bluuebunny/crossref_metadata_2025 huggingface dataset:
Regression-Related Factors before and after Laser in situ Keratomileusis
Authors: Qi Hong , Hao Yansheng , Xia Yingjie , Chen Yueguo
Published: June 2006

The aim of this study was to evaluate the refractive regression-related factors before and after laser in situ keratomileusis (LASIK) for myopia and give a reasonable way to prevent it. The consecutive patients who underwent LASIK from January to June 2004 were reviewed retrospectively. Thirteen eyes from 8 patients with myopic regression and 60 eyes from 42 patients with no myopic regression within 12 months of follow-up were enrolled. We compared the pre- and postoperative data which were associated with regression in the two groups. The mean preoperative intraocular pressure (IOP) was significantly higher in the regression group than in the nonregression group (p = 0.03). During the period of 12 months, the two groups differed in corneal bowing. In the regression group, both posterior and anterior corneal surfaces were significantly bowing (all p < 0.05). In contrast, in the nonregression group, both posterior and anterior surfaces were relatively stable (all p > 0.05). The higher preoperative IOP and the progressive postoperative biomechanical bowing in the posterior and anterior surfaces of the cornea are two factors related to myopic regression in this study. Lowering the IOP preoperatively and postoperatively may be an effective way to prevent the myopic regression after LASIK.
D2-40: A Reliable Marker in the Diagnosis of Pleural Mesothelioma
Authors: Müller Annette M. , Franke Folker E. , Müller Klaus-Michael
Published: June 2006

Objective: Malignant mesotheliomas of the pleura, peritoneum and pericardium can easily be confused with either metastatic adenocarcinomas or reactive pleural lesions. D2-40, a monoclonal antibody used as a marker for seminomatous germ cell tumours and lymphatic endothelial cells, was recently described in mesothelial cells and type I but not type II pneumocytes. Method: The immunoreactivities of D2-40 in 76 lung carcinomas of different histological types (adenocarcinomas, squamous cell, small cell, and bronchioloalveolar carcinomas) were compared with those of 36 pleural epithelioid and sarcomatoid mesotheliomas and 5 specimens of chronic pleuritis. Results: While all 18 analysed epithelioid mesotheliomas displayed a strong membranous immunostaining, 18 sarcomatoid mesotheliomas showed no, or a merely faint, cytoplasmic signal, comparable with fibroblasts in chronic pleuritis. Out of all analysed lung carcinomas, 49 showed no immunoreactivity for D2-40 (64%), while the other 27 (36%) showed a focal weak to moderate and only cytoplasmic signal. Conclusions: We regard D2-40 as a valid marker in the differential diagnosis of epithelioid mesotheliomas versus pulmonary adenocarcinomas. However, this marker may not properly label sarcomatoid mesotheliomas or distinguish them from reactive pleural lesions.
Multislice Computed Tomographic Angiography in Evaluating Dysfunction of the Vascular Access in Hemodialysis Patients
Authors: Ye Chaoyang , Mao Zhiguo , Rong Shu , Zhang Yuqiang , Mei Changlin , Li Huimin , Dong Sheng
Published: June 2006

Aims: To introduce our preliminary experience in using multislice computed tomographic (CT) angiography (MSCTA) to assess stenoses of the hemodialysis vascular access and to guide revising operation or percutaneous transluminal angioplasty (PTA). Methods: Contrast-enhanced 16-slice spiral CT was used to examine 22 hemodialysis patients with various dysfunctions of their vascular access. The transverse source images were reformatted as maximum intensity projection, volume-rendering, and multiple/curved planar reconstruction images. Results: The whole spectrum of arteriovenous fistulas (AVF) with the feeding artery, anastomoses, and outflow tract up to the superior caval vein was clearly displayed in all patients. According to the results of MSCTA, AVF-revising surgery was done in 11 patients, and PTA under the guide of digital subtraction angiography (DSA) was done in 5 patients. The results of MSCTA coincide with the findings of surgery or DSA in these 16 patients. Conclusions: In our opinion, MSCTA is a good noninvasive diagnostic technique to detect various hemodialysis vascular access abnormalities. It is more economical than DSA in the present medical settings and could replace DSA in the imaging of hemodialysis vascular access and provide important information for further AVF-revising surgery or PTA.
Hypertension and Left Ventricular Hypertrophy in Pediatric Peritoneal Dialysis Patients: Ambulatory Blood Pressure Monitoring and Echocardiographic Evaluation
Authors: Özçakar Z. Birsin , Yalçınkaya Fatoş , Tutar Ercan , Çakar Nilgün , Uçar Tayfun , Elhan Atilla , Acar Banu , Yüksel Selçuk , Uncu Nermin , Kara Nazlı , Atalay Semra , Ekim Mesiha
Published: June 2006

