bluuebunny/crossref_metadata_2025_split huggingface dataset:
Halofuginone inhibits multiple myeloma growth in vitro and in vivo and enhances cytotoxicity of conventional and novel agents
Authors: Leiba Merav , Jakubikova Jana , Klippel Steffen , Mitsiades Constantine S. , Hideshima Teru , Tai Yu‐Tzu , Leiba Adi , Pines Mark , Richardson Paul G. , Nagler Arnon , Anderson Kenneth C. 
Published: April 2012

SummaryMultiple Myeloma (MM), a malignancy of plasma cells, remains incurable despite the use of conventional and novel therapies. Halofuginone (HF), a synthetic derivative of quinazolinone alkaloid, has recently been shown to have anti‐cancer activity in various preclinical settings. This study demonstrated the anti‐tumour activity of HF against a panel of human MM cell lines and primary patient‐derived MM cells, regardless of their sensitivity to conventional therapy or novel agents. HF showed anti‐MM activity in vivo using a myeloma xenograft mouse model. HF suppressed proliferation of myeloma cells alone and when co‐cultured with bone marrow stromal cells. Similarly, HF induced apoptosis in MM cells even in the presence of insulin‐like growth factor 1 or interleukin 6. Importantly, HF, even at high doses, did not induce cytotoxicity against CD40 activated peripheral blood mononuclear cells from normal donors. HF treatment induced accumulation of cells in the G0/G1 cell cycle and induction of apoptotic cell death associated with depletion of mitochondrial membrane potential; cleavage of poly (ADP‐ribose) polymerase and caspases‐3, 8 and 9 as well as down‐regulation of anti‐apoptotic proteins including Mcl‐1 and X‐IAP. Multiplex analysis of phosphorylation of diverse components of signalling cascades revealed that HF induced changes in P38MAPK activation; increased phosphorylation of c‐jun, c‐jun NH(2)‐terminal kinase (JNK), p53 and Hsp‐27. Importantly, HF triggered synergistic cytotoxicity in combination with lenalidomide, melphalan, dexamethasone, and doxorubicin. Taken together, these preclinical studies provide the preclinical framework for future clinical studies of HF in MM.
Marked genetic heterogeneity in familial myelodysplasia/acute myeloid leukaemia
Authors: Holme Harriet , Hossain Upal , Kirwan Michael , Walne Amanda , Vulliamy Tom , Dokal Inderjeet 
Published: April 2012

SummaryThe myelodysplastic syndromes (MDS) are heterogeneous and can evolve into acute myeloid leukaemia (AML). Rare familial cases are reported in which five disease genes have been identified to date (RUNX1, CEBPA, TERC, TERT and GATA2). Here we report the genetic categorization of 27 families with familial MDS/AML. All of these families were screened for RUNX1, CEBPA, TERC, TERT and GATA2 as well as TET2 and NPM1. Five of the 27 families had telomerase mutations; one had a RUNX1 mutation, while none were found to have TET2, CEBPA or NPM1 mutations. We identified four families with heterozygous GATA2 mutations, each associated with a different phenotype. While one of these mutations is novel, three have been previously reported: one has been described in dendritic cell, monocyte, B and NK lymphoid (DCML) deficiency and one is in a family that has been reported in a series with primary lymphoedema with a predisposition to AML (Emberger syndrome). In summary, genetic characterization was shown in 10 (four GATA2, three TERT, two TERC, one RUNX1) of these families; however 17 remain uncharacterized, highlighting marked genetic heterogeneity in familial MDS/AML and the scope for further functional pathways that could give rise to this group of disorders.
Distinct expression pattern of claudin‐6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomas
Authors: Ushiku Tetsuo , Shinozaki‐Ushiku Aya , Maeda Daichi , Morita Shigeki , Fukayama Masashi 
Published: April 2012

