bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Complications Less Common in Deep Brain Stimulation than in Ablative Procedures for Movement Disorders?
Authors: Blomstedt Patric , Hariz Marwan I.
Published: June 2006

The side effects and complications of deep brain stimulation (DBS) and ablative lesions for tremor and Parkinson’s disease were recorded in 256 procedures (129 DBS and 127 lesions). Perioperative complications (seizures, haemorrhage, confusion) were rare and did not differ between the two groups. The rate of hardware-related complications was 17.8%. In ventral intermediate (Vim) thalamotomies, the rate of side effects was 74.5%, in unilateral Vim-DBS 47.3%, while in 7 bilateral Vim-DBS 13 side effects occurred. Most of the side effects of Vim-DBS were reversible upon switching off, or altering, stimulation parameters. In unilateral pallidotomy, the frequency of side effects was 21.9%, while in bilateral staged pallidotomies it was 33.3%. Eight side effects occurred in 11 procedures with pallidal DBS. In 22 subthalamic nucleus DBS procedures, 23 side effects occurred, of which 8 were psychiatric or cognitive. Unilateral ablative surgery may not harbour more postoperative complications or side effects than DBS. Some of the side effects following lesioning are transient and most but not all DBS side effects are reversible. In the Vim DBS is safer than lesioning, while in the pallidum, unilateral lesions are well tolerated.
Colonoscopy Demand and Practice in a Regional Hospital over 9 Years in Hong Kong: Resource Implication for Cancer Screening
Authors: Chan Annie O.O. , Hui Wai Mo , Chan Chi Kuen , Lai Kam Chuen , Hu Wayne H.C. , Yuen Man Fung , Wong Wai Man , Lau George K.K. , Hui Chi Kin , Lam Shiu Kum , Wong Benjamin C.Y.
Published: June 2006

Background: The incidence of colorectal cancer (CRC) in Hong Kong is rising. The trend of colonoscopy demand is uncertain. Aim: To investigate colonoscopy demand and practice in a Hong Kong regional hospital over the past nine years. Methods: Colonoscopy data from 1st January 1997 to 31st August 2005 were retrieved and divided into two equal periods for comparison. Colonoscopy practice and findings between the two periods were compared. Results: There was no change in the number of endoscopists and colonoscopy sessions in the two periods. The number of colonoscopy done in the two periods was 2,681 and 2,871, respectively. The indications for screening of CRC/polyp (9.3 vs. 24.7%, p < 0.0001) and surveillance of CRC/polyp (4.7 vs. 10.9%, p < 0.0001) were increased, but decreased for diarrhea (18 vs. 10.2%, p < 0.0001) and per rectal bleeding (19 vs. 8.1%, p < 0.0001). The waiting time was lengthened from 2 to 4 weeks (p < 0.0001). The percentage of colonic adenomas (19.9 vs. 27.2%, p < 0.0001) was increased. A right-shift was observed in both CRC (37 vs. 50%, p = 0.018) and adenoma (21.6 vs. 38.1%, p < 0.0001). Conclusion: The number of colonoscopies performed was governed by capacity partly through lengthening of waiting time to cope with demand. Ways to improve capacity for colonoscopies is needed.
Update on Clarithromycin Resistance in Helicobacter pylori in Hong Kong and Its Effect on Clarithromycin-Based Triple Therapy
Authors: Gu Q. , Xia H.H.X. , Wang J.D. , Wong W.M. , Chan A.O.O. , Lai K.C. , Chan C.K. , Yuen M.F. , Fung F.M.Y. , Wong K.W. , Lam S.K. , Wong B.C.Y.
Published: June 2006

Aim: To determine the antibiotic susceptibility of Helicobacter pylori and evaluate the efficacy of a clarithromycin-based triple therapy in relation to antibiotic resistance. Methods: Consecutive patients referred for upper endoscopy due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the CLO test, histology and culture. Antibiotic susceptibility was assessed by the E-test. Patients with H. pylori infection received rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. Results: Of 234 patients recruited, 124 were H. pylori-positive and culture was successful in 102 patients. The updated prevalences of resistance to clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%, respectively. A total of 86 patients received 1-week triple therapy with rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily, and 81 patients attended the follow-up test. Eradication rates by per-protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The eradication rate by per protocol was significantly higher in patients with clarithromycin-susceptible strains than in those with clarithromycin-resistant strains (98.6 vs. 28.6%, p < 0.001). Conclusion: Clarithromycin resistance reduces the clinical efficacy of clarithromycin-based triple therapy. However, due to the low prevalence of clarithromycin resistance, clarithromycin-based therapy is still the first choice for clinical use.
Lactobacillus acidophilus as a Cause of Liver Abscess in a NOD2/CARD15-Positive Patient with Crohn’s Disease
Authors: Cukovic-Cavka S. , Likic R. , Francetic I. , Rustemovic N. , Opacic M. , Vucelic B.
Published: June 2006

