bluuebunny/crossref_metadata_2025 huggingface dataset:
Non–SCF-type F-box protein Roy1/Ymr258c interacts with a Rab5-like GTPase Ypt52 and inhibits Ypt52 function
Authors: Liu Yuan , Nakatsukasa Kunio , Kotera Michiko , Kanada Akira , Nishimura Takashi , Kishi Tsutomu , Mimura Satoru , Kamura Takumi
Published: March 2011

Skp1/Cul1/F-box (SCF)–type F-box proteins are a component of the Cullin-RING SCF ubiquitin E3 ligase, which is involved in numerous cellular processes. However, the function of non–SCF-type F-box proteins remains largely unknown. The Rab5-like small guanosine 5′-triphosphatase Vps21/Ypt51 is a key regulator of intracellular transportation; however, deletion of its isoforms, Ypt52 and Ypt53, results in only a modest inhibition of intracellular trafficking. The function of these proteins therefore remains largely elusive. Here we analyze the role of a previously uncharacterized non–SCF-type F-box protein, Roy1/Ymr258c, in cell growth and intracellular transport in Saccharomyces cerevisiae. Roy1 binds to Ypt52 under physiological conditions, and Skp1 is indispensable for the association of Roy1 with Ypt52. The vps21Δ yeast cells exhibit severe deficiencies in cell growth and intracellular trafficking, whereas simultaneous deletion of roy1 alleviates the defects caused by deletion of vps21. However, additional disruption of ypt52 in roy1Δvps21Δ cells largely suppresses the cell growth and trafficking observed in roy1Δvps21Δ cells. We demonstrate that Roy1 interacts with guanosine 5′-diphosphate–bound and nucleotide-free Ypt52 and thereby inhibits the formation of guanosine 5′-triphosphate–bound, active Ypt52. These results thus indicate that Roy1 negatively modulates cell viability and intracellular transport by suppressing Ypt52.
Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of β-arrestin2
Authors: Yin Chenlei , Zhang Ru , Xu Yongyu , Chen Qiuyan , Xie Xin
Published: March 2011

β-arrestins are well known for their roles in desensitization and sequestration of G protein–coupled receptors. Unlike β-arrestin1, β-arrestin2 exhibits a predominant cytoplasmic distribution at steady state. However, the mechanism and functional significance underlying the regulation of β-arrestin2 subcellular localization remains undefined. Here we report that the subcellular localization and function of β-arrestin2 is tightly regulated by Mdm2 E3 ligase activity. Inhibition of Mdm2 E3 ligase activity either by expressing Mdm2 RING finger mutants or using specific Mdm2 E3 ligase inhibitor is sufficient to stabilize the Mdm2/β-arrestin2 complex and cause abnormal nuclear localization of β-arrestin2. Next we demonstrate that lysine residues at position 11 and 12 of β-arrestin2 are required for the interaction between Mdm2 RING finger mutant H457S (Mdm2H457S) and β-arrestin2, mutation of which prevents Mdm2H457S/β-arrestin2 interaction and subsequent nuclear localization of β-arrestin2. Finally, β-arrestin2–dependent signalings, such as receptor internalization and extracellular signal–regulated protein kinase activation, are found to be impaired once the β-arrestin2 is sequestered in the nuclei by Mdm2H457S. Our findings depict the essential role of Mdm2 E3 ligase activity in determining β-arrestin2 subcellular localization and corresponding signaling.
The Economics of Grain Price Volatility
Authors: Wright Brian D.
Published: March 2011

Recent volatility of prices of major grains has generated a wide array of analyses and policy prescriptions that reveal the inability of economists to approach a consensus on the nature of the phenomenon and its implications for policy. This review of market events and their economic interpretations finds that recent price spikes are not as unusual as many discussions imply. Further, the balance between consumption, available supply, and stocks seems to be as relevant for our understanding of these markets as it was decades ago. Though there is much to be learned about commodity markets, the tools at hand are capable of explaining the main forces at work, and of giving good guidance to policymakers confronted with a bewildering variety of expensive policy prescriptions.
Uncertainties in projecting spatial distributions of marine populations
Authors: Planque Benjamin , Bellier Edwige , Loots Christophe
Published: March 2011

Planque, B., Bellier, E., and Loots, C. 2011. Uncertainties in projecting spatial distributions of marine populations. – ICES Journal of Marine Science, 68: 1045–1050. Projection of future spatial distributions of marine populations is a central issue for ecologists and managers. The measure of projection uncertainty is particularly important, because projections can only be useful if they are given with a known and sufficiently high level of confidence. Uncertainties can arise for the observation process, conceptual and numerical model formulations, parameter estimates, model evaluation, appropriate consideration of spatial and temporal scales, and finally the potential of adaptation of living systems. Comprehensive analyses of these multiple sources of uncertainty have not been carried out so far, and how these uncertainties are considered in current studies has not yet been described. To analyse how these different sources of uncertainty are currently considered in marine research, we did a survey of published literature during the period 2005–2009. From the 75 publications selected, we calculated how frequently each type of uncertainty was considered. We found that little attention is given to most sources of uncertainty, except for uncertainty in parameter estimates. As a result, most current projections are expected to be far less reliable than usually assumed. The conclusion is that, unless uncertainty can be better accounted for, such projections may be of limited use, or even risky to use for management purposes.
A general equilibrium model for Atlantic herring (Clupea harengus) with ecosystem considerations
Authors: Kirkley James E. , Walden John , Färe Rolf
Published: March 2011

