bluuebunny/crossref_metadata_2025 huggingface dataset:
Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early‐onset prostate cancer
Authors: Arsova‐Sarafinovska Zorica , Matevska Nadica , Petrovski Daniel , Banev Saso , Dzikova Sonja , Georgiev Vladimir , Sikole Aleksandar , Sayal Ahmet , Aydin Ahmet , Suturkova Ljubica , Dimovski Aleksandar J.
Published: July 2008

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer‐related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T→C single nucleotide substitution, resulting in a Val→Ala change at position 9 (Ala‐9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala‐9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69–2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non‐aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2‐fold increased risk of early‐onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease. Copyright © 2008 John Wiley & Sons, Ltd.
Comparative study of the residues 63 and 67 on the HLA‐B molecule in patients with Takayasu's arteritis and tuberculosis
Authors: Vargas‐Alarcón Gilberto , Soto María Elena , Pérez‐Hernández Nonanzit , Cicero‐Sabido Raúl , Ramírez Ernestina , Alvarez‐León Edith , Reyes Pedro A.
Published: July 2008

Takayasu's arteritis (TA) and tuberculosis (TB) have been associated with major histocompatibility complex genes, especially HLA‐B alleles. However, different HLA‐B alleles have been detected in these diseases. The aim of the study was to compare the distribution of the residues 63 and 67 on the HLA‐B molecule in patients with TA and TB in order to establish a genetic relationship between these two diseases. HLA‐B sequences obtained in 30 patients with TB were compared to those previously reported in TA and healthy controls. 8 out of 30 TB patients studied (26.6%) presented at least one allele with glutamic acid at position 63 and serine at position 67. This was observed in 73% of the TA patients (p = 0.0005). Ten TB (10/30 = 33.3%) and two TA patients (2/26 = 7.7%) did not show similarity at the mentioned positions (p = 0.019). This preliminary study suggests a difference in the distribution of the residues 63 and 67 of the HLA‐B alleles in patients with TA and TB. Copyright © 2008 John Wiley & Sons, Ltd.
Photoluminescent Microporous Lanthanide Silicate AV‐21 Frameworks
Authors: Kowalchuk Collin M. , Paz Filipe A. A. , Ananias Duarte , Pattison Philip , Carlos Luís D. , Rocha João
Published: July 2008

The hydrothermal synthesis and structural characterization of the lanthanide silicate system [Na6Ln2Si12O30⋅x H2O] (Ln=La3+, Sm3+, Eu3+, Gd3+, and Tb3+), named AV‐21, has been reported. Structural elucidation of the Sm3+ analogue (isomorphous with the Eu3+, Gd3+, and Tb3+ frameworks) using single‐crystal synchrotron X‐ray diffraction and solid‐state NMR spectroscopy reveal disorder in the Si(1) second coordination sphere. La‐AV‐21 presents a distinct framework. These materials combine microporosity and interesting photoluminescence features with structural flexibility that allows the introduction of a second or third type of lanthanide center. Room‐temperature lifetime decay dynamics have been used to estimate the Ln3+Ln3+ distances and the maximum distance over which energy transfer is active. Though the majority of Ln3+ centers occupy regular framework positions, the Ln(2) defect centers are disordered over the Na(1) sites in the pores and greatly influence the energy‐transfer process, providing a unique opportunity for studying the relationship between structural disorder and photoluminescence properties in framework solids.
A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post–liver transplantation hepatitis B prophylaxis
Authors: Angus Peter W. , Patterson Scott J. , Strasser Simone I. , McCaughan Geoffrey W. , Gane Edward
Published: July 2008

Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen–positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 μmol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was $8,290 versus $13,718 IM HBIG/lamivudine.

Conclusion:

Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost. (Hepatology 2008.)
An abnormal gene expression of the β-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats
Authors: Ceolotto Giulio , Papparella Italia , Sticca Antonietta , Bova Sergio , Cavalli Maurizio , Cargnelli Gabriella , Semplicini Andrea , Gatta Angelo , Angeli Paolo
Published: July 2008

Decreased cardiac contractility and β-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study β-adrenergic–stimulated contractility and β-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10−10 to 10−6 M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha–inhibiting subunit 2 (Gαi2), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of Gαi2, PDE2a, and RGS2 down-regulates the β-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. (Hepatology 2008;48:1913-1923.)
Low‐dose oral fludarabine plus cyclophosphamide in elderly patients with untreated and relapsed or refractory chronic lymphocytic Leukaemia
Authors: Forconi Francesco , Fabbri Alberto , Lenoci Mariapia , Sozzi Elisa , Gozzetti Alessandro , Tassi Maristella , Raspadori Donatella , Lauria Francesco
Published: July 2008

