bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apo‐nitrophorin 4 at atomic resolution
Authors: Amoia Angela M. , Montfort William R. 
Published: July 2007

AbstractThe nitrophorins from Rhodnius prolixus, the kissing bug, are heme‐containing proteins used for the transport of nitric oxide to aide the insect in obtaining a blood meal. The Rhodnius nitrophorins display an eight‐stranded antiparallel beta‐barrel motif, typical of lipocalins, with a histidine‐linked heme in the open end of the barrel. Heme is stabilized in the ferric state and highly distorted, displaying a ruffled conformation that may be of importance in the setting of the reduction potential. To help in understanding the means by which the protein matrix, an inherently soft material, is able to distort the heme from its low‐energy planar conformation, we have determined the crystal structure of apo‐nitrophorin 4–1.1 Å resolution. Removal of the heme from nitrophorin 4 has very little effect on its structure: The heme binding cavity remains open and the loops near the cavity entrance respond to lower pH in the same manner as the intact protein. We conclude that the general stability of the lipocalin fold and apparent rigidity of the beta‐barrel provide the means for distorting the heme cofactor.
What difference does training make? A randomized trial with waiting‐list control of general practitioners seeking advanced training in drug misuse
Authors: Strang John , Hunt Claire , Gerada Clare , Marsden John 
Published: July 2007

ABSTRACTAim  To measure changes in knowledge, attitudes and clinical practice of general practitioners (GPs) enrolled to receive training in the management of drug misusers.Design  Two‐group randomized trial with training (T) and waiting‐list (WL) control comparison conditions.Setting and participants  A total of 112 GPs working in primary care practices in England.Interventions  A 6‐month, part‐time, mixed‐methods training course provided by the Royal College of General Practitioners. GPs randomized to the WL control received no special training or guidance during the study period.Outcome measures and analysis  Knowledge, therapeutic attitudes (commitment, role security, situational constraints and prescribing confidence) and clinical practice behaviour change (numbers of drug misusers seen, treated). Intention‐to‐treat/train (ITT) analysis, supplemented by treatment/training received (TR) analysis.Findings  Training applicants had positive attitudes towards and were already involved in the care of drug misusers. Improvements in attitudes and behaviour were greatest among the T group, although only ‘role security’ and ‘situational constraint’ reached statistical significance (ITT). A subgroup in the WL group circumvented their allocation and received training, prompting supplementary analysis by TR. Overall, GPs who received training showed markedly greater improvements in knowledge, attitudinal and prescribing confidence measures and remained more actively involved in treating drug misusers than GPs who remained in the WL control group (TR analysis).Conclusions  GPs seeking special training for the care of drug misusers are both positively disposed to this patient population and clinically active. Benefits unambiguously attributable to the course were modest. While a TR effect was observed, strict adherence to ITT analysis failed to identify significant benefits observed with the training provided. Randomisation and waiting‐list controls design are insufficient as a research method for training evaluation studies if ITT analysis is used exclusively.
Lenalidomide‐induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment‐naïve patients undergoing front‐line lenalidomide and dexamethasone therapy
Authors: Niesvizky Ruben , Naib Tara , Christos Paul J. , Jayabalan David , Furst Jessica R. , Jalbrzikowski Jessica , Zafar Faiza , Mark Tomer , Lent Richard , Pearse Roger N. , Ely Scott , Leonard John P. , Mazumdar Madhu , Chen‐Kiang Selina , Coleman Morton 
Published: August 2007

SummaryData on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide‐induced myelosuppression. Eight of 14 patients with grade ≥3 myelosuppression had baseline creatinine clearance (CrCl) ≤0·67 ml/s. Kaplan–Meier analysis by log‐rank test demonstrated a significant association (P < 0·0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8·4; 95% confidence interval 2·9–24·7, P = 0·0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients.
Detection of phospho‐STAT5 in mast cells: a reliable phenotypic marker of systemic mast cell disease that reflects constitutive tyrosine kinase activation
Authors: Zuluaga Toro Tania , Hsieh Fred H. , Bodo Juraj , Dong Henry Y. , Hsi Eric D. 
Published: July 2007

