bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Overuse Headache: Predictors and Rates of Relapse in Migraine Patients With Low Medical Needs. A 1-Year Prospective Study
Authors: Rossi P , Faroni JV , Nappi G
Published: August 2008

The aim of this study was to evaluate the rates and predictors of relapse, after successful drug withdrawal, in migraine patients with medication overuse headache (MOH) and low medical needs. The study population, study design, inclusion criteria and short-term effectiveness of the medication withdrawal strategies have been described elsewhere (Rossi et al., Cephalalgia 2006; 26:1097). Relapsers were defined as those patients fulfilling, at follow-up, the new International Classification of Headache Disorders, 2nd edn, appendix criteria for MOH. Complete datasets were available for 83 patients. At 1 year's follow up, the relapse rate was 20.5±. Univariate analysis showed that patients who relapsed had a longer duration of migraine with more than eight headache days/month, a longer duration of drug overuse, had tried a greater number of preventive treatments in the past, had a lower reduction of headache frequency after withdrawal, and had previously consulted a greater number of specialists. Binary logistic regression analysis was performed, and three variables emerged as significant predictors of relapse: duration of migraine with more than eight headache days/month [odds ratio (OR) 1.57, P = 0.01], a higher frequency of migraine after drug withdrawal (OR 1.48, P = 0.04) and a greater number of previous preventive treatments (OR 1.54, P = 0.01). In patients with migraine plus MOH and low medical needs, relapse seems to depend on a greater severity of baseline migraine.
Symptoms of Migraine in The Paediatric Population by Age Group
Authors: Eidlitz-Markus T , Gorali O , Haimi-Cohen Y , Zeharia A
Published: August 2008

The revised criteria of the International Headache Society (IHS) for paediatric headache do not differentiate among age groups. This study aims to determine if different symptoms of migraine are specific or typical of different age groups of children. The files of 160 children (79 boys, 81 girls, mean age 10.39 ± 3.71 years) with migraine treated at the paediatric headache clinic of a tertiary centre were reviewed. The diagnosis was based on the criteria of the IHS (ICHD-II). The patients were divided by age into three groups according to educational status, ≤6 years (preschool, group 1), >6 to ≤12 years (elementary school, group 2) and >12 to ≤18 years (secondary school, group 3), and compared by symptoms and signs. Symptoms of migraine with and without aura were also compared. There was no significant difference among the groups in rates of unilateral headache, phonophobia, photophobia, awakening pain, nausea or worsening of pain during physical activity. The parameters found to be statistically significant were dizziness and duration of migraine, and aura which increased with time. Frequency of attacks increased with age. The single statistically significant parameter found to be more frequent in younger age was vomiting. The statistically significant parameters of nausea and duration of migraine were more frequent in migraine with aura compared with migraine without aura. In conclusion, most of the migraine symptoms included in the 2004 recommendations of the IHS are not typical for specific paediatric age groups, probably because brain maturity is a continuous process. A familial history of migraine is a frequent finding among all age groups and should be considered in the paediatric criteria, especially in younger children in whom diagnosis is more difficult. Vomiting may help the diagnosis of migraine in young children with a familial history of migraine.
The Blood-Brain Barrier in Migraine Treatment
Authors: Edvinsson L , Tfelt-Hansen P
Published: August 2008

Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access to the central nervous system by diffusion, whereas other substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized arteriography method. The drugs, given both luminally and abluminally, provide important notions regarding antimigraine site of action, probably abluminal to the BBB. The problems with the BBB in animal models designed to study the pathophysiology, acute treatment models and preventive treatments are discussed with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other vascular beds also. We discuss how this can be related to genuine migraine attacks. Our view is that there exists no clear proof of breakdown or leakage of the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB for efficacy.
Lack of Seasonal Variation in Menstrually-Related Migraine
Authors: Bekkelund SI , Alstadhaug KB , Salvesen R
Published: August 2008

The aim of the study was to study seasonal variation in migraine headache in a group of women with menstrually-related migraine (MRM) compared with non-menstrual migraine. Via newspaper advertisement, women with migraine living in North Norway were invited. The patients were included by questionnaire and telephone interview. We prospectively recorded migraine attacks from a 12-month headache diary performed by a group of 62 women with a mean age of 36.0 years (range 16-46 years), who fulfilled the criteria of migraine without aura. Of these, 29 had MRM and 33 non-menstrual migraine. Mean ratio between number of attacks in the light arctic season (May-June-July) divided with total number of migraine attacks during 12 months was 0.24 (9.4/38.4) in the group of MRM compared with 0.25 (5.6/22.1) in others (confidence interval -4.2, 6.3, P = 0.84). Nor were there more migraine attacks in the dark season in an arctic area (November-December-January) in any group. We found a higher migraine attack rate in those with MRM, but no indication of more or less frequency of attacks during the bright arctic season. These findings support the assumption that MRM and seasonal variation of migraine are due to different mechanisms.
The Visual Aura Rating Scale as an Outcome Predictor for Persistent Visual Aura Without Infarction
Authors: Wang Y-F , Fuh J-L , Chen W-T , Wang S-J
Published: August 2008

