bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat shock protein 70‐binding protein 1 is highly expressed in high‐grade gliomas, interacts with multiple heat shock protein 70 family members, and specifically binds brain tumor cell surfaces
Authors: Graner Michael W. , Raynes Deborah A. , Bigner Darell D. , Guerriero Vince
Published: July 2009

Chaperone proteins and heat shock proteins (HSP) are essential components of cellular protein folding systems under normal conditions; their expression and activities are upregulated during stress. Chronically stressed tumors frequently exhibit high chaperone protein levels, exploiting their anti‐apoptotic mechanisms and general proteome homeostasis amidst a background of genetic instability. Co‐chaperones interact with chaperones as malleable regulatory components of protein folding activity and may represent a conduit for modification of chaperone activity to the detriment of the tumor. We have initially characterized one such co‐chaperone, heat shock protein 70‐binding protein (HspBP) 1 from human brain tumors, their xenografts grown in immune‐compromised mice, and in syngeneic murine models in immune‐competent mice. Immunohistochemical analyses show HspBP1 overexpression (with unusual subcellular localizations) in patient brain tumors relative to normal brain tissue. This holds true for the xenograft and syngeneic murine tumor models. In biochemical affinity chromatography assays, HspBP1 interacts with members of the HSP70 family from brain tumor lysates and from surface‐derived samples, including HSP70, glucose regulated protein (GRP)75, GRP78, and HSP110. From normal brain lysates, only heat shock cognate (HSC)70, GRP75, and HSP110 bind to HspBP1. FACS analyses indicate that HspBP1 binds to brain tumor cell surfaces, possibly via HSP70 family members, and internalizes into cells. This has implications for HspBP1 biology as well as its utility as a tumor‐targeting agent. Our results suggest that HspBP1 may play a role in tumor (dys)regulation of chaperone proteins, and that HspBP1 may have extracellular roles with therapeutic implications. (Cancer Sci 2009; 100: 1870–1879)
Immunotherapy of ovarian cancer with cell wall skeleton of Mycobacterium bovis Bacillus Calmette‐Guérin: Effect of lymphadenectomy
Authors: Hayashi Akira , Nishida Yuichi , Yoshii Saiji , Kim Seo Young , Uda Hirotsugu , Hamasaki Toshimitsu
Published: July 2009

The significance of lymphadenectomy in surgery for various kinds of cancer has been widely debated, particularly in the gynecological field. The cell wall skeleton of Mycobacterium bovis Bacillus Calmette‐Guérin (BCG‐CWS) has been used as an effective adjuvant for immunotherapy of a variety of cancer patients. Here we tested the immunological importance of lymph nodes in treatment of ovarian cancer patients with BCG‐CWS. After surgical removal of tumors, 73 ovarian cancer patients were intracutaneously inoculated with BCG‐CWS in the antigen‐unloaded state in the upper arm at 4‐week intervals at a dosage of 2–200 µg. Significant correlation of lymphadenectomy and reduced survival of patients was observed (stages I, II, III, IV; hazard ratio 2.38, 95% confidence interval 1.02–5.12, Cox regression model). Lymphadenectomy also compromised with induction of interferon‐γ. In view of the importance of the role of lymph nodes in stimulation of Toll‐like receptors by BCG‐CWS, it is suggested that lymph nodes should be kept as much as possible to preserve the patient's immunity against cancer. Application of these results to surgery for other cancers should be considered. (Cancer Sci 2009; 100: 1991–1995)
Probiotics for the treatment of eczema: a systematic review
Authors: Boyle R. J. , Bath‐Hextall F. J. , Leonardi‐Bee J. , Murrell D. F. , Tang M. L‐K
Published: July 2009

Background
Probiotics have been proposed as a treatment for eczema, but the results of intervention trials have been mixed.

Objective
To evaluate the efficacy of probiotics for treating eczema by performing a systematic review of randomized‐controlled trials (RCTs).

Design
We searched the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, AMED, LILACS, ISI Web of Science, the reference lists of articles, ongoing clinical trial registers and conference proceedings. RCTs of live orally ingested microorganisms for the treatment of eczema were eligible for inclusion.

Results
Twelve trials (781 participants) were identified. Meta‐analysis of data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment compared with placebo (mean difference −0.90 points on a 20‐point visual analogue scale; 95% confidence interval −2.84, 1.04). Meta‐analysis of data from seven trials showed no significant difference in investigator rated eczema severity between probiotic and placebo treatments. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective. There was significant heterogeneity between studies; however, the results of three studies that used the same probiotic strain were concordant. The adverse events search identified case reports of sepsis and bowel ischaemia caused by probiotics.