Ushiku T, Shinozaki‐Ushiku A, Maeda D, Morita S & Fukayama M  (2012) Histopathology Distinct expression pattern of claudin‐6, a primitive phenotypic tight junction molecule, in germ cell tumours and visceral carcinomasAims:  This study aimed to clarify claudin‐6 expression patterns in cancers.Methods and results:  We surveyed claudin‐6 expression by immunohistochemistry using tissue microarray in 860 tumours, including germ cell tumours and major carcinomas. Claudin‐6 was expressed consistently in germ cell tumours (28 of 28, 100%), whereas only 64 (8%) of 832 non‐germ cell tumours demonstrated claudin‐6 expression. Further immunohistochemical study in full tissue sections demonstrated diffuse claudin‐6 staining in all seminomas (n = 14), embryonal carcinomas (n = 10), yolk sac tumours (n = 12) and mononuclear trophoblastic cells of choriocarcinomas (n = 3), and focal staining in immature epithelial components of immature teratomas (n = 6). Additionally, because alpha‐fetoprotein (AFP)‐producing gastric adenocarcinomas and pulmonary high‐grade fetal adenocarcinomas were among the claudin‐6 expressing non‐germ cell tumours in the microarray studies, we predicted that claudin‐6 may be a biomarker for them and studied additional tumours in full sections, which showed claudin‐6 expression in AFP‐producing gastric adenocarcinomas (18 of 20, 90%) and pulmonary high‐grade fetal adenocarcinomas (four of five, 80%). Only one of 11 hepatoblastomas demonstrated focal claudin‐6 staining.Conclusions:  This study demonstrated that claudin‐6 is a novel diagnostic marker for primitive germ cell tumours and is also expressed frequently in some cancers with a primitive phenotype.
Interactive effects of landscape context constrain the effectiveness of local agri‐environmental management
Authors: Concepción Elena D. , Díaz Mario , Kleijn David , Báldi András , Batáry Péter , Clough Yann , Gabriel Doreen , Herzog Felix , Holzschuh Andrea , Knop Eva , Marshall E. Jon P. , Tscharntke Teja , Verhulst Jort 
Published: April 2012

Summary1. Ecological theory predicts that the effectiveness of local agri‐environmental management to enhance species richness at field scales will be the highest at intermediate levels of landscape complexity because of nonlinear effects of landscape context on field‐scale diversity.2. We examined how landscape complexity determined effectiveness of local agri‐environmental management in terms of effects on species richness of birds, plants, spiders and bees in 232 extensive and intensive paired fields (112 arable fields and 120 grasslands) from 18 regions located in six European countries.3. As predicted, landscape complexity enhanced field‐scale species richness in a mostly nonlinear (sigmoidal) way, with earlier species richness increases in extensive than in intensive fields along landscape complexity gradients. Length of semi‐natural boundaries (for arable fields) and proportion of unfarmed habitat (for grasslands) were the landscape features influencing species richness.4. The relationships between effectiveness of local management and landscape complexity for all taxa were best described with hump‐shaped curves, indicating the highest effectiveness at intermediate landscape complexities.5. Synthesis and applications. We used models to investigate how and why effects of local management intensity on species richness vary along wide gradients of landscape complexity. We conclude that landscape‐scale management options should take priority over local extensification measures within agri‐environmental programmes. These programmes should follow a hierarchical multi‐scale approach directed to address landscape‐scale constraints on local diversity.
The involvement of parents in healthcare decisions where adult children are at risk of lacking decision‐making capacity: a qualitative study of treatment decisions in epilepsy
Authors: Redley M. , Prince E. , Bateman N. , Pennington M. , Wood N. , Croudace T. , Ring H. 
Published: April 2012

AbstractBackground  Patients with intellectual disabilities (ID) receive health care by proxy. It is family members and/or paid support staff who must recognise health problems, communicate with clinicians, and report the benefits, if any, of a particular treatment. At the same time international and national statutes protect and promote the right of people with disabilities to access the highest attainable standards of health on the basis of free and informed consent.Methods  To consider the role of parent‐proxies in the management of epilepsy in adult children with ID who are at risk of lacking capacity to make decisions about their health care we interviewed 21 mothers.Findings  These mothers are not pursuing changes in treatment that might improve their son or daughter's epilepsy, nor are they willing to countenance changes in treatment. Clinicians concerned to build and sustain therapeutic alliances with these mothers, our evidence suggests, may well avoid going against their wishes.Discussion  Our research highlights the interactional contingencies of a hitherto neglected three‐way clinical relationship comprising parent‐proxy, an adult at risk of lacking decision‐making capacity, and a treating clinician. This is a relationship, our findings suggest, where little importance is attached to either patient consent, or involvement in treatment decisions.
Validation of the attitudes toward intellectual disability – ATTID questionnaire
Authors: Morin D. , Crocker A. G. , Beaulieu‐Bergeron R. , Caron J. 
Published: April 2012