Kirkley, J. E., Walden, J., and Färe, R. 2011. A general equilibrium model for Atlantic herring (Clupea harengus) with ecosystem considerations. – ICES Journal of Marine Science, 68: 860–866. A framework is presented for assessing the economic ramifications of ecosystem-based management decisions, with attention focused on Atlantic herring (Clupea harengus) in New England. The Atlantic herring has often been referred to as the most important fish in the northeastern United States because it is a filter-feeder, is believed to improve water quality, and is very important to the health, growth, and abundance of major gamefish, marine mammals, seabirds, and several species of fish. Although many approaches for examining the potential economic ramifications of ecosystem-based management are possible, attention is focused on one method that can be used given existing data. A static, deterministic input/output (I/O) optimization (IOLP, input/output linear programming) model is developed that breaks out the impact of different decisions on herring allocation on the 2006 New England regional economy of Maine, New Hampshire, Massachusetts, and Rhode Island. The IOLP model is a promising approach for informing policy-makers of the economic implications of various allocation choices. The framework is also flexible enough to allow further disaggregation of the small model presented to include additional fishing and non-fishing sectors.
Genetic Diversity in the 3′ Terminal 4.7-kb Region of Grapevine leafroll-associated virus 3
Authors: Wang Jinbo , Sharma Abhineet M. , Duffy Siobain , Almeida Rodrigo P. P.
Published: March 2011

Grapevine leafroll-associated virus 3 (GLRaV-3; Ampelovirus, Closteroviridae), associated with grapevine leafroll disease, is an important pathogen found across all major grape-growing regions of the world. The genetic diversity of GLRaV-3 in Napa Valley, CA, was studied by sequencing 4.7 kb in the 3′ terminal region of 50 isolates obtained from Vitis vinifera ‘Merlot’. GLRaV-3 isolates were subdivided into four distinct phylogenetic clades. No evidence of positive selection was observed in the data set, although neutral selection (ratio of nonsynonymous to synonymous substitution rates = 1.1) was observed in one open reading frame (ORF 11, p4). Additionally, the four clades had variable degrees of overall nucleotide diversity. Moreover, no geographical structure among isolates was observed, and isolates belonging to different phylogenetic clades were found in distinct vineyards, with one exception. Considered with the evidence of purifying selection (i.e., against deleterious mutations), these data indicate that the population of GLRaV-3 in Napa Valley is not expanding and its effective population size is not increasing. Furthermore, research on the biological characterization of GLRaV-3 strains might provide valuable insights on the biology of this species that may have epidemiological relevance.
Toll-Like Receptor 4 Inhibitor TAK-242 Attenuates Acute Kidney Injury in Endotoxemic Sheep
Authors: Fenhammar Johan , Rundgren Mats , Forestier Jakob , Kalman Sigridur , Eriksson Stefan , Frithiof Robert
Published: March 2011

Background

This study was conducted to investigate the role of toll-like receptor 4 (TLR4) in mediating acute kidney injury in endotoxemic sheep using the selective TLR4 inhibitor TAK-242.

Methods

A randomized, controlled, experimental study was performed with 20 adult Texel crossbred sheep. Before an Escherichia coli lipopolysaccharide infusion (3 μg · kg(-1) · h(-1) for 24 h), sheep were randomized to receive a bolus dose (2 mg/kg), followed by a continuous infusion (4 mg · kg(-1) · 24 h(-1)) of either TAK-242 (n = 7) or vehicle (n = 7). A third group of lipopolysaccharide-treated sheep (n = 6) received norepinephrine, titrated to maintain baseline arterial blood pressure.

Results

Endotoxin infusion established a state of hyperdynamic circulation, with an increased cardiac index, hypotension, and tachycardia. Urine output and creatinine clearance decreased throughout the experiment, together with increasing plasma creatinine, blood urea nitrogen, and arterial lactate concentrations. After 24 h, TLR4 inhibition had significantly (P ≤ 0.001) attenuated the mean ± SEM decrease in arterial pressure (97 ± 3 vs. 71 ± 4 mmHg), urine output (1.16 ± 0.15 vs. 0.13 ± 0.05 ml · kg(-1) · h(-1)), and creatinine clearance (126 ± 13 vs. 20 ± 7 ml/min) compared with vehicle-treated animals. Furthermore, arterial lactate, plasma creatinine, and blood urea nitrogen concentrations were significantly lower in the TAK-242 group versus the vehicle-treated animals. Compared with TLR4 inhibition, norepinephrine caused similar effects on arterial pressure, cardiac index, and heart rate; however, it did not attenuate the decrease in urine output or creatinine clearance.

Conclusions

These results indicate a critical role for TLR4 in impairing renal function during ovine endotoxemia that is independent of changes in central hemodynamics.
Cytokine signatures of transformed B cells with distinct Epstein–Barr virus latencies as a potential diagnostic tool for B cell lymphoma
Authors: Miyauchi Kosuke , Urano Emiko , Yoshiyama Hironori , Komano Jun
Published: March 2011