Introduction: The development of a fistula and/or an abscess are major complications in patients with Crohn’s disease. An abscess can involve any of the major viscera, including the liver and spleen. Case Report: A 27-year-old male patient with a 6-month history of NOD2/CARD15-positive Crohn’s disease with stenosis of the terminal ileum, previously treated with corticosteroids, was admitted with fever, chills, diarrhea, fatigue and cachexia. Diagnostic work-up revealed sepsis, an abscess in the right hepatic lobe, multiple abdominal collections and right-sided pleural effusion. It was felt that his poor general condition prevented surgical intervention and complex conservative treatment was initiated. It consisted of total parenteral nutrition, antibiotics, percutaneous drainage of the liver abscess, and thoracocentesis. Pus and blood cultures showed Lactobacillus acidophilus. There was a gradual improvement in the patient’s condition and the liver abscess decreased in diameter from 14 to 2 cm. Aminosalicylates and enteral nutrition were gradually introduced. The patient was discharged after 9 weeks in good general condition. Conclusion: Although extremely rarely, L. acidophilus can cause hepatic abscess and sepsis. This can be explained by immunologic incompetence due to corticosteroid treatment of Crohn’s disease.
Food Hypersensitivity Reactions Visualised by Ultrasonography and Magnetic Resonance Imaging in a Patient Lacking Systemic Food-Specific IgE
Authors: Arslan Gülen , Lillestøl Kristine , Mulahasanovic Arna , Florvaag Erik , Berstad Arnold
Published: June 2006

Background: Abdominal complaints related to food intake might be due to hypersensitivity. A firm diagnosis of food allergy is often difficult to establish, particularly in the absence of systemic food-specific IgE. Using ultrasonography and magnetic resonance imaging (MRI) we were able to visualise the intestinal response in one such case. Methods: A 24-year-old female presented with self-reported food hypersensitivity, particularly related to the intake of egg. Nausea and diarrhoea were predominant symptoms. Double-blind placebo-controlled food challenge with raw egg was positive, but all other conventional tests of food hypersensitivity, including skin prick test, total and food-specific IgE in serum, were negative. A thorough investigation programme could not reveal any organic disease of the gastrointestinal tract. We extended the evaluation to include two new provocation tests, where intestinal wall thickening and the amount of luminal liquid were monitored by external abdominal ultrasound and MRI. Results: Both ultrasound and MRI investigations indicated intestinal wall thickening and influx of large amounts of fluid into the proximal small intestines within 10 min of duodenal challenge with egg. The response was associated with abdominal pain and bloating. Conclusions: The response to provocation was typical of an immediate allergic reaction. Our results indicate that local food-induced hypersensitivity reactions can occur in the gut in the absence of systemic indications of IgE-mediated allergy. Abdominal ultrasonography and MRI might become valuable tools for documenting such responses.
Immunology of Helicobacter pylori Infection
Authors: Velin Dominique , Michetti Pierre
Published: June 2006

Helicobacter pylori is a Gram-negative, spiral bacterium that colonizes the gastric mucosa of at least 50% of the world’s population and plays a causative role in the development of chronic gastritis as well as in gastric and duodenal ulcers. H. pylori triggers vigorous humoral and cellular immune responses in both systemic and mucosal compartments. In spite of this response, the vast majority of infected hosts are unable to clear the infection, and it persists for decades. Although Helicobacter is tolerated by a naïve host organism, preclinical studies have demonstrated that prophylactic or therapeutic vaccinations efficiently clear Helicobacter from the stomach. The understanding of the mechanisms leading to the Helicobacter persistence or the vaccine-induced eradication of Helicobacter in animal models will help to define optimal immunization strategies for future anti-Helicobacter vaccination clinical trials.
Signaling Pathway Involved in the Pro-Apoptotic Effect of Dopamine in the GH3 Pituitary Cell Line
Authors: Jaubert Arnaud , Ichas François , Bresson-Bepoldin Laurence
Published: June 2006

