bluuebunny/crossref_metadata_2025 huggingface dataset:
Prostacyclin stimulates embryonic development via regulation of the cAMP response element-binding protein - cyclo-oxygenase-2 signalling pathway in cattle
Authors: Song Bong-Seok , Kim Ji-Su , Kim Cheol-Hee , Han Yong-Mahn , Lee Dong-Seok , Lee Kyung-Kwang , Koo Deog-Bon
Published: March 2009

Prostacyclin (PGI2) in oviducal fluid is synthesised from arachidonic acid by cyclo-oxygenase (COX) and prostacyclin synthetase and enhances the implantation and live birth potential of mouse embryos. In the present study, we investigated the developmental competence of bovine embryos by examining the effects of the PGI2 analogue iloprost on blastocyst development, quality and COX-2 expression during IVF and somatic cell nuclear transfer (SCNT). Bovine IVF and SCNT embryos were cultured in CR1-aa medium supplemented with 0.3% bovine serum albumin in either the presence or absence of 1 μm iloprost at 38.5°C and 5% CO2. After 3 days of culture, cleaved embryos were cultured for 4 days in the same medium supplemented with 10% fetal bovine serum. For both IVF and SCNT embryos, iloprost improved the blastocyst developmental rate and cell numbers. In the presence of iloprost, the proportion of expanded blastocysts was significantly higher among the IVF embryos and fewer apoptotic cell nuclei were observed. Expression of COX-2 mRNA and protein, evaluated using real-time polymerase chain reaction and immunoblotting, respectively, was increased in the presence of iloprost. These results suggest that PGI2 improves the developmental competence of embryos via regulation of the cAMP response element-binding protein–COX-2 signalling pathway in cattle.
Fibronectin type II-module proteins in the bovine genital tract and their putative role in cell volume control during sperm maturation
Authors: Sahin Evrim , Petrunkina Anna M. , Ekhlasi-Hundrieser Mahnaz , Hettel Christiane , Waberski Dagmar , Harrison Robin A. P. , Töpfer-Petersen Edda
Published: March 2009

The male reproductive tract of ungulates contains two protein families bearing tandemly arranged fibronectin II (Fn2) modules; one (small Fn2 proteins) bears two modules (e.g. BSP–A1/2), the other (long Fn2 proteins) bears four (e.g. epididymal sperm-binding protein 1 (ELSPBP1)). While it is well known that small Fn2 proteins are present in bull semen, nothing is known about long Fn2 proteins. In the present study, the presence of ELSPBP1 proteins in the bull epididymis and their association with maturing spermatozoa were investigated using a specific antibody against canine ELSPBP1. Analysis of western blots showed ELSPBP1 to be present in the caput, corpus and cauda regions of the epididymis. The protein, which bound phosphorylcholine (PC) strongly, appeared to associate with the spermatozoa during maturation because it was absent from caput spermatozoa but present on cauda spermatozoa. Immunocytochemistry of cauda spermatozoa showed the protein to be bound to the post-acrosomal and midpiece regions. ELSPBP1 could not be detected on freshly ejaculated spermatozoa but was revealed after a capacitating treatment. Our previous studies have shown differences between bovine caput and cauda spermatozoa in terms of their ability to control cell volume. Because of the close homology of BSP–A1/2 PC binding regions with Fn2 regions in ELSPBP1, BSP–A1/2 was used as a model to investigate the effect of a PC-binding Fn2 protein on cell volume control. While the protein had no effect on cauda spermatozoa, it caused caput spermatozoa to swell more in response to hypotonic stress, similarly to untreated cauda spermatozoa.
Diel echolocation activity of harbour porpoises (Phocoena phocoena) around North Sea offshore gas installations
Authors: Todd Victoria L. G. , Pearse William D. , Tregenza Nick C. , Lepper Paul A. , Todd Ian B.
Published: March 2009

Todd, V. L. G., Pearse, W. D., Tregenza, N. C., Lepper, P. A., and Todd, I. B. 2009. Diel echolocation activity of harbour porpoises (Phocoena phocoena) around North Sea offshore gas installations. – ICES Journal of Marine Science, 66: 734–745. Echolocation clicks of harbour porpoises (Phocoena phocoena) were detected with T-PODs, autonomous, passive, acoustic-monitoring devices, deployed from an offshore-exploration-drilling-rig and gas-production-platform complex in the Dogger Bank region of the North Sea from 2005 to 2006. Echolocation-click trains were categorized into four phases of the diel cycle: morning, day, evening, and night. Porpoises were present near (<200 m) the platform, and there was a pronounced diel pattern in echolocation activity; the number of porpoise encounters (visits) was greater by night than by day. The number of click trains with a minimum inter-click interval of <10 ms also increased at night. This was confirmed by a comparison of the ratios of feeding buzzes to search-phase clicks (feeding buzz ratios) and an analysis of the changes in pulse-repetition frequencies within each train. A reasonable interpretation of this pattern was that porpoises were feeding below or around the platform at night. The evidence for changes in activity during the morning and evening was less clear, so these may be transitional phases. The pattern of porpoise-echolocation behaviour around this platform is related most probably to the diel activity of their prey. If porpoises cluster regularly around such installations within 500-m shipping exclusion zones, they may be omitted from population surveys. We conclude that offshore installations may play an important role as nocturnal porpoise-feeding stations in an overfished environment, but that further replicated and controlled studies are required. These findings should be taken into consideration during offshore-installation-decommissioning decisions in the North Sea.
CFC1 Gene Involvement in Biliary Atresia With Polysplenia Syndrome
Authors: Davit‐Spraul Anne , Baussan Christiane , Hermeziu Bogdan , Bernard Olivier , Jacquemin Emmanuel
Published: March 2009