Immunocompromised individuals, including those infected with human immunodeficiency virus (HIV), are at increased risk of Epstein–Barr virus (EBV)‐associated aggressive B cell malignancies such as Burkitt’s lymphoma (BL) or diffuse large B cell lymphoma (DLBCL). Differential diagnosis of these lymphomas requires histopathological, immunohistochemical and cytogenetic assessments. Rapid, less invasive approaches to the diagnosis of EBV‐associated B cell lymphomas are needed. Here, high‐throughput cytokine profiling of BL cell lines and EBV‐transformed B lymphoblastoid cell lines (B‐LCL), representing DLBCL, was carried out. By monitoring the production of 42 different cytokines, unique cytokine signatures were identified for BL and B‐LCL/DLBCL. The BL cells produced interleukin (IL)‐10, 10 kDa interferon gamma‐induced protein (IP‐10)/CXCL10, macrophage‐derived chemokine (MDC)/CCL22, macrophage inflammatory protein (MIP)‐1α/CCL3 and MIP‐1β/CCL4. In addition to these five cytokines, the cytokine signature of B‐LCL/DLBCL cells included IL‐8/CXCL8, IL‐13, platelet‐derived growth factor (PDGF)‐AA, and regulated upon activation, normal T cell expressed and secreted (RANTES)/CCL5. Epstein–Barr virus latency was responsible for the increased production of IL‐10, MDC/CCL22 and MIP‐1α/CCL3 in BL cells, suggesting that EBV‐mediated BL‐genesis involves these three cytokines. These results suggest that high‐throughput cytokine profiling might be a valuable tool for the differential diagnosis and might deepen our understanding of the pathogenesis of EBV‐associated B cell malignancies. (Cancer Sci 2011; 102: 1236–1241)
Fertility considerations and preservation in haemato‐oncology patients undergoing treatment
Authors: Leader Avi , Lishner Michael , Michaeli Jennia , Revel Ariel
Published: March 2011

The improved survival rates among patients with haematological malignancies, such as lymphoma and leukaemia, are shifting areas of focus towards understanding and preventing treatment‐induced sequelae. Of these, infertility is one of the most devastating consequences for patients with reproductive potential. The degree of treatment‐induced gonadal dysfunction depends on age and gender‐related differences, the type and dosage of chemotherapy used and the field and cumulative dose of abdomino‐pelvic irradiation. There is also the interesting phenomenon of reduced pre‐treatment fertility among male lymphoma patients. At present, the only established methods of fertility preservation are cryopreservation of sperm, oocytes and embryos, as well as gonadal shielding and transposition of ovaries during irradiation. Several other methods, such as cryopreservation and subsequent transplantation of gonadal tissue and the gonadoprotective role of hormonal suppression, are under investigation. Pre‐pubertal patients present a unique constellation of fertility considerations, especially as embryo and sperm cryopreservation are not applicable to this age group.
Human immunodeficiency virus associated thrombotic thrombocytopenic purpura – favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy
Authors: Hart Daniel , Sayer Ruth , Miller Robert , Edwards Simon , Kelly Anne , Baglin Trevor , Hunt Beverley , Benjamin Sylvia , Patel Raj , Machin Samuel , Scully Marie
Published: March 2011

Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder. Human immunodeficiency virus (HIV) is an identified precipitant. This study reviewed 30 episodes of HIV‐associated TTP in 24 patients from the South‐East England Apheresis units, over the last 10 years. All patients were heterosexual Black Africans. First presentation of TTP revealed a new diagnosis of HIV in eight patients. TTP relapse occurred on six occasions (in four patients) as a result of non‐adherence to highly active antiretroviral therapy (HAART). Prompt initiation/re‐initiation of HAART in parallel with plasma exchange (PEX) ± steroid led to prompt remission. Adjunct immunomodulatory agents (e.g. Rituximab) were required in 10% of cases. Once‐daily HAART regimens are recommended, being compatible with PEX requirement, maximizing drug exposure between PEX. High viral loads (>500 000 copies/ml) require more PEX to remission. ADAMTS13 activity was reduced (<5%) as detected by collagen‐binding assay and anti‐ADAMTS13 immunoglobulin G antibodies were raised in 80%. Continued HAART‐adherence ensured a durable TTP remission with associated viral control resulting in no evidence of relapse. PEX and HAART are associated with replenishment of ADAMTS13 and viral suppression. More PEX is required in cases with higher viral loads. Continued HAART maintains remission. In a small proportion of cases, further immunomodulatory therapy may be required.
Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome
Authors: Alecsandru D , Valor L , Sánchez-Ramón S , Gil J , Carbone J , Navarro J , Rodríguez J J , Rodríguez-Sainz C , Fernández-Cruz E
Published: March 2011

Recurrent respiratory tract infections (RRTIs) are common clinical conditions in individuals with alterations of the immune function. A prospective open pilot study in a cohort of patients with RRTIs has been performed to assess whether sublingual immunization with a polyvalent bacterial vaccine could exert an immunomodulatory effect on the antigen-specific immunological responses and have an impact on the clinical outcome. Seventeen patients with RRTIs were recruited. An oral polyvalent bacterial preparation (Bactek®) was administered to all patients daily for 6 months. Immunological assessment was performed at baseline and at the end of immunization. Immunological measurements included: T cell-specific proliferations of CD3+CD4+ and CD3+CD8+ to Bactek® antigens, total immunoglobulin levels, antibodies to pneumococcal polysaccharide and tetanus toxoid and B, T and natural killer (NK) cell subsets. There was a significant increase in the proliferative capacity of CD3+CD4+ T cells specific to Bactek® antigens at month 6 in comparison to baseline (P < 0·0001). A significant increase in total CD3+ T cells was also observed (P < 0·05). No significant differences were observed between baseline and month 6 in levels of total immunoglobulins, specific antibodies and B, T or NK cell subsets. A significant reduction in the patient's rate of RRTIs was observed compared with 1 year prior to initiation of therapy (P < 0·0001). The results demonstrate that long-term administration of a sublingual polyvalent bacterial preparation in patients with RRTIs exerts an immune stimulating effect on CD4+ T helper cell responses to bacterial antigens which could be associated with clinical benefit.
Ursolic acid promotes robust tolerance to cardiac allografts in mice
Authors: Liu Y , Huang X , Li Y , Li C , Hu X , Xue C , Meng F , Zhou P
Published: March 2011

