bluuebunny/crossref_metadata_2025 huggingface dataset:
Present state of reproductive medicine in Japan – ethical issues with a focus on those seen in court cases
Authors: Mayeda Mayumi
Published: April 2006

Background

Against a background of on the one hand, a declining demography and a conservative family register system that emphasizes the importance of the blood line, and on the other hand, an increase in the number of people undergoing fertility treatment, the absence of a legal regulatory framework concerning ART matters is likely to result in an increasing number of contradictory situations. It is against this background that the paper sets out to examine the judgements of court cases related to ART, with a particular focus on the legal determination of parental status, and to link these to aspects of the legal and socio-ethical environment within which the courts make their judgements.

Methods

The methods used were thorough investigation of all the court cases concerning ART in the public domain in Japan, including the arguments of the concerned parties and the judgements so far delivered. With the court cases as a central focal point, trends in Japan, including deliberations by government and academic societies, are reviewed, and the findings of surveys on the degree of understanding and attitudes among the people toward ART are summarized.

Results

In terms of the judgements to date, the central criteria used by the courts in determining parental status were the act of parturition and the consent of the husband of the concerned couple. The government and academic societies have displayed a cautious attitude toward ART, but the findings of attitude surveys among the people at large show a generally positive attitude toward ART. Attitudes toward the overwhelming importance hitherto attached to the bloodline are also seen to be changing.

Conclusion

The main conclusion is that in the absence of a legal regulatory framework for ART, there is likely to be an increase in the contradictions between the use of outdated legal precedents and the technical development of ART. Since much of the specialist discussion necessary for the formulation of a legal framework has already been carried out, the speedy enactment of comprehensive and at the same time flexible legislation would be highly desirable, but further wide-ranging discussion involving the general public is likely to be needed first.
The implementation of quality management systems in hospitals: a comparison between three countries
Authors: Wagner C , Gulácsi L , Takacs E , Outinen M
Published: April 2006

Background

Is the implementation of Quality Management (QM) in health care proceeding satisfactorily and can national health care policies influence the implementation process? Policymakers and researchers in a country need to know the answer to this question. Cross country comparisons can reveal whether sufficient progress is being made and how this can be stimulated.

The objective of the study was to investigate agreement and disparities in the implementation of QMS between The Netherlands, Hungary and Finland with respect to the evaluation model used and the national policy strategy of the three countries.

Methods

The study has a cross sectional design, based on measurements in 2000. Empirical data about QM-activities in hospitals were gathered by a self-administered questionnaire. The questionnaires were answered by the directors of the hospitals or the quality coordinators. The analyses are based on data from 101 hospitals in the Netherlands, 116 hospitals in Hungary and 59 hospitals in Finland.

Outcome measures are the developmental stage of the Quality Management System (QMS), the development within five focal areas, and distinct QM-activities which were listed in the questionnaire.

Results

A mean of 22 QM-activities per hospital was found in the Netherlands and Finland versus 20 QM-activities in Hungarian hospitals. Only a small number of hospitals has already implemented a QMS (4% in The Netherlands,0% in Hungary and 3% in Finland). More hospitals in the Netherlands are concentrating on quality documents, whereas Finnish hospitals are concentrating on training in QM and guidelines. Cyclic quality improvement activities have been developed in the three countries, but in most hospitals the results were not used for improvements. All three countries pay hardly any attention to patient participation.

Conclusion

The study demonstrates that the implementation of QM-activities can be measured at national level and that differences between countries can be assessed. The hypothesis that governmental legislation or financial reimbursement can stimulate the implementation of QM-activities, more than voluntary recommendations, could not be confirmed. However, the results show that specific obligations can stimulate the implementation of QM-activities more than general, framework legislation.
LDL cholesterol estimation in patients with the metabolic syndrome
Authors: Gazi Irene , Tsimihodimos Vasilis , Filippatos Theodosios D , Saougos Vasilios G , Bairaktari Eleni T , Tselepis Alexandros D , Elisaf Moses
Published: April 2006

Background

The Friedewald formula (LDL-F) for the estimation of low-density lipoprotein (LDL) cholesterol concentrations is the most often used formula in clinical trials and clinical practice. However, much concern has been raised as to whether this formula is applicable in all patient populations such as the presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present study was to evaluate various LDL cholesterol calculation formulas as well as LDL cholesterol levels provided by the Lipoprint LDL System (LDL-L) in patients with the metabolic syndrome (MetSyn).