The present report describes CFC1 gene analysis in 10 patients with polysplenia syndrome. The heterozygous transition c.433G>A (Ala145Thr) located in exon 5 was identified in 5 patients, with a twice‐higher frequency than in control patients. These results suggest that heterozygous CFC1 mutation may represent a genetic predisposition to biliary atresia splenic malformation syndrome.
Approach to Vasculitic Neuropathies
Authors: Lacomis David , Živković Saša A
Published: March 2009

Since vasculitic neuropathy is treatable and potentially debilitating, clinicians should develop an approach to neuropathy that increases the likelihood of uncovering existing systemic or nonsystemic vasculitis. The presence of a connective tissue disease, systemic vasculitis, asymmetric or non-length-dependent axonal polyneuropathy, or multiple axonal mononeuropathies should heighten suspicion, but vasculitic neuropathy can also present as a distal symmetric polyneuropathy with or without other organ involvement. Electrodiagnostic testing utilizing extensive nerve conductions may be helpful in identifying features suggestive of vasculitic neuropathy and in selecting an abnormal nerve and muscle for biopsy confirmation. An array of laboratory tests may lead to identification of a systemic disorder that is either characterized by or predisposes to vasculitic neuropathy. The mainstays of treatment are corticosteroids and cyclophosphamide, but other drugs are used in specific conditions. With early diagnosis and careful monitoring of treatment regimens, the prognosis is usually good.
Recurrence of Childhood Guillain-Barré Syndrome After a Long Asymptomatic Interval: A Case Report
Authors: Martic Vesna , Lepic Toplica
Published: March 2009

We present a patient who rapidly developed flaccid paralysis in all 4 limbs on 2 separate occasions 19 years apart. Each episode was accompanied by a respiratory failure that required intubation. Both times, clinical response to immunotherapy was favorable with a near complete recovery. Clinical course, laboratory and electrodiagnostic findings, and favorable response to therapy suggest 2 separate attacks of Guillain-Barré syndrome. The reported case adds to a small series of cases of recurrent Guillain-Barré syndrome after a long asymptomatic period. In such cases, the distinction from chronic inflammatory demyelinating polyradiculoneuropathy should be made.
Vocal Fold Immobility: A Longitudinal Analysis of Etiology Over 20 Years
Authors: Rosenthal Laura H. Swibel , Benninger Michael S. , Deeb Robert H.
Published: March 2009

Objectives: To determine the current etiology of vocal fold immobility, identify changing trends over the last 20 years, and compare results to historical reports.

Study Design: The present study is a retrospective analysis of all patients seen within a tertiary care institution between 1996 and 2005 with vocal fold immobility. The results were combined with a previous study of patients within the same institution from 1985 through 1995. Results were compared to the literature.

Methods: The medical records of all patients assigned a primary or additional diagnostic code for vocal cord paralysis were obtained from the electronic database.

Results: Eight hundred twenty‐seven patients were available for analysis (435 from the most recent cohort), which is substantially larger than any reported series to date. Vocal fold immobility was most commonly associated with a surgical procedure (37%). Nonthyroid surgeries (66%), such as anterior cervical approaches to the spine and carotid endarterectomies, have surpassed thyroid surgery (33%) as the most common iatrogenic causes. These data represent a change from historical figures in which extralaryngeal malignancies were considered the major cause of unilateral immobility. Thyroidectomy continues to cause the majority (80%) of iatrogenic bilateral vocal fold immobility and 30% of all bilateral immobility.

Conclusions: This 20‐year longitudinal assessment revealed that the etiology of unilateral vocal fold immobility has changed such that there has been a shift from extralaryngeal malignancies to nonthyroid surgical procedures as the major cause. Thyroid surgery remains the most common cause of bilateral vocal fold immobility.
Vitamins A and E and Pulmonary Exacerbations in Patients With Cystic Fibrosis
Authors: Hakim Fahed , Kerem Eitan , Rivlin Joseph , Bentur Lea , Stankiewicz Halina , Bdolach‐Abram Tali , Wilschanski Michael
Published: March 2009

Background:

Increased levels of oxidative stress result in pulmonary damage contributing to the development of chronic lung disease in cystic fibrosis (CF). The aim of this study was to investigate the longitudinal effect of serum vitamin A and E levels on the incidence of pulmonary exacerbations in pancreatic insufficient (PI) and pancreatic sufficient (PS) patients with CF.

Materials and Methods:

Patient records were retrospectively examined over a 3‐year period and serum vitamin A and E levels were retrieved. Subsequently, levels of vitamin A and E were prospectively measured over a 2‐year period at the onset of intravenous antibiotic therapy for acute exacerbation and at the first recovery visit.

Results:

Retrospectively, 597 pulmonary exacerbations were identified in 102 patients, 74 PI and 28 PS, with a mean age of 11.1 ± 6.4 years (range, 1.5–27 y). An increased number of exacerbations was directly correlated with lower vitamin A and E levels, even within the normal range. Prospectively, 62 exacerbations were analyzed (43 PI patients and 19 PS patients). At onset of exacerbation, vitamin A and E levels were reduced in the PI patients (P < 0.001; P < 0.001) and the PS patients (P < 0.005; P < 0.07).