Fludarabine plus cyclophosphamide (FC) at conventional doses is an effective treatment for chronic lymphocytic leukaemia (CLL). However, FC at standard doses may give hematological and non‐hematological toxicity, predominantly in the elderly. Intravenous or oral low‐dose FC regimens remain highly effective in elderly patients with Low‐Grade Lymphomas other than CLL and are well tolerated. We tested efficacy and toxicity of oral FC at reduced doses in 26 elderly patients (median 71 years) with previously untreated (UT‐CLL, n = 14) or relapsed/refractory CLL (R‐CLL, n = 12), unfit for conventional treatments. Twentyfour‐of‐26 (92%) patients (14/14, 100% UT‐CLL; 10/12, 83.5% R‐CLL) obtained a response, with 12/26 (46%) complete responses (9/14, 64.2% in UT‐CLL; 3/12, 25% in R‐CLL). Non‐hematological toxicity was mild and myelosuppression was documented in 8/26 (31%) patients (4/14, 28% UT‐CLL; 4/12, 33% R‐CLL). With a median follow‐up of 24 months, median event‐free survival was 48 months with no differences between UT‐CLL and R‐CLL and all responders were alive. Low‐dose oral FC treatment showed good efficacy in both untreated and refractory/relapsed CLL. The treatment is useful in elderly patients who cannot benefit of more aggressive schedules and is easy to administer on an outpatient basis. Copyright © 2008 John Wiley & Sons, Ltd.
An approach to health system strengthening in the Democratic Peoples Republic of Korea (North Korea)
Authors: Grundy John , Moodie Rob
Published: July 2008

Background

The Democratic Peoples Republic of Korea (DPRK), under the leadership of the Ministry of Public Health (MOPH), undertook the development of a Health System Strengthening (HSS) proposal through the support of the Global Alliance for Vaccines and Immunization (GAVI). The aim of this paper is to outline the approach to the development of the HSS strategy in DPRK, and describe opportunities and challenges associated with its development and future implementation. Sources of information for this review have included national programme plans, in country social sector reviews, information generated through HSS proposal developments and the international literature.

Findings

Updated assessments in DPRK indicate some recent improvements in the health situation for women and children, but there remain ongoing concerns regarding health management, human resource and physical infrastructure barriers to health services access. In response to this situation, the DPRK developed a health system strengthening strategy, the main elements of which are the strengthening of health management and service delivery systems at the implementing agency levels of county (district) and Ri (sub district). Three success factors were associated with the reaching of consensus on HSS strategy in DPRK. These were partnerships formed between system planners and programme planners, the identification of an overall health sector strategic framework, and high‐level leadership of the MOPH.

Conclusion

Although DPRK is in the very early stages of health system reconstruction, there are significant and new opportunities to alleviate the health conditions of women and children in DPRK, through implementation of health system strengthening strategies that are nationally coordinated and internationally supported. Copyright © 2008 John Wiley & Sons, Ltd.
Association between plasma cholesterol and prostate cancer in the PSA era
Authors: Platz Elizabeth A. , Clinton Steven K. , Giovannucci Edward
Published: July 2008

We previously found that statin users had a lower risk of advanced and possibly high‐grade prostate cancer compared with nonusers. We hypothesize that statins' effects on cholesterol synthesis may explain those findings because prostate cancer cells exhibit cholesterol dysregulation. Thus, we investigated whether low plasma cholesterol is associated with prostate cancer overall and by stage and grade. Participants were drawn from the 18,018 members of the Health Professionals Follow‐Up Study who provided blood in 1993–1995. We ascertained 698 incident cases through January 2000. Controls were 698 men who had a PSA test and were matched to cases. Plasma cholesterol was measured enzymatically. Conditional logistic regression was used to estimate multivariable ORs and 95% CIs of total, clinically organ‐confined (n = 518), advanced (T3b or worse; n = 61), low‐grade (Gleason sum < 7; n = 386) and high‐grade (Gleason sum ≥ 7, n = 247) disease. Low cholesterol (<25th percentile vs. ≥25th percentile) was not associated with total (OR = 0.93, 95% CI: 0.72–1.20), organ‐confined (OR = 0.87, 95% CI: 0.64–1.18) or low‐grade (OR = 1.06, 95% CI: 0.75–1.51) disease. However, men with low cholesterol had a lower risk of high‐grade disease (OR = 0.61, 95% CI: 0.39–0.98), especially if organ‐confined (OR = 0.54, 95% CI: 0.29–0.99). The association for advanced disease appeared inverse, but number of cases was small (OR = 0.42, 95% CI: 0.13–1.36). Associations remained after excluding cholesterol‐lowering drug users. These results coupled with prior statin findings suggest that mechanistic studies on cholesterol metabolism should be pursued to understand a possible target for preventing poorly differentiated prostate cancers. © 2008 Wiley‐Liss, Inc.
Racial/ethnic variation in EBV‐positive classical Hodgkin lymphoma in California populations
Authors: Glaser Sally L. , Gulley Margaret L. , Clarke Christina A. , Keegan Theresa H. , Chang Ellen T. , Shema Sarah J. , Craig Fiona E. , DiGiuseppe Joseph A. , Dorfman Ronald F. , Mann Risa B. , Anton‐Culver Hoda , Ambinder Richard F.
Published: July 2008