Results

LDL-F showed significant differences from other formulas in the total cohort, as well as in MetSyn individuals. This was not the case in nonMetSyn subjects, where LDL-F did not differ with other formulas, with the exception of one formula (LDL by Planella, LDL-P). The bias between LDL-F and other LDL estimation formulas were significantly higher in MetSyn subjects compared to nonMetSyn individuals, except for LDL-L which produced similar bias with LDL-F in both study groups.

Conclusion

LDL-F seems to exhibit some limitations as far as the calculation of LDL-C levels in patients with the MetSyn is concerned. LDL-L might be more accurate in MetSyn subjects, but so far its use is limited for the estimation of small, dense LDL (sdLDL) cholesterol levels and mean LDL particle size for research purposes only.
Solitary pulmonary metastasis from primary melanoma of the oesophagus 5 years after resection of the primary tumor
Authors: Dionigi Gianlorenzo , Rovera Francesca , Boni Luigi , Imperatori Andrea , Dionigi Renzo
Published: April 2006

Background

Primary malignant melanoma of the oesophagus (PMME) is an uncommon tumor. PMME has an aggressive biological behavior, similar to melanomas developed elsewhere in the body. Most patients die from distant metastases, and the overall 5 year survival rate is approximately 4%.

Case presentation

We report a rare case of a solitary pulmonary metastasis found 5 years after curative resection of primary esophageal melanoma. No other sites of metastatic disease were identified. Video-assisted lung wedge resection of the lung nodule was carried out successfully.

Conclusion

This supports the concept that patients with primary melanoma of the oesophagus treated should be carefully followed up.
A statistical method for predicting splice variants between two groups of samples using GeneChip® expression array data
Authors: Fan Wenhong , Khalid Najma , Hallahan Andrew R , Olson James M , Zhao Lue Ping
Published: April 2006

Background

Alternative splicing of pre-messenger RNA results in RNA variants with combinations of selected exons. It is one of the essential biological functions and regulatory components in higher eukaryotic cells. Some of these variants are detectable with the Affymetrix GeneChip® that uses multiple oligonucleotide probes (i.e. probe set), since the target sequences for the multiple probes are adjacent within each gene. Hybridization intensity from a probe correlates with abundance of the corresponding transcript. Although the multiple-probe feature in the current GeneChip® was designed to assess expression values of individual genes, it also measures transcriptional abundance for a sub-region of a gene sequence. This additional capacity motivated us to develop a method to predict alternative splicing, taking advance of extensive repositories of GeneChip® gene expression array data.

Results

We developed a two-step approach to predict alternative splicing from GeneChip® data. First, we clustered the probes from a probe set into pseudo-exons based on similarity of probe intensities and physical adjacency. A pseudo-exon is defined as a sequence in the gene within which multiple probes have comparable probe intensity values. Second, for each pseudo-exon, we assessed the statistical significance of the difference in probe intensity between two groups of samples. Differentially expressed pseudo-exons are predicted to be alternatively spliced. We applied our method to empirical data generated from GeneChip® Hu6800 arrays, which include 7129 probe sets and twenty probes per probe set. The dataset consists of sixty-nine medulloblastoma (27 metastatic and 42 non-metastatic) samples and four cerebellum samples as normal controls. We predicted that 577 genes would be alternatively spliced when we compared normal cerebellum samples to medulloblastomas, and predicted that thirteen genes would be alternatively spliced when we compared metastatic medulloblastomas to non-metastatic ones. We checked the consistency of some of our findings with information in UCSC Human Genome Browser.

