bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative promoter methylation analysis of multiple cancer-related genes in renal cell tumors
Authors: Costa Vera L , Henrique Rui , Ribeiro Franclim R , Pinto Mafalda , Oliveira Jorge , Lobo Francisco , Teixeira Manuel R , Jerónimo Carmen
Published: July 2007

Background

Aberrant promoter hypermethylation of cancer-associated genes occurs frequently during carcinogenesis and may serve as a cancer biomarker. In this study we aimed at defining a quantitative gene promoter methylation panel that might identify the most prevalent types of renal cell tumors.

Methods

A panel of 18 gene promoters was assessed by quantitative methylation-specific PCR (QMSP) in 85 primarily resected renal tumors representing the four major histologic subtypes (52 clear cell (ccRCC), 13 papillary (pRCC), 10 chromophobe (chRCC), and 10 oncocytomas) and 62 paired normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters.

Results

Significant differences in methylation levels among the four subtypes of renal tumors were found for CDH1 (p = 0.0007), PTGS2 (p = 0.002), and RASSF1A (p = 0.0001). CDH1 hypermethylation levels were significantly higher in ccRCC compared to chRCC and oncocytoma (p = 0.00016 and p = 0.0034, respectively), whereas PTGS2 methylation levels were significantly higher in ccRCC compared to pRCC (p = 0.004). RASSF1A methylation levels were significantly higher in pRCC than in normal tissue (p = 0.035). In pRCC, CDH1 and RASSF1A methylation levels were inversely correlated with tumor stage (p = 0.031) and nuclear grade (p = 0.022), respectively.

Conclusion

The major subtypes of renal epithelial neoplasms display differential aberrant CDH1, PTGS2, and RASSF1A promoter methylation levels. This gene panel might contribute to a more accurate discrimination among common renal tumors, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.
Rare clinical experiences for surgical treatment of melanoma with osseous metastases in Taiwan
Authors: Huang Kuo-Yuan , Wang Chrong-Reen , Yang Rong-Sen
Published: July 2007

Background

Malignant melanoma occurs infrequently in Taiwan. Once it has progressed into osseous metastases, the prognosis is poor. There are no reported clinical experiences of surgical management in this area.

Methods

To improve our understanding of the rare clinical experiences, we retrospectively investigated clinical characteristics, radiological findings, treatment modalities, survival outcomes and prognoses of 11 Taiwanese patients with osseous metastasis of melanoma treated surgically at two national medical centers, National Taiwan University Hospital and National Cheng Kung University Hospital from January 1983 to December 2006.

Results

Six patients suffered from acral-lentiginous melanoma. Nine patients sustained multiple osseous metastases and most lesions were osteolytic. Nine patients also had sustained metastases to other organs including liver, lungs, lymph nodes, brain and spleen. Second malignancies including lung cancer, thyroid papillary carcinoma, renal cell carcinoma and cervical cancer co-existed in four patients. The interval from the initial diagnosis of melanoma to the clinical detection of osseous metastases varied from 0–37.8 months (mean 9.75 months). Metastatic melanoma was invariably fatal; the mean survival time from bone metastases to death was 5.67 months.

Conclusion

Due to the high morbidity and poor survival of Taiwanese patients with osseous metastases of melanoma, surgical treatment should be directed towards pain relief and the prevention of skeletal debilitation in order to maintain their quality of life.
A Pragmatic Randomised, Controlled Trial of Intensive Care follow up programmes in improving Longer-term outcomes from critical illness. The PRACTICAL study
Authors: Cuthbertson Brian H , Rattray Janice , Johnston Marie , Wildsmith J Anthony , Wilson Edward , Hernendez Rodolfo , Ramsey Craig , Hull Alastair M , Norrie John , Campbell Marion
Published: July 2007

Background

A number of intensive care (ICU) patients experience significant problems with physical, psychological, and social functioning for some time after discharge from ICU. These problems have implications not just for patients, but impose a continuing financial burden for the National Health Service. To support recovery, a number of hospitals across the UK have developed Intensive Care follow-up clinics. However, there is a lack of evidence base to support these, and this study aims to test the hypothesis that intensive care follow up programmes are effective and cost-effective at improving physical and psychological quality of life in the year after intensive care discharge.

Methods/Design

This is a multi-centre, pragmatic, randomised controlled trial. Patients (n = 270) will be recruited prior to hospital discharge from three intensive care units in the UK, and randomised to one of two groups. The control group will receive standard in-hospital follow-up and the intervention group will participate in an ICU follow-up programme with clinic appointments 2–3 and 9 months after ICU discharge.

The primary outcome measure is Health-related Quality of Life (HRQoL) 12 months after ICU discharge as measured by the Short Form-36. Secondary measures include: HRQoL at six months; Quality-adjusted life years using EQ-5D; posttraumatic psychopathology as measured by Davidson Trauma Scale; and anxiety and depression using the Hospital Anxiety and Depression Scale at both six and twelve months after ICU discharge. Contacts with health services in the twelve months after ICU discharge will be measured as part of the economic analysis.