Background: Hypertension is a frequent complication of end-stage renal disease and left ventricular hypertrophy (LVH) is common in patients with poorly controlled hypertension. The aim of this study was to evaluate hypertension in pediatric peritoneal dialysis (PD) patients, to compare casual and ambulatory blood pressure (BP) measurements and to evaluate the impact of BP parameters on LVH. Methods: The study comprised 25 PD patients (9 M, 16 F; mean age 14.14 ± 3.32 years) that have been followed in outpatient clinics. Medical records were reviewed for demographic features; casual BP measurements, ambulatory blood pressure monitoring (ABPM) and echocardiographic evaluation were applied to all patients. Results: The mean 24-hour and daytime systolic blood pressure (SBP) values were found to be higher than casual SBP (p < 0.001). Significant difference was present in the frequency of hypertension between casual SBP (32%) and the mean daytime SBP (56%) (p < 0.05). Nighttime systolic hypertension was detected in 14 (56%) and diastolic hypertension in 16 (64%) patients. Elevated daytime SBP load and DBP load were detected in 64 and 76% of the patients, respectively. Elevated nighttime SBP load and DBP load were detected in 72% of the patients. Seventeen (68%) patients had attenuated dipping for SBP. The mean left ventricular mass index (LVMI) was 52.65 ± 18.17 g/m2.7 and 13 (52%) patients had LVH. LVMI was significantly correlated with casual BP measurements and the majority of ABPM parameters. Conclusion: The majority of pediatric PD patients had BP abnormalities in which severity was most accurately assessed with ABPM. Casual BP and majority of ABPM parameters were found to be significantly correlated with LVMI. Ambulatory blood pressure monitoring should be performed in all pediatric PD patients.
Implantation of the Human Embryo: Research Lines and Models
Authors: Bischof P. , Aplin J.D. , Bentin-Ley U. , Brannstrom M. , Casslen B. , Castrillo J.L. , Classen-Linke I. , Critchley H.O.D. , Devoto L. , D’Hooghe T. , Horcajadas J.A. , Groothuis P. , Ivell R. , Pongrantz I. , Macklon N.S. , Sharkey A. , Vicovac L. , White J.O. , Winterhager E. , von Wolff M. , Simon C. , Stavreus-Evers A.
Published: June 2006

Infertility is an increasing problem all over the world, and it has been estimated that 10–15% of couples in fertile age have fertility problems. Likewise induced unsafe abortion is a serious threat to women’s health. Despite advances made in assisted reproduction techniques, little progress has been made in increasing the success rate during fertility treatment. This document describes a wide range of projects carried out to increase the understanding in the field of embryo implantation research. The ‘Fruitful’ research network was created to encourage collaborations within the consortium and to describe our different research potentials to granting agencies or private sponsors.
The NK1 Receptor Antagonist SR140333 Inhibits Capsaicin-Induced ERK Phosphorylation in Sensory Neurons
Authors: Donnerer J. , Liebmann I.
Published: June 2006

Primary sensory neurons respond to a vigorous excitation via the capsaicin receptor/TRPV1 cation channel by a phosphorylation of the Jak/STAT pathway as measured by phospho-STAT3, and of the Ras/Raf-MAPK pathway as measured by phospho-MAPK/ERK1/2. In the present investigation a possible involvement of NK1 receptors in the capsaicin-induced activation of these signal transduction pathways was investigated by protein extraction and Western immunoblotting. Phospho-MAPK/ERK1/2 and phospho-STAT3 were determined in the dorsal root ganglia (DRG) and in the sciatic nerve of rats at 3 and 6 h following a systemic capsaicin treatment without or with the pretreatment of the selective NK1 receptor antagonist SR140333 (1 mg/kg s.c.; 3 h before capsaicin). Capsaicin evoked a threefold increase in phospho-ERK in the sciatic nerve and a two- to threefold increase in the DRG at 3 h and 6 h after the treatment. SR140333 markedly attenuated the capsaicin-induced increase in phosphorylated ERK. In the sciatic nerve the difference was significant at each individual time point (3 and 6 h, p < 0.001). In the DRG the difference was significant when the data at 3 h and 6 h were combined (p < 0.05), but not when individual time points were considered. Capsaicin evoked a four- to fivefold increase in phospho-STAT3 in the sciatic nerve and a twofold increase in the DRG at 3 and 6 h after the treatment. SR140333 less markedly attenuated the capsaicin-induced increase in phosphorylated STAT3: whereas in the sciatic nerve the difference was significant when the data at 3 h and 6 h were combined (p < 0.05), no such treatment effect of SR140333 was observed in the DRG. The expression of TRPV1 mRNA, a specific marker of capsaicin-sensitive small sensory neurons, was investigated by RT-PCR 4 days after the capsaicin treatment. Treatment of rats with SR140333 had no influence on the long-term downregulation of TRPV1 mRNA by capsaicin. Based on the present results and previous findings it can be postulated that the capsaicin-induced ERK phosphorylation in sensory neurons is not a direct effect by capsaicin, but that rather substance P release from the stimulated sensory neurons with an NK1-mediated nerve growth factor (NGF) production is involved.
CyberKnife Radiosurgery for Extremity Schwannomas: Technical Note and Case Report
Authors: Lim Michael , Adler John R.
Published: June 2006

Peripheral nerve sheath tumors are uncommon. Although surgical resection remains the treatment of choice for most symptomatic lesions, the potential for intraoperative injury to the nerve is not insignificant. This concern is of particular relevance in those patients with a genetic proclivity to develop multiple peripheral nerve sheath tumors. Here we report four symptomatic peripheral extremity schwannomas all in 1 patient who was treated with CyberKnife radiosurgery. The radiosurgical Dmax in each case was between 24.4 and 25.32 Gy. At 1-year follow-up, patient symptoms had been ameliorated, no tumor had increased in size and there was no compromise in neurological function. Although this experience is still very preliminary, it represents the first published description of a peripheral nerve sheath tumor being treated with stereotactic radiosurgery.
Gamma Knife Radiosurgery for Refractory Epilepsy Caused by Hypothalamic Hamartomas
Authors: Mathieu David , Kondziolka Douglas , Niranjan Ajay , Flickinger John , Lunsford L. Dade
Published: June 2006

