bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective T‐cell function leading to reduced antibody production in a kleisin‐β mutant mouse
Authors: Gosling Katharine M. , Goodnow Christopher C. , Verma Naresh K. , Fahrer Aude M.
Published: April 2008

The recently described nessy (Ncaph2nes/nes) mutant mouse strain has a defect in T‐cell development caused by a mutation in the ubiquitous kleisin‐β (also known as Ncaph2). Kleisin‐β is a subunit of the condensin II complex involved in chromosome condensation during mitosis. The nessy phenotype is characterized by CD44hi CD8+ peripheral T cells, 10–20% of normal thymocyte numbers and 2·5‐fold fewer αβ T cells in the spleen compared with wild‐type mice. In this study we examined the effect of the nessy mutation in kleisin‐β on the immune response by challenging mice with an attenuated strain of Salmonella. Results showed that nessy mice control bacterial load as effectively as wild‐type mice but exhibit a reduced antibody titre. Further experiments revealed that while the T‐dependent antibody response was diminished in nessy mice the T‐independent response was normal, suggesting that the defect was the result of T‐cell function and not B‐cell function. In vitro activation assays showed that nessy T cells have a lower capacity to up‐regulate the early activation marker CD69 than wild‐type T cells. Upon transfer into RAG−/− mice, nessy and wild‐type CD4 T cells showed equivalent homeostatic proliferation, while nessy CD8 T cells proliferated more than their wild‐type counterparts. When cultured with anti‐T‐cell receptor β or concanavalin A, nessy T cells were found to die faster than wild‐type T cells. These data indicate that kleisin‐β is required for a normal immune response, and represent the first demonstration of a role for kleisin‐β in T‐cell function.
Human B cells express the orphan chemokine receptor CRAM‐A/B in a maturation‐stage‐dependent and CCL5‐modulated manner
Authors: Hartmann Tanja N. , Leick Marion , Ewers Susann , Diefenbacher Andrea , Schraufstatter Ingrid , Honczarenko Marek , Burger Meike
Published: April 2008

Chemokines orchestrate the organization of leucocyte recruitment during inflammation and homeostasis. Despite growing knowledge of chemokine receptors, some orphan chemokine receptors are still not characterized. The gene CCRL2 encodes such a receptor that exists in two splice variants, CRAM‐A and CRAM‐B. Here, we report that CRAM is expressed by human peripheral blood and bone marrow B cells, and by different B‐cell lines dependent on the B‐cell maturation stage. Intriguingly, CRAM surface expression on the pre‐B‐cell lines Nalm6 and G2 is specifically upregulated in response to the inflammatory chemokine CCL5 (RANTES), a chemokine that is well known to play an important role in modulating immune responses. Although Nalm6 cells do not express any of the known CCL5 binding receptors, extracellular signal‐regulated kinases 1 and 2 (ERK1/2) are phosphorylated upon CCL5 stimulation, suggesting a direct effect of CCL5 through the CRAM receptor. However, no calcium mobilization or migratory responses upon CCL5 stimulation are induced in B‐cell lines or in transfected cells. Also, ERK1/2 phosphorylation cannot be inhibited by pertussis toxin, suggesting that CRAM does not couple to Gi proteins. Our results describe the expression of a novel, non‐classical chemokine receptor on B cells that is potentially involved in immunomodulatory functions together with CCL5.
Managing change in an information systems development organization: understanding developer transitions from a structured to an object‐oriented development environment1
Authors: Shaft Teresa M. , Albert Leslie Jordan , Jasperson Jon (Sean)
Published: April 2008

Abstract.  Object‐oriented systems development has attracted great interest in the information systems (IS) field because of a belief that using object‐oriented development (OD) makes it easier to develop and maintain software plus achieve software reuse. However, the transition from structured to OD may be especially challenging for IS developers. In fact, some argue that structured development (SD) knowledge may interfere with the ability to learn OD approaches because of a form of proactive interference.

To understand how knowledge of SD concepts influences the ability to gain OD knowledge, we assessed a team of IS developers' understanding of structured and object‐oriented concepts at the beginning of their first OD project and repeated our assessment 1 year later. Developers increased their understanding of some object‐oriented concepts, but these changes were associated with increases in understanding of one of the SD concepts. Further, at the beginning and end of the project, developers' mental models were highly consistent with one another and that of an OD expert with regard to most OD concepts. It appears that the formal training that developers received allowed them to attain a good understanding of most object‐oriented concepts. These findings challenge the idea that structured developers must ‘unlearn’ SD to adopt OD approaches. Future research may wish to examine the different types of software development knowledge to ascertain which are amenable to positive transfer and which are more likely to suffer from proactive interference.
Cardiac involvement in adults with Pompe disease
Authors: Soliman O. I. I. , Van Der Beek N. A. M. E. , Van Doorn P. A. , Vletter W. B. , Nemes A. , Van Dalen B. M. , Ten Cate F. J. , Van Der Ploeg A. T. , Geleijnse M. L.
Published: April 2008

Background.  Glycogen storage disease type II or Pompe disease is a neuromuscular disorder caused by deficiency of lysosomal acid α‐ glucosidase. Classic infantile Pompe disease results in massive left ventricular (LV) hypertrophy and failure. Although Pompe disease is often included in the differential diagnosis of LV hypertrophy the true frequency of cardiac involvement in adults with Pompe disease is not known.

