bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes #
Authors: Vick Binje , Weber Achim , Urbanik Toni , Maass Thorsten , Teufel Andreas , Krammer Peter H. , Opferman Joseph T. , Schuchmann Marcus , Galle Peter R. , Schulze-Bergkamen Henning
Published: November 2008

Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 protein family. It interacts with proapoptotic Bcl-2 family members, thereby inhibiting mitochondrial activation and induction of apoptosis. Mcl-1 is essential for embryonal development and the maintenance of B cells, T cells, and hematopoietic stem cells. We have recently shown that induction of Mcl-1 by growth factors rescues primary human hepatocytes from CD95-mediated apoptosis. This prompted us to further analyze the relevance of Mcl-1 for hepatocellular homeostasis. Therefore, we generated a hepatocyte-specific Mcl-1 knockout mouse (Mcl-1flox/flox-AlbCre). Deletion of Mcl-1 in hepatocytes results in liver cell damage caused by spontaneous induction of apoptosis. Livers of Mcl-1flox/flox-AlbCre mice are smaller compared to control littermates, due to higher apoptosis rates. As a compensatory mechanism, proliferation of hepatocytes is enhanced in the absence of Mcl-1. Importantly, hepatic pericellular fibrosis occurs in Mcl-1 negative livers in response to chronic liver damage. Furthermore, Mcl-1flox/flox-AlbCre mice are more susceptible to hepatocellular damage induced by agonistic anti-CD95 antibodies or concanavalin A. Conclusion: The present study provides in vivo evidence that Mcl-1 is a crucial antiapoptotic factor for the liver, contributing to hepatocellular homeostasis and protecting hepatocytes from apoptosis induction. (Hepatology 2009.)
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

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

Objective

The 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.

Methods

We 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.

Results

We 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.

Conclusions

In 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

We 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

Unbalanced 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

The 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

Deletion 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

A 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

Silicon 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

Notch 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

Studies 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

To 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

Radioimmunoassay (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

In 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

In 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.
Identification of Caenorhabditis elegans K02H8.1 (CeMBL), a functional ortholog of mammalian MBNL proteins
Authors: Sasagawa Noboru , Ohno Eriko , Kino Yoshihiro , Watanabe Yuichiro , Ishiura Shoichi
Published: November 2008

The genome of the nematode Caenorhabditis elegans possesses an orthologous sequence to the Drosophila muscleblind (mbl) and mammalian muscleblind‐like genes (MBNLs). This ortholog, K02H8.1, which has a high degree of homology (about 50%) to human MBNLs, encodes two zinc finger domains, as does the sequence of the Drosophila mbl gene. This distinguishes it from human MBNLs, which encode four zinc finger domains. In this study, we cloned six major isoforms of K02H8.1 using cDNA generated from C. elegans total RNA. All six of the cloned isoforms had an SL1 leader sequence at the 5′‐position. Interestingly, one of the isoforms lacked a zinc finger domain‐encoding sequence. To understand better the function of K02H8.1, we performed yeast three‐hybrid experiments to characterize the binding of K02H8.1 to bait RNAs. K02H8.1 exhibited strong binding affinity for CUG and CCUG repeats, and the binding affinity was very similar to that of MBNLs. In addition, promoter analysis was performed using promoter‐green fluorescent protein (GFP) fusion constructs. The expression of GFP driven by the K02H8.1 promoter was absent in muscle; however, significant GFP expression was detected in the neurons around the pharynx. © 2008 Wiley‐Liss, Inc.
Revisitation of the phenylisothiocyanate‐derivatives procedure for amino acid determination by HPLC‐UV
Authors: Checa‐Moreno Ramón , Manzano Eloisa , Mirón Gloria , Capitán‐Vallvey Luis Fermín
Published: November 2008

