bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in neurogenically mediated contractile responses of urinary bladder in rats with diabetes
Authors: Liu Guiming , Daneshgari Firouz
Published: February 2005

Diabetic bladder dysfunction (DBD) is among the most common and bothersome complications of diabetes mellitus. Autonomic neuropathy has been counted as the cause of DBD. In the present study, we compared the alterations in the neurogenically mediated contractile responses of urinary bladder in rats with streptozocin-induced diabetes, 5% sucrose-induced diuresis, and age-matched controls. Male Sprague-Dawley rats were divided into three groups: 9-wk diabetic rats, diuretic rats, and age-matched controls. Micturition and morphometric characteristics were evaluated using metabolic cage and gross examination of the bladder. Bladder detrusor muscle strips were exposed to either periodic electrical field stimulation (EFS) or to EFS in the presence of atropine, α,β-methylene adrenasine 5′-triphosphate, or tetrodotoxin. The proportions of cholinergic, purinergic, and residual nonadrenergic-noncholinergic (NANC) components of contractile response were compared among the three groups of animals. Diabetes caused a significant reduction of body weight compared with diuresis and controls, although the bladders of diabetic and diuretic rats weighed more than the controls. Both diabetes and diuresis caused significant increase in fluid intake, urine output, and bladder size. Diabetes and diuresis caused similarly increased response to EFS and reduced response to cholinergic component compared with controls. However, the purinergic response was significantly smaller in diuretic bladder strips compared with controls but not in diabetic rats. A residual NANC of unknown origin increased significantly but differently in diabetics and diuretics compared with controls. In conclusion, neurogenically mediated bladder contraction is altered in the diabetic rat. Diabetic-related changes do not parallel diuretic-induced changes, indicating that the pathogenesis of DBD needs further exploration.
Transforming Growth Factor-β Receptor Mutations and Pulmonary Arterial Hypertension in Childhood
Authors: Harrison Rachel E. , Berger Rolf , Haworth Sheila G. , Tulloh Robert , Mache Christoph J. , Morrell Nicholas W. , Aldred Micheala A. , Trembath Richard C.
Published: February 2005

Background—

Pulmonary arterial hypertension (PAH) is a potentially fatal vasculopathy that can develop at any age. Adult-onset disease has previously been associated with mutations in
BMPR2
and
ALK-1
. Presentation in early life may be associated with congenital heart disease but frequently is idiopathic.

Methods and Results—

We performed mutation analysis in genes encoding receptor members of the transforming growth factor-β cell-signaling pathway in 18 children (age at presentation <6 years) with PAH. Sixteen children were initially diagnosed with idiopathic PAH and 2 with PAH in association with congenital heart defects. Germ-line mutations were observed in 4 patients (22%) (age at disease onset, 1 month to 6 years), all of whom presented with idiopathic PAH. The
BMPR2
mutations (n=2, 11%) included a partial gene deletion and a nonsense mutation, both arising de novo in the proband. Importantly, a missense mutation of
ALK-1
and a branch-site mutation of
endoglin
were also detected. Presenting clinical features or progression of pulmonary hypertension did not distinguish between patients with mutations in the different genes or between those without mutations.

Conclusions—

The cause of PAH presenting in childhood is heterogeneous in nature, with genetic defects of transforming growth factor-β receptors playing a critical role.
Fibroblasts Can Be Genetically Modified to Produce Excitable Cells Capable of Electrical Coupling
Authors: Kizana Eddy , Ginn Samantha L. , Allen David G. , Ross David L. , Alexander Ian E.
Published: February 2005

Background—

Cardiac conduction occurs in an electrical syncytium of excitable cells connected by gap junctions. Disruption of these electrophysiological properties causes conduction slowing or block. Depending on the location of affected cells within the heart, this has the potential to result in clinical syndromes such as atrioventricular block. With a view to developing gene therapy strategies for repairing cardiac conduction defects, we sought to establish whether the phenotype of fibroblasts can be modified by gene transfer to produce cells capable of electrical excitation and coupling.