Conclusions
Currently, probiotics cannot be recommended for treating eczema. The heterogeneity between studies may be attributable to probiotic strain‐specific effects, which means that novel probiotic strains may still have a role in eczema management.
Plasticity in vertical behaviour of migrating juvenile southern bluefin tuna (Thunnus maccoyii) in relation to oceanography of the south Indian Ocean
Authors: BESTLEY SOPHIE , GUNN JOHN S. , HINDELL MARK A.
Published: July 2009

Electronic tagging provides unprecedented information on the habitat use and behaviour of highly migratory marine predators, but few analyses have developed quantitative links between animal behaviour and their oceanographic context. In this paper we use archival tag data from juvenile southern bluefin tuna (Thunnus maccoyii, SBT) to (i) develop a novel approach characterising the oceanographic habitats used throughout an annual migration cycle on the basis of water column structure (i.e., temperature‐at‐depth data from tags), and (ii) model how the vertical behaviour of SBT altered in relation to habitat type and other factors. Using this approach, we identified eight habitat types occupied by juvenile SBT between the southern margin of the subtropical gyre and the northern edge of the Subantarctic Front in the south Indian Ocean. Although a high degree of variability was evident both within and between fish, mixed‐effect models identified consistent behavioural responses to habitat, lunar phase, migration status and diel period. Our results indicate SBT do not act to maintain preferred depth or temperature ranges, but rather show highly plastic behaviours in response to changes in their environment. This plasticity is discussed in terms of the potential proximate causes (physiological, ecological) and with reference to the challenges posed for habitat‐based standardisation of fishery data used in stock assessments.
Theory, methods and tools for determining environmental flows for riparian vegetation: riparian vegetation‐flow response guilds
Authors: MERRITT DAVID M. , SCOTT MICHAEL L. , LeROY POFF N. , AUBLE GREGOR T. , LYTLE DAVID A.
Published: July 2009

1. Riparian vegetation composition, structure and abundance are governed to a large degree by river flow regime and flow‐mediated fluvial processes. Streamflow regime exerts selective pressures on riparian vegetation, resulting in adaptations (trait syndromes) to specific flow attributes. Widespread modification of flow regimes by humans has resulted in extensive alteration of riparian vegetation communities. Some of the negative effects of altered flow regimes on vegetation may be reversed by restoring components of the natural flow regime.

2. Models have been developed that quantitatively relate components of the flow regime to attributes of riparian vegetation at the individual, population and community levels. Predictive models range from simple statistical relationships, to more complex stochastic matrix population models and dynamic simulation models. Of the dozens of predictive models reviewed here, most treat one or a few species, have many simplifying assumptions such as stable channel form, and do not specify the time‐scale of response. In many cases, these models are very effective in developing alternative streamflow management plans for specific river reaches or segments but are not directly transferable to other rivers or other regions.

3. A primary goal in riparian ecology is to develop general frameworks for prediction of vegetation response to changing environmental conditions. The development of riparian vegetation‐flow response guilds offers a framework for transferring information from rivers where flow standards have been developed to maintain desirable vegetation attributes, to rivers with little or no existing information.

4. We propose to organise riparian plants into non‐phylogenetic groupings of species with shared traits that are related to components of hydrologic regime: life history, reproductive strategy, morphology, adaptations to fluvial disturbance and adaptations to water availability. Plants from any river or region may be grouped into these guilds and related to hydrologic attributes of a specific class of river using probabilistic response curves.

5. Probabilistic models based on riparian response guilds enable prediction of the likelihood of change in each of the response guilds given projected changes in flow, and facilitate examination of trade‐offs and risks associated with various flow management strategies. Riparian response guilds can be decomposed to the species level for individual projects or used to develop flow management guidelines for regional water management plans.
Greenhouse gas fluxes from tropical peatlands in south‐east Asia
Authors: COUWENBERG JOHN , DOMMAIN RENÉ , JOOSTEN HANS
Published: July 2009

The lowland peatlands of south‐east Asia represent an immense reservoir of fossil carbon and are reportedly responsible for 30% of the global carbon dioxide (CO2) emissions from Land Use, Land Use Change and Forestry. This paper provides a review and meta‐analysis of available literature on greenhouse gas fluxes from tropical peat soils in south‐east Asia. As in other parts of the world, water level is the main control on greenhouse gas fluxes from south‐east Asian peat soils. Based on subsidence data we calculate emissions of at least 900 g CO2 m−2 a−1 (∼250 g C m−2 a−1) for each 10 cm of additional drainage depth. This is a conservative estimate as the role of oxidation in subsidence and the increased bulk density of the uppermost drained peat layers are yet insufficiently quantified. The majority of published CO2 flux measurements from south‐east Asian peat soils concerns undifferentiated respiration at floor level, providing inadequate insight on the peat carbon balance. In contrast to previous assumptions, regular peat oxidation after drainage might contribute more to the regional long‐term annual CO2 emissions than peat fires. Methane fluxes are negligible at low water levels and amount to up to 3 mg CH4 m−2 h−1 at high water levels, which is low compared with emissions from boreal and temperate peatlands. The latter emissions may be exceeded by fluxes from rice paddies on tropical peat soil, however. N2O fluxes are erratic with extremely high values upon application of fertilizer to wet peat soils. Current data on CO2 and CH4 fluxes indicate that peatland rewetting in south‐east Asia will lead to substantial reductions of net greenhouse gas emissions. There is, however, an urgent need for further quantitative research on carbon exchange to support the development of consistent policies for climate change mitigation.
The importance of mesophyll conductance in regulating forest ecosystem productivity during drought periods
Authors: KEENAN TREVOR , SABATE SANTI , GRACIA CARLOS
Published: July 2009

