bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Atherosclerosis in Mice Lacking Apolipoprotein A-I Attributable to Both Impaired Reverse Cholesterol Transport and Increased Inflammation
Authors: Moore Ryan E. , Navab Mohamad , Millar John S. , Zimetti Francesca , Hama Susan , Rothblat George H. , Rader Daniel J.
Published: September 2005

To test the hypothesis that apolipoprotein A-I (apoA-I) functions specifically to inhibit atherosclerosis independent of the level of high-density lipoprotein cholesterol (HDL-C) by promoting both reverse cholesterol transport and HDL antiinflammatory function in vivo, we established a murine atherosclerosis model of apoA-I deficiency in which the level of HDL-C is well maintained. ApoA-I
−/−
mice were crossed with atherosclerosis susceptible low-density lipoprotein receptor
−/−
/apobec
−/−
(LA) mice to generate LA mice with apoA-I
+/+
, apoA-I
+/−
, and apoA-I
−/−
genotypes. There were no major differences in the amounts of non–HDL-C and HDL-C in the plasma between different apoA-I genotypes. A significant inverse relationship was observed, however, between apoA-I gene dose and atherosclerosis in both female and male mice. Compared with LA-apoA-I
+/+
mice, serum from LA-apoA-I
−/−
mice had a significantly reduced capacity to function as an acceptor of ABCA1- and SR-BI-mediated cellular cholesterol efflux, and also had markedly reduced lecithin cholesterol acyltransferase activity. In addition, LA-apoA-I
−/−
mice had significantly reduced macrophage-derived cholesterol esterification and reverse cholesterol transport in vivo. There was significantly reduced plasma paraoxonase (PON-1) activity, impaired HDL vascular antiinflammatory function, and increased basal levels of monocyte chemotactic protein-1 in the plasma of LA-apoA-I
−/−
mice compared with LA-apoA-I
+/+
mice. In LA-apoA-I
−/−
mice, there was also greater induction of some, but not all, inflammatory cytokines and chemokines in response to intraperitoneal injection of lipopolysaccharide than in LA-apoA-I
+/+
mice. We conclude that apoA-I inhibits atherosclerosis by promoting both macrophage reverse cholesterol transport and HDL antiinflammatory function, and that these anti-atherogenic functions of apoA-I are largely independent of the plasma level of HDL-C in this mouse model.
Novel Role of Lactosylceramide in Vascular Endothelial Growth Factor–Mediated Angiogenesis in Human Endothelial Cells
Authors: Rajesh Mohanraj , Kolmakova Antonina , Chatterjee Subroto
Published: September 2005

Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis associated with coronary heart disease, vascular complications in diabetes, inflammatory vascular diseases, and tumor metastasis. The mechanism of VEGF-driven angiogenesis involving glycosphingolipids such as lactosylceramide (LacCer), however, is not known. To demonstrate the involvement of LacCer in VEGF-induced angiogenesis, we used small interfering RNA (siRNA)-mediated silencing of LacCer synthase expression (GalT-V) in human umbilical vein endothelial cells. This gene silencing markedly inhibited VEGF-induced platelet endothelial cell adhesion molecule-1 (PECAM-1) expression and angiogenesis. Second, we used D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of LacCer synthase and glucosylceramide synthase, that significantly mitigated VEGF-induced PECAM-1 expression and angiogenesis. Interestingly, these phenotypic changes were reversed by LacCer but not by structurally related compounds such as glucosylceramide, digalactosylceramide, and ceramide. In a human mesothelioma cell line (REN) that lacks the endogenous expression of PECAM-1, VEGF/LacCer failed to stimulate PECAM-1 expression and tube formation/angiogenesis. In REN cells expressing human PECAM-1 gene/protein, however, both VEGF and LacCer-induced PECAM-1 protein expression and tube formation /angiogenesis. In fact, VEGF-induced but not LacCer-induced angiogenesis was mitigated by SU-1498, a VEGF receptor tyrosine kinase inhibitor. Also, VEGF/LacCer-induced PECAM-1 expression and angiogenesis was mitigated by protein kinase C and phospholipase A
2
inhibitors. These results indicate that LacCer generated in VEGF-treated endothelial cells may serve as an important signaling molecule for PECAM-1 expression and in angiogenesis. This finding and the reagents developed in our report may be useful as anti-angiogenic drugs for further studies in vitro and in vivo.
The Association of C-Reactive Protein Levels With Carotid Intima-Media Complex Thickness and Plaque Formation in the General Population
Authors: Makita Shinji , Nakamura Motoyuki , Hiramori Katsuhiko
Published: September 2005

Background and Purpose—

An inflammatory response has been associated with the development of atherosclerosis. Our aim was to clarify which atherosclerotic changes (intima-media complex thickness [IMT] increase, plaque formation, and arterial dilatation) are associated with C-reactive protein (CRP) levels and to determine whether there are any gender differences.

Methods—

Carotid ultrasound and measurement of high-sensitivity CRP (hs-CRP) levels were performed in 2056 subjects selected from a general population (mean age 58.3 years; 1290 men).