Discussion

The provision of intensive care follow-up clinics within the UK has developed in an ad hoc manner, is inconsistent in both the number of hospitals offering such a service or in the type of service offered. This study provides the opportunity to evaluate such services both in terms of patient benefit and cost-effectiveness. The results of this study therefore will inform clinical practice and policy with regard to the appropriate development of such services aimed at improving outcomes after intensive care.

Trial Registration

ISRCTN24294750.
Numerical modelling of label-structured cell population growth using CFSE distribution data
Authors: Luzyanina Tatyana , Roose Dirk , Schenkel Tim , Sester Martina , Ehl Stephan , Meyerhans Andreas , Bocharov Gennady
Published: July 2007

Background

The flow cytometry analysis of CFSE-labelled cells is currently one of the most informative experimental techniques for studying cell proliferation in immunology. The quantitative interpretation and understanding of such heterogenous cell population data requires the development of distributed parameter mathematical models and computational techniques for data assimilation.

Methods and Results

The mathematical modelling of label-structured cell population dynamics leads to a hyperbolic partial differential equation in one space variable. The model contains fundamental parameters of cell turnover and label dilution that need to be estimated from the flow cytometry data on the kinetics of the CFSE label distribution. To this end a maximum likelihood approach is used. The Lax-Wendroff method is used to solve the corresponding initial-boundary value problem for the model equation. By fitting two original experimental data sets with the model we show its biological consistency and potential for quantitative characterization of the cell division and death rates, treated as continuous functions of the CFSE expression level.

Conclusion

Once the initial distribution of the proliferating cell population with respect to the CFSE intensity is given, the distributed parameter modelling allows one to work directly with the histograms of the CFSE fluorescence without the need to specify the marker ranges. The label-structured model and the elaborated computational approach establish a quantitative basis for more informative interpretation of the flow cytometry CFSE systems.
An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein
Authors: Butler-Cole Christine , Wagner Mary J , Da Silva Melissa , Brown Gordon D , Burke Robert D , Upton Chris
Published: July 2007

Background

Profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. In this study, a poxviral profilin homolog, ectromelia virus strain Moscow gene 141 (ECTV-PH), was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins.

Results

Profilin-like proteins are encoded by all orthopoxviruses sequenced to date, and share over 90% amino acid (aa) identity. Sequence comparisons show highest similarity to mammalian type 1 profilins; however, a conserved 3 aa deletion in mammalian type 3 and poxviral profilins suggests that these homologs may be more closely related. Structural analysis shows that ECTV-PH can be successfully modelled onto both the profilin 1 crystal structure and profilin 3 homology model, though few of the surface residues thought to be required for binding actin, poly(L-proline), and PIP2 are conserved. Immunoprecipitation and mass spectrometry identified two proteins that interact with ECTV-PH within infected cells: alpha-tropomyosin, a 38 kDa cellular actin-binding protein, and the 84 kDa product of vaccinia virus strain Western Reserve (VACV-WR) 148, which is the truncated VACV counterpart of the orthopoxvirus A-type inclusion (ATI) protein. Western and far-western blots demonstrated that the interaction with alpha-tropomyosin is direct, and immunofluorescence experiments suggest that ECTV-PH and alpha-tropomyosin may colocalize to structures that resemble actin tails and cellular protrusions. Sequence comparisons of the poxviral ATI proteins show that although full-length orthologs are only present in cowpox and ectromelia viruses, an ~ 700 aa truncated ATI protein is conserved in over 90% of sequenced orthopoxviruses. Immunofluorescence studies indicate that ECTV-PH localizes to cytoplasmic inclusion bodies formed by both truncated and full-length versions of the viral ATI protein. Furthermore, colocalization of ECTV-PH and truncated ATI protein to protrusions from the cell surface was observed.

Conclusion

These results suggest a role for ECTV-PH in intracellular transport of viral proteins or intercellular spread of the virus. Broader implications include better understanding of the virus-host relationship and mechanisms by which cells organize and control the actin cytoskeleton.
Prevalence and associated factors of physical fighting among school-going adolescents in Namibia
Authors: Rudatsikira Emmanuel , Siziya Seter , Kazembe Lawrence N , Muula Adamson S
Published: July 2007

Background

Interpersonal physical violence is an important global public health concern that has received limited attention in the developing world. There is in particular a paucity of data regarding physical violence and its socio-demographic correlates among in-school adolescents in Namibia.

Methods

We analysed cross-sectional data from the Namibia Global School-Based Health Survey (GSHS) conducted in 2004. We aimed to estimate the prevalence and socio-demographic correlates of physical fighting within the last 12 months. We obtained frequencies of socio-demographic attributes. We also assessed the association between self-reported history of having engaging in a physical fight and a selected list of independent variables using logistic regression analysis.