Conclusion

The two-step approach described in this paper is capable of predicting some alternative splicing from multiple oligonucleotide-based gene expression array data with GeneChip® technology. Our method employs the extensive repositories of gene expression array data available and generates alternative splicing hypotheses, which can be further validated by experimental studies.
Modes of transmission and genetic diversity of foamy viruses in a Macaca tonkeanacolony
Authors: Calattini Sara , Wanert Fanélie , Thierry Bernard , Schmitt Christine , Bassot Sylviane , Saib Ali , Herrenschmidt Nicolas , Gessain Antoine
Published: April 2006

Background

Foamy viruses are exogenous complex retroviruses that are highly endemic in several animal species, including monkeys and apes, where they cause persistent infection. Simian foamy viral (SFV) infection has been reported in few persons occupationally exposed to non-human primates (NHP) in zoos, primate centers and laboratories, and recently in few hunters from central Africa. Most of the epidemiological works performed among NHP populations concern cross-sectional studies without long-term follow-up. Therefore, the exact timing and the modes of transmission of SFVs remain not well known, although sexual and oral transmissions have been suspected. We have conducted a longitudinal study in a free-breeding colony of Macaca tonkeana in order (1) to determine the prevalence of the infection by foamy viruses, (2) to characterize molecularly the viruses infecting such animals, (3) to study their genetic variability overtime by long-term follow-up of several DNA samples in a series of specific animals, and (4) to get new insights concerning the timing and the modes of SFVs primary infection in these monkeys by combining serology and molecular means, as well as studies of familial structures and long-term behavioral observations.

Results/conclusion

We first demonstrated that this colony was highly endemic for SFVs, with a clear increase of seroprevalence with age. Only 4.7% of immatures, and 43,7% of sub-adults were found seropositive, while 89.5% of adults exhibited antibodies directed against SFV. We further showed that 6 different strains of foamy viruses (exhibiting a very low intra-strain and overtime genetic variability in the integrase gene) are circulating within this group. This suggests a possible infection by different strains within an animal. Lastly, we provide strong evidence that foamy viruses are mostly acquired through severe bites, mainly in sub-adults or young adults. Most cases of seroconversion occur after 7 years of age; from this age individuals competed for access to sexual partners, thus increasing the likelihood of being wounded. Furthermore, all the serological and molecular data, obtained in this free-breeding colony, argue against a significant transmission of SFVs from mother or father to infants as well as between siblings.
Application of real-time PCR to quantify hepatitis B virus DNA in chronic carriers in The Gambia
Authors: Mendy Maimuna E , Kaye Steve , van der Sande Marianne , Rayco-Solon Pura , Waight Pauline A , Shipton Deborah , Awi Dorka , Snell Paul , Whittle Hilton , McConkey Samuel J
Published: April 2006

Background/Aim

The study aimed at developing a real-time quantitative PCR assay to monitor HBV serum virus load of chronic carriers enrolled in therapeutic trials.

Method

Quantitative real-time PCR assay was carried out using SYBR-Green signal detection and primers specific to the S gene. Thermal cycling was performed in an ABi 5700 sequence detection system. The assay was calibrated against an international HBV DNA standard and inter- and intra-assay reproducibility determined. Levels of viral load were monitored for 1-year in lamivudine treated carriers. Correlation between HBV DNA levels and HBeAg sero-status was determined in untreated carriers.

Results

The qPCR assay showed good intra- and inter-assay reproducibility over a wide dynamic range (1.5 × 103 to 1.5 × 108 copies/mL) and correlated well with those from a commercial assay (r = 0.91, (p < 0.001). Viral load levels dropped dramatically but temporarily during and after a short course of lamivudine therapy. HBV DNA was a more reliable indicator of the presence of virus than HBe antigen and was detected in 77.0% (161/209) of HBeAg negative and in all HBeAg positive carriers.

Conclusion

This method is reliable, accurate, and reproducible. HBV DNA Quantification by qPCR can be used to monitor the efficacy of HBV therapy and useful in understanding the natural history of HBV in an endemic area.
Retrograde transport pathways utilised by viruses and protein toxins
Authors: Spooner Robert A , Smith Daniel C , Easton Andrew J , Roberts Lynne M , Lord Michael J
Published: April 2006

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised.
What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies
Authors: McDonald Alison M , Knight Rosemary C , Campbell Marion K , Entwistle Vikki A , Grant Adrian M , Cook Jonathan A , Elbourne Diana R , Francis David , Garcia Jo , Roberts Ian , Snowdon Claire
Published: April 2006

Background

A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme.