Results—

In both genders, IMT significantly increased with increasing hs-CRP quartile (
P
<0.001), but this relationship disappeared after adjustment for age and other traditional cardiovascular risk factors. In men, but not women, carotid luminal diameter significantly increased with increasing hs-CRP levels (
P
<0.05), but again, this relationship disappeared with adjustment for age and other risk factors. However, in men, but not women, plaque score increased significantly with increasing hs-CRP quartile (
P
<0.01), even after adjustment for age and other traditional risk factors.

Conclusions—

CRP level was closely associated with early atherosclerotic changes represented by carotid plaque formation. However, the IMT increase was strongly associated with aging and other traditional cardiovascular risk factors rather than CRP level. In the general population, CRP may serve as a complementary and quantitative marker for atherosclerotic plaque formation in men but not women.
NIHSS Score and Arteriographic Findings in Acute Ischemic Stroke
Authors: Fischer Urs , Arnold Marcel , Nedeltchev Krassen , Brekenfeld Caspar , Ballinari Pietro , Remonda Luca , Schroth Gerhard , Mattle Heinrich P.
Published: September 2005

Background and Purpose—

To test the hypothesis that the National Institutes of Health Stroke Scale (NIHSS) score is associated with the findings of arteriography performed within the first hours after ischemic stroke.

Methods—

We analyzed NIHSS scores on hospital admission and clinical and arteriographic findings of 226 consecutive patients (94 women, 132 men; mean age 62±12 years) who underwent arteriography within 6 hours of symptom onset in carotid stroke and within 12 hours in vertebrobasilar stroke.

Results—

From stroke onset to hospital admission, 155±97 minutes elapsed, and from stroke onset to arteriography 245±100 minutes elapsed. Median NIHSS was 14 (range 3 to 38), and scores differed depending on the arteriographic findings (
P
<0.001). NIHSS scores in basilar, internal carotid, and middle cerebral artery M1 and M2 segment occlusions (central occlusions) were higher than in more peripherally located, nonvisible, or absent occlusions. Patients with NIHSS scores ≥10 had positive predictive values (PPVs) to show arterial occlusions in 97% of carotid and 96% of vertebrobasilar strokes. With an NIHSS score of ≥12, PPV to find a central occlusion was 91%. In a multivariate analysis, NIHSS subitems such as “level of consciousness questions,” “gaze,” “motor leg,” and “neglect” were predictors of central occlusions.

Conclusions—

There is a significant association of NIHSS scores and the presence and location of a vessel occlusion. With an NIHSS score ≥10, a vessel occlusion will likely be seen on arteriography, and with a score ≥12, its location will probably be central.
Synoptic Reorganization of Atmospheric Flow during the Last Glacial Maximum*
Authors: Justino Flávio , Timmermann Axel , Merkel Ute , Souza Enio P.
Published: September 2005

A coupled global atmosphere–ocean model of intermediate complexity is used to study the influence of glacial boundary conditions on the atmospheric circulation during the Last Glacial Maximum in a systematical manner. A web of atmospheric interactions is disentangled, which involves changes in the meridional temperature gradient and an associated modulation of the atmospheric baroclinicity. This in turn drives anomalous transient eddy momentum fluxes that feed back onto the zonal mean circulation. Moreover, the modified transient activity (weakened in the North Pacific and strengthened in the North Atlantic) leads to a meridional reorganization of the atmospheric heat transport, thereby feeding back onto the meridional temperature structure. Furthermore, positive barotropic conversion and baroclinic production rates over the Laurentide ice sheets and the far eastern North Pacific have the tendency to decelerate the westerlies, thereby feeding back to the stationary wave changes triggered by orographic forcing.
Response of the Kuroshio Extension to Rossby Waves Associated with the 1970s Climate Regime Shift in a High-Resolution Ocean Model*
Authors: Taguchi Bunmei , Xie Shang-Ping , Mitsudera Humio , Kubokawa Atsushi
Published: September 2005

The response of the Kuroshio Extension (KE) to large-scale Rossby waves remotely excited by wind stress changes associated with the 1970s climate regime shift is studied using a high-resolution regional ocean model. Two ensemble simulations are conducted: The control run uses monthly climatological forcing while, in the second ensemble, anomalous forcing is imposed at the model eastern boundary around 165°E derived from a hindcast of decadal changes in subsurface temperature and salinity using a coarser-resolution model of the Pacific basin.

