bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for cell‐specific changes with age in expression of oestrogen receptor (ER) α and β in bone fractures from men and women
Authors: Batra Gaurav S , Hainey Linda , Freemont Anthony J , Andrew Glynne , Saunders Philippa TK , Hoyland Judith A , Braidman Isobel P 
Published: April 2003

AbstractOestrogen is recognized as important for maintaining bone mass in men and women. Oestrogen receptor (ER) α and the recently described ER‐β are both expressed in bone cells, but have different affinities for oestrogen agonists and plant oestrogens, which could be important in developing treatments for bone loss in both men and women. It is unclear, however, which isoform predominates in bone; cell type and age may influence their relative expression. The present study has compared ER‐α and ER‐β expression in serial sections of human fracture callus from males (n = 19, age range 5–72 years) and females (n = 15, age range 3–86 years) by indirect immunoperoxidase. Fracture callus was used as it can be readily obtained from individuals over a wide age range and contains a variety of bone cells. Antibody specificity was confirmed by western blotting and comparison of immunoreactivity in sections of breast tumour and benign prostate hyperplasia. No gender difference in ER expression was found in bone from individuals less than 40 years old. Proliferative chondrocytes were positive for both isoforms, but few larger hypertrophic cells were immunoreactive. ER‐α and ER‐β were co‐expressed in osteoclasts, suggesting that oestrogen may act directly on these cells. Osteoblasts, osteocytes, and mesenchymal cells also expressed both isoforms. In women over 40 years of age, however, relatively fewer biopsies contained osteocytes positive for ER‐α and ER‐β. Likewise, the proportions of osteoblasts and mesenchymal cells expressing ER‐β were reduced but ER‐α remained unaffected. In contrast, in men over 40 years, only the proportion of biopsies containing ER‐β‐positive mesenchymal cells was lower. In these older men and women, ER‐α and ER‐β expression was retained by the small proliferative chondrocytes. These results demonstrate that gender, age, and cell type are important determinants of ER isoform expression in skeletal cells. Copyright © 2003 John Wiley & Sons, Ltd.
The evolution of crescentic nephritis and alveolar haemorrhage following induction of autoimmunity to glomerular basement membrane in an experimental model of Goodpasture's disease
Authors: Reynolds John , Moss Jill , Duda Mark A , Smith Jennifer , Karkar Ayman M , Macherla Vamshi , Shore Ian , Evans David J , Woodrow David F , Pusey Charles D 
Published: April 2003

AbstractGoodpasture's, or anti‐glomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis and lung haemorrhage, and is caused by autoimmunity to the NC1 domain of the α3 chain of type IV collagen (α3(IV)NC1). This study examines the development of crescentic nephritis and alveolar haemorrhage in a model of Goodpasture's disease, experimental autoimmune glomerulonephritis (EAG), induced in WKY rats by immunization with rat GBM in adjuvant. An increase in circulating anti‐GBM antibodies and albuminuria was observed by week 2, which increased further by weeks 3 and 4, while a decrease in creatinine clearance was observed by week 2, which decreased further by weeks 3 and 4. The kidneys of animals with EAG showed linear deposits of IgG on the GBM and a transient glomerular infiltration by CD4+ T cells at week 2. By week 3 there were large deposits of fibrin in Bowman's space, and glomerular infiltration by CD8+ T cells and macrophages, accompanied by focal necrotizing glomerulonephritis with crescent formation. Ultrastructural studies showed glomerular endothelial cell swelling and epithelial cell foot process effacement at week 2. As the lesion progressed, capillary loops became occluded and the mesangium became expanded by mononuclear cells. By week 3 there was detachment of the endothelium from the GBM, and accumulation of fibrin beneath the disrupted endothelial cells and in Bowman's space. Occasional breaks were observed in the continuity of the basement membrane, and cytoplasmic projections from infiltrating mononuclear cells could be seen crossing the capillary wall between the lumen and the crescent. The lungs of animals with EAG showed patchy binding of IgG to the alveolar basement membrane (ABM) at week 2, and infiltration of the interstitium by CD8+ T cells and macrophages by weeks 3 and 4, accompanied by both interstitial and alveolar haemorrhage. Ultrastructural studies showed focal mononuclear cell infiltrates in alveolar walls at week 2. Occasional breaks were observed in the basement membrane and adjacent endothelium by weeks 3 and 4, together with accumulation of surfactant and erythrocytes within the alveolar spaces. This study defines for the first time the relationship between the immunological and pathological events during the evolution of EAG, and provides the basis for further work on the pathogenesis of Goodpasture's disease. Copyright © 2003 John Wiley & Sons, Ltd.
The pattern of expression of protease‐activated receptors (PARs) during early trophoblast development
Authors: Even‐Ram Sharona Cohen , Grisaru‐Granovsky Sorina , Pruss Diana , Maoz Miriam , Salah Zaidoun , Yong‐Jun Yin , Bar‐Shavit Rachel 
Published: April 2003

