bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: A comparative population‐based study in Singapore and Sweden
Authors: Chia Kee‐Seng , Reilly Marie , Tan Chuen‐Seng , Lee Jeannette , Pawitan Yudi , Adami Hans‐Olov , Hall Per , Mow Benjamin 
Published: September 2004

AbstractBreast cancer incidence in Sweden has always been approximately twice as high as in Singapore. In recent years, this difference is limited to postmenopausal women. The aim of this study was to explore the reasons behind these differences through the use of age‐period‐cohort modeling. This population‐based study included all breast cancer cases reported to the Swedish and the Singapore cancer registries from 1968 to 1997, with a total of 135,581 Swedish and 10,716 Singaporean women. Poisson regression using age‐period and age‐cohort models was used to determine the effects of age at diagnosis, calendar period and birth cohort. Incidence rate ratios were used to summarize these effects. An age‐cohort model provided the best fit to the data in both countries, indicating that changes over lifetime, rather than recent differences in medical surveillance, might account for the observed differences in these 2 populations. The changes over birth cohort were much greater among Singaporean women. The relative effect of age was very similar in the 2 countries. Analyses show that age and cohort effects may explain the differences in trends of female breast cancer incidence between Sweden and Singapore. The larger cohort effect seen in Singaporean women may be attributed to more rapid changes in reproduction and lifestyle patterns than that of Swedish women during the period studied. The incidence of breast cancer in postmenopausal women in Singapore will probably continue to rise in the coming decades to match the current Swedish rates.
Mutations of BRAF and RAS are rare events in germ cell tumours
Authors: Sommerer Florian , Hengge Ulrich R. , Markwarth Annett , Vomschloss Susanne , Stolzenburg Jens‐Uwe , Wittekind Christian , Tannapfel Andrea 
Published: September 2004

AbstractThe BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. Recently, somatic missense mutations in the BRAF gene have been detected in a variety of human tumors. We have studied male germ cell tumours (GCT) for probable mutations of the BRAF and Ras oncogene. Microsatellite instability (MSI) was analysed using mono‐ or di‐nucleotide marker. Mutational analysis of 62 GCT (30 seminomas and 32 nonseminomas) was performed after microdissection of the different tumour components. The expression of Erk1/2, an important downstream point of convergence in the Ras‐RAF‐MEK‐Erk pathway was assessed immunohistochemically. Activating BRAF missense mutations were identified in 3 out of 32 cases of nonseminomas (9%) but not in seminomas. The mutations were 1796T>A mutations and were found within the embryonic carcinoma component of these tumors. Two out of 30 seminomas (7%) and 3 out of 32 nonseminomas (9%) exhibited KRAS gene mutations. MSI was observed in 4 out 62 tumours (7%) [1 seminoma and 3 nonseminomas (embryonal carcinoma)]. All of the microsatellite instable embryonal carcinomas had a mutated BRAF gene. All 5 GCT with RAS mutations had an intact BRAF gene. We identified constitutively activated Erk in almost all tumours tested. Our data indicate that BRAF gene mutations are a rare event in GCT and are independent of KRAS mutations. In embryonal carcinomas, BRAF mutations may be linked to the proficiency of these tumours in repairing mismatched bases in DNA. The finding of activated Erk suggests a causative role for MAPK activation in GCT independent of activating BRAF or RAS mutations.
Overexpression and significance of prion protein in gastric cancer and multidrug‐resistant gastric carcinoma cell line SGC7901/ADR
Authors: Du Jingping , Pan Yanglin , Shi Yongquan , Guo Changcun , Jin Xiaohang , Sun Li , Liu Na , Qiao Taidong , Fan Daiming 
Published: September 2004