Near the KE, ocean adjustment deviates strongly from the linear Rossby wave dynamics. Most notably, the eastward acceleration of the KE is much narrower in meridional extent than that associated with the incoming Rossby waves imposed on the eastern boundary. This KE acceleration is associated with an enhanced potential vorticity (PV) gradient across the front that is consistent with the inertial western boundary layer theory: the arrival of the Rossby waves at the western boundary causes the eastward current to accelerate, leading to enhanced advection of low (high) PV water of subtropical (subarctic) origin along the western boundary layer. The meridional dipole of PV anomalies results in a pair of anomalous recirculations with a narrow eastward jet in between. A three-layer quasigeostrophic model is used to demonstrate this inertial adjustment mechanism. Finally, transient eddy activity increases significantly and the eddy momentum transport acts to strengthen the mean flow response. The result that ocean physical response to broad-scale atmospheric forcing is large near the KE front has important implications for fisheries research.
Discrepancy of Interdecadal Changes in the Asian Region among the NCEP–NCAR Reanalysis, Objective Analyses, and Observations
Authors: Wu Renguang , Kinter J. L. , Kirtman B. P.
Published: September 2005

This study compares decadal means and interdecadal changes of surface and sea level pressures, tropospheric heights, and winds in the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis with objective analyses and observations. It is found that over Asia the NCEP–NCAR reanalysis pressures and heights are systematically lower than objective analyses and observations before the late 1970s. The magnitude of the differences changes from one decade to another and shows obvious seasonal dependence. The nonuniform spatial distribution of pressure and height differences is consistent with the discrepancy in lower-level meridional winds along the east Asian coast. The seasonal dependence of pressure differences affects the strength of the seasonal cycle over Asia. More importantly, large changes in the discrepancies from one decade to another lead to inconsistent interdecadal changes between the reanalysis and objective analyses or observations in the Asian region. While the reanalysis displays a large increase of pressure around 1977 and in the mid-1960s and an obvious decrease in the late 1950s, the changes are small in objective analyses and observations. Inconsistent interdecadal changes are also present in tropospheric heights and winds. The results indicate that the reanalysis may overestimate interdecadal changes over Asia. This calls for caution in utilizing the reanalysis output to study the interdecadal variability or the interannual variability without removal of interdecadal variations in the Asian region.
Junta by Another Name? The 1974 Metapolitefsi and the Greek Extra-parliamentary Left
Authors: Kassimeris George
Published: September 2005

In the years following metapolitefsi (the 1974 transition from dictatorship to multi-party democracy) a plethora of groups from the far left appeared on the Greek post-junta political scene. Obsessed with the dynamics of the Athens Polytechnic revolt of November 1973, these marginal but vocal and persistent groups viewed the process of constitutional change and democratic consolidation with deep scepticism. Many of them did not accept the legitimacy of the transfer of power and used confrontational anti-regime rhetoric and radical forms of action to denounce constitutional structures and attack the regime’s legality, conservative ethos and lack of structured political solutions. The purpose of this article is to describe the emergence and evolution of the major extra-parliamentary groups of the left and to examine their analyses and interpretations of Greek political circumstances in the late 1970s.
mTOR regulates cell survival after etoposide treatment in primary AML cells
Authors: Xu Qing , Thompson James E. , Carroll Martin
Published: September 2005

Acute myeloid leukemia cells have constitutive activation of phosphatidylinositol 3(PI3) kinase and require PI3 kinase activation for survival; however, the function of the PI3 kinase pathway in the survival of leukemic cells is poorly defined. We have studied the role of one PI3 kinase substrate, mTOR (mammalian target of rapamycin), in primary leukemic cells. In initial experiments, we have defined a novel growth medium that improves survival of acute myeloid leukemia (AML) blasts in long-term suspension culture and the survival of leukemic stem cells in short-term cultures. Inhibition of mTOR using rapamycin leads to a modest decrease in cell survival after 2 days of incubation with more significant decrease in survival after 7 days of culture. However, when rapamycin is added to etoposide in 2-day cultures, there is a dramatic increase in the cytotoxicity of etoposide against AML blasts. Furthermore, etoposide consistently decreased the engraftment of AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals, and this effect was enhanced by coincubation with rapamycin, demonstrating that mTOR regulates survival of AML stem cells after etoposide treatment. These results suggest that rapamycin in combination with etoposide-based chemotherapy may be efficacious in the treatment of AML.
Total body irradiation selectively induces murine hematopoietic stem cell senescence
Authors: Wang Yong , Schulte Bradley A. , LaRue Amanda C. , Ogawa Makio , Zhou Daohong
Published: September 2005

Exposure to ionizing radiation (IR) and certain chemotherapeutic agents not only causes acute bone marrow (BM) suppression but also leads to long-term residual hematopoietic injury. This latter effect has been attributed to damage to hematopoietic stem cell (HSC) self-renewal. Using a mouse model, we investigated whether IR induces senescence in HSCs, as induction of HSC senescence can lead to the defect in HSC self-renewal. It was found that exposure of C57BL/6 mice to a sublethal dose (6.5 Gy) of total body irradiation (TBI) resulted in a sustained quantitative and qualitative reduction of LKS+ HSCs. In addition, LKS+ HSCs from irradiated mice exhibited an increased expression of the 2 commonly used biomarkers of cellular senescence, p16Ink4a and SA-β-gal. In contrast, no such changes were observed in irradiated LKS- hematopoietic progenitor cells. These results provide the first direct evidence demonstrating that IR exposure can selectively induce HSC senescence. Of interest, the induction of HSC senescence was associated with a prolonged elevation of p21Cip1/Waf1, p19Arf, and p16Ink4a mRNA expression, while the expression of p27Kip1 and p18Ink4c mRNA was not increased following TBI. This suggests that p21Cip1/Waf1, p19Arf, and p16Ink4a may play an important role in IR-induced senescence in HSCs.
FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma
Authors: Hutchings Martin , Loft Annika , Hansen Mads , Pedersen Lars Møller , Buhl Thora , Jurlander Jesper , Buus Simon , Keiding Susanne , D'Amore Francesco , Boesen Anne-Marie , Berthelsen Anne Kiil , Specht Lena
Published: September 2005

Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET–positive patients progressed and 2 died. Three of 61 FDG-PET–negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.
XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report
Authors: Mehta Parinda A. , Alonzo Todd A. , Gerbing Robert B. , Elliott James S. , Wilke Tiffany A. , Kennedy Rebekah J. , Ross Julie A. , Perentesis John P. , Lange Beverly J. , Davies Stella M.
Published: September 2005

Genetic polymorphisms result in interindividual variation in DNA repair capacity and may, in part, account for susceptibility of a cell to genotoxic agents and to malignancy. Polymorphisms in XPD, a member of the nucleotide excision repair pathway, have been associated with development of treatment-related acute myeloid leukemia (AML) and with poor outcome of AML in elderly patients. We hypothesized that XPD Lys751Gln polymorphism may play a role in causation of AML in children and, as shown in adults, may affect the outcome of childhood AML therapy. Genotyping of 456 children treated for de novo AML was performed at XPD exon 23. Genotype frequencies in patients were compared with healthy control subject frequencies, and patient outcomes were analyzed according to genotype. Gene frequencies in AML patients and healthy controls were similar. There were no significant differences in overall survival (P = .82), event-free survival (P = .78), treatment-related mortality (P = .43), or relapse rate (RR) (P = .92) between patients with XPD751AA versus 751AC versus 751CC genotypes, in contrast to reports in adult AML. These data, representing the only data in pediatric AML, suggest that XPD genotype does not affect the etiology or outcome of childhood AML.
KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2
Authors: Cannon Mark , Cesarman Ethel , Boshoff Chris
Published: September 2005

Kaposi sarcoma (KS) remains the most common AIDS-associated malignancy worldwide. In sub-Saharan Africa especially, this aggressive endothelial-cell tumor is a cause of widespread morbidity and mortality. Infection with Kaposi sarcoma-associated herpesvirus (KSHV) is now known to be an etiologic force behind KS and primary-effusion lymphoma (PEL). Over time, KSHV has pirated many human genes whose products regulate angiogenesis, inflammation, and the cell cycle. One of these, the KSHV vGPCR, is a lytic product that is a constitutively active homolog of the IL-8 receptor. Although it is considered a viral oncogene and causes KS-like lesions in mice, vGPCR expression results in cell-cycle arrest of KSHV-infected PEL cells. In the present study, we show that this arrest is mediated by p21 in a p53-independent manner; the resulting Cdk2 inhibition decreases the efficiency of chemical induction of KSHV lytic transcripts ORF 50 and 26. Importantly, Cdk2 activity is also essential for replication in other human herpesviruses. The ability of vGPCR to delay or abort KSHV replication may explain how despite being a lytic product, this potent signaling molecule has a vital role in tumor formation via its induction of various KS-associated cytokines.
Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+CD25+ T-cell–dependent mechanism
Authors: Matsuoka Ken-ichi , Ichinohe Tatsuo , Hashimoto Daigo , Asakura Shoji , Tanimoto Mitsune , Teshima Takanori
Published: September 2005

The lack of donor availability is a major limitation to the widespread use of allogeneic hematopoietic stem cell transplantation, and therefore it would be beneficial to identify less immunogenic HLA mismatches. The maternal and fetal antigens that are transmitted through the bidirectional transplacental passage during pregnancy may induce tolerance to noninherited maternal antigens (NIMAs) in offspring and to inherited paternal antigens (IPAs) in the mother. Using mouse models of bone marrow transplantation (BMT), we found that a “child-to-mother” BMT from a NIMA-exposed donor reduced the morbidity and mortality of graft-versus-host disease in an antigen-specific manner; however, a “mother-to-child” BMT from an IPA-exposed donor did not. The NIMA-complementary BMT preserved the graft-versus-leukemia effects and favored the immune reconstitution, thus resulting in a marked improvement of the outcome after BMT. These tolerogenic NIMA effects were completely abolished by the depletion of CD4+CD25+ cells from the donor inocula, thus suggesting the involvement of CD4+CD25+ regulatory T cells in the tolerogenic NIMA effects. Our findings may therefore have profound implications on the performance of clinical BMT while also potentially helping to develop new strategies for using a NIMA-mismatched donor in the absence of an HLA-identical donor.
Micro-Mar: a database for dynamic representation of marine microbial biodiversity
Authors: Pushker Ravindra , D'Auria Giuseppe , Alba-Casado Jose Carlos , Rodríguez-Valera Francisco
Published: September 2005

Background

The cataloging of marine prokaryotic DNA sequences is a fundamental aspect for bioprospecting and also for the development of evolutionary and speciation models. However, large amount of DNA sequences used to quantify prokaryotic biodiversity requires proper tools for storing, managing and analyzing these data for research purposes.