Nuclear factor (NF)-κB is an important molecule in T cell activation. Our previous work has found that T cell-restricted NF-κB super-repressor (IκBαΔN-Tg) mice, expressing an inhibitor of NF-κB restricted to the T cell compartment, can permanently accept fully allogeneic cardiac grafts and secondary donor skin grafts. In this study, we explore if transient NF-κB inhibition by a small molecular inhibitor could induce permanent graft survival. Ursolic acid, a small molecular compound, dose-dependently inhibited T cell receptor (TCR)-triggered NF-κB nuclear translocation and T cell activation in vitro. In vivo, ursolic acid monotherapy prolonged significantly the survival of cardiac allograft in mice. Assisted with donor-specific transfusion (DST) on day 0, ursolic acid promoted 84·6% of first cardiac grafts to survive for more than 150 days. While the mice with long-term surviving grafts (LTS) did not reject the second donor strain hearts for more than 100 days without any treatment, they all promptly rejected the third-party strain hearts within 14 days. Interestingly, this protocol did not result in an increased proportion of CD4+CD25+forkhead box P3+ regulatory T cells in splenocytes. That adoptive transfer experiments also did not support regulation was the main mechanism in this model. Splenocytes from LTS showed reduced alloreactivity to donor antigen. However, depletion of CD4+CD25+ regulatory T cells did not alter the donor-reactivity of LTS splenocytes. These data suggest that depletion of donor-reactive T cells may play an important role in this protocol.
Pentraxin 3 (PTX3) is associated with cardiovascular risk factors: the Health 2000 Survey
Authors: Jylhävä J , Haarala A , Kähönen M , Lehtimäki T , Jula A , Moilanen L , Kesäniemi Y A , Nieminen M S , Hurme M
Published: March 2011

Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in individuals with cardiovascular disease (CVD). Despite being a member of the same pentraxin protein family as C-reactive protein (CRP), PTX3 probably reflects different aspects of CVD pathogenesis. In this study, we assessed plasma PTX3 correlates and determinants in the Health 2000 Survey population, which comprised n = 403 insulin-resistant subjects, n = 845 hypercholesterolaemic subjects and n = 311 hypertensive subjects, all aged between 46 and 76 years. In insulin-resistant subjects the PTX3 concentration was found to correlate directly with age, pulse pressure and indoleamine 2,3-dioxygenase (IDO) enzyme activity and inversely with total and low-density lipoprotein (LDL) cholesterol. In hypercholesterolaemic subjects, the PTX3 concentration correlated directly with HDL cholesterol, systolic blood pressure and pulse pressure, whereas in hypertensive subjects, the PTX3 concentration correlated directly with systolic blood pressure, pulse pressure and IDO activity. No correlation was observed between the concentrations of PTX3 and CRP, adiposity indicators or indicators of subclinical atherosclerosis in any of the subject groups. PTX3 concentration variations were attributed to variations in LDL cholesterol and IDO activity in insulin-resistant subjects and to pulse pressure in hypercholesterolaemic and hypertensive subjects. These results indicate that, in individuals at high risk of CVD, the PTX3 concentration is associated with cardiovascular risk factors but not with subclinical atherosclerosis.
Activation of natural killer T cells by α-carba-GalCer (RCAI-56), a novel synthetic glycolipid ligand, suppresses murine collagen-induced arthritis
Authors: Yoshiga Y , Goto D , Segawa S , Horikoshi M , Hayashi T , Matsumoto I , Ito S , Taniguchi M , Sumida T
Published: March 2011

Alpha-carba-GalCer (RCAI-56), a novel synthetic analogue of α-galactosylceramide (α-GalCer), stimulates invariant natural killer T (NK T) cells to produce interferon (IFN)-γ. IFN-γ exhibits immunoregulatory properties in autoimmune diseases by suppressing T helper (Th)-17 cell differentiation and inducing regulatory T cells and apoptosis of autoreactive T cells. Here, we investigated the protective effects of α-carba-GalCer on collagen-induced arthritis (CIA) in mice. First, we confirmed that α-carba-GalCer selectively induced IFN-γ in CIA-susceptible DBA/1 mice in vivo. Then, DBA/1 mice were immunized with bovine type II collagen (CII) and α-carba-GalCer. The incidence and clinical score of CIA were significantly lower in α-carba-GalCer-treated mice. Anti-IFN-γ antibodies abolished the beneficial effects of α-carba-GalCer, suggesting that α-carba-GalCer ameliorated CIA in an IFN-γ-dependent manner. Treatment with α-carba-GalCer reduced anti-CII antibody production [immunoglobulin (Ig)G and IgG2a] and CII-reactive interleukin (IL)-17 production by draining lymph node (DLN) cells, did not induce apoptosis or regulatory T cells, and significantly increased the ratio of the percentage of IFN-γ-producing T cells to IL-17-producing T cells (Th1/Th17 ratio). Moreover, the gene expression levels of IL-6 and IL-23p19, Th17-related cytokines, were reduced significantly in mice treated with α-carba-GalCer. In addition, we observed higher IFN-γ production by NK T cells in α-carba-GalCer-treated mice in the initial phase of CIA. These findings indicate that α-carba-GalCer polarizes the T cell response toward Th1 and suppresses Th17 differentiation or activation, suggesting that α-carba-GalCer, a novel NK T cell ligand, can potentially provide protection against Th17-mediated autoimmune arthritis by enhancing the Th1 response.
Modulation of M2 muscarinic receptor–receptor interaction by immunoglobulin G antibodies from Chagas' disease patients
Authors: Beltrame S P , Auger S R , Bilder C R , Waldner C I , Goin J C
Published: March 2011