Conclusions:

Reduced serum levels of vitamin A and E even in the normal range are associated with an increased rate of pulmonary exacerbations in CF. Further studies are required to confirm the necessity of supplementation of vitamins A and E to PS patients.
Effect of Long‐term Low‐dose Prednisone on Height Velocity and Disease Activity in Pediatric and Adolescent Patients with Crohn Disease
Authors: Navarro Fernando A , Hanauer Stephen B , Kirschner Barbara S
Published: March 2009

Objectives:

To determine whether long‐term low‐dose prednisone (LTLDP) therapy has a decelerating effect on growth velocity and whether this therapy is effective in the maintenance of remission in the subgroup of pediatric patients with Crohn disease (CD) who had previously experienced flares on more than 1 occasion when prednisone was discontinued.

Patients and Methods:

A retrospective chart review of patients was done. Our sample consisted of patients 6 to 17 years of age with CD who had received uninterrupted prednisone at an average daily dose of 0.1 to 0.4 mg · kg−1 · day−1 for at least 8 weeks. Their heights were plotted on sex‐appropriate growth charts at 4 time points: 1 year before LTLDP, at therapy onset, at therapy discontinuation, and 1 year after therapy was discontinued. The height velocities (HVs) were compared with the normal HV established by Tanner. The disease activities of 2 groups were compared: LTLDP plus azathioprine/6‐mercaptopurine (AZA/6‐MP) and LTLDP alone.

Results:

One hundred two patients were included. The mean age of our sample was 13.7 ± 2.7 years (standard deviation). The mean dose of prednisone dose was 0.18 ± 0.07 mg · kg−1 · day−1), for a mean duration of therapy of 14.4 ± 7.2 months. Throughout the study, 78% of patients had normal HV. Growth deceleration was seen in 19% of patients with prior normal growth. Of this group, 31% had “catch‐up” growth 1 year after prednisone was discontinued; the remaining 69% did not. Catch‐up growth was more likely in patients who had reached the expected age peak HV, which is defined as 12.5 years for girls and 13.5 years for boys (P = 0.04). In addition, 6 patients reached the peak HV after LTLDP discontinuation; 13 did not. We found no difference in the maintenance of remission rate between the compared groups.

Conclusions:

A minority of our study population had growth deceleration. Age was an important factor for subsequent catch‐up growth. LTLDP efficacy to maintain remission was not different from that of LTLDP plus AZA/6‐MP; differences in concomitant therapies (eg, antibiotics, infliximab) between the 2 groups were not statistically significant.
Oral Tacrolimus for Steroid‐dependent and Steroid‐resistant Ulcerative Colitis in Children
Authors: Ziring David A , Wu Steven S , Mow William S , Martín Martín G , Mehra Mini , Ament Marvin E
Published: March 2009

Purpose:

To evaluate tacrolimus in 3 situations: for the induction of remission in children with severe steroid‐resistant ulcerative colitis (UC); for steroid sparing in children with steroid‐dependent UC in whom treatment with other immunosuppressants fails; and for the maintenance of remission in children with steroid‐dependent and steroid‐resistant UC.

Patients and Methods:

We retrospectively evaluated 18 consecutive patients (13 with pancolitis) who were treated with oral tacrolimus at our institution from May 1999 to October 2005. Nine patients had steroid‐resistant UC and 9 patients were steroid‐dependent. We started patients initially on tacrolimus 0.2 mg/kg divided twice daily, with a goal plasma trough level of 10 to 15 ng/mL for the first 2 weeks, and then titrated doses to achieve plasma levels between 7 and 12 ng/mL after induction.

Results:

Of the 18 patients in this study, 17 showed a positive response to tacrolimus therapy (ie, cessation of diarrhea and other symptoms) and 5 showed a prolonged response to tacrolimus. The mean time from initiation of tacrolimus therapy until response was 8.5 days. The mean duration of response was 260 days. Eleven of 18 patients required colectomy, including all of the patients with steroid‐resistant UC, but only 2 of 9 who were steroid‐dependent. The mean time from initiation of tacrolimus until colectomy was 392 days.

Conclusions:

It is possible that tacrolimus may benefit selected patients with steroid‐dependent UC, including those who are intolerant of 6‐mercaptopurine or azathioprine. Conversely, patients with steroid‐resistant UC are unlikely to sustain a prolonged clinical response to tacrolimus and seem to require colectomy eventually. Careful considerations of risk versus benefit, as well as close monitoring for adverse effects, are essential in all patients.
Increased Interleukin‐10 in Helicobacter pylori Infection Could Be Involved in the Mechanism Protecting From Allergy
Authors: Oderda Giuseppina , Vivenza Daniela , Rapa Anna , Boldorini Renzo , Bonsignori Ilaria , Bona Gianni
Published: March 2009

Background:

A protective effect of Helicobacter pylori infection against allergic diseases has been reported. The increasing incidence of childhood allergy in developed countries may be a result of reduced stimulation of the immune system by early chronic infections, with the protective effect of gastrointestinal microbes being mediated by regulatory T lymphocytes and production of interleukin (IL)‐10. To elucidate a possible mechanism involved in protecting against the development of atopy, we measured expression of IL‐10 in gastric mucosa of children with H pylori gastritis.

Patients and Methods:

Gastric biopsies were performed during endoscopy in 48 children (median age, 9 years), 32 of whom had H pylori gastritis and 16 of whom served as controls. Interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β), and IL‐10 were measured in tissue homogenate by quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR). The amounts of IFN‐γ, IL‐1β, and IL‐10 transcripts were quantified via competitive RT‐PCR with use of dilution series of specific competitors.