Water availability is the most limiting factor to global plant productivity, yet photosynthetic responses to seasonal drought cycles are poorly understood, with conflicting reports on which limiting process is the most important during drought. We address the problem using a model‐data synthesis approach to look at canopy level fluxes, integrating twenty years of half hour data gathered by the FLUXNET network across six Mediterranean sites. The measured canopy level, water and carbon fluxes were used, together with an inverse canopy ecophysiological model, to estimate the bulk canopy conductance, bulk mesophyll conductance, and the canopy scale carbon pools in both the intercellular spaces and at the site of carboxylation in the chloroplasts. Thus the roles of stomatal and mesophyll conductance in the regulation of internal carbon pools and photosynthesis could be separated. A quantitative limitation analysis allowed for the relative seasonal responses of stomatal, mesophyll, and biochemical limitations to be gauged. The concentration of carbon in the chloroplast was shown to be a potentially more reliable estimator of assimilation rates than the intercellular carbon concentration. Both stomatal conductance limitations and mesophyll conductance limitations were observed to regulate the response of photosynthesis to water stress in each of the six species studied. The results suggest that mesophyll conductance could bridge the gap between conflicting reports on plant responses to soil water stress, and that the inclusion of mesophyll conductance in biosphere–atmosphere transfer models may improve their performance, in particular their ability to accurately capture the response of terrestrial vegetation productivity to drought.
Last‐century changes of alpine grassland water‐use efficiency: a reconstruction through carbon isotope analysis of a time‐series of Capra ibex horns
Authors: BARBOSA INÊS C. R. , KÖHLER IRIS H. , AUERSWALD KARL , LÜPS PETER , SCHNYDER HANS
Published: July 2009

The ecophysiological response of an alpine grassland to recent climate change and increasing atmospheric CO2 concentration was investigated with a new strategy to go back in time: using a time‐series of Capra ibex horns as archives of the alpine grasslands' carbon isotope discrimination (13Δ). From the collection of the Natural History Museum of Bern, horns of 24 males from the population of the Augstmatthorn–Brienzer Rothorn mountains, Switzerland, were sampled covering the period from 1938 to 2006. Samples were taken from the beginning of each year‐ring of the horns, representing the beginning of the horn growth period, the spring. The horns' carbon 13C content (Δ13C) declined together with that of atmospheric CO2 over the 69‐year period, but 13Δ increased slightly (+0.4‰), though significantly (P<0.05), over the observation period. Estimated intercellular CO2 concentration increased (+56 μmol mol−1) less than the atmospheric CO2 concentration (+81 μmol mol−1), so that intrinsic water‐use efficiency increased by 17.8% during the 69‐year period. However, the atmospheric evaporative demand at the site increased by approximately 0.1 kPa between 1955 and 2006, thus counteracting the improvement of intrinsic water‐use efficiency. As a result, instantaneous water‐use efficiency did not change. The observed changes in intrinsic water‐use efficiency were in the same range as those of trees (as reported by others), indicating that leaf‐level control of water‐use efficiency of grassland and forests followed the same principles. This is the first reconstruction of the water‐use efficiency response of a natural grassland ecosystem to last century CO2 and climatic changes. The results indicate that the alpine grassland community has responded to climate change by improving the physiological control of carbon gain to water loss, following the increases in atmospheric CO2 and evaporative demand. But, effective leaf‐level water‐use efficiency has remained unchanged.
Community‐level restoration profiles in Mediterranean vegetation: nurse‐based vs. traditional reforestation
Authors: Rey Pedro J. , Siles Gemma , Alcántara Julic M.
Published: July 2009

Many restoration projects aim to transform degraded vegetation into mature native plant communities. The recovery of the structure and properties of reference native plant communities is acknowledged as a landmark of restoration, and the success of restoration practices is measured in terms of community metrics. Nurse‐assisted planting has been proposed as a promising technique for the restoration of Mediterranean and arid vegetation based on its success at seedling establishment rather than on the recovery of reference community properties. We investigate the adequacy of this restoration practice by shifting the focus of restoration from the species to the community level.

 In contrast to previous studies in the Mediterranean region, we assessed the efficacy of several management techniques, including nurse‐based planting, in the recovery of the structure and properties of mature native reference communities. In a burned area of southern Spain, we applied widely used community analysis tools (rarefaction and species accumulation curves, Chao 2 richness estimator, species evenness and beta diversity) to compare the profiles of a reference native community and the community achieved through different management practices: traditional planting, nurse‐based planting and controls where natural regeneration was allowed to occur.

 Our results showed that post‐fire establishment of planted seedlings was higher under the canopy of nurses than in open ground. More importantly, nurse‐based restoration increased the species richness and evenness of tall‐shrubs and trees as well as the life‐form diversity, with the restored community approaching the reference community in terms of both composition and structure of the bank of juveniles.

 Synthesis and applications. We conclude that in contrast to traditional reforestation, where diversity is constrained by the elimination of pioneer and regenerated tall‐shrubs, nurse‐based restoration contributes to accelerated recovery of important community structure and properties. Thus, it should be used preferentially over traditional reforestation in Mediterranean mountains where restoration of native communities, and not merely tree establishment, is dictated under current habitat directives.
The life circumstances of persons with a psychiatric disability: a survey in a region in southern Sweden
Authors: NORDSTRÖM M. , SKÄRSÄTER I. , BJÖRKMAN T. , WIJK H.
Published: July 2009

Accessible summary

This article describes the life circumstances of persons with a psychiatric disability living in a region in southern Sweden. The respondents themselves describe their life circumstances in terms of their living conditions, occupation and activities, health, and formal and informal support.