Methods and Results—

High-titer lentiviral vectors encoding MyoD, a myogenic transcription factor, and connexin43, a gap junction protein, were produced by established methods. Human dermal fibroblasts (HDFs) were efficiently (>80%) transduced at a multiplicity of infection of 50. HDFs transduced with the MyoD-encoding vector underwent myogenic conversion, as evidenced by myotube formation and detection of muscle-specific proteins. Importantly, calcium transients indicative of membrane excitability were observed in MyoD-induced myotubes after loading with a calcium-sensitive dye and electrical stimulation. Transients from adjacent myotubes displayed different excitation thresholds, indicating an absence of coupling between cells, consistent with skeletal muscle biology. In contrast, simultaneous transduction of HDFs with MyoD and connexin43-encoding vectors resulted in the appearance of transients in adjacent myotubes with identical thresholds, indicative of electrical coupling. Notably, dye transfer studies confirmed gap junctional intercellular communication.

Conclusions—

Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling. These observations strengthen the prospect of developing gene-based strategies for repairing cardiac conduction defects.
Tissue-Engineered Human Vascular Media With a Functional Endothelin System
Authors: Laflamme Karina , Roberge Charles J. , Labonté Julie , Pouliot Stéphanie , D’Orléans-Juste Pédro , Auger François A. , Germain Lucie
Published: February 2005

Background—

Cardiovascular diseases remain a major cause of death and disability in the Western world. Among the various approaches adopted to counteract the morbidity associated with these diseases, surgical procedures and cardiac and vascular xenotransplantations or allotransplantations are routinely performed. The suitable vascular graft would be as close as possible to the native and healthy vessel composed exclusively of human components provided by the patient and would adapt to the donor’s hemodynamics. We have developed such a tissue-engineered human blood vessel reconstructed with human cells. Because endothelin is the most potent vasopressor known to date, we were interested in investigating the functionality of the endothelinergic system in our reconstructed human blood vessel.

Methods and Results—

Vasoconstriction studies were performed with nonselective and selective agonists and antagonists to demonstrate that ET
A
receptors were present and functional in tissue-engineered human vascular media constructed with the self-assembly method. Reverse-transcriptase polymerase chain reaction studies demonstrated that mRNA of the ET
A
but not the ET
B
receptor was present in these human tissue–engineered blood vessels. Furthermore, we demonstrated that the endothelin-converting enzyme, the main enzyme responsible for the formation of the biologically active endothelin peptides, was present and functional in these same bioengineered vascular media.

Conclusions—

Our results suggest that the media component of our tissue-engineered blood vessel has the potential of controlling vascular resistance via the presence of functional endothelin ET
A
receptors and endothelin-converting enzyme.
A school programme contributes to the environmental knowledge of blind people
Authors: Papadopoulos Konstantinos S.
Published: January 2005

The knowledge visually-impaired people have of the space around them is a subject of great interest to the scientific community. This article describes a school programme and the effect it had on the environmental knowledge of the school where it was carried out. A group of sighted students chose as a project to construct, with the author’s help, a tactile-visual model of the area around the school. The model was constructed entirely by the students in the group. This was followed by a study to investigate the environmental knowledge of the area represented in the model of, primarily, the visually-impaired students and, secondarily, of the sighted students. The first stage involved an investigation of the area before a reading of the model, and the second stage involved a repetition of the investigation after the students had studied the model. The article presents an analysis and comparison of the results of the two stages, together with a number of conclusions concerning the environmental knowledge of visually-impaired people.
Construction of Higher-Order Accurate Time-Step Integration Algorithms by Equal-Order Polynomial Projection
Authors: Fung T. C.
Published: January 2005

