bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient #
Authors: Calvaruso Vincenza , Burroughs Andrew Kenneth , Standish Richard , Manousou Pinelopi , Grillo Federica , Leandro Gioacchino , Maimone Sergio , Pleguezuelo Maria , Xirouchakis Ilias , Piero Guerrini Gian , Patch David , Yu Dominic , O'Beirne James , Dhillon Amar Paul 
Published: November 2008

Abstract
Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. Conclusion: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis. (Hepatology 2009.)
Are antidepressants warranted in the treatment of patients who present suicidal behavior?
Authors: Raja Michele , Azzoni Antonella 
Published: November 2008

AbstractObjectiveThe aim of the study was to ascertain the clinical course of patients admitted to a psychiatric intensive care unit (PICU) just after a suicide attempt (SA) and to evaluate the effectiveness of 2nd generation antipsychotics and mood stabilizers in these patients.MethodsWe examined all the 129 patients discharged in a three‐year period, who had been admitted after a SA and considered in the analysis the 82 cases non‐transferred (in the first 72 h) to other PICUs for administrative or logistic reasons. Among them, 47 received a complete neuropsychiatric assessment. We distinguished between patients who had been treated with Antidepressants (AD) or not in the three months preceding hospitalization.ResultsWe treated all patients with mood stabilizers and 2nd generation antipsychotics. Only one patient was treated with AD in the course of current hospitalization. Both cases treated and not treated with AD before admission improved significantly, especially in symptoms of anxiety and depression, as well as in suicidality. The suicidal risk abated without AD treatment.ConclusionsIn patients with impending suicide risk, AD should not be considered standard treatment. Mood stabilizers and 2nd generation antipsychotics can be effective. Copyright © 2008 John Wiley & Sons, Ltd.
Trichomonosis and subsequent risk of prostate cancer in the Prostate Cancer Prevention Trial
Authors: Sutcliffe Siobhan , Alderete John F. , Till Cathee , Goodman Phyllis J. , Hsing Ann W. , Zenilman Jonathan M. , De Marzo Angelo M. , Platz Elizabeth A. 
Published: November 2008

AbstractWe previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow‐up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men (≥55 years of age) with no evidence of prostate cancer at enrollment (n = 18,882). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end‐of‐study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end‐of‐study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end‐of‐study biopsy (n = 616). Controls were frequency‐matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti‐T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 [95% confidence interval (CI): 0.63–1.09), and that for men with high seropositivity was 0.97 (95% CI: 0.70–1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings and to further investigate this hypothesis from a variety of different approaches. © 2008 Wiley‐Liss, Inc.
Valproic acid enhances bosutinib cytotoxicity in colon cancer cells
Authors: Mologni Luca , Cleris Loredana , Magistroni Vera , Piazza Rocco , Boschelli Frank , Formelli Franca , Gambacorti‐Passerini Carlo 
Published: November 2008

AbstractUnbalanced histone deacetylase (HDAC) hyperactivity is a common feature of tumor cells. Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy. It has recently been recognized as a promising anticancer drug. We investigated the effects of VPA on growth and survival of colon cancer cells. VPA caused growth inhibition and programmed cell death that correlated with histone hyperacetylation. VPA modulated the expression of various factors involved in cell cycle control and apoptosis and induced caspase activation. Interestingly, VPA induced downregulation of c‐Src and potentiated the cytotoxic effects of the c‐Src inhibitor bosutinib, both in vitro and in vivo. The combination of sublethal doses of VPA and bosutinib led to massive apoptosis of colon cancer cells, irrespective of their genetic background. These results suggest that VPA may be employed as a positive modulator of bosutinib antitumor activity in colorectal cancer. © 2008 Wiley‐Liss, Inc.
Increased claudin‐4 expression is associated with poor prognosis and high tumour grade in breast cancer
Authors: Lanigan Fiona , McKiernan Eadaoin , Brennan Donal J. , Hegarty Shauna , Millikan Robert C. , McBryan Jean , Jirstrom Karin , Landberg Goran , Martin Finian , Duffy Michael J. , Gallagher William M. 
Published: November 2008