AbstractHuman fetal development depends on the ability of the embryo to gain access to the maternal circulation. Thus, specialized stem cells of the newly formed placenta, trophoblast, invade the uterus and its arterial network to establish an efficient feto‐maternal molecular exchange. To accomplish this task, trophoblast differentiation during the first trimester of pregnancy involves cell proliferation, invasion, and extracellular matrix (ECM) remodelling. Trophoblast invasion shares many features with tumour cell invasion, with the distinction that it is strictly spatially and temporally controlled. We have previously demonstrated that PAR1, the first member of the protease‐activated receptor (PAR) family, plays a central role in tumour cell invasion. In the present study we have examined the pattern of expression of PAR1 and other PAR family candidates during early human placental development. We show that PAR1 and PAR3 are highly and spatially expressed between the 7th and 10th weeks of gestation but not at the 12th week and thereafter. Likewise, high expression levels of PAR1 and PAR3 were observed in the cytotrophoblast cells of complete hydatidiform mole as compared to minimal levels in normal age‐matched placenta. Together, our data suggest the involvement of PAR1 and PAR3 in restricted and unrestricted pathological trophoblast invasion. Copyright © 2003 John Wiley & Sons, Ltd.
Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann–Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease
Authors: Treiber‐Held Stephanie , Distl Roland , Meske Volker , Albert Frank , Ohm Thomas G 
Published: April 2003

AbstractNiemann–Pick type C (NPC) disease is a fatal hereditary neurovisceral disorder with diagnostically relevant intracellular accumulation of cholesterol in non‐brain tissue, for example the spleen and fibroblasts. In the brain, many ballooned neurons are seen. Using filipin microfluorodensitometry, significant accumulations of free cholesterol in specified neurons have been described in NPC patients. The present study demonstrates spatial and temporal accumulation of free cholesterol in the brains of homozygous NPC (−npc/−npc) mice, a widely acknowledged mouse model, and in primarily cultured neurons therefrom. Intraneuronal storage of free cholesterol was already prominent at a pre‐clinical stage in various grey matter areas of the murine cerebral cortex. Hippocampal areas showed differential development of the pathological distribution of free cholesterol. The pyramidal cells in the CA3 sector of Ammon's horn were affected much earlier than in CA1. Some of the deeper cerebral nuclei were affected only slightly, even at the final stage. Neurons (E15–E17) cultured in a cholesterol‐free medium also showed massive accumulation of intracellular free cholesterol. In addition, brains from the murine NPC model for Alzheimer's disease (AD)‐like changes in the microtubule‐associated protein tau were tested using the Gallyas silver technique and AT8‐immunolabelling, since both human diseases are accompanied by intraneuronal tangles made up of tau protein aggregations. Although the analysis failed to show classical silver‐stainable tangles of the AD type in the NPC mice, tau protein phosphorylated at epitopes considered to represent early stages of AD was found. This further strengthens the concept that an alteration in cholesterol metabolism may play an important role in AD. The NPC mouse model may thus serve as a tool to analyse the role of cholesterol in initial changes of tau that eventually lead to the formation of tangles in both NPC and AD. Copyright © 2003 John Wiley & Sons, Ltd.
Epithelial carcinogenesis: challenging monoclonality
Authors: Going James J 
Published: April 2003

