bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTPurpose: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

ABSTRACTBackground: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

ABSTRACTObjectives: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

AbstractIn 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

SummarySaPI1 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

SummaryArchaeal 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

SummaryThe 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

SummaryMutS 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.

SummaryThe 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

AbstractEEG 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

AbstractThe 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.