Epstein‐Barr virus (EBV) is detected in the tumor cells of some but not all Hodgkin lymphoma (HL) patients, and evidence indicates that EBV‐positive and ‐negative HL are distinct entities. Racial/ethnic variation in EBV‐positive HL in international comparisons suggests etiologic roles for environmental and genetic factors, but these studies used clinical series and evaluated EBV presence by differing protocols. Therefore, we evaluated EBV presence in the tumors of a large (n = 1,032), racially and sociodemographically diverse series of California incident classical HL cases with uniform pathology re‐review and EBV detection methods. Tumor EBV‐positivity was associated with Hispanic and Asian/Pacific Islander (API) but not black race/ethnicity, irrespective of demographic and clinical factors. Complex race‐specific associations were observed between EBV‐positive HL and age, sex, histology, stage, neighborhood socioeconomic status (SES), and birth place. In Hispanics, EBV‐positive HL was associated not only with young and older age, male sex, and mixed cellularity histology, but also with foreign birth and lower SES in females, suggesting immune function responses to correlates of early childhood experience and later environmental exposures, respectively, as well as of pregnancy. For APIs, a lack of association with birth place may reflect the higher SES of API than Hispanic immigrants. In blacks, EBV‐positive HL was associated with later‐stage disease, consistent with racial/ethnic variation in certain cytokine polymorphisms. The racial/ethnic variation in our findings suggests that EBV‐positive HL results from an intricate interplay of early‐ and later‐life environmental, hormonal, and genetic factors leading to depressed immune function and poorly controlled EBV infection. © 2008 Wiley‐Liss, Inc.
Chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a COX‐2 inhibitor
Authors: Oba Masaru , Miwa Koichi , Fujimura Takashi , Harada Shinichi , Sasaki Shozo , Hattori Takanori
Published: July 2008

Duodenogastric reflux (DGR) causes glandular stomach carcinogenesis in rats without carcinogens. We aimed to investigate how this carcinogenesis might be prevented by a selective COX‐2 inhibitor, meloxicam. A series of 188 Fisher 344 rats underwent a surgical DGR procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other an experimental chow containing meloxicam [0.3 mg/kg bw/day] (meloxicam group). The animals were sequentially sacrificed at weeks 20, 30, 40, 50 and 60 after surgery. The stomachs were removed and examined for the presence of carcinoma, incidence of reflux‐induced morphologic changes, COX‐2 expression and its activity. Adenocarcinoma in the glandular stomach developed in 7 of 21 animals (33%) in the control group at week 60, but none of 20 (0%) in the meloxicam group (p < 0.01). Moreover, reflux‐induced gastritis was definitely alleviated in the meloxicam group compared with the control group. COX‐2 immunoreactivity was predominantly detected in stromal cells such as macrophages and fibroblasts. Compared with nonsurgical rats, RNA expression of COX‐2 in the mucosa increased, reaching peak at an early phase of week 20 in both groups (p < 0.005). Expression of microsomal prostaglandin E synthase‐1 was lower in the meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group (p < 0.01). Gastric carcinogenesis via duodenal reflux was mediated by the COX‐2 pathway in rats. Administration of meloxicam prevented this carcinogenesis by suppressing the inflammatory process. © 2008 Wiley‐Liss, Inc.
In vitro degradation of a biodegradable polyurethane foam, based on 1,4‐butanediisocyanate: A three‐year study at physiological and elevated temperature
Authors: Zuidema J. , van Minnen B. , Span M. M. , Hissink C. E. , van Kooten T. G. , Bos R. R. M.
Published: July 2008

Biodegradable polyesterurethanes (PUs) may be used as scaffold materials for tissue regeneration applications, because of their excellent mechanical properties. In this study, the degradation of highly porous PU foams was evaluated in vitro. The PU had amorphous soft segments of DL‐lactide/ϵ‐caprolactone and uniform hard segments, synthesized from 1,4‐butanediisocyanate and butanediol. The foams were degraded for 3 years in a Sörensen buffer solution (pH 7.4) at 37 and 60°C. Dimensions of the foams, intrinsic viscosity, mass loss, thermal properties, and composition of the remaining material were evaluated. Copolyester (CP) foams of DL‐lactide/ϵ‐caprolactone served as controls. The PU foams kept their dimensions for 20 weeks at 37°C, whereas CP foams collapsed after 3 weeks. PU mass loss reached a maximum of 80% at both 37 and 60°C. CP mass loss reached 99.9% at 60°, and 92% at 37°C after 3 years. The degradation processes at 37 and 60°C are initially the same, but eventually degradation products with different thermal properties are being formed. 1H NMR studies showed that the hard urethane segments of the PU do not degrade in vitro at pH 7.4. It was concluded that the PU material has favorable characteristics for a scaffold material. Compared to long‐term in vivo results of the same PU these in vitro results are not representative for the in vivo situation and therefore total resorption has to be investigated in long‐term in vivo studies. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
A potential mechanism for short time exposure to hypoxia‐induced DNA synthesis in primary cultured chicken hepatocytes: Correlation between Ca2+/PKC/MAPKs and PI3K/Akt/mTOR
Authors: Lee Sang Hun , Lee Min Young , Lee Jang Hern , Han Ho Jae
Published: July 2008