The results show that 77.5% are unmarried, which differ considerably from corresponding figures for the Swedish population in general, of whom only 34% are single. Approximately 23% reported some sort of regular work, while only 8.7% declared that they earned a salary. Nine of 10 participants reported that their income came from sickness benefits and disability pensions, which can be compared with 10% (approximately) of the general Swedish population. Ninety per cent of participants reported receiving two or three different types of support – e.g. practical, social and medical – and having extensive contacts with municipal services to help them cope with their daily lives.

People with psychiatric disability need both formal and informal support in coping with their everyday lives. The family plays an important role and it is essential to establish cooperation between the formal and informal support systems.

The socio‐political goal of fostering access to work and gainful employment is far from having been attained.

This article describes the life circumstances of persons with a psychiatric disability living in one urban and six rural areas in a single region in Sweden. Furthermore, the life circumstances of persons with a psychiatric disability are discussed in relation to the aims of social policies in Sweden. Data were collected by means of a survey study exploring the formal support provided by local authorities to its citizens and the informal support given by family members and volunteers. The results reveal how the respondents themselves describe their life circumstances in terms of their living conditions, occupation and activities, health, and formal and informal support. The results indicate that persons with a psychiatric disability, regardless of where they live, need both formal and informal support in order to cope with their everyday lives. The family plays an important role in this, and it is essential for the formal and informal support systems to cooperate with each other. The lack of activities and opportunities for work experienced by persons with a psychiatric disability indicates that the sociopolitical goal of fostering access to employment and work and to earning a living for this group is far from having been attained.
Response of a southern temperate marsupial, the Tasmanian pademelon (Thylogale billardierii), to historical and contemporary forest fragmentation
Authors: MACQUEEN PEGGY , GOLDIZEN ANNE W. , SEDDON JENNIFER M.
Published: July 2009

Despite only limited Pleistocene glacial activity in the southern hemisphere, temperate forest species experienced complex distributional changes resulting from the combined effects of glaciation, sea level change and increased aridity. The effects of these historical processes on population genetic structure are now overlain by the effects of contemporary habitat modification. In this study, 10 microsatellites and 629 bp of the mitochondrial control region were used to assess the effects of historical forest fragmentation and recent anthropogenic habitat change on the broad‐scale population genetic structuring of a southern temperate marsupial, the Tasmanian pademelon. A total of 200 individuals were sampled from seven sites across Tasmania and two islands in Bass Strait. High mitochondrial and nuclear genetic diversity indicated the maintenance of large historical population sizes. There was weak phylogeographical structuring of haplotypes, although all King Island haplotypes and three Tasmanian haplotypes formed a divergent clade implying the mid‐Pleistocene isolation of a far northwestern population. Both the mitochondrial and nuclear data indicated a division of Tasmanian populations into eastern and western regions. This was consistent with a historical barrier resulting from increased aridity in the lowland ‘midlands’ region during glacial periods, and with a contemporary barrier resulting from recent habitat modification in that region. In Tasmania, gene flow appears to have been relatively unrestricted during glacial maxima in the west, while in the east there was evidence for historical expansion from at least one large glacial refuge and recolonization of Flinders Island.
Diversification within glacial refugia: tempo and mode of evolution of the polytypic fish Barbus sclateri
Authors: GANTE HUGO F. , MICAEL JOANA , OLIVA‐PATERNA FRANCISCO J. , DOADRIO IGNACIO , DOWLING THOMAS E. , ALVES MARIA JUDITE
Published: July 2009

A diversity of evolutionary processes can be responsible for generating and maintaining biodiversity. Molecular markers were used to investigate the influence of Plio‐Pleistocene climatic oscillations on the evolutionary history of taxa restricted to the freshwaters of a classical glacial refugium. Population genetic, phylogenetic and phylogeographical methods allowed the inference of temporal dynamics of cladogenesis and processes shaping present‐day genetic constitution of Barbus sclateri, a polytypic taxon found in several independent river drainages in southern Iberian Peninsula. Results from different analyses consistently indicate several range expansions, high levels of allopatric fragmentation, and admixture following secondary contacts throughout its evolutionary history. Using a Bayesian demographical coalescent model on mitochondrial DNA sequences calibrated with fossil evidence, all cladogenetic events within B. sclateri are inferred to have occurred during the Pleistocene and were probably driven by environmental factors. Our results suggest that glaciation cycles did not inhibit cladogenesis and probably interacted with regional geomorphology to promote diversification. We conclude that this polytypic taxon is a species complex that recently diversified in allopatry, and that Pleistocene glaciation–deglaciation cycles probably contributed to the generation of biological diversity in a classical glacial refugium with high endemicity.
Population differentiation of temperate amphibians in unpredictable environments
Authors: CHAN LAUREN M. , ZAMUDIO KELLY R.
Published: July 2009