AbstractThe role of intercellular tight junctions in breast epithelial cells is traditionally thought to be in maintaining polarity and barrier function. However, claudin‐4, a tight junction protein, is overexpressed in breast tumour cells compared to normal epithelial cells, which generally corresponds to a loss in polarity. The aim of this study was to investigate the distribution and potential clinical value of claudin‐4 in breast cancer, and to evaluate its usefulness as a prognostic and predictive biomarker. Expression of claudin‐4 was initially examined by Western blot analysis in a cohort of 88 breast tumours, and was found to correlate positively with tumour grade and negatively with ER. Claudin‐4 expression was then evaluated by immunohistochemistry in a larger cohort of 299 tumours represented on a tissue microarray. Claudin‐4 expression correlated positively with tumour grade and Her2, and negatively with ER. High claudin‐4 expression was also associated with worse breast cancer‐specific survival (p = 0.003), recurrence‐free survival (p = 0.025) and overall survival (p = 0.034). Multivariate analysis revealed that claudin‐4 independently predicted survival in the entire cohort (HR 1.95; 95%CI 1.01–3.79; p = 0.047) and in the ER positive subgroup treated with adjuvant tamoxifen (HR 4.34; 95%CI 1.14–16.53; p = 0.032). This relationship between increased claudin‐4 expression and adverse outcome was validated at the mRNA level in a DNA microarray dataset of 295 breast tumours. We conclude that high levels of claudin‐4 protein are associated with adverse outcome in breast cancer patients, including the subgroup of patients treated with adjuvant tamoxifen. © 2008 Wiley‐Liss, Inc.
Downregulation of ZIP kinase is associated with tumor invasion, metastasis and poor prognosis in gastric cancer
Authors: Bi Jiong , Lau Sze‐Hang , Hu Liang , Rao Hui‐Lan , Liu Hai‐Bo , Zhan Wen‐Hua , Chen Gong , Wen Jian‐Ming , Wang Qian , Li Bin , Guan Xin‐Yuan 
Published: November 2008

AbstractDeletion of 19p13 is one of the most frequent genetic changes in gastric carcinoma (GC), implying the existence of a tumor suppressor gene (TSG) that plays an important role in GC development. To identify the candidate TSG at 19p, array‐comparative genomic hybridization (CGH) was applied to study DNA copy‐number changes on chromosomes 3, 5p, 13, 16q and 19. The result showed that gains of 16q21, 19q13.1, 5p15.1 and 3q26.31, and losses of 3p21.32, 3p22.2, 19q13.33 and 19p13.3, were frequently detected by array‐CGH. One candidate TSG, ZIP kinase (ZIPK), at 19p13.3 was further characterized by immunohistochemistry using a tissue microarray containing 172 primary GCs. Downregulation of ZIPK was detected in 111/162 informative GCs, which was significantly associated with invasion, metastasis and poorer prognosis of GC. To investigate the association of the downregulation of ZIPK with apoptosis, apoptosis assay (TUNEL) was used to compare the apoptotic index between GCs with normal expression and downregulation of ZIPK. TUNEL assay showed that the apoptotic index in GCs with normal ZIPK expression was significantly higher than that in GCs with downregulation of ZIPK (p < 0.001), indicating that ZIPK plays an important pro‐apoptotic role in GC. Taken together, we demonstrated here that ZIPK is a tumor suppresser gene and plays an important role in GC development through its pro‐apoptotic function. Downregulation of ZIPK can be used to evaluate tumor invasiveness, metastasis and to predict survival of GC. © 2008 Wiley‐Liss, Inc.
Cytokine profiling of chemical allergens in mice: impact of mitogen on selectivity of response
Authors: Dearman Rebecca Jane , Betts Catherine Jean , Caddick Helen Theresa , Kimber Ian 
Published: November 2008