Persistent visual aura without infarction is rare. Its pathogenic mechanism is unknown, and the response to migraine prophylactic agents varies. A systematic analysis of 29 patients (23 from the literature and six in the present report; 6M/23F, mean age 37.6 years) was carried out in terms of demographics, headache and visual symptom profiles, treatment regimens and outcomes. Patterns of visual disturbances (VDs) were re-assessed with the Visual Aura Rating Scale (VARS, score 0-10). Even though the majority of patients had headache improvement, only eight (27.6±) had complete resolution of persistent VD, without definite relevance to any specific agent. Patients with complete resolution of VD tended to have scotoma (50.0± vs. 0±; P = 0.003), unilateral/homonymous involvement (62.5± vs. 9.5±; P = 0.008), higher VARS scores (1.88 ± 1.73 vs. 0.10 ± 0.30; P< 0.001) and shorter duration of illness (10.0 ± 12.9 vs. 60.2 ± 90.9 months, P = 0.008) compared with those without. These findings remained even when the six current patients were not included for analyses. In conclusion, the prognosis of persistent VD was poor, and higher VARS scores, i.e. more typical of migraine visual aura, predicted a better outcome. For those with a potential for complete resolution, improvement would occur early in the course.
Pleiotrophin receptor RPTP‐ζ/β expression is up‐regulated by l‐DOPA in striatal medium spiny neurons of parkinsonian rats
Authors: Ferrario Juan Esteban , Rojas‐Mayorquín Argelia Esperanza , Saldaña‐Ortega Marisa , Salum Cristiane , Gomes Margarete Zanardo , Hunot Stéphane , Raisman‐Vozari Rita
Published: August 2008

l‐DOPA is still the drug of choice to treat Parkinson’s disease although adverse side effects appear after several years of treatment. These are thought to be the consequence of plastic re‐arrangements of the nigrostriatal connections, such as sprouting of the dopaminergic terminals or post‐synaptic changes. Pleiotrophin, a trophic factor that we have shown to be up‐regulated in the striatum of parkinsonian rats after long‐term l‐DOPA treatment may play a role in these plastic changes. To determine whether one of the three known pleiotrophin receptors [N‐syndecan, receptor protein tyrosine phosphatase type zeta beta (RPTP‐ζ/β) and anaplastic lymphoma kinase] might be implicated in these putative plastic effects, we quantified their expression levels by real‐time RT‐PCR in the striatum and mesencephalon of rats with partial lesions of the nigrostriatal pathway undergoing l‐DOPA treatment. Both pleiotrophin and RPTP‐ζ/β expression was up‐regulated in the striatum but not in the mesencephalon of lesioned rats and RPTP‐ζ/β expression was even further increased by l‐DOPA. The levels of the RPTP‐ζ/β protein were also increased in the striatum of l‐DOPA‐treated lesioned rats. Immunofluorescence labeling showed the protein to be constitutively expressed in striatal medium spiny neurons, which are innervated by both the corticostriatal glutamatergic and nigrostriatal dopaminergic systems. RPTP‐ζ/β might therefore be implicated in the plastic changes triggered by l‐DOPA treatment and might merit further study as a potential candidate for Parkinon’s disease therapy.
Age‐dependent effects of chronic stress on brain plasticity and depressive behavior
Authors: Toth Erika , Gersner Roman , Wilf‐Yarkoni Adi , Raizel Hagit , Dar Dalit E. , Richter‐Levin Gal , Levit Ofir , Zangen Abraham
Published: August 2008

Exposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with induction of depression in humans. However, the behavioral effects of CMS in young animals have not yet been characterized, and little is known about the long‐term neurochemical effects of CMS in either young or adult animals. Here, we found that CMS induces anhedonia in adult but not in young animals, as measured by a set of behavioral paradigms. Furthermore, while CMS decreased neurogenesis and levels of brain‐derived neurotrophic factor (BDNF) in the hippocampus of adult animals, it increased these parameters in young animals. We also found that CMS altered α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor GluR1 subunit levels in the hippocampus and the nucleus accumbens of adult, but not young animals. Finally, no significant differences were observed between the effects of CMS on circadian corticosterone levels in the different age groups. The substantially different neurochemical effects chronic stress exerts in young and adult animals may explain the behavioral resilience to such stress young animals possess.
Variation in mitochondrial genotype has substantial lifespan effects which may be modulated by nuclear background
Authors: Clancy David J.
Published: August 2008