SummarySystemic mastocytosis (SM) is characterized by the abnormal proliferation and accumulation of mast cells (MCs). Constitutive activation of kit, a receptor tyrosine kinase (TK), has been associated with all types of SM. Signal transducers and activators of transcription (STATs), such as STAT5, mediate downstream kit signalling. We hypothesized that nuclear phospho‐STAT5 (pSTAT5) in MCs might reflect TK activation and would be a marker of abnormal MCs in SM. Expression of tryptase, CD25, CD2 and pSTAT5 was evaluated by immunohistochemistry (IHC) on archival cases of SM and cutaneous mastocytosis (CM). pSTAT5 was detected in 23/23 of SM and 1/9 of CM MC nuclei. 23/23 SM had CD25 + MCs. Control tissue MCs were negative for pSTAT5. Nuclear pSTAT5 in MCs from SM reflects abnormal TK activation. We propose nuclear pSTAT5 positivity in MCs as an additional minor phenotypic criterion for diagnosis of SM in future World Health Organization classification schemes.
AKAP12, a gene with tumour suppressor properties, is a target of promoter DNA methylation in childhood myeloid malignancies
Authors: Flotho Christian , Paulun Annika , Batz Christiane , Niemeyer Charlotte M. 
Published: August 2007

SummaryA‐kinase anchor protein 12 (AKAP12) is a scaffold protein that participates in mitotic regulation and other signalling processes and probably exerts tumour suppressor function. We hypothesized that epigenetic repression of the AKAP12 gene might occur in malignant myeloid disorders. This study demonstrated that the 5′ CpG island of AKAP12 was unmethylated in normal haematopoietic progenitors and granulocytes but exhibited profound methylation in Kasumi‐1 and SKNO‐1 leukaemic myeloblasts. Correspondingly, AKAP12 was expressed in normal progenitors but transcriptionally silent in leukaemic blasts. Re‐expression of AKAP12 in Kasumi‐1 and SKNO‐1 cells was accomplished by treatment with MS275 alone or in combination with zebularine, indicating epigenetic mechanisms of gene repression. AKAP12 hypermethylation was found in one case of refractory anaemia with excess blasts (RAEB) and two cases of acute myeloid leukaemia (AML) in a panel of 21 blood or bone marrow samples from children with malignant myeloid disorders including refractory cytopenia, RAEB, juvenile myelomonocytic leukaemia and AML. While AKAP12 function has not been previously linked to leukaemogenesis, our results raise the possibility that epigenetic silencing of AKAP12 is involved in myeloid malignancies.
Frequent occurrence of B‐cell lymphomas in angioimmunoblastic T‐cell lymphoma and proliferation of Epstein–Barr virus‐infected cells in early cases
Authors: Willenbrock Klaus , Bräuninger Andreas , Hansmann Martin‐Leo 
Published: August 2007

SummarySecondary lymphomas occurring in the setting of angioimmunoblastic T‐cell lymphoma (AILT) are considered to be rare. Their occurrence has been attributed to Epstein–Barr virus (EBV)‐associated lymphoproliferations. A previous study detected a dysregulated hypermutation process in B‐cells of AILT. The present study aimed at estimating the frequency of B‐cell lymphomas in AILT. By studying the expression of EBV and activation‐induced cytidine deaminase (AID) as an indicator of hypermutating cells, we assessed whether B‐cell lymphoproliferations in AILT were strictly associated with EBV and whether hypermutation might contribute to lymphomagenesis. Among 161 cases of AILT, diagnosed between 1996 and 2005 at the lymph node registry, Frankfurt, Germany, 19 cases were detected that also had B‐cell non‐Hodgkin lymphoma (NHL) and two cases had classical Hodgkin lymphoma (HL). EBV was detected in tumour cells of 7/18 NHL and both HL, suggesting that factors other than EBV contribute to lymphomagenesis. AID was expressed in AILT in large cells disseminated in the tissue, implying that the process of somatic hypermutation is ongoing in AILT, although the GC architecture is disrupted. This might be relevant in the development of secondary lymphomas.
Storage of small bale silage and haylage – influence of storage period on fermentation variables and microbial composition
Authors: Müller C. E. , Pauly T. M. , Udén P. 
Published: August 2007

AbstractAn experiment investigating changes in fermentation variables and microbial composition during storage of small‐bale silage and haylage was performed. Haylage was defined as silage with a dry‐matter (DM) content exceeding 500 g kg−1. Grass was wilted to three different DM contents, and baled into silage (350 g DM kg−1), haylage with a low DM content (550 g kg−1) and haylage with high DM content (700 g kg−1) in small rectangular‐shaped bales (0·80 m × 0·48 m × 0·36 m) that were individually wrapped. Bales were stored for short (2 months) or long (14 months) periods before opening and sampling. Silage had higher concentrations of fermentation products and a lower pH than either of the two haylage types. In general, long‐term storage influenced all fermentation variables except concentrations of butyric acid and succinic acid, and yeast counts were higher after 14 months than 2 months of storage. However, silage changed in more fermentation variables during storage than the two haylage types. Although differences between short‐ and long‐term stored silage were found, linear correlations between short‐ and long‐term stored bales were present for all chemical variables. Pearson's correlation coefficients were highest for lactic acid, followed by pH.
Seasonal changes in herbage mass and nutritive value of a range of grazed legume swards under Mediterranean and cool temperate conditions
Authors: Sölter U. , Hopkins A. , Sitzia M. , Goby J. P. , Greef J. M. 
Published: August 2007