Background: Hypothalamic hamartomas are associated with precocious puberty and chronic epilepsy characterized by gelastic seizures. The seizure disorder is usually refractory to most antiepileptic drugs. Gamma knife surgery has emerged as an alternative to microsurgical removal or radiofrequency ablation to improve seizure control. We present our experience with radiosurgery in 4 patients afflicted by this disorder. Methods: Using gamma knife radiosurgery, 4 patients with intractable gelastic seizures and complex epilepsy were managed. Patient age varied from 5 to 29 years. The duration of symptoms was 4–28 years. A conformal radiosurgery plan was designed with a mean of 4.25 isocenters to cover the hamartoma at the 50% isodose line. A mean margin dose of 17.5 Gy was used. The clinical outcome was evaluated with the Engel scale. Results: No complication occurred. After a median follow-up of 22 months, 3 patients had shown some improvement, with 2 attaining Engel class II status. Conclusion: Gamma knife surgery is a promising alternative to microsurgical removal for patients with refractory epilepsy caused by hypothalamic hamartomas.
Three-Dimensional Numerical Simulation of the Pressing Process in TV Panel Production
Authors: Zhou Huamin , Yan Bo , Li Dequn
Published: June 2006

A mathematical model of the behavior of molten glass during the pressing operation of a TV panel is developed in this article. The molten glass is modeled by an incompressible Newtonian liquid undergoing flow. Then a three-dimensional finite element method is used to perform the simulations of the fluid and heat flow. The simulation employs an equal-order velocity-pressure interpolation method. The relation between velocity and pressure is obtained from the discretized momentum equations in order to derive the pressure equation. The glass simulation is coupled with the mold temperature simulation by matching the temperature and heat flux on the glass-mold interface.
Ostpolitik before Ostpolitik
Authors: Berger Stefan , LaPorte Norman
Published: June 2006

In 1955 West Germany joined NATO, while East Germany joined the Warsaw Pact. The GDR was not recognized by Britain, as it followed the FRG’s Hallstein doctrine, according to which the FRG was the only legitimate German state. The Labour Party officially had no relations with the GDR, but after 1955 an increasing number of Labour MPs, including some senior figures, travelled to the GDR and openly voiced their opinion that the GDR should be recognized. Such visits produced tensions between the SPD and the Labour Party. The article analyses why the Labour Party risked those tensions. It asks where it differed in its assessment and its priorities from the SPD. And it explores how it sought to overcome the Cold War division of the continent by propagating a new Ostpolitik which preceded the better-known Ostpolitik pursued by Willy Brandt and Egon Bahr in the FRG after 1963
The Wilson Governments and the Italian Centre-Left Coalitions: Between ‘Socialist’ Diplomacy and Realpolitik, 1964-70
Authors: Favretto Ilaria
Published: June 2006

The purpose of this article (based on archival material from the National Archives, Kew, and the Labour archive in Manchester) is to explore the relationship between the British Labour Party and the Italian Socialist Party during the Wilson governments and the Italian centre-left coalitions between 1964 and 1970. The inclusion of the PSI within the Italian government was very much appreciated (and promoted) by Labour as it was expected it would be of great help with regard to issues such as the Multilateral Force or Britain’s second application to join the EEC. For this reason, the British Labour government did its best to support the success of the centre-left formula and was similarly very active in promoting socialist reunification, which was eventually achieved in 1966. As regards the PSI’s occasional radical departures in foreign policy matters - as, for instance, in relation to Vietnam - the Italian socialists’ ‘filial admiration’ for their British counterparts enabled Labour on more than one occasion to bring Nenni’s party into line
Microwave Synthesis of Phenylethynyl Imide Oligomers: Neat Resin and Composite Properties of PETI-2982-4
Authors: Smith Joseph G. , Connell John W. , Li Chao-Jun , Wu Wei , Criss Jim M.
Published: June 2006

PETI-298 is a high temperature/high performance matrix resin that is processable into composites by resin transfer molding (RTM), resin infusion, and vacuum-assisted RTM techniques. It is prepared by the conventional amide acid approach in a polar aprotic solvent from the reaction of an aromatic anhydride and a combination of diamines and endcapped with phenylethynylphthalic anhydride. As a means to eliminate solvent and decrease reaction time in order to address final resin cost, the microwave synthesis of PETI-298 was investigated. The monomers were manually mixed and placed in a microwave oven for various times to determine optimum conditions. The resultant materials were characterized for thermal and rheological properties and compared with PETI-298 prepared by the classic amide acid approach. The synthetic process was subsequently scaled-up to 330 g. Three batches were prepared and combined to give ° 1 kg of material that was subsequently used to fabricate flat laminates on T650 carbon fabric by RTM. The composite panels were analyzed and mechanical properties determined. These properties were compared with those fabricated from PETI-298 prepared by the classic amide acid approach. Based on solubility characteristics, melt viscosity and Fourier transform infrared spectroscopy, the phenylethynyl group did not react under the conditions investigated. This approach is applicable to the synthesis of a variety of phenylethynyl-terminated imide oligomers
Organizing the Self-Employed: Theoretical Considerations and Empirical Findings
Authors: Pernicka Susanne
Published: June 2006