AbstractA major constraint in the development of methods for the identification of chemical respiratory allergens is the continuing uncertainty regarding the mechanisms of this disease and in particular the role of IgE antibody. There is, however, increasing evidence that respiratory sensitization is favoured by the induction of a selective type 2 cytokine response. The current investigations focus on the potential application of cytokine profiling to the identification of chemical respiratory sensitizers. The objective is to determine the optimal configuration of the method for discrimination between chemical contact and respiratory sensitizers. The reference contact sensitizer 2,4‐dinitrochlorobenzene (DNCB) and reference respiratory sensitizer trimellitic anhydride (TMA), which have been shown to induce type 1 and type 2 cytokine profiles, respectively, were utilized. Variables investigated included cell concentration, time in culture, dosing regimens (a 13 day and a truncated 8 day protocol) and the impact of restimulation in vitro with T cell mitogens. Cell culture conditions were critical for the selectivity of the response, with the addition of mitogen resulting in a less discriminatory pattern of cytokine expression, particularly for the type 1 cytokine interferon γ (IFN‐γ). Furthermore, a 13 day exposure period was required for vigorous expression of IFN‐γ by DNCB‐activated cells, whereas type 2 cytokine expression by TMA‐stimulated cells was recorded after 8 days. These data demonstrate that the most optimal method for cytokine profiling is a chronic (13 day) exposure regime followed by culture of lymph node cells at 107 cells ml−1 for120 h in the absence of mitogen. Copyright © 2008 John Wiley & Sons, Ltd.
The effects of silicate ions on human osteoblast adhesion, proliferation, and differentiation
Authors: Zou S. , Ireland D. , Brooks R. A. , Rushton N. , Best S. 
Published: November 2008

AbstractSilicon has been shown to have important effects on skeletal development and repair, and soluble silicate ions have been found to stimulate the expression of type‐I collagen in osteoblast‐like cell cultures. Furthermore, silicon has been incorporated into the hydroxyapatite lattice and enhanced metabolic activity of human osteosarcoma cells was observed when cells were cultured on this material. In vivo assessments have demonstrated enhanced bioactivity of silicon‐substituted hydroxyapatite (Si‐HA) over pure HA. However, detailed mechanisms for the stimulative effects of Si‐HA have not been described. In this study, we found that silicon substitution into hydroxyapatite affects the adhesion of human osteoblast‐like cells (HOBs) in culture, with 0.8 wt % silicon substitution being optimal. In addition, metabolic activity and proliferation of HOBs were increased by supplementation of the growth medium with 30 μM silicon. It was determined that this response may depend on the proportion of cells at different stages of differentiation within the cultures. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Calcium/calmodulin‐dependent kinase II regulates notch‐1 signaling in prostate cancer cells
Authors: Mamaeva Olga A. , Kim Junghyun , Feng Gong , McDonald Jay M. 
Published: November 2008

AbstractNotch signaling is associated with prostate osteoblastic bone metastases and calcium/calmodulin‐dependent kinase II (CaMKII) is associated with osteoblastogenesis of human mesenchymal stem cells. Here we show that prostate cancer cell lines C4‐2B and PC3, both derived from bone metastases and express Notch‐1, have all four isoforms of CaMKII (α, β, γ, δ). In contrast, prostate cancer cell lines LNcaP and DU145, which are not derived from bone metastases and lack the Notch‐1 receptor, both lack the alpha isoform of CaMKII. In addition, DU145 cells also lack the β‐isoform. In C4‐2B cells, inhibition of CaMKII by KN93 or γ‐secretase by L‐685,458 inhibited the formation of the cleaved form of Notch‐1 thus inhibiting Notch signaling. KN93 inhibited down stream Notch‐1 signaling including Hes‐1 gene expression, Hes‐1 promoter activity, and c‐Myc expression. In addition, both KN93 and L‐685,458 inhibited proliferation and Matrigel invasion by C4‐2B cells. The activity of γ‐secretase was unaffected by KN93 but markedly inhibited by L‐685,458. Inhibition of the expression of α, β, or γ‐isoform by siRNA did not affect Hes‐1 gene expression, however when expression of one isoform was inhibited by siRNA, there were compensatory changes in the expression of the other isoforms. Over‐expression of CaMKII‐α increased Hes‐1 expression, consistent with Notch‐1 signaling being at least partially dependent upon CaMKII. This unique crosstalk between CaMKII and Notch‐1 pathways provides new insight into Notch signaling and potentially provides new targets for pharmacotherapeutics. J. Cell. Biochem. 106: 25–32, 2009. © 2008 Wiley‐Liss, Inc.
The RelA/p65 subunit of NF‐κB specifically regulates cyclin D1 protein stability: Implications for cell cycle withdrawal and skeletal myogenesis
Authors: Dahlman Jason M. , Wang Jingxin , Bakkar Nadine , Guttridge Denis C. 
Published: November 2008