Besides its physiological role as a neurotransmitter, dopamine (DA) induces apoptosis in the central nervous system. This effect is mediated partly by the DA transporter (DAT) and involves reactive oxygen species (ROS) formation as well as oxidative stress. In the pituitary, the inhibitory control by DA of prolactin release and synthesis and lactotrope cell proliferation is well known, while the pro-apoptotic effect of DA remains unclear. Our aim was to study the pro-apoptotic effect of DA in the GH3 mammosomatotrope cell line and determine the DA mechanism that leads to apoptosis in these cells. Using flow cytometry, Western blot, and confocal microscopy, we showed for the first time that DA induced: (1) loss of mitochondrial potential; (2) relocation of Bax to the mitochondria; (3) cytochrome c release; (4) caspase-3 activation, and (5) nuclear fragmentation, resulting in apoptosis. We observed that DAT was expressed in GH3 cells and participated in the DA effect, as apoptosis was significantly reversed in the presence of DAT inhibitors. Direct measurement showed that DA rapidly increased the formation of intracellular ROS. The antioxidant N-acetyl-L-cysteine (NAC) effectively blocked DA-induced ROS formation and apoptosis. Neither JNK nor p38 were involved in this process, so we suggest that the mitochondrial pore of transition is the likely target of the ROS generated by DA. These data provide the first evidence that DA triggers apoptosis in pituitary cells via a mechanism involving DAT and oxidative stress. These findings may be particularly relevant in understanding lactotrope apoptosis during postnatal life.
Slowing Sovietization: The Labour Party, the Hungarian Social Democrats and the Elections of 1947
Authors: McStea Ullin Jodah
Published: June 2006

Between 1945 and 1947 the Hungarian Social Democratic Party (MSzDP) and the British Labour Party developed a relationship which resulted in regular contacts, visits and communications between the two parties. From the British perspective a major motivation in pursuing this relationship was to discourage the Hungarian Socialists from making themselves subservient to the Communist Party, which at that time was very influential. The summer of 1947 was the most intense period of this unusual Anglo-Hungarian relationship, with leading British diplomatic and Labour Party figures actively encouraging the MSzDP to take a stand against Communist demands. This work examines the relationship between the British Foreign Office and Labour Party and the MSzDP in the context of the events that surrounded the general election that was held in Hungary in the summer of 1947. It focuses predominantly on events in Hungary but it also examines an unusual set of discussions that took place in London in September 1947
The Sociology of Globalization
Authors: Martin Dominique , Metzger Jean-Luc , Pierre Philippe
Published: June 2006

Although the word ‘globalization’ is widely used, its sociological meaning needs clarification. The aim of this article is to achieve that, while returning to the basic premise that sociology is the primary discipline that charts changes within the world-society. Two typical subjects for the sociology of globalization can be distinguished: defining what is ‘global’ at first sight and the identification of similar changes in (almost) all countries. However, can national-born concepts help to explain these subjects? This is debated by considering the sociology of social movements (Touraine) and the sociology of the elite (Aron and Rocher) to explain power in the study of alterglobalist movements. The authors conclude that in order to understand world metamorphosis, there is an urgency to make available accurate and reliable data and match universally recognized definitions. Both of these suggestions bring us to the broader yet fundamental issue of the specific principles required within the social sciences.
Globalization and Mixing in the Visual Arts
Authors: Quemin Alain
Published: June 2006

While there has been an increasing amount of research into globalization since the 1990s, empirical sociological studies in this area remain all too scarce. By analysing specific cases in contemporary visual art, this article shows that the widespread art world discourse on globalization, mixing and the abolition of borders is to a large extent based on illusion. By objectifying the positions occupied by different countries in the field of art, the article brings to light a marked hierarchy that reveals that, beyond the development of international exchanges, the art world still has a clearly defined centre comprising a small number of western countries, among which the US and Germany are pre-eminent, and a vast periphery, comprising all the other states. The specific example empirically analysed here leads to a reconsideration of earlier studies of cultural globalization, most of which are essentially abstract.
Noah’s Library: Sources for 1 Enoch 6-11
Authors: Bhayro Siam
Published: June 2006

This article presents three case studies that explore the literary antecedents to 1 Enoch 6-11. The first case suggests that we can see a clear Mesopotamian influence on this narrative, while the second extends our understanding of the manner in which the author was incorporating rewritten biblical narrative into the text. The third case discusses, in a pan-Eastern Mediterranean context, the origins of the angel name Shemihazah. Taken together, these three examples illustrate the richness of the traditions and literary resources available to those who composed and edited this text.
Noachic Traditions and the Book of Noah
Authors: Baxter Wayne
Published: June 2006

This article examines the existence of the Book of Noah, arguing that this document existed during the Second Temple period and that it was a repository for some but not all of the diverse Noachic traditions of the time. The study will begin by analyzing Second Temple Noachic narratives and references to the writings of Noah, explaining why the data support the existence of a Book of Noah, and conclude by applying insights from Gospel Criticism to determine the baseline content of this document.
Firstborn Shor and Rem
Authors: Mitchell David C.
Published: June 2006