Methods.  Forty‐six consecutive adult patients (mean age 48 ± 12, 22 men) with Pompe disease were included. Each patient underwent a clinical examination, electrocardiography, and rest and low‐dose dobutamine (in 20 patients) two‐dimensional echocardiography including contrast and tissue Doppler imaging.

Results.  All patients had limited exercise tolerance; a rollator walking aid was used in seven patients (15%), a wheelchair in 13 patients (28%), and assisted ventilation in 14 patients (30%). Prior to this study, one patient was known with permanent atrial fibrillation, His‐bundle ablation and a VVI pacemaker and another patient was known with fluid retention. The first patient had increased LV end‐diastolic diameter, impaired LV ejection fraction, low systolic mitral annular velocities and diastolic dysfunction grade II. The patient with fluid retention was wheelchair bound and dependent on 24‐h assisted ventilation and showed right ventricular and LV hypertrophy (septum 16 mm, posterior wall 15 mm). LV hypertrophy was not seen in any of the other patients. One woman of advanced age had isolated low systolic mitral annular velocities. Mean global systolic LV function, including contractile reserve, was not decreased in patients with Pompe disease. Eight patients (17%) had mild diastolic dysfunction grade I, related to hypertension in four and advanced age in seven.

Conclusions.  In adult patients with Pompe disease without objective signs of cardiac affection by 12‐leads electrocardiography or physical examination, echocardiographic screening for LV hypertrophy seems not effective.
Developing Antibacterial Vaccines in Genomics and Proteomics Era
Authors: Kaushik D. K. , Sehgal D.
Published: April 2008

Infectious diseases are the greatest cause of global morbidity and mortality. About half of this burden is caused by pathogenic bacteria. One of the most effective ways to prevent infectious diseases is to use vaccines. Limitations in the traditional approaches may be one of the reasons why vaccines are yet not available against some infectious bacterial agents. Recent advancements in high‐throughput ‘omics’ technologies and the availability of complete genome sequences of microbial pathogens and multiple isolates of the same species have dramatically changed the time frame and scope for identifying novel vaccine candidates. At present, 582 microbial genomes have been sequenced and sequencing of 1733 is in progress. There are more than 50 bacterial species for which the genome sequence is available for three or more isolates. Development of tools for in silico analysis has led to the identification of novel virulence genes, metabolic pathways and cell surface proteins that represent potential new targets for anti‐microbial drug and vaccine strategies. In this review, we provide an overview of the ‘omics’‐based techniques that can be used to advance and accelerate the discovery of vaccine candidates against extracellular bacterial pathogens. By citing specific examples, we discuss how high‐throughput molecular profiling techniques, such as genomics, transcriptomics and proteomics have contributed to the discovery of novel vaccine candidates. We end by contemplating on the emerging technologies that are likely to have a high impact on the field of vaccinology in the near future.
Plant virus infection‐induced persistent host gene downregulation in systemically infected leaves
Authors: Havelda Zoltán , Várallyay Éva , Válóczi Anna , Burgyán József
Published: April 2008

Understanding of virus infection‐induced alterations in host plant gene expression and metabolism leading to the development of virus disease symptoms is both scientifically and economically important. Here, we show that viruses belonging to various RNA virus families are able to induce efficient host gene mRNA downregulation (shut‐off) in systemically infected leaves. We demonstrate that the host gene mRNA shut‐off overlaps spatially with virus‐occupied sectors, indicating the direct role of virus accumulation in this phenomenon. The establishment of shut‐off was not directly connected to active viral replication or the RNA‐silencing machinery. Importantly, the induced shut‐off phenomenon persisted for several weeks, resulting in severe deficiency of mRNA for important housekeeping genes in the infected plants. Interestingly, we found that some other RNA viruses do not induce or only slightly induce the shut‐off phenomenon for the same set of genes, implicating genetic determination in this process. Nuclear run‐on experiments suggest that plant viruses, similarly to animal viruses, mediate suppression of host mRNA synthesis in the nucleus. By investigating various host–virus interactions, we revealed a correlation between the intensity of the shut‐off phenomenon and the severity of disease symptoms. Our data suggest that efficient and persistent downregulation of host genes may be an important component of symptom development in certain host–virus interactions.
Cytokinins negatively regulate the root iron uptake machinery in Arabidopsis through a growth‐dependent pathway
Authors: Séguéla Mathilde , Briat Jean‐François , Vert Grégory , Curie Catherine
Published: April 2008