Amphibians are a globally distributed and diverse lineage, but much of our current understanding of their population genetic structure comes from studies in mesic temperate habitats. We characterize the population genetic structure of two sympatric explosive breeding amphibians in the southwestern deserts of the United States: the Great Plains toad (Anaxyrus cognatus) and Couch’s spadefoot toad (Scaphiopus couchii). For both species, we find limited genetic differentiation even between populations in adjacent valleys separated by dispersal barriers such as mountainous habitats. To understand how population genetic patterns in these two arid‐adapted species compare to taxa in more mesic environments, we computed a standardized measure of population differentiation forA. cognatus,S. couchii, and for pond‐breeding amphibians that inhabit mesic temperate environments. Our results indicate that the arid‐adapted species have lower population genetic structure at fine and moderate scales than most other amphibian species we surveyed. We hypothesize that stochasticity in the availability of appropriate breeding sites as well as landscape homogeneity may result in increased population connectivity in desert‐adapted frogs. Future work examining fine‐scale population structure in amphibians from a diversity of habitats will test the generality of our findings. Intraspecific comparisons among localities with varied seasonality and habitats will be particularly useful for investigating the interaction between species‐typical population dynamics and environmental characteristics as determinants of population connectivity in pond‐breeding amphibians.
Screening of vesicoureteral reflux in pediatric patients with kidney transplantation showing non‐specific interstitial fibrosis and tubular atrophy with interstitial Tamm–Horsfall protein deposits in protocol allograft biopsy
Authors: Akioka Yuko , Chikamoto Hiroko , Horita Shigeru , Yago Rie , Tanabe Kazunari , Yamaguchi Yutaka , Hattori Motoshi
Published: July 2009

Abstract Interstitial fibrosis and tubular atrophy (IF/TA) in kidney allografts are induced by multiple factors, and although much effort has been devoted on the classification of IF/TA, clarification of the causes of non‐specific IF/TA is equally important for appropriate therapy. Tamm–Horsfall protein (THP) in renal tissue can be a useful marker for the histological expression of urine backflow and suspected vesicoureteral reflux (VUR). Here, we examined the presence of VUR in pediatric recipients with interstitial THP deposits in kidney allografts to clarify the cause of non‐specific IF/TA. Ten pediatric patients showing interstitial THP deposits with non‐specific IF/TA were enrolled and voiding cystourethrography was performed. Major histological findings of these patients were interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits. The semiquantitative grading scores of IF/TA were as follows: (i) mild IF/TA (n = 3); (ii) moderate IF/TA (n = 3); and (iii) severe IF/TA (n = 4). In the severe grade, diffuse interstitial mononuclear cell infiltrates were prominent with the appearance of thyroidization classically observed in chronic pyelonephritis. Eight of ten patients (80%) had VUR into the graft. Although symptomatic pyelonephritis was not observed in any of the patients, asymptomatic bacteriuria was detected in 40.0% of the patients. There was no significant correlation between VUR grade and IF/TA histological score. The patients without VUR also showed mild or severe IF/TA. Therefore, VUR and urinary flow stasis accompanied by asymptomatic urinary tract infection appear to be the causes of interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits in kidney allografts.
Clinicopathologic evaluation of short‐term outcome after early corticosteroid discontinuation in kidney transplantation
Authors: Miura Masayoshi , Ogawa Yayoi , Kubota Kanako C. , Harada Hiroshi , Shimoda Naohiko , Seki Toshimori , Hirano Tetsuo , Nonomura Katsuya
Published: July 2009

Abstract: Objectives:  Steroids have been a gold‐standard drug of immunosuppressive regimens in kidney transplantation. Steroid minimization protocols have been applied to minimize the adverse effects of steroids. We have evaluated the short‐term outcomes of our early steroid discontinuation regimen.

Methods:  A total of 128 recipients who received kidney from ABO‐compatible, flow crossmatch‐negative living‐related donors were included in this study. Immunosuppressive regimens consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), and basiliximab. In a cohort of recipients, designated as a steroid early discontinuation (ESD) group, only three doses of methylprednisolone (MP) were given (500, 250, 125 mg). In the other cohort of recipients, designated as a chronic steroid (CS) group, MP was given chronically, being tapered to 4 mg at one month post‐transplant. TAC and mycophenolic acid (MPA) blood levels were monitored. The following data were retrospectively compared between the two groups at 1, 3, 6, 9, 12 months post‐transplant: serum creatinine (sCr), urine protein per gCr (uP/Cr), the incidence of biopsy‐proven acute rejection (BPAR), graft survival (GS), area‐under‐the‐curve of blood levels of tacrolimus (TAC‐AUC0–12, ng h/mL) and mycophenolic acid (MPA‐AUC0–12, μg h/mL), MMF dose (mg), the incidence of opportunistic infection, post‐transplant diabetes mellitus (PTDM), and histopathologic findings of protocol biopsy according to the Banff ‘07 classification.