Circulating immunoglobulin (Ig)G antibodies against M2 muscarinic acetylcholine receptors (M2 mAChR) have been implicated in Chagas' disease (ChD) pathophysiology. These antibodies bind to and activate their target receptor, displaying agonist-like activity through an unclear mechanism. This study tested the ability of serum anti-M2 mAChR antibodies from chronic ChD patients to modulate M2 muscarinic receptor–receptor interaction by bioluminescence resonance energy transfer (BRET). Human embryonic kidney (HEK) 293 cells co-expressing fusion proteins M2 mAChR-Renilla luciferase (RLuc) and M2 mAChR-yellow fluorescent protein (YFP) were exposed to the serum IgG fraction from ChD patients, and BRET between RLuc and YFP was assessed by luminometry. Unlike serum IgG from healthy subjects and conventional muscarinic ligands, ChD IgG promoted a time- and concentration-dependent increase in the BRET signal. This effect neither required cellular integrity nor occurred as a consequence of receptor activation. Enhancement of M2 receptor–receptor interaction by ChD IgG was receptor subtype-specific and mediated by the recognition of the second extracellular loop of the M2 mAChR. The monovalent Fab fragment derived from ChD IgG was unable to reproduce the effect of the native immunoglobulin. However, addition of ChD Fab in the presence of anti-human Fab IgG restored BRET-enhancing activity. These data suggest that the modulatory effect of ChD IgG on M2 receptor–receptor interaction results from receptor cross-linking by bivalent antibodies.
Agrobacterium‐mediated transformation of the barley pathogen Ramularia collo‐cygni with fluorescent marker tags and live tissue imaging of infection development
Authors: Thirugnanasambandam A. , Wright K. M. , Havis N. , Whisson S. C. , Newton A. C.
Published: March 2011

Ramularia collo‐cygni, the causal agent of ramularia leaf spot disease in barley was transformed to express the green fluorescent protein and DsRed fluorescent protein using a combined protoplast and Agrobacterium tumefaciens‐mediated transformation technique. Regenerated protoplasts from mycelial fragments were transformed with A. tumefaciens strain AGL1 containing either pCAMBgfp or pCAMBDsRed plasmids. Two different isolates of R. collo‐cygni were transformed and several stable transformants were recovered. These transformants infected detached barley leaves and characteristic swan’s‐neck‐shaped conidiophores were seen on detached leaves 9 days after inoculation, as well as spore‐like structures formed from hyphal swellings. This first successful transformation of R. collo‐cygni has enabled better description of the stages of disease development and pathogen behaviour during the endophytic/asymptomatic stage of its life cycle.
Density of CD163+CD11c+ Dendritic Cells Increases and CD103+ Dendritic Cells Decreases in the Coeliac Lesion
Authors: Beitnes A.‐C. R. , Ráki M. , Lundin K. E. A. , Jahnsen J. , Sollid L. M. , Jahnsen F. L.
Published: March 2011

Coeliac disease is a chronic inflammation of the intestinal mucosa controlled by gluten‐specific T cells restricted by disease‐associated HLA‐DQ molecules. We have previously reported that mucosal CD11c+ dendritic cells (DCs) are responsible for activation of gluten‐reactive T cells within the coeliac lesion. In mice, intestinal CD11c+ DCs comprise several functionally distinct subsets. Here, we report that HLA‐DQ+ antigen‐presenting cells (APCs) in normal human duodenal mucosa can be divided into four subsets with striking similarities to those described in mice: CD163+CD11c− macrophages (74%), and CD11c+ cells expressing either CD163 (7%), CD103 (11%) or CD1c (13%). CD103+ and CD1c+ DCs belonged to partly overlapping populations, whereas CD163+CD11c+ APCs appeared to be a distinct population. In the coeliac lesion, we found increased density of CD163+CD11c+ APCs, whereas the density of CD103+ and CD1c+ DCs was decreased, suggesting that distinct subpopulations of APCs in coeliac disease may exert different functions in the pathogenesis.
Polyphase seismic faulting in the Ivrea zone (Italian Alps) revealed by 40Ar/39Ar dating of pseudotachylytes
Authors: Souquière François , Monié Patrick , Fabbri Olivier , Chauvet Alain
Published: March 2011

Terra Nova, 23, 162–170, 2011

Most fault‐related pseudotachylytes in the Val Sesia area, Ivrea zone, NW Italian Alps, occur in two areas: near the Canavese Line in the Kinzigite Formation paragneisses and in an elongate belt in the Mafic Complex gabbros away from the Canavese Line. 40Ar/39Ar dating indicates that pseudotachylytes from the Kinzigite Formation were formed in the late Eocene, likely during the early stages of the collision between the NW corner of the Adriatic indenter and the European margin. Pseudotachylytes from the Mafic Complex were formed under a transpressive strain regime, as suggested by kinematic indicators, and yield Early Cretaceous (Albian) 40Ar/39Ar ages. Their formation is possibly related to shortening during the inception of the tectonic inversion of the Adriatic passive margin.
Stroke: a realistic approach to a growing problem in sub‐Saharan Africa is urgently needed
Authors: Kolapo Kehinde O. , Vento Sandro
Published: March 2011