Plants display a number of biochemical and developmental responses to low iron availability in order to increase iron uptake from the soil. The ferric‐chelate reductase FRO2 and the ferrous iron transporter IRT1 control iron entry from the soil into the root epidermis. In Arabidopsis, expression of IRT1 and FRO2 is tightly controlled to maintain iron homeostasis, and involves local and long‐distance signals, as well as transcriptional and post‐transcriptional events. FIT encodes a putative basic helix‐loop‐helix (bHLH) transcription factor that regulates iron uptake responses in Arabidopsis. Here, we uncover a new regulation of the root iron uptake genes. We show that IRT1, FRO2 and FIT are repressed by the exogenous addition of cytokinins (CKs), and that this repression acts at the level of transcript accumulation, and depends on the AHK3 and CRE1 CK receptors. The CKs and iron‐deficiency signals act through distinct pathways to regulate the soil iron uptake genes, as (i) CK repression is independent of the iron status, (ii) IRT1 and FRO2 downregulation is unchanged in a fit loss‐of‐function mutant, indicating that FIT does not mediate CK repression, and (iii) the iron‐regulated genes AtNRAMP3 and AtNRAMP4 are not downregulated by CKs. We show that root growth‐inhibitory conditions, such as abiotic stresses (mannitol, NaCl) and hormonal treatments (auxin, abscissic acid), repress the iron starvation response genes. We propose that CKs control the root iron uptake machinery through a root growth dependent pathway in order to adapt nutrient uptake to the demand of the plant.
RLM3, a TIR domain encoding gene involved in broad‐range immunity of Arabidopsis to necrotrophic fungal pathogens
Authors: Staal Jens , Kaliff Maria , Dewaele Ellen , Persson Mattias , Dixelius Christina
Published: April 2008

Here, we describe the rapid cloning of a plant gene, Leptosphaeria maculans 3 (RLM3Col), which encodes a putative Toll interleukin‐1 receptor‐nucleotide binding (TIR‐NB) class protein, which is involved in defence against the fungal pathogen L. maculans and against three other necrotrophic fungi. We have, through microarray‐based case control bulk segregant comparisons of transcriptomes in pools of Col‐0 × An‐1 progeny, identified the absence of a locus that causes susceptibility in An‐1. The significance of this locus on chromosome 4 for L. maculans resistance was supported by PCR‐based mapping, and denoted resistance to RLM3Col. Differential susceptible phenotypes in four independent T‐DNA insertion lines support the hypothesis that At4g16990 is required for RLM3Col function. The mutants in RLM3Col also exhibited an enhanced susceptibility to Botrytis cinerea, Alternaria brassicicola and Alternaria brassicae. Complementations of An‐1 and T‐DNA mutants using overexpression of a short transcript lacking the NB‐ARC domain, or a genomic clone, restored resistance to all necrotrophic fungi. The elevated expression of RLM3Col on B. cinerea‐susceptible mutants further suggested convergence in signalling and gene regulation between defence against B. cinerea and L. maculans. In the case of L. maculans, RLM3Col is required for efficient callose deposition downstream of RLM1Col.
Mixed‐linkage β‐glucan : xyloglucan endotransglucosylase, a novel wall‐remodelling enzyme from Equisetum (horsetails) and charophytic algae
Authors: Fry Stephen C. , Mohler Kyle E. , Nesselrode Bertram H.W.A. , Franková Lenka
Published: April 2008

Mixed‐linkage (1→3,1→4)‐β‐d‐glucan (MLG), a hemicellulose long thought to be confined to certain Poales, was recently also found in Equisetum; xyloglucan occurs in all land plants. We now report that Equisetum possesses MLG:xyloglucan endotransglucosylase (MXE), which is a unique enzyme that grafts MLG to xyloglucan oligosaccharides (e.g. the heptasaccharide XXXGol). MXE occurs in all Equisetum species tested (Equisetum arvense, Equisetum fluviatile, Equisetum hyemale, Equisetum scirpoides, Equisetum telmateia and Equisetum variegatum), sometimes exceeding xyloglucan endotransglucosylase (XET) activity. Charophytic algae, especially Coleochaete, also possess MXE, which may therefore have been a primordial feature of plant cell walls. However, MXE was negligible in XET‐rich extracts from grasses, dicotyledons, ferns, Selaginella and bryophytes. This and the following four additional observations indicate that MXE activity is not the result of a conventional xyloglucan endotransglucosylase/hydrolase (XTH): (i) XET, but not MXE, activity correlates with the reaction rate on water‐soluble cellulose acetate, hydroxyethylcellulose and carboxymethylcellulose, (ii) MXE and XET activities peak in old and young Equisetum stems, respectively, (iii) MXE has a higher affinity for XXXGol (Km ∼ 4 μM) than any known XTH, (iv) MXE and XET activities differ in their oligosaccharide acceptor‐substrate preferences. High‐molecular‐weight (Mr) xyloglucan strongly competes with [3H]XXXGol as the acceptor‐substrate of MXE, whereas MLG oligosaccharides are poor acceptor‐substrates. Thus, MLG‐to‐xyloglucan grafting appears to be the favoured activity of MXE. In conclusion, Equisetum has evolved MLG plus MXE, potentially a unique cell wall remodelling mechanism. The prominence of MXE in mature stems suggests a strengthening/repairing role. We propose that cereals, which possess MLG but lack MXE, might be engineered to express this Equisetum enzyme, thereby enhancing the crop mechanical properties.
Regulation of root‐wave response by extra large and conventional G proteins in Arabidopsis thaliana
Authors: Pandey Sona , Monshausen Gabriele B. , Ding Lei , Assmann Sarah M.
Published: April 2008