Results:

Expression of IFN‐γ and IL‐10 were significantly higher in H pylori–infected children. No direct correlation with age was found, but a further increase in IL‐10 expression was found in H pylori–infected children older than 4 years, whereas in control subjects, IL‐10 expression tended to be lower in older children. IL‐1β expression was similar in infected children and control subjects. In H pylori–infected children, the prevalence of allergy was significantly higher in children with lower cytokine expression in gastric mucosa.

Conclusions:

In children, H pylori–induced inflammatory response is associated with development of cell‐mediated immunity of T‐helper 1 type, as demonstrated by increased IFN‐γ expression. The significantly increased expression of gastric IL‐10 in H pylori–infected children and its further increase in older children suggest that this chronic infection may influence IL‐10 production even beyond the age of 4 years. H pylori may be one of the infections with the potential to modulate immune responses.
A National Sample of Individuals Who Acquired Hepatitis C Virus Infections in Childhood or Adolescence: Risk Factors for Advanced Disease
Authors: Harris Helen E , Mieli‐Vergani Giorgina , Kelly Deirdre , Davison Suzanne , Gibb Diana M , Ramsay Mary E ,   HCV National Register Steering Group
Published: March 2009

Objectives:

To describe hepatitis C virus (HCV)–related liver disease in a national cohort of patients who acquired their infections in childhood or adolescence and to assess risk factors for progressive disease and response to antiviral therapy.

Patients and Methods:

Demographic, laboratory, and clinical outcome data on 246 individuals who acquired HCV infection before the age of 16 years were extracted from the UK HCV National Register database. Logistic regression analysis was used to investigate the independent effects of sex, age, duration and route of infection, and comorbidity on histological stage of liver disease.

Results:

Median ages at enrollment and follow‐up were 14.0 years (range, 2.2–29.6 years) and 19.2 years (range, 2.3–35.5 years), respectively. Mean duration of infection at enrollment was 8.5 years (standard deviation [SD], 3.3 years), and mean duration of follow‐up was 4.5 years (SD, 4.5 years). Fifty‐nine (24%) had persistently abnormal liver aminotransferase levels; 22% reported physical signs and symptoms of liver disease. Among 123 individuals with liver biopsies, 117 (95%) had abnormal histological findings. Ninety‐eight individuals had biopsies referred for independent blind scoring; median Ishak grade and stage scores were 3 and 1, respectively. Presence of comorbidities (odds ratio [OR], 7.19; 95% CI, 2.00–26.17; P = 0.003) and female sex (OR, 0.31; 95% CI, 0.10–1.00; P = 0.05) were independently associated with histological stage scores greater than the median. A total of 110 individuals received antiviral therapy; 47% achieved a sustained response.

Conclusions:

HCV‐related liver disease in those who acquired the infection in childhood or adolescence was mild for most, although comorbidity and female sex were associated with more advanced disease. Antiviral therapy in childhood or adolescence successfully eradicates the virus for many patients.
The WUSCHEL-Related Homeobox GeneWOX11Is Required to Activate Shoot-Borne Crown Root Development in Rice
Authors: Zhao Yu , Hu Yongfeng , Dai Mingqiu , Huang Limin , Zhou Dao-Xiu
Published: March 2009

In rice (Oryza sativa), the shoot-borne crown roots are the major root type and are initiated at lower stem nodes as part of normal plant development. However, the regulatory mechanism of crown root development is poorly understood. In this work, we show that a WUSCHEL-related Homeobox (WOX) gene, WOX11, is involved in the activation of crown root emergence and growth. WOX11 was found to be expressed in emerging crown roots and later in cell division regions of the root meristem. The expression could be induced by exogenous auxin or cytokinin. Loss-of-function mutation or downregulation of the gene reduced the number and the growth rate of crown roots, whereas overexpression of the gene induced precocious crown root growth and dramatically increased the root biomass by producing crown roots at the upper stem nodes and the base of florets. The expressions of auxin- and cytokinin-responsive genes were affected in WOX11 overexpression and RNA interference transgenic plants. Further analysis showed that WOX11 directly repressed RR2, a type-A cytokinin-responsive regulator gene that was found to be expressed in crown root primordia. The results suggest that WOX11 may be an integrator of auxin and cytokinin signaling that feeds into RR2 to regulate cell proliferation during crown root development.
Specificity of staphylococcal phage and SaPI DNA packaging as revealed by integrase and terminase mutations
Authors: Ubeda Carles , Olivarez Nicholas P. , Barry Peter , Wang Huaibin , Kong Xiangpeng , Matthews Avery , Tallent Sandra M. , Christie Gail E. , Novick Richard P.
Published: March 2009

SaPI1 and SaPIbov1 are chromosomal pathogenicity islands in Staphylococcus aureus that carry tst and other superantigen genes. They are induced to excise and replicate by certain phages, are efficiently encapsidated in SaPI‐specific small particles composed of phage virion proteins and are transferred at very high frequencies. In this study, we have analysed three SaPI genes that are important for the phage–SaPI interaction, int (integrase) terS (phage terminase small subunit homologue) and pif (phage interference function). SaPI1 int is required for SaPI excision, replication and packaging in a donor strain, and is required for integration in a recipient. A SaPI1 int mutant, following phage induction, produces small SaPI‐specific capsids which are filled with partial phage genomes. SaPIbov1 DNA is efficiently packaged into full‐sized phage heads as well as into SaPI‐specific small ones, whereas SaPI1 DNA is found almost exclusively in the small capsids. TerS, however, determines DNA packaging specificity but not the choice of large versus small capsids. This choice is influenced by SaPIbov1 gene 12, which prevents phage DNA packaging into small capsids, and which is also primarily responsible for interference by SaPIbov1 with phage reproduction.
An ssDNA virus infecting archaea: a new lineage of viruses with a membrane envelope
Authors: Pietilä Maija K. , Roine Elina , Paulin Lars , Kalkkinen Nisse , Bamford Dennis H.
Published: March 2009

