bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful unrelated umbilical cord blood cell transplantation without conditioning for a neonate with severe combined immunodeficiency
Authors: Taga Takashi , Itoh Eisuke , Noda Yasuyo , Kato Hirofumi , Maruo Yoshihiro , Takano Tomoyuki , Ohta Shigeru , Takeuchi Yoshihiro , Kumaki Satoru
Published: June 2010

Taga T, Itoh E, Noda Y, Kato H, Maruo Y, Takano T, Ohta S, Takeuchi Y, Kumaki S. Successful unrelated umbilical cord blood cell transplantation without conditioning for a neonate with severe combined immunodeficiency. Pediatr Transplantation 2011: 15: E152–E155. © 2010 John Wiley & Sons A/S.

Abstract:  A neonate was diagnosed as having SCID from his umbilical cord blood cells immediately after birth because his older brother had died of SCID eight months earlier. One locus‐mismatched unrelated umbilical cord blood cell transplantation without conditioning was performed at the age of 30 days. The CD3‐positive cells were detected on day 14 post‐transplantation. There were no peri‐transplantation complications. Four yr after transplantation, the boy is in excellent condition and T and NK cell engraftments are complete. His peripheral B cells with a common gamma chain were not detected by flow cytometry, and he still needs IgG replacement; however, his IgM and IgA levels have gradually increased, and the dosage of IVIG per body weight has gradually decreased. We speculate that the very few B cells that proliferate from transplanted cord blood cells produce gamma globulin. Unrelated cord blood cell transplantation, even though mismatched, without conditioning would be a treatment option for neonates with severe combined immunodeficiency.
Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment
Authors: Castro‐Silva A.N. , Freire A.O. , Grinbaum R.S. , Elmor de Araújo M.R. , Abensur H. , Araújo M.R.T. , Romão J.E. , Sampaio J.L.M. , Noronha I.L.
Published: June 2010

A.N. Castro‐Silva, A.O. Freire, R.S. Grinbaum, M.R. Elmor de Araújo, H. Abensur, M.R.T. Araújo, J.E. Romão Jr, J.L.M. Sampaio, I.L. Noronha. Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment. Transpl Infect Dis 2011: 13: 33–37. All rights reserved

Abstract: Mycobacterium haemophilum is a slow‐growing nontuberculous mycobacterium that can cause disease in both immunocompetent and immunocompromised patients. The most common clinical presentations of infection are the appearance of suppurative and ulcerated skin nodules. For the diagnosis, samples collected from suspected cases must be processed under the appropriate conditions, because M. haemophilum requires lower incubation temperatures and iron supplementation in order to grow in culture. In this case report, we describe the occurrence of skin lesions in a kidney transplant recipient, caused by M. haemophilum, associated with acupuncture treatment. The diagnosis was established by direct smear and culture of material aspirated from cutaneous lesions. Species identification was achieved by characterization of the growth requirements and by partial sequencing of the hsp65 gene. The patient was successfully treated with clarithromycin and ciprofloxacin for 12 months. Considering that the number of patients receiving acupuncture treatment is widely increasing, the implications of this potential complication should be recognized, particularly in immunosuppressed patients.
Reinforced postmating reproductive isolation barriers inNeurospora, an Ascomycete microfungus
Authors: TURNER E. , JACOBSON D. J. , TAYLOR J. W.
Published: June 2010

Maladaptive hybridization promotes reinforcement, selection for stringent reproductive isolation barriers during speciation. Reinforcement is suspected when barriers between sympatric populations are stronger than allopatric barriers, and particularly when stronger barriers evolve in the species and sex suffering the greatest costs of hybridization. Canonically, reinforcement involves premating barriers. Selection for postmating barriers is controversial, but theoretically possible. We examined geographical patterns in reproductive isolation barriers betweenNeurospora crassaandNeurospora intermedia, fungi with pheromone‐mediated mate recognition and maternal care. We find that isolation is stronger between sympatric populations than allopatric populations, and stronger barriers are associated with the species (N. crassa) and mating role (maternal) suffering the greater costs of hybridization. Notably, reinforced isolation involves a postmating barrier, abortion of fruitbodies. We hypothesize that fruitbody abortion is selectively advantageous if it increases the likelihood that maternalNeurosporaindividuals successfully mate conspecifically after maladaptive hybrid fertilization.
Competitive environments induce shifts in host fidelity
Authors: ROVA E. , BJÖRKLUND M.
Published: June 2010

Recent models support the idea of sympatric speciation as a result of the joint effects of disruptive selection and assortative mating. We present experimental data, testing models of speciation through frequency‐dependent selection. We show that under high competition on a mixture of resources/hosts, strains of the Seed beetle, Callosobruchus maculatus, change their host fidelity and evolve a more generalistic behaviour in resource utilization among females. The change in host fidelity did not result in disruptive selection and was not followed by assortative mating. This means that only one of three fundamental prerequisites for sympatric speciation evolved as a result of the frequency‐dependent selection. We conclude that for this process to work, a shift to a novel food resource as a result of selection must also lead to a loss of preference for the original resource such that individuals are only able to use either one of the two.
Complex genotype interactions influence social fitness during the developmental phase of the social amoebaDictyostelium discoideum
Authors: BUTTERY N. J. , THOMPSON C. R. L. , WOLF J. B.
Published: June 2010