Stroke is an increasing problem in sub‐Saharan Africa, even in children. High rates of hypertension, diabetes, alcohol abuse, smoking, insufficient fruit and vegetable consumption, sickle cell disease, HIV infection, antiretroviral use and race are likely contributing factors. Although often considered as related to increasing wealth, stroke is more strongly related to poverty, and in turn increases it. Case‐fatality rates are high and premature death and years of life lost are a major problem. We propose an approach to stroke prevention and treatment that takes into account the real situation on the ground and can be applied in sub‐Saharan Africa, an area where stroke units are largely not feasible and many patients do not reach hospitals. Involvement of community and faith‐based organisations, use of simple diagnostic tests, emphasis on clinical examination to differentiate between haemorrhagic and ischaemic stroke, prompt initiation of aspirin therapy and training of community nurses on essential management of stroke should be urgently implemented.
Hypertrophic scar in a dog: histological and clinical features
Authors: Avallone Giancarlo , Bonaldi Martina , Caniatti Mario , Lombardo Rocco
Published: March 2011

An adult male bullmastiff dog was treated for paraparesis and ataxia due to discospondylitis and disc herniation. At this time, the dog had a nonhealing ulcer between the pads of the left hindfoot. At re‐evaluation, the dog had developed a large exophitic mass in the previously ulcerated area. Cytological examination revealed occasional spindle cells with mild atypia, and a soft tissue tumour was suspected. The mass was excised and submitted for histology. The lesion was characterized by superficial ulceration, an intermediate layer of granulation tissue and a deep portion containing vertically orientated capillaries and perpendicularly arranged fibroblasts and collagen. The histological features led to a diagnosis of hypertrophic scar. Eight weeks after surgery, the lesion recurred and was treated with an intralesional injection of methylprednisolone acetate. The lesion regressed in 10 days, but recurred after 3 months following severe self‐trauma. Hypertrophic scars and keloids are two types of exuberant scarring reported in human beings, the pathogenesis of which is still unclear but seems to involve several cytokines, growth factors and inflammatory cells. The histological features identified in this case paralleled those reported in hypertrophic scars in humans. In this case, intralesional corticosteroid therapy was useful in the management of the lesion, but the severe self‐trauma could have influenced the recurrence. Even if uncommon, hypertrophic scar should be included among the differential diagnoses of spindle cell tumours in dogs.
Novel mutation in GLRB in a large family with hereditary hyperekplexia
Authors: Al‐Owain M , Colak D , Al‐Bakheet A , Al‐Hashmi N , Shuaib T , Al‐Hemidan A , Aldhalaan H , Rahbeeni Z , Al‐Sayed M , Al‐Younes B , Ozand PT , Kaya N
Published: March 2011

Al‐Owain M, Colak D, Al‐Bakheet A, Al‐Hashmi N, Shuaib T, l‐Hemidan A, Aldhalaan H, Rahbeeni Z, Al‐Sayed M, Al‐Younes B, Ozand PT, Kaya N. Novel mutation in GLRB in a large family with hereditary hyperekplexia.

Hereditary hyperekplexia (HH) is a disorder of the inhibitory glycinergic neurotransmitter system. Mutations in five genes have been reported to cause the disease. However, only single mutation in GLRB, the gene encoding beta‐subunit of the glycine receptor, in a singleton patient with HH has been found to date. In this study, 13 patients with HH were identified through neurology and genetic clinics. Formal clinical examinations, linkage analysis, homozygosity mapping, in‐mutation screening of GLRB and in silico functional analyses were carried out. A novel mutation in GLRB among nine patients was identified. This c.596 T>G perturbation results in the change of the highly conserved methionine at position 177 to arginine. Besides the classical HH phenotype, seven patients had esotropia and few of them had behavioral problems. This study presents a large family with HH as a result of homozygous mutation in GLRB and expands the clinical spectrum of HH to include eye misalignment disorder. Moreover, the report of these familial cases supports the previous evidence in a single patient of an autosomal recessive inheritance of HH because of defects in GLRB.
Pre‐transplant course and risk of kidney transplant failure in IgA nephropathy patients
Authors: Bjørneklett Rune , Vikse Bjørn Egil , Smerud Hilde Kloster , Bostad Leif , Leivestad Torbjørn , Hartmann Anders , Iversen Bjarne M.
Published: March 2011

Bjørneklett R, Vikse BE, Smerud HK, Bostad L, Leivestad T, Hartmann A, Iversen BM. Pre‐transplant course and risk of kidney transplant failure in IgA nephropathy patients. Clin Transplant 2011: 25: E356–E365. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  There is lack of knowledge to what degree clinical/morphological presentation and course of IgA nephropathy (IgAN) prior to end‐stage renal disease are risk factors for graft loss after kidney transplantation.

Material and Methods:  Patients with IgAN between 1988 and 2006 (registered in the Norwegian Kidney Biopsy Registry) who later received a kidney transplant (registered in the Norwegian Renal Registry) were included. The cohort was followed up regarding death‐censored graft loss throughout 2008. Graft survival with a rapid progressive (RP) vs. a slow progressive (SP) course of pre‐Tx IgAN (annual GFR > or <30 mL/min/1.73 m2) was studied.

