bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term outcomes following total minimally invasive oesophagectomy
Authors: Berrisford R G , Wajed S A , Sanders D , Rucklidge M W M
Published: March 2008

Background

Minimally invasive oesophagectomy (MIO; thoracoscopy, laparoscopy, cervical anastomosis) is a complex procedure and few substantial series have been published. This study documented the morbidity, mortality and challenges of adopting MIO in a specialist unit in the UK.

Methods

A prospective group of 77 patients was listed consecutively with the intention of performing MIO. Three other patients underwent open oesophagectomy during the study period.

Results

MIO was attempted in 77 patients, completed successfully in 70, abandoned in six patients (8 per cent) with unsuspected metastatic disease, and converted to a thoracoscopic anastomosis in one patient. There was one in-hospital death (1 per cent). Complications occurred in 33 patients (47 per cent), including nine gastric conduit-related complications (13 per cent). Median lymph node harvest was 21 (range 7–48) nodes. Mean overall and disease-free survival times were 35 and 33 months respectively. Median disease-free survival for patients with stage III disease was 26 months.

Conclusion

MIO can be performed with acceptable mortality and morbidity rates in an unselected series of patients. There was more morbidity related to gastric tube ischaemia than was expected.
Predictive value of common symptom combinations in diagnosing colorectal cancer (Br J Surg 2007; 94: 1260–1265)
Authors: Cade D
Published: March 2008

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved,appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.
Controllability analysis of modified Petlyuk structures
Authors: Tamayo‐Galván Victoria E. , Segovia‐Hernández Juan Gabriel , Hernández Salvador , Hernández Héctor
Published: March 2008

Fully thermally coupled distillation columns (Petlyuk‐type columns) represent an interesting alternative to conventional distillation sequences used in multicomponent mixture separation processes, due to potential savings in both energy and capital costs. However, possible operational difficulties have limited the industrial applications of Petlyuk systems. Some of the control challenges result from the transfer of vapour stream back and forth between columns. This means that those columns do not display a uniform lower or higher pressure with respect to the other. Recently, some alternative Petlyuk‐type schemes that might provide better operation properties than the traditional Petlyuk column have been proposed. In this work, the theoretical control properties of six alternative schemes to the Petlyuk system were obtained and compared. This was performed by using the singular value decomposition (SVD) technique in the frequency domain. Also, dynamic closed‐loop responses for set point tracking and disturbance rejection were obtained to support the theoretical control properties. The results showed that the reduction in the number of interconnections and the use of unidirectional flows affected the dynamic properties of the complex schemes leading to potential operational advantages in thermally coupled distillation sequences.
Asymmetric Bioreduction of Activated C=C Bonds Using Zymomonas mobilis NCR Enoate Reductase and Old Yellow Enzymes OYE 1–3 from Yeasts (Eur. J. Org. Chem. 9/2008)
Authors: Hall Mélanie , Stueckler Clemens , Hauer Bernhard , Stuermer Rainer , Friedrich Thomas , Breuer Michael , Kroutil Wolfgang , Faber Kurt
Published: March 2008

The cover picture shows a culture of yeast cells, whose flavin‐dependent reductases – their three‐dimensional structure is depicted in the magnifying glass – catalyse the asymmetric bioreduction of C=C bonds. Although these enzymes have been identified already in 1932, their true physiological role remains largely a mystery. Thanks to advances in genetic engineering, these biocatalysts are now becoming available in sufficient amounts to allow their application for preparative‐scale biotransformations: Although their “natural” substrates are still unknown, the study of K. Faber et al. on p. 1511 ff shows that they accept an astonishing variety of alkenes bearing an electron‐withdrawing group – such as a enals, enones, α,β‐unsaturated imides, or nitroalkenes – to furnish the corresponding alkanes with excellent stereoselectivities. S. Kohlwein and G. Oberdorfer are thanked for their contribution in the design of the graphic.
Computation of AC flashover voltage of polluted HV insulators using a dynamic arc model
Authors: Gencoglu M. T. , Cebeci M.
Published: March 2008

Flashover of polluted insulators is still a serious threat to the safe operation of a power transmission system. Despite the extensive investigations carried out on the pollution performance of the insulators, the flashover characteristics are not well understood. Recent theoretical and experimental research on polluted insulators is yet to yield a perfect generalized mathematical model which can accurately predict critical flashover voltage. In this paper, the pollution flashover on the high voltage insulators has been investigated and a new dynamic arc model has been proposed. For this purpose, firstly the concerned insulators' scaled shapes were partitioned into triangular elements, then finite element method (FEM) was implemented for obtaining potential distribution on the surface of insulator and finally flashover voltages were determined by using the developed arc model. For a number of common insulators of different geometries the computed results of flashover voltages on the selected string insulators have been compared to experimental results of some other research. Pollution flashover behaviors of the insulators have been taken into consideration and the validity of the model was thus verified. Copyright © 2008 John Wiley & Sons, Ltd.
E‐selectin regulates gene expression in metastatic colorectal carcinoma cells and enhances HMGB1 release
Authors: Aychek Tegest , Miller Keren , Sagi‐Assif Orit , Levy‐Nissenbaum Orlev , Israeli‐Amit Mira , Pasmanik‐Chor Metsada , Jacob‐Hirsch Jasmin , Amariglio Ninette , Rechavi Gideon , Witz Isaac P.
Published: March 2008