This paper presents a new framework to construct higher-order accurate time-step integration algorithms based on weakly enforcing the differential/integral relation. The dependent variable and its time derivatives are assumed to be polynomials of equal order. A differential equation is then transformed into an algebraic equation directly. The main issue is how to approximate the integral of a polynomial by another polynomial of the same degree. Various methods to determine the optimal representation (or projection) are considered. It is shown that to reproduce numerical results equivalent to the Padé or generalized Padé approximations, the coefficients of the optimal polynomial representation are related to the weighting parameters derived previously for time-step integration algorithms with predetermined coefficients. A special feature for the present formulation is that the same procedure can be used to solve first-, second-, and even higher-order non-homogeneous initial value problems in a unified manner. The resultant algorithms are higher-order accurate and unconditionally A-stable with controllable numerical dissipation. It is also shown that for the numerical results to maintain higher-order accuracy at the end of a time interval, the higher-order terms in the excitation have to be projected as polynomials of lower degree within the present framework as well. Numerical examples are given to illustrate the validity of the present formulations.
Active Control of Linear Time-Varying Structures by Confinement of Vibrations
Authors: Choura S. , Yigit A. S.
Published: January 2005

We propose a control strategy for the simultaneous suppression and confinement of vibrations in linear time-varying structures. The proposed controller has time-varying gains and can also be used for linear time-invariant systems. The key idea is to alter the original modes by appropriate feedback forces to allow parts of the structure reach their steady states at faster rates. It is demonstrated that the convergence of these parts to zero is improved at the expense of slowing down the settling of the remaining parts to their steady states. The proposed control strategy can be applied for the rapid removal of vibration energy in sensitive parts of a flexible structure for safety or performance reasons. The stability of the closed-loop system is proven through a Lyapunov approach. An illustrative example of a five-link manipulator with a periodic follower force is given to demonstrate the effectiveness of the method for time-varying as well as time-invariant systems.
Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms
Authors: Song Man-Gen , Gao Shen-Meng , Du Ke-Ming , Xu Min , Yu Yun , Zhou Yu-Hong , Wang Qiong , Chen Zhu , Zhu Yuan-Shan , Chen Guo-Qiang
Published: January 2005

As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. In the present study, we report that NSC606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (AML) cells NB4 and U937 and inhibits the proliferation without cell death in breakpoint cluster region–Abelson murine leukemia (bcr-abl) kinase-carrying leukemic K562 cells. For apoptosis induction or growth arrest, nanomolar concentrations of NSC606985 are sufficient. At such low concentrations, this agent also significantly inhibits the clonogenic activity of hematopoietic progenitors from patients with AML. For apoptosis induction, NSC606985 rapidly induces the proteolytic activation of protein kinase Cδ (PKCδ) with loss of mitochondrial transmembrane potential (ΔΨm) and caspase-3 activation. Cotreatment with rottlerin, a PKCδ-specific inhibitor, completely blocks NSC606985-induced mitochondrial ΔΨm loss and caspase-3 activation, while the inhibition of caspase-3 by z-DEVD-fluoromethyl ketone (Z-DEVD-fmk) only partially attenuates PKCδ activation and apoptosis. These data indicate that NSC606985-induced PKCδ activation is an early event upstream to mitochondrial ΔΨm loss and caspase-3 activation, while activated caspase-3 has an amplifying effect on PKCδ proteolysis. In addition, NSC606985-induced apoptosis by PKCδ also involves caspase-3–independent mechanisms. Taken together, our results suggest that NSC606985 is a potential agent for the treatment of AML.
Evaluating concentration estimation errors in ELISA microarray experiments
Authors: Daly Don Simone , White Amanda M , Varnum Susan M , Anderson Kevin K , Zangar Richard C
Published: January 2005

Background

Enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay to estimate a protein's concentration in a sample. Deploying ELISA in a microarray format permits simultaneous estimation of the concentrations of numerous proteins in a small sample. These estimates, however, are uncertain due to processing error and biological variability. Evaluating estimation error is critical to interpreting biological significance and improving the ELISA microarray process. Estimation error evaluation must be automated to realize a reliable high-throughput ELISA microarray system.