AbstractBackground  Individuals with an intellectual disability (ID) continue to experience major obstacles towards social, educational and vocational integration. Negative attitudes toward persons with ID has remained relevant over time and has led to discrimination and stigma.Objective  The present study describes the development of a new questionnaire for tapping into the general population's attitudes toward individuals with ID and addresses its psychometric properties.Methods  Adopting a multidimensional perspective, the Attitudes Toward Intellectual Disability Questionnaire (ATTID) was developed from a series of previously validated instruments and principles from the Montreal Declaration on Intellectual Disability (2004). The ATTID was administered by phone to 1605 randomly selected adult men and women, stratified by region in the Province of Quebec, Canada.Results  The ATTID yielded a five‐factor structure overlapping the tri‐partite model of attitudes. The cognitive component was represented by two factors: knowledge of capacity and rights and knowledge of causes of ID. The affective component tapped into two factors: discomfort and sensitivity/compassion. Finally, the behavioural component emerged as a single factor. The ATTID had good internal consistency with Cronbach's alpha coefficients ranging from 0.59 to 0.89 for the five factors and of 0.92 for the overall questionnaire. Test–retest reliability yielded correlations from 0.62 to 0.83 for the five factors.Conclusion  The ATTID can be used to measure attitudes among different populations and allows comparisons over time within the same population as a function of various intervention strategies for de‐stigmatising ID.
Family functioning in families with a child with Down syndrome: a mixed methods approach
Authors: Povee K. , Roberts L. , Bourke J. , Leonard H. 
Published: April 2012

AbstractBackground  This study aimed to explore the factors that predict functioning in families with a child with Down syndrome using a mixed methods design. The quantitative component examined the effect of maladaptive and autism‐spectrum behaviours on the functioning of the family while the qualitative component explored the impact of having a child with Down syndrome on family holidays, family activities and general family functioning.Methods  Participants in this study were 224 primary caregivers of children with Down syndrome aged 4–25 years (57.1% male; 42.9% female) currently residing in Western Australia (74.0% in metropolitan Perth and 26.0% in rural Western Australia).Results  Maladaptive and autism‐spectrum behaviour were associated with poorer family functioning. Mean total scores on the measures of family functioning and marital adjustment were comparable to that of families of typically developing children. Consistent with the quantitative findings, normality was the most common theme to emerge in the qualitative data. Child problem behaviours were also identified by parents/carers as having a negative impact on the family.Conclusions  This study has implications for the development of programs to support families with a child with Down syndrome and may dispel some of the myths surrounding the impact of intellectual disability on the family.
Parents of children with and without intellectual disability: couple relationship and individual well‐being
Authors: Norlin D. , Broberg M. 
Published: April 2012

AbstractBackground  Research on parents of children with intellectual disability (ID) has identified a range of risk and protective factors for parental well‐being. In family research, the association between marital quality and depression is a vital field of investigation. Still little research has addressed how aspects of the couple relationship affect the adaptation of parents of children with ID. The present study examined predictive links between couple relationship factors (marital quality and coparenting quality) and individual well‐being.Methods  Data were obtained through self‐report questionnaires completed by parents of children with ID (mothers, n = 58; and fathers, n = 46) and control children (mothers, n = 178; and fathers, n = 141). To test the hypothesis that couple relationship factors predicted individual well‐being, multiple regression analyses were performed controlling for the following risk factors identified by previous research: child self‐injury/stereotypic behaviour, parenting stress, and economic risk.Results  Marital quality predicted concurrent well‐being, and coparenting quality predicted prospective well‐being. Mothers of children with ID reported lower well‐being than other parents.Conclusions  There is a continued need for investigation of the details of the links between couple relationship and individual well‐being in parents of children with ID. Couple relationship factors should be given consideration in clinical interventions.
Disposition kinetics of albendazole and metabolites in laying hens
Authors: BISTOLETTI M. , ALVAREZ L. , LANUSSE C. , MORENO L. 
Published: April 2012