Extravasation of cancer cells is a pivotal step in the formation of hematogenous metastasis. Extravasation is initiated by the loose adhesion of cancer cells to endothelial cells via an interaction between endothelial selectins and selectin ligands expressed by the tumor cells. The present study shows that the interaction between recombinant E‐selectin (rE‐selectin) and colorectal cancer (CRC) cells alters the gene expression profile of the cancer cells. A DNA microarry analysis indicated that E‐selectin‐mediated alterations were significantly more pronounced in the metastatic CRC variants SW620 and KM12SM than in the corresponding non‐metastatic local SW480 and KM12C variants. The number of genes altered by E‐selectin in the metastatic variants was about 10‐fold higher than the number of genes altered in the corresponding local variants. Aiming to identify genes involved in CRC metastasis, we focused, by using a DNA microarry analysis, on genes that were altered by E‐selectin in a similar fashion exclusively in both metastatic variants. This analysis indicated that E‐selectin down regulated (at least by 1.6‐folds) the expression of 7 genes in a similar fashion, in both metastatic cells. The DNA microarry analysis was validated by real time PCR or by RT‐PCR. HMGB1 was among these genes. Confocal microscopy indicated that E‐selectin down regulated the cellular expression of the HMGB1 protein and enhanced the release of HMGB1 into the culture medium. The released HMGB1 in turn, activated endothelial cells to express E‐selectin. © 2008 Wiley‐Liss, Inc.
Usefulness of monitoring the circulating Krebs von den Lungen‐6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors
Authors: Ishikawa Nobuhisa , Hattori Noboru , Yokoyama Akihoto , Tanaka Sonosuke , Nishino Ryohei , Yoshioka Koji , Ohshimo Shinichiro , Fujitaka Kazunori , Ohnishi Hiroshi , Hamada Hironobu , Arihiro Koji , Kohno Nobuoki
Published: March 2008

Krebs von den Lungen‐6 (KL‐6) is a high molecular weight glycoprotein classified in the category of human MUC1 mucin. KL‐6 has been reported to serve as a sensitive marker for interstitial pneumonia; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. To further elucidate the clinicopathological significance of circulating KL‐6 in lung cancer, we monitored the circulating KL‐6 levels in advanced nonsmall cell lung cancer (NSCLC) patients and analyzed the association between these levels and the clinical outcome of EGFR‐TKI treatment. The pretreatment levels of circulating KL‐6 were found to be significantly higher in progressive disease (PD) patients than disease‐controlled (partial response (PR) and stable disease (SD)) patients. Multivariate analyses revealed the circulating KL‐6 level to be an independent prognostic factor for overall survival as well as progression‐free survival. In addition to these observations, we found that changes in circulating KL‐6 levels at 2 weeks after the start of EGFR‐TKI treatment from the baseline could quite precisely discriminate PD cases from PR or SD patients and the clinical outcome of EGFR‐TKI in NSCLC patients. These results indicate that the monitoring of circulating KL‐6 levels in NSCLC patients is effective for both selecting patients to be treated with EGFR‐TKI and predicting the clinical outcome of EGFR‐TKI. In addition, the findings suggest that the circulating KL‐6 level could be used as a clinically relevant biomarker in patients with NSCLC, particularly those who are candidates for EGFR‐TKI treatment. © 2008 Wiley‐Liss, Inc.
Transient ectopic expression as a method to detect genes conferring drug resistance
Authors: Witham James , Vidot Susanne , Agarwal Roshan , Kaye Stanley B. , Richardson Alan
Published: March 2008

Ectopic expression provides an alternative to RNAi to conduct functional genomic screens. We have determined whether transient expression can be used to identify genes which confer drug resistance. We constructed a bigenic vector that allows high throughput cloning and which also encodes a red fluorescent protein to monitor transfection. Assay conditions were optimized to allow detection of changes in sensitivity to carboplatin or paclitaxel. Following transient expression of MDR‐1 and MCJ, changes in the sensitivity of Sk‐Ov‐3 cells to paclitaxel were detected whereas expression of Src, Bcl‐2 and Bcl‐XL decreased the sensitivity of Sk‐Ov‐3 cells to carboplatin. This approach may potentially be used as an independent screen or as a method to help rank hit identified in screens utilizing methods such as RNAi. © 2008 Wiley‐Liss, Inc.
Reversible translocation of p115‐RhoGEF by G12/13‐coupled receptors
Authors: Meyer Bruno H. , Freuler Felix , Guerini Danilo , Siehler Sandra
Published: March 2008