When individuals interact, phenotypic variation can be partitioned into direct genetic effects (DGEs) of the individuals’ own genotypes, indirect genetic effects (IGEs) of their social partners’ genotypes and epistatic interactions between the genotypes of interacting individuals (‘genotype‐by‐genotype (G×G) epistasis’). These components can all play important roles in evolutionary processes, but few empirical studies have examined their importance. The social amoebaDictyostelium discoideumprovides an ideal system to measure these effects during social interactions and development. When starved, free‐living amoebae aggregate and differentiate into a multicellular fruiting body with a dead stalk that holds aloft viable spores. By measuring interactions among a set of natural strains, we quantify DGEs, IGEs and G×G epistasis affecting spore formation. We find that DGEs explain most of the phenotypic variance (57.6%) whereas IGEs explain a smaller (13.3%) but highly significant component. Interestingly, G×G epistasis explains nearly a quarter of the variance (23.0%), highlighting the complex nature of genotype interactions. These results demonstrate the large impact that social interactions can have on development and suggest that social effects should play an important role in developmental evolution in this system.
Arabidopsis shoot organogenesis is enhanced by an amino acid change in the ATHB15 transcription factor
Authors: Duclercq J. , Assoumou Ndong Y. P. , Guerineau F. , Sangwan R. S. , Catterou M.
Published: June 2010

The hoc mutant displays high organogenic competence for in vitro shoot regeneration without addition of exogenous phytohormones. The genetic basis of this phenotype is investigated here. Using genetic mapping, the HOC locus was identified on chromosome 1. A point mutation was found in the At1g52150 gene, which encodes ATHB15/CORONA/INCURVATA4, a class III HD‐ZIP transcription factor. The mutation replaced a serine with a cysteine in the MEKHLA domain of the protein. The wild‐type ATHB15 gene was able to complement the hoc phenotype. Organogenesis response experiments revealed that hoc organogenic capacity was affected by the genetic background, and that it was not caused by a loss of ATHB15 function but by an effect of the mutation on protein function.
Application of multiple‐trait finite mixture model to test‐day records of milk yield and somatic cell score of Canadian Holsteins
Authors: Jamrozik J. , Schaeffer L.R.
Published: June 2010

Multiple‐trait (MT) finite mixture random regression (MIX) model was applied using Bayesian methods to first lactation test‐day (TD) milk yield and somatic cell score (SCS) of Canadian Holsteins, allowing for heterogeneity of distributions with respect to days in milk (DIM) in lactation. The assumption was that the associations between patterns of variation in these traits and mastitis would allow revealing the hidden structure in the data distribution because of unknown health status of cows. The MIX model assumed separate means and residual co‐variance structures for two components in four intervals of lactation, in addition to fitting the fixed effect of herd‐test‐day, and fixed and random regressions with Legendre polynomials. Results indicated that the mixture model was superior to standard MT model, as supported by the Bayes factor. Approximately 20% of TD records were classified as originated from cows with a putative, sub‐clinical form of mastitis. The proportion of records from mastitic cows was the largest at the beginning of lactation. The MIX model exhibited different distributions of data from healthy and infected cows in different parts of lactation. Records from sick cows were characterized by larger (smaller) means for SCS (milk) and larger variances. Residual, and daily genetic and environmental correlations between milk and SCS were smaller from the MIX model when compared with MT estimates. Heritabilities of both traits differed significantly among records from healthy, sick and MT model estimates. Both models fitted milk records from healthy cows relatively well. The ability of the MT model in handling SCS records, measured by model residuals, was low, but improved substantially, however, where the data were allowed to be separated into two components in the MIX parameterization. Correlations between estimated breeding values (EBV) for sires from both models were very high for cumulative milk yield (>0.99) and slightly lower (0.95 in the interval from 5 to 45 DIM) for daily SCS. EBV for SCS from MT and MIX models were weakly correlated with posterior probability of sub‐clinical mastitis on the phenotypic scale.
Enhanced mating competitiveness of Ceratitis capitata males following exposure to citrus compounds
Authors: Kouloussis N. A. , Katsoyannos B. I. , Papadopoulos N. T. , Ioannou C. S. , Iliadis I. V.
Published: June 2010