1 Enoch 90.37-38 feature a messianic white bull and a nagar. Following a discussion of interpretational cruces, this article concludes that the latter represents the aurochs. A comparison is made with Deut. 33.17 in which the same two oxen represent an anticipated Joseph-Joshua deliverer, who is on the one hand servile and destined to sacrificial death and on the other regnant and free. The coincidence of imagery in the two passages suggests that 1 En. 90.37-38 is dependent on Deut. 33.17, leading to the conclusion that the oxen of 1 En. 90.37.38 depict a Joseph-Joshua Messiah destined to sacrificial death then resurgence in power. This has implications for the dating of beliefs about the Josephite Messiah, for the integrity of other second-century BCE texts, and for Christian origins.
How is Justice Restored?
Authors: Skotnicki Andrew
Published: June 2006

Restorative justice is an approach to crime and punishment that seeks to bypass the dynamics of the courtroom. It features the opportunity for victim and offender to construct a mutually agreed-upon means of reparation. Its proponents frequently invoke three ethical claims in defence of the practice: that punishment is not a necessary response to crime, that justice must be understood in a contextual rather than a foundational sense, and that the character of the offender can be amended through the restorative encounter. Each claim will be analysed and critiqued from perspectives drawn from traditional and contemporary Christian ethics.
Living improvement: a case study of a secondary school in England®
Authors: Hollins Kevin , Gunter Helen M. , Thomson Pat
Published: June 2006

Schools in England are being urged to personalize the curriculum and make school experiences more responsive to all students. We report on an evaluation project which investigated innovation in teaching and learning in a successful secondary school in the north of England. Data were gathered from a sample of teaching staff, a questionnaire to all students, lesson and meeting observations, and meetings with the governing body and parents: the student-guided evaluation canvassed recent and planned changes to the structure and experience of teaching and learning. This article illuminates how one school is breaking the ‘traditional schooling rules’ that limit improvement and how in doing so it is developing new insights about the nature and process of improvement. We show how staff and students have been engaged in the change process, and focus in particular on analysing the interplay between improvement as a plan, a practice and a lived experience.
What else do students need?
Authors: Baker Amanda
Published: June 2006

This article considers university staff’s place in students’ worlds from a psychodynamic perspective. It looks at ‘studenthood’ as a psychological stage, in which relationship to university and university staff is seen as being recruited into a personal developmental context. It sketches some psychodynamic background for understanding the role students unconsciously assign to staff, in terms of concepts such as transference, projection and containment. It makes connections between mechanisms for early infancy social learning about self/identity and the identity-establishing responses which students need at their stage too. It uses this understanding to explain some of the difficulties which can be experienced in responding to troubled students. We can extrapolate from the more difficult end of the spectrum to inform our general understanding about the dynamics of students’ need for responsiveness and ‘help’, and the article finally briefly considers ‘help’ and ‘problems’ as usually being developmental rather than pathological agents of students’ learning process.
The relation between self-regulated strategies and individual study time, prepared participation and achievement in a problem-based curriculum
Authors: van Den Hurk Marianne
Published: June 2006

In problem-based learning (PBL) students are encouraged to take responsibility for their own self-regulated learning process. The present study focuses on two self-regulated learning strategies, namely time planning and self-monitoring. Time planning involves time management, scheduling and planning one’s study time. Self-monitoring involves setting goals, focusing attention and monitoring study activities. The aim of this study was first, to assess students’ time planning and self-monitoring skills and second, to investigate how time planning and self-monitoring skills are related to actual individual study time, (un)prepared participation in the tutorial group and cognitive achievement. 165 first-year psychology students, enrolled in a problem-based curriculum, filled in a questionnaire (response 77%) and their scores on two tests of cognitive achievement were used. Results showed that students who are better time-planners and who have better self-monitoring skills were more efficient in allocating their individual study time (spent less time on individual study), prepared more appropriately for the tutorial group meeting (although not significant [n.s.]) and achieved higher scores on cognitive tests.
Rousseau versus Rawls on International Relations
Authors: Roosevelt Grace
Published: June 2006

This article uses Rousseau’s little-known responses to the Abbé de Saint-Pierre’s Project for Perpetual Peace and his fragments on ‘The State of War’ as a foil for Rawls’s claim that the international society he envisions in The Law of Peoples constitutes a ‘realistic utopia’. The main conclusion is that in a post-9/11 world Rousseau may have more to teach us about the possibilities for international security than Rawls does, since Rousseau’s theory accounts for the moral corruptibility of both individuals and groups. Most of the article focuses on comparing Rousseau’s and Rawls’s assumptions about human nature, but the final section also includes a brief discussion of their contrasting views of reason and the common good. The two philosophers agree, however, that the possibilities for international justice can only evolve out of the careful practice of local justice
Representative Democracy as Tautology
Authors: Näsström Sofia
Published: June 2006