G protein‐coupled receptors (GPCRs) are important targets for medicinal agents. Four different G protein families, Gs, Gi, Gq, and G12, engage in their linkage to activation of receptor‐specific signal transduction pathways. G12 proteins were more recently studied, and upon activation by GPCRs they mediate activation of RhoGTPase guanine nucleotide exchange factors (RhoGEFs), which in turn activate the small GTPase RhoA. RhoA is involved in many cellular and physiological aspects, and a dysfunction of the G12/13‐Rho pathway can lead to hypertension, cardiovascular diseases, stroke, impaired wound healing and immune cell functions, cancer progression and metastasis, or asthma. In this study, regulator of G protein signaling (RGS) domain‐containing RhoGEFs were tagged with enhanced green fluorescent protein (EGFP) to detect their subcellular localization and translocation upon receptor activation. Constitutively active Gα12 and Gα13 mutants induced redistribution of these RhoGEFs from the cytosol to the plasma membrane. Furthermore, a pronounced and rapid translocation of p115‐RhoGEF from the cytosol to the plasma membrane was observed upon activation of several G12/13‐coupled GPCRs in a cell type‐independent fashion. Plasma membrane translocation of p115‐RhoGEF stimulated by a GPCR agonist could be completely and rapidly reversed by subsequent application of an antagonist for the respective GPCR, that is, p115‐RhoGEF relocated back to the cytosol. The translocation of RhoGEF by G12/13‐linked GPCRs can be quantified and therefore used for pharmacological studies of the pathway, and to discover active compounds in a G12/13‐related disease context. J. Cell. Biochem. 104: 1660–1670, 2008. © 2008 Wiley‐Liss, Inc.
Hypomanic symptoms among first‐time suicide attempters predict future multiple attempt status
Authors: Bryan Craig J. , Johnson Leigh G. , David Rudd M. , Joiner Thomas E.
Published: March 2008

Past conceptual and empirical works have identified unique differences between multiple suicide attempters, single attempters, and zero attempters, but have overlooked two distinct subgroups of single attempters: true single attempters who will not attempt suicide again, and future multiple attempters who will. Consistent with fluid vulnerability theory, the authors hypothesized that subgroups should have differences in personality traits that can predict if a first‐time attempter is likely to attempt suicide again. In a sample of 127 military members (81% male, 19% female) participating in a clinical intervention study for suicidal behaviors, hypomanic symptoms—not personality traits—predicted future multiple attempters, and future multiple attempters more frequently met criteria for a bipolar‐spectrum disorder. Clinical implications and convergence of findings with fluid vulnerability theory and existing research are discussed. © 2008, Wiley Periodicals, Inc. J Clin Psychol 64: 1–12, 2008.
Early childhood temperament in Pediatric bipolar disorder and attention deficit hyperactivity disorder
Authors: West Amy E. , Schenkel Lindsay S. , Pavuluri Mani N.
Published: March 2008

Recent theories suggest that children with pediatric bipolar disorder (PBD) may exhibit more difficult temperaments premorbidly, including traits such as behavioral disinhibition and difficulty with emotion regulation. We investigated temperament characteristics retrospectively during infancy and toddlerhood in subjects with PBD (n=25), attention‐deficit/hyperactivity disorder (ADHD; n=25), and healthy controls (n=25). Children with PBD were reported to experience increased difficult temperament in both infancy and toddlerhood compared to children with ADHD. Several characteristics of difficult temperament were associated with residual symptoms of mania and depression. Difficult premorbid temperament characteristics may be a specific indicator of a bipolar diathesis, or might signal underlying dysfunction in affective processes that significantly increase risk for a mood disorder. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1–20, 2008.
Investigations with O‐linked protein glycosylations by matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry
Authors: Williams Taufika Islam , Saggese Diana A. , Toups Kristina L. , Frahm Jennifer L. , An Hyun Joo , Li Bensheng , Lebrilla Carlito B. , Muddiman David C.
Published: March 2008

Posttranslational modifications such as glycosylation can play a fundamental role in signaling pathways that transform an ordinary cell into a malignant one. The development of a protocol to detect these changes in the preliminary stages of disease can lead to a sensitive and specific diagnostic for the early detection of malignancies such as ovarian cancer in which differential glycan patterns are linked to etiology and progression. Small variations in instrument parameters and sample preparation techniques are known to have significant influence on the outcome of an experiment. For an experiment to be effective and reproducible, these parameters must be optimized for the analyte(s) under study. We present a detailed examination of sample preparation and matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI‐FT‐ICR‐MS) analysis of O‐linked glycans globally cleaved from mucin glycoproteins. Experiments with stable isotope‐labeled biomolecules allowed for the establishment of appropriate acquisition times and excitation voltages for MALDI‐FT‐ICR‐MS of oligosaccharides. Quadrupole ion guide optimization studies with mucin glycans identified conditions for the comprehensive analysis of the entire mass range of O‐linked carbohydrates in this glycoprotein. Separately optimized experimental parameters were integrated in a method that allowed for the effective study of O‐linked glycans. Copyright © 2008 John Wiley & Sons, Ltd.
Prevalence and Significance of Occult Hepatitis B in a Liver Transplant Population With Chronic Hepatitis C
Authors: Shetty Kirti , Hussain Munira , Nei Lei , Reddy Rajender K. , Lok Anna S.F.
Published: March 2008

