bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose transporter‐1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor‐1α
Authors: Lidgren Anders , Bergh Anders , Grankvist Kjell , Rasmuson Torgny , Ljungberg Börje 
Published: October 2007

OBJECTIVETo evaluate transcription factor hypoxia inducible factor‐1α (HIF‐1α) activity, by analysing a target gene for HIF‐1α, glucose transporter‐1 (GLUT‐1), using a tissue microarray (TMA) in different types of renal cell carcinoma (RCC, a tumour with a variable clinical course, partly due to angiogenic activity), as angiogenesis is important for tumour progression and metastatic spread, and is activated by hypoxia.PATIENTS AND METHODSGLUT‐1 and HIF‐1α expressions were semiquantitatively analysed using immunohistological staining of a prepared TMA, using samples from 187 patients, including 148 with conventional, 26 with papillary and 13 with chromophobe RCC.RESULTSGLUT‐1 staining was found mainly in the cytoplasm. The tumours were subdivided into GLUT −1LOW and GLUT‐1HIGH, based on staining intensity. There was a significant difference in GLUT‐1 expression between RCC types (P < 0.05). In conventional RCC, GLUT‐1 had no correlation with clinicopathological variables. By contrast there was a correlation with tumour stage in papillary RCC. There was an insignificant trend to better survival of patients with GLUT‐1LOW expression in both conventional and papillary RCC. GLUT‐1 correlated significantly (P = 0.008) with HIF‐1α.CONCLUSIONSMost patients with conventional RCC had GLUT‐1HIGH staining and there was a significant correlation with HIF‐1α. In papillary RCC, GLUT‐1 expression was associated with stage; GLUT‐1 expression was significantly higher in conventional RCC than in papillary and chromophobe RCC. GLUT‐1LOW in both papillary and conventional RCC appeared to correspond with a better prognosis.
Prognostic significance of altered p120ctn expression in bladder cancer
Authors: Neto Brasil Silva , Smith Gjanje L. , Mandeville Jessica A. , Vanni Alex J. , Wotkowicz Chad , Rieger‐Christ Kimberly M. , Baumgart Egbert , Jacobs Micah A. , Cohen Michael S. , Zeheb Ron , Loda Massimo , Libertino John A. , Summerhayes Ian C. 
Published: October 2007

OBJECTIVETo identify the frequency of change in the expression and localization of p120ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120ctn in the migratory and invasive behaviour of bladder carcinoma cells.MATERIALS AND METHODSIn all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2–T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120ctn immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120ctn was achieved using small‐interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays.RESULTSThe expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non‐membranous localization of p120ctn correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN‐positive disease (P = 0.02). A low expression level of p120ctn was linked to a poor outcome in cancer‐specific survival analysis. Knockdown of p120ctn using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells.CONCLUSIONSOur findings suggest that p120ctn acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.
Trauma to male genital organs: a 10‐year review of 156 patients, including 118 treated by surgery
Authors: Lee Sung Hoon , Bak Chong Won , Choi Min Ho , Lee Han Sae , Lee Min Sung , Yoon Sang Jin 
Published: October 2007

OBJECTIVETo assess testicular rupture, scrotal haematoma, penile fracture and penile injury, comparing the prognoses of surgery and conservative management, as trauma to male external genital organs can cause devastating effects on patients and their partners.PATIENTS AND METHODSWe reviewed the medical records of 156 male patients who presented to our emergency centre with trauma to the external genital organs between January 1996 and March 2006.RESULTSIn all, 74 patients had testicular rupture, 32 penile fracture, 26 a penile injury and 24 a scrotal haematoma (mean age 27.8 years). The main cause of trauma was assault (52, 33%). Four of 14 patients with penile trauma who were managed conservatively had complications. Of 20 patients, 17 had a partial orchidectomy and were followed for a month after surgery; scrotal ultrasonography showed three cases of testicular atrophy. The mean hospital stay was less for patients with surgical intervention, at 6.4 days, than for those managed conservatively, at 8.7 days (P < 0.05). A visual analogue pain scale showed less pain in patients who were surgically treated (P < 0.05).CONCLUSIONPrompt surgical intervention is crucial; it should be considered by urologists, and is strongly recommended. Ultrasonography was highly sensitive and specific, and should be used in all patients with trauma to the external genital organs, to aid diagnosis and evaluation before surgery.
Can non‐malignant biopsy features identify men at increased risk of biopsy‐detectable prostate cancer at re‐screening after 4 years?
Authors: Wolters Tineke , Roobol Monique J. , Schröder Fritz H. , Van Der Kwast Theodorus H. , Roemeling Stijn , Van Der Cruijsen‐Koeter Ingrid W. , Bangma Chris H. , Van Leenders Geert J.L.H. ,   (ERSPC Rotterdam section)
Published: October 2007