Mitochondria are thought to play a central role in aging. In humans, specific naturally occurring mitochondrial genetic variants are overrepresented among centenarians, but only in certain populations; therefore, we cannot tell whether this effect is due solely to mitochondrial genetics or to nuclear‐mitochondrial gene complexes, nor do we know the magnitude of the effect in terms we can relate to, such as mean lifespan differences. To examine the effects of natural mitochondrial DNA (mtDNA) variation on lifespan, we need to vary the mitochondrial genotype while controlling the nuclear genotype. Here, nuclear genome replacement is achieved using strains ofDrosophila melanogasterbearing multiply inverted ‘balancer’ chromosomes that suppress recombination, and an isogenic donor strain, thus forcing replacement of entire chromosomes in a single cross while suppressing recombination. Lifespans of wild‐type mtDNA variants on the chromosome replacement background vary substantially, and sequencing of the entire protein coding mitochondrial genomes indicates that these lifespan differences are sometimes associated with single amino acid differences. On other nuclear genetic backgrounds, the magnitude and direction of these lifespan effects can change dramatically, and this can be due to changes in baseline mortality risk, rate of aging and/or time of onset of aging. The limited mtDNA variation inD. melanogastermakes it an ideal organism for biochemical studies to link genotype and aging phenotype.
The LoTrach™ system: its role in the prevention of ventilator‐associated pneumonia
Authors: Fletcher Andrew JW , Ruffell Alison J , Young Peter J
Published: August 2008

Objectives:  To discuss the development of the LoTrach™ system in light of current evidence around the prevention of ventilator‐associated pneumonia (VAP) and its practical application in the intensive care setting.

Background:  VAP causes substantial morbidity and mortality in ventilated patients in the Intensive Care Unit (ICU), increases length of stay in ICU and is extremely costly. Strategies are needed to reduce the risk of VAP.

Method:  We examine the need for an endotracheal tube (ETT) specifically designed for the critically‐ill patient, the development of the LoTrach system from conception to production, and the role of the various components of the system in preventing VAP. Early issues in implementing this revolutionary equipment into ICU are explored and three case studies highlight advantages of this system.

Conclusion:  The LoTrach system has been designed to facilitate the provision of a number of evidence‐based interventions that have been shown to reduce VAP. Pulmonary aspiration is ubiquitous with conventional cuffs but prevented by the cuff of the LoTrach system when held at a constant and safe pressure against the tracheal wall with a cuff pressure controller. Other aspects incorporated in the ETT are aimed at clearing the secretions from the subglottic space, preventing tube occlusion and accidental extubation, and avoiding damage to the airway. In this way the LoTrach system employs a multifactorial approach to the prevention of VAP and the cost savings from LoTrach rather than a standard ETT will be considerable because of an average 3 day reduction in ICU length of stay related to this. It thus has the potential to be a very useful tool in the ICU setting in the prevention of VAP.
Ventilator‐associated pneumonia in paediatric intensive care: a literature review
Authors: Turton Patrick
Published: August 2008

Background:  Ventilator‐associated pneumonia (VAP) has been identified as the most common nosocomial infection in intensive care units (ICUs) with associated health and financial costs. To date, more research has been carried out in adult ICUs than in paediatric units, thus prompting a review and investigation of the implications for paediatric practice.

Aims:  To identify relevant paediatric literature surrounding VAP and use this in association with research carried out in the adult environment to establish the implications of VAP and possible management strategies.

Search strategies:  A literature search was undertaken using databases within DialogDatastar to identify the extent to which VAP has been researched in both paediatric and adult centres. This information was used to try and gain a clearer concept of the impact and management of VAP in the paediatric setting. Key words and combinations included VAP, intensive care, paediatric, antibiotics, positioning, suction, economics, management, nosocomial and morbidity and mortality.

Results of analysis:  Despite the documented significance of VAP in terms of its financial and health implications, discrepancies and inconsistencies exist surrounding the identification and treatment of VAP. This is reflected in paediatric centres by a dearth of literature on the subject and the lack of a national standard as to the management and prevention of VAP. Inappropriate management of VAP plays an important role in the development and spread of multiresistant bacteria within hospitals.

Conclusions:  While inadequate paediatric research exists, extrapolating from adult research suggests that the financial and health costs of VAP are substantial and can be reduced by introducing simple low‐cost measures. Such measures include improving education surrounding VAP and its implications and making small changes in practice to improve and maintain oral hygiene standards.

Implications:  With a growing cohort of paediatric patients requiring short‐ and long‐term ventilation, progress must be made in identifying the extent and impact of VAP in paediatric ICUs and among the community ventilated patients. This will require changes in practice and attitudes towards VAP for which an appropriate knowledge base would need to be established using audit and research. These issues are particularly relevant in the current environment given the links with multiresistant strains of bacteria within hospitals and the community.
Mentoring in times of change
Authors: Hurley Ciarán , Snowden Sally
Published: August 2008

Objective:  The aim of this study was to establish the barriers to nurses performing the mentor role in three critical care wards.