In this paper, we present a statistical method based on propagation of error to evaluate concentration estimation errors in the ELISA microarray process. Although propagation of error is central to this method and the focus of this paper, it is most effective only when comparable data are available. Therefore, we briefly discuss the roles of experimental design, data screening, normalization, and statistical diagnostics when evaluating ELISA microarray concentration estimation errors.

Results

We use an ELISA microarray investigation of breast cancer biomarkers to illustrate the evaluation of concentration estimation errors. The illustration begins with a description of the design and resulting data, followed by a brief discussion of data screening and normalization. In our illustration, we fit a standard curve to the screened and normalized data, review the modeling diagnostics, and apply propagation of error.

We summarize the results with a simple, three-panel diagnostic visualization featuring a scatterplot of the standard data with logistic standard curve and 95% confidence intervals, an annotated histogram of sample measurements, and a plot of the 95% concentration coefficient of variation, or relative error, as a function of concentration.

Conclusions

This statistical method should be of value in the rapid evaluation and quality control of high-throughput ELISA microarray analyses. Applying propagation of error to a variety of ELISA microarray concentration estimation models is straightforward. Displaying the results in the three-panel layout succinctly summarizes both the standard and sample data while providing an informative critique of applicability of the fitted model, the uncertainty in concentration estimates, and the quality of both the experiment and the ELISA microarray process.
Influence of intense multidisciplinary follow-up and orlistat on weight reduction in a primary care setting
Authors: Feigenbaum Amiel , Pasternak Shmuel , Zusk Efrat , Sarid Miri , Vinker Shlomo
Published: February 2005

Background

Obesity is the most common health problem in developed countries. Recently, several physicians' organizations have issued recommendations for treating obesity to family physicians, including instructions in nutrition, physical activity and medications. The aim of this study was to examine if effective weight-reducing treatment can be given by a family physician. It compares regular treatment with intensive treatment that include close follow-up and orlistat treatment.

Methods

The study was conducted in three primary care clinics. 225 patients were divided into three groups according to their choice. Group A received a personal diet with fortnightly meetings with the family physician and dietitian and orlistat treatment. Group B received a general diet, monthly meetings with the family physician only and orlistat treatment. Group C received a personal diet, monthly meetings with the dietitian only and no drug treatment. The primary endpoint was reduction of at least 5% of the initial weight during the study period.

Results

A greater percentage of patients in group A achieved their weight reduction goals than in other groups (51%, 13% and 9% in groups A, B and C, respectively, p < 0.001). There was a significant reduction in triglycerides in all groups, a significant reduction of low density lipids (LDL) in groups A and B and no significant difference in high density lipids (HDL) in any group.

Conclusions

Significant weight reduction was obtained in a family physician setting. Further research is needed to evaluate if, by providing the family physician with the proper tools, similar success can be achieved in more clinics.
Comparing the clinical effectiveness of different new-born hearing screening strategies. A decision analysis
Authors: Grill Eva , Hessel Franz , Siebert Uwe , Schnell-Inderst Petra , Kunze Silke , Nickisch Andreas , Wasem Jürgen
Published: February 2005

Background

Children with congenital hearing impairment benefit from early detection and treatment. At present, no model exists which explicitly quantifies the effectiveness of universal newborn hearing screening (UNHS) versus other programme alternatives in terms of early diagnosis. It has yet to be considered whether early diagnosis (within the first few months) of hearing impairment is of importance with regard to the further development of the child compared with effects resulting from a later diagnosis. The objective was to systematically compare two screening strategies for the early detection of new-born hearing disorders, UNHS and risk factor screening, with no systematic screening regarding their influence on early diagnosis.