A revisitation of the well known chromatographic procedure for the determination of amino acids as phenylthiocarbamyl derivatives (PTC) is performed. The method was developed for a microbore column that it is more appropriate to our later aims, the characterization of proteinaceous binders present in microsamples coming from the Cultural Heritage field. Several variables relating to chromatographic aspects were studied such as the pH and temperature of the mobile phase, buffer and modifier (triethylamine) concentrations in mobile phase and the stability of PTC‐derivatives in solution. The calibration function was studied in depth. To prevent the heteroscedastic behaviour that it is observed, we used the weighed least squares fitting as the best strategy among other normalizing transformations, such as square root and logarithmic functions. Finally, the proposed method showed results similar to the traditional method in terms of efficiency, runtime, LODs and other characteristics, but with two additional advantages: a lower mobile phase consumption and the possibility of working with a lower sample volume. The usefulness of proposed method is checked against easel painting samples of Pictorial Heritage.
Simultaneous quantification of both triterpenoid and steroidal saponins in various Yunnan Baiyao preparations using HPLC–UV and HPLC–MS
Authors: Liu Xiao‐Xiao , Wang Lei , Chen Xiao‐Qing , Deng Xue‐Tao , Cao Yuan , Wang Qiang
Published: November 2008

Yunnan Baiyao (YNBY) is one of the best known traditional Chinese medicines. Saponins are considered to be its active components. In this study, an HPLC method was first developed for the simultaneous quantitative analysis of thirteen saponins, including five triterpenoid saponins and eight steroidal saponins, in a series of YNBY preparations, i. e., powder, capsules, aerosol, toothpaste, plaster, and adhesive bandage. The pre‐treatment methods for each dosage form were investigated and optimized. The HPLC separation was performed on a Shim‐pack C18 reversed‐phase column in gradient mode with UV detection at 203 nm. All calibration curves showed good linear regression (r2 ⪈ 0.9981) within the test ranges. Precisions and repeatabilities of the methods were better than 4.22 and 4.78%, respectively. Recoveries were better than 90.5%, even in the analysis of the least abundant saponins in a complex YNBY plaster. HPLC–ESI‐TOF/MS was used for definite identification of compounds in the preparations. This proposed method was successfully applied to quantify the 13 bioactive constituents in 27 commercial samples to evaluate the quality of YNBY preparations. The overall results demonstrate that this method is simple, reliable, and suitable for the quality control of YNBY. Furthermore, the retention behavior of these saponins in reversed‐phase chromatography is described.
The relevance of knowledge management and intellectual capital Research
Authors: Booker Lorne D. , Bontis Nick , Serenko Alexander
Published: November 2008

In recent years, there has been a growing pressure on business schools to make their research more useful to practitioners. Consequently, the AASCB International dedicated an entire report to the subject. In order to assess the relevance of knowledge management/intellectual capital (KM/IC) research, 12 semi‐structured interviews were undertaken with KM/IC professionals. Based on the findings, a framework was constructed and eight implications were suggested. Overall, this study is the first documented attempt to empirically investigate the issue of relevance of KM/IC academic output. Copyright © 2008 John Wiley & Sons, Ltd.
Probing protein structure by amino acid‐specific covalent labeling and mass spectrometry
Authors: Mendoza Vanessa Leah , Vachet Richard W.
Published: November 2008

For many years, amino acid‐specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI‐ or MALDI‐MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site‐specific structural information. In this review, we describe the reagents that are most commonly used in these residue‐specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 28:785–815, 2009
Treatment of the symptoms of Huntington's disease: Preliminary results comparing aripiprazole and tetrabenazine
Authors: Brusa Livia , Orlacchio Antonio , Moschella Vincenzo , Iani Cesare , Bernardi Giorgio , Mercuri Nicola Biagio
Published: November 2008

Aripiprazole (AP), a dopamine (DA) D2 receptor partial agonist, has recently been used to reduce schizophrenic symptoms, while tetrabenazine (TBZ), a DA depletor, has been used to treat hyperkinesias in Huntington's disease (HD). The aim of this study is to define the role of AP on chorea, motor performance, and functional disability, and to compare the effects of AP vs. TBZ in a small study of six patients with HD. Both AP and TBZ increased the Unified Huntington's Disease Rating Scale (UHDRS) chorea score in a similar way. However, AP caused less sedation and sleepiness than TBZ and was better tolerated by the patients on the trial. Moreover, AP showed a slight but not significant improvement of depression in the patients as compared to TBZ. A larger group of patients and a longer period of observation are an important prerequisite for further evaluations of AP's therapeutic use. © 2008 Movement Disorder Society
The management of tics
Authors: Shprecher David , Kurlan Roger
Published: November 2008