Results:  Among 106 included patients, there were 14 graft losses giving a graft loss rate of 1.9/100 patient years. Follow‐up until the first kidney transplant was 6.9 ± 4.4 (range 0.1–19) yr. Patients with pre‐Tx RP had a higher graft loss rate compared with SP patients (6.3 vs.1.3/100 patient years, p < 0.001). Graft loss rate with living‐related donor (LRD) was similar to unrelated donor (UD) grafts. Most RP patients had received LRD grafts, and in SP patients, graft survival with LRD grafts was better than UD grafts (0.3 vs.2.1/100 patient years, p = 0.055).

Conclusions:  A rapid pre‐transplant course is a strong risk factor for transplant failure in patients with IgAN.
Living donor liver transplantation for ornithine transcarbamylase deficiency
Authors: Wakiya T. , Sanada Y. , Mizuta K. , Umehara M. , Urahasi T. , Egami S. , Hishikawa S. , Fujiwara T. , Sakuma Y. , Hyodo M. , Murayama K. , Hakamada K. , Yasuda Y. , Kawarasaki H.
Published: March 2011

Wakiya T, Sanada Y, Mizuta K, Umehara M, Urahasi T, Egami S, Hishikawa S, Fujiwara T, Sakuma Y, Hyodo M, Murayama K, Hakamada K, Yasuda Y, Kawarasaki H. Living donor liver transplantation for ornithine transcarbamylase deficiency. Pediatr Transplantation 2011: 15: 390–395. © 2011 John Wiley & Sons A/S.

Abstract:  Ornithine transcarbamylase deficiency, the most common urea cycle disorder, causes hyperammonemic encephalopathy and has a poor prognosis. Recently, LT was introduced as a radical OTCD treatment, yielding favorable outcomes. We retrospectively analyzed LT results for OTCD at our facility. Twelve children with OTCD (six boys and six girls) accounted for 7.1% of the 170 children who underwent LDLT at our department between May 2001 and April 2010. Ages at LT ranged from nine months to 11 yr seven months. Post‐operative follow‐up period was 3–97 months. The post‐operative survival rate was 91.7%. One patient died. Two patients who had neurological impairment preoperatively showed no alleviation after LT. All patients other than those who died or failed to show recovery from impairment achieved satisfactory quality‐of‐life improvement after LT. The outcomes of LDLT as a radical OTCD treatment have been satisfactory. However, neurological impairment associated with hyperammonemia is unlikely to subside even after LT. It is desirable henceforth that more objective and concrete guidelines for OTCD management be established to facilitate LDLT with optimal timing while avoiding the risk of hyperammonemic episodes.
Birt–Hogg–Dubé syndrome with a renal angiomyolipoma: Further evidence of a relationship between Birt–Hogg–Dubé syndrome and tuberous sclerosis complex
Authors: Byrne Marguerite , Mallipeddi Raj , Pichert Gabriella , Whittaker Sean
Published: March 2011

Birt‐Hogg‐Dubé syndrome (BHDS) is an autosomal dominant condition caused by mutations in the gene which codes for folliculin (FLCN). It is characterised clinically by fibrofolliculomas, trichodiscomas, pulmonary cysts, spontaneous pneumothoraces and renal cancers. This case illustrates a patient with BHDS and a renal angiomyolipoma. Angiomyolipomas are not described as a feature of BHDS, but rather they can occur sporadically or in tuberous sclerosis complex (TSC). Recent studies suggest that clinical similarities between BHDS and TSC may be explained by FLCN and TSC proteins functioning on a common pathway, mammalian target of rapamycin. This case adds to the literature of cases with clinical similarities.
Primary care practice and health professional determinants of immunisation coverage
Authors: Grant Cameron C , Petousis‐Harris Helen , Turner Nikki , Goodyear‐Smith Felicity , Kerse Ngaire , Jones Rhys , York Deon , Desmond Natalie , Stewart Joanna
Published: March 2011

Aim:  To identify primary care factors associated with immunisation coverage.

Methods:  A survey during 2005–2006 of a random sample of New Zealand primary care practices, with over‐sampling of practices serving indigenous children. An immunisation audit was conducted for children registered at each practice. Practice characteristics and the knowledge and attitudes of doctors, nurses and caregivers were measured. Practice immunisation coverage was defined as the percentage of registered children from 6 weeks to 23 months old at each practice who were fully immunised for age. Associations of practice, doctor, nurse and caregiver factors with practice immunisation coverage were determined using multiple regression analyses.

Results:  One hundred and twenty‐four (61%) of 205 eligible practices were recruited. A median (25th–75th centile) of 71% (57–77%) of registered children at each practice was fully immunised. In multivariate analyses, immunisation coverage was higher at practices with no staff shortages (median practice coverage 76% vs 67%, P= 0.004) and where doctors were confident in their immunisation knowledge (72% vs 67%, P= 0.005). Coverage was lower if the children's parents had received information antenatally, which discouraged immunisation (67% vs 73%, P= 0.008). Coverage decreased as socio‐economic deprivation of the registered population increased (P < 0.001) and as the children's age (P= 0.001) and registration age (P= 0.02) increased.

Conclusions:  Higher immunisation coverage is achieved by practices that establish an early relationship with the family and that are adequately resourced with stable and confident staff. Immunisation promotion should begin antenatally.
Metabolic bone disease of prematurity and secondary hyperparathyroidism
Authors: Lothe Ashish , Sinn John , Stone Monique
Published: March 2011

Aim:  To illustrate, via case histories, the importance of laboratory investigations for the early diagnosis and management of metabolic bone disease (MBD).

