and language preference, to guide planning for reproductive health services in this growing population. Methods. We used personal interview and medical examination data from the 1999 to 2004 National Health and Nutrition Examination Surveys. We used SUDAAN for calculating age-adjusted prevalence estimates of demographic and health characteristics. The Satterthwaite adjusted F test and Student t test were used for subgroup comparisons. Results. The women had different health profiles (P < .05) by generation and language preference. Second- and later-generation women and women who used more English were more likely to be sexually active, to have been younger at first intercourse, and to have had more male sexual partners than were first-generation women and women who used more Spanish. Compared with their first-generation counterparts, second- and later-generation women drank more alcohol, were better educated, had higher incomes, and were more likely to have health insurance. Third-generation women were more likely to have delivered a low-birthweight baby than were first-generation women. Conclusions. Differences by generation and language preference suggest that acculturation should be considered when planning interventions to promote healthy reproductive behaviors among Mexican American women.
Childhood Abuse and Early Menarche: Findings From the Black Women's Health Study
Authors: Wise Lauren A. , Palmer Julie R. , Rothman Emily F. , Rosenberg Lynn 
Published: May 2009

Objectives. We examined the association between childhood abuse and early menarche in a sample of US Black women. Methods. We conducted multivariable log-binomial regression on data from 35 330 participants in the Black Women's Health Study to estimate risk ratios and 95% confidence intervals for the relation of childhood physical and sexual abuse with early age at menarche (i.e., < 12 years). Results. In adjusted analyses, sexual abuse was positively associated with early menarche, and the risk of early menarche increased with increasing frequency of sexual abuse incidents. We observed a weak but statistically significant association between physical abuse and early menarche. Associations between sexual abuse and early menarche were stronger when we used a more stringent cutpoint for early menarche (i.e., < 11 years). Conclusions. Our data suggest an increased risk of early menarche among Black women who experienced childhood sexual abuse. Evidence for an association between childhood physical abuse and early menarche was equivocal.
Treatability studies of textile wastewater on an aerobic fluidized bed biofilm reactor (FABR): a case study
Authors: Arun Kumar Thalla , Saravanan S. 
Published: May 2009

The performance of a pilot scale aerobic fluidized bed biofilm process and chemical coagulation for textile wastewater treatment was studied. In order to enhance biological treatment efficiency of textile wastewater, poly urethane cubes were incorporated as a supporting media for attached growth. Fenton's reagent was used as a coagulant in the present study. The fluidized bed biofilm process was operated at four HRTs (3, 4.5, 6 and 8 hour) and the results showed that the COD removal efficiency increased from 69% to 94% when the HRT increased from 3 to 4.5 and there of the removal efficiency remained constant around 94%, even though using relatively low MLSS concentration and short sludge retention time. COD and TDS removals of 94.2% and 93.3% were achieved by overall combined process (FABR + Coagulation aided Sedimentation). After the treatment there is remarkable decrease in colour in addition to COD and TDS.
This combined process was highly competitive in comparison to the other similar combined systems. It was concluded that this combined process was successfully employed and much effectively decreased they COD, TDS and color of textile wastewater treatment at pilot scale.
A review of published reports regarding zoonotic pathogen infection in veterinarians
Authors: Baker Whitney S. , Gray Gregory C. 
Published: May 2009

Abstract
Objective—To identify published reports regarding zoonotic pathogen infection among veterinarians.
Design—Literature review.
Procedures—The PubMed electronic database of medical literature published between 1966 and November 2007 was searched. Clinical case reports and reports of outbreak investigations were also identified through searches of the literature outside of PubMed and searches of references listed in included articles. Reports eligible for inclusion included controlled and uncontrolled studies examining seroprevalence of animal pathogens in veterinarians, serosurveys involving veterinarians, and reports of zoonotic pathogen infections causing clinical illness.
Results—66 relevant articles were identified. This included 44 seroepidemiologic studies (some examined > 1 pathogen), 12 case reports, 3 outbreak investigations, and 7 self-reported surveys (including 4 related to personal protective equipment use). Of the 44 seroepidemiologic studies, 37 (84%) identified an increased risk of zoonotic pathogen infection among veterinarians, and 7 (16%) identified no increased risk or a decreased risk. Surveys also documented that veterinarians often failed to use recommended personal protective equipment.
Conclusions and Clinical Relevance—Our review indicated that veterinarians had an increased risk of infection with a number of zoonotic pathogens. It also suggested that veterinarians may inadvertently serve as biological sentinels for emerging pathogens and could potentially spread zoonotic pathogens to their families, community members, and the animals for which they provide care. Professional and policy measures should be implemented to reduce the risk that veterinarians will become infected with, or transmit, zoonotic pathogens.