Archaeal organisms are generally known as diverse extremophiles, but they play a crucial role also in moderate environments. So far, only about 50 archaeal viruses have been described in some detail. Despite this, unusual viral morphotypes within this group have been reported. Interestingly, all isolated archaeal viruses have a double‐stranded DNA (dsDNA) genome. To further characterize the diversity of archaeal viruses, we screened highly saline water samples for archaea and their viruses. Here, we describe a new haloarchaeal virus, Halorubrum pleomorphic virus 1 (HRPV‐1) that was isolated from a solar saltern and infects an indigenous host belonging to the genus Halorubrum. Infection does not cause cell lysis, but slightly retards growth of the host and results in high replication of the virus. The sequenced genome (7048 nucleotides) of HRPV‐1 is single‐stranded DNA (ssDNA), which makes HRPV‐1 the first characterized archaeal virus that does not have a dsDNA genome. In spite of this, similarities to another archaeal virus were observed. Two major structural proteins were recognized in protein analyses, and by lipid analyses it was shown that the virion contains a membrane. Electron microscopy studies indicate that the enveloped virion is pleomorphic (approximately 44 × 55 nm). HRPV‐1 virion may represent commonly used virion architecture, and it seems that structure‐based virus lineages may be extended to non‐icosahedral viruses.
The mntH gene encodes the major Mn2+ transporter in Bradyrhizobium japonicum and is regulated by manganese via the Fur protein
Authors: Hohle Thomas H. , O'Brian Mark R.
Published: March 2009

The bacterial Nramp family protein MntH is a divalent metal transporter, but mntH mutants have little or no phenotype in organisms where it has been studied. Here, we identify the mntH homologue of Bradyrhizobium japonicum, and demonstrate that it is essential for Mn2+ transport and for maintenance of cellular manganese homeostasis. Transport activity was induced under manganese deficiency, and Fe2+ did not compete with 54Mn2+ for uptake by cells. The steady‐state level of mntH mRNA was negatively regulated by manganese, but was unaffected by iron. Control of mntH expression and Mn2+ transport by manganese was lost in a fur strain, resulting in constitutively high activity. Fur protected a 35 bp region of the mntH promoter in DNase I footprinting analysis that includes three imperfect direct repeat hexamers that are needed for full occupancy. Mn2+ increased the affinity of Fur for the mntH promoter by over 50‐fold, with a Kd value of 2.2 nM in the presence of metal. The findings identify MntH as the major Mn2+ transporter in B. japonicum, and show that Fur is a manganese‐responsive regulator in that organism. Furthermore, Fe2+ is neither a substrate for MntH nor a regulator of mntH expression in vivo.
Disruption of a mitochondrial MutS DNA repair enzyme homologue confers drug resistance in the parasiteToxoplasma gondii
Authors: Garrison Erin M. , Arrizabalaga Gustavo
Published: March 2009

MutS homologues (MSHs) are critical components of the eukaryotic mismatch repair machinery. In addition to repairing mismatched DNA, mismatch repair enzymes are known in higher eukaryotes to directly signal cell cycle arrest and apoptosis in response to DNA‐damaging agents. Accordingly, mammalian cells lacking certain MSHs are resistant to chemotherapeutic drugs. Interestingly, we have discovered that the disruption ofTgMSH‐1, an MSH in the pathogenic parasite,Toxoplasma gondii, confers drug resistance. Through a genetic selection forT. gondiimutants resistant to the antiparasitic drug monensin, we have isolated a strain that is resistant not only to monensin but also to salinomycin and the alkylating agent, methylnitrosourea. We have shown that this phenotype is due to the disruption ofTgMSH‐1as the multidrug‐resistance phenotype is complemented by a wild‐type copy ofTgMSH‐1and is recapitulated by a directed disruption of this gene in a wild‐type strain. We have also shown that, unlike previously described MSHs involved in signalling, TgMSH‐1 localizes to the parasite mitochondrion. These results provide the first example of a mitochondrial MSH that is involved in drug sensitivity and implicate the induction of mitochondrial stress as a mode of action of the widely used drug, monensin.
Aortoiliac surgery concomitant with kidney transplantation: a single center experience
Authors: Tsivian Matvey , Neri Flavia , Nardo Bruno , Bertelli Riccardo , Cavallari Giuseppe , Fuga Giovanni , Faenza Alessandro
Published: March 2009

Abstract: Introduction: Aortoiliac pathology in kidney allograft recipients is not rare but treatment timing is controversial. As most publications on this topic are case reports it’s difficult to evaluate long‐term outcomes of those clinical challenges. Herein we report long‐term results of these procedures.

Methods: From 1970 to 2006, 1544 kidney transplants were performed in our center. Thirty patients underwent aortoiliac surgery simultaneously with kidney transplantation. We analyzed their clinical records to come up with outcomes of these complex clinical challenges.

Results: Vascular pathology was distributed as following: 19 stenoses treated with endarterectomy (15), aortoiliac bypass (two), aorto‐bi‐iliac bypass (one) and aorto‐bifemoral bypass (one); and 11 aneurysms treated with arterioplasty (four), aorto‐bi‐iliac bypass (four) and iliac‐iliac bypass (three). In 24 cases (80%) the necessity of vascular surgery was established intraoperatively as vessels’ conditions did not permit safe anastomoses and jeopardized graft survival. Mean follow‐up was 59 months (12–125). Five (16.7%) grafts were lost and three (10%) patients died in the first post‐operative month: acute myocardial infarction (two) and non‐viable kidney (one). Three patients died six, seven and 10 yr after the procedure. Nineteen patients are currently well with functioning grafts.