Heterotrimeric G proteins composed of α, β and γ subunits regulate a number of fundamental processes concerned with growth and development in plants. In addition to the canonical heterotrimeric G proteins, plants also contain a small family of extra large G proteins (XLGs) that show significant similarity to the G‐protein α subunit in their C‐terminal regions. In this paper we show that one of the three XLG genes, XLG3, and the Gβ subunit (AGB1) of the Arabidopsis G‐protein heterotrimer are specifically involved in the regulation of a subset of root morphological and growth responses. Based on analysis of T‐DNA insertional mutant phenotypes, XLG3 and AGB1 each positively regulate root waving and root skewing. Since these responses are regulated by physical as well as physiological cues, we assessed the roles of AGB1 and XLG3 in gravitropism, thigmotropism and hormonal responses. Our data show that mutants lacking either XLG3 or AGB1 genes are hypersensitive to ethylene and show growth responses consistent with alterations in auxin transport, while maintaining an essentially wild‐type response to the physical cues of gravity and touch. These results suggest that XLG3 and AGB1 proteins regulate the hormonal determinants of root‐waving and root‐skewing responses in plants and possibly interact in a tissue‐specific or signal‐specific manner. Because plants harboring knockout mutations in the Gα subunit gene, GPA1, exhibit wild‐type root waving and skewing, our results may indicate that the AGB1 subunit functions in these processes without formation of a classic Gαβγ heterotrimer.
Food allergy in children suffering from atopic eczema
Authors: Rancé Fabienne
Published: April 2008

Whilst the association between eczema and food allergy is well established, the role of dietary manipulation in children with eczema remains controversial. These case histories highlight the differing outcomes that dietary manipulation may have in an infant with early onset, severe eczema and an older child with milder eczema. Management strategies and the evidence to support them are presented, followed by a review of clinical recommendations.
Primary jejunal adenocarcinoma as part of multiple primary cancers of the digestive tract
Authors: Kato Yutaro , Tsuyuki Akira , Kikuchi Kiyoshi , Fujishiro Yasuo , Tanabe Minoru , Watanabe Masahiko , Ozawa Soji , Kitajima Masaki
Published: April 2008

Multiple primary cancers including small intestinal tumors are rare. We describe the first curative resection case of metachronous triple early cancers involving the jejunum as well as the stomach and esophagus. The patient had undergone total gastrectomy for a gastric adenocarcinoma and subsequent esophagectomy for an esophageal squamous cell carcinoma. A jejunal adenocarcinoma, the third primary, occurred at the blind stump of the jejunal limb of a Roux‐en‐Y esophagojejunostomy reconstructed previously. This tumor was removed by partial resection of the limb with the preservation of the esophagojejunostomy. The patient died from complications of acute pancreatitis 3 years after the last operation, without overt clinical signs of cancer recurrence. Immunohistochemistry of the specimen showed the increased expression of p53 and cyclin D1 proteins in all three cancers, suggesting their involvement in metachronous carcinogenesis in this case. Early diagnosis of each cancer was made possible by regular endoscopic follow‐up and favorable anatomical location of each tumor, which were considered to allow less invasive surgery as well as to contribute to the favorable outcome. This case suggests the importance of regular surveillance for metachronous carcinogenesis, especially when the preceding cancers carry genetic abnormalities that may potentially increase the risk for subsequent carcinogenesis.
Immunohistochemical expression of cell‐cycle proteins in gastric precancerous lesions
Authors: Anagnostopoulos George K , Stefanou Dimitrios , Arkoumani Evdokia , Karagiannis John , Paraskeva Konstantina , Chalkley Lisa , Habilomati Erminia , Tsianos Epaminondas , Agnantis Niki J
Published: April 2008

Background:  The early indicator for the subject predisposed to gastric cancer is abnormal proliferation of gastric epithelial cells, such as atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia, which have been considered as precancerous lesions of gastric cancer. To determine whether p53 protein, cyclins D1, and D3, and p27kip1 play a role in the carcinogenesis pathway of gastric cancer, we performed an immunohistochemical study of their expression in gastric precancerous lesions.

Methods:  A total of 1 45 endoscopic gastric biopsy specimens of AG, IM, and gastric dysplasia were studied. These molecular markers were localized by immunohistochemistry.

Results:  P53 was expressed in 15% of cases with gastric dysplasia and not in the pre‐dysplastic stages of the gastric mucosa. All cases were concerning high‐grade dysplasia. Cyclin D1 protein was almost undetectable in the precancerous lesions of gastric cancer. Cyclin D3 protein overexpression was seen in 10% of biopsies with IM, and 50% of biopsies with gastric dysplasia. High expression of p27kip1 protein was demonstrated in all cases of chronic gastritis. As atrophy, IM, and dysplasia develop, expression of p27kip1 protein is suppressed. In total, 15% of dysplastic cases showed no expression of p27kip1 protein.