Occult hepatitis B virus (HBV) infection is defined as the detection of HBV deoxyribonucleic acid (DNA) in the serum or liver tissue of individuals who test negative for hepatitis B surface antigen (HBsAg). We undertook a prospective study to evaluate the significance and course of occult HBV in patients with hepatitis C virus (HCV) cirrhosis undergoing orthotopic liver transplantation (OLT). A sensitive real-time polymerase chain reaction assay was utilized to test for serum HBV DNA at enrollment and for hepatic HBV DNA within the explant liver. Patients were followed with serum HBsAg and HBV DNA post-OLT. A total of 56 patients with HCV cirrhosis were enrolled between October 2002 and July 2004; of these, 44 underwent OLT. The overall prevalence of occult HBV based on positive serum HBV DNA was 16 of 56 (28%), and based on positive hepatic HBV DNA (“occult HBV liver”) was 22 of 44 (50%). The presence of serum hepatitis B core antibody (anti-HBc) and a past history of injection drug use correlated with occult HBV. Explant-proven hepatocellular carcinoma (HCC) was found in 13 of 22 (59%) patients with occult HBV liver compared to 8 of 22 (36%) patients without occult HBV liver (

P

= 0.04, odds ratio = 3.1; confidence interval = 2.1-5.4). Post-OLT, no cases of HBV reactivation were noted, and there was no significant association between occult HBV and recurrent HCV. In conclusion, occult HBV is far more prevalent in patients with end-stage HCV than would be expected from its prevalence in the general population. Occult HBV infection is strongly associated with the presence of anti-HBc, history of injection drug use, and explant-proven HCC.
The innovator's non‐dilemma: the case of next‐generation lithography
Authors: Appleyard Melissa M. , Wang Clara Y. , Liddle J. Alexander , Carruthers John
Published: March 2008

Previous studies have analyzed how incumbents may falter when they focus too narrowly on satisfying the needs of current customers at the expense of pursuing innovations that will ensure future market leadership. This paper examines this ‘dilemma’ faced by incumbents and considers cases where incumbents do spearhead innovation on the technology frontier thus enabling future product generations. In particular, we examine the case of the semiconductor industry confronting a technological discontinuity in the production of chips. In anticipation of a discontinuity in the lithography production module, leading firms in the semiconductor industry have initiated next‐generation lithography (NGL) projects. These projects have exhibited an unprecedented level of horizontal and vertical cooperation. Our research analyzes how such cooperative research and development (R&D) programs allow incumbent innovators to mitigate four areas of uncertainty—leadership, preemption, performance, and industry adoption. We adapt a Hotelling location model to demonstrate the tension between mitigating these uncertainties through interfirm cooperation and the possibility of increased downstream competition. Such tensions have influenced cooperation within and across the R&D consortia pursuing NGL led by IBM, Intel, and Bell Labs. Copyright © 2008 John Wiley & Sons, Ltd.
Nε‐carboxymethyllysine‐modified proteins are unable to bind to RAGE and activate an inflammatory response
Authors: Buetler Timo M. , Leclerc Estelle , Baumeyer Alexandra , Latado Helia , Newell John , Adolfsson Oskar , Parisod Véronique , Richoz Janique , Maurer Sarah , Foata Francis , Piguet Dominique , Junod Sylviane , Heizmann Claus W. , Delatour Thierry
Published: March 2008

Advanced glycation endproducts (AGEs) containing carboxymethyllysine (CML) modifications are generally thought to be ligands of the receptor for AGEs, RAGEs. It has been argued that this results in the activation of pro‐inflammatory pathways and diseases. However, it has not been shown conclusively that a CML‐modified protein can interact directly with RAGE. Here, we have analyzed whether beta‐lactoglobulin (bLG) or human serum albumin (HSA) modified chemically to contain only CML (10–40% lysine modification) can (i) interact with RAGE in vitro and (ii) interact with and activate RAGE in lung epithelial cells. Our results show that CML‐modified bLG or HSA are unable to bind to RAGE in a cell‐free assay system (Biacore). Furthermore, they are unable to activate pro‐inflammatory signaling in the cellular system. Thus, CML probably does not form the necessary structure(s) to interact with RAGE and activate an inflammatory signaling cascade in RAGE‐expressing cells.
Developmental potential of selectively enucleated immature mouse oocytes upon nuclear transfer
Authors: Mohammed A.A. , Karasiewicz J. , Modliński J.A.
Published: March 2008