AbstractHow carcinomas begin remains unclear, but experimental data do not entirely exclude the participation of more than one clone of neoplastic cells, even in relatively advanced epithelial tumour growth. Microdissection and new PCR clonality assays exploiting X‐linked polymorphisms, some of which (including XIST) are expressed in RNA, create investigational opportunities complementary to other molecular analyses, but a reliable in situ assay of X‐inactivation remains desirable. The necessity for stringent controls in clonality analysis is emphasized. While it may be possible to reconcile ‘pluriclonal’ (oligoclonal or polyclonal) carcinogenesis with widely accepted paradigms of genetic/epigenetic change and clonal selection in epithelial neoplasia, it deserves critical study as novel carcinogenic mechanisms would be implied. Copyright © 2003 John Wiley & Sons, Ltd.
Pathobiology of autochthonous prostate cancer in a pre‐clinical transgenic mouse model
Authors: Kaplan‐Lefko Paula J. , Chen Tsuey‐Ming , Ittmann Michael M. , Barrios Roberto J. , Ayala Gustavo E. , Huss Wendy J. , Maddison Lisette A. , Foster Barbara A. , Greenberg Norman M. 
Published: April 2003

AbstractBackgroundAnimal models that closely mimic clinical disease can be exploited to hasten the pace of translational research. To this end, we have defined windows of opportunity in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of prostate cancer as a paradigm for designing pre‐clinical trials.MethodsThe incidence of cancer, metastasis, and distribution of pathology were examined as a function of time in TRAMP mice. The expression of various markers of differentiation were characterized.ResultsThe TRAMP model develops progressive, multifocal, and heterogeneous disease. Each lobe of the prostate progressed at a different rate. Cytokeratin 8, E‐cadherin, and androgen receptor (AR) were expressed during cancer progression but levels were reduced or absent in late stage disease. A distinct epithelial to neuroendocrine (ENT) shift was observed to be a stochastic event related to prostate cancer progression in TRAMP.ConclusionsThis study will serve as the basis for the rational design of pre‐clinical studies with genetically engineered mouse models. Prostate 55: 219–237, 2003. © 2003 Wiley‐Liss, Inc.
Growth inhibition and differentiation in human prostate carcinoma cells induced by the vitamin D analog 1α,24‐dihydroxyvitamin D2
Authors: Bauer Joshua A. , Thompson Todd A. , Church Dawn R. , Ariazi Eric A. , Wilding George 
Published: April 2003

AbstractBackgroundVitamin D has been suggested as a chemopreventive and therapeutic modality for prostate cancer. However, hypercalcemic toxicity has limited the use of 1α,25‐dihydroxyvitamin D3 (1,25‐(OH)2D3) in clinical trials, prompting the search for analogs of vitamin D with less toxicity while retaining efficacy as a modality for cancer intervention. In this study, the less hypercalcemic vitamin D analog 1α,24‐dihydroxyvitamin D2 (1,24‐(OH)2D2) was examined for its effects on cellular growth inhibition and differentiation induction in the LNCaP human prostate carcinoma cell line.MethodsLNCaP cell growth was determined by quantifying DNA levels. Protein levels were determined using the ELISA method and immunoblotting. Levels of mRNA were determined using real‐time quantitative reverse transcriptase PCR.ResultsLNCaP growth was decreased 50% by exposure to 0.01 nM 1,24‐(OH)2D2 after 96 hr in the presence of a growth stimulatory 0.1 nM dose of the androgen R1881. Prostate specific antigen (PSA) levels were increased 3.5‐fold with 10 nM 1,24‐(OH)2D2 treatment compared to a 1.9‐fold increase in PSA levels found with 10 nM 1,25‐(OH)2D3 under low androgen conditions. Neither 1,24‐(OH)2D2 nor 1,25‐(OH)2D3 affected the expression of cytokeratin 18 protein levels. Treatment with 10 nM 1,24‐(OH)2D2 alone produced a 1.3‐fold increase in AR mRNA and a 2.2‐fold increase in AR protein levels after 96 hr. Surprisingly, the addition of 1.0 nM R1881 alone or in combination with 10 nM 1,24‐(OH)2D2 produced an approximately 60% decrease in AR mRNA, whereas AR protein levels were increased 1.6‐fold.ConclusionsOverall, 1,24‐(OH)2D2 was found to be at least as effective as 1,25‐(OH)2D3 at inhibiting growth and inducing differentiation markers in LNCaP prostate carcinoma cells and may thus prove useful in prostate cancer treatment. Prostate 55: 159–167, 2003. © 2003 Wiley‐Liss, Inc.
Variation in chromogranin A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma
Authors: Sciarra Alessandro , Monti Salvatore , Gentile Vincenzo , Mariotti Gianna , Cardi Antonio , Voria Giuseppe , Lucera Rossana , Di Silverio Franco 
Published: April 2003