Previous work has demonstrated that exposure of males of the Mediterranean fruit fly, Ceratitis capitata (Diptera: Tephritidae), to the scent of sweet orange increases their mating success relative to non‐exposed males. Here, we demonstrate that exposure to the commercial essential oils of bitter orange, mandarin orange, lemon and grapefruit confer to males a significant mating advantage as well. Likewise, exposure to peel‐wounded mandarin oranges and lemons, and to peel‐wounded sweet oranges of the Merlin, Newhole and Naveline varieties, also conferred a significant mating advantage. Exposure to peel‐wounded grapefruits and bitter oranges as well as to sweet oranges of the local Greek variety Xino Artas enhanced mating success, however, not significantly. These results suggest that the chemicals responsible for mating enhancement in C. capitata are present in several citrus fruit species and varieties. In an experiment involving different doses of commercial sweet orange peel oil, males exposed to medium doses of 12.5 or 25 μl achieved significantly higher numbers of matings with virgin females than control males. Lower doses did not increase mating success, whereas higher doses killed a number of males. In another experiment we tested the effect of the seven most abundant individual chemical compounds of citrus oil (some of them also existing in the pheromone of males) and detected compounds with some potential for further trials. In a final experiment we created a mixture of those compounds (geraniol, α‐pinene, limonene, β‐myrcene and linalool) and found that wild or sterile males exposed to it achieved over 70% of all matings when competing with non‐exposed males. Since the mixture did not contain α‐copaene (an expensive compound that is often invoked as responsible for the phenomenon of mating enhancement) our data could lead in a more cost‐effective and efficient implementation of sterile insect technique (SIT) programmes against C. capitata.
Assessment of Vascular Perfusion Kinetics Using Contrast‐enhanced Ultrasound for the Diagnosis of Prostatic Disease in Dogs
Authors: Vignoli M , Russo M , Catone G , Rossi F , Attanasi G , Terragni R , Saunders JH , England GCW
Published: June 2010

Contents

Vascular perfusion was assessed in 10 dogs without prostatic abnormalities and 26 dogs with prostatic disease using contrast‐enhanced ultrasound. The time to reach peak contrast intensity (TTP) and peak perfusion intensity (PPI) were measured, and histological biopsies were collected from each dog. Biopsies confirmed normal prostate (n = 10), benign prostatic hyperplasia (n = 11), mixed benign pathology (n = 9), prostatitis (n = 1), prostatic malignancy [adenocarcinoma (n = 4); leiomyosarcoma (n = 1)]. In normal dogs, mean PPI was 16.8% ± 5.8 SD, and mean TTP was 33.6 ± 6.4 s. Benign conditions overall were not statistically different from normal dogs (p > 0.05); for benign prostatic hyperplasia, mean PPI was 16.9 ± 3.8%, and mean TTP was 26.2 ± 5.8 s; for mixed benign pathology mean PPI was 14.8 ± 7.8%, and mean TTP was 31.9 ± 9.7 s; for prostatitis, PPI was 14.2%, and TTP was 25.9 s. The malignant conditions overall had perfusion values that differed from the normal dogs (p < 0.05), although evaluation of the data for individual malignancies did not demonstrate a consistent trend; for adenocarcinomas, the PPI was numerically higher with a mean of 23.7 ± 1.9%, and the mean TTP was 26.9 ± 4.8 s, whilst for the dog with leiomyosarcoma values were numerically lower with a PPI of 14.1% and TTP of 41.3 s. Contrast‐enhanced ultrasound appears to offer some ability to document differences in perfusion that may differentiate between malignant and benign lesions, although studies with larger numbers of animals are required to confirm this contention.
Inbreeding Depression on Semen Quality in Austrian Dual‐Purpose Simmental Bulls
Authors: Maximini L , Fuerst‐Waltl B , Gredler B , Baumung R
Published: June 2010

Contents

Using pedigree data, the inbreeding coefficients of 715 Austrian dual‐purpose Simmental (Fleckvieh) bulls stationed in two artificial insemination (AI) centres in Upper and Lower Austria were calculated and incorporated in statistical models for the analysis of semen quality. Five semen quality parameters (volume, concentration, motility, number of spermatozoa per ejaculate and percentage of viable spermatozoa) of approximately 30 000 ejaculates, used in two separate data sets, were investigated. The mixed model included the fixed effects age class of the bull, bull handler, semen collector, month and year of collection, number of collection per bull and day, time interval since last collection, the linear continuous effect of the inbreeding coefficient of the bull, interactions between age class and month, and age class and interval since last collection, respectively, as well as the random effect of the bull and the random residual effect. Non‐linear effects of inbreeding were significant for motility only. Despite the quite low inbreeding coefficients (mean 1.3%), all semen quality traits showed inbreeding depression, in four of the five traits significantly in at least one of the data sets. The magnitude of inbreeding depression was small, which might partly be caused by the low inbreeding levels and a potential pre‐selection of the bulls in the AI centres. However, monitoring of inbreeding depression on fertility traits is recommended to avoid unrecognized deterioration of such traits.
Subhorizontal tectonic framework of the Horoman peridotite complex and enveloping crustal rocks, south‐central Hokkaido, Japan
Authors: Yamamoto Hiroshi , Nakamori Natsumi , Terabayashi Masaru , Rehman Hafiz Ur , Ishikawa Masahiro , Kaneko Yoshiyuki , Matsui Takashi
Published: June 2010

Geological observations in the Horoman area, south‐central Hokkaido, show that the Horoman peridotite complex of the Hidaka metamorphic belt is a tectonic slice about 1200 m thick. The peridotite slab is intercalated into a gently east‐dipping structure. The underlying unit is a Cretaceous–Paleogene accretionary complex. Riedel shear planes in the sedimentary layers of the accretionary complex near the structural bottom of the peridotite slab indicate top‐to‐the‐west (thrust) displacement. The overlying unit is composed of felsic–pelitic gneisses and mafic–felsic intrusive rocks (the Hidaka metamorphic rocks). The boundary surface between the peridotite complex and metamorphic rocks forms a domal structure. Microstructures of sheared metamorphic rocks near the structural top of the peridotite slab indicate top‐to‐the‐east (normal) displacement. The results combined with previous studies suggest that the Horoman peridotite complex was emplaced onto the Asian margin (Northeast Japan) during the collision between the Asian margin and the Hidaka crustal block.
Patency and clinical outcomes of transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene‐covered stents versus bare stents: A meta‐analysis
Authors: Yang Zhiping , Han Guohong , Wu Qiong , Ye Xiaofei , Jin Zhichao , Yin Zhanxin , Qi Xingshun , Bai Ming , Wu Kaichun , Fan Daiming
Published: June 2010