A tic is a stereotyped repetitive involuntary movement or sound, frequently preceded by premonitory sensations or urges. Most tic disorders are genetic or idiopathic in nature, possibly due to a developmental failure of inhibitory function within frontal‐subcortical circuits modulating volitional movements. Currently available oral medications can reduce the severity of tics, but rarely eliminate them. Botulinum toxin injections can be effective if there are a few particularly disabling motor tics. Deep brain stimulation has been reported to be an effective treatment for the most severe cases, but remains unproven. A comprehensive evaluation accounting for secondary causes, psychosocial factors, and comorbid neuropsychiatric conditions is essential to successful treatment of tic disorders. © 2008 Movement Disorder Society
Microsubthalamotomy effect at day 3: Screening for determinants
Authors: Maltête David , Chastan Nathalie , Derrey Stéphane , Debono Bertrand , Gérardin Emmanuel , Lefaucheur Romain , Mihout Bruno , Hannequin Didier
Published: November 2008

A microsubthalamotomy (mSTN) effect has been frequently reported after implantation that improves Parkinson's motor disability. It is usually believed that mSTN effect reflects the post‐traumatic tissue reaction within the STN. However, it has never, to our knowledge, been reported whether pre and intraoperative factors could predict this mSTN effect. Preoperative clinical characteristics, that is, age, disease duration, Mattis Dementia Rating Scale score, levodopa responsiveness, severity of motor fluctuations and dyskinesia, and intraoperative parameters, that is, the number of tracks, distance of typical STN neuronal activity recorded along all microelectrodes, and along the definitive electrodes, were assessed in 40 consecutive PD patients submitted for STN stimulation. Multiple stepwise regression analysis showed that only the number of tracks used for microelectrodes recordings was predictor of the contralateral mSTN effect (F (4,73) = 1.83, P = 0.02). This result suggests that the contralateral mSTN depends on the tissue changes along the entirety of surgical trajectories affecting both STN and its adjacent structures. © 2008 Movement Disorder Society
Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study
Authors: Nobili Flavio , Abbruzzese Giovanni , Morbelli Silvia , Marchese Roberta , Girtler Nicola , Dessi Barbara , Brugnolo Andrea , Canepa Cinzia , Drosos Giorgos Chr. , Sambuceti Gianmario , Rodriguez Guido
Published: November 2008

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD‐MCI). Perfusion single photon emission computed tomography was performed in 15 PD‐MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS‐III scores were considered as confounding variables. PD‐MCI group (P < 0.05, false discovery rate–corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI‐PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI‐PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal‐parietal‐occipital region, including middle occipital and superior temporal gyri, and cuneus‐precuneus, as compared to PD. aMCI versus PD‐MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD‐MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies. © 2008 Movement Disorder Society
Peritoneo‐cutaneous perforators in deep inferior epigastric perforator flaps: A cadaveric dissection and computed tomographic angiography study
Authors: Whitaker Iain S. , Rozen Warren M. , Smit Jeroen M. , Dimopoulou Angeliki , Ashton Mark W. , Acosta Rafael
Published: November 2008

Background: Cutaneous perforators that do not originate from the deep inferior epigastric artery (DIEA) are rare, but may significantly affect operative outcome. Peritoneal‐cutaneous perforators have been described as a source for augmenting the blood flow to a deep inferior epigastric perforator (DIEP) flap, however if unrecognized, may compromise flap survival. Methods: We reviewed 375 DIEA perforator (DIEP) flaps (325 with preoperative CTA and 50 cadaveric dissections) to investigate the incidence of this anomaly. Results: We detected this variation in 3/325 (1%) of DIEP flaps following preoperative computed tomography. In 1/50 (2%) of the cadaveric specimens, a peritoneal‐cutaneous perforator was found and injected with lead oxide contrast. It was shown to fill the cutaneous veins of the majority of the lower abdominal integument. Conclusion: Peritoneal‐cutaneous perforators are rare anatomical variations (4/375: 1.1%) that may have significant ramifications for surgery utilizing the vasculature of the abdominal wall. CTA was significantly able to detect this anomaly and aid operative planning. Preoperative CTA helps to safely identify individual vascular anatomy including rare variations. © 2008 Wiley‐Liss, Inc. Microsurgery, 2009.
Fluoroelastomer‐MWNT nanocomposites‐1: Dispersion, morphology, physico‐mechanical, and thermal properties
Authors: Pham Thanh Tu , Sridhar V. , Kim Jin Kuk
Published: November 2008