Results

Of the 6283 respondents, 50.6% (55.2% males and 46.2% females) reported having been in a physical fight in the past 12 months. Males were more likely to have been in a physical fight than females (OR = 1.71, 95% CI (1.44, 2.05)). Smoking, drinking alcohol, using drugs and bullying victimization were positively associated with fighting (OR = 1.91, 95% CI (1.49, 2.45); OR = 1.48, 95% CI (1.21, 1.81); OR = 1.55, 95% CI (1.22, 1.81); and OR = 3.12, 95% CI (2.62, 3.72), respectively). Parental supervision was negatively associated with physical fighting (OR = 0.82, 95% CI (0.69, 0.98)). Both male and female substance users (cigarette smoking, alcohol and drug use) were more likely to engage in physical fighting than non-substance users (OR = 3.53, 95% CI (2.60, 4.81) for males and OR = 11.01, 95% CI (7.25, 16.73) for females). Parental supervision was negatively associated with physical fighting (OR = 0.85, 95% CI (0.72, 0.99)).

Conclusion

Prevalence of physical fighting within the last 12 months was comparable to estimates obtained in European countries. We also found clustering of problem behaviours or experiences among adolescents who reported having engaged in physical violence in the past 12 months. There is a need to bring adolescent violent behaviour to the fore of the public health agenda in Namibia.
Transcriptional profiling of the model Archaeon Halobacteriumsp. NRC-1: responses to changes in salinity and temperature
Authors: Coker James A , DasSarma Priya , Kumar Jeffrey , Müller Jochen A , DasSarma Shiladitya
Published: July 2007

Background

The model halophile Halobacterium sp. NRC-1 was among the first Archaea to be completely sequenced and many post-genomic tools, including whole genome DNA microarrays are now being applied to its analysis. This extremophile displays tolerance to multiple stresses, including high salinity, extreme (non-mesophilic) temperatures, lack of oxygen, and ultraviolet and ionizing radiation.

Results

In order to study the response of Halobacterium sp. NRC-1 to two common stressors, salinity and temperature, we used whole genome DNA microarrays to assay for changes in gene expression under differential growth conditions. Cultures grown aerobically in rich medium at 42°C were compared to cultures grown at elevated or reduced temperature and high or low salinity. The results obtained were analyzed using a custom database and microarray analysis tools. Growth under salt stress conditions resulted in the modulation of genes coding for many ion transporters, including potassium, phosphate, and iron transporters, as well as some peptide transporters and stress proteins. Growth at cold temperature altered the expression of genes involved in lipid metabolism, buoyant gas vesicles, and cold shock proteins. Heat shock showed induction of several known chaperone genes. The results showed that Halobacterium sp. NRC-1 cells are highly responsive to environmental changes at the level of gene expression.

Conclusion

Transcriptional profiling showed that Halobacterium sp. NRC-1 is highly responsive to its environment and provided insights into some of the specific responses at the level of gene expression. Responses to changes in salt conditions appear to be designed to minimize the loss of essential ionic species and abate possible toxic effects of others, while exposure to temperature extremes elicit responses to promote protein folding and limit factors responsible for growth inhibition. This work lays the foundation for further bioinformatic and genetic studies which will lead to a more comprehensive understanding of the biology of a model halophilic Archaeon.
Short-term prolactin administration causes expressible galactorrhea but does not affect bone turnover: pilot data for a new lactation agent
Authors: Page-Wilson Gabrielle , Smith Patricia C , Welt Corrine K
Published: July 2007

Background

Medications used to augment lactation increase prolactin secretion but can have intolerable side effects. We examined the biological activity of recombinant human prolactin (r-hPRL) as preliminary data for its use to augment lactation.

Methods

Healthy, non-postpartum women (n = 21) with regular menstrual cycles underwent a seven day randomized, double-blind, placebo-controlled trial of r-hPRL. Expressible galactorrhea, markers of bone turnover, calcium homeostasis and gonadal function were measured and side effects recorded.

Results

Prolactin levels increased during r-hPRL administration (20.0 ± 2.8 to 231.7 ± 48.9 μg/L at 6 hours; p < 0.05). Five of nine participants who received r-hPRL developed expressible galactorrhea (p < 0.001). Urinary deoxypyridinoline decreased and bone specific alkaline phosphatase increased in r-hPRL and placebo groups. Menstrual cycle lengths were not altered and side effects were similar between r-hPRL and placebo groups.

Conclusion

In summary, r-hPRL can cause expressible galactorrhea. Seven days of r-hPRL administration does not adversely affect bone turnover or menstrual cyclicity. Thus, r-hPRL may be a viable option for short-term lactation augmentation.

Trial registration

Clinical Trials.gov NCT00438490
Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer
Authors: Uitterhoeve Apollonia LJ , Koolen Mia GJ , van Os Rob M , Koedooder Kees , van de Kar Marlou , Pieters Bradley R , Koning Caro CE
Published: July 2007

Background

Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.

Material

Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).

Treatment

Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m2: 56 pts (standard).

Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m2 d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.

Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.

Results

The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.

At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.

Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.