AbstractIn our previous work, cellular prion protein (PrPc) was identified as an upregulated gene in adriamycin‐resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Here we investigate the expression of PrPc in gastric cancer and whether it was involved in multidrug resistance (MDR) of gastric cancer. We demonstrated that PrPc was ubiquitously expressed in gastric cancer cell lines and tissues. PrPc conferred resistance of both P‐glycoprotein (P‐gp)‐related and P‐gp‐nonrelated drugs on SGC7901, which was accompanied by decreased accumulation and increased releasing amount of adriamycin in PrPc‐overexpressing cell line. Inhibition of PrPc expression by antisense or RNAi technology could partially reverse multidrug‐resistant phenotype of SGC7901/ADR. PrPc significantly upregulated the expression of the classical MDR‐related molecule P‐gp but not multidrug resistance associated protein and glutathione S‐transferase pi. The PrPc‐induced MDR could be partially reversed by P‐gp inhibitor verapamil. PrPc could also suppress adriamycin‐induced apoptosis and alter the expression of Bcl‐2 and Bax, which might be another pathway contributing to PrPc‐related MDR. The further study of the biological functions of PrPc may be helpful for understanding the mechanisms of occurrence and development of clinical gastric carcinoma and PrPc‐related MDR and developing possible strategies to treat gastric cancer.
Gelatin‐embedded cell–polymer constructs for histological cryosectioning
Authors: Brown David A. , Chou Yu Fen , Beygui Ramin E. , Dunn James C.Y. , Wu Benjamin M. 
Published: September 2004

AbstractMany tissue‐engineering strategies involve the delivery of cells via porous polymer scaffolds. Obtaining histological sections of the emerging tissue is often necessary to analyze numerous characteristics of the microscopic environment. However, difficulties arise upon applying standard histological techniques to cell‐seeded polymer scaffolds. This report describes a simple and reliable method for cryosectioning cell–polymer constructs embedded in gelatin. Solvent‐soluble (PLGA) and insoluble (PGA) scaffolds were cultured in vitro with preosteoblasts, followed by histological processing with paraffin, OCT, or gelatin. Although paraffin‐embedded PGA scaffolds withstood standard sectioning and rinsing steps, paraffin‐embedded PLGA scaffolds were partially dissolved during the clearing step. OCT‐embedded scaffolds produced sections that did not adhere well to slides, and most of the sample was lost during rinsing steps. In contrast, gelatin‐embedded scaffolds exhibited adequate structural integrity during cryosectioning, adhered well to the slides, retained the actual polymer morphology, and exhibited compatibility with common stains. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 79–85, 2005
TNF receptor type 1 regulates RANK ligand expression by stromal cells and modulates osteoclastogenesis
Authors: Abu‐Amer Yousef , Abbas Sabiha , Hirayama Teruhisa 
Published: September 2004

AbstractTNFα is a major osteoclastogenic cytokine and a primary mediator of inflammatory osteoclastogenesis. We have previously shown that this cytokine directly targets osteoclasts and their precursors and that deletion of its type‐1 receptor (TNFr1) lessens osteoclastogenesis and impacts RANK signaling molecules. Osteoclastogenesis is primarily a RANK/RANKL‐dependent event and occurs in an environment governed by both hematopoietic and mesenchymal compartments. Thus, we reasoned that TNF/TNFr1 may regulate RANKL and possibly RANK expression by stromal cells and osteoclast precursors (OCPs), respectively. RT‐PCR experiments reveal that levels of RANKL mRNA in WT stromal cells are increased following treatment with 1,25‐VD3 compared to low levels in TNFr1‐null cells. Expression levels of OPG, the RANKL decoy protein, were largely unchanged, thus supporting a RANKL/OPG positive ratio favoring WT cells. RANK protein expression by OCPs was lower in TNFr1‐null cells despite only subtle differences in mRNA expression in both cell types. Mix and match experiments of different cell populations from the two mice phenotypes show that WT stromal cells significantly, but not entirely, restore osteoclastogenesis by TNFr1‐null OCPs. Similar results were obtained when the latter cells were cultured in the presence of exogenous RANKL. Altogether, these findings indicate that in the absence of TNFr1 both cell compartments are impaired. This was further confirmed by gain of function experiments using TNFr1‐ null cultures of both cell types at which exogenous TNFr1 cDNA was virally expressed. Thus, restoration of TNFr1 expression in OCPs and stromal cells was sufficient to reinstate osteoclastogenesis and provides direct evidence that TNFr1 integrity is required for optimal RANK‐mediated osteoclastogenesis. © 2004 Wiley‐Liss, Inc.
Modulation of O‐GlcNAc glycosylation during Xenopus oocyte maturation
Authors: Lefebvre Tony , Baert Frédéric , Bodart Jean‐François , Flament Stéphane , Michalski Jean‐Claude , Vilain Jean‐Pierre 
Published: September 2004