Methods

The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate.

Results

Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed.

Conclusion

Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.
A novel fluorescent pH probe for expression in plants
Authors: Schulte Alexander , Lorenzen Inken , Böttcher Markus , Plieth Christoph
Published: April 2006

Background

The pH is an important parameter controlling many metabolic and signalling pathways in living cells. Recombinant fluorescent pH indicators (pHluorins) have come into vogue for monitoring cellular pH. They are derived from the most popularAequorea victoriaGFP (Av-GFP). Here, we present a novel fluorescent pH reporter protein from the orange seapenPtilosarcus gurneyi(Pt-GFP) and compare its properties with pHluorins for expression and use in plants.

Results

pHluorins have a higher pH-sensitivity. However,Pt-GFP has a broader pH-responsiveness, an excellent dynamic ratio range and a better acid stability. We demonstrate howPt-GFP expressingArabidopsis thalianareport cytosolic pH-clamp and changes of cytosolic pH in the response to anoxia and salt-stress.

Conclusion

Pt-GFP appears to be the better choice when used forin vivo-recording of cellular pH in plants.
Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low – results from RABBIT, the German biologics register
Authors: Listing Joachim , Strangfeld Anja , Rau Rolf , Kekow Jörn , Gromnica-Ihle Erika , Klopsch Thilo , Demary Winfried , Burmester Gerd-Rüdiger , Zink Angela
Published: April 2006

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis – Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2–3.2)); ARA remission, OR 2.05 (95% CI 1.2–3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7–8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04–4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.
The in vivoexpression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus
Authors: Manderson Anthony P , Carlucci Francesco , Lachmann Peter J , Lazarus Robert A , Festenstein Richard J , Cook H Terence , Walport Mark J , Botto Marina
Published: April 2006

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of these autoantibodies is an antigen-driven process and that immune complexes involving DNA-containing antigens play a key role in the disease process. In rodents, DNase I is the major endonuclease present in saliva, urine and plasma, where it catalyses the hydrolysis of DNA, and impaired DNase function has been implicated in the pathogenesis of SLE. In this study we have evaluated the effects of transgenic over-expression of murine DNase I endonucleases in vivo in a mouse model of lupus. We generated transgenic mice having T-cells that express either wild-type DNase I (wt.DNase I) or a mutant DNase I (ash.DNase I), engineered for three new properties – resistance to inhibition by G-actin, resistance to inhibition by physiological saline and hyperactivity compared to wild type. By crossing these transgenic mice with a murine strain that develops SLE we found that, compared to control non-transgenic littermates or wt.DNase I transgenic mice, the ash.DNase I mutant provided significant protection from the development of anti-single-stranded DNA and anti-histone antibodies, but not of renal disease. In summary, this is the first study in vivo to directly test the effects of long-term increased expression of DNase I on the development of SLE. Our results are in line with previous reports on the possible clinical benefits of recombinant DNase I treatment in SLE, and extend them further to the use of engineered DNase I variants with increased activity and resistance to physiological inhibitors.
The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis
Authors: Shen Zhenxin , Crotti Tania N , McHugh Kevin P , Matsuzaki Kenichiro , Gravallese Ellen M , Bierbaum Benjamin E , Goldring Steven R
Published: April 2006

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β3 integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties.
The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis
Authors: Sunahori Katsue , Yamamura Masahiro , Yamana Jiro , Takasugi Kouji , Kawashima Masanori , Yamamoto Hiroshi , Chazin Walter J , Nakatani Yuichi , Yui Satoru , Makino Hirofumi
Published: April 2006

S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-κB) inhibitors. NF-κB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-κB and p38 MAPK pathways in RA.
Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo
Authors: Wärnberg Fredrik , White Daniel , Anderson Elizabeth , Knox Fiona , Clarke Robert B , Morris Julie , Bundred Nigel J
Published: April 2006

Introduction

The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested.

Method

In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours.

Results

The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (± 26 nmol/l) for SKBR3 to 5.9 μmol/l(± 0.8 μmol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts.