AbstractObjectivesIt has been hypothesized that continuous androgen‐suppression therapy produces hyperactivation of neuroendocrine (NE) cells and an increase in chromogranin A (CgA) in prostate carcinoma (PC). The aim of this study was to verify whether the intermittent administration of androgen deprivation (IAD) reduces the risk of CgA increase in PC cases treated with complete androgen deprivation (CAD).Materials and MethodsWe analyzed changes in serum CgA levels in patients with PC who successfully responded to the first 24 months of IAD versus continuous CAD therapy. Two different populations were analyzed: Type 1 = pT3pN0M0 prostate cancers with biochemical (PSA) progression after RRP; Type 2 = metastatic PC directly submitted to CAD. Cases in Type 1 and Type 2 population were randomly assigned to IAD versus continuous CAD therapy. Forty cases each in Type 1 and Type 2 population were included in the analysis. At 1, 3, 6, 12, 18, 24 months of IAD versus continuous therapy, serum levels of CgA compared to PSA levels were analyzed.ResultsIn population Type 1 and Type 2, in the group of cases continuously treated with CAD (Group 2), there was a significant trend to increase for CgA levels from baseline to 24 months of therapy. On the contrary, no significant variations were found in cases treated with IAD (Group 1). Either in population Type 1 or Type 2, at 12‐ and 24‐month follow‐up, mean and median serum levels of CgA were significantly (P < 0.005) lower in Group 1 than in Group 2.ConclusionsThe present study represents the first evidence in the literature that the intermittent administration of CAD therapy significantly reduces the increase in serum CgA levels during CAD therapy. Prostate 55: 168–179, 2003. © 2003 Wiley‐Liss, Inc.
Intraepithelial and stromal lymphocytes in the normal human prostate
Authors: Bostwick David G. , de la Roza Gustavo , Dundore Paul , Corica Federico A. , Iczkowski Kenneth A. 
Published: April 2003

AbstractBACKGROUNDThe distribution and significance of lymphocytes in the normal human prostate is uncertain. It may be important as a determinant of the immune response, playing a role in hyperplasia and carcinogenesis.METHODSWe studied 28 normal autopsy prostates from patients between 1 and 64 years of age. Cases with nodular hyperplasia, intraepithelial neoplasia, cancer, and florid prostatitis were excluded. Each prostate was routinely processed to paraffin and immunohistochemically stained for CD20, CD45, and CD45RO. Three frozen samples obtained from these cases were stained for CD8 and CD4. One low power field (25× magnification, 50 mm2) was randomly chosen for examination from each anatomic zone of the prostate, namely the peripheral, transition, and central zone. Lymphocytes were visually counted in the stroma and epithelium of each zone. Lymphocyte counts were converted to number of cells per square millimeter based on the area of the slide per field and the percentage of field that was glandular.RESULTSStromal lymphocytes were more numerous than epithelial lymphocytes (mean, 7.32 and 2.04 cells/mm2, respectively). They were mostly T cells (stromal lymphocytes: 93% CD45RO +; epithelial lymphocytes: 99% CD45RO +). Helper/inducer (CD4 +) T cells predominated in the stroma, whereas those in epithelium were chiefly cytotoxic/suppressor (CD8 +). No difference was found in the number of stromal and epithelial T or B cells according to patient age, race, or location within the prostate (peripheral, central, and transition zones) (all P > 0.05), although the number of lymphocytes in the peripheral zone tended to exceed that in the other zones after correcting for gland:stroma ratio.CONCLUSIONSThe immune response in the prostate is primarily cell‐mediated. Cell distribution is constant according to patient age, race, and anatomic zonal location within the prostate. The greatest concentration is in the stroma with a small but significant number of intraepithelial cells. The inverted CD4/CD8 ratio in the intraepithelial compartment suggests that cytotoxic/suppressor T cells are the first line of defense against luminal foreign agents reaching the prostate through retrograde flow. Prostate 55: 187–193, 2003. © 2003 Wiley‐Liss, Inc.
Reduced circulating androgen bioactivity in patients with prostate cancer
Authors: Raivio Taneli , Santti Henrikki , Schatzl Georg , Gsur Andrea , Haidinger Gerald , Palvimo Jorma J. , Jänne Olli A. , Madersbacher Stephan 
Published: April 2003