Representative democracy is often assessed from the standpoint of direct democracy. Recently, however, many theorists have come to argue that representation forms a democratic model in its own right. The most powerful claim in this direction is to be found within two quite different strands of thinking: the aesthetic theory of Frank Ankersmit and the savage theory of Claude Lefort. In this article, I show that while Ankersmit and Lefort converge in their critique of direct rule, they provide us with two distinct models of democracy. Aesthetic democracy, I argue, in the end falls short as a democratic recuperation of representation. It reduces representation to delegation. Savage democracy proves more fruitful in this respect. It offers a representative view of politics without committing itself to the premises associated with political delegation
Secession as a Human Right
Authors: Tideman Nicolaus
Published: June 2006

If people are to have rights to themselves, then they must have the right to affiliate in sovereign entities composed of people who mutually agree to affiliate with one another. This requires that any individual or group has a right to secede from any sovereign entity. The article develops the idea that a right of secession is natural when rights to territory and other gifts of nature are regarded as belonging equally to all persons, and all persons have rights to themselves. The article also argues that a world that recognizes a right of secession is feasible.
The metastasis-associated 67-kDa laminin receptor is involved in G-CSF–induced hematopoietic stem cell mobilization
Authors: Selleri Carmine , Ragno Pia , Ricci Patrizia , Visconte Valeria , Scarpato Nicola , Carriero Maria Vincenza , Rotoli Bruno , Rossi Guido , Montuori Nunzia
Published: June 2006

The 67-kDa laminin receptor (67LR) is a nonintegrin cell-surface receptor with high affinity for laminin, which plays a key role in tumor invasion and metastasis. We investigated the role of 67LR in granulocyte colony-stimulating factor (G-CSF)–induced mobilization of CD34+ hematopoietic stem cells (HSCs) from 35 healthy donors. G-CSF–mobilized HSCs, including CD34+/CD38– cells, showed increased 67LR expression as compared with unstimulated marrow HSCs; noteworthy, also, is the fact that the level of 67LR expression in G-CSF–mobilized HSCs correlated significantly with mobilization efficiency. During G-CSF–induced HSC mobilization, the expression of laminin receptors switched from α6 integrins, which mediated laminin-dependent adhesion of steady-state human marrow HSCs, to 67LR, responsible for G-CSF–mobilized HSC adhesion and migration toward laminin. In vitro G-CSF treatment, alone or combined with exposure to marrow-derived endothelial cells, induced 67LR up-regulation in marrow HSCs; moreover, anti-67LR antibodies significantly inhibited transendothelial migration of G-CSF–stimulated marrow HSCs. Finally, G-CSF–induced mobilization in mice was associated with 67LR up-regulation both in circulating and marrow CD34+ cells, and anti-67LR antibodies significantly reduced HSC mobilization, providing the first in vivo evidence for 67LR involvement in stem-cell egress from bone marrow after G-CSF administration. In conclusion, 67LR up-regulation in G-CSF–mobilized HSCs correlates with their successful mobilization and reflects its increase in marrow HSCs, which contributes to the egress from bone marrow by mediating laminin-dependent cell adhesion and transendothelial migration.
CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities
Authors: Lee Young-Jin , Jones Letetia C. , Timchenko Nikolai A. , Perrotti Danilo , Tenen Daniel G. , Kogan Scott C.
Published: June 2006

CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them to differentiate into mature neutrophils, an effect thought to be mediated by C/EBPs. In this study, we assess the potential for cooperativity between increased C/EBP activity and ATRA therapy. We demonstrate that although both C/EBPα and C/EBPϵ can significantly prolong survival in a mouse model of APL, they are not functionally equivalent in this capacity. We also show that forced expression of C/EBPα or C/EBPϵ in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone.
Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation
Authors: Rowe Vanessa , Banovic Tatjana , MacDonald Kelli P. , Kuns Rachel , Don Alistair L. , Morris Edward S. , Burman Angela C. , Bofinger Helen M. , Clouston Andrew D. , Hill Geoffrey R.
Published: June 2006

Host antigen-presenting cells (APCs) are known to be critical for the induction of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but the relative contribution of specific APC subsets remains unclear. We have studied the role of host B cells in GVHD by using B-cell–deficient μMT mice as BMT recipients in a model of CD4-dependent GVHD to major histocompatibility complex antigens. We demonstrate that acute GVHD is initially augmented in μMT recipients relative to wild-type recipients (mortality: 85% vs 44%, P < .01), and this is the result of an increase in donor T-cell proliferation, expansion, and inflammatory cytokine production early after BMT. Recipient B cells were depleted 28-fold at the time of BMT by total body irradiation (TBI) administered 24 hours earlier, and we demonstrate that TBI rapidly induces sustained interleukin-10 (IL-10) generation from B cells but not dendritic cells (DCs) or other cellular populations within the spleen. Finally, recipient mice in which B cells are unable to produce IL-10 due to homologous gene deletion develop more severe acute GVHD than recipient mice in which B cells are wild type. Thus, the induction of IL-10 in host B cells during conditioning attenuates experimental acute GVHD.
Gene expression profiling of Spodoptera frugiperda hemocytes and fat body using cDNA microarray reveals polydnavirus-associated variations in lepidopteran host genes transcript levels
Authors: Barat-Houari M , Hilliou F , Jousset F-X , Sofer L , Deleury E , Rocher J , Ravallec M , Galibert L , Delobel P , Feyereisen R , Fournier P , Volkoff A-N
Published: June 2006