Background:  Imminent changes affecting mentors to preregistration students in our wards and our awareness of their ill‐preparedness prompted us to design interventions to prepare colleagues for the changes. Literature shows a range of perceived barriers to mentoring, we wanted to compare these to our colleagues’ perceptions

Design:  Prospective, self‐administered service evaluation questionnaire of a saturation sample of nurses in intensive care and high dependency wards.

Results:  Of the 118 questionnaire proformas issued, 43 were returned (36%). Key results include: lack of time to perform the mentor role because of patient care workload, lack of opportunity to update knowledge and skills of mentoring and lack of familiarity with the programme of study and the documents used to record assessment of a student’s proficiency.

Conclusions:  Mentor update opportunities must be delivered alongside the competing demands of safe and effective patient care and the need to ensure the development of individuals as well as the profession as a whole through fostering its students.

Relevance to practice:  To ensure future generations of patients enjoy quality critical care, we must invest time and resources in mentoring the nurses who will deliver critical care in the future.
The Role of GABRA2 in Alcohol Dependence, Smoking, and Illicit Drug Use in an Australian Population Sample
Authors: Lind Penelope A. , Macgregor Stuart , Agrawal Arpana , Montgomery Grant W. , Heath Andrew C. , Martin Nicholas G. , Whitfield John B.
Published: August 2008

Background:  Multiple studies have shown that genetic variation in the α‐2 subunit of the gamma‐aminobutyric acid type A (GABAA) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol’s intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population.

Methods:  We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co‐twin did not participate. Family‐based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use.

Results:  We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM‐IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use.

Conclusions:  The GABRA2 allelic associations found in clinical case–control studies have detectable but minor effects on DSM‐defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.
Entrepreneurial Policy: The Case of Regional Specialization vs. Spontaneous Industrial Diversity
Authors: Desrochers Pierre , Sautet Frederic
Published: August 2008

Regional economic development policy is recognized as a key tool governments use to foster economic prosperity. Whether specialization (or diversity) of economic activities should be a regional development policy goal is often debated. We address this question in a local–diversity context, by reviewing traditional arguments in its favor, supplemented with evidence for more entrepreneurial concepts like industrial symbiosis and Jacobs externalities. We show that the context of entrepreneurship matters more to policy than the type and form of resulting industries. Policies enabling entrepreneurs to exploit opportunities in a context of spontaneously evolved industrial diversity are better facilitators of regional development.
The Impact of Economic Integration on Cross–Border Venture Capital Investments: Evidence from the European Union
Authors: Alhorr Hadi S. , Moore Curt B. , Payne G. Tyge
Published: August 2008

Despite major policies surrounding economic integration among countries (e.g., the European Union [EU], North Atlantic Free Trade Area, and Mercosur), the theoretical and empirical research addressing the impact of such policies on various countries’ entrepreneurial activities has yet to fully emerge. To address this issue, this paper draws on institutional, economic, and entrepreneurship literatures to examine if two specific economic integration mechanisms, namely market and currency commonality, increase cross–border venture capital flows made by participating nations in the EU. Findings suggest that broad scale economic integration policies do influence the extent of foreign venture capital investments made into other member countries.
Computable Entrepreneurship
Authors: Koppl Roger
Published: August 2008

The mathematics of “computable economics” proves that entrepreneurship policy is unlikely to succeed if it presumes policy makers can replace the unplanned results of the entrepreneurial market process with ex ante judgments about which enterprises are best. It is mathematically impossible for policy makers or their assignees to make the required computations of opportunity costs. Some business professors dream of finding a grand algorithm that will allow them to guide entrepreneurial decisions and to judge in advance which decisions are good and which bad. The logic of computable economics, however, reveals this dream to be a form of magical thinking.
Non‐canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development
Authors: Liu Katherine , Wong Elaine W. , Schutzer Steven E. , Connell Nancy D. , Upadhyay Alok , Bryan Margarette , Rameshwar Pranela
Published: August 2008