Description

The Micro-Mar database has been created to collect DNA diversity information from marine prokaryotes for biogeographical and ecological analyses. The database currently includes 11874 sequences corresponding to high resolution taxonomic genes (16S rRNA, ITS and 23S rRNA) and many other genes including CDS of marine prokaryotes together with available biogeographical and ecological information.

Conclusion

The database aims to integrate molecular data and taxonomic affiliation with biogeographical and ecological features that will allow to have a dynamic representation of the marine microbial diversity embedded in a user friendly web interface. It is available online at http://egg.umh.es/micromar/.
Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: genes and pseudogenes
Authors: de Parseval Nathalie , Diop Gora , Blaise Sandra , Helle François , Vasilescu Alexandre , Matsuda Fumihiko , Heidmann Thierry
Published: September 2005

Background

The human genome carries a high load of proviral-like sequences, called Human Endogenous Retroviruses (HERVs), which are the genomic traces of ancient infections by active retroviruses. These elements are in most cases defective, but open reading frames can still be found for the retroviral envelope gene, with sixteen such genes identified so far. Several of them are conserved during primate evolution, having possibly been co-opted by their host for a physiological role.

Results

To characterize further their status, we presently sequenced 12 of these genes from a panel of 91 Caucasian individuals. Genomic analyses reveal strong sequence conservation (only two non synonymous Single Nucleotide Polymorphisms [SNPs]) for the two HERV-W and HERV-FRD envelope genes, i.e. for the two genes specifically expressed in the placenta and possibly involved in syncytiotrophoblast formation. We further show – using an ex vivo fusion assay for each allelic form – that none of these SNPs impairs the fusogenic function. The other envelope proteins disclose variable polymorphisms, with the occurrence of a stop codon and/or frameshift for most – but not all – of them. Moreover, the sequence conservation analysis of the orthologous genes that can be found in primates shows that three env genes have been maintained in a fully coding state throughout evolution including env W and env FRD.

Conclusion

Altogether, the present study strongly suggests that some but not all envelope encoding sequences are bona fide genes. It also provides new tools to elucidate the possible role of endogenous envelope proteins as susceptibility factors in a number of pathologies where HERVs have been suspected to be involved.
The use of end-quintile comparisons to identify under-servicing of the poor and over-servicing of the rich: A longitudinal study describing the effect of socioeconomic status on healthcare
Authors: Brameld Kate J , Holman C D'Arcy J
Published: September 2005

Background

To demonstrate the use of end-quintile comparisons in assessing the effect of socio-economic status on hospital utilisation and outcomes in Western Australia.

Methods

Hospital morbidity records were extracted from the WA Data Linkage System for the period 1994–99, with follow-up to the end of 2000. Multivariate modelling was used to estimate the effect of socio-economic status on hospital admission rates, average and total length of stay (LOS), cumulative incidence of readmission at 30 days and one year, and case fatality at one year.

Results

The study demonstrated higher rate ratios of hospital admission in the more disadvantaged quintiles: rate ratios were 1.31 (95% CI 1.25–1.37) and 1.32 (1.26–1.38) in the first quintile (most disadvantaged) and the second quintile respectively, compared with the fifth quintile (most advantaged). There was a longer total LOS in the most disadvantaged quintile compared with quintile 5 (LOS ratio 1.24; 1.23–1.26). The risk of readmission at 30 days and one year and the risk of death at one year were also greater in those with greater disadvantage: the hazard ratios for quintiles 1:quintile 5 were 1.07 (1.05–1.09), 1.17 (1.16–1.18) and 1.10 (1.07–1.13) respectively. In contradiction to the trends towards higher hospital utilisation and poorer outcomes with increasing social disadvantage, in some MDC's the rate ratio of quintile 1:quintile 2 was less than 1, and quintile 4:quintile 5 was greater than 1. For all surgical admissions the most disadvantaged had a significantly lower admission rate than the second quintile.

Conclusion

This study has shown that the disadvantaged within Western Australia are more intensive users of hospital services but their outcomes following hospitalisation are worse, consistent with their health status. Instances of overuse in the least disadvantaged and under use in the most disadvantaged have also been identified.
hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer
Authors: Franklin Renty B , Feng Pei , Milon B , Desouki Mohamed M , Singh Keshav K , Kajdacsy-Balla André , Bagasra Omar , Costello Leslie C
Published: September 2005

Background

The genetic and molecular mechanisms responsible for and associated with the development and progression of prostate malignancy are largely unidentified. The peripheral zone is the major region of the human prostate gland where malignancy develops. The normal peripheral zone glandular epithelium has the unique function of accumulating high levels of zinc. In contrast, the ability to accumulate zinc is lost in the malignant cells. The lost ability of the neoplastic epithelial cells to accumulate zinc is a consistent factor in their development of malignancy. Recent studies identified ZIP1 (SLC39A1) as an important zinc transporter involved in zinc accumulation in prostate cells. Therefore, we investigated the possibility that down-regulation of hZIP1 gene expression might be involved in the inability of malignant prostate cells to accumulate zinc. To address this issue, the expression of hZIP1 and the depletion of zinc in malignant versus non-malignant prostate glands of prostate cancer tissue sections were analyzed. hZIP1 expression was also determined in malignant prostate cell lines.