Conclusion

In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.
Identification of an altered peptide ligand based on the endogenously presented, rheumatoid arthritis-associated, human cartilage glycoprotein-39(263–275) epitope: an MHC anchor variant peptide for immune modulation
Authors: Boots Annemieke MH , Hubers Henk , Kouwijzer Milou , den Hoed-van Zandbrink Leontien , Westrek-Esselink Bernice M , van Doorn Cindy , Stenger Rachel , Bos Ebo S , van Lierop Marie-jose C , Verheijden Gijs F , Timmers Cornelis M , van Staveren Catharina J
Published: July 2007

We sought to identify an altered peptide ligand (APL) based on the endogenously expressed synovial auto-epitope of human cartilage glycoprotein-39 (HC gp-39) for modulation of cognate, HLA-DR4-restricted T cells. For this purpose we employed a panel of well-characterized T cell hybridomas generated from HC gp-39-immunized HLA-DR4 transgenic mice. The hybridomas all respond to the HC gp-39(263–275) epitope when bound to HLA-DR4(B1*0401) but differ in their fine specificities. First, the major histocompatibility complex (MHC) and T-cell receptor (TCR) contact residues were identified by analysis of single site substituted analogue peptides for HLA-DR4 binding and cognate T cell recognition using both T hybridomas and polyclonal T cells from peptide-immunized HLA-DR4 transgenic mice. Analysis of single site substituted APL by cognate T cells led to identification of Phe265 as the dominant MHC anchor. The amino acids Ala268, Ser269, Glu271 and Thr272 constituted the major TCR contact residues, as substitution at these positions did not affect HLA-DR4(B1*0401) binding but abrogated T cell responses. A structural model for visualisation of TCR recognition was derived. Second, a set of non-classical APLs, modified at the MHC key anchor position but with unaltered TCR contacts, was developed. When these APLs were analysed, a partial TCR agonist was identified and found to modulate the HC gp-39(263–275)-specific, pro-inflammatory response in HLA-DR4 transgenic mice. We identified a non-classical APL by modification of the p1 MHC anchor in a synovial auto-epitope. This APL may qualify for rheumatoid arthritis immunotherapy.
Application of the multicellular tumour spheroid model to screen PET tracers for analysis of early response of chemotherapy in breast cancer
Authors: Monazzam Azita , Josephsson Raymond , Blomqvist Carl , Carlsson Jörgen , Långström Bengt , Bergström Mats
Published: July 2007

Introduction

Positron emission tomography (PET) is suggested for early monitoring of treatment response, assuming that effective anticancer treatment induces metabolic changes that precede morphology alterations and changes in growth. The aim of this study was to introduce multicellular tumour spheroids (MTS) to study the effect of anticancer drugs and suggest an appropriate PET tracer for further studies.

Methods

MTS of the breast cancer cell line MCF7 were exposed to doxorubicin, paclitaxel, docetaxel, tamoxifen or imatinib for 7 days for growth pattern studies and for 3 or 5 days for PET tracer studies. The effect on growth was computed using the semi-automated size determination method (SASDM). The effect on the uptake of PET tracers [18F]3'-deoxy-3'-fluorothymidine (FLT), [1-11C]acetate (ACE), [11C]choline (CHO), [11C]methionine (MET), and 2-[18F]fluoro-2-deoxyglucose (FDG) was calculated in form of uptake/viable volume of the MTS at the end of the drug exposures, and finally the uptake was related to effects on growth rate.

Results

The drugs paclitaxel, docetaxel and doxorubicin gave severe growth inhibition, which correlated well with inhibition of the FLT uptake. FLT had, compared with ACE, CHO, MET and FDG, higher sensitivity in monitoring the therapy effects.

Conclusion

SASDM provides an effective, user-friendly, time-saving and accurate method to record the growth pattern of the MTS, and also to calculate the effect of the drug on PET tracer uptake. This study demonstrate the use of MTS and SASDM in combination with PET tracers as a promising approach to probe and select PET tracer for treatment monitoring of anticancer drugs and that can hopefully be applied for optimisation in breast cancer treatment.
Vasopressin improves survival in a porcine model of abdominal vascular injury
Authors: Stadlbauer Karl H , Wagner-Berger Horst G , Krismer Anette C , Voelckel Wolfgang G , Konigsrainer Alfred , Lindner Karl H , Wenzel Volker
Published: July 2007

Introduction

We sought to determine and compare the effects of vasopressin, fluid resuscitation and saline placebo on haemodynamic variables and short-term survival in an abdominal vascular injury model with uncontrolled haemorrhagic shock in pigs.