AbstractO‐linked N‐acetylglucosamine (O‐GlcNAc) glycosylation is a post‐translational modification, which is believed antagonises phosphorylation. We have studied the O‐GlcNAc level during Xenopus oocyte meiotic resumption, taking advantage of the high synchrony of this model which is dependent upon a burst of phosphorylation. Stimulation of immature stage VI oocytes using progesterone was followed by a 4.51 ± 0.32 fold increase in the GlcNAc content, concomitantly to an increase in phosphorylation, notably on two cytoplasmic proteins of 66 and 97 kDa. The increase of O‐GlcNAc for the 97 kDa protein, which we identified as β‐catenin was partly related to its accumulation during maturation, as was demonstrated by the use of the protein synthesis inhibitor—cycloheximide. Microinjection of free GlcNAc, which inhibits O‐glycosylated proteins–lectins interactions, delayed the progesterone‐induced maturation without affecting the O‐GlcNAc content. Our results suggest that O‐GlcNAc glycosylation could regulate protein–protein interactions required for the cell cycle kinetic. © 2004 Wiley‐Liss, Inc.
Quantitative structure–activity relationships for phenyl triazolinones of protoporphyrinogen oxidase inhibitors: A density functional theory study
Authors: Wan Jian , Zhang Li , Yang Guangfu 
Published: September 2004

AbstractThe equilibrium geometries, electronic structures, and electrostatic potentials of a series of substituted phenyl triazolinones of protoporphyrinogen oxidase (PPO) inhibitors have been investigated by using the density functional theory (DFT) method. The quantum chemical descriptors, highest occupied molecular orbital and lowest unoccupied molecular orbital energy gap (ΔE), weighted electrophilic, and nucleophilic atomic frontier electron density (F and F), and net atomic charge (QA), were computed at the same DFT level. Based on these precise quantum chemical descriptors, a quantitative structure–activity relationships study has been carried out and shown that Q, F, F, and ΔE of individual molecules are most likely to be responsible for the in vitro biological activity and greenhouse preemergence activity of phenyl triazolinones. The ability to quite accurately predict the biological activity of phenyl triazolinones by using DFT‐based QSAR can be expected to help facilitate the design of additional substituted phenyl triazolinones as PPO inhibitors with good biological activity. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1827–1832, 2004
Simultaneously multi‐parameter determination of hematonosis cell apoptosis by two‐photon and confocal laser scanning microscopy
Authors: Wang Yi , Wang Xue‐Feng , Wang Chen , Ma Hui 
Published: September 2004

AbstractFlow cytometry (FCM), TdT‐mediated dUTP Nick End Labeling (TUNEL), and DNA ladder are conventional methods to detect apoptosis of drug‐treated cells. However, the assumption of cell number restricts their applications in clinics. In this paper, we report a cell‐saving imaging method for quick identification of the hematonosis cell apoptosis induced by chemotherapeutic drugs. By the combination of two‐photon and confocal microscopy, three main apoptosis parameters (the change of nuclear morphology, collapse of mitochondrial membrane potential, and increase of intracellular calcium) were recorded simultaneously for single As2O3‐induced Molt‐4 cells. The results are highly in accordance with those produced by classical flow cytometry. This work suggests that this new imaging method would be promising in the quick identification of hematonosis cell apoptosis. J. Clin. Lab. Anal. 18:271–275, 2004. © 2004 Wiley‐Liss, Inc.
Urokinase gene 3′‐UTR T/C polymorphism is associated with oral cancer
Authors: Tsai Ming‐Hsui , Chen Wen‐Chi , Chen Huey‐Yi , Tsai Fuu‐Jen 
Published: September 2004

