bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐endothelial KDR/flk‐1 expression is associated with increased survival of patients with urothelial bladder carcinomas
Authors: Gakiopoulou‐Givalou H , Nakopoulou L , Panayotopoulou E G , Zervas A , Mavrommatis J , Giannopoulos A 
Published: December 2004

Aims:  To investigate the immunohistochemical expression of KDR/flk‐1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl‐2 protein expression and patient survival. KDR/flk‐1 is a high‐affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk‐1 is also expressed by normal non‐endothelial and tumour cells.Methods and results:  Immunohistochemistry was performed on paraffin sections using monoclonal and polyclonal antibodies. Statistical analysis was univariate (χ2 log rank test) and multivariate (Cox's model). KDR/flk‐1 expression was observed in the cytoplasm of cancerous cells in 68.4% of cases. No statistically significant associations were observed between KDR/flk‐1 expression and grade or stage of urothelial carcinomas, Ki67, p53 or Bcl‐2 expression. In contrast, widespread KDR/flk‐1 expression in more than 50% of cancerous cells was associated with increased survival, on univariate and multivariate analysis (P = 0.0119 and P = 0.042, respectively).Conclusions:  Although the biological significance of non‐endothelial KDR/flk‐1 expression has not yet been elucidated, its association with better patient survival may be related to the failure of non‐endothelial KDR/flk‐1 to mediate angiogenic and mitogenic effects.
Loss of oestrogen receptor β, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours
Authors: Staibano S , Franco R , Mezza E , Chieffi P , Sinisi A , Pasquali D , Errico M E , Nappi C , Tremolaterra F , Somma P , Mansueto G , De Rosa G 
Published: December 2004

Aims:  Ovarian granulosa cell tumour (OGCT) is a sex‐cord stromal tumour with a general trend toward late relapse and/or metastasis. However, mortality rate corrected for long‐term follow‐up shows that about 50% of patients die within 20 years of diagnosis. Classical clinicopathological parameters are unable to predict the biological behaviour of OGCT. The involvement of a recently characterized subtype of oestrogen receptor, ERβ, in ovarian carcinogenesis has been hypothesized.Methods and results:  We examined by immunohistochemistry the expression of ERβ, proliferating cell nuclear antigen (PCNA) and p53 in a selected series of 30 OGCT, to evaluate their role in the prognostic evaluation of this tumour. Immunohistochemistry was performed on formalin‐fixed paraffin‐embedded sections. Results were compared with the DNA‐ploidy of the tumours (evaluated by image analysis) and with the follow‐up data of the patients.Conclusions:  Loss of ERβ expression, high PCNA expression and aneuploidy, characterized a subgroup of OGCT with a worse outcome. The identification of a high‐risk subclass of OGCT may be of primary importance in addressing appropriate therapeutic strategies, offering the chance to prevent relapses and metastases by using adjunctive, specifically targetted, more aggressive therapies.
Bone marrow histopathology following cytoreductive therapy in chronic idiopathic myelofibrosis
Authors: Thiele J , Kvasnicka H M , Schmitt‐Graeff A , Diehl V 
Published: December 2004

Aims: To analyse systematically therapy‐induced lesions of haematopoiesis in chronic idiopathic myelofibrosis (IMF).Methods and results: A total of 759 sequential bone marrow (BM) biopsies (median interval 32 months) were performed in 261 patients with IMF. Besides a control group (symptomatic treatment), monotherapies included busulfan, hydroxyurea and interferon. In all therapy groups hypoplasia of varying degree was a frequent finding and often accompanied by a patchy distribution of haematopoiesis. Most conspicuous was gelatinous oedema showing a tendency to develop discrete reticulin fibrosis (scleroedema). Minimal to moderate maturation defects of megakaryopoiesis and erythroid precursors occurred, but overt myelodysplastic features were most prominent following hydroxyurea and busulfan therapy. Acceleration and blastic crisis were characterized by the appearance of immature and CD34+ progenitor cells. Concerning the dynamics of fibrosis, no differences were observed between controls and the various therapy groups. In 143 patients (55%) without or with little reticulin at onset, an increase in myelofibrosis was detectable that progressed to overt collagen fibrosis.Conclusions: Therapy‐related bone marrow lesions in IMF comprise a strikingly variable spectrum that may include aplasia with scleroedema and a patchy distribution of myelodysplastic haematopoiesis associated with progressive myelofibrosis.
A CR1 polymorphism associated with constitutive erythrocyte CR1 levels affects binding to C4b but not C3b
Authors: Birmingham Daniel J. , Chen Wei , Liang Grace , Schmitt Holly C. , Gavit Katie , Nagaraja Haikady N. 
Published: December 2004