Methods

During general anaesthesia, a midline laparotomy was performed on 19 domestic pigs, followed by an incision (width about 5 cm and depth 0.5 cm) across the mesenterial shaft. When mean arterial blood pressure was below 20 mmHg, and heart rate had declined progressively, experimental therapy was initiated. At that point, animals were randomly assigned to receive vasopressin (0.4 U/kg; n = 7), fluid resuscitation (25 ml/kg lactated Ringer's and 25 ml/kg 3% gelatine solution; n = 7), or a single injection of saline placebo (n = 5). Vasopressin-treated animals were then given a continuous infusion of 0.08 U/kg per min vasopressin, whereas the remaining two groups received saline placebo at an equal rate of infusion. After 30 min of experimental therapy bleeding was controlled by surgical intervention, and further fluid resuscitation was performed. Thereafter, the animals were observed for an additional hour.

Results

After 68 ± 19 min (mean ± standard deviation) of uncontrolled bleeding, experimental therapy was initiated; at that time total blood loss and mean arterial blood pressure were similar between groups (not significant). Mean arterial blood pressure increased in both vasopressin-treated and fluid-resuscitated animals from about 15 mmHg to about 55 mmHg within 5 min, but afterward it decreased more rapidly in the fluid resuscitation group; mean arterial blood pressure in the placebo group never increased. Seven out of seven vasopressin-treated animals survived, whereas six out of seven fluid-resuscitated and five out of five placebo pigs died before surgical intervention was initiated (P < 0.0001).

Conclusion

Vasopressin, but not fluid resuscitation or saline placebo, ensured short-term survival in this vascular injury model with uncontrolled haemorrhagic shock in sedated pigs.
Global analysis of patterns of gene expression during Drosophilaembryogenesis
Authors: Tomancak Pavel , Berman Benjamin P , Beaton Amy , Weiszmann Richard , Kwan Elaine , Hartenstein Volker , Celniker Susan E , Rubin Gerald M
Published: July 2007

Background

Cell and tissue specific gene expression is a defining feature of embryonic development in multi-cellular organisms. However, the range of gene expression patterns, the extent of the correlation of expression with function, and the classes of genes whose spatial expression are tightly regulated have been unclear due to the lack of an unbiased, genome-wide survey of gene expression patterns.

Results

We determined and documented embryonic expression patterns for 6,003 (44%) of the 13,659 protein-coding genes identified in the Drosophila melanogaster genome with over 70,000 images and controlled vocabulary annotations. Individual expression patterns are extraordinarily diverse, but by supplementing qualitative in situ hybridization data with quantitative microarray time-course data using a hybrid clustering strategy, we identify groups of genes with similar expression. Of 4,496 genes with detectable expression in the embryo, 2,549 (57%) fall into 10 clusters representing broad expression patterns. The remaining 1,947 (43%) genes fall into 29 clusters representing restricted expression, 20% patterned as early as blastoderm, with the majority restricted to differentiated cell types, such as epithelia, nervous system, or muscle. We investigate the relationship between expression clusters and known molecular and cellular-physiological functions.

Conclusion

Nearly 60% of the genes with detectable expression exhibit broad patterns reflecting quantitative rather than qualitative differences between tissues. The other 40% show tissue-restricted expression; the expression patterns of over 1,500 of these genes are documented here for the first time. Within each of these categories, we identified clusters of genes associated with particular cellular and developmental functions.
Combined analysis reveals a core set of cycling genes
Authors: Lu Yong , Mahony Shaun , Benos Panayiotis V , Rosenfeld Roni , Simon Itamar , Breeden Linda L , Bar-Joseph Ziv
Published: July 2007

Background

Global transcript levels throughout the cell cycle have been characterized using microarrays in several species. Early analysis of these experiments focused on individual species. More recently, a number of studies have concluded that a surprisingly small number of genes conserved in two or more species are periodically transcribed in these species. Combining and comparing data from multiple species is challenging because of noise in expression data, the different synchronization and scoring methods used, and the need to determine an accurate set of homologs.

Results

To solve these problems, we developed and applied a new algorithm to analyze expression data from multiple species simultaneously. Unlike previous studies, we find that more than 20% of cycling genes in budding yeast have cycling homologs in fission yeast and 5% to 7% of cycling genes in each of four species have cycling homologs in all other species. These conserved cycling genes display much stronger cell cycle characteristics in several complementary high throughput datasets.

Essentiality analysis for yeast and human genes confirms these findings. Motif analysis indicates conservation in the corresponding regulatory mechanisms. Gene Ontology analysis and analysis of the genes in the conserved sets sheds light on the evolution of specific subfunctions within the cell cycle.

Conclusion

Our results indicate that the conservation in cyclic expression patterns is much greater than was previously thought. These genes are highly enriched for most cell cycle categories, and a large percentage of them are essential, supporting our claim that cross-species analysis can identify the core set of cycling genes.
Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial
Authors: Suter Thomas M. , Procter Marion , van Veldhuisen Dirk J. , Muscholl Michael , Bergh Jonas , Carlomagno Chiara , Perren Timothy , Passalacqua Rodolfo , Bighin Claudia , Klijn Jan G.M. , Ageev Fail T. , Hitre Erika , Groetz Juergen , Iwata Hiroji , Knap Malgorzata , Gnant Michael , Muehlbauer Susanne , Spence Alison , Gelber Richard D. , Piccart-Gebhart Martine J.
Published: July 2007

Purpose

The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy.