Less information is available concerning the molecular mechanisms of cell survival after hypoxia in hepatocytes. Therefore, this study examined the effect of hypoxia on DNA synthesis and its related signal cascades in primary cultured chicken hepatocytes. Hypoxia increased [3H] thymidine incorporation, which was increased significantly after 0–24 h of hypoxic exposure. Indeed, the percentage of cell population in the S phase was increased in hypoxia condition. However, the release of LDH indicating cellular injury was not changed under hypoxic conditions. Hypoxia increased Ca2+ uptake and PKC translocation from the cytosol to the membrane fraction. Among the PKC isoforms, hypoxia stimulated the translocation of PKC α and ε. Hypoxia also phosphorylated the p38 and p44/42 mitogen‐activated protein kinases (MAPKs), which were blocked by the inhibition of PKC. On the other hand, hypoxia increased Akt and mTOR phosphorylation, which was blocked in the absence of intra/extracellular Ca2+. The inhibition of PKC/MAPKs or PI3K/Akt pathway blocked the hypoxia‐induced [3H] thymidine incorporation. However, hypoxia‐induced Ca2+ uptake and PKC translocation was not influenced by LY 294002 or Akt inhibitor and hypoxia‐induced MAPKs phosphorylation was not changed by rapamycin. In addition, LY 294002 or Akt inhibitor has no effect on the phosphorylation of MAPKs. It suggests that there is no direct interaction between the two pathways, which cooperatively mediated cell cycle progression to hypoxia in chicken hepatocytes. Hypoxia also increased the level of the cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin‐dependent kinase (CDK) 2, and CDK 4] and p‐RB protein but decreased the p21 and p27 expression levels, which were blocked by inhibitors of upstream signal molecules. In conclusion, short time exposure to hypoxia increases DNA synthesis in primary cultured chicken hepatocytes through cooperation of Ca2+/PKC, p38 MAPK, p44/42 MAPKs, and PI3K/Akt pathways. J. Cell. Biochem. 104: 1598–1611, 2008. © 2008 Wiley‐Liss, Inc.
Development and characterization of a triple combination gene therapy vector inhibiting HIV‐1 multiplication
Authors: Asparuhova Maria B. , Barde Isabelle , Trono Didier , Schranz Karin , Schümperli Daniel
Published: July 2008

Background

RNA‐based approaches are promising for long‐term gene therapy against HIV‐1. They can target virtually any step of the viral replication cycle. It is also possible to combine anti‐HIV‐1 transgenes targeting different facets of HIV replication to compensate for limitations of any individual construct, maximizing efficacy and decreasing chances of escape mutations. We have previously developed two strategies to inhibit HIV‐1 multiplication. One was a short hairpin RNA targeting the host factor cyclophilin A implicated in HIV‐1 replication. Additionally, an antisense derivative of U7 small nuclear RNA was designed to induce the skipping of the HIV‐1 Tat and Rev internal exons.

Results

In the present study, we have established an additional tRNAval promoter‐driven shRNA against the coding sequence of viral infectivity factor. When human T‐cell lines or primary CD4+ T cells are transduced with a triple lentiviral vector encoding these three therapeutic RNAs, HIV‐1 multiplication is very efficiently suppressed. Moreover, all three therapeutic RNAs exhibit antiviral effects at early stages of the viral replication cycle (i.e. prior to viral cDNA integration or gene expression).

Conclusions

These findings make this triple lentiviral vector an attractive candidate for a gene therapy against HIV/AIDS. Copyright © 2008 John Wiley & Sons, Ltd.
Pitx3‐transfected astrocytes secrete brain‐derived neurotrophic factor and glial cell line‐derived neurotrophic factor and protect dopamine neurons in mesencephalon cultures
Authors: Yang Dehua , Peng Changgeng , Li Xuping , Fan Xiaolan , Li Liang , Ming Ming , Chen Sheng , Le Weidong
Published: July 2008