Background and Aim:  Transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene‐(PTFE)‐covered stent has been increasingly used for patients with complications of portal hypertension. It is still debated whether the new endoprostheses will improve some clinical outcomes (except for shunt patency) compared to the bare stents. The aims of our meta‐analysis were to explore the patency and clinical outcomes of TIPS with PTFE‐covered stent‐grafts versus bare stents.

Methods:  Pertinent studies were retrieved through PubMed (1950–2010), MEDLINE (1950–2010), and reference lists of key articles. Outcome measures were primary patency, risk of encephalopathy and survival. Time‐to‐event data analysis was used to calculate the overall hazard ratios (HR).

Results:  Six studies were identified including a total of 1275 patients (346 TIPS with PTFE‐covered stent‐grafts and 929 TIPS with bare stents). Pooled shunt patency data from four eligible studies suggested a significant improvement of primary patency in patients who were treated with PTFE‐covered stent‐grafts (HR = 0.28, 95% confidence interval [CI] 0.20–0.35). Pooled encephalopathy data from three eligible studies suggested a significant reduction of risk in the PTFE‐covered group (HR = 0.65, 95%CI 0.45–0.86). Pooled survival data from four eligible studies also suggested a significant decrease of mortality in the PTFE‐covered group (HR = 0.76, 95%CI 0.58–0.94). No statistical heterogeneity was observed between studies for either outcome.

Conclusions:  This meta‐analysis shows that the use of PTFE‐covered stent‐grafts clearly improves shunt patency without increasing the risk of hepatic encephalopathy and with a trend towards better survival.
Endoscopic resection of gastrointestinal lesions: Advancement in the application of endoscopic submucosal dissection
Authors: Conlin Abby , Kaltenbach Tonya , Kusano Chika , Matsuda Takahisa , Oda Ichiro , Gotoda Takuji
Published: June 2010

Curative endoscopic resection is now a viable option for a range of neoplastic lesions of the gastrointestinal tract (GIT) with low invasive potential. Risk of lymph node metastasis is the most important prognostic factor in selecting appropriate lesions for endoscopic therapy, and assessment of invasion depth is vital in this respect. To determine appropriate treatment, detailed endoscopic diagnosis and estimation of depth using magnifying chromoendoscopy is the gold standard in Japan. En bloc resection is the most desirable endoscopic therapy as risk of local recurrence is low and accurate histological diagnosis of invasion depth is possible. Endoscopic mucosal resection is established worldwide for the ablation of early neoplasms, but en bloc removal using this technique is limited to small lesions. Evidence suggests that a piecemeal resection technique has a higher local recurrence risk, therefore necessitating repeated surveillance endoscopy and further therapy. More advanced endoscopic techniques developed in Japan allow effective en bloc removal of early GIT neoplasms, regardless of size. This review discusses assessment of GIT lesions and options for endoscopic therapy with special reference to the introduction of endoscopic submucosal dissection into Western countries.
Economic evaluation of sorafenib in unresectable hepatocellular carcinoma
Authors: Carr Brian I. , Carroll Stuart , Muszbek Noemi , Gondek Kathleen
Published: June 2010

Background and Aim: A double‐blind, randomized phase III trial of sorafenib in advanced hepatocellular carcinoma demonstrated that sorafenib significantly prolonged overall survival compared to placebo (median overall survival = 10.7 monthsvs7.9 months,P < 0.001). Sorafenib is the first and only systemic agent demonstrating survival benefit in these patients. The aim of this study was to assess the cost‐effectiveness of sorafenib versus best supportive care in the treatment of advanced hepatocellular carcinoma in the USA.

Methods: A Markov model was developed following time‐to‐progression and survival using phase III trial data. Health effects are expressed as life‐years gained. Resource utilization included drugs, physician visits, laboratory tests, scans, and hospitalizations. Unit costs, expressed in 2007 $US, came from diagnosis‐related groupings, fee schedules, and the Red Book. Costs and effects were evaluated over a patient's lifetime and discounted at 3%.

Results: Results are presented as incremental cost/life‐year gained. Deterministic and probabilistic sensitivity analyses were conducted. Life‐years gained were increased for sorafenib compared to best supportive care (mean ± standard deviation: 1.58 ± 0.17vs1.05 ± 0.10 life‐years gained/sorafenib patient and best supportive care, respectively). Lifetime total costs were $US40 639 ± $US3052 for sorafenib and $US7 804 ± $US1349 for best supportive care. The incremental cost‐effectiveness ratio was $US62 473/life‐year gained.