Bistoletti, M., Alvarez, L., Lanusse, C., Moreno, L. Disposition kinetics of albendazole and metabolites in laying hens. J. vet. Pharmacol. Therap. 36, 161–168.An increasing prevalence of roundworm parasites in poultry, particularly in litter‐based housing systems, has been reported. However, few anthelmintic drugs are commercially available for use in avian production systems. The anthelmintic efficacy of albendazole (ABZ) in poultry has been demonstrated well. The goal of this work was to characterize the ABZ and metabolites plasma disposition kinetics after treatment with different administration routes in laying hens. Twenty‐four laying hens Plymouth Rock Barrada were distributed into three groups and treated with ABZ as follows: intravenously at 10 mg/kg (ABZ i.v.); orally at the same dose (ABZ oral); and in medicated feed at 10 mg/kg·day for 7 days (ABZ feed). Blood samples were taken up to 48 h posttreatment (ABZ i.v. and ABZ oral) and up to 10 days poststart feed medication (ABZ feed). The collected plasma samples were analyzed using high‐performance liquid chromatography. ABZ and its albendazole sulphoxide (ABZSO) and ABZSO2 metabolites were recovered in plasma after ABZ i.v. administration. ABZ parent compound showed an initial concentration of 16.4 ± 2.0 μg/mL, being rapidly metabolized into the ABZSO and ABZSO2 metabolites. The ABZSO maximum concentration (Cmax) (3.10 ± 0.78 μg/mL) was higher than that of ABZSO2Cmax (0.34 ± 0.05 μg/mL). The area under the concentration vs time curve (AUC) for ABZSO (21.9 ± 3.6 μg·h/mL) was higher than that observed for ABZSO2 and ABZ (7.80 ± 1.02 and 12.0 ± 1.6 μg·h/mL, respectively). The ABZ body clearance (Cl) was 0.88 ± 0.11 L·h/kg with an elimination half‐life (T1/2el) of 3.47 ± 0.73 h. The T1/2el for ABZSO and ABZSO2 were 6.36 ± 1.50 and 5.40 ± 1.90 h, respectively. After ABZ oral administration, low ABZ plasma concentrations were measured between 0.5 and 3 h posttreatment. ABZ was rapidly metabolized to ABZSO (Cmax, 1.71 ± 0.62 μg/mL) and ABZSO2 (Cmax, 0.43 ± 0.04 μg/mL). The metabolite systemic exposure (AUC) values were 18.6 ± 2.0 and 10.6 ± 0.9 μg·h/mL for ABZSO and ABZSO2, respectively. The half‐life values after ABZ oral were similar (5.91 ± 0.60 and 5.57 ± 1.19 h for ABZSO and ABZSO2, respectively) to those obtained after ABZ i.v. administration. ABZ was not recovered from the bloodstream after ABZ feed administration. AUC values of ABZSO and ABZSO2 were 61.9 and 92.4 μg·h/mL, respectively. The work reported here provides useful information on the pharmacokinetic behavior of ABZ after both i.v. and oral administrations in hens, which is a useful first step to evaluate its potential as an anthelmintic tool for use in poultry.
An Outer Membrane Vesicle Vaccine for Prevention of Serogroup A and W‐135 Meningococcal Disease in the African Meningitis Belt
Authors: Norheim G. , Tunheim G. , Næss L. M. , Kristiansen P. A. , Caugant D. A. , Rosenqvist E. 
Published: April 2012

AbstractThe bacterium Neisseria meningitidis of serogroups A and W‐135 has in the recent decade caused most of the cases of meningococcal meningitis in the African meningitis belt, and there is currently no efficient and affordable vaccine available demonstrated to protect against both these serogroups. Previously, deoxycholate‐extracted outer membrane vesicle (OMV) vaccines against serogroup B meningococci have been shown to be safe and induce protection in humans in clonal outbreaks. The serogroup A and W‐135 strains isolated from meningitis belt epidemics demonstrate strikingly limited variation in major surface‐exposed protein structures. We have here investigated whether the OMV vaccine strategy also can be applied to prevent both serogroups A and W‐135 meningococcal disease. A novel vaccine combining OMV extracted from recent African serogroup A and W‐135 strains and adsorbed to aluminium hydroxide was developed and its antigenic characteristics and immunogenicity were studied in mice. The specificity of the antibody responses was analysed by immunoblotting and serum bactericidal activity (SBA) assays. Moreover, the bivalent A+W‐135 vaccine was compared with monovalent A and W‐135 OMV vaccines. The bivalent OMV vaccine was able to induce similar SBA titres as the monovalent A or W‐135 OMV towards both serogroups. High SBA titres were also observed against a meningococcal serogroup C strain. These results show that subcapsular antigens may be of importance when developing broadly protective and affordable vaccines for the meningitis belt.
Chimerism but not Neonatal Antigen Exposure Induces Transplant Tolerance
Authors: Peiguo Z. , Shijie Z. , Liang M. 
Published: April 2012