Results:  sCr and uP/Cr were comparable between the two groups up to 12 months except for sCr at one month (ESD group > CS group). TAC‐AUC0–12 was significantly higher in ESD group at one month but was equivalent thereafter, while the prevalence of biopsy‐proven tubulotoxicity was not different. MMF dose was comparable throughout the period between two groups. The incidence of BPAR until 12 months was equivalent. Of note, 60% of BPAR cases in ESD group occurred within one month. Prevalence of opportunistic infection or PTDM was equivalent. Graft survival was 100% in both groups. The following histopathologic scores up to 12 months were also equivalent: t, i, g, v, ci, ct, cg, cv, mm, ah, and ptc.

Conclusions:  Favorable short‐term outcomes were achieved both clinically and histologically using our early steroid discontinuation protocol compared with the conventional protocol with chronic steroid treatment.
Successful rescue of late‐onset acute T‐cell mediated rejection with anti‐CD25 antibody: a case report
Authors: Osawa Takahiro , Harada Hiroshi , Miura Masayoshi , Ogawa Yayoi , Morooka Kanako , Nakamura Michiko , Tanabe Tatsu , Takada Norikata , Seki Toshimori , Togashi Masaki , Takenouchi Toshinao , Hirano Tetsuo
Published: July 2009

Abstract:  A 56‐yr‐old Japanese male with a history of diabetic nephropathy underwent a HLA 5/6 mismatch and ABO‐compatible living‐related kidney transplantation (donor: his 49‐yr‐old wife). A pre‐transplant standard NIH complement‐dependent cytotoxicity cross‐match (Xm) test, a flow‐cytometric T‐cell Xm, and a FlowPRA™ test were totally negative. Inductionimmunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab (BAS). The patient’s post‐operative course was almost uneventful, and the graft was functioning well (sCr 1.1 mg/dL). He developed general fatigue, and his sCr was elevated to 2.2 mg/dL 792 d after transplant. A graft biopsy showed acute T‐cell mediated rejection Banff grade IB (i3, t3, g0, v0, ptc0, C4d staining negative). The conventional anti‐rejection therapy could not improve his graft function; therefore, we added BAS to eliminate activated graft‐infiltrating T‐cells. He responded to the rescue therapy, and the improvement in graft function was confirmed by a subsequent graft biopsy. He enjoyed his health without any opportunistic infections.
Subclinical peritubular capillaritis in serial graft biopsies in cadaveric kidney transplant recipient with pre‐transplant anti‐HLA antibodies
Authors: Masutani Kohsuke , Kitada Hidehisa , Noguchi Hideko , Tsuruya Kazuhiko , Katafuchi Ritsuko , Tanaka Masao , Iida Mitsuo
Published: July 2009

Abstract:  A 63‐yr‐old Japanese woman on 18‐yr hemodialysis (HD) program underwent cadaveric kidney transplantation from non‐heart beating donor. Pre‐transplant lymphocytotoxicity test was negative, but flow cytometric cross‐match and flow‐cytometric panel reactive antibody (PRA) screening tests were positive. Flow‐PRA single‐antigen test revealed several anti‐HLA antibodies including donor‐specific antibody (DSA). She was treated with plasma exchange (PEX) and rituximab to prevent antibody‐mediated rejection (AMR). Urinary output increased from post‐operative day (POD) 5 and HD was discontinued from POD8. Graft biopsy performed on POD11 showed severe peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was negative, the case was diagnosed as subclinical AMR based on the presence of pre‐transplant DSA and PTCitis with predominant PMNs. The patient was treated with additional PEX and rituximab, which increased urinary output and reduced serum creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was negative again. The patient was discharged from the hospital on POD40. During the seven months follow‐up at the outpatient clinic, the sCr level has shown a slight increase. In this case, the patient had DSA, which can be detected only by flow‐PRA. In both graft biopsies, C4d on PTC was negative despite the presence of severe PTCitis, and thus the diagnosis of AMR could not be established. However, the significance of subclinical PTCitis is reported perhaps as an early marker for chronic AMR and to emphasize the importance of close follow‐up.
Clinicopathological analysis of transplant glomerulopathy cases
Authors: Shimizu Tomokazu , Ishida Hideki , Shirakawa Hiroki , Omoto Kazuya , Tsunoyama Kuniko , Iida Shoichi , Tanabe Kazunari , Yamaguchi Yutaka
Published: July 2009

Abstract:  Introduction:  Transplant glomerulopathy (TG) is involved in the criteria of chronic active antibody‐mediated rejection (c‐AMR) in Banff 07 classification. In this report, we discuss the clinico‐pathological analysis of TG cases after renal transplantation, and analysis of whether all TG cases are applied to c‐AMR.

Patients:  Transplant glomerulopathy, defined by double contours of glomerular basement membranes, was diagnosed in 13 patients from 13 renal transplant patients followed‐up in our institute between January 2007 and April 2008. We retrospectively reviewed these 13 patients.