AbstractBackgroundPrevious studies on immunoreactive androgen levels in serum have revealed equivocal associations with the risk of prostate cancer (CaP). The aim of this study was to compare serum biological androgen activity between men with newly diagnosed CaP and age‐matched men with benign prostatic hyperplasia (BPH).MethodsCaucasian men with newly diagnosed, untreated CaP (n = 101) and age‐matched patients with BPH (n = 103) were investigated. Serum androgen bioactivity (ABA) levels were measured using a recently developed recombinant cell bioassay.ResultsIn comparison to men with BPH, CaP patients with Gleason score ≥8 (n = 16) had lower serum ABA (P < 0.05), and patients with Gleason score ≤5 (P < 0.05) or ≥8 (P = 0.07) displayed suppressed ABA levels in relation to serum testosterone. As the entire group, men with CaP (n = 101) had significantly lower serum ABA than age‐matched men with BPH (n = 103): median 3.0 nM (range, 0.8–6.4 nM) versus 3.2 nM (range, 0.8–7.9 nM) testosterone equivalents, respectively (P < 0.005). By contrast, serum immunoreactive testosterone and SHBG concentrations and free androgen indices did not differ significantly between the two groups.ConclusionsPatients with CaP have lower serum ABA than controls with BPH, and men with low or high Gleason score display suppressed circulating ABA‐to‐testosterone ratio. These features may reflect interaction between variables such as the degree of tumor differentiation and tumor volume with androgen metabolism. Prostate 55: 194–198, 2003. © 2003 Wiley‐Liss, Inc.
Hypermethylation of GSTP1, CD44, and E‐cadherin genes in prostate cancer among US Blacks and Whites
Authors: Woodson Karen , Hayes Richard , Wideroff Louise , Villaruz Liza , Tangrea Joseph 
Published: April 2003

AbstractBackgroundIn the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter‐region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes).MethodsUsing real‐time methylation‐sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E‐cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64).ResultsWe found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7‐fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E‐cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race.ConclusionsThese preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies. Prostate 55: 199–205, 2003. © 2003 Wiley‐Liss, Inc.
Expression of ERα and ERβ in prostate cancer
Authors: Linja Marika J. , Savinainen Kimmo J. , Tammela Teuvo L.J. , Isola Jorma J. , Visakorpi Tapio 
Published: April 2003

AbstractBACKGROUNDIt has been suggested that estrogens and their receptors (ERs) may be involved in the development and progression of prostate cancer. To elucidate the significance of these receptors, expression of both ERα and ERβ was measured in benign and malignant prostate tumors, as well as in cell lines.METHODSExpression of ERα and ERβ was measured in prostate hyperplasia (BPH, n = 7), androgen‐dependent (n = 30) as well as hormone‐refractory (n = 12) prostate carcinomas, and in four prostate cancer cell lines (LNCaP, DU145, PC‐3, and 22Rv1) using real‐time quantitative RT‐PCR.RESULTSOnly low‐level expression of ERα was found in all tumor types and cell lines. The level of expression was similar to that observed in breast carcinomas found to be negative for ERα by immunohistochemistry. All cell lines showed low, but detectable, levels of ERβ expression. The mean expression of ERβ in the hormone‐refractory carcinomas was about half that seen in BPH or the androgen‐dependent carcinomas; however, the difference was not statistically significant.CONCLUSIONSThe data suggest it is unlikely that alterations in the expression of either ER are commonly involved in the progression of prostate cancer. Prostate 55: 180–186, 2003. © 2003 Wiley‐Liss, Inc.