Conclusions: Surgical correction of aortoiliac pathology may be performed simultaneously with kidney transplantation with acceptable outcome. This complex surgery can be performed in centers with experienced vascular surgeons. Specific vascular imaging should be performed regularly on patient at risk of aortoiliac disease before insertion and while on waiting list.
As the last resort: reducing the use of restrictive physical interventions using organisational approaches
Authors: Deveau Roy , McDonnell Andrew
Published: March 2009

Accessible summary

People living in a home should not be restrained unless they are really hurting themselves or somebody else.

People living in a home should be helped to manage their own behaviour without being restrained.

The development of restrictive physical interventions (RPI) to manage challenging behaviours based upon control and restraint during the 1980s and 1990s led to widespread professional disquiet and campaigning to improve the policies, training and application of physical techniques. This included the promotion of a value base within which physical techniques should be used. This value base may be summarised as any use of physical interventions must be in the person’s best interests, ‘least restrictive’ and used as the last resort following preventive strategies. The last resort principle implies that services should be able to demonstrate support plans to prevent or reduce the frequency and/or restrictiveness of PI used in individual cases. This paper proposes that adopting explicit policies and practice to reduce restrictive PI is likely to be more effective in improving quality of support as opposed to solely managing PI use. Discussion of current policy and practice is followed by discussion of organisations’ roles in relation to RPI reduction, with international comparisons.
Validation of regression‐based myogenic correction techniques for scalp and source‐localized EEG
Authors: McMenamin Brenton W. , Shackman Alexander J. , Maxwell Jeffrey S. , Greischar Lawrence L. , Davidson Richard J.
Published: March 2009

EEG and EEG source‐estimation are susceptible to electromyographic artifacts (EMG) generated by the cranial muscles. EMG can mask genuine effects or masquerade as a legitimate effect—even in low frequencies, such as alpha (8–13 Hz). Although regression‐based correction has been used previously, only cursory attempts at validation exist, and the utility for source‐localized data is unknown. To address this, EEG was recorded from 17 participants while neurogenic and myogenic activity were factorially varied. We assessed the sensitivity and specificity of four regression‐based techniques: between‐subjects, between‐subjects using difference‐scores, within‐subjects condition‐wise, and within‐subject epoch‐wise on the scalp and in data modeled using the LORETA algorithm. Although within‐subject epoch‐wise showed superior performance on the scalp, no technique succeeded in the source‐space. Aside from validating the novel epoch‐wise methods on the scalp, we highlight methods requiring further development.
The cognitive control of distraction by novelty in children aged 7–8 and adults
Authors: Wetzel Nicole , Widmann Andreas , Schröger Erich
Published: March 2009

The study focused on the development of cognitive control of distraction. Novel sounds were interspersed in a sequence of a constant environmental sound, while subjects were engaged in a task not related to novelty. In both children (7–8 years) and adults, unpredictable novel sounds caused prolonged reaction times (RT), the P3a and the Reorienting Negativity (RON) components of the event‐related potential, indicating distraction and reorienting of attention. With predictable novels, RT prolongation and RON‐amplitude were reduced in both groups, whereas P3a‐amplitude reduction was confined to adults. Thus, although children reveal some indication for control of distraction, they do not yet achieve the level of adults. This differential pattern of the development of RT prolongation, P3a, and RON across age groups indicates different maturation of processes involved in the control of distraction and suggests partly independent underlying processes.
The phosphodiesterase‐5 inhibitor vardenafil improves cardiovascular dysfunction in experimental diabetes mellitus
Authors: Radovits T , Bömicke T , Kökény G , Arif R , Loganathan S , Kécsán K , Korkmaz S , Barnucz E , Sandner P , Karck M , Szabó G
Published: March 2009

Background and purpose:  Patients with diabetes mellitus exhibit generalized endothelial and cardiac dysfunction with decreased nitric oxide production. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective cardioprotection in different pathophysiological conditions. In this study, we investigated whether chronic treatment with the phosphodiesterase‐5 inhibitor vardenafil could improve diabetic cardiovascular dysfunction by up‐regulating the nitric oxide–cGMP pathway in the vessel wall and myocardium.

Experimental approach:  Diabetes was induced in young rats by a single intraperitoneal injection of streptozotocin (60 mg·kg−1). In the treatment group, vardenafil (10 mg·kg−1·day−1) was given orally for 8 weeks. Diabetic control animals received vehicle for the same time. Left ventricular pressure–volume relations were measured by using a microtip Millar pressure–volume conductance catheter, and indexes of contractility, such as the slope of end‐systolic pressure–volume relationship (Emax) and preload recruitable stroke work (PRSW), were calculated. In organ bath experiments for isometric tension with rings of isolated aortae, endothelium‐dependent and independent vasorelaxation was investigated by using acetylcholine and sodium nitroprusside.

Key results:  When compared with the non‐diabetic controls, diabetic rats showed increased myocardial and vascular transforming growth factor‐β1 expression, impaired left ventricular contractility (impairment of Emax by 53%, PRSW by 40%; P < 0.05) and vascular dysfunction. Treatment with vardenafil resulted in higher cGMP levels, reduced transforming growth factor‐β1 expression, significantly improved cardiac function (improvement of Emax by 95%, PRSW by 69%; P < 0.05) and greater vasorelaxation to acetylcholine and sodium nitroprusside in aortae from diabetic animals.