Patients and Methods

The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction.

Results

Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index.

Conclusion

Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.
A conserved role for kinesin-5 in plant mitosis
Authors: Bannigan Alex , Scheible Wolf-Rüdiger , Lukowitz Wolfgang , Fagerstrom Carey , Wadsworth Patricia , Somerville Chris , Baskin Tobias I.
Published: July 2007

The mitotic spindle of vascular plants is assembled and maintained by processes that remain poorly explored at a molecular level. Here, we report that AtKRP125c, one of four kinesin-5 motor proteins in arabidopsis, decorates microtubules throughout the cell cycle and appears to function in both interphase and mitosis. In a temperature-sensitive mutant, interphase cortical microtubules are disorganized at the restrictive temperature and mitotic spindles are massively disrupted, consistent with a defect in the stabilization of anti-parallel microtubules in the spindle midzone, as previously described in kinesin-5 mutants from animals and yeast. AtKRP125c introduced into mammalian epithelial cells by transfection decorates microtubules throughout the cell cycle but is unable to complement the loss of the endogenous kinesin-5 motor (Eg5). These results are among the first reports of any motor with a major role in anastral spindle structure in plants and demonstrate that the conservation of kinesin-5 motor function throughout eukaryotes extends to vascular plants.
ZRP-1 controls Rho GTPase-mediated actin reorganization by localizing at cell-matrix and cell-cell adhesions
Authors: Bai Chen-Yu , Ohsugi Miho , Abe Yoshinori , Yamamoto Tadashi
Published: July 2007

Focal adhesion protein ZRP-1/TRIP6 has been implicated in actin reorganization and cell motility. The role of ZRP-1, however, remained obscure because previously reported data are often conflicting one another. In the present study, we examined roles of ZRP-1 in HeLa cells. ZRP-1 is localized to the cell-cell contact sites as well as to cell-matrix contact sites in HeLa cells. RNA-interference-mediated depletion of ZRP-1 from HeLa cells revealed that ZRP-1 is essential not only for the formation of stress fibers and assembly of mature focal adhesions, but also for the actin reorganization at cell-cell contact sites and for correct cell-cell adhesion and, thus, for collective cell migration. Impairment of focal adhesions and stress fibers caused by ZRP-1 depletion has been associated with reduced tyrosine phosphorylation of FAK. However, maturation of focal adhesions could not be recovered by expression of active FAK. Interestingly, stress fibers in ZRP-1-depleted cells were ameliorated by exogenous expression of RhoA. We also found that total Rac1 activity is elevated in ZRP-1-depleted cells, resulting in abnormal burst of actin polymerization and dynamic membrane protrusions. Taken together, we conclude that that ZRP-1 plays a crucial role in coupling the cell-matrix/cell-cell-contact signals with Rho GTPase-mediated actin remodeling by localizing at cell-matrix and cell-cell contact sites.
Recovery of the germfree status of rats and mice monocontaminated with Aspergillus species
Authors: Nicoli J. R. , Silva M. E. , Moraes-Santos T. , Vieira E. C.
Published: July 2007

The decontamination of monocontaminated rats and mice is reported in this paper. The monocontaminant micro-organism was an Aspergillus species, and the decontamination was applied with success using nystatin and phenol solutions for animals and materials respectively.
Inherited seborrheic dermatitis - a new mutant in mice
Authors: Höger H. , Gialamas J. , Adamiker D.
Published: July 2007

A new mutation, affecting skin and hair, occurred in an expansion colony of Him:OF1 mice. Test crosses showed that a single autosomal recessive gene was responsible for this trait. Homozygotes have sparse greasy fur and lower viability and fertility than normal littermates. Histological observations showed hypertrophy of sebaceous glands, hyperkeratosis, parakeratosis, acanthosis and signs of inflammation. The disease was named 'inherited seborrheic dermatitis' and the gene name seb is proposed.
Rationalization and computerization of the drug supply to an animal unit
Authors: Wootton R. , Henderson F.
Published: July 2007

Drug stocks in an animal unit were rationalized by discarding out-of-date or unwanted items and drawing up an approved stock list. A computerized system of stock control which enables a regular and accurate inventory of pharmaceuticals to be made was then established. In addition, the paperwork required for re-ordering drugs is produced automatically.

Pharmaceuticals to a total value of £1650 were discarded during the rationalization phase. The value of drugs stocked in the animal unit then stabilized at about one-third of previous levels. In the first 6 months of operation of the new system drug expenditure fell by about 40% in comparison with the same period 1 year previously.