The present article reports the preparation and characterization of fluoroelastomer/multi‐walled nanotube hybrid nanocomposites prepared by conventional rubber mixing using a two‐roll mill. The morphology of the resulting hybrid nanocomposites were characterized by X‐ray diffraction (XRD), scanning (SEM) and transmission electron microscopies (TEM). SEM photographs showed the formation of completely exfoliated and uniformly dispersed nanotubes in the polymer matrix during the high shear mixing process. Magnetic force microscopy (MFM) has been used to further study the topography of the composites which also showed complete exfoliation. The effect of increasing MWNT loadings on the mechanical properties like tensile strength, modulus, elongation at break, hardness, and tear resistance has also been studied. The fracture surface of the composite has been studied by SEM. A “cross hatched pattern” has been observed. The thermal stability of the composites has been studied by TGA and increase in decomposition temperature with increase in MWNT loadings has been observed which was attributed to the antioxidant nature of nanotubes. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers.
Relaxation map of PETg‐montmorillonite composites: Nanofiller concentration influence on α and β relaxation processes
Authors: Couderc H. , Saiter A. , Grenet J. , Saiter J.M. , Boiteux G. , Nikaj E. , Stevenson I. , D'Souza N.
Published: November 2008

Samples of polyethylene‐1.4‐cyclohexylenedimethylene terephthalate glycol (PETg) with different filler contents were prepared by a master batch process. The intercalated dispersion state of montmorillonite (MMT) was characterized using X‐Ray Diffraction. Two different sample series are put in evidence with different basal distances (3.31 and 3.48 nm). The influence of nanofiller on α and β relaxations was studied by Dielectric Relaxation Spectroscopy and Differential Scanning Calorimetry. The use of these two techniques allowed us to determine accurately the fragility index m at the glass transition temperature Tg. For Tg, m, the Kauzmann temperature TK, and the relaxation time at Tg τ(Tg), we showed a decrease of the values more important for 3.48 nm basal distance than for 3.31 nm. The β did not seem affected in its apparent activation energy Ea by the MMT addition. POLYM. ENG. SCI., 2009. © 2008 Society of Plastics Engineers
Kinetic and morphological study of a magnesium ethoxide‐based Ziegler–Natta catalyst for propylene polymerization
Authors: Dashti Ali , Ramazani SA Ahmad , Hiraoka Yuichi , Kim Sang Yull , Taniike Toshiaki , Terano Minoru
Published: November 2008

BACKGROUND: Kinetic and morphological aspects of slurry propylene polymerization using a MgCl2‐supported Ziegler–Natta catalyst synthesized from a Mg(OEt)2 precursor are investigated in comparison with a ball‐milled Ziegler–Natta catalyst.

RESULTS: The two types of catalyst show completely different polymerization profiles: mild activation and long‐standing activity with good replication of the catalyst particles for the Mg(OEt)2‐based catalyst, and rapid activation and deactivation with severe fragmentation of the catalyst particles for the ball‐milled catalyst. The observed differences are discussed in relation to spatial distribution of TiCl4 on the outermost part and inside of the catalyst particles.

CONCLUSION: The Mg(OEt)2‐based Ziegler–Natta catalyst is believed to show highly stable polymerization activity and good replication because of the uniform titanium distribution all over the catalyst particles. Copyright © 2008 Society of Chemical Industry
Effect of cancer diagnosis on patient employment status: a nationwide longitudinal study in Korea
Authors: Park Jae‐Hyun , Park Jong‐Hyock , Kim Sung‐Gyeong
Published: November 2008

Background: Cancer diagnosis may adversely affect employment status. Our aim was to investigate whether cancer diagnosis effects employment status by comparing employment status changes in cancer patients withto that of cancer‐free workers over a 5–6‐year period.