OBJECTIVESTo identify pathological features in non‐malignant sextant prostate needle biopsies and assess their predictive value for detecting prostate cancer on biopsy 4 years later.PATIENTS AND METHODSWe selected and reviewed the biopsy specimens of 121 men that were diagnosed as non‐malignant during the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Of these 61 (50.4%) were positive for cancer during the second round (the result of a matched random sample). The biopsies were indicated by prostate‐specific antigen levels of ≥ 3.0 ng/mL. Specimens were scored for high‐grade prostatic intraepithelial neoplasia (HGPIN), active and chronic inflammation, biopsy core length and glandular core length. The predictive value of the pathological features for detecting prostate cancer after 4 years was assessed.RESULTSIn the first‐round biopsies the incidence of HGPIN was 7.1%; there was active inflammation in 22.4% and chronic inflammation in 51.0%. The mean core length was 9.3 mm and mean glandular core length 7.4 mm; the mean total biopsy length (sum of core lengths) was 56.3 mm and mean total glandular length (sum of glandular core lengths) was 44.6 mm. None of the pathological features in the initial round was significantly related to the detection of cancer in the second round.CONCLUSIONSIn this study of non‐malignant prostate biopsy specimens from a screened population, no pathological features could be identified that were predictive for detecting prostate cancer on biopsy 4 years later.
Impact of prostate‐specific antigen testing on the clinical and pathological outcomes after radical prostatectomy for Gleason 8–10 cancers
Authors: Boorjian Stephen A. , Karnes R. Jeffrey , Rangel Laureano J. , Bergstralh Eric J. , Frank Igor , Blute Michael L. 
Published: October 2007

OBJECTIVETo investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate‐specific antigen (PSA) testing for patients with Gleason 8–10 cancers.PATIENTS AND METHODSWe identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan‐Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models.RESULTSThe median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P < 0.001), while the rate of organ‐confined disease increased from 22.9% to 35.1% (P = 0.007). However, the 7‐year biochemical recurrence‐free (37% vs 45%, P = 0.087) and cancer‐specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level (P < 0.001), seminal vesicle invasion (P < 0.001) and positive lymph nodes (P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion (P = 0.005), positive nodes (P < 0.001) and positive surgical margins (P = 0.03) predicted death from cancer.CONCLUSIONAlthough the pathological features of Gleason 8–10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long‐term cancer control in a subset of these patients, continued investigation of multi‐modal treatment options is warranted.
Redistributive Taxation under Ethical Behaviour*
Authors: Boadway Robin , Marceau Nicolas , Mongrain Steeve 
Published: October 2007

AbstractWe consider the implications of ethical behaviour on the effect of a redistributive tax‐transfer system. In choosing their labour supplies, individuals take into account whether their tax liabilities correspond to what they view as ethically acceptable. If tax liabilities are viewed as ethically acceptable, a taxpayer behaves ethically, does not distort her behaviour, and chooses to work as if she were not taxed. On the other hand, if ethical behaviour results in tax liabilities that exceed those that are ethically acceptable, she behaves egoistically (partially or fully), distorts her behaviour, and chooses her labour supply taking into account the income tax. We establish taxpayers' equilibrium behaviour and obtain that labour supply is less elastic when taxpayers may behave ethically than when they act egoistically. We characterise and compare the egoistic voting equilibrium linear tax schedules under potentially ethical and egoistic behaviour. We also compare our results to those obtained under altruism, an alternative benchmark.
Comparisons of regression constants fitted by maximum likelihood to four common transformations of binomial data*
Authors: NAYLOR A. F. 
Published: October 2007