Background

Genomic approaches provide unique opportunities to study interactions of insects with their pathogens. We developed a cDNA microarray to analyze the gene transcription profile of the lepidopteran pest Spodoptera frugiperda in response to injection of the polydnavirus HdIV associated with the ichneumonid wasp Hyposoter didymator. Polydnaviruses are associated with parasitic ichneumonoid wasps and are required for their development within the lepidopteran host, in which they act as potent immunosuppressive pathogens. In this study, we analyzed transcriptional variations in the two main effectors of the insect immune response, the hemocytes and the fat body, after injection of filter-purified HdIV.

Results

Results show that 24 hours post-injection, about 4% of the 1750 arrayed host genes display changes in their transcript levels with a large proportion (76%) showing a decrease. As a comparison, in S. frugiperda fat body, after injection of the pathogenic JcDNV densovirus, 8 genes display significant changes in their transcript level. They differ from the 7 affected by HdIV and, as opposed to HdIV injection, are all up-regulated. Interestingly, several of the genes that are modulated by HdIV injection have been shown to be involved in lepidopteran innate immunity. Levels of transcripts related to calreticulin, prophenoloxidase-activating enzyme, immulectin-2 and a novel lepidopteran scavenger receptor are decreased in hemocytes of HdIV-injected caterpillars. This was confirmed by quantitative RT-PCR analysis but not observed after injection of heat-inactivated HdIV. Conversely, an increased level of transcripts was found for a galactose-binding lectin and, surprisingly, for the prophenoloxidase subunits. The results obtained suggest that HdIV injection affects transcript levels of genes encoding different components of the host immune response (non-self recognition, humoral and cellular responses).

Conclusion

This analysis of the host-polydnavirus interactions by a microarray approach indicates that the presence of HdIV induces, directly or indirectly, variations in transcript levels of specific host genes, changes that could be responsible in part for the alterations observed in the parasitized host physiology. Development of such global approaches will allow a better understanding of the strategies employed by parasites to manipulate their host physiology, and will permit the identification of potential targets of the immunosuppressive polydnaviruses.
Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study
Authors: Fecteau Shirley , Lassonde Maryse , Théoret Hugo
Published: June 2006

Background

The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections.

Methods

Intracortical excitatory and inhibitory systems were tested in three individuals with complete agenesis of the corpus callosum and sixteen healthy individuals. These systems were assessed using transcranial magnetic stimulation (TMS) protocols: motor threshold at rest, paired-pulse curve, and cortical silent period.

Results

TMS revealed no difference between the patient and control groups on the motor threshold measure, as well as intracortical facilitation and intracortical inhibition systems as tested by paired stimulation. However, intrahemispheric inhibitory function was found to be abnormal in participants without callosal projections, as the cortical silent period duration was significantly increased in the patient group.

Conclusion

These data suggest that in addition to previously reported impaired interhemispheric function, patients lacking the entire corpus callosum also display abnormal intrahemispheric excitability of the primary motor cortex.
Effects of equipment and technique on peak flow measurements
Authors: Bongers Thomas , O'Driscoll B Ronan
Published: June 2006

Background

Different lung function equipment and different respiratory manoeuvres may produce different Peak Expiratory Flow (PEF) results. Although the PEF is the most common lung function test, there have been few studies of these effects and no previous study has evaluated both factors in a single group of patients.

Methods

We studied 36 subjects (PEF range 80–570 l/min). All patients recorded PEF measurements using a short rapid expiration following maximal inspiration (PEF technique) or a forced maximal expiration to residual volume (FVC technique). Measurements were made using a Wright's peak flow meter, a turbine spirometer and a Fleisch pneumotachograph spirometer.

Results

The mean PEF was 8.7% higher when the PEF technique was used (compared with FVC technique, p < 0.0001). The mean PEF recorded with the turbine spirometer was 5.5% lower than the Wright meter reading. The Fleisch spirometer result was 19.5% lower than the Wright reading. However, adjustment of the Wrights measurements from the traditional Wright's scale to the new EU Peak Flow scale produced results that were only 7.2% higher than the Fleisch pneumotachograph measurements.