Methods

Design: Clinical effectiveness analysis using a Markov Model.

Data Sources: Systematic literature review, empirical data survey, and expert opinion. Target Population: All newborn babies.

Time scale: 6, 12 and 120 months.

Perspective: Health care system.

Compared Strategies: UNHS, Risk factor screening (RS), no systematic screening (NS). Outcome Measures: Quality weighted detected child months (QCM).

Results

UNHS detected 644 QCM up until the age of 6 months (72,2%). RS detected 393 child months (44,1%) and no systematic screening 152 child months (17,0%). UNHS detected 74,3% and 86,7% weighted child months at 12 and 120 months, RS 48,4% and 73,3%, NS 23,7% and 60,6%. At the age of 6 months UNHS identified approximately 75% of all children born with hearing impairment, RS 50% and NS 25%. At the time of screening UNHS marked 10% of screened healthy children for further testing (false positives), RS 2%. UNHS demonstrated higher effectiveness even under a wide range of relevant parameters. The model was insensitive to test parameters within the assumed range but results varied along the prevalence of hearing impairment.

Conclusion

We have shown that UNHS is able to detect hearing impairment at an earlier age and more accurately than selective RS. Further research should be carried out to establish the effects of hearing loss on the quality of life of an individual, its influence on school performance and career achievement and the differences made by early fitting of a hearing aid on these factors.
The Darlington and Northallerton Long Term Asthma Study: pulmonary function
Authors: Connolly C Kevin , Prescott Robin J
Published: February 2005

Background

The Darlington and Northallerton Asthma Study is an observational cohort study started in 1983. At that time little was published about long term outcome in asthma and the contribution of change in reversible disease or airway remodelling to any excess deterioration in function. The study design included regular review of overall and fixed function lung. We report the trends over fifteen years.

Methods

All asthmatics attending secondary care in 1983, 1988 and 1993 were recruited. Pulmonary function was recorded at attendance and potential best function estimated according to protocol. Rate of decline was calculated over each 5-year period and by linear regression analysis in those seen every time. The influence of potential explanatory variables on this decline was explored.

Results

1724 satisfactory 5-year measurements were obtained in 912 subjects and in 200 subjects on all occasions. Overall rate of decline (ml/year (95%CI)) calculated from 5-year periods was FEV1 ♂41.0 (34.7–47.3), ♀28.9 (23.2–34.6) and best FVC ♂63.1 (55.1–71.2)ml/year, ♀45.8 (40.0–51.6).The principal association was with age. A dominant cubic factor suggested fluctuations in the rate of change in middle life with less rapid decline in youth and more rapid decline in the elderly. Rapid decline was possibly associated with short duration. Treatment step did not predict rate of deterioration.

Conclusions

Function declined non-linearly and more rapidly than predicted from normal subjects. It reports for the first time a cubic relationship between age and pulmonary function. This should be taken into account when interpreting other articles reporting change in function over time.
clc is co-expressed with clf or cntfr in developing mouse muscles
Authors: de Bovis Béatrice , Derouet Damien , Gauchat Jean-François , Elson Greg , Gascan Hugues , deLapeyrière Odile
Published: February 2005

Background

The ciliary neurotrophic factor (CNTF) receptor is composed of two signalling receptor chains, gp130 and the leukaemia inhibitory factor receptor, associated with a non-signalling CNTF binding receptor α component (CNTFR). This tripartite receptor has been shown to play important roles in the development of motor neurons, but the identity of the relevant ligand(s) is still not clearly established. Recently, we have identified two new ligands for the CNTF receptor complex. These are heterodimeric cytokines composed of cardiotrophin-like cytokine (CLC) associated either with the soluble receptor subunit cytokine-like factor-1 (CLF) or the soluble form of the binding receptor itself (sCNTFR).