Conclusions:  (i) P53 mutation must be a late event during the development of gastric cancer. (ii) Cyclin D1 protein overexpression may not play a role in the progression from normal to neoplastic gastric mucosa, while overexpression of cyclin D3 is an earlier event during gastric carcinogenesis, and its role must be further evaluated. (iii) Reduced expression of p27kip1 is a rather early event in gastric tumorigenesis, before dysplastic changes occur.
Subepithelial mass lesions in the upper gastrointestinal tract
Authors: Humphris Jeremy L , Jones D Brian
Published: April 2008

The finding of a mass lesion in the upper gastrointestinal tract at endoscopy with apparent normal overlying mucosa is common. The differential diagnosis of such lesions is broad and includes those of intramural or extramural origin. Endoscopic ultrasound provides accurate imaging of subepithelial mass lesions and characterizes them according to size, echogenicity, and origin including the histologic layer if the lesion is intramural which narrows the differential diagnosis. Endoscopic ultrasound allows a guided tissue sample to be obtained for histologic confirmation which is especially important for hypoechoic lesions arising from the 3rd or 4th echogenic layers. The purpose of this article is to review the diagnosis of the more common subepithelial mass lesions with an emphasis on endoscopic ultrasound and the subsequent management or monitoring.
Correlation of transforming growth factor beta‐1 gene polymorphisms C‐509T and T869C and the risk of gastric cancer in China
Authors: Li Tao , Cao Bang‐Wei , Dai Yue , Cui Hong , Yang Hong‐Li , Xu Chang‐Qing
Published: April 2008

Background and Aim:  As an important cytokine that modulate the cell cycle, the involvement of transforming growth factor beta‐1 (TGF‐β1) in carcinogenesis has been extensively studied for many years. Literatures have demonstrated that TGF‐β1 gene polymorphisms may alter the risk of various cancers, such as lung, prostate and breast. To investigate whether polymorphisms of the TGF‐β1 gene can modify the risk of gastric cancer, we conduct this hospital‐based, case‐control study.

Methods:  One hundred and sixty‐seven cases and 193 gender, age‐matched healthy controls were enrolled in this case‐control study. TGF‐β1 polymorphisms C‐509T and T + 869C were identified by PCR‐RFLP and ARMS‐PCR protocols, respectively.

Results:  Significantly different distributions of both genes were demonstrated between the case and control. Variant genotypes −509CT, −509TT, +869TC and +869CC were associated with increased risk of gastric cancer (P = 0.001, OR = 2.54; P = 0.016, OR = 2.09; P < 0.001, OR = 3.46; P < 0.001, OR = 4.04, respectively). With haplotype analysis, wild type CT (−509C and +869T) led to a lower frequency in case than that in control (P < 0.001), while haplotype TC was more frequent in case than in control (P < 0.001). Multiple logistic regression analysis revealed that individuals with haplotype TC had an increased likelihood of developing gastric cancer (OR = 3.19, 95%CI = 1.72–5.90).

Conclusions:  Our findings imply that −509C > T and +869T > C gene polymorphisms in TGF‐β1 may be a critical risk factor of genetic susceptibility to gastric cancer in the Chinese population.
Prospective study of short‐term peginterferon‐α‐2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapy
Authors: Jeong Soocheol , Kawakami Yoshiiku , Kitamoto Mikiya , Ishihara Hiroto , Tsuji Keiji , Aimitsu Shiomi , Kawakami Hiroiku , Uka Kiminori , Takaki Shintaro , Kodama Hideaki , Waki Koji , Imamura Michio , Aikata Hiroshi , Takahashi Shoichi , Chayama Kazuaki
Published: April 2008

Background and Aims:  Long‐term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short‐term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN‐α‐2a therapy for 8 or 24 weeks.

Methods:  After excluding patients with high titers of genotype‐1, 55 HCV patients received pegIFN‐α‐2a. Patients who became negative for HCV‐RNA at week 2 were allocated to either an 8‐week (n = 19) or 24‐week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy.

Results:  The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8‐week group, but in six patients of the 24‐week group (P = 0.028). Treatment was completed by all patients of the 8‐week group, but discontinued in five patients of the 24‐week group (P = 0.011).

Conclusions:  The 8‐week IFN therapy is more tolerable than the 24‐week therapy and had similar outcomes. Excluding the patients with high titers of genotype‐1, we recommend switching to an 8‐week course of pegIFN‐α monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy.
Economic evaluation of chronic hepatitis B treatments in Taiwan
Authors: Lacey Laurence , Chien Rong‐Nan , Chuang Wan‐Long , Pwu Raoh‐Fang
Published: April 2008

Background and Aims:  Chronic hepatitis B (CHB) and its sequelae are major health problems in Taiwan. The purpose of the present study was the economic evaluation of short‐duration treatments of CHB and longer duration antiviral treatment for up to 5 years.