The drug stock control system has proved economical to operate and accurate, and can be run by persons without computer expertise. Valuable savings in both cost and labour have resulted. Effective management of drug expenditure by the animal unit is now possible.
Haematology of Mystromys albicaudatus
Authors: Cantrell C. , Padovan D.
Published: July 2007

Haemograms were determined for 90 Mystromys, 3-24 months of age, to establish normal values and to evaluate the influence of age and gender. Males over 6 months of age had higher red blood cell counts, packed cell volumes and haemoglobin levels than females of the same age. The haemograms of females 3-5 months old resembled those of males. Age and gender did not cause detectable differences in leucocyte numbers in animals over 6 months old.
Risk Ownership in Contract Manufacturing
Authors: Ülkü Sezer , Toktay L. Beril , Yücesan Enver
Published: July 2007

We consider a supply chain where a contract manufacturer (CM) serves a number of original equipment manufacturers (OEMs). Investment into productive resources is made before demand realization, hence the supply chain faces the risk of under- or overinvestment. The CM and OEMs differ in their forecast accuracy and in their resource pooling capabilities, leading to a disparity in their ability to minimize costs due to demand uncertainty. We consider two scenarios in which this risk is borne by the OEM and CM, respectively. We determine which party should bear the risk so that maximum supply chain profits are achieved. We investigate the effectiveness of premium-based schemes in inducing the best party to bear the risk, and conclude that they function well despite information asymmetry when double marginalization is not very high.
Two-Wholesale-Price Contracts: Push, Pull, and Advance-Purchase Discount Contracts
Authors: Dong Lingxiu , Zhu Kaijie
Published: July 2007

The allocation of inventory ownership affects the inventory availability in a supply chain, which in turn determines the supply chain performance. In this paper, we consider a supplier-retailer supply chain in which the supplier starts production well in advance of the selling season, and the retailer is offered two ordering opportunities at different points in time. An early order is allowed before the supplier’s production decision, and a late order is allowed after the completion of production and after observing the demand. When the two wholesale prices change, we illustrate how the inventory decision rights and ownership are shifted and/or shared between the two firms, resulting in push, pull, or advance-purchase discount contracts. We then characterize the complete set of Pareto-dominant contracts for any given two-wholesale-price contract. We find that Pareto improvement can be achieved when inventory ownership is shifted from individual to shared and sometimes vice versa. In the latter case, push contracts not only are more likely to offer Pareto improvement, but also can achieve higher supply chain efficiency than pull contracts. We also identify conditions that enable Pareto improvement by introducing a new ordering opportunity to firms that had been bound by a single ordering opportunity without renegotiating the existing wholesale price, and we demonstrate through a numerical study that the adoption of the new ordering opportunity can significantly improve supply chain efficiency. We show that such Pareto improvement is more likely to happen when demand is more volatile.
Decentralization Cost in Scheduling: A Game-Theoretic Approach
Authors: Bukchin Yossi , Hanany Eran
Published: July 2007

Decentralized organizations may incur inefficiencies because of scheduling issues associated with competition among decision makers (DMs) for limited resources. We analyze the decentralization cost (DC), i.e., the ratio between the Nash equilibrium cost and the cost attained at the centralized optimum. Solution properties of a dispatching-sequencing model are derived and subsequently used to develop bounds on the DC for an arbitrary number of jobs and DMs. A scheduling-based coordinating mechanism is then provided, ensuring that the centralized solution is obtained at equilibrium.
Coordination Mechanisms for Supply Chains Under Price and Service Competition
Authors: Bernstein Fernando , Federgruen Awi
Published: July 2007

In a decentralized supply chain, with long-term competition between independent retailers facing random demands and buying from a common supplier, how should wholesale and retail prices be specified in an attempt to maximize supply-chain-wide profits? We show what types of coordination mechanisms allow the decentralized supply chain to generate aggregate expected profits equal to the optimal profits in a centralized system, and how the parameters of these (perfect) coordination schemes can be determined. We assume that the retailers face stochastic demand functions that may depend on all of the firms’ prices as well as a measure of their service levels, e.g., the steady-state availability of the products. We systematically compare the coordination mechanisms when retailers compete only in terms of their prices, and when they engage in simultaneous price and service competition.
Characterization of Community-Acquired Staphylococcus aureus Infections in Children
Authors: Johnson Peter N , Rapp Robert P , Nelson Christopher T , Butler JS , Overman Sue , Kuhn Robert J
Published: July 2007

Background:

Limited data exist concerning characteristics of community-acquired Staphylococcus aureus infections (CA-SAI) in central and eastern Kentucky.

Objective:

To describe the incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from January 1, 2004 through December 31, 2005, compare the number of CA-MRSA infections between years, and contrast treatment interventions and antibiotic susceptibility patterns of CA-SAI.

Methods:

A concurrent and retrospective study was conducted in 125 patients less than 18 years of age with CA-SAI admitted to the hospital/clinic based on criteria from the Centers for Disease Control and Prevention. Data on demographics, length of stay, antibiotic therapy, and antibiotic susceptibilities were collected.