The transcription factor Pitx3 is crucial for the development and differentiation of dopamine (DA) neurons. Our previous work has shown the Pitx3 can up‐regulate the expression of brain‐derived neurotrophic factor (BDNF) and glial cell line‐derived neurotrophic factor (GDNF) in neuroblastoma cell line SH‐SY5Y. Primary astrocytes are the major nonneuronal cells and can be easily modified genetically to deliver therapeutic molecules into the brain, so we investigated whether Pitx3 can increase the expression and secretion of BDNF and GDNF in primary astrocytes. We first transfected Pitx3 plasmid in purified rat astrocytes and collected the conditioned medium (CM) from the Pitx3‐transfected cultures, and then we measured the BDNF and GDNF levels from the CM and tested the protective effect of the CM against rotenone‐induced DA neuron injury in ventral mesencephalon (VM) cultures. We found that the BDNF and GDNF levels were 1.4‐fold and 1.5‐fold higher in the CM from Pitx3‐transfected astrocytes than empty vectors‐transfected controls. Incubation with the CM from Pitx3‐transfected astrocytes significantly attenuated the rotenone‐induced DA neuron injury, and such protection can be significantly blocked by preincubation with antibodies against either BDNF or GDNF, whereas preincubation with purified BDNF or GDNF replicated the neuroprotection against rotenone‐induced injury in VM cultures. These results demonstrate that Pitx3‐transfection in astrocytes can up‐regulate BDNF and GDNF expression and produce protective benefit to DA neurons, which might be a potential therapeutic alternative for Parkinson's disease. © 2008 Wiley‐Liss, Inc.
Differential MRI patterns of brain atrophy in double or single transgenic mice for APP and/or SOD
Authors: Borg Jacques , Chereul Emmanuel
Published: July 2008

Clinical magnetic resonance imaging (MRI) offers a noninvasive diagnostic tool for neurodegenerative diseases. MRI was performed on mice to investigate a relationship between brain atrophy and overexpression of two genes involved in such diseases, SOD1 (superoxide dismutase) and APP (amyloid precursor protein), which have been associated with pathogenesis of Alzheimer's disease or Down syndrome. Additionaly, we investigated how life span and growth rate were affected by genetic background. T2‐weighted MRI made possible the measurement of the volume of brain regions of interest in living transgenic mice that overexpress normal APP, SOD1, or both. The most pronounced alterations in gray matter volume were observed in 1‐year‐old double APP/SOD1 transgenic mice. Hippocampus, entorhinal, and cingulate cortex volumes were decreased by 8% to 25%. In contrast, mice homozygous for SOD1 exhibited atrophy specifically in cortex regions (cingulate, retrosplenial, and temporoparietal cortex), but no significant modification was found in the hippocampus region. None of these alterations was seen in single APP transgenics. However, the life span of these mice was significantly shortened. SOD1 overexpression prevented APP toxicity with regard to premature death, especially in double APP/SOD1 transgenic animals homozygous for SOD1, and increase in life span was significantly correlated to SOD1 activity. In conclusion, overexpression of both APP and SOD1, in contrast to single APP transgenics, produced a robust effect on brain anatomy but did not impair growth or life span. Consequences of genotype alterations on brain atrophy may be dissociated from their effect on life span. © 2008 Wiley‐Liss, Inc.
Identification of new markers for neurodegeneration process in the mouse model of Sly disease as revealed by expression profiling of selected genes
Authors: Richard Magali , Arfı Audrey , Rhinn Hervé , Gandolphe Christelle , Scherman Daniel
Published: July 2008

Sly disease (MPS VII) is an autosomal‐recessive lysosomal storage disorder resulting from beta‐glucuronidase deficiency, which is characterized by a severe neurological impairment. MPS VII mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, thus appearing to be an excellent tool to delineate disease pathogenesis. The relationship between abnormal glycosaminoglycan storage and neurodysfunction is not yet well understood, but inflammatory components can be involved, as in several neurological lysosomal disorders. Inflammatory biomarkers are thus good candidates to evaluate the neurodegeneration state of the disease. By using quantitative polymerase chain reaction, we have compared the expression of selected genes of normal and MPS VII cerebral tissues, focusing on inflammation and apoptosis‐related genes. The gene expression was evaluated in various brain regions throughout the lifetime of the animals. We have identified a specific expression profile for 27 genes, which was strongly marked in the central nervous system posterior region. Finally, new Sly disease markers were characterized that reflect neurological deterioration state, and that can be used in preclinical follow‐up studies. © 2008 Wiley‐Liss, Inc.
Oxidative impairment of hippocampal long‐term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies
Authors: Maalouf Marwan , Rho Jong M.
Published: July 2008

Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease. In the present study, we explored the effects of the KB acetoacetate (ACA) and β‐hydroxybutyrate (BHB) on impairment of hippocampal long‐term potentiation (LTP) in rats by hydrogen peroxide (H2O2) using electrophysiological, fluorescence imaging, and enzyme assay techniques. We found that: 1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H2O2 (200 μM); 2) KB significantly lowered intracellular levels of reactive oxygen species (ROS)—measured with the fluorescent indicator carboxy‐H2DCFDA (carboxy‐2′,7′‐dichlorodihydrofluorescein diacetate)—in CA1 pyramidal neurons exposed to H2O2; 3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; 4) KB prevented impairment of LTP by the PP2A activator C6 ceramide; 5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H2O2, and C6 ceramide did not increase ROS levels; 6) PP2A activity was enhanced by both H2O2 and rotenone (a mitochondrial complex I inhibitor that increases endogenous superoxide production); and 7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H2O2 or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism. © 2008 Wiley‐Liss, Inc.
An analysis of late twentieth century trends in Australian rainfall
Authors: Taschetto Andréa S. , England Matthew H.
Published: July 2008