AbstractStudies support that NF‐κB functions in cellular growth through the transcriptional regulation of cyclin D1, but whether such regulation is attributed to a single NF‐κB subunit remains unclear. To address this issue we examined endogenous cyclin D1 levels during cell cycle re‐entry in mouse embryonic fibroblasts (MEFs) lacking specific NF‐κB signaling subunits. Results showed that each of these subunits were dispensable for regulating cyclin D1 transcription. However, we found that resulting cyclin D1 protein was severely reduced in MEFs lacking only RelA/p65. Cyclohexamide treatment revealed that this regulation was due to an increase in protein turnover. Similar downregulation of cyclin D1 protein, but not RNA, was observed in vivo in multiple tissues lacking RelA/p65. Co‐immunoprecipitation analysis also showed that RelA/p65 and cyclin D1 were capable of interacting, thus providing a possible explanation for cyclin D1 protein stability. In addition, although the decrease in cyclin D1 in RelA/p65−/− MEFs was concomitant with lower CDK4 activity during cell cycle re‐entry, this was not sufficient to affect S phase progression. Nevertheless, similar decreases in cyclin D1 protein in primary RelA/p65−/− myoblasts was adequate to accelerate cell cycle exit and differentiation of these cells. Based on these findings we conclude that RelA/p65 functions as a specific regulator of cyclin D1 protein stability, necessary for proper cell cycle withdrawal during skeletal myogenesis. J. Cell. Biochem. 106: 42–51, 2009. © 2008 Wiley‐Liss, Inc.
Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage‐deprivation in human keratinocytes
Authors: Nishi Kayoko , Inoue Hirokazu , Schnier Joachim B. , Rice Robert H. 
Published: November 2008

AbstractTo understand the relationship between permanent cell cycle exit and differentiation the immortalized keratinocyte cell line, SIK and the squamous cell carcinoma, SCC9 were compared during differentiation induced by anchorage‐deprivation. The SIK cells when placed in suspension culture promptly lost almost all ability to reinitiate growth by 2 days concomitantly expressing the differentiation specific proteins, transglutaminase (TGK) and involucrin. These cells rapidly underwent G1 cell cycle arrest with complete disappearance of phosphorylated RB. In contrast SCC9 cells neither showed TGK expression nor increase in involucrin. They decreased their colony‐forming ability much more slowly, which coordinated well with a gradual decrease in phosphorylated RB, demonstrating the significant resistance to loss of colony‐forming ability and cell cycle exit. In accordance, cyclin D1, a positive regulator of cyclin‐dependent kinase (CDK) 4/6 which phosphorylates RB decreased drastically in anchorage deprived SIK but not in SCC9 cells. Endogenous cyclin D1 knockdown in SCC9 cells by siRNA enhanced loss of the colony‐forming ability during anchorage‐deprivation. Conversely enforced expression of cyclin D1 in SIK cells and in another immortalized keratinocyte cell line, HaCaT, partly prevented loss of their colony‐forming abilities. Cyclin D1 overexpression antagonized Keratin 10 expression in suspended HaCaT cells. The result demonstrates the importance of cyclin D1 down regulation for proper initiation of keratinocyte differentiation. J. Cell. Biochem. 106: 63–72, 2009. © 2008 Wiley‐Liss, Inc.
Assessment of urinary total testosterone production by a highly sensitive time‐resolved fluorescence immunoassay
Authors: Bao Shihua , Peng Yifeng , Sheng Shile , Lin Qide 
Published: November 2008