SummaryThe erythrocyte type one complement receptor (E‐CR1) mediates erythrocyte binding of complement‐opsonized immune complexes (IC), and helps protect against random deposition of circulating IC. Two linked CR1 polymorphisms occur in binding domains, at I643T and Q981H. In Caucasians, the variant alleles (643T, 981H) are associated with low constitutive E‐CR1 expression levels. This study was conducted to determine if these polymorphisms affect ligand binding, and if so, represent risk factors for the autoimmune IC disease, systemic lupus erythematosus (SLE). In an ELISA comparing relative ligand binding differences, E‐CR1 from individuals homozygous for the variant residues (643TT/981HH) exhibited greater binding to C4b, but not C3b, than homozygous wild‐type E‐CR1. Analysis of single‐binding domain CR1 constructs demonstrated that the 981H residue imparted this enhanced C4b binding. No differences were observed in the 981H allele frequency between Caucasian controls (0·170, n = 100) and SLE patients (0·130, n = 150, P = 0·133), or between African American controls (0·169, n = 71) and SLE patients (0·157, n = 67). In a subset of individuals assessed for CR1 size, excluding from this analysis those expressing at least one B allele revealed a trend for over‐representation of the 981H allele in Caucasian controls (0·231 frequency, n = 26) versus SLE patients (0·139, n = 83, P = 0·089), but again no difference between African American controls (0·188, n = 24) and SLE patients (0·191, n = 34). These data suggest that the 981H residue compensates for low constitutive expression of E‐CR1 in Caucasians by enhancing C4b binding. This may contribute protection against SLE.
B‐lymphocyte subpopulations are equally susceptible to Epstein–Barr virus infection, irrespective of immunoglobulin isotype expression
Authors: Ehlin‐Henriksson Barbro , Gordon John , Klein George 
Published: December 2004

SummaryWhile Epstein–Barr virus (EBV) is known to establish latency in the memory B‐cell compartment, there is controversy as to whether the memory or the naïve B cell is the initial target for infection. Here we have explored the infectability of the B‐cell subsets contained in peripheral blood and tonsils, as distinguished by their surface expression of the immunoglobulin isotypes that help to define naïve and memory pools. First we show that both CD21 and major histocompatibility complex (MHC) class II molecules – respectively, the major receptor and co‐receptor for EBV on B cells – are expressed at similar levels on blood and tonsillar B cells, irrespective of surface immunoglobulin class, indicating that each of the subsets demonstrate an equal potential, at least for infection. Then, following in vitro infection of total tonsillar B cells, we found that the relative frequencies of immunoglobulin (Ig)M‐, IgG‐ and IgA‐positive cells containing EBV‐encoded Epstein–Barr virus nuclear antigen 5 (EBNA5) protein at 48 hr were similar to those of the starting population. However, IgD expression was uniformly decreased, probably as a consequence of cellular activation. These data indicate that recirculating B cells have both the potential for, and susceptibility to, initial infection by EBV, irrespective of the immunoglobulin isotype expressed.
Transmembrane T‐cell receptor peptides inhibit B‐ and natural killer‐cell function
Authors: Huynh Nghi T. , Ffrench Rosemary A. , Boadle Ross A. , Manolios Nicholas 
Published: December 2004