SUMMARYAn electronic computer was used to fit regression constants of arcsine, logit, log‐log and inverse normal (probit) transforms of binomial data. The data ranged over a variety of types, biologically and mathematically, but were ‘complex’(with several independent variables). This empirical study leads one to assume, very unequivocally, that there is no practical difference in analyses using these four transformations.I thank Drs Daphne Trasler and Dorothy Warburton for permission to quote unpublished data and the McGill Computing Centre for advice and assistance.
Genetic studies of the syndrome of congenital deafness and simple goitre
Authors: THOULD A. K. , SCOWEN E. F. 
Published: October 2007

SUMMARYTwenty‐six pedigrees containing thirty examples of the syndrome of congenital deafness and sporadic goitre are presented. Evidence is put forward to support our conclusion that the mode of inheritance is that of a recessive character. There were insufficient data, due to the small numbers involved, for us to obtain any significant evidence of linkage to the ABO blood groups and other marker genes.We would like to thank Dr C. F. Harris for enabling us to investigate family no. 22, and Dr H. W. Balme for family no. 20. Thanks are also due to the Biochemical, Haematological, Isotope and Statistical Departments of St Bartholomew's Hospital for their assistance. Particularly, we would like to thank Professor H. Harris for his help and advice.
Establishment of a human in vitro model of the outer blood–retinal barrier
Authors: Hamilton R. D. , Foss A. J. , Leach L. 
Published: October 2007

AbstractThe outer blood–retinal barrier is composed of a monolayer of retinal pigment epithelium, Bruch's membrane and the choriocapillaris which is fenestrated. Endothelial proliferation and breaching of Bruch's membrane leads to the neovascular form of age‐related macula degeneration (ARMD). The aim of this study was to generate an in vitro model that mimics more faithfully the phenotype of the choriocapillaris and the trilayer architecture in vitro. A trilayer culture model was generated with retinal pigment epithelium (ARPE‐19) cell cultures on the epithelial surface of amniotic membrane and with human umbilical vein‐derived endothelial cells on the other surface. A control model for the effect of retinal pigment epithelium on endothelial changes was generated with corneal epithelial cells replacing the ARPE‐19. Both human umbilical vein‐derived endothelial and ARPE‐19 cells formed confluent monolayers on respective surfaces of the amnion. The human umbilical vein‐derived endothelial cells in the trilayer became fenestrated when co‐cultured with the ARPE‐19 cells, but not with corneal epithelial cells, or when grown as monolayers on the amnion, showing a loss of fidelity of origin in the presence of ARPE‐19 cells. These cells also revealed VE‐cadherin and ZO‐1 at cell–cell contacts from 24 h in the trilayer. The tight junctional molecules, occludin and ZO‐1, were localized to cell–cell contact regions in the retinal pigment epithelium, both in the monolayer and in the trilayer system. Permeability of the trilayer was tested by using fluorescein and fluorescein‐conjugated tracers under flow. At 72 h the trilayer severely restricted transfer of sodium fluorescein (NaF) (ten‐fold reduction) whilst transfer of a 4 kDa FITC‐conjugated dextran was virtually occluded, confirming a restrictive barrier. Ultrastructural studies showed the retinal pigment epithelium monolayer was polarized with microvilli present on the apical surface. Paracellular clefts showed numerous tight junctional‐like appositions, similar to that seen on amnion alone. This study demonstrates that ARPE‐19 and human umbilical vein‐derived endothelial cells can be co‐cultured on the amniotic membrane and that the resultant cross‐talk leads to formation of a fenestrated endothelium, whilst maintaining a polarized restrictive epithelial layer. The fenestrated endothelial phenotype achieved in this human in vitro trilayer model is a first and offers an outer‐retinal barrier which approaches the in vivo state and has potential for studies into induced junctional disruption, endothelial proliferation and migration: features of ARMD.
PACAP‐38 induces neuronal differentiation of human SH‐SY5Y neuroblastoma cells via cAMP‐mediated activation of ERK and p38 MAP kinases1
Authors: Monaghan T. K. , MacKenzie C. J. , Plevin R. , Lutz E. M. 
Published: October 2007