Selective enucleation (SE) was applied to germinal vesicle (GV) oocytes by removing the chromatin attached to nuclear envelope, and leaving the liquid contents of GV in the cytoplast. However, after reconstruction with 1/8 blastomeres or fetal fibroblasts (FFs) neither the maturation efficiency nor the frequency of normal (asymmetric) division was improved as compared with completely enucleated (CE) oocytes. Chromosomal aberrations introduced with somatic nuclei were not rescued in SE oocytes either. On the other hand, timing of maturation division in SE GV oocytes, but not in CE GV oocytes, reconstructed with GV‐karyoplasts was like in the control. After maturation and fertilization in vitro, SE oocytes reconstructed with 1/8 blastomeres developed nucleolated donor pronuclei, contrary to CE oocytes. The latter could be rescued with nucleoli‐containing nucleus, but not anucleolate nucleus, from a 1/2 blastomere. SE oocytes reconstructed with FFs contained nucleolated pronuclei upon activation, unlike CE GV oocytes. These experiments show that the ooplast nucleolar material and/or embryonic nucleolus are indispensable for pronuclei formation. SE oocytes reconstructed with 1/8 blastomeres or FFs failed to cleave after activation or in vitro fertilization. Control GV oocytes enucleolated before fertilization seized cleavage at the 6‐cell stage, as oppose to intact GV oocytes, which in 50.9% yielded morulae/blastocysts. These results suggest that ooplast nucleolar material is essential for the cleavage divisions. Activation of cumulus‐enclosed SE GV oocytes matured in hormone‐supplemented medium and fused to 1/2 blastomere‐karyoplasts, yielded morulae, and blastocysts in 45.5% and 23.4% of reconstructed oocytes, respectively. Mol. Reprod. Dev. 75: 1269–1280, 2008. © 2008 Wiley‐Liss, Inc.
Inhibition of a novel sperm gelatinase in prawn sperm by the male reproduction‐related kazal‐type peptidase inhibitor
Authors: Li Ye , Ma Wen‐Ming , Dai Jie‐Qiong , Feng Chen‐Zhuo , Yang Fan , Ohira Tsuyoshi , Nagasawa Hiromichi , Yang Wei‐Jun
Published: March 2008

Previously, we have identified and characterized a male reproduction‐related kazal‐type peptidase inhibitor (MRPINK) gene from the prawn, Macrobrachium rosenbergii. In the present study, MRPINK was discovered to have an inhibitory effect on the gelatinolytic activity of M. rosenbergii sperm and immunofluorescence analysis revealed it bound specifically onto the base of sperm. The proteolytic activity of sperm extracts to vitelline coat components was also detected to be interfered by MRPINK. Furthermore, a novel gelatinase on sperm was found to be specifically inhibited by MRPINK and was named M. rosenbergii sperm gelatinase (MSG). MSG was then isolated and purified by reversed‐phase high performance liquid chromatography combining with gelatinolytic assay. By amino‐terminal amino acid sequence analysis and molecular cloning, the primary structure of MSG was determined. The data presented in this study provided evidence that MRPINK has an inhibitory effect on the gelatinolytic activity as well as proteolytic activity of prawn sperm and specifically blocks the activity of MSG. Mol. Reprod. Dev. 75: 1327–1337, 2008. © 2008 Wiley‐Liss, Inc.
Germ cell‐specific expression of GFP gene induced by chicken vasa homologue (Cvh) promoter in early chicken embryos
Authors: Minematsu Takeo , Harumi Takashi , Naito Mitsuru
Published: March 2008

In the present study, we cloned the promoter sequence of the chicken vasa homologue (Cvh) gene, and observed the induction of germ cell‐specific gene expression regulated by Cvh promoter in vitro and in vivo. The 2,718‐bp Cvh promoter sequence involved putative binding sites of transcription factors such as Oct‐1, Nkx2‐5, HNF‐4 and v‐Myb, and a putative CpG island. The reporter vectors, which expressed humanized recombinant green fluorescent protein (hrGFP) under the control of one of three lengths (827, 1,555 and 2,718 bp) of Cvh promoter, were transfected to the dispersed gonadal cells of 7‐day incubated embryos in vitro. Every length of promoter‐induced germ cell‐specific hrGFP expression was verified by immunohistochemistry for germ cell‐specific antigens, and the intensity of fluorescence was significantly higher in the transfected gonadal cells using 1,555‐ and 2,718‐bp Cvh promoter compared with 827‐bp promoter. These results suggested that the germ cell‐specific and enhanced gene expression required at least a 1,555‐bp sequence of the 5′ flanking region of Cvh gene. In vivo transfection of the reporter vector with 1,555‐bp Cvh promoter, which was performed by injecting liposome‐DNA complex into the blood vessels of 2‐day incubated embryos, also induced germ cell‐specific hrGFP expression. The Cvh promoter could provide the basis for a methodology for the visualization, purification and genetical modification of germ cells, and might further contribute to our understanding of the development, proliferation, migration and differentiation of germ cells in the chicken. Mol. Reprod. Dev. 75: 1515–1522 © 2008 Wiley‐Liss, Inc.
Effect of prostaglandin E2 and tumor necrosis factor α on the VEGF‐Receptor system expression in cultured porcine luteal cells
Authors: Kowalczyk Anna E. , Kaczmarek Monika M. , Schams Dieter , Ziecik Adam J.
Published: March 2008