Methods:  Ten‐health state CHB disease progression Markov models were used for hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative CHB patients, respectively, that included the emergence of antiviral resistance. The perspective of this economic evaluation was the Taiwan health‐care system. Costs and benefits were discounted at 3% per annum.

Results:  Short‐course therapies of up to 1‐year treatment had limited impact on improving patient survival. Long‐term viral suppression with lamivudine and adefovir sequential rescue therapies (including add‐on therapies) for up to 5 years were found to be highly cost‐effective by international standards (estimated to be NT$580 000 per quality adjusted life year [QALY] for Taiwan). When Taiwan‐specific model inputs were used for HBeAg‐positive CHB, the cost per QALY for lamivudine plus adefovir sequential antiviral therapy increased by approximately 100% over the base‐case estimate, but was still well within the estimated NT$580 000 per QALY threshold.

Conclusions:  In Taiwan, treatment of CHB patients with lamivudine and adefovir sequential antiviral therapies for up to 5 years results in survival benefits and is highly cost‐effective.
Hepatitis B virus/hepatitis C virus coinfection: Epidemiology, clinical features, viral interactions and treatment
Authors: Chu Chi‐Jen , Lee Shou‐Dong
Published: April 2008

Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia–Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow‐up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<104 IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant “flare” of hepatitis activity may cause liver function deterioration. For coinfected patients with dually‐active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.
Involvement of the ABC transporter BcAtrB and the laccase BcLCC2 in defence of Botrytis cinerea against the broad‐spectrum antibiotic 2,4‐diacetylphloroglucinol
Authors: Schouten Alexander , Maksimova Olesya , Cuesta‐Arenas Yaite , Van Den Berg Grardy , Raaijmakers Jos M.
Published: April 2008

The genetic and biochemical basis of defence mechanisms in plant pathogenic fungi against antifungal compounds produced by antagonistic microorganisms is largely unknown. The results of this study show that both degradative and non‐degradative defence mechanisms enable the plant pathogenic fungus Botrytis cinerea to resist the broad‐spectrum, phenolic antibiotic 2,4‐diacetylphloroglucinol (2,4‐DAPG). The efflux pump BcAtrB provides the first line of defence for B. cinerea, preventing accumulation of 2,4‐DAPG in the cell to toxic concentrations, whereas the extracellular laccase BcLCC2 mediates, via conversion of tannic acid, subsequent degradation of 2,4‐DAPG. Expression of BcatrB is induced by 2,4‐DAPG and efflux gives B. cinerea sufficient time to more effectively initiate the process of BcLCC2‐mediated antibiotic degradation. This is supported by the observations that the BcatrB mutant is significantly more sensitive to 2,4‐DAPG than its parental strain, and is substantially less effective in 2,4‐DAPG degradation. The results of this study further showed that BcLCC2 itself is not able to degrade 2,4‐DAPG, but requires tannic acid as a mediator for 2,4‐DAPG degradation. To our knowledge, this is the first time that the laccase‐mediator system is shown to play a role in the detoxification of a broad‐spectrum antibiotic compound from bacterial origin. We postulate that yet unknown constituents present in tannic acid act as substrate(s) of BcLCC2, thereby generating radicals that mediate 2,4‐DAPG degradation.
A novel platform for biologically active recombinant human interleukin‐13 production
Authors: Wang David J. , Brandsma Martin , Yin Ziqin , Wang Aiming , Jevnikar Anthony M. , Ma Shengwu
Published: April 2008

Interleukin‐13 (IL‐13) is a pleiotropic regulatory cytokine with the potential for treating several human diseases, including type‐1 diabetes. Thus far, conventional expression systems for recombinant IL‐13 production have proven difficult and are limited by efficiency. In this study, transgenic plants were used as a novel expression platform for the production of human IL‐13 (hIL‐13). DNA constructs containing hIL‐13 cDNA were introduced into tobacco plants. Transcriptional expression of the hIL‐13 gene in transgenic plants was confirmed by reverse transcriptase‐polymerase chain reaction and Northern blotting. Western blot analysis showed that the hIL‐13 protein was efficiently accumulated in transgenic plants and present in multiple molecular forms, with an expression level as high as 0.15% of total soluble protein in leaves. The multiple forms of plant‐derived recombinant hIL‐13 (rhIL‐13) are a result of differential N‐linked glycosylation, as revealed by enzymatic and chemical deglycosylation, but not of disulphide‐linked oligomerization. In vitro trypsin digestion indicated that plant rhIL‐13 was more resistant than unglycosylated control rhIL‐13 to proteolysis. The stability of plant rhIL‐13 to digestion was further supported with simulated gastric and intestinal fluid digestion. In vitro bioassays using a factor‐dependent human erythroleukaemic cell line (TF‐1 cells) showed that plant rhIL‐13 retained the biological functions of the authentic hIL‐13 protein. These results demonstrate that transgenic plants are superior to conventional cell‐based expression systems for the production of rhIL‐13. Moreover, transgenic plants synthesizing high levels of rhIL‐13 may prove to be an attractive delivery system for direct oral administration of IL‐13 in the treatment of clinical diseases such as type‐1 diabetes.
Social Desirability of Earnings Tests
Authors: Cremer Helmuth , Pestieau Pierre , Lozachmeur Jean-Marie
Published: April 2008