Conclusions and implications:  Our results demonstrate that impaired vascular cGMP signalling contributes to the development of diabetic vascular and cardiac dysfunction, which can be prevented by chronic phosphodiesterase‐5 inhibition.
Myrtucommulone, a natural acylphloroglucinol, inhibits microsomal prostaglandin E2 synthase‐1
Authors: Koeberle A , Pollastro F , Northoff H , Werz O
Published: March 2009

Background and purpose:  The selective inhibition of prostaglandin (PG)E2 formation via interference with microsomal PGE2 synthase (mPGES)‐1 could have advantages in the treatment of PGE2‐associated diseases, such as inflammation, fever and pain, compared with a general suppression of all PG biosynthesis, provided by inhibition of cyclooxygenase (COX)‐1 and 2. Here, we addressed whether the naturally occurring acylphloroglucinol myrtucommulone (MC) from Myrtus communis L. (myrtle) affected mPGES‐1.

Experimental approach:  The effect of MC on PGE2 formation was investigated in a cell‐free assay by using microsomal preparations of interleukin‐1β‐stimulated A549 cells as the source of mPGES‐1, in intact A549 cells, and in lipopolysaccharide‐stimulated human whole blood. Inhibition of COX‐1 and COX‐2 activity in cellular and cell‐free assays was assessed by measuring 12(S)‐hydroxy‐5‐cis‐8,10‐trans‐heptadecatrienoic acid and 6‐oxo PGF1α formation.

Key results:  MC concentration‐dependently inhibited cell‐free mPGES‐1‐mediated conversion of PGH2 to PGE2 (IC50 = 1 µmol·L−1). PGE2 formation was also diminished in intact A549 cells as well as in human whole blood at low micromolar concentrations. Neither COX‐2 activity in A549 cells nor isolated human recombinant COX‐2 was significantly affected by MC up to 30 µmol·L−1, and only moderate inhibition of cellular or cell‐free COX‐1 was evident (IC50 > 15 µmol·L−1).

Conclusions and implications:  MC is the first natural product to inhibit mPGES‐1 that efficiently suppresses PGE2 formation without significant inhibition of the COX enzymes. This provides an interesting pharmacological profile suitable for interventions in inflammatory disorders, without the typical side effects of coxibs and non‐steroidal anti‐inflammatory drugs.
Notes on the origins of Epilepsia and the International League Against Epilepsy
Authors: Shorvon Simon D. , Weiss Giselle , Goodkin Howard P.
Published: March 2009

The recent discovery of archival material has shed interesting light on the origins of Epilepsia and also the International League Against Epilepsy (ILAE). The idea of an international journal devoted to epilepsy seems first to have arisen from talks between Dr. L. J. J. Muskens and Dr. W. Aldren Turner in 1905. A protracted series of subsequent letters between Muskens and a Haarlem publisher show how the idea slowly took shape. The committee of patronage, editorial board, and editorial assistants was probably first approached at the First International Congress of Psychiatry, Neurology, Psychology, and Nursing of the Insane, held in Amsterdam in 1907. At this meeting, the concept of an international organization to fight epilepsy (to become the ILAE) was also first proposed in public, again by Muskens. The concept of the ILAE was clearly modeled on another international organization—the International Commission for the Study of the Causes of Mental Diseases and Their Prophylaxis. This Commission had been first publicly proposed in 1906 by Ludwig Frank, at the Second International Congress for the Care and Treatment of the Insane. The proposed Commission and ILAE shared many features, aims, and personnel. Despite an auspicious start, the International Commission was prevented by personal and political differences from ever actually coming into being. However, the first issue of Epilepsia appeared in March 1909 and the ILAE was inaugurated in August 1909; and both have flourished and celebrate their centenaries this year.
A Randomized, Double‐Blind, Placebo‐Controlled Study of Preemptively Administered Intravenous Parecoxib: Effect on Anxiety Levels and Procedural Pain During Epidural Catheter Placement for Surgical Operations or for Chronic Pain Therapy
Authors: Vadalouca Athina , Moka Eleni , Chatzidimitriou Anna , Siafaka Ioanna , Sikioti Panayiota , Argyra Erifilli
Published: March 2009

Background:  The effect of parecoxib, when used perioperatively or during interventional techniques, is well demonstrated in the literature. Little is known about its effects on anxiety levels before the analgesic technique application. The aim of this prospective, randomized, double‐blind, placebo‐controlled, clinical study is to investigate whether parecoxib, preemptively administrated, has an effect on anxiety levels reported prior to an epidural puncture, and if it influences the reported pain of the interventional technique itself.

Material and Methods:  The study protocol involved 110 patients, scheduled for epidural catheter placement for chronic pain therapy—Group I, as well as 112 patients scheduled for orthopedic operations under epidural anesthesia—Group II. Patients in each group were randomly allocated into two subgroups in relation to parecoxib/placebo administration before epidural catheter placement: Group Ia, parecoxib 40 mg i.v. (n = 54), Group Ib, placebo (n = 56), Group IIa, parecoxib 40 mg i.v. (n = 57), Group IIb, placebo (n = 55). Patients were given a self‐administered inventory to measure the anxiety level of the presurgical/preprocedural state (State‐Trait Spielberger Anxiety Inventory) and anxiety levels were recorded 1 hour before epidural puncture, 20 minutes postdosing, and 1 hour after epidural catheter placement. Anxiety levels were also measured and recorded using visual analog scale (VAS). One hour after epidural puncture, reported procedural pain was recorded (VAS). One hour and 6 hours postepidural, patients' satisfaction was also recorded, on a 4‐point scale.