Anthrax receptor (ATR) shares similarities with molecules relevant to haematopoiesis. This suggests that anthrax proteins might bind to these mimicking molecules and exert non‐specific haematopoietic effects. The haematopoietic system is the site of immune cell development in the adult. As such, ATR ligand, protective antigen (PA) and the other anthrax proteins, lethal factor, edema factor, could be significant to haematopoietic responses against Bacillus anthracis infection. Because haematopoiesis is the process of immune cell development, effects by anthrax proteins could be relevant to vaccine development. Here, we report on effects of anthrax proteins and toxins on early and late haematopoiesis. Flow cytometry shows binding of PA to haematopoietic cells. This binding might be partly specific because flow cytometry and Western blots demonstrate the presence of ATR1 on haematopoietic cell subsets and the supporting stromal cells. Functional studies with long‐term initiating cell and clonogenic assays determined haematopoietic suppression by anthrax toxins and stimulation by monomeric proteins. The suppressive effects were not attributed to cell death, but partly through the induction of haematopoietic suppressors, interleukin (IL)‐10 and CCL3 (MIP‐1α). In summary, anthrax proteins affect immune cell development by effects on haematopoiesis. The type of effect, stimulation or suppression, depend on whether the stimulator is a toxin or monomeric protein. The studies show effects of anthrax proteins beginning at the early stage of haematopoiesis, and also show secondary mediators such as IL‐10 and CCL3. The roles of other cytokines and additional ATR are yet to be investigated.
Functional linkage of Na+‐Ca2+‐exchanger to sarco/endoplasmic reticulum Ca2+ pump in coronary artery: comparison of smooth muscle and endothelial cells
Authors: Davis Kim A. , Samson Sue E. , Hammel Kaitlin E. , Kiss Lorand , Fulop Ferenc , Grover Ashok K.
Published: August 2008

An increase in cytosolic Ca2+ concentration in coronary artery smooth muscle causes a contraction but in endothelium it causes relaxation. Na+‐Ca2+‐exchanger (NCX) may play a role in Ca2+ dynamics in both the cell types. Here, the NCX‐mediated 45Ca2+ uptake was compared in Na+‐loaded pig coronary artery smooth muscle and endothelial cells. In both the cell types, this uptake was inhibited by KB‐R7943, SEA 0400 and by monensin, but not by cariporide. Prior loading of the cells with the Ca2+ chelator BAPTA increased the NCX‐mediated 45Ca2+ uptake in smooth muscle but not in endothelial cells. In the presence or absence of BAPTA loading, the Na+‐mediated 45Ca2+ uptake was greater in endothelial than in smooth muscle cells. In smooth muscle cells without BAPTA loading, thapsigargin diminished the NCX‐mediated 45Ca2+ entry. This effect was not observed in endothelial cells or in either cell type after BAPTA loading. The results in the smooth muscle cells are consistent with a limited diffusional space model in which the NCX‐mediated 45Ca2+ uptake was enhanced by chelation of cytosolic Ca2+ or by its sequestration by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). They suggest a functional linkage between NCX and SERCA in the smooth muscle but not in the endothelial cells. The concept of a linkage between NCX and SERCA in smooth muscle was also confirmed by similar distribution of NCX and SERCA2 proteins when detergent‐treated microsomes were fractionated by flotation on sucrose density gradients. Thus, the coronary artery smooth muscle and endothelial cells differ not only in the relative activities of NCX but also in its functional linkage to SERCA.
Raman tweezers provide the fingerprint of cells supporting the late stages of KSHV reactivation
Authors: Dyson Ossie F. , Ford Patrick W. , Chen De , Li Yong‐Qing , Akula Shaw M.
Published: August 2008

Kaposi’s sarcoma‐associated herpesvirus (KSHV) has both latent and lytic phases of replication. The molecular switch that triggers a reactivation is still unclear. Cells from the S phase of the cell cycle provide apt conditions for an active reactivation. In order to specifically delineate the Raman spectra of cells supporting KSHV reactivation, we followed a novel approach where cells were sorted based on the state of infection (latent versus lytic) by a flow cytometer and then analysed by the Raman tweezers. The Raman bands at 785, 813, 830, 1095 and 1128 cm−1 are specifically altered in cells supporting KSHV reactivation. These five peaks make up the Raman fingerprint of cells supporting KSHV reactivation. The physiological relevance of the changes in these peaks with respect to KSHV reactivation is discussed in the following report.
Prognostic role of global DNA‐methylation and histone acetylation in pT1a clear cell renal carcinoma in partial nephrectomy specimens
Authors: Minardi D. , Lucarini G. , Filosa A. , Milanese G. , Zizzi A. , Primio R. Di , Montironi R. , Muzzonigro G.
Published: August 2008

Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin‐embedded sections, using anti‐5‐methylcytosine (5mc) and anti‐Acetyl‐Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P= 0.033), whereas the percentage of histone acetylation was significantly lower (P= 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.
Gyrating Clathrin: Highly Dynamic Clathrin Structures Involved in Rapid Receptor Recycling
Authors: Zhao Yanqiu , Keen James H.
Published: August 2008