SummaryA synthetic hydrophobic peptide (core peptide; CP) containing two positively charged amino acids, lysine and arginine was derived from the transmembrane sequence of the T‐cell receptor (TCR) α chain and has been shown to inhibit T‐cell‐mediated inflammation. In this study, we investigated the specificity of CP (10 μm) on lymphocyte function and found that it significantly inhibited interleukin‐2 production in T cells and natural killer cytotoxicity by 46–58% compared to positive control. CP had no effects on B‐cell proliferative responses when used at these concentrations; however, it suppressed B‐cell proliferation at higher concentrations (50 μm). Inhibition by CP was not the result of membrane pore formation or cytotoxicity when examined by trypan blue, propidium iodide staining or transmission electron microscopy. CP analogues, with both lysine and arginine replaced by neutral or negatively charged amino acids, or by randomly distributing charges in the peptide sequence, had no effect on lymphocyte function. These results suggest that peptide inhibition is affected by its structure and charge interactions, and may involve common signalling molecules in T, B and natural killer cells. The potential of the immuno‐inhibitory effects of CP as a novel anti‐inflammatory peptide in therapy should be further explored.
The CAG repeat polymorphism within the androgen receptor gene and maleness1
Authors: Zitzmann Michael , Nieschlag Eberhard 
Published: December 2004

SummaryThe androgen testosterone and its metabolite dihydrotestosterone exert their effects on gene expression and thus effect maleness via the androgen receptor (AR). A diverse range of clinical conditions starting with complete androgen insensitivity has been correlated with mutations in the AR. Subtle modulations of the transcriptional activity induced by the AR have also been observed and frequently assigned to a polyglutamine stretch of variable length within the N‐terminal domain of the receptor. This stretch is encoded by a variable number of CAG triplets in exon 1 of the AR gene located on the X chromosome. First observations of pathologically elongated AR CAG repeats in patients with X‐linked spino‐bulbar muscular atrophy showing marked hypoandrogenic traits were supplemented by partially conflicting findings of statistical significance also within the normal range of CAG repeat length: an involvement of prostate tissue, spermatogenesis, bone density, hair growth, cardiovascular risk factors and psychological factors has been demonstrated. The highly polymorphic nature of glutamine residues within the AR protein implies a subtle gradation of androgenicity among individuals within an environment of normal testosterone levels providing relevant ligand binding to ARs. This modulation of androgen effects may be small but continuously present during a man's lifetime and, hence, exerts effects that are measurable in many tissues as various degrees of androgenicity and represents a relevant effector of maleness. It remains to be elucidated whether these insights are important enough to become part of individually useful laboratory assessments.
Effects of NCX 4050, a new NO donor, in rabbit and human corpus cavernosum
Authors: Filippi S. , Crescioli C. , Vannelli G. B. , Fazzini A. , Natali A. , Riffaud J. P. , Maggi M. , Ledda F. 
Published: December 2004

SummaryThe effects of NCX 4050, a drug belonging to a new class of NO donors, was investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and in human foetal corpora cavernosa (hfCC) smooth muscle cells. In strips of rabbit CC, NCX 4050 (0.001–100 μM) induced a concentration‐dependent relaxation which was influenced neither by Nw‐nitro‐l‐arginine‐methyl‐ester (l‐NAME; 100 μm) nor by endothelium deprivation. The NCX 4050‐induced relaxation was significantly reduced by the guanylate cyclase inhibitor 1H‐[1,2,4]‐oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 1 μm) and enhanced by a specific phosphodiesterase 5 inhibitor, sildenafil (300 nm). Moreover, NCX 4050 (0.01–1 μm), induced a concentration‐dependent potentiation of the relaxant response induced by electrical field stimulation (EFS) in rabbit preparations pre‐treated with guanethidine and indomethacin. The relaxant effect of NCX 4050 was similar to that obtained by increasing concentrations (0.001–100 μm) of sodium nitroprusside (SNP) in either rabbit or human preparations. To further investigate the activity of NCX 4050 on human corpora cavernosa, we exposed cultured hfCC smooth muscle cells to increasing concentrations of NCX 4050 and SNP. We found that both compounds dose‐dependently reduced cell proliferation. The antiproliferative effect of all the concentration tested of NCX 4050 was completely blocked by ODQ (1 μm). These results suggest that in rabbit and human corpora cavernosa NCX 4050 acts by activating guanylate cyclase activity, induces smooth muscle relaxation and quiescence. Our results provide a rationale for a possible future use of NCX 4050 in the pharmacotherapy of erectile dysfunction linked to an impaired release of NO from the endothelium.
A novel animal model of thymic tumour: Development of epithelial thymoma in transgenic rats carrying human T lymphocyte virus type I pX gene
Authors: Kikuchi Kazunori , Ikeda Hitoshi , Tsuchikawa Takahiro , Tsuji Takahiro , Tanaka Satoshi , Fugo Kazunori , Sugaya Toshiaki , Tanaka Yuetsu , Tateno Masatoshi , Maruyama Naoki , Yoshiki Takashi 
Published: December 2004