Trade unions across Europe have pursued various strategies in their attempt to revitalize. Austria’s largest trade union has chosen to broaden its membership base by organizing and representing new membership groups such as dependent self-employed workers. We argue that this new category of workers poses a distinct challenge to a union’s identity, since their heterogeneous and highly individualized working conditions contribute to very individualistic personality traits. This article draws a picture of identity conceptions, normative orientations and prospective behaviour of dependent self-employed workers towards unions and suggests union strategies to deal with them.
Collective Bargaining and Social Pacts: Greece in Comparative Perspective
Authors: Zambarloukou Stella
Published: June 2006

What are the institutional prerequisites for the creation and maintenance of centralized collective bargaining and social pacts? This article compares Greek experience since 1990 with that in other countries, arguing that societies are likely to diverge on how they respond to the issues of changing bargaining structure and tripartite policy-making. While neo-institutionalist approaches, and particularly their ‘varieties of capitalism’ variant, can go a long way in interpreting these diverse responses, they have problems accounting for institutional change. To accomplish this we need a more dynamic understanding of how past institutional arrangements in combination with current tensions over particular issues, and the costs and opportunities presented to actors, give rise to distinctive responses.
Feminism and Peace Studies
Authors: John Moolakkattu Stephen
Published: June 2006

This article selectively surveys the feminist literature to identify ideas and practices that have had an impact on the relatively young discipline of peace studies, taking the last 25 years as the main reference period. Feminism has deconstructed some of the dominant discourses in peace studies, opened up new frontiers of enquiry, provided new meanings to concepts like peace, security, development and power, and helped generate a number of useful hypotheses. Feminist contributions to peace studies can be discerned in seven areas. Each of these areas is discussed in the article with suitable illustrations from the South Asian context.
Multilingual conferencing: effective teaching of children from refugee and asylum-seeking families®
Authors: Smyth Geri
Published: June 2006

What happens when a monolingual school in an economically deprived area of an inner city becomes a multilingual, multiracial school as a result of government policy (The Immigration and Asylum Act)? How do children from asylum-seeking families, many of whom have never had formal education prior to arriving in Scotland and all of whom are new to the English language, make meaning of the school community? This article will report on how a bilingual unit has become an integral part of the mainstream school due to creative pedagogy. The article will discuss how this highly mobile pupil population has enabled the school to take more cognisance of learner perspectives and has allowed a creative pedagogy to emerge in the school.
Collective teacher efficacy, pupil attainment and socio-economic status in primary school®
Authors: Parker Karen , Hannah Elizabeth , Topping Keith J.
Published: June 2006

Collective teacher efficacy (CTE) refers to the collective perception in a school that teachers make an educational difference to their pupils over and above the impact of their social circumstances. This study explored the relationships between CTE, socio-economic status (SES) and pupil attainment levels in reading, writing and mathematics (at the whole primary school level). Sixty-six teachers in 15 out of 19 schools in a small Local Authority participated. Significant positive relationships were found between SES and attainment in reading and mathematics (but not writing). However, significant positive relationships were also found between CTE and attainment in reading and writing (but not mathematics). Neither SES nor CTE independently accounted for a statistically significant proportion of the total variance in attainment. However, CTE appeared to have a much stronger independent impact than SES in writing (and also a modest independent impact in reading). One school with an atypical pattern of high CTE and high attainment despite low SES was studied in depth. Here, school climate or ethos, high quality in-service training and a focus upon pedagogy were perceived as the most potent factors in raising attainment. When these factors serve to heighten CTE, the impact of SES on pupil attainment may be reduced, and this may be easier in some subjects than others.
Service-learning
Authors: Bordelon Thomas D. , Phillips Iris
Published: June 2006

This exploratory study conducted at a mid-sized American Midwestern metropolitan university explores service-learning. The study describes the characteristics of students choosing service-learning and examines learning from the students’ perspective. A survey instrument was used to assess the attitudes of 500 randomly selected students, some of whom participated in service-learning projects. Their responses were contrasted with students who did not participate in a service-learning opportunity. The results of this study create a profile of students’ perception of service-learning.
What is the impact of subject benchmarking?
Authors: Pidcock Steve
Published: June 2006

The introduction of subject benchmarking led to fears of increased external intervention in the activities of universities and a more restrictive view of institutional autonomy, accompanied by an undermining of the academic profession, particularly through the perceived threat of the introduction of a national curriculum for higher education. For this study, semi-structured interviews were conducted in one old and one new university with higher education professionals in chemistry, history and quality assurance, who were asked about their perceptions of subject benchmarking and its impact. The investigation did not bear out the fears articulated at the inception of subject benchmarking. Furthermore, the investigation showed that subject benchmarking was not perceived as having the principal characteristic normally associated with a benchmarking system, in that it was not perceived as leading to improvement. The article ends with suggestions for future research.
Sallust and Skinner on Civil Liberty
Authors: Walker William
Published: June 2006