Methods:  We report three cases of extreme premature infants with MBD.

Results:  These three infants had several risk factors for MBD of prematurity: very low birthweight, delayed enteral feeds, cholestatic liver disease, intolerance of fortification, the use of glucocorticoids and diuretics. Serum alkaline phosphatase and parathyroid hormone (PTH) were elevated despite relatively normal calcium and phosphate levels. These parameters were corrected with additional supplementation of calcium, phosphate and vitamin D.

Conclusions:  Infants born extremely prematurely have significant calcium and phosphate depletion by the time they reach full term compared with the normal fetal accretion rate. This is exacerbated if there is poor tolerability to feeds where extra calcium and phosphate could not be added either by additives or via human milk fortifier. Serum calcium and phosphate levels may be normal despite inadequate intake or stores due to the counter‐regulatory effect of PTH. In infants at risk of MBD, testing serum alkaline phosphatase, vitamin D and PTH with calcium and phosphate may assist in the monitoring and management of MBD.
Testicular microlithiasis: The importance of self‐examination
Authors: Price Neil R , Charlton Amanda , Simango Itayi , Smith Grahame HH
Published: March 2011

Aim:  To explore the issue of appropriate management of testicular microlithiasis. We report the third ever case of tumour arising from a testis previously known to have microlithiasis in childhood and review the literature to provide an evidence‐based approach to management of testicular microlithiasis.

Methods:  Case report and review of previous literature.

Results and Conclusions:  Although there is a strong association between testicular microlithiasis and testicular malignancy at diagnosis, there are only three reported cases of subsequent tumour development in childhood. Testicular microlithiasis is an increasingly recognised entity. There is insufficient evidence in the current literature to support any regime of clinical surveillance. Self‐examination is the most important factor in the early detection of testicular malignancy.
Triple flap vaginoplasty for agenesis of the vagina
Authors: Prakash Vishwa
Published: March 2011

Aim:  Various procedures have been described for the creation of neovagina. McIndoe operation is gold standard for vaginoplasty in which split thick skin graft is used for lining the neovagina. However the rate of contraction of the graft is very high. We have used labia minora flaps along with the third flap created from suburethral tissue for lining the neovaginal space in 17 patients with good results.

Methods:  The method was used in 17 patients. After creation of neovaginal space three flaps were raised – two labia minora flaps and the third flap from suburethral tissue. The flaps were inturned and lined the neovaginal space. If whole space was not lined with flaps, supplementary grafting was used to cover the unlined space.

Results:  Thirteen patients came for follow up out of whom in one patient the labia minora flap necrosed and patient developed contracture of the vagina. In all other patients the result was satisfactory. There was no need of added lubrication during sex in any of the patients.

Conclusion:  A three flap method of vaginoplasty in agenesis of the vagina has been described with good result.
Sleep deprivation, physical activity and low income are risk factors for inadequate weight gain during pregnancy: A cohort study
Authors: Abeysena Chrishantha , Jayawardana Pushpa
Published: March 2011

Aim:  To determine the possible risk factors for inadequate gestational weight gain.

Methods:  A population‐based cohort study was carried out in Sri Lanka from May 2001 to April 2002. Pregnant women were recruited on or before 16 weeks' gestation and followed up until delivery; the sample size was 710. Trimester‐specific exposure status and potential confounding factors were gathered on average at the 12th, 28th and 36th weeks of gestation. Maternal weight was measured at the first antenatal clinic visit and at delivery. Inadequate weight gain was defined as weight gain below the Institute of Medicine recommendations in 2009. Multiple logistic regression was applied and the results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI).

Results:  The risk factors for inadequate weight gain were low per‐capita monthly income (OR 1.63, 95% CI 1.03, 2.58), multiparity (OR 1.96, 95% CI 1.34, 2.87), sleeping <8 h/day during the second, third, or both second and third trimesters (OR 1.60, 95% CI 1.05, 2.46), standing and walking ≥5 h/day during the second trimester (OR 1.50, 95% CI 1.04, 2.15), and the newborn being of the male sex (OR 1.50, 95% CI 1.04, 2.16), controlling for the effect of body mass index and gestational age.

Conclusions:  Risk factors for inadequate gestational weight gain were low income, being multiparous, sleep deprivation, physical activity in terms of standing and walking, and the male sex of baby.
Pheochromocytoma‐related cardiomyopathy during the antepartum period in a preterm pregnant woman
Authors: Nakajima Yoshiyuki , Masaoka Naoki , Sodeyama Masako , Tsuduki Yoko , Sakai Masato
Published: March 2011

We report a rare case of pheochromocytoma‐related cardiomyopathy during the preterm period. The patient was a 33‐year‐old woman who was referred to our hospital at 34 weeks' gestation. Her pulse was 130 beats/min, blood pressure of 186/90 mmHg and oxygen saturation was 30–40%. Fetal bradycardia prompted an emergency cesarean section and, nine minutes after admission, a boy weighing 2774 g was delivered with Apgar scores of 2 at 1 min and 5 at 5 min. A preoperative echocardiogram showed reduced fractional shortening of 19%. At 8 h after the operation, cardiac arrest developed. An intra‐aortic balloon pump and percutaneous cardiopulmonary support were inserted, and continuous hemodiafiltration was also commenced, after which her cardiac function and respiratory function gradually improved. Urinary catecholamine levels were elevated and abdominal computerized tomography confirmed the presence of a right suprarenal mass. Four months after delivery, she underwent a laparoscopic adrenalectomy and the mass was found to be a pheochromocytoma.