Conclusions: The economic evaluation indicates that sorafenib is cost‐effective compared to best supportive care, with a cost‐effectiveness ratio within the established threshold that US society is willing to pay (i.e. $US50 000–$US100 000) and significantly lower than alternative thresholds suggested in recent years ($US183 000–$US264 000/life‐year gained, or $US300 000/quality‐adjusted life‐year) in oncology.
Repeat participation in colorectal cancer screening utilizing fecal occult blood testing: A community‐based project in a rural setting
Authors: Janda Monika , Hughes Karen L , Auster Josephine F , Leggett Barbara A , Newman Beth M
Published: June 2010

Background and Aim:  To investigate participation in a second round of colorectal cancer screening using a fecal occult blood test (FOBT) in an Australian rural community, and to assess the demographic characteristics and individual perspectives associated with repeat screening.

Methods:  Potential participants from round 1 (50–74 years of age) were sent an intervention package and asked to return a completed FOBT (n = 3406). Doctors of participants testing positive referred to colonoscopy as appropriate. Following screening, 119 participants completed qualitative telephone interviews. Multivariable logistic regression models evaluated the association between round‐2 participation and other variables.

Results:  Round‐2 participation was 34.7%; the strongest predictor was participation in round 1. Repeat participants were more likely to be female; inconsistent screeners were more likely to be younger (aged 50–59 years). The proportion of positive FOBT was 12.7%, that of colonoscopy compliance was 98.6%, and the positive predictive value for cancer or adenoma of advanced pathology was 23.9%. Reasons for participation included testing as a precautionary measure or having family history/friends with colorectal cancer; reasons for non‐participation included apathy or doctors' advice against screening.

Conclusion:  Participation was relatively low and consistent across rounds. Unless suitable strategies are identified to overcome behavioral trends and/or to screen out ineligible participants, little change in overall participation rates can be expected across rounds.
Serious infections in patients with inflammatory bowel disease receiving anti‐tumor‐necrosis‐factor‐alpha therapy: An Australian and New Zealand experience
Authors: Lawrance Ian C , Radford‐Smith Graham L , Bampton Peter A , Andrews Jane M , Tan Pok‐Kern , Croft Anthony , Gearry Richard B , Florin Timothy H J
Published: June 2010

Background and Aim:  Anti‐tumor‐necrosis‐factor‐alpha (anti‐TNF‐α) medications are effective in inflammatory bowel disease (IBD), but have an increased risk of tuberculosis (TB) and serious infections. The aim of this study was to examine the Australian/New Zealand experience of serious infections and TB in IBD patients receiving anti‐TNF‐α therapy from 1999–2009.

Methods:  Serious infections, defined as ‘requiring hospital admission’ and TB cases in patients receiving, or within 3 months following, anti‐TNF‐α therapy were analyzed across Australia and New Zealand. Patient demographics, IBD medications, duration of anti‐TNF‐α therapy, and infection details were collected.

Results:  A total of 5562 IBD patients were managed across the centers. Of these, 489 (16.8%) Crohn's disease and 137 (5.2%) ulcerative colitis patients received anti‐TNF‐α therapy. There were three cases of latent TB that received prophylaxis prior to anti‐TNF‐α therapy. No cases of active TB were reported. Fourteen (2.2%) serious infections occurred. Seven occurred in patients receiving anti‐TNF‐α therapy for less than 6 months, including two cases of primary Varicella zoster (VZV), two cases of Pneumocystis jiroveci pneumonia, two cases of Staphylococcus aureus bacteremia, and one severe flu‐like illness. Six patients were taking additional immunosuppressive medications. The other seven infections occurred after 6 months (mean 32.6 ± 24.3 months) and included one case of primary VZV, one flu‐like illness, and five bacterial infections. All infections resolved with treatment.

Conclusion:  TB is a very rare complication of anti‐TNF‐α therapy in Australia and New Zealand. Serious infections are uncommon but early opportunistic infections with Pneumocystis jiroveci pneumonia suggest a need for vigilance in patients on multiple immunosuppressive medications. VZV vaccination prior to immunosuppressive therapy should be considered in VZV‐naïve patients.
Triptolide attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction
Authors: YUAN XIAO‐PENG , HE XIAO‐SHUN , WANG CHANG‐XI , LIU LONG‐SHAN , FU QIAN
Published: June 2010

Aim: Extracts ofTripterygium wilfordiiHook F. have been used to treat glomerulonephritis for more than 30 years in China. Most of the anti‐inflammatory and immunosuppressive activities of these extracts can be attributed to triptolide (Trip). The present study was to investigate the effect of Trip on renal interstitial fibrosis in a model of unilateral ureteral obstruction (UUO).

Methods: UUO or sham‐operated rats were randomly assigned to receive mycophenolate mofetil (MMF), Trip or vehicle and were killed on days 7 and 14 after UUO or sham operation. Kidney specimens were fixed for immunohistochemistry for myofibroblasts (α‐smooth muscle actin, α‐SMA), macrophages (ED‐1), monocyte chemoattractant protein‐1 (MCP‐1) and osteopontin. Interstitial collagen deposition and amounts of transforming growth factor‐β1 (TGF‐β1) were determined by Sirius red staining and enzyme‐linked immunosorbent assay, respectively. The mRNA expression of TGF‐β1, connective tissue growth factor (CTGF), MCP‐1 and osteopontin were measured by real‐time polymerase chain reaction analysis.