AbstractUrokinase is thought to be involved in the formation of oral cancer, although there is a lack of genetic evidence. Our aim was to study single nucleotide polymorphisms in order to investigate the possibility. A total of 130 oral cancer patients and 105 controls were studied. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene, which is located on the 3′‐untranslated region (3′‐UTR) of chromosome 10. There was a significant difference in the distribution of the urokinase gene 3′‐UTR C/T polymorphism frequency between cancer patients and the normal control group (P<0.05). The “T” allele was prominent in the cancer group. The odds ratio for the risk of the “T” allele in cancer patients was 2.71 (95% CI=1.325∼5.562). The cancer patients were further categorized according to gender and whether or not they were habitual smokers or betel nut chewers. These clinical parameters were then compared with tumor cell differentiation and tumor progression. No significant differences were found. Therefore, the urokinase gene 3′‐UTR “T” allele is associated with oral cancer and may play a role in oral cancer formation. However, we did not find the relationship between tumor progression and this polymorphism. J. Clin. Lab. Anal. 18:276–279, 2004. © 2004 Wiley‐Liss, Inc.
Measurement of C‐reactive protein: Two high sensitivity methods compared
Authors: Dominici Roberto , Luraschi Paola , Franzini Carlo 
Published: September 2004

AbstractC‐reactive protein (CRP) is an acute phase marker and a predictor of the risk of developing atherosclerotic complications. However, as a predictor of this risk, high sensitivity measurements are needed, and high sensitive CRP (hsCRP) assays have been developed. In this study, we experimentally compared two hsCRP assays, based on nephelometry and turbidimetry, both implemented on automated analyzers. Linearity, imprecision, turbidity interference, and results in the assay of 96 samples have been compared. Method comparison of the same two analytical systems in the assay of CRP was also performed on the basis of results in an interlaboratory external quality assessment scheme (EQAS). The two systems were found to perform substantially equally, both in hsCRP and in CRP measurement, but in the hsCRP assay the precision of nephelometry (CV% in the interval 3.0–5.8) was lower than that of turbidimetry (CV% in the interval 1.8–2.3). The classification of results by the two methods into three predefined relative risk classes gave 18% rate of discordance, in any case by one class only. The two methods proved reliable and comparable in the measurement of hsCRP, but precision should be improved. J. Clin. Lab. Anal. 18:280–284, 2004. © 2004 Wiley‐Liss, Inc.
Challenges in treating obsessive‐compulsive disorder: Introduction
Authors: Wilhelm Sabine , Tolin David F. , Steketee Gail 
Published: September 2004

AbstractThis issue of In Session is devoted to challenges in the treatment of obsessive‐compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises. Articles focus on the treatment of OCD with comorbid depression, compulsive hoarding, incompleteness, and repugnant obsessions, and on treatment of children who have OCD. The final article describes pharmacotherapy for OCD. All articles feature case vignettes and provide practitioners with clinical recommendations. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Treatment of compulsive hoarding
Authors: Saxena Sanjaya , Maidment Karron M. 
Published: September 2004

AbstractCompulsive hoarding and saving symptoms, found in many patients who have obsessive‐compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to antiobsessional medications and cognitive‐behavioral therapy (CBT). Specific CBT strategies targeting the characteristic features of the compulsive hoarding syndrome have had better results. This article provides an overview of the compulsive hoarding syndrome, a review of treatment approaches and their efficacy, a case presentation, and a detailed discussion of intensive, multimodal CBT for compulsive hoarding. New insights into the neurobiological characteristics of compulsive hoarding that might direct future treatment development are also presented. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Cognitive‐behavioral treatment of repugnant obsessions
Authors: Purdon Christine 
Published: September 2004

AbstractObsessions often occur in the form of repugnant sexual, aggressive, or blasphemous thoughts, images, impulses, or doubts. This article describes the phenomenon of repugnant obsessions and reviews the cognitive‐behavioral model of obsessive‐compulsive disorder (OCD). Caveats and recommendations are provided and a case illustration is presented. Repugnant obsessions are highly amenable to treatment; but developing an idiographic conceptualization of the client's obsessive‐compulsive cycle is important. Treatment resources are presented throughout. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Pharmacotherapy for obsessive‐compulsive disorder
Authors: Dougherty Darin D. , Rauch Scott L. , Jenike Michael A. 
Published: September 2004