Summary.The pX region encodes a major product of human T lymphocyte virus type I (HTLV‐I) that has been implicated previously in tumour formation. To investigate the pathogenesis of pX gene in lymphoid tissues, we established a series of novel transgenic rats carrying the pX gene under the control of a rat lymphocyte‐specific protein tyrosine kinase (p56lck) proximal promoter.The transgene was constructed with the −269 to +26 region of a rat p56lck proximal promoter and the pX cDNA, and was microinjected into fertilized ova of Fischer 344/jcl female rats. Six transgenic lines from 114 pups were established. Integration and expression of the transgene were detected by polymerase chain reaction (PCR) and Southern hybridization or by reverse transcriptase‐PCR, northern hybridization, and immunostaining. Thymic tumours with lethal expansion occurred in 4 of 6 transgenic lines. The tumour consisted of spindle shaped cells. Immunohistochemical and ultra‐structural analysis characterized the tumour cells to as epithelial cell type, and in the tumour arose in the medulla. Therefore, the tumour is classified into predominantly epithelial and spindle cell of medullary thymoma (type A of the new World Health Organization classification), as based on the human classification. Tumor occurrence increased in proportion to levels of the pX transcription in the thymus, for each line, and sex distinction was evident regarding rates related to tumour expansion. The transgenic rat model described here is suitable as a model for analysing tumorigenesis in epithelial thymoma occurring in humans.
Quality and sensory acceptance of fish sauce partially substituting sodium chloride or natural salt with potassium chloride during the fermentation process
Authors: Sanceda N. , Suzuki E. , Kurata T. 
Published: December 2004

SummaryFish sauce was prepared with sodium chloride or natural salt partially replaced by potassium chloride at three ratios, 90 : 10, 75 : 25 and 60 : 40. Volatile acids were collected by steam distillation under reduced pressure and measured. The sensory property of the products was evaluated. The amino acid content was also measured. Most of the volatile acids in all the samples with added KCl were higher than in the controls, suggesting a role for KCl in the formation of volatile acids in fish sauce manufacture. Sensory evaluation showed slight differences in odour between the samples with added KCl and the controls, but the differences did not affect the acceptability of the product. However, acceptance of taste terminated at a 75 : 25 NaCl or natural salt : KCl ratio. Almost all the amino acids in the control and in the fish sauces with added KCl were comparable to those of commercial fish sauce. Partial substitution of NaCl or natural salt with KCl up to a ratio of 75 : 25 seems feasible.
Population dynamics of the pipistrelle bat: effects of sex, age and winter weather on seasonal survival
Authors: Sendor Thomas , Simon Matthias 
Published: December 2004

Summary

Life‐history theory assumes increased mortality at certain stages such as hibernation. However, seasonal variation of survival rates of hibernating mammals has rarely been estimated. In this study, apparent survival of pipistrelle bats (Pipistrellus pipistrellus) hibernating and performing summer swarming at a large hibernaculum (Marburg Castle, Hesse, Germany), was modelled using seasonal (summer/winter) capture–recapture data for the years 1996–2000. The spring survival interval includes the period of arousal at the end of hibernation and therefore validly measures survival associated with hibernation.
In five summers and four winters, 15 839 bats were captured and released (13 082 individuals) and 3403 recaptures recorded. Analysis was complicated by transience and trap‐dependence. Recapture rates varied seasonally and by group. The autumnal survival estimates were negatively biased due to transience effects that could not be taken into account.
Survival could be modelled using two age‐classes, with reduced first‐year juvenile survival. The age effect persisted over the first autumn and spring. There was virtually no evidence for sex‐specific survival rates; male and female survival were found to be almost equal. In the best‐fitting models, survival rates varied over time and differed among sexes and age‐classes by a constant amount. Between years, there was only a small variation in spring survival, which could not be explained by winter severity.
Adult spring survival was surprisingly high, averaging 0·892 (= 0·028). No evidence for increased mortality during hibernation could be found. This contradicted the expectation of reduced over‐winter survival due to depleted fat reserves at the end of hibernation. Thus, hibernation does apparently not entail a survival cost for the pipistrelle bat. Rough estimates of annual adult survival averaged 0·799 ( = 0·051), which considerably exceeds previous estimates; annual juvenile survival was estimated at 0·527 ( = 0·095). Hence, previous studies have substantially underestimated pipistrelle bat survival. Possible consequences of these findings for various aspects of life histories are discussed.
Teaching and learning about skills in minor surgery
Authors: Nestel Debra , Kneebone Roger , Kidd Jane 
Published: December 2004