AbstractThe intracellular signaling pathways mediating the neurotrophic actions of pituitary adenylate cyclase‐activating polypeptide (PACAP) were investigated in human neuroblastoma SH‐SY5Y cells. Previously, we showed that SH‐SY5Y cells express the PAC1and VIP/PACAP receptor type 2 (VPAC2) receptors, and that the robust cAMP production in response to PACAP and vasoactive intestinal peptide (VIP) was mediated by PAC1receptors (Lutzet al.2006). Here, we investigated the ability of PACAP‐38 to differentiate SH‐SY5Y cells by measuring morphological changes and the expression of neuronal markers. PACAP‐38 caused a concentration‐dependent increase in the number of neurite‐bearing cells and an up‐regulation in the expression of the neuronal proteins Bcl‐2, growth‐associated protein‐43 (GAP‐43) and choline acetyltransferase: VIP was less effective than PACAP‐38 and the VPAC2receptor‐specific agonist, Ro 25‐1553, had no effect. The effects of PACAP‐38 and VIP were blocked by the PAC1receptor antagonist, PACAP6‐38. As observed with PACAP‐38, the adenylyl cyclase activator, forskolin, also induced an increase in the number of neurite‐bearing cells and an up‐regulation in the expression of Bcl‐2 and GAP‐43. PACAP‐induced differentiation was prevented by the adenylyl cyclase inhibitor, 2′,5′‐dideoxyadenosine (DDA), but not the protein kinase A (PKA) inhibitor, H89, or by siRNA‐mediated knock‐down of the PKA catalytic subunit. PACAP‐38 and forskolin stimulated the activation of extracellular signal‐regulated kinase (ERK), mitogen‐activated protein kinase (MAP; p38 MAP kinase) and c‐Jun N‐terminal kinase (JNK). PACAP‐induced neuritogenesis was blocked by the MEK1 inhibitor PD98059 and partially by the p38 MAP kinase inhibitor SB203580. Activation of exchange protein directly activated by cAMP (Epac) partially mimicked the effects of PACAP‐38, and led to the phosphorylation of ERK but not p38 MAP kinase. These results provide evidence that the neurotrophic effects of PACAP‐38 on human SH‐SY5Y neuroblastoma cells are mediated by the PAC1receptor through a cAMP‐dependent but PKA‐independent mechanism, and furthermore suggest that this involves Epac‐dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway.
Over‐expression of GTP‐binding proteins and GTPase activity in mouse astrocyte membranes in response to Theiler’s murine encephalomyelitis virus infection
Authors: Rubio Nazario , Gonzalez‐Tirante Maria , Arevalo Maria‐Angeles , Aranguez Isabel 
Published: October 2007

AbstractIntracerebral infection with Theiler’s murine encephalomyelitis virus (TMEV) induces a demyelinating disease that resembles human multiple sclerosis. In order to delineate the early events in this virus‐induced neuroinflammatory disease, we have analyzed global GTPases gene activation following TMEV infection of murine brain astrocytes. DNA hybridization microchip analysis demonstrated that 10 sequences described as GTPbinding proteins and GTPases in different protein databases were over‐expressed, in response to this infectious agent in astroglial cells. We have first characterized both the GTP‐binding and GTPase activities in uninfected astrocyte membranes from a biochemical point of view. The increase in such activities was further validated in TMEV‐infected astrocytes, peaking 2–4 h after infection. Over‐expression is also induced by the inflammation‐related chemokines interleukin‐6 and interferon‐γ but not by interleukin‐1α or tumor necrosis factor‐α. From the many GTPases that could be over‐expressed we have studied two, because of its biological significance; Ras p21 and the subunit αi2 of G proteins. Western blots revealed increases in both proteins after infection with TMEV, in accordance with the previous enzymologic results. An increase in the active form of Ras (the GTP bound form) in cell lysates was also confirmed by affinity binding to a glutathione‐S‐transferase‐fusion protein, following TMEV infection. A final demonstration of physiological up‐regulation is provided by UV cross‐linking of membrane proteins with the hydrolysis‐resistant GTP agonist GTP [γ‐35S]. This technique allow us to detect, after SDS‐PAGE, the increase of two further majoritary GTPbinding proteins with MW of 62 and 49 KDa. A quantitative analysis of four selected genes coding for p21 ras, Gαi2 subunit of protein G, Munc‐18 and protein interacting with C kinase 1, was performed by real‐time RT‐PCR to verify the microarray results. The study of GTPase activity and of the above genes by RT‐PCR in brains of sick mice, demonstrated a significative increase in mRNA coding for p21ras and protein interacting with C kinase 1 in vivo. Here we demonstrate that one of the mechanisms triggered by TMEV infection of astrocytes is the up‐regulation of proteins related to GTP metabolism, one important signal transduction system in mammalian cells.
Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood–brain barrier
Authors: Miecz Dorota , Januszewicz Elżbieta , Czeredys Magdalena , Hinton Barry T. , Berezowski Vincent , Cecchelli Roméo , Nałęcz Katarzyna A. 
Published: October 2007