Results: The scores for the density of α‐SMA‐ and ED‐1‐positive cells, the staining of MCP‐1 and osteopontin, interstitial collagen deposition and amounts of TGF‐β1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF‐β1, CTGF, MCP‐1 and osteopontin.

Conclusion: Trip significantly attenuated tubulointerstitial fibrosis in a rat UUO model and the effect of Trip on renal fibrosis was similar to that of MMF. Trip may be useful as a potential candidate in the treatment of renal fibrosis.
Cut‐off values for serum matrix metalloproteinase‐9: Is there a threshold to predict renal involvement for Henoch–Schonlein purpura in children?
Authors: QIN YUAN‐HAN , ZHOU TIAN‐BIAO , LEI FENG‐YING , HUANG WEI‐FANG , ZHAO YAN‐JUN , LIN FA‐QUAN , SU LI‐NA
Published: June 2010

Aim:  To clarify whether the level of matrix metalloproteinase‐9 (MMP‐9), tissue inhibitor matrix metalloproteinase‐1 (TIMP‐1) or the ratio of MMP‐9/TIMP‐1 was associated with the renal involvement in Henoch–Schonlein purpura (HSP); and to explore whether there existed early diagnostic measure for HSP nephritis (HSPN).

Methods:  Sixty‐six patients with HSPN, 68 patients with HSP and 60 healthy children (control group) were enrolled into our study. Serum and urine samples before treatment were collected for detection.

Results:  Compared with the HSP group and control group, serum MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in the HSPN group were significantly higher (P < 0.05 and P < 0.01, respectively). Urine MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in the HSPN group were obviously higher than those of the control group (P < 0.05) and the HSP group (P < 0.05). Receiver–operator curve (ROC) analysis was performed to obtain the area under the curve (AUC) and the AUC and its 95% confidence interval (CI) of serum MMP‐9 were 0.97 and 0.95–0.99, respectively. The optimal cut‐off point (sensitivity; specificity) of serum MMP‐9 for diagnosing HSPN was 179.79 mg/L (0.96; 0.88).

Conclusion:  Levels of MMP‐9, TIMP‐1 and ratio of MMP‐9/TIMP‐1 in serum and urine were remarkably high in the patients with HSPN, but the serum MMP‐9 was more sensitive. Serum MMP‐9 may be associated with the occurrence and development of renal involvement in HSPN and become an important indicator for early diagnosis of HSPN.
Intra‐dialytic hypotension and blood volume and blood temperature monitoring
Authors: DAMASIEWICZ MATTHEW J , POLKINGHORNE KEVAN R
Published: June 2010

Intra‐dialytic hypotension (IDH) is a common problem affecting haemodialysis patients. Its aetiology is complex and influenced by multiple patient and dialysis factors. IDH occurs when the normal cardiovascular response cannot compensate for volume loss associated with ultrafiltration, and is exacerbated by a myriad of factors including intra‐dialytic fluid gains, cardiovascular disease, antihypertensive medications and the physiological demands placed on patients by conventional haemodialysis. The use of blood volume monitoring and blood temperature monitoring technologies is advocated as a tool to predict and therefore prevent episodes of IDH. We review the clinical utility of these technologies and summarize the current evidence of their effect on reducing the incidence of IDH in haemodialysis population.
Review: The role of microRNAs in kidney disease
Authors: LI JORDAN YZ , YONG TUCK Y , MICHAEL MICHAEL Z , GLEADLE JONATHAN M
Published: June 2010

MicroRNAs (miRNAs) are short non‐coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte‐specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR‐192) can also act as an effector of transforming growth factor‐β activity in the high‐glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.
Combined diode laser cyclophotocoagulation and intravitreal bevacizumab (Avastin) in neovascular glaucoma
Authors: Ghosh Sudipta , Singh Dalveer , Ruddle Jonathan B , Shiu Michael , Coote Michael A , Crowston Jonathan G
Published: June 2010

Abstract

Background:  Intravitreal injection of bevacizumab (Avastin) in eyes with neovascular glaucoma (NVG) has recently been shown to induce rapid regression of anterior segment neovascularization and has promise as adjunct treatment to diode laser cyclophotocoagulation (CPC) to control intraocular pressure (IOP). This study presents the outcome of concomitant treatment with CPC and intravitreal bevacizumab in painful poor visual potential eyes in a case series of consecutively diagnosed NVG.

Methods:  Twelve patients (14 eyes) were treated with CPC and concurrent intravitreal bevacizumab 0.05 mL (1.25 mg) and study end‐points were IOP lowering, regression of anterior segment neovascularization and resolution of pain.

Results:  The mean preoperative IOP was 42.1 ± 11.4 and was lowered to 16.6 ± 7.1 mmHg at 1‐month postoperatively. Anterior segment neovascularization regressed dramatically within 1 week of intravitreal bevacizumab in 12 eyes. Thirteen eyes reported persistent relief of ocular pain at 6 months following treatment.