This article provides an account of what may reasonably be inferred from Sallust’s historical writing about how he understands civil liberty, what he feels is necessary for it to exist in any given political society, why he feels it is important, and the extent to which he feels it is properly enjoyed by the plebeian citizens of Rome. On the basis of this account, the article revises recent arguments presented by Quentin Skinner, Philip Pettit and others concerning Sallust’s political thought and how it is related to Aristotelian, republican, ‘neo-Roman’, and liberal traditions of political thought
Arendt, Scholem, Benjamin
Authors: Eddon Raluca
Published: June 2006

Walter Benjamin’s idiosyncratic theory of revolutionary messianism was at the very crux of his influence on Hannah Arendt and Gershom Scholem. This article argues that Arendt adopted important aspects of Benjamin’s idea of revolution, but rejected his messianism, while Scholem rejected Benjamin’s belief in revolution and accepted his emphasis on the power of messianism as a political idea, but in a historical rather than metaphysical sense. As a result, in Arendt’s and Scholem’s political thought both the category of revolution and that of messianism as Benjamin understood them were radically transformed. This transformation attests to the wide-ranging impact of Benjamin’s political philosophy, as well as to the complex and hitherto misrecognized intellectual relationship between Arendt and Scholem
A Change of Heart: Moral Emotions, Transformation, and Moral Virtue
Authors: Stark Susan
Published: June 2006

Inspired in part by a renewed attention to Aristotle's moral philosophy, philosophers have acknowledged the important role of the emotions in morality. Nonetheless, precisely how emotions matter to morality has remained contentious. Aristotelians claim that moral virtue is constituted by correct action and correct emotion. But Kantians seem to require solely that agents do morally correct actions out of respect for the moral law. There is a crucial philosophical disagreement between the Aristotelian and Kantian moral outlooks: namely, is feeling the correct emotions necessary to virtue or is it an optional extra, which is permitted but not required. I argue that there are good reasons for siding with the Aristotelians: virtuous agents must experience the emotions appropriate to their situations. Moral virtue requires a change of heart.
International research collaboration
Authors: Freshwater Dawn , Sherwood Gwen , Drury Vicki
Published: June 2006

It has been argued that whilst globalisation brings with it significant challenges, it also provides an opportunity for unifying health care activity and that of related research practices across international boundaries. Internationalisation, often confused with globalisation, is a process that can lead to a more extensive pattern of activity and collaboration. International research collaboration in health care has intensified and is frequently regarded as an indicator of quality and a way in which to develop and disseminate scientific knowledge to newly developing countries. There is however little substantive information for researchers new to the global research network on how best to manage the challenges posed by international collaboration, nor ways in which to measure the effectiveness of the same. In this paper we begin by examining the importance of international research collaboration before outlining some of the challenges of global information management. Drawing upon our own experience of jointly funded research initiatives and transnational working, alongside the available literature, we signpost some of the possible processes, practicalities and problems encountered when attempting to establish common ground.
c-Myc mediates pre-TCR-induced proliferation but not developmental progression
Authors: Dose Marei , Khan Irum , Guo Zhuyan , Kovalovsky Damian , Krueger Andreas , von Boehmer Harald , Khazaie Khashayarsha , Gounari Fotini
Published: June 2006

Constitutive and cell-autonomous signals emanating from the pre-T-cell receptor (pre-TCR) promote proliferation, survival and differentiation of immature thymocytes. We show here that induction of pre-TCR signaling resulted in rapid elevation of c-Myc protein levels. Cre-mediated thymocyte-specific ablation of c-Myc in CD25+CD44- thymocytes reduced proliferation and cell growth at the pre-TCR checkpoint, resulting in thymic hypocellularity and a severe reduction in CD4+CD8+ thymocytes. In contrast, c-Myc deficiency did not inhibit pre-TCR-mediated differentiation or survival. Myc-/- double-negative (DN) 3 cells progressed to the double-positive (DP) stage and up-regulated TCRαβ surface expression in the absence of cell proliferation, in vivo as well as in vitro. These observations indicate that distinct signals downstream of the pre-TCR are responsible for proliferation versus differentiation, and demonstrate that c-Myc is only required for pre-TCR-induced proliferation but is dispensable for developmental progression from the DN to the DP stage.
Web-based analysis of the mouse transcriptome using Genevestigator
Authors: Laule Oliver , Hirsch-Hoffmann Matthias , Hruz Tomas , Gruissem Wilhelm , Zimmermann Philip
Published: June 2006

Background

Gene function analysis often requires a complex and laborious sequence of laboratory and computer-based experiments. Choosing an effective experimental design generally results from hypotheses derived from prior knowledge or experimentation. Knowledge obtained from meta-analyzing compendia of expression data with annotation libraries can provide significant clues in understanding gene and network function, resulting in better hypotheses that can be tested in the laboratory.

Description

Genevestigator is a microarray database and analysis system allowing context-driven queries. Simple but powerful tools allow biologists with little computational background to retrieve information about when, where and how genes are expressed. We manually curated and quality-controlled 3110 mouse Affymetrix arrays from public repositories. Data queries can be run against an annotation library comprising 160 anatomy categories, 12 developmental stage groups, 80 stimuli, and 182 genetic backgrounds or modifications. The quality of results obtained through Genevestigator is illustrated by a number of biological scenarios that are substantiated by other types of experimentation in the literature.