AbstractCarnitine β‐hydroxy‐γ‐(trimethylammonio)butyrate – a compound necessary in the peripheral tissues for a transfer of fatty acids for their oxidation within the cell, accumulates in the brain despite low β‐oxidation in this organ. In order to enter the brain, carnitine has to cross the blood–brain barrier formed by capillary endothelial cells which are in close interaction with astrocytes. Previous studies, demonstrating expression of mRNA coding two carnitine transporters – organic cation/carnitine transporter 2 (OCTN2) and B0,+in endothelial cells, did not give any information on carnitine transporters polarity in endothelium. Therefore more detailed experiments were performed on expression and localization of a high affinity carnitine transporter OCTN2 in anin vitromodel of the blood–brain barrier by real‐time PCR, western blot analysis, and immunocytochemistry. The amount of mRNA was comparable in endothelial cells and kidney, when referred to house‐keeping genes, it was, however, significantly lower in astrocytes. Polarity of OCTN2 localization was further studied in anin vitromodel of the blood–brain barrier with use of anti‐OCTN2 antibodies.Z‐axis analysis of the confocal microscope pictures of endothelial cells, with anti‐P‐glycoprotein antibodies as the marker of apical membrane, showed OCTN2 localization at the basolateral membrane and in the cytoplasmic region in the vicinity of nuclei. Localization of OCTN2 suggest that carnitine can be also transported from the brain, playing an important role in removal of certain acyl esters.
Microtubule‐associated STOP protein deletion triggers restricted changes in dopaminergic neurotransmission
Authors: Bouvrais‐Veret Caroline , Weiss Stéphanie , Hanoun Naima , Andrieux Annie , Schweitzer Annie , Job Didier , Hamon Michel , Giros Bruno , Martres Marie‐Pascale 
Published: October 2007

AbstractThe microtubule‐associated stable tubule only polypeptide (STOP) protein plays a key‐role in neuron architecture and synaptic plasticity. Recent studies suggest that schizophrenia is associated with alterations in the synaptic connectivity. Mice invalidated for the STOP gene display phenotype reminiscent of some schizophrenic‐like symptoms, such as behavioral disturbances, dopamine (DA) hyper‐reactivity, and possible hypoglutamatergia, partly improved by antipsychotic treatment. In the present work, we examined potential alterations in some DAergic key proteins and behaviors in STOP knockout mice. Whereas the densities of the DA transporter, the vesicular monoamine transporter and the D1 receptor were not modified, the densities of the D2 and D3 receptors were decreased in some DAergic regions in mutant versus wild‐type mice. Endogenous DA levels were selectively decreased in DAergic terminals areas, although the in vivo DA synthesis was diminished both in cell bodies and terminal areas. The DA uptake was decreased in accumbic synaptosomes, but not significantly altered in striatal synaptosomes. Finally, STOP knockout mice were hypersensitive to acute and subchronic locomotor effects of cocaine, although the drug equally inhibited DA uptake in mutant and wild‐type mice. Altogether, these data showed that deletion of the ubiquitous STOP protein elicited restricted alterations in DAergic neurotransmission, preferentially in the meso‐limbic pathway.