Methods: All 25–55‐year‐old, non‐self‐employed, Korean workers who were diagnosed with cancer for the first time in 2001 were identified as first baseline study subjects (n=4991). Of these, those who lost their jobs within 1 year of cancer diagnosis were selected as second baseline subjects (n=1334). Sex‐ and age‐matched cancer‐free individuals from the general population were used as a reference group. We compared the time until job loss from the first baseline and the time until re‐employment from the second baseline between these two groups during the 5–6‐year follow‐up period while adjusting for sex, age group, job‐type, and equivalent household income using the National Health Insurance administrative database.

Results: Cancer patients were more likely to lose their jobs after cancer diagnosis and were less likely to be re‐employed than cancer‐free individuals in almost all sex and age groups. Most major cancer sites were also associated with decreased employment status, with the exception of thyroid cancer.

Conclusion: Cancer diagnosis adversely affects employment status in Korea, and the effects are widespread in almost all sex and age groups. Significant efforts are needed to improve the employment status of cancer patients in Korea, as well as in developing or newly developed countries that have similar social security systems. Copyright © 2008 John Wiley & Sons, Ltd.
A HIF‐1α‐dependent autocrine feedback loop promotes survival of serum‐deprived prostate cancer cells
Authors: Thomas Rusha , Kim Myoung H.
Published: November 2008

BACKGROUND

We previously reported that normoxic, serum‐deprived prostate cancer (PCa) cells upregulate hypoxia‐inducible factor‐1α (HIF‐1α) protein, which promotes survival during serum deprivation via insulin‐like growth factor‐2 (IGF‐2) upregulation. This study investigated the molecular mechanism of autocrine regulation of HIF‐1α, IGF‐2 and cell survival in serum‐deprived PC‐3 and LNCaP PCa cells.

METHODS

Cell viability was assessed by trypan blue assay. PI3K activity was inhibited with LY294002, and PTEN overexpression. mRNA was assessed by RT‐PCR, and IGF‐2 protein by ELISA. Activated insulin‐like growth factor‐I receptor (IGF‐IR) was detected by probing immunoprecipitated IGF‐IR for phospho‐tyrosine. IGF‐IR activity was inhibited with IGF‐2 neutralizing antibody and IGF‐IR‐specific siRNA. HIF‐1α, phospho‐Akt, total‐Akt and IGF‐IR protein was assessed by immunoblots. HIF‐1α was suppressed with siRNA.

RESULTS

We detected a time‐dependent increase in Akt activation during serum deprivation, and inhibition of Akt activation attenuated the serum deprivation‐mediated increase in HIF‐1α and cell survival. Importantly, IGF‐2 secretion significantly increased during serum deprivation, and was accompanied by increased activation of its receptor, IGF‐IR. Additionally, inhibition of IGF‐2 activity markedly attenuated the serum deprivation‐mediated increase in IGF‐IR and Akt activation, HIF‐1α expression, and also its own transcription, suggesting autocrine regulation of HIF‐1α expression via IGF‐2. Cross‐talk between IGF‐2/ IGF‐IR system and PI3K‐Akt pathway was further demonstrated by findings wherein IGF‐IR suppression inhibited Akt activation, and IGF‐IR activation was inhibited following PI3K inhibition. Furthermore, HIF‐1α suppression attenuated the serum deprivation‐mediated increase in Akt and IGF‐IR activation.

CONCLUSION

Collectively, our study demonstrates existence of a pro‐survival HIF‐1α‐dependent autocrine feedback loop in normoxic, serum‐deprived PCa cells. Prostate 69:263–275, 2009. © 2008 Wiley‐Liss, Inc.
Corrosion under insulation
Authors: De Vogelaere Frank
Published: November 2008

Corrosion under insulation (CUI) is a major problem for petroleum and chemical process industries. CUI can result in sudden and hazardous leaks (safety concern), and plant shutdowns with high losses of production‐volumes (economical concern). A few examples are described in this article to illustrate the problems with CUI. This article discusses the root causes of CUI and recommendations to prevent it. One of the major recommendations is the use of risk‐based inspections (RBI) and the details of this RBI method are described. CUI can be especially avoided through a good cooperation between operations, inspection, and maintenance departments. © 2008 American Institute of Chemical Engineers Process Saf Prog, 2009