Conclusion

The Genevestigator-Mouse database effectively provides biologically meaningful results and can be accessed at https://www.genevestigator.ethz.ch.
The tip of the iceberg: a giant pelvic atypical lipoma presenting as a sciatic hernia
Authors: Skipworth Richard JE , Smith Graeme HM , Stewart Ken J , Anderson David N
Published: June 2006

Background

This case report highlights two unusual surgical phenomena: lipoma-like well-differentiated liposarcomas and sciatic hernias. It illustrates the need to be aware that hernias may not always simply contain intra-abdominal viscera.

Case presentation

A 36 year old woman presented with an expanding, yet reducible, right gluteal mass, indicative of a sciatic hernia. However, magnetic resonance imaging demonstrated a large intra- and extra-pelvic fatty mass traversing the greater sciatic foramen. The tumour was surgically removed through an abdomino-perineal approach. Subsequent pathological examination revealed an atypical lipomatous tumour (synonym: lipoma-like well-differentiated liposarcoma). The patient remains free from recurrence two years following her surgery.

Conclusion

The presence of a gluteal mass should always suggest the possibility of a sciatic hernia. However, in this case, the hernia consisted of an atypical lipoma spanning the greater sciatic foramen. Although lipoma-like well-differentiated liposarcomas have only a low potential for recurrence, the variable nature of fatty tumours demands that patients require regular clinical and radiological review.
Measles viral load may reflect SSPE disease progression
Authors: Kühne Simmonds M , Brown DWG , Jin L
Published: June 2006

Subacute sclerosing panencephalitis (SSPE) is a rare, slowly progressive neurological disorder caused by the persistent infection with measles virus (MV). Despite much research into SSPE, its pathology remains obscure. We examined autopsy tissues of eight SSPE patients by real time quantitative PCR, immunohistochemistry and immunoblotting to determine viral load. MV N, M and H gene RNA could be detected in the central nervous system (CNS) of all patients and in two non-CNS tissues of one patient. The viral burden between patients differed up to four-fold by quantitative PCR and corresponded with detection of MV protein. The level of both viral RNA and antigen in the brain may correlate with disease progression.
The distinct clinical profile of chronically critically ill patients: a cohort study
Authors: Estenssoro Elisa , Reina Rosa , Canales Héctor S , Saenz María Gabriela , Gonzalez Francisco E , Aprea María M , Laffaire Enrique , Gola Victor , Dubin Arnaldo
Published: June 2006

Introduction

Our goal was to describe the epidemiology, clinical profiles, outcomes, and factors that might predict progression of critically ill patients to chronically critically ill (CCI) patients, a still poorly characterized subgroup.

Methods

We prospectively studied all patients admitted to a university-affiliated hospital intensive care unit (ICU) between 1 July 2002 and 30 June 2005. On admission, we recorded epidemiological data, the presence of organ failure (multiorgan dysfunction syndrome (MODS)), underlying diseases (McCabe score), acute respiratory distress syndrome (ARDS) and shock. Daily, we recorded MODS, ARDS, shock, mechanical ventilation use, lengths of ICU and hospital stay (LOS), and outcome. CCI patients were defined as those having a tracheotomy placed for continued ventilation. Clinical complications and time to tracheal decannulation were registered. Predictors of progression to CCI were identified by logistic regression.

Results

Ninety-five patients (12%) fulfilled the CCI definition and, compared with the remaining 690 patients, these CCI patients were sicker (APACHE II, 21 ± 7 versus 18 ± 9 for non-CCI patients, p = 0.005); had more organ dysfunctions (SOFA 7 ± 3 versus 6 ± 4, p < 0.003); received more interventions (TISS 32 ± 10 versus 26 ± 8, p < 0.0001); and had less underlying diseases and had undergone emergency surgery more frequently (43 versus 24%, p = 0.001). ARDS and shock were present in 84% and 83% of CCI patients, respectively, versus 44% and 48% in the other patients (p < 0.0001 for both). CCI patients had higher expected mortality (38% versus 32%, p = 0.003), but observed mortality was similar (32% versus 35%, p = 0.59). Independent predictors of progression to CCI were ARDS on admission, APACHE II and McCabe scores (odds ratio (OR) 2.26, p < 0.001; OR 1.03, p < 0.01; and OR 0.34, p < 0.0001, respectively). Lengths of mechanical ventilation, ICU and hospital stay were 33 (24 to 50), 39 (29 to 55) and 55 (37 to 84) days, respectively. Tracheal decannulation was achieved at 40 ± 19 days.

Conclusion

CCI patients were a severely ill population, in which ARDS, shock, and MODS were frequent on admission, and who suffered recurrent complications during their stay. However, their prognosis was equivalent to that of the other ICU patients. ARDS, APACHE II and McCabe scores were independent predictors of evolution to chronicity.
Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study
Authors: Rommers Mirjam K , Van Der Lely Netty , Egberts Toine CG , van den Bemt Patricia MLA
Published: June 2006

Introduction

Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.

Methods

This non-randomized open parallel group follow-up pilot study was conducted in two mixed medical-surgical intensive care units at two teaching hospitals. Seven ICU patients with subcutaneous oedema (index group) and seven ICU patients without subcutaneous oedema (reference group) were studied. Anti-Xa activity was determined at 0, 3, 4, 6, 8, 12 and 24 hours after subcutaneous administration of 2,500 IU dalteparin. Plasma concentrations of factor anti-Xa activity were measured using a chromogenic factor Xa inhibition assay.