Trends in Australian precipitation from 1970 to 2006 are examined using a daily rainfall dataset. Results suggest a linkage between changes in the monsoon trough and rainfall trends over northwestern Australia. The late twentieth century drought observed along the Queensland coast is a response to changes in the atmospheric circulation that generates anomalous subsidence at high and middle levels of the atmosphere, thus inhibiting convection over the region. In addition, an anomalous anticyclonic circulation at low levels over Queensland tends to weaken the easterlies in the tropical western Pacific, thus diminishing the transport of moist air onto the coast. Trends in the frequency and magnitude of different rainfall events are also examined. This reveals that changes in total rainfall are dominated by trends in very heavy rainfall events across Australia. For example, some parts of western Australia reveal an increase in heavy rainfall events that are not accompanied by a rise in modest rainfall events, resulting in changes in the shape of the distribution towards a more skewed precipitation distribution. On the other hand, the frequency of extreme rainfall events along the Queensland coast has declined during summer and autumn consistently with the total rainfall decrease, indicating changes in the position of the precipitation distribution rather than its shape. Copyright © 2008 Royal Meteorological Society
Out‐of‐plane deformations of the heme group in different ferrocytochrome c proteins probed by resonance Raman spectroscopy
Authors: Hagarman Andrew , Wallace Carmichael J. , Laberge Monique M. , Schweitzer‐Stenner Reinhard
Published: July 2008

We measured the low‐wavenumber polarized resonance Raman spectra of horse heart (hhc), chicken (chc) and yeastC102T (yc) ferrocytochromes c with Soret excitation. We examined the out‐of‐plane (oop) deformations of the heme groups by virtue of relative intensities and depolarization ratios of a variety of oop and in‐plane (ip) Raman active bands. Analysis of relative Raman intensities shows differences in deviation from planarity of the heme groups of yeast, horse heart and chicken cytochromes c. The heme groups in cytochrome c proteins have been shown by normal coordinate static deformation (NSD) analysis from crystal structures to exhibit a dominant ruffling (B1u) deformation. As a consequence the B1u modes, γ10 − γ12, become resonance Raman active. We used normalized Raman intensity ratios and depolarization ratios of oop Raman active modes, whose intensities are attributable to specific nonplanar deformations, to estimate and compare their Franck‐Condon‐type and Jahn‐Teller‐type coupling magnitudes for horse heart, chicken and yeast ferrocytochrome c at neutral pH. These coupling magnitudes allow for a quantitative comparison of oop deformations between individual heme groups. Chicken ferrocytochrome was found to have the largest ruffling deformation of the three investigated proteins, followed by horse heart and yeast cytochrome c. The heme group of the former is slightly more ruffled than the corresponding active site of the latter, while saddling in both proteins is substantially larger than in chicken ferrocytochrome c. The Raman data are sensitive enough to allow a comparison of lesser deformations. Doming, which is a kinetic coordinate in many heme proteins, is largest in chicken and smallest in yeast cytochrome c. Waving is largest in yeast, followed by horse heart and chicken cytochrome c. Propellering deformations could be compared for chicken and horse heart cytochrome c and were found to be substantially larger in the latter. A comparison with heme deformations obtained from X‐ray structures (for horse heart and yeast cytochrome c) and from molecular dynamics simulations (MDS) (performed for all three proteins) yields some agreement with the main ruffling and saddling deformations derived from the crystal structures, whereas the heme conformations produced by MDS seem to account better for smaller deformations like doming and propellering. The present study demonstrates the usefulness of resonance Raman spectroscopy for the analysis of nonplanar deformations in heme proteins. Copyright © 2008 John Wiley & Sons, Ltd.
Expression of mismatch repair proteins, hMLH1/hMSH2, in non‐small cell lung cancer tissues and its clinical significance
Authors: Kouso Hidenori , Yoshino Ichiro , Miura Naoko , Takenaka Tomoyoshi , Ohba Taro , Yohena Tomofumi , Osoegawa Atsushi , Shoji Fumihiro , Maehara Yoshihiko
Published: July 2008

Background

hMLH1 and hMSH2 have been implicated to be involved in the DNA mismatch repair (MMR) system. The purpose of this study is to investigate the expression of hMLH1 and hMSH2 DNA MMR proteins in non‐small cell lung cancer (NSCLC) tissue and to elucidate their clinical significance.

Methods

The hMLH1 and hMSH2 protein expression was evaluated by immunohistochemistry for a consecutive series of 113 NSCLC patients. The expressions of each protein were examined for an association with the clinicopathological variables, including genetic alterations analyzed by high resolution fluorescent microsatellite analysis.

Results

Regarding the hMLH1 expression, the MSI‐positive patients showed significantly lower scores than the MSI‐negative patients. For hMSH2 expression, the patients with a 20 or higher pack‐year index (PYI) showed significantly higher scores than the patients with a PYI less than 20. The expression status of proteins did not affect both the disease free and overall survival of the patients. No significant correlation was observed among the scores for the proteins.