SummarySeasonal changes in herbage mass and herbage quality of legume‐based swards under grazing by sheep or cattle were investigated at four locations in climatically different zones of Europe: Sardinia (Italy), southern France, northern Germany and south‐west England (UK). At each location standard treatments were applied to legumes typical of species widely used in each locality:Medicago polymorphain Italy,Medicago sativain France, andTrifolium repensin Germany and in UK. At each site comparisons were made of two other legumes:Trifolium subterraneumandHedysarum coronariumin Italy,Onobrychis sativaandTrifolium incarnatumin France,Trifolium pratenseandLotus corniculatusin Germany, andTrifolium ambiguumandL. corniculatusin UK. Legumes were sown in mixture with locally appropriate companion grasses, and measurements were made over two or three grazing periods. In ItalyM. polymorphaswards gave the greatest herbage mass in grazing period 1 butH. coronariumwas more persistent. At the French site all legumes established poorly with no significant herbage mass differences between treatments. At both the UK and German sitesL. corniculatusmaintained a high proportion of legume in the sward;T. repensshowed poor persistence under continuous sheep grazing in UK but persisted under cattle grazing in Germany, whileT. ambiguumwas slow to establish in the UK, andT. pratenseproved to be of comparable herbage mass to the standardT. repens‐based sward in the last year of the experiment. The concentration of crude protein andin vitrodigestibility of organic matter in the dry matter of herbage showed greater within‐season variation than between treatments at each site. It is concluded that, in addition to currently used species, legume‐based swards containingH. coronarium, O. sativaandL. corniculatusall have potential to contribute to forage production for low‐input grazing and their use merits further consideration in systems of livestock production in Europe.
Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell‐clonotypic monoclonal antibody, 6B11
Authors: Montoya Carlos J. , Pollard David , Martinson Jeffrey , Kumari Kumud , Wasserfall Clive , Mulder Candice B. , Rugeles Maria T. , Atkinson Mark A. , Landay Alan L. , Wilson S. Brian 
Published: July 2007

SummaryIdentification of human CD1d‐restricted T‐cell receptor (TCR)‐invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T‐cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical Vα24Jα18 TCR α chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0·01–0·92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8+ iNKT cells being a phenotypic and functionally different subset from CD4+ and double negative iNKT cells; in particular, LAG‐3 was preferentially expressed on CD8+ iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4+ subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first‐degree relatives. Moreover, peripheral blood CD4+ iNKT cells were the highest producers of interleukin‐4, while the production of interferon‐γ and tumour necrosis factor‐α was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune‐mediated diseases.
Role stress and job satisfaction for nurse specialists
Authors: Chen Yao‐Mei , Chen Sue‐Hui , Tsai Chiu‐Yueh , Lo Liang‐Yueh 
Published: August 2007

AbstractTitle.  Role stress and job satisfaction for nurse specialists Aim.  This paper is a report of a study to illustrate the unique relationship between role stress and job satisfaction and provide recommendations for advanced nursing practice in Taiwan.Background.  International literature has shown that work role‐related stress experienced by staff nurses predicts role strain, which in turn influences job satisfaction and intention to leave the job. In this study, the direct relationship between role stress and job satisfaction of nurse specialists was examined after controlling for personality trait and personal characteristics.Method.  In 2004 a convenience sample of 129 nurse specialists from five acute care teaching hospitals in Taiwan participated. They completed a questionnaire (response rate 81%) focusing on personal characteristics, the Five Factor Model of personality traits, role stress (i.e. ambiguity, conflict, overload, incompetence) and job satisfaction (i.e. professionalism, interaction, demand/reward, control/recognition). Data were analysed using hierarchical regression models.Results.  After controlling for personality traits and personal characteristics, role stress variables predicted 24·8% of the variance in job satisfaction. Role ambiguity (P < 0·001) and role overload (P < 0·01) were the best predictors, but role conflict was not statistically significant. Role stress explained statistically significant proportions of the variance for each component of job satisfaction: professionalism (10·6%), interaction (16·7%), demand/reward (27·1%) and control/recognition (18·5%). Role ambiguity predicted all four satisfaction components, role overload predicted demand/reward and role incompetence predicted interaction.Conclusion.  Organizational restructuring and administrative support are recommended to address the issues raised. Appropriate training, sufficient communications and supportive legislation are required. Future research should be conducted to evaluate the impact of these interventions.
An innovative approach to integrated medicines management
Authors: Scullin Claire , Scott Michael G. , Hogg Anita , McElnay James C. 
Published: July 2007