Results

The characteristics of the index group were: age, 58 years; male/female ratio, 5/2; body mass index at admission, 23.4 kg/m2 (at study day, 30.6 kg/m2). The characteristics of the reference group were: age, 49 years; male/female ratio, 6/1; body mass index at admission, 24.8 kg/m2 (at study day, 25.0 kg/m2). In the index group, creatinine clearance was lower compared to the reference group (71 versus 131 ml/minute, p = 0.003). Sequential organ failure assessment score did not differ between index and reference groups (4 versus 5). Mean arterial pressure was comparable between index and reference groups (91 versus 95 mmHg) and within the normal range. The mean Cmax value was not different between ICU patients with and without subcutaneous oedema (0.15 ± 0.02 versus 0.14 ± 0.02 IU/ml, p = 0.34). In the index group, the mean AUC(0–24 h) value was slightly higher compared with the reference group (1.50 ± 0.31 versus 1.15 ± 0.25 h·IU/ml, p = 0.31). This difference was not significant.

Conclusion

In this pilot study, there was no clinically relevant difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for venous thromboembolism prophylaxis between ICU patients with and without subcutaneous oedema. Critically ill patients seem to have lower anti-Xa activity levels than healthy volunteers.
Systems analysis of circadian time-dependent neuronal epidermal growth factor receptor signaling
Authors: Zak Daniel E , Hao Haiping , Vadigepalli Rajanikanth , Miller Gregory M , Ogunnaike Babatunde A , Schwaber James S
Published: June 2006

Background

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology. Epidermal growth factor receptor (EGFR) has been implicated in circadian function and is expressed in the suprachiasmatic nuclei (SCN), the core circadian pacemaker. The transcription networks downstream of EGFR in the SCN are unknown but, by analogy to other SCN inputs, we expect the response to EGFR activation to depend on circadian timing.

Results

We have undertaken a systems-level analysis of EGFR circadian time-dependent signaling in the SCN. We collected gene-expression profiles to study how the SCN response to EGFR activation depends on circadian timing. Mixed-model analysis of variance (ANOVA) was employed to identify genes with circadian time-dependent EGFR regulation. The expression data were integrated with transcription-factor binding predictions through gene group enrichment analyses to generate robust hypotheses about transcription-factors responsible for the circadian phase-dependent EGFR responses.

Conclusion

The analysis results suggest that the transcriptional response to EGFR signaling in the SCN may be partly mediated by established transcription-factors regulated via EGFR transription-factors (AP1, Ets1, C/EBP), transcription-factors involved in circadian clock entrainment (CREB), and by core clock transcription-factors (Rorα). Quantitative real-time PCR measurements of several transcription-factor expression levels support a model in which circadian time-dependent EGFR responses are partly achieved by circadian regulation of upstream signaling components. Our study suggests an important role for EGFR signaling in SCN function and provides an example for gaining physiological insights through systems-level analysis.
A steganalysis-based approach to comprehensive identification and characterization of functional regulatory elements
Authors: Wang Guandong , Zhang Weixiong
Published: June 2006

The comprehensive identification of cis-regulatory elements on a genome scale is a challenging problem. We develop a novel, steganalysis-based approach for genome-wide motif finding, called WordSpy, by viewing regulatory regions as a stegoscript with cis-elements embedded in 'background' sequences. We apply WordSpy to the promoters of cell-cycle-related genes of Saccharomyces cerevisiae and Arabidopsis thaliana, identifying all known cell-cycle motifs with high ranking. WordSpy can discover a complete set of cis-elements and facilitate the systematic study of regulatory networks.
Quality of Life Is Decreased after Treatment for Nonfunctioning Pituitary Macroadenoma
Authors: Dekkers O. M. , van der Klaauw A. A. , Pereira A. M. , Biermasz N. R. , Honkoop P. J. , Roelfsema F. , Smit J. W. A. , Romijn J. A.
Published: June 2006

Objective: Although a reduced quality of life (QoL) has been reported after long-term cure of functioning pituitary adenomas, the effect of successful treatment of nonfunctioning pituitary macroadenoma (NFMA) on QoL has not been fully addressed. Therefore, we evaluated a broad spectrum of QoL parameters in patients successfully treated for NFMA in our center.

Design: We conducted a case-control study.

Patients and Methods: We assessed QoL in 99 adult patients (mean age, 61.9 yr; range, 24–86 yr) in remission during long-term follow-up after surgical (n = 99) and additional radiotherapeutic (n = 37) treatment for NFMA by four validated health-related questionnaires (Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index, Nottingham Health Profile, and Short Form-36). Patient outcomes were compared with 125 controls and with age-adjusted reference values derived from the literature.

Results: NFMA patients reported significantly impaired QoL in all questionnaires compared with the 125 controls and the age-adjusted reference values. All subscales of fatigue, assessed using the Multidimensional Fatigue Index (general fatigue, physical fatigue, reduction in activity, reduction in motivation, and mental fatigue) were impaired. The scores in the Nottingham Health Profile pointed toward reduced energy and affected emotional reaction. In several subscales of the Short Form-36 (social functioning, role limitations due to physical problems, role limitations due to emotional problems, and general health perception), NFMA patients reported a reduced QoL.