The purpose of the present study was to investigate the effects of prostaglandin (PG) E2 and tumor necrosis factor (TNF) α on expression of vascular endothelial growth factor (VEGF) and its receptors, fms‐like tyrosine kinase (Flt‐1) and fetal liver kinase‐1/kinase insert domain‐containing receptor (Flk‐1/KDR), in cultured porcine luteal cells. Real‐time PCR was used for quantification of VEGF and its receptors mRNA, whereas VEGF release by luteal cells was determined by radioimmunoassay (RIA). Only the highest dose of PGE2 (1 µM) after 6 hr of incubation stimulated VEGF release by luteal cells collected in the mid‐luteal phase (P < 0.05). Moreover, PGE2 (100 nM, 1 µM) significantly stimulated VEGF secretion by luteal cells in the late phase and during pregnancy on Days 10–12 (P < 0.05). Elevated mRNA expression of both VEGF 120 and VEGF 164 isoforms was found in luteal cells cultured with PGE2. The lack of an effect of PGE2 on VEGF receptors mRNA expression was observed. TNFα was able to significantly stimulate VEGF release from cells obtained in the mid‐ and late luteal phase or during early pregnancy. All tested doses enhanced mRNA levels of VEGF 120 isoform, but not VEGF 164. Additionally, TNFα was able to decrease Flk‐1/KDR mRNA expression, whereas Flt‐1 mRNA levels were not affected. These results indicated that PGE2 and TNFα influenced VEGF ligand‐receptor system expression in porcine luteal cells and may therefore play an important role in regulation of luteal functions during the estrous cycle and pregnancy in pigs. Mol. Reprod. Dev. 75: 1558–1566 © 2008 Wiley‐Liss, Inc.
Stability and convergence of the spectral Galerkin method for the Cahn‐Hilliard equation
Authors: He Yinnian , Liu Yunxian
Published: March 2008

A spectral Galerkin method in the spatial discretization is analyzed to solve the Cahn‐Hilliard equation. Existence, uniqueness, and stabilities for both the exact solution and the approximate solution are given. Using the theory and technique of a priori estimate for the partial differential equation, we obtained the convergence of the spectral Galerkin method and the error estimate between the approximate solution uN(t) and the exact solution u(t). © 2008 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2008
Is there gender bias in nursing research?
Authors: Polit Denise F. , Beck Cheryl Tatano
Published: March 2008

Using data from a consecutive sample of 259 studies published in four leading nursing research journals in 2005–2006, we examined whether nurse researchers favor females as study participants. On average, 75.3% of study participants were female, and 38% of studies had all‐female samples. The bias favoring female participants was statistically significant and persistent. The bias was observed regardless of funding source, methodological features, and other participant and researcher characteristics, with one exception: studies that had male investigators had more sex‐balanced samples. When designing studies, nurse researchers need to pay close attention to who will benefit from their research and to whether they are leaving out a specific group about which there is a gap in knowledge. © 2008 Wiley Periodicals, Inc. Res Nurs Health 31:417–427, 2008
Elevated expression of SerpinA1 and SerpinA3 in HLA‐positive cervical carcinoma
Authors: Kloth JN , Gorter A , Fleuren GJ , Oosting J , Uljee S , Haar N ter , Dreef EJ , Kenter GG , Jordanova ES
Published: March 2008

In cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune elimination. To investigate this hypothesis, genome‐wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial, and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defence response (n = 27) and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be up‐regulated in HLA‐positive tumours (3.6‐ and 8.2‐fold, respectively), and this was confirmed by real‐time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). Thus, HLA‐positive tumours are characterized by higher expression of genes associated with an inflammatory profile. In addition, expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA‐positive tumours is associated with worse prognosis. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Intra‐ and interobserver reproducibility study of early fetal growth parameters
Authors: Verburg Bero O. , Mulder Paul G. H. , Hofman Albert , Jaddoe Vincent W. V. , Witteman Jacqueline C. M. , Steegers Eric A. P.
Published: March 2008

Objective

To assess the intra‐ and interobserver reproducibility of fetal biometry measurements by transabdominal ultrasound in early pregnancy.

Methods

The study consisted of 21 singleton pregnancies with a gestational age between 9 and 14 weeks. Intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) were calculated. Bland and Altman plots were computed to analyze agreement for measurements between and among observers. Limits of agreement ± 2 SD for the differences in fetal biometry measurements in proportions of the mean of the measurements were derived.

Results

High intra‐ and interobserver ICCs were found, ranging from 0.998, crown‐rump length (CRL) to 0.982, femur length (FL) and CVs ranging from 1.4% (CRL) to 5.9% (FL). Limits of agreement in the Bland and Altman plots ranged from − 2.7 to 2.3% (CRL) difference from the mean to − 13 to 23% (FL) difference. Agreement for fetal biometry increased with fetal size.

Conclusions

This study demonstrated good reproducibility of most measurements of fetal biometry in early pregnancy by abdominal ultrasound. CRL and biparietal diameter (BPD) showed high reproducibility and agreement, and head circumference (HC) to a lesser extend, from 9 weeks of gestational age onwards. abdominal circumference (AC) is only reliable from circa 11 weeks onwards. FL has a poor reproducibility before 14 weeks of gestational age. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of labor on postpartum clearance of cell‐free fetal DNA from the maternal circulation
Authors: Hui L. , Vaughan J. I. , Nelson M.
Published: March 2008

Objective

The aim of this study was to compare the effect of mode of delivery on the postpartum clearance of cell‐free fetal (cff) DNA.

Methods

Women who gave birth to a single‐term male infant by any mode of delivery had blood collected on three occasions: within 3 h of birth, on day 1–2 postpartum and at 2 weeks postpartum. The SRY sequence was used as a marker of cff DNA, and was detected using conventional PCR.