We report here detection of novel intracellular clathrin‐coated structures revealed by continuous high‐speed imaging of cells expressing green fluorescent protein fusion proteins. These structures, which we operationally term ‘gyrating clathrin’ (G‐clathrin), are characterized by localized but extremely rapid movement, leading to the hypothesis that they are coated buds on waving membrane tubules. G‐clathrin structures have structurally and functionally distinct features. They lack detectable adaptor proteins AP‐1 and AP‐2 but contain GGA1 [Golgi‐localized, γ‐ear‐containing, Arf (ADP‐ribosylation factor)‐binding protein] as well as the cation‐dependent mannose‐6‐phosphate receptor. While they accumulate internalized transferrin (Tf), they do not contain detectable levels of cargos targeted for the late endosome/lysosome pathway such as EGF and dextran. Pulse‐chase studies indicate that Tf appears in G‐clathrin structures in the cell periphery after sorting endosomes (SEs), but before filling of the perinuclear endocytic recycling compartment. Furthermore, the inhibitors LY294002 and wortmannin, which inhibit direct recycling of Tf from SEs to the plasma membrane, also block its appearance in G‐clathrin. These observations suggest that peripheral G‐clathrin contributes to rapid recycling, a kinetically defined compartment that has largely eluded structural identification. More generally, the rapid continuous live cell imaging reported here reveals new aspects of membrane trafficking.
The ESCRT‐I Subunit TSG101 Controls Endosome‐to‐Cytosol Release of Viral RNA
Authors: Luyet Pierre‐Philippe , Falguières Thomas , Pons Véronique , Pattnaik Asit K. , Gruenberg Jean
Published: August 2008

Like other enveloped viruses, vesicular stomatitis virus infects cells through endosomes. There, the viral envelope undergoes fusion with endosomal membranes, thereby releasing the nucleocapsid into the cytoplasm and allowing infection to proceed. Previously, we reported that the viral envelope fuses preferentially with the membrane of vesicles present within multivesicular endosomes. Then, these intra‐endosomal vesicles (containing nucleocapsids) are transported to late endosomes, where back‐fusion with the endosome limiting membrane delivers the nucleocapsid into the cytoplasm. In this study, we show that the tumor susceptibility gene 101 (Tsg101) subunit of the endosomal sorting complexes required for transport (ESCRT)‐I complex, which mediates receptor sorting into multivesicular endosomes, is dispensable for viral envelope fusion with endosomal membranes and viral RNA transport to late endosomes but is necessary for infection. Our data indicate that Tsg101, in contrast to the ESCRT‐0 component Hrs, plays a direct role in nucleocapsid release from within multivesicular endosomes to the cytoplasm, presumably by controlling the back‐fusion process. We conclude that Tsg101, through selective interactions with its partners including Hrs and Alix, may link receptor sorting and lysosome targeting to the back‐fusion process involved in viral capsid release.
ORIGINAL ARTICLE: A Role for Mannose‐Binding Lectin, a Component of the Innate Immune System in Pre‐Eclampsia
Authors: Than Nandor Gabor , Romero Roberto , Erez Offer , Kusanovic Juan Pedro , Tarca Adi L. , Edwin Samuel S. , Kim Jung‐Sun , Hassan Sonia S. , Espinoza Jimmy , Mittal Pooja , Mazaki‐Tovi Shali , Friel Lara , Gotsch Francesca , Vaisbuch Edi , Camacho Natalia , Papp Zoltan
Published: August 2008

Problem Mannose‐binding lectin (MBL) is a pattern‐recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre‐eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre‐eclampsia.

Method of study This cross‐sectional study included normal pregnant women (n = 187) and patients with pre‐eclampsia (n = 99). Maternal plasma MBL concentrations were determined by ELISA.

Results Women with pre‐eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three‐modal, the subintervals in normal pregnancy were low (<143.7), intermediate (143.7–1898.9) and high (>1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with pre‐eclampsia was larger in the high subinterval (P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals (P = 0.02).

Conclusions The median maternal plasma MBL concentration is elevated in patients with pre‐eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre‐eclampsia.
Effects of long‐term exogenous bovine somatotropin on glucose metabolism and the utilization of glucose by the mammary gland in different stages of lactation of crossbred Holstein cattle
Authors: CHAIYABUTR Narongsak , KOMOLVANICH Siripen , THAMMACHAROEN Sumpun , CHANPONGSANG Somchai
Published: August 2008

The effects of long‐term administration of recombinant bovine somatotropin (rbST) on glucose turnover and the utilization of glucose in the mammary gland using a continuous infusion of [3‐3H]glucose and [U‐14C]glucose in lactating crossbred Holstein Friesian(HF) cattle were investigated. Glucose turnover of rbST‐treated animals was significantly higher than those of control animals (P < 0.05) in mid lactation, while plasma glucose concentrations were not affected. The utilization of glucose of non‐mammary tissues of rbST‐treated animals significantly increased (P < 0.05) as lactation advanced. The glucose taken up by the mammary gland in early lactation increased flux through the lactose synthesis and the pentose cycle pathway with significant increases in NADPH formation for fatty acid synthesis during rbST administration. The utilization of glucose carbon incorporation into milk appeared to increase in milk citrate and milk triacylglycerol but not for milk lactose as lactation advances in rbST‐treated animals. The stimulant effect for milk yield by rbST treatment was transiently and significantly increased in early lactation and was decreased in late lactation even though there was a high level of udder blood flow. These findings demonstrate that the regulation of biosynthetic capacity within the mammary gland would be influenced more by local than by systemic factors. The proportion of glucose would be metabolized less for lactose synthesis, but metabolized more via the Embden‐Meyerhof pathway and the tricarboxylic acid cycle as lactation advances.
The effect of replacing brewers' grains with barley tea grounds in total mixed ration silage on feed intake, digestibility and ruminal fermentation in wethers
Authors: XU Chuncheng , CAI Yimin , FUKASAWA Michiru , MATSUYAMA Hiroki , MORIYA Naoko
Published: August 2008