Results

hZIP1 gene expression, ZIP1 transporter protein, and cellular zinc were prominent in normal peripheral zone glandular epithelium and in benign hyperplastic glands (also zinc accumulating glands). In contrast, hZIP1 gene expression and transporter protein were markedly down-regulated and zinc was depleted in adenocarcinomatous glands and in prostate intra-epithelial neoplastic foci (PIN). These changes occur early in malignancy and are sustained during its progression in the peripheral zone. hZIP1 is also expressed in the malignant cell lines LNCaP, PC-3, DU-145; and in the nonmalignant cell lines HPr-1 and BPH-1.

Conclusion

The studies clearly establish that hZIP1 gene expression is down regulated and zinc is depleted in adenocarcinomatous glands. The fact that all the malignant cell lines express hZIP1 indicates that the down-regulation in adenocarcinomatous glands is likely due to in situ gene silencing. These observations, coupled with the numerous and consistent reports of loss of zinc accumulation in malignant cells in prostate cancer, lead to the plausible proposal that down regulation of hZIP1 is a critical early event in the development prostate cancer.
Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-beta1 and bax genes
Authors: Johnson M Cecilia , Torres Marisa , Alves Alessandra , Bacallao Ketty , Fuentes Ariel , Vega Margarita , Boric M Angélica
Published: September 2005

Background

Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes.

Methods

Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants.

Results

Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05).

Conclusion

An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium.
Amyloid Precursor Protein: From Synaptic Plasticity to Alzheimer's Disease
Authors: MILEUSNIC RADMILA , LANCASHIRE CHRISTINE L. , ROSE STEVEN P. R.
Published: September 2005

Abstract:The amyloid precursor protein (APP) has been shown to be implicated in age‐associated plastic changes at synapses that might contribute to memory loss in Alzheimer's disease. As APP has previously been reported to have multiple functions during normal development, and as human and avian APP share 95% homology in amino acid sequence, we have employed a one‐trial passive avoidance task in day‐old chicks to study its role in the process of memory formation. Administration of anti‐APP antibodies, raised against human APP, APP‐antisense, and Aβ during pre‐training, prevented memory formation without effects on general behavior or initial acquisition. Amnesia is apparent by 30 min post‐training and lasts for at least 24 hours. Injection of APP‐derived peptides RERMS (APP328‐332) and RER (APP328‐330) homologous to the short stretches of amino acids in the Kang sequence (APP319‐335), rescue the memory in animals rendered amnestic by previous (anti‐APP antibody, antisense, and Aβ pretreatments. The protected form of RER, with a prolonged half‐life (acetylated RER), proved to be effective when injected intracranially and peripherally. The tripeptide RER exerts its biological activity by binding to two neuronal plasma membrane proteins (60 and 110 kDa). The results obtained in this study suggest that RER alleviates memory deficits via receptor‐mediated events, and that short APP‐derived peptides might represent a novel group of therapeutically active molecules for the alleviation of memory deficits in age‐related dementias.
EPR Spin Trapping of Oxygen Radicals in Plants: A Methodological Overview
Authors: BAČIĆ GORAN , MOJOVIĆ MILOŠ
Published: September 2005

Abstract: We present a brief account of the difficulties involved in detection of oxygen free radicals in plants and give a rationale for using the EPR spin trapping technique in such studies. Comparative analysis of characteristics of different spin traps is given, having in mind their suitability in trapping oxygen‐centered free radicals. Certain technical aspects of EPR experiments related to successful trapping of free radicals are discussed. Previous studies of trapping of oxygen radicals in plants are reviewed in terms of how efficient the experimental approach employed has been in their detection and how this influences conclusions about the mechanisms of their production. In addition, we analyze the potential of spin labels in the analysis of free radical production in plants and demonstrate that the combination of EPR spin traps and spin labels is extremely efficient for this purpose.
The Coexistence of the Oxidative and Reductive Systems in Roots: The Role of Plasma Membranes
Authors: VULETIĆ M.RJANA , ŠUKALOVIĆ VESNA HADŽI‐TAŠKOVIĆ , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: Different components of the plasma membrane bound and associated redox system, which participate in the energy transfer from the predominantly reducing intercellular environment to the extracellular oxidizing environment, are reviewed. Special attention is given to plant root cells. An analysis of the plasma membrane‐associated redox components, such as the cytochromes, quinones, and different types of oxidoreductases (dehydrogenases, oxidases, peroxidases, and superoxide dismutases), is made, as well as their coupling with naturally occurring extracellular substrates, such as oxygen and its reactive forms, phenols, ascorbate, nitrate, ferric ion, and organic acids. The participation of different free radical species in most of the plasma membrane‐bound redox reactions is documented.
Gene Expression in the Conversion of Early‐Phase to Late‐Phase Long‐Term Potentiation
Authors: LEE PHILIP R. , COHEN JONATHAN E. , BECKER KEVIN G. , FIELDS R. DOUGLAS
Published: September 2005