In many countries, pension systems involve some form of earnings test; i.e. an individual’s benefits are reduced if he has labor income. This paper examines whether or not such earnings tests emerge when pension system and income tax are optimally designed. We use a simple model with individuals differing both in productivity and in their health status. The working life of an individual has two ‘endings’: an official retirement age at which he starts drawing pension benefits (while possibly supplementing them with some labor income) and an effective age of retirement at which professional activity is completely given up. Weekly work time is endogenous, but constant in the period before official retirement and again constant (but possibly at a different level), after official retirement. Earnings tests mean that earnings are subject to a higher tax after official retirement than before.We show under which conditions earnings tests emerge both under a linear and under a non-linear tax scheme. In particular, we show that earnings tests will occur if heterogeneities in health or productivity are more significant after official retirement than before.
Local Currency Pricing versus Producer Currency Pricing: Direct Evidence from German Exporters
Authors: Fendel Ralf , Swonke Christoph , Frenkel Michael
Published: April 2008

In new open-economy macroeconomic models, the assumption on the pricing behavior of firms in international trade plays a central role. Whether firms apply producer currency pricing (PCP) or local currency pricing (LCP) crucially affects, for example, the design of optimal monetary policy or the choice of the optimal exchange rate system. However, empirical evidence has so far been mixed and is furthermore mostly of an indirect nature. This paper draws direct evidence on the price-setting behavior of German exporters from a questionnaire-based survey. We find that PCP applies in more integrated markets. Differences between LCP firms and PCP firms mainly exist with respect to the use of mark-ups and in the validity of the law of one price for their respective products.
Return Guarantees with Delayed Payment
Authors: Mahayni Antje B. , Sandmann Klaus
Published: April 2008

A unit-linked insurance contract can be formulated in terms of a guaranteed amount together with a fraction of a positive excess return of a benchmark portfolio. Normally, the excess return is determined annually and accumulated until the maturity of the contract. The accumulation factor that is granted with respect to the delayed payments can either be deterministic or equal to the (stochastic) bank account. It turns out that the common choice of a deterministic accumulation factor gives rise to problems concerning the pricing and the risk management of the insurance contract.
An Assessment of Bank Merger Success in Germany
Authors: Koetter Michael
Published: April 2008

German banks have experienced a merger wave since the early 1990s. However, the success of bank mergers remains a continuous matter of debate.This paper suggests a taxonomy to evaluate post-merger performance on the basis of cost and profit efficiency (CE and PE). I identify successful mergers as those that fulfill simultaneously two criteria. First, merged institutes must exhibit efficiency levels above the average of non-merging banks. Second, banks must exhibit efficiency changes between merger and evaluation year above efficiency changes of nonmerging banks. I assess the post-merger performance up to 11 years after the mergers and relate it to the transfer of skills, the adequacy to merge distressed banks and the role of geographical distance. Roughly every second merger is a success in terms of either CE or PE. The margin of success in terms of CE is narrow, as efficiency differentials between merging and non-merging banks are around 1 and 2 percentage points. PE performance is slightly larger. More importantly, mergers boost in particular the change in PE, thus indicating persistent improvements of merging banks to improve the ability to generate profits.
Nordic policies on active ageing in the labour market and some European comparisons
Authors: Piekkola Hannu
Published: April 2008

Nordic countries have implemented general programmes for active ageing and well‐being in the workplace, promoted by tripartite cooperation between employees, employers and the state. The purpose for this is to influence work practices, which are seen as a natural extension of the wide coverage of health services provided for workers. Employers, particularly in the public sector, are starting to respond positively to age‐management principles, given the anticipated future labour shortages. Active ageing policies in Nordic countries and in Finland, in particular, may show the way for the whole of Europe, although they have so far been strictly limited to labour market issues.
Ideas and policies on active ageing in Norway and the UK
Authors: Ervik Rune , Helgøy Ingrid , Christensen Dag Arne
Published: April 2008

This article raises two questions: first, which active ageing ideas and policies/programmes can be identified in Norway and the UK? Second, do the two countries act differently, and if so why? The analysis is divided into four parts. First, we formulate an institutional framework for analysing active ageing policies. We then briefly map the demographic and social challenges in both Norway and the UK. The third part presents an empirical description of active ageing ideas and policies in the two countries. Finally, the findings are discussed and conclusions drawn. Based on secondary literature and commissioned reports in both countries, country‐specific statistics, interviews with Norwegian key policy actors, and a Norwegian expert panel debate, the article demonstrates that Norway and the UK belong to different types of welfare states and political economies and consequently adhere to and promote different conceptualisations and policies of active ageing. However, the analysis also finds parallel policy positions in terms of an increasing focus on the labour market and activation measures and a stronger normative linkage between contributions and benefits. These policy developments indicate that we also have to take into consideration the diffusion of ideas, ideologies, and policy solutions across national boundaries. In addition, institutional landscapes may change.
Reforming European pension systems for active ageing
Authors: Hinrichs Karl , Aleksandrowicz Paula
Published: April 2008