Results:  Among 13 cases of TG, three cases were mild (cg1 in Banff classification), four were moderate (cg2), and six were severe (cg3). Transplant glomerulitis and interstitial inflammation were present in all 13 biopsies, and peritubular capillaritis was present in 12 of 13 biopsies, interstitial fibrosis/tubular atrophy in 13, and the thickening of the peritubular capillary (PTC) basement membrane in 11. PTC C4d deposition was presented in six cases, three out of six cases had diffuse C4d deposits in PTC, and the remainder had focal deposits. By assaying with plastic beads coated with human leukocyte antigen (HLA) in 12 cases, the circulating anti‐HLA alloantibody was detected in all 12 patients of which only 3 of 12 were donor‐specific antibodies (DSA). In our cases, there was no patient who fully met criteria for c‐AMR in Banff classification, which included TG, C4d deposition in PTC, and existence of DSA, but seven patients were diagnosed suspicious for c‐AMR. Seven cases (54%) had proteinuria at the time of the biopsies and the severity of proteinuria was associated with the severity of TG. Deterioration of renal allografts’ function after biopsies was seen in seven (54%), and two of them lost their graft.

Conclusions:  We suggest that histopathological changes of TG accompanied by transplant glomerulitis, peritubular capillaritis, the thickening of the peritubular capillaries basement membrane, and circulating anti‐HLA antibodies may indicate c‐AMR, even if C4d deposition in PTC is negative. The severity of TG may be associated with proteinuria, reduced graft function, and reduced graft survival.
Clinical remission and pathological progression after tonsillectomy in a renal transplant patient with recurrent IgA nephropathy
Authors: Sakai Ken , Saneshige Manabu , Takasu Jirou , Yanagisawa Taketo , Aoki Yujirou , Kawamura Takeshi , Mizuiri Sonoo , Aikawa Atsushi
Published: July 2009

Abstract:  We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36‐year‐old man started on hemodialysis support in 1996 due to biopsy‐proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre‐tonsillectomy biopsy and the two post‐tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.
Renal insufficiency after liver transplantation in the MELD era compared to the pre‐MELD era
Authors: Feng Zhen‐Zhou , Tang Jeffrey , Kim Dean Y. , Brown Kimberly , Abouljoud Marwan , Gordon Stuart , Yoshida Atsushi , Huang Mary Ann , Divine George , Moonka Dilip Kumar
Published: July 2009

Abstract:  Because the model for end‐stage liver disease (MELD) system for liver allocation gives priority to patients with a higher creatinine, and because pre‐transplant renal function is one determinant of post‐transplant renal function, this study compares the burden of renal insufficiency in the pre‐MELD and MELD eras. Two hundred and elven patients, at our institution, transplanted in the pre‐MELD era, were compared to 143 in the MELD era. The GFR (mL/min/1.73 m2) was significantly higher in the MELD cohort than the pre‐MELD cohort at time of transplant, discharge, and 12 months post‐transplant (95.5 vs. 85.3, p = 0.039; 90.4 vs. 77.4, p = 0.002; 66.8 vs. 60.3, p = 0.026). There was no difference between the two groups in time to renal failure. There was a higher rate of sirolimus use in the MELD era (27% vs. 18%: p = 0.042) and a slightly higher use of kidney–liver transplant in the MELD era (p = 0.056). We did not identify greater renal insufficiency in the MELD era. There was greater renal function in the MELD era at time of transplant, discharge and month 12. Potential explanations include: absence of an increase in renal insufficiency prior to transplant in the MELD era, greater use of renal sparing immunotherapy and growing use of kidney–liver transplant.
Steroid‐free living donor liver transplantation in adults: impact on hepatitis C recurrence
Authors: Marubashi Shigeru , Dono Keizo , Nagano Hiroaki , Kim Chiwan , Asaoka Tadafumi , Hama Naoki , Kobayashi Shogo , Takeda Yutaka , Umeshita Koji , Monden Morito , Doki Yuichiro , Mori Masaki
Published: July 2009

Abstract:  Introduction:  Although steroid‐free immunosuppression has been proven to be safe and feasible for liver transplantation, its impact on hepatitis C virus (HCV) recurrence remains unknown. We aimed to clarify the impact of steroid‐free immunosuppression on post‐operative HCV recurrence after living donor liver transplantation (LDLT).

Patients and methods:  Of 32 adult patients with HCV cirrhosis who underwent LDLT between 1999 and 2007 at our hospital, 28 were enrolled in this prospective study. We used steroid‐free immunosuppression, consisting of a calcineurin inhibitor, mycophenolate mofetil and anti‐CD25 antibody in 18 patients (F‐group), and the remaining 10 patients received steroid‐based immunosuppression (S‐group) during the same period.

Results:  Patient characteristics were similar between the two groups. Steroid‐free immunosuppression was associated with lower incidence of CMV infection (p = 0.049) and higher incidence of instituting preemptive anti‐HCV therapy (p = 0.015) without increasing acute cellular rejection in the F‐group than that in the S‐group.

In the early period after LDLT, the serum HCV‐RNA level remained suppressed in the F‐group, whereas it increased rapidly in the S‐group (p < 0.05). HCV recurrence was less frequent in the F‐group (18.1% at one yr) than in the S‐group (46.0%) (p = 0.009).

Conclusions:  Steroid‐free immunosuppression was confirmed to be safe and feasible for HCV‐positive recipients in LDLT, and was associated with suppressed HCV replication and HCV recurrence after LDLT.
A comparison of prediction equations for estimating glomerular filtration rate in Chinese potential living kidney donors
Authors: Zhao Wen‐Yu , Zeng Li , Zhu You‐Hua , Wang Li‐Ming , Zhou Mei‐Sheng , Han Shu , Zhang Lei
Published: July 2009

Abstract:  Background:  Accurate measurement of donor renal function has important long‐term implications for both donors and recipients. In clinical practice, renal function may be estimated by using 24‐h urinary creatinine clearance (urine‐CrCl) and various specifically derived prediction equations. We assessed the suitability of urine‐CrCl and prediction equations for evaluating Chinese kidney donors.