Conclusion

Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.
Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort
Authors: Jacobs Eric J , Feigelson Heather Spencer , Bain Elizabeth B , Brady Kerri A , Rodriguez Carmen , Stevens Victoria L , Patel Alpa V , Thun Michael J , Calle Eugenia E
Published: April 2006

Introduction

Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region.

Method

We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls).

Results

We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00–2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02–2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88–1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37–0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer.

Conclusion

Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women.
Diagnostic value of real-time polymerase chain reaction to detect viruses in young children admitted to the paediatric intensive care unit with lower respiratory tract infection
Authors: van de Pol Alma C , Wolfs Tom FW , Jansen Nicolaas JG , van Loon Anton M , Rossen John WA
Published: April 2006

Introduction

The aetiology of lower respiratory tract infections in young children admitted to the paediatric intensive care unit (PICU) is often difficult to establish. However, most infections are believed to be caused by respiratory viruses. A diagnostic study was performed to compare conventional viral tests with the recently developed real-time PCR technique.

Method

Samples from children aged under 5 years presenting to a tertiary PICU suspected of having a lower respiratory tract infection were tested using conventional methods (viral culture and immunofluorescence) and real-time PCR during the winter season from December 2004 to May 2005. Conventional methods were used to check for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–3, rhinoviruses and adenoviruses. Real-time PCR was used to test for respiratory syncytial virus, influenzavirus, parainfluenzavirus 1–4, rhinoviruses, adenoviruses, human coronaviruses OC43, NL63 and 229E, human metapneumovirus, Mycoplasma pneumoniae and Chlamydia pneumoniae.

Results

A total of 23 patients were included, of whom 11 (48%) were positive for a respiratory virus by conventional methods. Real-time PCR confirmed all of these positive results. In addition, real-time PCR identified 22 more viruses in 11 patients, yielding a total of 22 (96%) patients with a positive sample. More than one virus was detected in eight (35%) children.

Conclusion

Real-time PCR for respiratory viruses was found to be a sensitive and reliable method in PICU patients with lower respiratory tract infection, increasing the diagnostic yield twofold compared to conventional methods.
Comparative analysis of Saccharomyces cerevisiaeWW domains and their interacting proteins
Authors: Hesselberth Jay R , Miller John P , Golob Anna , Stajich Jason E , Michaud Gregory A , Fields Stanley
Published: April 2006

Background

The WW domain is found in a large number of eukaryotic proteins implicated in a variety of cellular processes. WW domains bind proline-rich protein and peptide ligands, but the protein interaction partners of many WW domain-containing proteins in Saccharomyces cerevisiae are largely unknown.

Results

We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae. We observed 587 interactions between these 12 domains and 207 proteins, most of which have not previously been described. We analyzed the representation of functional annotations within the network, identifying enrichments for proteins with peroxisomal localization, as well as for proteins involved in protein turnover and cofactor biosynthesis. We compared orthologs of the interacting proteins to identify conserved motifs known to mediate WW domain interactions, and found substantial evidence for the structural conservation of such binding motifs throughout the yeast lineages. The comparative approach also revealed that several of the WW domain-containing proteins themselves have evolutionarily conserved WW domain binding sites, suggesting a functional role for inter- or intramolecular association between proteins that harbor WW domains. On the basis of these results, we propose a model for the tuning of interactions between WW domains and their protein interaction partners.

Conclusion

Protein microarrays provide an appealing alternative to existing techniques for the construction of protein interaction networks. Here we built a network composed of WW domain-protein interactions that illuminates novel features of WW domain-containing proteins and their protein interaction partners.
Promotional Chat on the Internet
Authors: Mayzlin Dina
Published: April 2006

Chat rooms, recommendation sites, and customer review sections allow consumers to overcome geographic boundaries and to communicate based on mutual interests. However, marketers also have incentives to supply promotional chat or reviews in order to influence the consumers’ evaluation of their products. Moreover, firms can disguise their promotion as consumer recommendations due to the anonymity afforded by online communities. We explore this new setting where advertising and word of mouth become perfect substitutes because they appear indistinguishable to the consumer. Specifically, we investigate here whether word of mouth remains credible and whether firms choose to devote more resources promoting their inferior or superior products.