Conclusions

The expressions of hMLH1 and hMSH2 are independently regulated and play different roles in NSCLC. The genetic instability is possibly due to the reduced expression of hMLH1 protein, and hMSH2 expression is associated with smoking status. J. Surg. Oncol. 2008;98:377–383. © 2008 Wiley‐Liss, Inc.
Response to interferon therapy affects risk factors for postoperative recurrence of hepatitis C virus‐related hepatocellular carcinoma
Authors: Uenishi Takahiro , Nishiguchi Shuhei , Tanaka Shogo , Yamamoto Takatsugu , Takemura Shigekazu , Kubo Shoji
Published: July 2008

Background

Interferon therapy might reduce recurrence after resection of hepatitis C virus‐related hepatocellular carcinoma, especially among sustained virologic or biochemical responders.

Methods

Of 209 patients who underwent curative resection for early‐stage hepatitis C virus related hepatocellular carcinoma, 70 patients underwent interferon therapy. A sustained virologic or biochemical response was achieved in 40 patients (SVR/BR group). Thirty no responders and 139 patients who had not received interferon therapy were classified as the NR/non‐IFN group. Risk factors for postoperative recurrence in each group were analyzed.

Results

The tumor‐free survival rates in the SVR/BR group were significantly higher than those in the NR/non‐IFN group. By multivariate analysis, the presence of multiple tumors was independently associated with recurrence after resection in both groups, while histologic evidence of cirrhosis was another independent risk factor for postoperative recurrence in the NR/non‐IFN group.

Conclusions

Newly multicentric carcinogenesis after resection could be suppressed when active hepatitis is controlled by interferon therapy. Patients with single hepatitis C virus related hepatocellular carcinoma detected after successful interferon therapy are good candidates for surgical resection. Adjuvant interferon therapy might be indicated for patients who undergo curative resection for single hepatocellular carcinoma associated with hepatitis C. J. Surg. Oncol. 2008;98:358–362. © 2008 Wiley‐Liss, Inc.
Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer
Authors: Lee Jun Ho , Ryu Keun Won , Kook Myeong‐Cherl , Lee Jong Yeul , Kim Chan Gyoo , Choi Il Ju , Kim Seok‐Ki , Jang Seyoun , Park Sook Ryun , Kim Young Woo , Nam Byung‐Ho , Bae Jae‐Moon
Published: July 2008

Background

The clinical applications of sentinel node (SN) biopsies in early gastric cancer are limited because of low sensitivity. Sentinel basin (SB) dissection has been suggested as alternative to SN biopsy to improve sensitivity. The aim of this study was to examine the feasibility of laparoscopic SB dissection.

Methods

Twenty‐one gastric adenocarcinoma patients of cT1N0 were enrolled. Technetium 99 m human serum albumin and indocyanine green were injected into the submucosal layer around tumor using an intraoperative endoscope. Green‐stained or radioactive lymphatic basins were detected and defined as SBs. After laparoscopic SB dissection, laparoscopy‐assisted gastrectomy with D2 lymphadenectomy was performed. Dissected SB nodes and non‐SB nodes were evaluated for metastasis pathologically.

Results

The SB detection rate was 95.2%. Numbers of SBs were one in 6, two in 10, and three in 4 patients. The mean number of SB nodes was 7.0. Two patients with lymph node metastasis were diagnosed by SB dissection. Mean time of laparoscopic SB dissection procedure was 15.2 min.

Conclusions

Above findings suggest that laparoscopic SB dissection is technically feasible, and it might have better sensitivity than SN biopsy. However, the validity of this procedure should be evaluated in a larger series before being clinically applied. J. Surg. Oncol. 2008;98:331–335. © 2008 Wiley‐Liss, Inc.
Stability of travelling wave solutions to a semilinear hyperbolic system with relaxation
Authors: Ueda Yoshihiro
Published: July 2008

We study a semilinear hyperbolic system with relaxation and investigate the asymptotic stability of travelling wave solutions with shock profile. It is shown that the travelling wave solution is asymptotically stable, provided the initial disturbance is suitably small. Moreover, we show that the time convergence rate is polynomially (resp. exponentially) fast ast→∞ if the initial disturbance decays polynomially (resp. exponentially) forx→∞. Our proofs are based on the space–time weighted energy method. Copyright © 2008 John Wiley & Sons, Ltd.
Minimization of energies related to the plate problem
Authors: Fuchs M.
Published: July 2008

We investigate the interior regularity of minimizers for an obstacle problem of higher order that can be seen as a model for the behaviour of a plate subject to a rather general constitutive law including nonlinear elastic materials. Copyright © 2008 John Wiley & Sons, Ltd.
Influence of glucose on cyanidin 3‐glucoside absorption in rats
Authors: Felgines Catherine , Texier Odile , Besson Catherine , Vitaglione Paola , Lamaison Jean‐Louis , Fogliano Vincenzo , Scalbert Augustin , Vanella Luca , Galvano Fabio
Published: July 2008