Results

Here we show that, during development, clc is expressed in lung, kidney, vibrissae, tooth, epithelia and muscles during the period of development corresponding to when motoneuron loss is observed in mice lacking a functional CNTF receptor. In addition, we demonstrate that it is co-expressed at the single cell level with clf and cntfr, supporting the idea that CLC might be co-secreted with either CLF or sCNTFR.

Conclusion

This expression pattern is in favor of CLC, associated either with CLF or sCNTFR, being an important player in the signal triggered by the CNTF receptor being required for motoneuron development.
Platelet-derived growth factor modulates rat vascular smooth muscle cell responses on laminin-5 via mitogen-activated protein kinase-sensitive pathways
Authors: Kingsley Karl , Plopper George E
Published: February 2005

Background

A treatment to remove vascular blockages, angioplasty, can cause damage to the vessel wall and a subsequent abnormal wound healing response, known as restenosis. Vascular smooth muscle cells (VSMC) lining the vessel wall respond to growth factors and other stimuli released by injured cells. However, the extracellular matrix (ECM) may differentially modulate VSMC responses to these growth factors, such as proliferation, migration and adhesion. Our previous reports of low-level expression of one ECM molecule, laminin-5, in normal and injured vessels suggest that laminin-5, in addition to growth factors, may mediate VSMC response following vascular injury. To elucidate VSMC response on laminin-5 we investigated-the role of platelet-derived growth factor (PDGF-BB) in activating the mitogen-activated protein kinase (MAPK) signaling cascade as a possible link between growth-factor initiated phenotypic changes in vitro and the ECM.

Results

Using a system of in vitro assays we assessed rat vascular smooth muscle cell (rVSMC) responses plated on laminin-5 to the addition of exogenous, soluble PDGF-BB. Our results indicate that although laminin-5 induces haptotactic migration of rVSMC, the addition of PDGF-BB significantly increases rVSMC migration on laminin-5, which is inhibited in a dose-dependent manner by the MAPK inhibitor, PD98059, and transforming growth factor (TGF-β1). In addition, PDGF-BB greatly reduces rVSMC adhesion to laminin-5, an effect that is reversible by MAPK inhibition or the addition of TGF-β1. In addition, this reduction in adhesion is less significant on another ECM substrate, fibronectin and is reversible using TGF-β1 but not MAPK inhibition. PDGF-BB also strongly increased rVSMC proliferation on laminin-5, but had no effect on rVSMC plated on fibronectin. Finally, plating rVSMC on laminin-5 did not induce an increase in MAPK activation, while plating on fibronectin or the addition of soluble PDGF-BB did.

Conclusion

These results suggest that rVSMC binding to laminin-5 activates integrin-dependent intracellular signaling cascades that are different from those of fibronectin or PDGF-BB, causing rVSMC to respond more acutely to the inhibition of MAPK. In contrast, our results suggest that fibronectin and PDGF-BB may activate parallel, reinforcing intracellular signaling cascades that converge in the activation of MAPK and are therefore less sensitive to MAPK inhibition. These results suggest a partial mechanism to explain the regulation of rVSMC behaviors, including migration, adhesion, and proliferation that may be responsible for the progression of restenosis.
T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years
Authors: Zijenah Lynn S , Katzenstein David A , Nathoo Kusum J , Rusakaniko Simbarashe , Tobaiwa Ocean , Gwanzura Christine , Bikoue Arsene , Nhembe Margaret , Matibe Petronella , Janossy George
Published: February 2005

Background

Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy.

Methods

Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry.

Results

Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%.

Conclusion

The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy.
Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague–Dawley rats by combination of lysine, proline, arginine, ascorbic acid and green tea extract
Authors: Roomi M Waheed , Roomi Nusrath W , Ivanov Vadim , Kalinovsky Tatiana , Niedzwiecki Aleksandra , Rath Matthias
Published: February 2005

Introduction

The limited ability of current treatments to control metastasis and the proposed antitumor properties of specific nutrients prompted us to examine the effect of a specific formulation (nutrient supplement [NS]) of lysine, proline, arginine, ascorbic acid, and green tea extract in vivo on the development of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in rats.