AbstractRadioimmunoassay (RIA) that involves purification of the analyte by organic solvent extraction is widely used. Although the extraction RIA is reliable when properly validated, it is time consuming and radioactive, we measure urinary total testosterone with a highly sensitive rapid and accurate time‐resolved fluorescence immunoassay (TRFIA) method. High affinity antitestosterone antibody and Eu3+ labeled Donkey antisheep IgG as tracers were used. The assay was evaluated for specificity, sensitivity, analytical recovery, precision and dilution linearity by the TRFIA method on urine samples. A satisfactory standard curve for testosterone TRFIA has been developed with good sensitivity (5.1 pmol/L). The validity of the assay for urinarytotal testosterone was confirmed by thegood correlation between the results obtained by TRFIA (X) and those RIA (Y) (Y=0.075+0.971X, R=0.992). Specificity, analytical recovery, precision and dilution linearity studies were determined and all found to be satisfactory. Male urinary total testosterone excretion ranged from 64.00 to 374.11 nmol/24 hr, which was about four times more than the range for women urinary testosterone excretion (14.16–100.65 nmol/24 hr), which suggests that a direct, reliable, easy to automate, highly sensitive and specific TRFIA type assay for the measurement of total testosterone in urine samples has been developed. J. Clin. Lab. Anal. 22:403–408, 2008. © 2008 Wiley‐Liss, Inc.
Synthesis, radiofluorination and first evaluation of (±)‐[18F]MDL 100907 as serotonin 5‐HT2A receptor antagonist for PET
Authors: Mühlhausen Ute , Ermert Johannes , Herth Matthias M. , Coenen Heinz H. 
Published: November 2008

AbstractIn some psychiatric disorders 5‐HT2A receptors play an important role. In order to investigate those in vivo there is an increasing interest in obtaining a metabolically stable, subtype selective and high affinity radioligand for receptor binding studies using positron emission tomography (PET). Combining the excellent in vivo properties of [11C]MDL 100907 for PET imaging of 5‐HT2A receptors and the more suitable half‐life of fluorine‐18, MDL 100907 was radiofluorinated in four steps using 1‐(2‐bromoethyl)‐4‐[18F]fluorobenzene as a secondary labelling precursor. The complex reaction required an overall reaction time of 140 min and (±)‐[18F]MDL 100907 was obtained with a specific activity of at least 30 GBq/µmol (EOS) and an overall radiochemical yield of 1–2%. In order to verify its binding to 5‐HT2A receptors, in vitro rat brain autoradiography was conducted showing the typical distribution of 5‐HT2A receptors and a very low non‐specific binding of about 6% in frontal cortex, using ketanserin or spiperone for blocking. Thus, [18F]MDL 100907 appears to be a promising new 5‐HT2A PET ligand. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis, labelling and first evaluation of [18F]R91150 as a serotonin 5‐HT2A receptor antagonist for PET
Authors: Mühlhausen Ute , Ermert Johannes , Coenen Heinz H. 
Published: November 2008

AbstractIn psychiatric disorders such as anxiety, depression and schizophrenia, 5‐HT2A receptors play an important role. In order to investigate them in vivo there is an increasing interest in selective and high‐affinity radioligands for receptor binding studies using positron emission tomography (PET). Since available radioligands have disadvantages, R91150, which is a selective and high‐affinity ligand for 5‐HT2A receptors, was labelled with fluorine‐18. This was accomplished in six steps via 4‐[18F]fluorophenol and 1‐(3‐bromopropoxy)‐4‐[18F]fluorobenzene within 190 min starting from no‐carrier‐added [18F]fluoride. The overall radiochemical yield was 3.8±2% and the specific activity was at least 335 GBq/µmol at the end of the synthesis. First ex vivo studies in mice proved the uptake of [18F]R91150 in the brain. Radiometabolite studies revealed no radiometabolites in the brain, whereas in the plasma at least two could be detected 30 min p.i. Further preclinical studies are encouraged to evaluate the potential of this new 5‐HT2A ligand as a radiotracer for PET. Copyright © 2008 John Wiley & Sons, Ltd.