Results:

Seventy patients were included for analysis (CA-MRSA, n = 51; community-acquired methicillin-susceptible S. aureus [CA-MSSA], n = 19). No statistically significant differences were noted between the number of CA-MRSA infections and the total CA-SAI (9/15 in 2004 vs 42/55 in 2005; p = 0.15). Approximately 75% of patients with CA-SAI were admitted to the hospital with no significant difference in length of stay. Ninety percent of CA-SAI were skin and soft tissue infections. There was a significant difference between groups with cutaneous abscesses (CA-MRSA, n = 37 vs CA-MSSA, n = 6; p = 0.002). Greater than 95% of all isolates were susceptible to vancomycin and trimethoprim/sulfamethoxazole. Half of CA-MRSA patients received inappropriate antibiotic therapy with β-lactam antibiotics or clindamycin without confirmatory disk diffusion test. Twenty-five (49%) patients with CA-MRSA received surgical debridement (S/D) and/or incision and drainage (I/D) with concomitant antibiotic therapy. Four patients with CA-MRSA were rehospitalized for subsequent infections; all 4 received appropriate antibiotic therapy.

Conclusions:

A noticeable increase in CA-MRSA infections with cutaneous abscess between 2004 and 2005 was noted. In patients receiving inappropriate antibiotic therapy, treatment success was attributed to concomitant S/D and I/D. Further analysis should focus on the impact of antibiotic therapy alone or in combination with S/D and I/D on the incidence of subsequent CA-MRSA infections.
Effects of Temperatures on Mortar Quantified by Surface Color Changes
Authors: Lin Deng-Fong , Luo Huan-Lin , Lee Jen-Rong
Published: July 2007

The purpose of this study is to explore the potential use of a digital image analysis method to quantify fire-related damages. Temperature regimes, durations of firing temperatures, and changes to color components are investigated. This research involves testing mortar specimens under different elevated temperatures, using a digital camera to capture images of the tested specimens, and applying the “image color intensity analyzer” to the images in order to obtain different intensities of color components in both the RGB and hue-saturation-intensity (HSI) color spaces. The study demonstrates that, as a result of elevated temperatures, red is the most dominant component in the color change, followed by green and blue. Parameters affecting the color change include maximum temperatures and duration of firing. This study also shows that hue and saturation correlate very well with temperatures, which implies that the HSI color space can be applied to study the behavior of fire-damaged concrete.
Nondestructive Testing for the Integrity Evaluation of Erosive and Abrasive Boundary Layers
Authors: Meged Y.
Published: July 2007

The test surfaces of erosion and abrasion specimens are prepared by electrical discharge machining, grinding, turning, and polishing. These machining operations form an affected material zone (AMZ), with mechanical and metallurgical alterations. As a result, the erosion properties of the AMZ vary from those of the base material, thereby affecting the cumulative mass loss-time curve. Erosion and abrasion standards loosely specify the preparation method of the specimens’ test surface and relate to the AMZ integrity in a qualitative way. Consequently, there is a large variation in the AMZ thickness and properties, and in the mass loss-time pattern. There are several nondestructive test (NDT) methods for determining subsurface integrity. These methods enable one to determine material isotropy, and hardness, residual stress, and grain size gradients in the subsurface layer of many materials. Applying NDT methods in inspection of erosion and abrasion specimens will enable one to conduct better controlled erosion and abrasion tests with high precision results.
A Very Early Strength Concrete for Highway Construction
Authors: Punurai Sun , Punurai Wonsiri , Hsu Cheng-Tzu Thomas
Published: July 2007

The purpose of this research study was to develop an improved very early strength (VES) concrete mix for highway construction. More than 50 concrete mixes were evaluated for strength, shrinkage, and curing rate (maturity), eventually leading to the development of an optimized VES concrete mix with improved performance characteristics. The new mix, which is detailed in the paper, can gain strength more reliably than the former standard New Jersey Department of Transportation (NJDOT) VES mix, reaching a flexural strength of 350 psi (2.4 MPa) in less than 6.5 h. The improved mix also exhibited 79 to 93 % less shrinkage. The study found that maintaining an initial mix temperature of 28°C (82°F) is crucial to attain target strengths.
Bilateral Spike-Triggered Average Effects in Arm and Shoulder Muscles from the Monkey Pontomedullary Reticular Formation
Authors: Davidson Adam G. , Schieber Marc H. , Buford John A.
Published: July 2007

Pontomedullary reticular formation (PMRF) neurons (309) were recorded simultaneously with electromyographic activity from arm and shoulder muscles in four monkeys performing arm-reaching tasks. Spike-triggered averages (SpikeTAs) were compiled for 292 neurons (3836 neuron–muscle pairs). Fourteen PMRF neurons located in a region ventral to the abducens nucleus produced 42 significant SpikeTA effects in arm and shoulder muscles. Of these 14 PMRF neurons, nine produced SpikeTA effects bilaterally. Overall, PMRF neurons facilitated ipsilateral flexors and contralateral extensors, while suppressing ipsilateral extensors and contralateral flexors. Spike- and stimulus-triggered averaging effects obtained from the same recording site were similar. These findings indicate that single PMRF neurons can directly influence movements of both upper limbs.