Abstract: Changes in gene expression associated with different forms of synaptic plasticity in rat hippocampus were investigated. Microarray analysis revealed differential expression of hundreds of genes 30 min after synaptic or antidromic stimulation in different patterns. Results of selected genes were verified by LightCycler RT‐PCR. Synaptic activation in a theta burst protocol, which induced long‐term potentiation (LTP), increased the mRNA abundance of BDNF‐exon 1, but antidromic stimulation in the presence of CNQX, APV, and MCPG (to block glutamatergic synapses) decreased the level of mRNA of this transcript, as did 1 Hz synaptic stimulation. The opposite regulation of this BDNF transcript after firing of the postsynaptic neuron, coincidently or uncorrelated with synaptic firing, is consistent with the effects of BDNF on synaptic transmission, suggesting possible involvement in strengthening and weakening CA1 synapses after correlated versus uncorrelated firing of the postsynaptic neurons with its synaptic inputs. Possible involvement of transcriptional regulation of BDNF in the conversion of early‐phase LTP to late‐phase LTP are discussed in the context of previous studies by Dudek & Fields (Proc. Natl. Acad. Sci. USA 99: 3962‐3967) showing that this conversion can be induced by antidromic stimulation of CA1 neurons in the absence of excitatory synaptic activity.
Altered Cellular Distribution of Phospho‐Tau Proteins Coincides with Impaired Retrograde Axonal Transport in Neurons of Aged Rats
Authors: NIEWIADOMSKA GRAZYNA , BAKSALERSKA‐PAZERA MARTA , RIEDEL GERNOT
Published: September 2005

Abstract: We hypothesize that the age‐related degeneration of cytoskeleton in basal forebrain cholinergic neurons renders the NGF‐TrkA signaling system non‐functional and thereby impairs trophic support. Comparing young (4 months) and aged (28 months) rat brain, we examined immunohistochemically the compartmentalization of phosphorylated Tau protein using antibodies phospho‐Tau404 and phospho‐Tau231 of the GSK3β kinase, known to phosphorylate Tau, the neurotrophin NGF, and its receptor P‐TrkA. Retrograde labeling of basal forebrain cholinergic cells after injection of fluorogold into multiple sites in cortex and hippocampus revealed a significantly lower number of fluorogold‐positive cells in aged brain. Despite a lower density of P‐TrkA immunoreactivity in cortex and hippocampus of aged rats, there was no difference in NGF expression. In young animals phospho‐Tau404, phospho‐Tau231, and GSK3 immunoreactivity was observed mainly in neuronal fibers with lower staining in somata both in cortex and hippocampus. By contrast, Tau and GSK3 labeling were confined to the cell bodies in aged rats. This is confirmation that aging leads to a redistribution of cytoskeletal proteins. Since a somatic localization of phospho‐Tau is indicative of cytoskeletal breakdown, we suggest that failure of axonal trafficking may be responsible for the lack of trophic support in aged cholinergic neurons of the basal forebrain.
Focus‐Drift Correction in Time‐Lapse Confocal Imaging
Authors: KREFT MARKO , STENOVEC MATJAŽ , ZOREC ROBERT
Published: September 2005

Abstract: In long‐term time‐lapse imaging of living cells, where recording takes several minutes or longer, a drift of focus may be significant. Focus‐drift is due to the slippage in the microscope focus mechanism and/or the thermal gradients in the microscope. Software and hardware solutions may be introduced to correct for the focus‐drift. Some autofocus techniques measure position of the specimen by sensing the light or sound reflected from a well‐defined surface, such as the microscope slide. An autofocusing approach, where a focus measure is computed for images acquired at different objective positions is less appropriate in confocal microscopy, since more than one section is in focus. To correct for the focal‐drift in long‐term time‐lapse confocal imaging, we acquired an image stack of the specimen periodically. The software calculated Pearson's correlation coefficient between each image in the z‐stack and the reference image in the stack, which was selected at the beginning of the experiment. The maximal correlation coefficient of pixel intensities was taken to identify the image, which corresponded to the focal plane of the reference image. To test our approach, we used confocal images of living rat lactotroph cells, which discharged preloaded green fluorescent probe from a single secretory granule. Simultaneously, an extracellularly applied FM 4–64 red fluorescent probe loaded the discharging vesicle and the plasma membrane. We show that our approach is appropriate to correct for focal‐drift in long term time‐lapse imaging and analysis of living cells.
The Mechanisms of 6‐Hydroxydopamine‐Induced Astrocyte Death
Authors: RAIČEVIĆ NEVENA , MLADENOVIĆ ALEKSANDRA , PEROVIĆ MILKA , MILJKOVIĆ DJORDJE , TRAJKOVIĆ VLADIMIR
Published: September 2005