AbstractRationale, aims and objectives  To determine whether an increased input by clinical pharmacists at each stage of the patient’s hospital journey, from admission through discharge, resulted in an enhanced level of patient care as measured by a number of clinical and economic outcomes.Methods  This project was designed to address medicines management issues in patients deemed at risk of drug‐related problems. During the project, these latter patients at the time of admission were randomly assigned to an integrated medicines management (IMM) service group (n = 371) or regular hospital care group (n = 391). The IMM service involved comprehensive pharmaceutical care provided by a pharmacy team throughout each of three stages: patient admission, inpatient monitoring and counselling, and patient discharge.Results  Patients who received the IMM service benefited from a reduced length of hospital stay [by 2 days (P = 0.003; independent samples t‐test loge)]. IMM patients also had a decreased rate of readmission over a 12‐month follow‐up period (40.8% vs. 49.3%; p = 0.027; Fisher’s exact test) and an increased time to readmission [20 days longer (P = 0.0356; log rank test)]. A numbers‐needed‐to‐treat calculation indicated that for approximately every 12 patients receiving the IMM service, one readmission to hospital, within 12 months of discharge, would be prevented. The new service was welcomed by cognate health care professionals.Conclusion  The IMM service proved very effective and can be used as a template to support the implementation of comprehensive pharmaceutical care as a routine service across Northern Ireland and beyond.
Effectiveness of a lifestyle modification programme in weight maintenance in obese subjects after cessation of treatment with Orlistat
Authors: Woo Jean , Sea Mandy M. M. , Tong Peter , Ko Gary T. C. , Lee Zoe , Chan Juliana , Chow Francis C. C. 
Published: July 2007

AbstractObjective  To examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat.Methods  Fifty‐five subjects with and without diabetes mellitus were randomized to a lifestyle modification programme or to usual care at the end of 6 months’ treatment with Orlistat. The intervention programme was nutritionist led, consisting of components of dietary management, physical activity, peer group support and discussion using techniques of self‐monitoring, stimulus control and cognitive restructuring. Anthropometric indices, body composition, basal metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid profile, 24‐hour urinary albumin excretion, dietary intake, physical activity level, and quality of life were assessed before and after the intervention period.Results  Subjects in the intervention group maintained their weight loss and favourable anthropometric, metabolic, dietary intake, physical activity and quality of life profiles, while most parameters deteriorated in the usual care group, being more marked in subjects with diabetes. The magnitude of weight gain was comparable to that lost during Orlistat treatment.Conclusion  A specially designed nutritionist‐led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat, in the absence of which the benefits of drug treatment were lost. The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat.
In vivo and In vitro Control of Leishmania mexicana due to Garlic‐induced NO Production
Authors: Gamboa‐León M. R. , Aranda‐González I. , Mut‐Martín M. , García‐Miss M. R. , Dumonteil E. 
Published: July 2007

Abstract Leishmania mexicana is the main causal agent of cutaneous leishmaniasis in the Yucatán peninsula in Mexico. Control of this disease is associated with a Th1‐type immune response and garlic extract has been reported as a Th1 immunomodulator in BALB/c mice infected with Leishmania major. In this study, we investigated the effect of garlic extracts on L. mexicana infection in vivo and in vitro. Garlic extract reduced footpad lesions in L. mexicana‐infected BALB/c mice by inducing IFN‐γ production from T cells. In vitro, garlic extract reduced macrophage infection through induction of nitric oxide (NO) production. Garlic extract may thus act on both T cells and macrophages to stimulate IFN‐γ production and NO synthesis for parasite killing. A 10‐ to 14‐kDa fraction was identified as responsible for the in vitro effect of the whole extract and may lead to the identification of novel immunomodulating drugs and therapeutic alternatives for the treatment of leishmaniasis.
The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients
Authors: Bora Emre , Vahip Simavi , Akdeniz Fisun , Gonul Ali Saffet , Eryavuz Ayse , Ogut Melise , Alkan Muge 
Published: August 2007

Objectives:  Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients.Methods:  The study participants were 40 euthymic psychotic, 25 non‐psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory.Results:  Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non‐psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. ‘Number of Wisconsin Card Sorting Test (WCST) categories’ achieved was the only measure on which psychotic patients performed significantly worse compared to non‐psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease.Conclusions:  Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.