Conclusions:  Combined intravitreal bevacizumab and CPC treatment for NVG provides rapid control of anterior segment neovascularization and may lead to improved symptomatic relief and IOP control.
Mortality rate of alcoholic liver disease and risk of hospitalization for alcoholic liver cirrhosis, alcoholic hepatitis and alcoholic liver failure in Australia between 1993 and 2005
Authors: Liang W. , Chikritzhs T. , Pascal R. , Binns C. W.
Published: June 2010

Background:  Alcoholic liver disease (ALD) is an important contributor to the total burden of alcohol‐related harm; however, the morbidity of different types of ALD in Australia has not been described. The aim of this study was to investigate recent trends in hospital admission rates among alcoholic liver cirrhosis, alcoholic hepatic failure and alcoholic hepatitis in Australia, as well as the mortality of ALD.

Method:  This is a population‐based cohort study including the total 15+ years Australian population. Data were obtained from the Australian Bureau of Statistics and the Australian Institute of Health and Welfare. Main outcome measures: (i) trend of standardized mortality rates and trend of standardized hospital admission rates for males and females for 1993/1994–2004/2005 (fiscal year), (ii) relative risk of alcoholic liver cirrhosis, alcoholic hepatic failure and alcoholic hepatitis hospital admissions for 1999/2000–2004/2005.

Results:  The mortality rate of ALD decreased significantly. Significant increases in hospital admissions for alcoholic hepatic failure among older adults and alcoholic hepatitis among younger age groups were observed. There is a significant 10‐fold increase in the risk of hospital admissions of alcoholic cirrhosis in 2002/2003 for the 20–29 years population.

Conclusion:  Reductions in overall ALD mortality observed are likely the result of advances in disease management. Significant increase in hospital admissions suggests an increase in the prevalence of ALD among the Australian population. Dramatic increases in hospital admissions for alcoholic cirrhosis in 2002/2003 for the 20–29 years population may have been due to an increase in screening of alcohol‐related harms in primary care settings.
Survival in scleroderma: results from the population‐based South Australian Register
Authors: Hissaria P. , Lester S. , Hakendorf P. , Woodman R. , Patterson K. , Hill C. , Ahern M. J. , Smith M. D. , Walker J. G. , Roberts‐Thomson P. J.
Published: June 2010

Aim:  To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR).

Methods:  The SASR is a population‐based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15‐year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n= 786).

Results:  Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28–1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti‐topoisomerase (Scl‐70) and anti‐U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5–75.7), diffuse scleroderma 62.9 years (95% CI 59.4–66.4) and overlap disease 57.8 years (95% CI 48.7–66.9). Survival improved over the 15‐year study period.

Conclusions:  Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma‐associated antibodies, Scl‐70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15‐year study period.
Implementing a web‐based oncology protocol system in Australia: evaluation of the first 3 years of operation
Authors: Hains I. M. , Ward R. L. , Pearson S.‐A.
Published: June 2010

Background:  EviQ is a web‐based oncology protocol system launched across Australia in 2005 (http://www.eviq.org.au). We evaluated eviQ use at the point‐of‐care and determined the factors impacting on its uptake and routine use in the first three years of operation.

Methods:  We conducted a suite of qualitative and quantitative studies with over 200 Australian oncology physicians, nurses and pharmacists working at treatment centres in diverse geographical locations.

Results:  EviQ was part of routine care at many hospitals; however, the way in which it was used at the point‐of‐care varies according to clinician roles and hospital location. We identified a range of factors impacting on eviQ uptake and routine use. Infrastructure, such as availability of point‐of‐care computers, and formal policies endorsing eviQ are fundamental to increasing uptake. Furthermore, the level of clinical and computer experience of end‐users, the attitudes and behaviour of clinicians, endorsement and promotion strategies, and level and type of eviQ education all need to be considered and managed to ensure that the system is being used to its full potential.

Conclusion:  Our findings show that the dissemination of web‐based treatment protocols does not guarantee widespread use. Organisational, environmental and clinician‐specific factors play a role in uptake and utilisation. The deployment of sufficient computer infrastructure, implementation of targeted training programmes and hospital policies and investment in marketing approaches are fundamental to uptake and continued use. This study highlights the value of ongoing monitoring and evaluation to ensure systems like eviQ achieve their primary purpose – reducing treatment variation and improving quality of care.
Temporal properties of spatial frequency tuning of surround suppression in the primary visual cortex and the lateral geniculate nucleus of the cat
Authors: Ishikawa Ayako , Shimegi Satoshi , Kida Hiroyuki , Sato Hiromichi
Published: June 2010

