bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach to health system strengthening in the Democratic Peoples Republic of Korea (North Korea)
Authors: Grundy John , Moodie Rob 
Published: July 2008

AbstractBackgroundThe 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.FindingsUpdated 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.ConclusionAlthough 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

AbstractWe 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

AbstractEpstein‐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

AbstractDuodenogastric 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

AbstractBiodegradable 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

AbstractLess 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

AbstractBackgroundRNA‐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.ResultsIn 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).ConclusionsThese 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

AbstractThe 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

AbstractClinical 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

AbstractSly 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

AbstractPrevious 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

AbstractTrends 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