Conclusion: QoL is considerably reduced in patients after successful treatment of NFMA.
Effect of Gastric Bypass and Gastric Banding on Proneurotensin Levels in Morbidly Obese Patients
Authors: Christ-Crain Mirjam , Stoeckli Rolf , Ernst Andrea , Morgenthaler Nils G. , Bilz Stefan , Korbonits Márta , Struck Joachim , Bergmann Andreas , Müller Beat , Keller Ulrich
Published: June 2006

Context: Neurotensin is produced mainly in the N cells of the ileum and has a role in appetite regulation; levels are decreased in obese subjects and increase after bariatric surgery. Mature neurotensin is very unstable, with a short half-life.

Objective: The objective of this study was to compare baseline and postoperative levels of the more stable neurotensin precursor, proneurotensin/neuromedin (pro-NT/NMN), in patients after gastric banding, gastric bypass, and nonoperated controls, respectively, during long-term follow-up.

Design and Setting: This was a prospective observational study in a university hospital.

Participants and Main Outcome Measures: Overnight fasting plasma pro-NT/NMN concentrations were measured with a new sandwich immunoassay in morbidly obese subjects at baseline and 6, 12, and 24 months after gastric banding (n = 8), Roux-en-Y gastric bypass (n = 5), and in nonoperated controls (n = 7).

Results: After gastric bypass and banding, body weight decreased by (mean ± sd) 29.5 ± 5.5 and 22.8 ± 5.9 kg, respectively. The decrease after 3 and 6 months was more pronounced after gastric bypass compared with gastric banding (P < 0.05). Plasma pro-NT/NMN levels in patients after gastric bypass increased from 246.3 ± 174.3 pmol/liter on admission to 748.3 ± 429.6 pmol/liter after 24 months (P < 0.01). In contrast, in patients with gastric banding, pro-NT/NMN concentrations remained stable (207.3 ± 60.5 pmol/liter at admission, 226.6 ± 116.8 pmol/liter after 24 months). Neither body weight nor plasma pro-NT/NMN levels changed in nonoperated controls.

Conclusion: Plasma pro-NT/NMN levels show a more pronounced increase after gastric bypass compared with gastric banding, suggesting that specific bariatric surgical procedures result in distinct alterations of gastrointestinal hormone metabolism. The more stable precursor pro-NT/NMN provides a new tool to quantify neurotensin levels in clinical practice.
Molecular Model of Human CYP21 Based on Mammalian CYP2C5: Structural Features Correlate with Clinical Severity of Mutations Causing Congenital Adrenal Hyperplasia
Authors: Robins Tiina , Carlsson Jonas , Sunnerhagen Maria , Wedell Anna , Persson Bengt
Published: June 2006

Enhanced understanding of structure-function relationships of human 21-hydroxylase, CYP21, is required to better understand the molecular causes of congenital adrenal hyperplasia. To this end, a structural model of human CYP21 was calculated based on the crystal structure of rabbit CYP2C5. All but two known allelic variants of missense type, a total of 60 disease-causing mutations and six normal variants, were analyzed using this model. A structural explanation for the corresponding phenotype was found for all but two mutants for which available clinical data are also discrepant with in vitro enzyme activity. Calculations of protein stability of modeled mutants were found to correlate inversely with the corresponding clinical severity. Putative structurally important residues were identified to be involved in heme and substrate binding, redox partner interaction, and enzyme catalysis using docking calculations and analysis of structurally determined homologous cytochrome P450s (CYPs). Functional and structural consequences of seven novel mutations, V139E, C147R, R233G, T295N, L308F, R366C, and M473I, detected in Scandinavian patients with suspected congenital adrenal hyperplasia of different severity, were predicted using molecular modeling. Structural features deduced from the models are in good correlation with clinical severity of CYP21 mutants, which shows the applicability of a modeling approach in assessment of new CYP21 mutations.
Interplay of PIWI/Argonaute protein MIWI and kinesin KIF17b in chromatoid bodies of male germ cells
Authors: Kotaja Noora , Lin Haifan , Parvinen Martti , Sassone-Corsi Paolo
Published: June 2006

Chromatoid bodies are thought to act as male-germ-cell-specific platforms for the storing and processing of haploid transcripts. The molecular mechanisms governing the formation and function of these germ-cell-specific structures have remained elusive. In this study, we show that the kinesin motor protein KIF17b, which is involved in the nucleocytoplasmic transport of RNA and of a transcriptional coactivator, localizes in chromatoid bodies. The chromatoid body moves actively and non-randomly in the cytoplasm of round spermatids, making frequent contacts with the nuclear envelope. The localization of KIF17b thereby offers a potential mechanism for microtubule-dependent mobility of chromatoid bodies, as well as for the transport of the specific components in and out of the chromatoid body. Interestingly, we demonstrate that KIF17b physically interacts with a testis-specific member of the PIWI/Argonaute family, MIWI, a component of chromatoid bodies implicated in RNA metabolism. A functional interplay between KIF17b and MIWI might be needed for the loading of haploid RNAs in the chromatoid body. Importantly, chromatoid bodies from round spermatids of miwi-null mice are not fully compacted and remain as a diffuse chromatoid material, revealing the essential role played by MIWI in the formation of chromatoid bodies. These results shed new light on the function of chromatoid bodies in the post-transcriptional regulation of gene expression in haploid germ cells.