AbstractPharmacotherapeutic options for obsessive‐compulsive disorder (OCD) have expanded over the past half‐century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first‐line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment‐refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device‐based approaches for treatment‐refractory OCD are reviewed. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Isolation of a stromal cell line from an early passage of a mouse mammary tumor line: A model for stromal parenchymal interactions
Authors: Lamb Caroline A. , Fabris Victoria , Gorostiaga María Alicia , Helguero Luisa A. , Efeyan Alejo , Bottino María Cecilia , Simian Marina , Soldati Rocío , Sanjuan Norberto , Molinolo Alfredo , Lanari Claudia 
Published: September 2004

AbstractWe have developed a murine mammary tumor cell line, MC4‐L4, and after 15 passages, a spindle‐shaped population became evident. The cuboidal cells, MC4‐L4E, cloned by limit dilution, proved to be epithelial tumor cells. When inoculated in syngeneic mice, they gave rise to invasive metastatic carcinomas expressing estrogen and progesterone receptors. These tumors regressed after anti‐progestin treatment and stopped growing after 17‐β‐estradiol administration. In vitro, they were insensitive to medroxyprogesterone acetate (MPA), 17‐β‐estradiol, and EGF and were inhibited by TGFβ1. They expressed mutated p53 and estrogen receptors α; progesterone receptors were undetectable. Cells were polyploid and shared the same four common marker chromosomes present in the parental tumor in addition to an exclusive marker. Spindle‐shaped cells, MC4‐L4F, were selected by differential attachment and detachment and proved to be non‐epithelial non‐tumorigenic cells. They were cytokeratin negative, showed mesenchymal features by electron microscopy, differentiated to adipocytes when treated with an adipogenic cocktail, were stimulated by TGFβ1 and EGF, showed a wild‐type p53, and did not exhibit the marker chromosomes of the parental tumor. Although they expressed estrogen receptors α, they were insensitive to 17‐β‐estradiol in proliferation assays. Co‐cultures of both cell types had a synergic effect on progesterone receptors expression and on cell proliferation, being the epithelial cells, the most responsive ones, and 17‐β‐estradiol increased cell proliferation only in co‐cultures. Cytogenetic studies and data on p53 mutations rule out the possibility of an epithelial mesenchymal transition. Their unique characteristics make them an excellent model to be used in studies of epithelial–stromal interactions in the context of hormone responsiveness in hormone related tumors. © 2004 Wiley‐Liss, Inc.
Induction of mitochondrial fusion by cysteine‐alkylators ethacrynic acid and N‐ethylmaleimide
Authors: Bowes Timothy J. , Gupta Radhey S. 
Published: September 2004

AbstractMitochondrial fusion and fission are important aspects of eukaryotic cell function that permit the adoption of varied mitochondrial morphologies depending upon cellular physiology. We previously observed that ethacrynic acid (EA) induced mitochondrial fusion in cultured BSC‐1 and CHO/wt cells. However, the mechanism responsible for it was not clear since EA has a number of known cellular effects including glutathione (GSH) depletion and alkylation of cysteine residues. To gain insight, we have tested the effects of a variety of compounds on EA induced cellular toxicity and mitochondrial fusion. N‐acetyl cysteine (NAC), a GSH precursor, was found to abrogate both the toxic and fusion‐inductive effects, whereas diethylmaleate (dEM), a GSH depletor, potentiated both these effects in a dose‐dependent manner. However, treatment with dEM alone, which depleted GSH to the same degree as EA, did not induce mitochondrial fusion. These results indicate that although detoxification of EA via formation of GSH conjugates is dependant upon GSH levels, the depletion of GSH by EA is not responsible for its effect on mitochondrial fusion. Dihydro‐EA (DH‐EA), a saturated EA analogue, lacked EA's toxicity and effect on fusion, indicating that the α,β‐unsaturated ketone is central to its observed effects. N‐ethylmaleimide (NEM), another well‐known cysteine‐alkylator, also induced mitochondrial fusion at near toxic concentrations. These data suggests that cysteine‐alkylation is the causative factor for fusion and toxicity. In live BSC‐1 cells, EA induced fusion of mitochondria occurred very rapidly (<20 min), which suggests that it is inducing fusion by modifying certain critical cysteine residue(s) in proteins involved in the process. © 2004 Wiley‐Liss, Inc.