Anthocyanins are natural dietary pigments that could be involved in various health effects. However their mechanisms of absorption are still not fully understood. The aim of this study was to evaluate the influence of glucose on anthocyanin absorption in rats. We first studied anthocyanin bioavailability in rats that received by gastric intubation ∼︁53 μmol cyanidin 3‐glucoside (Cy 3‐glc) equivalents from a red orange extract with or without 2.51 mmol glucose. Neither 24‐h urinary anthocyanin excretion nor plasma anthocyanin concentration was significantly affected by simultaneous ingestion of glucose. The influence of glucose (12, 42 or 72 mM) on intestinal absorption of Cy 3‐glc (pure or from a red orange extract; ∼︁12.3 μM) was further studied using anin situintestinal perfusion model. Absorption of pure Cy 3‐glc from the intestinal lumen was not significantly affected by the amount of glucose. However, intestinal absorption of Cy 3‐glc from the red orange extract (6.49 ± 1.44%,n= 6) was significantly less than that of pure Cy 3‐glc (17.5 ± 1.3%,n= 7) (p< 0.01) suggesting that the red orange extract contained other components that were able to interfere with Cy 3‐glc intestinal absorption. This study has thus shown that glucose did not interfere with anthocyanin glucoside absorption.
Identification of a molecular marker for type A spermatogonia by microarray analysis using gonadal cells from pvasa‐GFP transgenic rainbow trout (Oncorhynchus mykiss)
Authors: Yano Ayaka , von Schalburg Kris , Cooper Glenn , Koop Ben F. , Yoshizaki Goro
Published: July 2008

The spermatogonia of fish can be classified as being either undifferentiated type A spermatogonia or differentiated type B spermatogonia. Although type A spermatogonia, which contain spermatogonial stem cells, have been demonstrated to be a suitable material for germ cell transplantation, no molecular markers for distinguishing between type A and type B spermatogonia in fish have been developed to date. We therefore sought to develop a molecular marker for type A spermatogonia in rainbow trout. Using GFP‐dependent flow cytometry (FCM), enriched fractions of type A and type B spermatogonia, testicular somatic cells, and primordial germ cells were prepared from rainbow trout possessing the green fluorescent protein (GFP) gene driven by trout vasa regulatory regions (pvasa‐GFP rainbow trout). The gene‐expression profiles of each cell fraction were then compared with a microarray containing cDNAs representing 16,006 genes from several salmonid species. Genes exhibiting high expression for type A spermatogonia relative to above‐mentioned other types of gonadal cells were identified and subjected to RT‐PCR and quatitative PCR analysis. Since only the rainbow trout notch1 homologue showed significantly high expression in the type A spermatogonia‐enriched fraction, we propose that notch1 may be a useful molecular marker for type A spermatogonia. The combination of GFP‐dependent FCM and microarray analysis of pvasa‐GFP rainbow trout can therefore be applied to the identification of potentially useful molecular markers of germ cells in fish. Mol. Reprod. Dev. 76: 246–254, 2009. © 2008 Wiley‐Liss, Inc.
Functional assessment of centrosomes of spermatozoa and spermatids microinjected into rabbit oocytes
Authors: Tachibana Masahito , Terada Yukihiro , Ogonuki Narumi , Ugajin Tomohisa , Ogura Atsuo , Murakami Takashi , Yaegashi Nobuo , Okamura Kunihiro
Published: July 2008

Although intracytoplasmic sperm injection (ICSI) is a widely used assisted reproductive technique, the fertilization rates and pregnancy rates of immature spermatids especially in round spermatid injection (ROSI) remain very low. During mammalian fertilization, the sperm typically introduces its own centrosome which then acts as a microtubule organizing center (MTOC) and is essential for the male and female genome union. In order to evaluate the function of immature germ cell centrosomes, we used the rabbit gamete model because rabbit fertilization follows paternal pattern of centrosome inheritance. First, rabbit spermatids and spermatozoa were injected into oocytes using a piezo‐micromanipulator. Next, the centrosomal function to form a sperm aster was determined. Furthermore, two functional centrosome proteins (γ‐tubulin and centrin) of the rabbit spermatogenic cells were examined. Our results show that the oocyte activation rates by spermatozoa, elongated spermatids, and round spermatids were 86% (30/35), 30% (11/36), and 5% (1/22), respectively. Sperm aster formation rates after spermatozoa, elongated spermatids, and round spermatids injections were 47% (14/30), 27% (3/11), and 0% (0/1), respectively. The aster formation rate of the injected elongating/elongated spermatids was significantly lower than that of the mature spermatozoa (P = 0.0242). Moreover, sperm asters were not observed in round spermatid injection even after artificial activation. These data suggest that poor centrosomal function, as measured by diminished aster formation rates, is related to the poor fertilization rates when immature spermatogenic cells are injected. Mol. Reprod. Dev. 76: 270–277, 2009. © 2008 Wiley‐Liss, Inc.