In primary visual cortex (V1) neurons, a stimulus placed in the extraclassical receptive field suppresses the response to a stimulus within the classical receptive field (CRF), a phenomenon referred to as surround suppression. The aim of the present study was to elucidate the mechanisms of surround suppression in V1. Using stationary‐flashed sinusoidal grating as stimuli, we observed temporal changes of surround suppression in V1 and the lateral geniculate nucleus (LGN) and of the response to CRF stimulation in V1. The spatial frequency (SF) tuning of surround suppression in V1 neurons changed over time after the stimulus onset. In the early phase (< 50 ms), the SF tuning was low‐pass, but later became band‐pass that tuned to the optimal SF in response to CRF stimulation. On the other hand, the SF tuning of CRF responses in V1 was band‐pass throughout the response time whereas the SF peak shifted slightly toward high SF. Thus, SF tuning properties of the CRF response dissociated from that of surround suppression in V1 only in the early phase. We also confirmed that the temporal changes of the SF tuning of surround suppression in the LGN occurred in the same direction as surround suppression in V1, but the shift from low‐pass to band‐pass SF tuning started later than that in V1. From these results, we suggest that subcortical mechanisms contribute to early surround suppression in V1, whereas cortical mechanisms contribute to late surround suppression.
TARPs γ‐2 and γ‐7 are essential for AMPA receptor expression in the cerebellum
Authors: Yamazaki Maya , Fukaya Masahiro , Hashimoto Kouichi , Yamasaki Miwako , Tsujita Mika , Itakura Makoto , Abe Manabu , Natsume Rie , Takahashi Masami , Kano Masanobu , Sakimura Kenji , Watanabe Masahiko
Published: June 2010

The α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptors require auxiliary subunits termed transmembrane AMPA receptor regulatory proteins (TARPs), which promote receptor trafficking to the cell surface and synapses and modulate channel pharmacology and gating. Of six TARPs, γ‐2 and γ‐7 are the two major TARPs expressed in the cerebellum. In the present study, we pursued their roles in synaptic expression of cerebellar AMPA receptors. In the cerebellar cortex, γ‐2 and γ‐7 were preferentially localized at various asymmetrical synapses. Using quantitative Western blot and immunofluorescence, we found severe reductions in GluA2 and GluA3 and mild reduction in GluA4 in γ‐2‐knockout (KO) cerebellum, whereas GluA1 and GluA4 were moderately reduced in γ‐7‐KO cerebellum. GluA2, GluA3 and GluA4 were further reduced in γ‐2/γ‐7 double‐KO (DKO) cerebellum. The large losses of GluA2 and GluA3 in γ‐2‐KO mice and further reductions in DKO mice were confirmed at all asymmetrical synapses examined with postembedding immunogold. Most notably, the GluA2 level in the postsynaptic density fraction, GluA2 labeling density at parallel fiber–Purkinje cell synapses, and AMPA receptor‐mediated currents at climbing fiber–Purkinje cell synapses were all reduced to approximately 10% of the wild‐type levels in DKO mice. On the other hand, the reduction in GluA4 in γ‐7‐KO granular layer reflected its loss at mossy fiber–granule cell synapses, whereas that of GluA1 and GluA4 in γ‐7‐KO molecular layer was caused, at least partly, by their loss in Bergmann glia. Therefore, γ‐2 and γ‐7 cooperatively promote synaptic expression of cerebellar AMPA receptors, and the latter also promotes glial expression.
The neurobiology of amyotrophic lateral sclerosis
Authors: Bento‐Abreu André , Van Damme Philip , Van Den Bosch Ludo , Robberecht Wim
Published: June 2010

Amyotrophic lateral sclerosis is a degenerative disease affecting the motor neurons. In spite of our growing insights into its biology, it remains a lethal condition. The identification of the cause of several of the familial forms of ALS allowed generation of models to study this disease bothin vitroandin vivo. Here, we summarize what is known about the pathogenic mechanisms of ALS induced by hereditary mutations, and attempt to identify the relevance of these findings for understanding the pathogenic mechanisms of the sporadic form of this disease.
Secretagogin is a Ca2+‐binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon
Authors: Mulder Jan , Spence Lauren , Tortoriello Giuseppe , DiNieri Jennifer A. , Uhlén Mathias , Shui Bo , Kotlikoff Michael I. , Yanagawa Yuchio , Aujard Fabienne , Hökfelt Tomas , Hurd Yasmin L. , Harkany Tibor
Published: June 2010

The Ca2+‐binding proteins (CBPs) calbindin D28k, calretinin and parvalbumin are phenotypic markers of functionally diverse subclasses of neurons in the adult brain. The developmental dynamics of CBP expression are precisely timed: calbindin and calretinin are present in prospective cortical interneurons from mid‐gestation, while parvalbumin only becomes expressed during the early postnatal period in rodents. Secretagogin (scgn) is a CBP cloned from pancreatic β and neuroendocrine cells. We hypothesized that scgn may be expressed by particular neuronal contingents during prenatal development of the mammalian telencephalon. We find that scgn is expressed in neurons transiting in the subpallial differentiation zone by embryonic day (E)11 in mouse. From E12, scgn+ cells commute towards the extended amygdala and colonize the bed nucleus of stria terminalis, the interstitial nucleus of the posterior limb of the anterior commissure, the dorsal substantia innominata (SI) and the central and medial amygdaloid nuclei. Scgn+ neurons can acquire a cholinergic phenotype in the SI or differentiate into GABA cells in the central amygdala. We also uncover phylogenetic differences in scgn expression as this CBP defines not only neurons destined to the extended amygdala but also cholinergic projection cells and cortical pyramidal cells in the fetal nonhuman primate and human brains, respectively. Overall, our findings emphasize the developmentally shared origins of neurons populating the extended amygdala, and suggest that secretagogin can be relevant to the generation of functional modalities in specific neuronal circuitries.