Methods:  A total of 224 donors who had undergone 99mTc‐diethylenetriaminepentaacetic acid glomerular filtration rate (GFR) estimation were enrolled. We evaluated the performance of the Cockcroft–Gault equation (CG‐CrCl), the CG‐CrCl equation corrected for GFR (CG‐GFR), the isotope dilution mass spectrometry traceable modification of diet in renal disease (IDMS‐MDRD) study equation, the new MDRD study equation for Chinese (C‐MDRD 1), the modified MDRD study equation with a Chinese coefficient (C‐MDRD 2), the modified IDMS‐MDRD study equation with a Japanese coefficient (J‐MDRD), and urine‐CrCl in predicting GFR before donation.

Results:  Of 224 donors selected, 68 were male and 156 were female. Of all the prediction equations, C‐MDRD 1 was the least scattered and most precise. However, predictive performance was poor for all the equations.

Conclusion:  The performance of urine‐CrCl and all the equations was disappointing, and even the best performing equation C‐MDRD 1 was unacceptable. Considering the potential risk of living kidney donation, other more accurate methods of GFR measurement should be used in clinical practice.
Distribution of neurofibrillary tangles in diffuse neurofibrillary tangles with calcification
Authors: Ukai Katsuyuki , Shibayama Hiroto , Ishihara Ryoko , Ozaki Norio
Published: July 2009

Aims:  In this study, the appearance and distribution of neurofibrillary tangles (NFT) in diffuse neurofibrillary tangles with calcification (DNTC) were investigated neuropathologically in order to elucidate the detailed distribution pattern in this disease.

Methods:  The distribution of NFT in six cases neuropathologically diagnosed as DNTC (two men and four women) was studied using Gallyas–Braak silver stain. The age at death ranged from 56 to 73, with an average of 63.5 ± 7.5 years.

Results:  NFT were seen throughout the cerebral cortex, and were especially marked in the temporal and limbic cortices. The distribution pattern of NFT in the limbic lobe was similar to that in Alzheimer's disease as reported in the previous studies. In the temporal lobe, more NFT were distributed in the anterior than in the posterior area, which was confirmed in all six cases. The temporal pole showed the highest density of NFT including ghost tangles.

Conclusions:  The diffuse appearance of NFT in the cerebral cortex with the highest severity in the temporal pole was found to be a neuropathological characteristic of DNTC.
The hologenome theory of evolution contains Lamarckian aspects within a Darwinian framework
Authors: Rosenberg Eugene , Sharon Gil , Zilber‐Rosenberg Ilana
Published: July 2009

The hologenome theory of evolution emphasizes the role of microorganisms in the evolution of animals and plants. The theory posits that the holobiont (host plus all of its symbiont microbiota) is a unit of selection in evolution. Genetic variation in the holobiont that can occur either in the host and/or in the microbial symbiont genomes (together termed hologenome) can then be transmitted to offspring. In addition to the known modes of variation, i.e. sexual recombination, chromosomal rearrangement and mutation, variation in the holobiont can occur also via two mechanisms that are specific to the hologenome theory: amplification of existing microorganisms and acquisition of novel strains from the environment. These mechanisms are Lamarckian in that (i) they are regulated by ‘use and disuse’ (of microbes) and (ii) the variations in the hologenome are transmitted to offspring, thus satisfying also the Lamarckian principle of ‘inheritance of acquired characteristics’. Accordingly, the hologenome theory incorporates Lamarckian aspects within a Darwinian framework, accentuating both cooperation and competition within the holobiont and with other holobionts.
Risk disclosures on the second tier markets of the London Stock Exchange
Authors: Hill Paula , Short Helen
Published: July 2009

The identification, management and disclosure of risks have been the subject of recent legislation, directives and reporting standards issued across a number of international jurisdictions. To inform the disclosure debate, this paper provides a detailed analysis of the risk warning disclosures of initial public offering (IPO) companies and the factors that drive such disclosures. We find that risk disclosures of IPO companies contain a greater proportion of forward‐looking information but a lower proportion of information on internal controls and risk management than the disclosures of listed companies. We find evidence that such disclosure has increased across time but that larger directors’ shareholdings are associated with a reduction in risk disclosure.
Determination of stock closing prices and hedging performance with stock indices futures
Authors: Lee Hsiu‐Chuan , Chien Cheng‐Yi , Liao Tzu‐Hsiang
Published: July 2009

This paper examines the impact of the determination of stock closing prices on futures price efficiency and hedging effectiveness with stock indices futures. The empirical results indicate that the increase in the length of the batching period of the stock closing call improves price efficiency in the futures closing prices and then enhances hedging performance in terms of the hedging risks. Additionally, from a utility‐maximization point of view, hedging performance does not improve after the introduction of the 5 min stock closing call, which can be explained by an improvement in price efficiency at the futures market close.