Results:  All four subgroups were similar regarding demographic, operative/procedural data, and coexisting diseases. Preprocedural anxiety levels were significantly decreased with parecoxib administration in comparison with placebo in both groups (P < 0.05). Reported VAS regarding pain from epidural puncture was lower in Groups IA and Ib. Patients' satisfaction was greater with parecoxib in comparison with placebo.

Conclusion:  The levels of anxiety have been investigated in several medical procedures and early, in the study of pain. The higher the expectation of pain and the anxiety are, the higher the intensity of the pain. Parecoxib seems to exert positive influence on pain and anxiety levels of interventional procedure. Further studies are needed to elucidate the actual mechanisms that are involved.
Depression in Chronic Pain Patients: Prevalence and Measurement
Authors: Poole Helen , White Susie , Blake Chantal , Murphy Peter , Bramwell Ros
Published: March 2009

This study aimed to: (1) determine prevalence of depression in patients referred to specialist pain services using the Structured Clinical Interview (SCID) diagnostic interview, (2) compare results on the Beck Depression Inventory II (BDI‐II) with the SCID to determine the utility of the BDI‐II as a screening tool in this population.

Thirty‐six participants were recruited, mainly women, with a mean age = 47.83 years (standard deviation = 12.85 years), who were heterogeneous with regard to their pain. All completed the BDI‐II and SCID. The SCID diagnosed 26 (72%) cases of depression. BDI‐II scores showed 31 (86%) that reported at least mild depression. Agreement between BDI‐II scores over threshold for mild depression and SCID diagnosis were assessed by Cohen's kappa (= 0.6). ROC analysis for BDI‐II scores against SCID diagnosis gave a large area under the curve (0.97, 95% confidence interval 0.93 to 1.02), suggesting BDI‐II is an excellent screen for this population, although the curve was unusual in that sensitivity was high even when the false positive rate was zero. ROC analysis suggested 22 or above as an optimum cut‐off score for depression on the BDI‐II—higher than for a general population sample.

It has been suggested that the BDI overestimates incidence of depression in pain patients, but this study confirmed through diagnostic interview the very high incidence of depression in this population. It is therefore questionable whether there is value in screening referrals for depression. When using BDI‐II for screening, audit or evaluation purposes with a pain clinic population, we suggest a cut‐off of 22 or above.
Two Fission Yeast Rab7 Homologs, Ypt7 and Ypt71, Play Antagonistic Roles in the Regulation of Vacuolar Morphology
Authors: Kashiwazaki Jun , Iwaki Tomoko , Takegawa Kaoru , Shimoda Chikashi , Nakamura Taro
Published: March 2009

Small guanine triphosphatases (GTPases) of the Rab family are key regulators of membrane trafficking events between the various subcellular compartments in eukaryotic cells. Rab7 is a conserved protein required in the late endocytic pathway and in lysosome biogenesis. A Schizosaccharomyces pombe (S. pombe) homolog of Rab7, Ypt7, is necessary for trafficking from the endosome to the vacuole and for homotypic vacuole fusion. Here, we identified and characterized a second fission yeast Rab7 homolog, Ypt71. Ypt71 is localized to the vacuolar membrane. Cells deleted for ypt71+ exhibit normal growth rates and morphology. Interestingly, a ypt71 null mutant contains large vacuoles in contrast with the small fragmented vacuoles found in the ypt7 null mutant. Furthermore, the ypt71 mutation does not enhance or alleviate the temperature sensitivity or vacuole fusion defect of ypt7Δ cells. Like ypt7Δ cells, overexpression of ypt71+ caused fragmentation of vacuoles and inhibits vacuole fusion under hypotonic conditions. Thus, the two S. pombe Rab7 homologs act antagonistically in regulating vacuolar morphology. Analysis of a chimeric Ypt7/Ypt71 protein showed that Rab7‐directed vacuole dynamics, fusion versus fission, largely depends on the medial region of the protein, including a part of RabSF3/α3‐L7.
Array‐Based Genomics in Glioma Research
Authors: Idbaih Ahmed , Crinière Emmanuelle , Ligon Keith L. , Delattre Olivier , Delattre Jean‐Yves
Published: March 2009

Over the years, several relevant biomarkers with a potential clinical interest have been identified in gliomas using various techniques, such as karyotype, microsatellite analysis, fluorescent in situ hybridization and chromosome comparative genomic hybridization. Despite their pivotal contribution to our understanding of gliomas biology, clinical application of these approaches has been limited by technological and clinical complexities. In contrast, genomic arrays (array‐based comparative genomic hybridization and single nucleotide polymorphisms array) have emerged as promising technologies for clinical use in the setting of gliomas. Indeed, their feasibility and reliability have been rigorously assessed in gliomas and are discussed in this review. The well‐known genomic biomarkers in gliomas are in fact readily and reliably identified using genomic arrays. Moreover, it detects a multitude of new cryptic genomic markers, with potential biological and/or clinical significances. The main studies dedicated to genomic characterization of gliomas using genomic arrays are reviewed here. Interestingly, several recurrent genomic signatures have been reported by different teams, suggesting the validity of these genomic patterns. In light of this, genomic arrays are relatively simple and cost‐effective techniques whose implementation in molecular diagnostic laboratories should be encouraged as a valuable clinical tool for management of glioma patients.