Conclusion

Peak flow measurements are affected by the instruction given and by the device and Peak Flow scale used. Patient management decisions should not be based on PEF measurement made on different instruments.
Alteration of serotonin transporter density and activity in fibromyalgia
Authors: Bazzichi Laura , Giannaccini Gino , Betti Laura , Mascia Giovanni , Fabbrini Laura , Italiani Paola , De Feo Francesca , Giuliano Tiziana , Giacomelli Camillo , Rossi Alessandra , Lucacchini Antonio , Bombardieri Stefano
Published: June 2006

The aim of the study was to evaluate the kinetic parameters of a specific serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of patients with fibromyalgia. Platelets were obtained from 40 patients and 38 healthy controls. SERT expression and functionality were evaluated through the measurement of [3H]paroxetine binding and the [3H]serotonin uptake itself. The values of maximal membrane binding capacity (Bmax) were statistically lower in the patients than in the healthy volunteers, whereas the dissociation constant (Kd) did not show any statistically significant variations. Moreover, a decrease in the maximal uptake rate of SERT (Vmax) was demonstrated in the platelets of patients, whereas the Michaelis constant (Km) did not show any statistically significant variations. Symptom severity score (tiredness, tender points index and Fibromyalgia Impact Questionnaire) were negatively correlated with Bmax and with Vmax, and positively correlated with Km. A change in SERT seems to occur in fibromyalgic patients, and it seems to be related to the severity of fibromyalgic symptoms.
Keratin 6 is not essential for mammary gland development
Authors: Grimm Sandra L , Bu Wen , Longley Mary Ann , Roop Dennis R , Li Yi , Rosen Jeffrey M
Published: June 2006

Introduction

Keratin 6 (K6) has previously been identified as a marker of early mammary gland development and has also been proposed to be a marker of mammary gland progenitor cells. However, the function of K6 in the mammary gland was not known, so we examined the expression pattern of the protein during both embryonic and postnatal mammary development, as well as the mammary gland phenotype of mice that were null for both K6a and K6b isoforms.

Method

Immunostaining was performed to determine the expression pattern of K6a throughout mammary gland development, from the embryonic mammary bud to lactation. Double immunofluorescence was used to co-localize K6 with known markers of mammary gland development. Wild-type and K6ab-null mammary tissues were transplanted into the cleared fat pads of nude mice and the outgrowths were analyzed for morphology by whole-mount staining and for markers of mammary epithelium by immunostaining. Finally, progesterone receptor (PR) and bromodeoxyuridine co-localization was quantified by double immunofluorescence in wild-type and K6ab-null mammary outgrowths.

Results

Here we report that K6 is expressed earlier than described previously, by embryonic day 16.5. K6a is the predominant isoform expressed in the mammary gland, localized in the body cells and luminal epithelial cells but not in the cap cells or myoepithelial cells. Co-localization studies showed that most K6a-positive cells express steroid receptors but do not proliferate. When both the K6a and K6b genes are deleted, mammary gland development appears normal, with similar expression of most molecular markers examined in both the pubertal gland and the mature gland. Loss of K6a and K6b, however, leads to an increase in the number of steroid-receptor-positive cells, and increased co-localization of steroid receptor expression and proliferation was observed.

Conclusion

Although K6a was not essential for mammary gland development, loss of both K6a and K6b resulted in an increase in PR-positive mammary epithelial cells and decreased proliferation after exposure to steroid hormones. There was also increased co-localization of PR and bromodeoxyuridine, suggesting alterations in patterning events important for normal lobuloalveolar development.
The effect of the stromal component of breast tumours on prediction of clinical outcome using gene expression microarray analysis
Authors: Cleator Susan J , Powles Trevor J , Dexter Tim , Fulford Laura , Mackay Alan , Smith Ian E , Valgeirsson Haukur , Ashworth Alan , Dowsett Mitch
Published: June 2006

Introduction

The aim of this study was to examine the effect of the cellular composition of biopsies on the error rates of multigene predictors of response of breast tumours to neoadjuvant adriamycin and cyclophosphamide (AC) chemotherapy.

Materials and methods

Core biopsies were taken from primary breast tumours of 43 patients prior to AC, and subsequent clinical response was recorded. Post-chemotherapy (day 21) samples were available for 16 of these samples. Frozen sections of each core were used to estimate the proportion of invasive cancer and other tissue components at three levels. Transcriptional profiling was performed using a cDNA array containing 4,600 elements.

Results

Twenty-three (53%) patients demonstrated a 'good' and 20 (47%) a 'poor' clinical response. The percentage invasive tumour in core biopsies collected from these patients varied markedly. Despite this, agglomerative clustering of sample expression profiles showed that almost all biopsies from the same tumour aggregated as nearest neighbours. SAM (significance analysis of microarrays) regression analysis identified 144 genes which distinguished high- and low-percentage invasive tumour biopsies at a false discovery rate of not more than 5%. The misclassification error of prediction of clinical response using microarray data from pre-treatment biopsies (on leave-one-out cross-validation) was 28%. When prediction was performed on subsets of samples which were more homogeneous in their proportions of malignant and stromal cells, the misclassification error was considerably lower (8%–13%, p < 0.05 on permutation).