Abstract: Treatment with 6‐hydroxydopamine significantly reduced the viability of cultured rat primary astrocytes, rat astrocytoma cell line C6, and human astrocytoma cell line U251. 6‐Hydroxydopamine‐treated astrocytes exhibited altered nuclear morphology, DNA fragmentation, and reduced intracellular esterase activity, which indicated apoptotic cell death. Astrocytes were protected by neutralization of 6‐hydroxydopamine autooxidation products H2O2, O2•−, and •OH, but not by cell‐derived or chemically generated anti‐apoptotic free radical nitric oxide. Finally, 6‐hydroxydopamine activated extracellular signal‐regulated kinase in astrocytes and selective inhibitor of extracellular signal‐regulated kinase activation partially prevented astrocyte death. Taken together, these data indicate that 6‐hydroxydopamine‐triggered oxidative stress induces extracellular signal‐regulated kinase‐dependent apoptotic death of astrocytes.
Proximal Dystrophin Gene Deletions and Protein Alterations in Becker Muscular Dystrophy
Authors: NOVAKOVIĆ IVANA , BOJIĆ DRAGANA , TODOROVIĆ SLOBODANKA , APOSTOLSKI SLOBODAN , LUKOVIĆ LJILJANA , STEFANOVIĆ DEJAN , MILAŠIN JELENA
Published: September 2005

Abstract: Alterations in production of cytoskeletal protein dystrophin caused by in‐frame gene mutations lead to the Becker muscular dystrophy. In this study we analyzed genotype‐phenotype correlation in a group of Becker muscular dystrophy patients with deletions affecting the proximal part of dystrophin gene, encompassing exons 3–13. Four patients with deletions affecting N terminal dystrophin domain had early onset and faster progression of the disease, while three patients with deletions in the proximal part of dystrophin's rod domain had a more benign disease course. Our study suggests that proximal gene deletions in Becker muscular dystrophy have various phenotypic effects depending on the affected domain of protein dystrophin.
Correlation Properties and Regularity of Heart Period Time Series: Influence of Posture and Heart Disease
Authors: VUKSANOVIĆ VESNA , GAL VERA
Published: September 2005

Abstract: Nonlinear measures of heart period variability (HPV) were determined in supine rest and standing posture in children and young adults with heart disease and compared to the control. The aim was to study influence of posture and heart disease on heart period dynamics. It was found that standing increases short‐term scaling exponent in all subjects and decreases sample entropy in healthy and less severely ill patients. Severely ill patients compared to control have higher short‐term scaling exponent in supine. Changes in nonlinear measures of HPV upon standing are more pronounced in healthy than diseased subjects due to different vagal activity.
Characterization of Luminal and Peritubular Membrane K+ Selectivity in Proximal Tubular Cells of Frog Kidney
Authors: NEŠOVIĆ JELENA , ČEMERIKIĆ DUŠAN
Published: September 2005

Abstract: The functional significance of/KCNQ1/KCNE1 K+ secretory fluxes and the effects of 3 μmol/L Cd2+ on the peritubular cell membrane potential and its potassium selectivity were investigated in proximal tubular cells of the frog kidney. Perfusing the lumen with l‐phenylalanine plus/minus chromanol 293B, a specific blocker of KCNQ1, did not modify rapid depolarization and rate of slow repolarization of the peritubular cell membrane. Peritubular exposure to Cd2+ led to a sustained, reversible hyperpolarization of the peritubular membrane, paralleled by an increase in fractional K+ conductance. Peritubular barium blunted hyperpolarization of the peritubular cell membrane to Cd2+. Thus, the KCNQ1/KCNE1 K+ secretory fluxes are absent in proximal tubule of frog kidney, while Cd2+ increases K+ selectivity of the peritubular cell membrane.
The Mechanism of Hemolysis of Erythrocytes by Sodium Dodecyl Sulfate
Authors: ROZIN VLADIMIR V.
Published: September 2005

Abstract: The results of a study of vesicular‐hemolytic action of anionic detergent sodium dodecyl sulfate on human erythrocytes are presented. Possible molecular events underlying detergent‐induced pore formation in the erythrocyte membrane are discussed.
Characterization of Enzymatically Synthesized Diferulate
Authors: TUFEGDŽIĆ SRÐAN , BOGDANOVIĆ JELENA , MAKSIMOVIĆ VUK , VUČINIĆ ŽELJKO
Published: September 2005

Abstract: Horseradish peroxidase was used to synthesize diferulates by a procedure in which ethyl ferulate was used as substrate. Four different forms were obtained, of which two dominant were the 5‐5′ and 8‐5′ diferulate. Fluorescence emission spectra of the diferulates (excited at 284 nm) indicate that they contain two chromophores, as opposed to the substrate molecule. Fluorescence excitation spectra with emission at 417 nm further demonstrate the difference between the synthesized diferulates and starting substrates.