AbstractAcquired transplant tolerance could be readily induced during foetal or neonatal period through donor cell infusion, but it is not the case in adults. This phenomenon has been attributed to the variation of immune system development in neonatal and adult periods. To investigate the role of immature immune system and chimerism in neonatal transplant tolerance, irradiated spleen cells or cell fraction from F1 (BALB/c × C57BL/6) or GFP‐F1 mice were injected intravenously into neonatal C57BL/6 mice to induce tolerance. Irradiated cells or cell fraction could not induce chimerism and transplant tolerance in neonatal mice, even increasing the dose of donor cells to 5 × 107. Living donor cells induced tolerance in neonatal mice, and the quantity of living cells was correlated with the degree of chimerism and tolerance. At the amount of 3 × 107 F1 spleen cells, skin grafts were survived permanently in more than 80% of treated mice. However, the amount of 0.7 × 107 F1 spleen cells could only slightly prolong allografts’ survival. The more donor cells were infused, the higher level of chimerism was achieved, and the higher frequency of alloreactive T cells was deleted. Chimerism is prerequisite for the induction and maintenance of tolerance. Chimerism in long‐term tolerant mice was significantly higher than that in chronic graft rejected mice, with 6.48 ± 4.02% versus 1.41 ± 0.77%. It implies that transplant tolerance depends on the establishment of chimerism, but not on antigen exposure to immature immune system in foetus or neonates.
Antioxidation status and histidine dipeptides content in broiler blood and muscles depending on protein sources in feed
Authors: Kopeć W. , Jamroz D. , Wiliczkiewicz A. , Biazik E. , Hikawczuk T. , Skiba T. , Pudło A. , Orda J. 
Published: April 2012

SummaryOne‐day‐old chickens were fed mixtures containing different raw materials (fish by‐products meal, porcine blood cells meal, blood meal, wheat gluten, fodder yeast), as a source of histidine and β‐alanine – components of carnosine. Control birds were administered a feed mixture, in which soy bean meal was the main protein source. The bodyweight, feed consumption and conversion, antioxidant characteristics and histidine dipeptides content in blood and muscles, and also amino acid composition of chicken meat on day 34 post‐hatch were recorded. The best (p < 0.05) performance and feed conversion were observed in chickens fed mixture containing porcine blood cells meal. In blood plasma of control chickens, a significantly (p < 0.01) higher ability to scavenge DPPH radicals was found. However, the highest catalase activity in erythrocytes was determined in chickens fed mixtures with blood by‐products. Insignificant differences in both carnosine and anserine levels in plasma between treatments were noted. Breast muscles from control birds were characterized by lower activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) (p < 0.05; p < 0.01), than those from chickens fed blood by‐products. Improved ability to reduce ferric ions (FRAP) (p < 0.01) and carnosine content in meat from chickens fed blood cell meal were recorded. No direct relations between amino acids content in feed mixtures and in meat were observed.
TRANSPAPILLARY BILIARY FORCEPS BIOPSY TO DISTINGUISH BENIGN BILIARY STRICTURE FROM MALIGNANCY: HOW MANY TISSUE SAMPLES SHOULD BE OBTAINED?
Authors: KAWASHIMA HIROKI , ITOH AKIHIRO , OHNO EIZABURO , GOTO HIDEMI , HIROOKA YOSHIKI 
Published: April 2012

Background:  The sensitivity of transpapillary biliary forceps biopsy for malignancy has been reported as varying from 43–81%. Therefore, there are false negatives in more than 20% of patients, which makes it difficult to diagnose benign biliary stricture as benignancy in a clinical setting.Methods:  To clarify the number of tissue samples that should be obtained during transpapillary forceps biopsy to distinguish benign biliary stricture from malignancy, patients undergoing transpapillary biliary forceps biopsy at our institute were examined retrospectively in this study.Results:  Seventy‐two biliary forceps biopsy procedures were performed on 61 patients. The final diagnoses were malignant biliary stricture in 34 patients and benign stricture in 27 patients. The overall sensitivity and specificity for malignancy in this study were 76.5% and 100%, respectively. There were zero out of 10 (0%) false‐negative patients when three or more tissue samples were obtained. In contrast, when four or more tissue samples were obtained, eight out of eight (100%) patients had negative diagnoses for malignancy and were finally diagnosed with benignancy.Conclusion:  We suggest that three or more tissue samples are recommended for the diagnosis of biliary malignant stricture.