We develop a game theoretic model in which two products are differentiated in their value to the consumer. Unlike the firms, the consumers are uncertain about the products’ quality. The consumers read messages online that help them decide on the identity of the superior product. We find a unique equilibrium where online word of mouth is persuasive despite the promotional chat activity by competing firms. In this equilibrium, firms spend more resources promoting inferior products, in striking contrast to existing advertising literature. In addition, we discuss consumer welfare implications and how other marketing strategies might interact with promotional chat.
Does Community Policing Motivate Officers at Work and How?
Authors: Wang Yumin R.
Published: April 2006

This paper examines how community policing programmes motivate officers at work in line with prevailing theories of management. Questionnaires were administered to a total of 112 rank-and-files of the Taipei County Police Department, involving 59 Community Police Officers (CPOs) and 53 non-CPOs. Findings indicate that reforming management can be as effective as redesigning the work for officers in promoting their job satisfaction, and the former may be more important than the latter. CPOs as well as non-CPOs become satisfied with their job as long as they develop positive attitudes toward their supervisors and the department. Community policing is nonetheless a work design strategy suitable for officers of different role orientation and growth need strength. It serves as the best option for police administrators when other strategies for motivating officers at work are absent.
Isolation of Mutations That Bypass the Requirement of the Septation Initiation Network for Septum Formation and Conidiation inAspergillus nidulans
Authors: Kim Jung-Mi , Lu Ling , Shao Rongzhong , Chin Jaclyn , Liu Bo
Published: April 2006

The kinase cascade of the septation initiation network (SIN), first revealed in fission yeast, activates the contraction of the actomyosin ring, and plays an essential role in fungal septation. Mob1p, an evolutionarily conserved SIN protein, is associated with the most downstream kinase of this cascade in fission yeast. In this study, the mobA gene encoding a homologous protein was isolated from the filamentous fungus Aspergillus nidulans, whose mycelium is made of multinucleate cells. The MOBA protein was required for septation and conidiation, but was not essential for hyphal extension and colony formation. To identify genes that act antagonistically against the SIN, UV mutagenesis was carried out to isolate suppressor (smo) mutations that restored conidiation when MOBA was not expressed. Microscopic examination indicated that the restored conidiation was concomitant with restored septation in the absence of the MOBA protein. Eight recessive smo mutations in five complementation groups also bypassed the requirement of the SIN kinases SEPH and SIDB for septum formation and conidiation. However, none of these smo mutations affected the localization of MOBA. Among smo mutations, smoA and smoB mutations caused reduced hyphal growth and colony formation. They also rendered hypersensitivity to low doses of the microtubule-depolymerizing agent benomyl for conidiation. Therefore, in A. nidulans, proteins encoded by the smo genes likely have an antagonistic interaction against the SIN pathway to regulate septation and conidiation.
Saccharomyces cerevisiae Donor Preference During Mating-Type Switching Is Dependent on Chromosome Architecture and Organization
Authors: Coïc Eric , Richard Guy-Franck , Haber James E
Published: April 2006

Saccharomyces mating-type (MAT) switching occurs by gene conversion using one of two donors, HMLα and HMRa, located near the ends of the same chromosome. MATa cells preferentially choose HMLα, a decision that depends on the recombination enhancer (RE) that controls recombination along the left arm of chromosome III (III-L). When RE is inactive, the two chromosome arms constitute separate domains inaccessible to each other; thus HMRa, located on the same arm as MAT, becomes the default donor. Activation of RE increases HMLα usage, even when RE is moved 50 kb closer to the centromere. If MAT is inserted into the same domain as HML, RE plays little or no role in activating HML, thus ruling out any role for RE in remodeling the silent chromatin of HML in regulating donor preference. When the donors MAT and RE are moved to chromosome V, RE increases HML usage, but the inaccessibility of HML without RE apparently depends on other chromosome III-specific sequences. Similar conclusions were reached when RE was placed adjacent to leu2 or arg4 sequences engaged in spontaneous recombination. We propose that RE's targets are anchor sites that tether chromosome III-L in MATα cells thus reducing its mobility in the nucleus.
Adaptive Divergence in Experimental Populations ofPseudomonas fluorescens. II. Role of the GGDEF Regulator WspR in Evolution and Development of the Wrinkly Spreader Phenotype
Authors: Goymer Patrick , Kahn Sophie G , Malone Jacob G , Gehrig Stefanie M , Spiers Andrew J , Rainey Paul B
Published: April 2006