Four wethers were used in a 4 × 4 Latin square to study the feed intake, apparent digestibility, nitrogen balance and ruminal fermentation characteristics when fed total mixed ration (TMR) silages which included wet barley tea grounds (WBTG). The TMR silages were prepared using compound feed including wet brewers' grains (WBG), corn, oat hay, alfalfa hay, dried beet pulp, salt and vitamin‐mineral supplement in a ratio of 30.7:15:8:24:10:12:0.15:0.15, respectively, on a dry matter (DM) basis. The WBTG and soybean meal mixture (7:3 on DM basis) were substituted for WBG at ratio of 0% (Control), 5% (LTG), 10% (MTG), and 15% (HTG) on DM of TMR. WBTG addition to the TMR silages increased lactic acid concentration, decreased pH, acetic acid and ammonia‐N (P < 0.001). Feed intakes and digestibilities for LTG and MTG (except ether extract (EE) digestibility) treatments were not different from the control (P > 0.05). However, EE and neutral detergent fiber (NDF) intake, crude protein, EE and NDF digestibility was lower, but the DM and gross energy digestibility was higher for the HTG treatment compared to control (P < 0.01). With progressive increases in WBTG concentrations, nitrogen intake, fecal nitrogen and retention nitrogen did not differ, but the urinary nitrogen for MTG and HTG treatments were lower than that of the control (P = 0.001). The ruminal total volatile fatty acid concentration and the molar ratios of propionate and butyrate were higher, but the acetate, ratio of acetate to propionate and ammonia‐N content were lower for the HTG treatment compared with the control (P < 0.05). Therefore, the possible proportion of replacing WBG with WBTG for TMR silage can be 10% or less of the diet DM.
Differential cytokine expression in T cell subsets from bovine peripheral blood
Authors: TANAKA Sachi , NAGAI Yasuhiro , NOGUCHI Yoko , MIYAKE Masato , WATANABE Kouichi , OHWADA Shyuichi , ASO Hisashi , YAMAGUCHI Takahiro
Published: August 2008

Although distinct cytokine expression in T cell subsets is well understood in mice and humans, limited information is available on bovine T cell subsets. In the present study, we analyzed the mRNA expression of 10 kinds of cytokines and CD25 expression in CD4+, CD8+, WC1+ and WC1‐γδ T cell subsets in bovine peripheral blood by Concanavalin A (Con A) stimulation. CD25 expression was significantly increased in CD4+, CD8+ and WC1+γδ T cells, but not in WC1‐γδ T cells by Con A stimulation. In CD4+ T cells, the mRNAs of Interleukin (IL)‐2, IL‐6, IL‐10, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, TNF‐β and transforming growth factor (TGF)‐β were expressed in control cultures, and IL‐3, IL‐4 and granulocyte‐macrophage colony stimulating factor (GM‐CSF) were newly expressed when the cells were stimulated with Con A. CD8+ T cells expressed the mRNAs of IL‐6, TNF‐α, TNF‐β and TGF‐β in control cultures, and newly expressed those of IL‐2, IFN‐γ and GM‐CSF, but did not express those of IL‐3, IL‐4 or IL‐10 after Con A stimulation. The cytokine expression profile of WC1+γδ T cells was similar to that of CD8+ T cells. However, WC1‐γδ T cells did not express any cytokine mRNA except TGF‐â mRNA. These results will contribute to elucidate the participation of T cell subsets in immune responses against infectious disease in cattle.
Bacteriocin production of probiotic Lactobacillus gasseri LA39 isolated from human feces in milk‐based media
Authors: ARAKAWA Kensuke , KAWAI Yasushi , FUJITANI Kenji , NISHIMURA Junko , KITAZAWA Haruki , KOMINE Ken‐ichi , KAI Kenzo , SAITO Tadao
Published: August 2008