Results

Eighty‐seven women were included in the study. There were 28 women in the elective caesarean section group and 59 in the labor group. Cell‐free fetal DNA was detected in 38/87 (44%) of women within 3 h of birth. There was a significant difference between the group that labored and the group that did not (54 vs 21%, p = 0.003). Twelve percent of women who labored had persistent cff DNA on day 1–2 postpartum, compared with none of the women who delivered without labor. No woman had DNA that persisted up to 2 weeks postpartum.

Conclusion

The presence of labor increases the rate of detectable DNA in women within 3 h of birth and on day 1–2 postpartum. Postpartum clearance was completed by 2 weeks in all women tested regardless of mode of delivery. Copyright © 2008 John Wiley & Sons, Ltd.
Blood pressure control and ACE inhibitor/angiotensin receptor blocker usage
Authors: Woodward A , Mugarza J , Khan M , Smith E , Wilding J , Gill G
Published: March 2008

The aim of this audit was to determine the changes over a four‐year period in the numbers of type 2 patients with microalbuminuria (MA) and diabetic nephropathy (DN) treated with angiotensin converting enzyme inhibitor (ACE‐I) and/or angiotensin receptor blocker (ARB) therapy and who had achieved target blood pressure (BP) control.

We undertook a retrospective electronic case note audit of 200 type 2 patients attending hospital diabetes clinics. Patients were divided into three groups: MA, DN and normoalbuminuric. Results were compared with a similar audit carried out four years previously.

The three groups were well matched for numbers, age, sex and HbA1c. The numbers achieving target BP had not improved in all three groups. There was no improvement in systolic BP but diastolic BP improved significantly in all groups— MA 74±12 to 69±11 (p = 0.03); DN 78±12 to 70±13 (p = 0.02); and normoalbuminuric 73±12 to 69±11 (p = 0.006). Only the normoalbuminuric group showed a significant increase in the numbers prescribed ≥ three antihypertensive drugs (14% to 28%, p = 0.008). Treatment with ACE‐I and/or ARB had improved overall in the MA group (53% to 92%, p<0.0001), and in the normoalbuminuric group (41% to 57%, p = 0.01). Usage of ARB therapy increased significantly in all groups— MA 3% to 23% (p = 0.01); DN 13% to 47% (p = 0.003); and normoalbuminuric 2% to 15% (p = 0.0003).

We conclude that hypertension remains under‐treated, especially in the MA and DN groups despite an improvement in the usage of ACE‐I and ARB therapy. Widespread use of protocol‐driven, nurse‐led clinics may help to intensify management. Copyright © 2008 John Wiley & Sons.
The management of women with gestational diabetes can be stratified according to diagnostic oral glucose tolerance test results
Authors: Wong ML , Butson S , Gatling W , Masding MG
Published: March 2008

The ACHOIS trial (Australian Carbohydrate Intolerance Study in Pregnant Women) confirmed the benefits of treating gestational diabetes mellitus (GDM). Optimum management strategies remain uncertain. In our unit, women with GDM are allocated into two treatment groups according to their diagnostic oral glucose tolerance test (OGTT) result. Those with a fasting glucose <6mmol/L and two‐hour post‐load glucose of 7.8–9mmol/L are treated conservatively: dietitian‐led, with weekly blood glucose test two hours post‐meal; while those with a fasting glucose ≥ 6mmol/L or two‐hour post‐load glucose ≥ 9mmol/L are treated intensively: regular clinic reviews, with four times daily home blood glucose monitoring (HBGM).

This study aimed to investigate any difference in outcomes between the conservative group (n = 35) and the intensive group (n = 46).

Eighty‐one GDM patients attending the joint obstetric clinic between May 2001 and March 2004 were identified, and pregnancy outcomes in the two groups were compared.

There were no significant differences in mean birth weight (conservative group 3572±458g, intensive group 3601±666g, p = 0.597), rates of macrosomia [>4kg] (conservative 20%, intensive 30%, p = 0.3) and large for gestational age [>95th centile] (conservative 29%, intensive 41%, p = 0.2).

It was concluded that the care of women with GDM can be stratified based on diagnostic OGTT results and managed accordingly, which may allow for a more resource‐efficient management strategy in this group. Copyright © 2008 John Wiley & Sons.
Experimental therapy of prostate cancer with novel natural product anti‐cancer ginsenosides
Authors: Wang Wei , Rayburn Elizabeth R. , Hao Miao , Zhao Yuqing , Hill Donald L. , Zhang Ruiwen , Wang Hui
Published: March 2008

BACKGROUND

Ginseng and its components exert various biological effects, including antioxidant, anti‐carcinogenic, anti‐mutagenic, and anti‐tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25‐hydroxyprotopanaxadiol (25‐OH‐PPD) and 25‐hydroxyprotopanaxatriol (25‐OH‐PPT) from Panax ginseng and evaluated their anti‐cancer activity in vitro.

METHODS

We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds.

RESULTS

25‐OH‐PPD, but not 25‐OH‐PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25‐OH‐PPD inhibited tumor growth in a dose‐dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti‐tumor effects. Further, in both PC3 and LNCaP cell lines, 25‐OH‐PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25‐OH‐PPD demonstrated low toxicity to non‐cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies.