Conclusion

The non-tumour content of breast cancer samples has a significant effect on gene expression profiles. Consideration of this factor improves accuracy of response prediction by expression array profiling. Future gene expression array prediction studies should be planned taking this into account.
Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
Authors: Burcombe Russell , Wilson George D , Dowsett Mitch , Khan Ifty , Richman Paul I , Daley Frances , Detre Simone , Makris Andreas
Published: June 2006

Introduction

Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. This study evaluated changes in Ki-67 labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy.

Methods

Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. Tissue from pre-treatment biopsy, day 21 and surgery was analysed for Ki-67 index and AI.

Results

The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histological criteria; two patients had a near-complete pathological response. A reduction in Ki-67 index was observed in 68% of patients at day 21 and 72% at surgery; Ki-67 index increased between day 21 and surgery in 54%. AI decreased in 50% of tumours by day 21, increased in 45% and was unchanged in one patient; 56% demonstrated rebound increases in AI by the time of surgery. Neither pre-treatment nor post-chemotherapy median Ki-67 index nor median AI at all three time points or relative changes at day 21 and surgery differed significantly between clinical or pathological responders and non-responders. Clinical responders had lower median Ki-67 indices at day 21 (11.4% versus 27.0%, p = 0.02) and significantly greater percentage reductions in Ki-67 at day 21 than did non-responders (-50.6% versus -5.3%, p = 0.04). The median day-21 Ki-67 was higher in pathological responders (30.3% versus 14.1%, p = 0.046). A trend toward increased AI at day 21 in pathological responders was observed (5.30 versus 1.68, p = 0.12). Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively).

Conclusion

The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive markers is available, clinical decision-making should not be based upon individual biological tumour marker profiles.
Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results
Authors: Hernández M. I. , Martínez A. , Capurro T. , Peña V. , Trejo L. , Avila A. , Salazar T. , Asenjo S. , Iñiguez G. , Mericq V.
Published: June 2006

Context: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA).

Objective: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community.

Patients: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles.

Interventions: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 μg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone.

Results: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 ± 1.03 (7.8–12.5) yr, similar bone age/chronological age (1.02 ± 0.8 in AGA and 1 ± 0.76 in SGA), median height of 1.35 ± 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog.

Conclusions: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.
The Val279Phe Variant of the Lipoprotein-Associated Phospholipase A2 Gene Is Associated with Catalytic Activities and Cardiovascular Disease in Korean Men
Authors: Jang Yangsoo , Kim Oh Yoen , Koh Soo Jeong , Chae Jey Sook , Ko Young Guk , Kim Ji Young , Cho Hongkeun , Jeong Tae-Sook , Lee Woo Song , Ordovas Jose M. , Lee Jong Ho
Published: June 2006

Context and Objective: It is unclear whether lipoprotein-associated phospholipase A2 (Lp-PLA2) exerts a pro- or antiatherogenic effect on cardiovascular disease (CVD). We investigated the association between Lp-PLA2 variant (V279F and A379V) and CVD in Korean men.

Design: CVD patients (n = 532) and healthy controls (n = 670) were genotyped for the Lp-PLA2 polymorphism (V279F and A379V).

Main Outcome Measures: We calculated odds ratio (OR) on CVD risk and measured anthropometries, lipid profiles, low-density lipoprotein (LDL) particle size, oxidized LDL, lipid peroxides, and Lp-PLA2 activity.

Results: The presence of the 279F allele was associated with a lower risk of CVD [OR 0.646 (95% confidence interval 0.490–0.850), P = 0.002], and the association still remained after adjustments for age, body mass index, waist circumference, waist to hip ratio, cigarette smoking, and alcohol consumption [OR 0.683 (95% confidence interval 0.512–0.911), P = 0.009]. Lp-PLA2 activity was lower in CVD patients taking a lipid-lowering drug (31%), those not taking a lipid-lowering drug (26%), and control subjects (23%) with the V/F genotype, compared with those with the V/V genotype. Subjects with the F/F genotype in controls and two CVD patients groups showed no appreciable enzymatic activity. Control subjects with the V/F genotype had larger LDL particle size than those with the V/V genotype. In addition, control subjects carrying the F allele showed lower malondialdehyde concentrations. On the other hand, we found no significant relationship between A379V genotype and CVD risk.

Conclusions: The association of the F279 loss of function variant with the reduced risk of CVD supports the concept that Lp-PLA2 plays a proatherogenic and causative role in CVD.