Wrinkly spreader (WS) genotypes evolve repeatedly in model Pseudomonas populations undergoing adaptive radiation. Previous work identified genes contributing to the evolutionary success of WS. Here we scrutinize the GGDEF response regulator protein WspR and show that it is both necessary and sufficient for WS. Activation of WspR occurs by phosphorylation and different levels of activation generate phenotypic differences among WS genotypes. Five alleles of wspR, each encoding a protein with a single amino acid substitution, were generated by mutagenesis. Two alleles are constitutively active and cause the ancestral genotype to develop a WS phenotype; the phenotypic effects are allele specific and independent of phosphorylation. Three alleles contain changes in the GGDEF domain and when overexpressed in WS cause reversion to the ancestral phenotype. Ability to mimic this effect by overexpression of a liberated N-terminal domain shows that in WS, regulatory components upstream of WspR are overactive. To connect changes at the nucleotide level with fitness, the effects of variant alleles were examined in both structured and unstructured environments: alleles had adaptive and deleterious effects with trade-offs evident across environments. Despite the proclivity of mutations within wspR to generate WS, sequence analysis of wspR from 53 independently obtained WS showed no evidence of sequence change in this gene.
High-Resolution Radiation Hybrid Map of Wheat Chromosome 1D
Authors: Kalavacharla Venu , Hossain Khwaja , Gu Yong , Riera-Lizarazu Oscar , Vales M Isabel , Bhamidimarri Suresh , Gonzalez-Hernandez Jose L , Maan Shivcharan S , Kianian Shahryar F
Published: April 2006

Physical mapping methods that do not rely on meiotic recombination are necessary for complex polyploid genomes such as wheat (Triticum aestivum L.). This need is due to the uneven distribution of recombination and significant variation in genetic to physical distance ratios. One method that has proven valuable in a number of nonplant and plant systems is radiation hybrid (RH) mapping. This work presents, for the first time, a high-resolution radiation hybrid map of wheat chromosome 1D (D genome) in a tetraploid durum wheat (T. turgidum L., AB genomes) background. An RH panel of 87 lines was used to map 378 molecular markers, which detected 2312 chromosome breaks. The total map distance ranged from ∼3,341 cR35,000 for five major linkage groups to 11,773 cR35,000 for a comprehensive map. The mapping resolution was estimated to be ∼199 kb/break and provided the starting point for BAC contig alignment. To date, this is the highest resolution that has been obtained by plant RH mapping and serves as a first step for the development of RH resources in wheat.
Solvent Systems for the Isolation of Organic Components from Soils
Authors: Hayes Michael H. B.
Published: April 2006

The classical methods for the isolation of soil organic matter (SOM) components use aqueous base or neutral salt solutions, and combinations of aqueous base and pyrophosphate. Organic solvents have been rarely used, largely because of difficulties in recovering solutes. This review provides the relevant chemistry of aqueous and organic chemicals relevant to extracting and fractionating the components of SOM that are bound and are not bound by the soil mineral surfaces. Uses of aqueous media to separate the SOM components on the basis of charge density differences are described. Combinations of aqueous base and urea enhance the isolations of the SOM components that have a high degree of polarity [humic and fulvic acids (HAs and FAs), polysaccharides, peptides]. However, the nature of the associations between the solute molecules has prevented the isolation of any purified SOM component. Properties are listed of organic solvents that have potential for the isolation of SOM components, and novel procedures are described for the recovery of the SOM components dissolved in organic solvents. The procedures include the uses of resins with varying degrees of polarity and the recovery of the SOM components in aqueous media. No satisfactory solvent system has been found that can isolate all of the humin materials sorbed by the inorganic colloids. However, procedures are outlined that can extract much of the material classified as humin in the classical definitions. Because the polar components of the SOM can now be removed, it is likely that the compositions of the nonpolar humins strongly held by the mineral colloids will be resolved using procedures such as pyrolysis–mass spectrometry.