CONCLUSIONS

The newly identified ginsenoside 25‐OH‐PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809–819, 2008. © 2008 Wiley‐Liss, Inc.
Genetic changes and DNA damage responses in the prostate
Authors: Kiviharju‐af Hällström Taija M. , Laiho Marikki
Published: March 2008

The integrity of genomic DNA is challenged by genotoxic stress originating during normal cellular metabolism or by external insults. Cellular responses to DNA damage involve elegant checkpoint cascades enforcing cell cycle arrest, damage repair, apoptosis or cellular senescence. The loss or alterations of genes involved in the damage response pathways have been reported in many cancer susceptibility syndromes and in sporadic tumors. Furthermore, this surveillance pathway is activated during early tumourigenesis presumably due to uncontrolled replicative cycles and has been recognized as one of the main barriers against the development of cancer. This review discusses the relevance of prostatic epithelial cells in prostate tumourigenesis and highlights common molecular changes associated with prostate cancer. Furthermore, DNA damage responses of primary cultures of human prostatic epithelial cells and fresh human prostate tissues are discussed providing evidence for alterations in crucial DNA damage checkpoint molecules. New insights connecting prostate tumourigenesis to alterations and defects in the pathways maintaining genomic integrity will be discussed. Prostate 68:902–918, 2008. © 2008 Wiley‐Liss, Inc.
All‐atom replica exchange molecular simulation of protein BBL
Authors: Zhang Jian , Li Wenfei , Wang Jun , Qin Meng , Wang Wei
Published: March 2008

Downhill folding is one of the most important predictions of energy landscape theory. Recently, the Escherichia coli 2‐oxoglutarate dehydrogenase PSBD was described as a first example of global downhill folding (Garcia‐Mira et al., Science 2002;298:2191), classification that has been later subject of significant controversy. To help resolve this problem, by using intensive all‐atom simulation with explicit water model and the replica exchange method, we sample the phase space of protein BBL and depict the free energy landscape. We give an estimate of the free energy barrier height of 1–2 kBT, dependent on the way the energy landscape is projected. We also study the conformational distribution of the transition region and find that the three helices generally take the similar positions as that in the native states whereas their spatial orientations show large variability. We further detect the inconsistency between different signals by individually fitting the thermal denaturation curves of five structural features using two‐state model, which gives a wide spread melting temperature of 19 K. All of these features are consistent with a picture of folding with very low cooperativities. Compared with the experimental data (Sadqi et al., Nature 2006; 442:317), our results indicate that the Naf‐BBL (pH5.3) may have an even lower barrier height and cooperativity. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Scan2S: Increasing the precision of PROSITE pattern motifs using secondary structure constraints
Authors: Skrabanek Lucy , Niv Masha Y.
Published: March 2008

Sequence signature databases such as PROSITE, which include protein pattern motifs indicative of a protein's function, are widely used for function prediction studies, cellular localization annotation, and sequence classification. Correct annotation relies on high precision of the motifs. We present a new and general approach for increasing the precision of established protein pattern motifs by including secondary structure constraints (SSCs). We use Scan2S, the first sequence motif‐scanning program to optionally include SSCs, to augment PROSITE pattern motifs. The constraints were derived from either the DSSP secondary structure assignment or the PSIPRED predictions for PROSITE‐documented true positive hits. The secondary structure‐augmented motifs were scanned against all SwissProt sequences, for which secondary structure predictions were precalculated. Against this dataset, motifs with PSIPRED‐derived SSCs exhibited improved performance over motifs with DSSP‐derived constraints. The precision of 763 of the 782 PSIPRED‐augmented motifs remained unchanged or increased compared to the original motifs; 26 motifs showed an absolute precision increase of 10–30%. We provide the complete set of augmented motifs and the Scan2S program at http://physiology.med.cornell.edu/go/scan2s. Our results suggest a general protocol for increasing the precision of protein pattern detection via the inclusion of SSCs. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Internal wave drag in stratified flow over mountains on a beta plane
Authors: Teixeira M. A. C. , Grisogono Branko
Published: March 2008

The impact of the variation of the Coriolis parameter f on the drag exerted by internal Rossby‐gravity waves on elliptical mountains is evaluated using linear theory, assuming constant wind and static stability and a beta‐plane approximation. Previous calculations of inertia‐gravity wave drag are thus extended in an attempt to establish a connection with existing studies on planetary wave drag, developed primarily for fluids topped by a rigid lid. It is found that the internal wave drag for zonal westerly flow strongly increases relative to that given by the calculation where f is assumed to be a constant, particularly at high latitudes and for mountains aligned meridionally. Drag increases with mountain width for sufficiently wide mountains, reaching values much larger than those valid in the non‐rotating limit. This occurs because the drag receives contributions from a low wavenumber range, controlled by the beta effect, which accounts for the drag amplification found here. This drag amplification is shown to be considerable for idealized analogues of real mountain ranges, such as the Himalayas and the Rocky mountains, and comparable to the barotropic Rossby wave drag addressed in previous studies. Copyright © 2008 Royal Meteorological Society