The article explores the trend towards early exit that has established itself over the last decades in most European countries, and the policies that 10 countries (Austria, Finland, France, Germany, Italy, Norway, Poland, Switzerland, the Czech Republic, and the UK) have developed to tackle that problem. The research question is whether those reforms contribute to active ageing. The authors also analyse factors that may foster or hinder the success of pension reforms in achieving higher effective retirement ages. Among those factors, individual workers' retirement preferences, company policies, and general employment levels are of particular importance.
Towards a “society for all ages”: meeting the challenge or missing the boat
Authors: Zelenev Sergei
Published: April 2008

This article explores the evolution of thinking and conceptual approaches to ageing in the context of intergovernmental processes. The author argues that uneven progress on the road towards achieving a society for all ages has been largely the result of capacity constraints to mainstreaming ageing and implementing ageing‐specific policies at the national level. Issues of empowerment of older persons and protection of their dignity and human rights are crucial in this context.
Governance and poverty in sub‐Saharan Africa: rethinking best practices in migration management
Authors: Truong Thanh‐Dam
Published: April 2008

This article explores the interface between migration and human trafficking in sub‐Saharan Africa fromthe two angles of governance and poverty. A salient feature in the emerging frameworks of migration management is its implicit bifurcated vision of mobility. Trade‐connected mobility is well protected by government rules whereas mobility to sustain livelihoods is subject to a punitive regime with a limited scope for resolving the discrepancy between the legal and social interpretations of human rights and well‐being. The rise of migration by women, children and young people within and outside traditional practices under risky conditions may reflect deeper structural transformations than are commonly acknowledged by policy‐makers. Reactions based on human rights concerns have contributed to new international, regional and national legislative frameworks for preventing abusive and exploitative practices in migration. The prevalence of glaring differences of interests in the variant policy approaches to all these issues – migration management, crime control, labour standards, poverty reduction and the particular needs of communities at risk – requires the concept of best practices to address the relationship between dominant forms of social knowledge and the policy field to situate and tackle issues of rights violation in different scales of governance and their interrelationships.
Comparative capitalism and sustainable development: Stakeholder capitalism and co‐management in the Kenyan fisheries sub sector
Authors: Obote Ochieng Cosmas Milton
Published: April 2008

This paper argues that stakeholder capitalism is more appropriate to natural resource management and rural development in Africa than other varieties of capitalism. It examines different management arrangements in Kenyan Lake Victoria fisheries resources to argue that whilst stakeholder capitalism is still far from being the mainstream model of capitalism in Kenya, theoretically and empirically, it is more appropriate to sustainable development than the Anglo‐Saxon variety of capitalism that the country inherited from its British colonizers. The paper demonstrates that the concepts of ownership and management rights are social, economic and political constructs that are continuously contested, with huge implications for sustainable development and natural resource management.
Protecting the environment through public procurement: The case of South Africa
Authors: Bolton Phoebe
Published: April 2008

This article deals with the use of the procurement or purchasing power of governments to protect the environment. The focus is on South Africa and the aim is to show that South African organs of state can use procurement as an environmental policy tool to contribute to sustainable development as they have commendably done so to address past discriminatory policies and practices. It is argued that such use does not fall outside the current legislative framework governing procurement and suggestions are made as to how environmental considerations could be incorporated throughout the procurement process, namely the preparatory stage; the drawing up of tender or technical specifications; ensuring the capability or responsibility of contractors; the use of criteria to compare different tenders; and ensuring that eventual performance under a contract is environmentally sound.
Toward an improved legislative framework for China's land degradation control
Authors: Ke Zhou , Xia Cao , Baiping Tan
Published: April 2008

The Chinese government has recently been attaching increasing importance to the application of effective legal tools to tackle land degradation (LD) issues. Based on the concept of sustainable development, China began developing and reaping the benefits of environmental and natural resources legislation including LD control regulations in the 1990s. In the past three years, some central‐western provinces in China have been implementing a “

People's Republic of China/Global Environment Facility (PRC/GEF

) Partnership on LD Control of Dryland Ecosystems”, which is based on an integrated ecosystem management (IEM) approach. IEM is designed to achieve a balanced, scientific and participatory approach to natural resources management, which creates the potential to improve the quality of Chinese environmental law and policy procedures. The paper studies the existing Chinese national laws and regulations pertinent to LD control within 9 areas covering land, desertification, soil erosion, grassland, forest, water, agriculture, wild animals and plants, and environment protection in detail, against IEM principles and basic legal elements. The main objective is to identify problems and provide feasible solutions and recommendations for the improvement of the existing laws and regulations. The authors conclude that the development of an improved national legislative framework is essential if LD control is to be successfully achieved. The paper is partly based on Component 1 — Improving Policies, Laws and Regulations for Land Degradation Control under PRC/GEF Partnership on Land Degradation in Dryland Ecosystems (TA 4357).