The use of bacteriocins from Lactobacillus gasseri, a probiotic lactic acid bacterium, as bio‐preservatives in the food industry and animal formulations has been limited because few strains of Lb. gasseri are cultivated and produce a bacteriocin in natural media such as milk and milk‐based media. By the determination of the growth‐supplements to milk among the 47 nutrients, Lb. gasseri JCM1131T, LA39 and LA158 isolated from human feces were successfully cultured in reconstituted skim milk and cheese whey using proteose peptone as a nutrient supplement, where Lb. gasseri LA39 produced a useful bacteriocin, gassericin A, with effective growth‐inhibiting activity against Gram‐positive food‐borne pathogens. The data suggest these developed low‐cost safe media supporting enough production of bacteriocins by the probiotic Lb. gasseri LA39 could be used to improve the safe bio‐preservation of foods and therapy of bovine mastitis, and extra cheese whey produced by cheese making industry is reused in the cultivation for probiotics effectively.
Scaling of Frond Form in Hawaiian Tree Fern Cibotium glaucum: Compliance with Global Trends and Application for Field Estimation
Authors: Arcand Naomi , Kagawa Aurora K. , Sack Lawren , Giambelluca Thomas W.
Published: August 2008

Large‐fronded tree ferns are critical components of many tropical forests. We investigated frond and whole‐plant allometries for Hawaiian keystone species Cibotium glaucum, for prediction and to compare with global scaling relationships. We found that C. glaucum fronds maintain geometric proportionality across a wide range of plant and frond sizes. These relationships result in strong allometries that permit rapid field estimation of frond size from simple linear dimensions. C. glaucum frond allometries complied with intra‐ and interspecific global trends for leaf area versus mass established for much smaller‐leafed species, indicating ‘diminishing returns’ in photosynthetic area per investment in mass for larger fronds. The intraspecific trend was related to declining water content in larger fronds, but not to a significantly larger investment in stipe or rachis relative to lamina. However, C. glaucum complied with the global interspecific trends for greater allocation to support structures in larger leaves. Allometries for frond number and size versus plant height showed that as plants increase in height, frond production and/or retention progressively declines, and the increases of leaf size tend to level off. These frond and whole plant‐level relationships indicate the potential for estimating frond area and mass at landscape scale to enrich studies of forest dynamics.
Combined Effects of Host Plant Quality and Predation on a Tropical Lepidopteran: A Comparison between Treefall Gaps and the Understory in Panama
Authors: Richards Lora A. , Coley Phyllis D.
Published: August 2008

In tropical forests, light‐gaps created from treefalls are a frequent source of habitat heterogeneity. The increase in productivity, through gap formation, can alter food quality, predation and their impact on insect herbivores. We hypothesized that in gaps, herbivores would be less resource‐limited and more predator limited, whereas in the understory, we predicted the reverse. In this study, we investigate the combined effects of food quality and predation on the lepidopteran larva Zunacetha annulata feeding on its host plant Hybanthus prunifolius in two habitats; sunny treefall gaps and the shaded understory in Panama. In bioassays, Z. annulata feeding on sun leaves ate 22 percent less leaf area, grew 25 percent faster, and had higher pupal weights than larvae feeding on shade leaves. However, shade leaves had higher nitrogen content and specific leaf area. In gaps, predation was 26.4 percent compared to 13.8 percent in the understory. Larvae on understory plants traveled greater distances and spent more time searching and traveling than larvae on gap plants. These differences in behavior are consistent with lower predation risk and lower quality food in the understory. Using data from bioassays and field experiments we calculated 0.22 percent and 1.02 percent survival to adulthood for larvae in gaps and the understory, respectively. In conclusion, although these habitats were in close proximity, we found that larvae in the understory are more resource‐limited and larvae in gaps are more predator limited.
Secondary Rain Forests are not Havens for Reptile Species in Tropical Mexico
Authors: Luja Víctor H. , Herrando‐Pérez Salvador , González‐Solís David , Luiselli Luca
Published: August 2008

A widely accepted biodiversity crisis in the tropics has been recently challenged by claims that secondary forests will gradually restore biodiversity losses. This prediction was examined for the herpetofauna in Quintana Roo, Mexico. Quantitative sampling (108 transects) of reptiles was undertaken monthly (January–September 2004) along a vegetation gradient covering induced grasslands, and regrowth and primary rain forests. A total of 35 species was found, 14 being present in and five showing dependence on mature forests. Lizards contributed > 90 per cent of the individuals observed. Reptile abundance and snake species richness was highest in primary forests, even though the lower abundance and richness did not differ between regrowth forest and induced grasslands. Multivariate ordinations and ANOSIM tests displayed clear differences in assemblage structure among vegetation types, mainly caused by contrasting abundances of lizard species having distinctive arboreal or terrestrial habits. There was no evidence that snake assemblages differed between secondary forests and induced grasslands. Microhabitat availability had a key role in shaping species composition through the vegetation gradient. Our results dismiss the hypothesis that secondary forests can act as reservoirs of primary forest reptile diversity on the basis that many taxa depend largely on habitat quality and have specialized life‐history traits, and that biological succession does not guarantee the recovery of assemblage complexity.