Summary• The aim of this study was to assess the feasibility of a scenario‐based approach to learning minor surgery skills.• After learning component technical skills for ellipse excision and wound closure, nurses were provided with an opportunity to integrate these skills with communication skills and contextual factors in a quasi‐clinical environment.• Feasibility was assessed using observation of procedures and a group interview with participants, simulated patients and tutors.• The scenario‐based approach to teaching and learning about technical and communication skills proved feasible and was valued by participants in this course on minor surgery.• Although all participants expressed anxiety about integrating skills in the quasi‐clinical setting, they valued the opportunity to undergo a formative assessment prior to working in supervised settings with real patients.• Learners valued highly the opportunity to reflect on their performance and to receive feedback on technical and communication skills.• Future courses should include focused teaching on communication skills prior to the scenario‐based exercise.• Limitations of the study centre on the small numbers of participants and the novelty of the course. Repeating the evaluations on a subsequent course will provide insight into the ways in which nurses acquire and integrate new skills.
Bridging the divide: a survey of nurses’ opinions regarding barriers to, and facilitators of, research utilization in the practice setting
Authors: Hutchinson Alison Margaret , Johnston Linda 
Published: December 2004

Background.  Many researchers have explored the barriers to research uptake in order to overcome them and identify strategies to facilitate research utilization. However, the research–practice gap remains a persistent issue for the nursing profession.Aims and objectives.  The aim of this study was to gain an understanding of perceived influences on nurses’ utilization of research, and explore what differences or commonalities exist between the findings of this research and those of studies that have been conducted in various countries during the past 10 years.Design.  Nurses were surveyed to elicit their opinions regarding barriers to, and facilitators of, research utilization. The instrument comprised a 29‐item validated questionnaire, titled Barriers to Research Utilisation Scale (BARRIERS Scale), an eight‐item scale of facilitators, provision for respondents to record additional barriers and/or facilitators and a series of demographic questions.Method.  The questionnaire was administered in 2001 to all nurses (n = 761) working at a major teaching hospital in Melbourne, Australia. A 45% response rate was achieved.Results.  Greatest barriers to research utilization reported included time constraints, lack of awareness of available research literature, insufficient authority to change practice, inadequate skills in critical appraisal and lack of support for implementation of research findings. Greatest facilitators to research utilization reported included availability of more time to review and implement research findings, availability of more relevant research and colleague support.Conclusion.  One of the most striking features of the findings of the present study is that perceptions of Australian nurses are remarkably consistent with reported perceptions of nurses in the US, UK and Northern Ireland during the past decade.Relevance to clinical practice.  If the use of research evidence in practice results in better outcomes for our patients, this behoves us, as a profession, to address issues surrounding support for implementation of research findings, authority to change practice, time constraints and ability to critically appraise research with conviction and a sense of urgency.
Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic outpatient clinic – a pilot study
Authors: Taylor F. C. , Irons L. J. , Finn P. , Summerbell C. D. 
Published: December 2004

AbstractBackground  Outpatient dietary weight reduction for obesity is unsatisfactory. The objective of this study was to compare the efficacy of an energy prescription diet with usual care (a healthy eating diet) in adult overweight patients referred to a NHS hospital dietetic outpatient clinic, in terms of weight change over 12 weeks.Methods  Controlled clinical trial (systematic allocation).Results  Of the 53 patients who attended their first appointment, 27 completed the trial. Mean weight loss (kg) after 12 weeks was 4.2 (sd 3.8) on the energy prescription diet (n = 16) and 6.0 (sd 2.8) on the healthy eating diet (n = 11).Conclusions  Patients on a weight reducing diet based on energy prescription or healthy eating lost, on average, clinically significant amounts of body weight by 12 weeks. Mean weight loss was greater by about 50% in the energy prescription group and supports the development of a larger trial to estimate true effect.