Methods

A single intraperitoneal dose of MNU was injected into each of 20 female Sprague–Dawley rats (aged 50 days) to induce tumors. Two weeks after MNU treatment, a time by which the animals had recovered from MNU-induced toxicity, the rats were divided into two groups. Rats in group 1 (n = 10) were fed Purina chow diet, whereas those in group 2 (n = 10) were fed the same diet supplemented with 0.5% NS. After a further 24 weeks, the rats were killed and tumors were excised and processed.

Results

NS reduced the incidence of MNU-induced mammary tumors and the number of tumors by 68.4%, and the tumor burden by 60.5%. The inhibitory effect of NS was also reflected by decreased tumor weight; the tumor weights per rat and per group were decreased by 41% and 78%, respectively. In addition, 30% of the control rats developed ulcerated tumors, in contrast to 10% in the nutrient supplemented rats.

Conclusion

These findings suggest that the specific formulation of lysine, proline, arginine, ascorbic acid, and green tea extract tested significantly reduces the incidence and growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development.
Patients' recollections of experiences in the intensive care unit may affect their quality of life
Authors: Granja Cristina , Lopes Alice , Moreira Sara , Dias Claudia , Costa-Pereira Altamiro , Carneiro António
Published: February 2005

Introduction

We wished to obtain the experiences felt by patients during their ICU stay using an original questionnaire and to correlate the memories of those experiences with health-related quality of life (HR-QOL).

Methods

We conducted a prospective study in 10 Portuguese intensive care units (ICUs). Six months after ICU discharge, an original questionnaire on experiences of patients during their ICU stay, the recollection questionnaire, was delivered. HR-QOL was evaluated simultaneously, with the EQ-5D questionnaire. Between 1 September 2002 and 31 March 2003 1433 adult patients were admitted. ICU and hospital mortalities were 21% and 28%, respectively. Six months after ICU discharge, 464 patients completed the recollection questionnaire.

Results

Thirty-eight percent of the patients stated they did not remember any moment of their ICU stay. The ICU environment was described as friendly and calm by 93% of the patients. Sleep was described as being good and enough by 73%. The experiences reported as being more stressful were tracheal tube aspiration (81%), nose tube (75%), family worries (71%) and pain (64%). Of respondents, 51% experienced dreams and nightmares during their ICU stay; of these, 14% stated that those dreams and nightmares disturb their present daily life and they exhibit a worse HR-QOL. Forty-one percent of patients reported current sleep disturbances, 38% difficulties in concentrating in current daily activities and 36% difficulties in remembering recent events. More than half of the patients reported more fatigue than before the ICU stay. Multiple and linear regression analysis showed that older age, longer ICU stay, higher Simplified Acute Physiology Score II, non-scheduled surgery and multiple trauma diagnostic categories, present sleep disturbances, daily disturbances by dreams and nightmares, difficulties in concentrating and difficulties in remembering recent events were independent predictors of worse HR-QOL. Multicollinearity analysis showed that, with the exception of the correlation between admission diagnostic categories and length of ICU stay (0.47), all other correlations between the independent variables and coefficient estimates included in the regression models were weak (below 0.30).

Conclusion

This study suggests that neuropsychological consequences of critical illness, in particular the recollection of ICU experiences, may influence subsequent HR-QOL.
Identification of ciliated sensory neuron-expressed genes in Caenorhabditis elegans using targeted pull-down of poly(A) tails
Authors: Kunitomo Hirofumi , Uesugi Hiroko , Kohara Yuji , Iino Yuichi
Published: February 2005

It is not always easy to apply microarray technology to small numbers of cells because of the difficulty in selectively isolating mRNA from such cells. We report here the preparation of mRNA from ciliated sensory neurons of Caenorhabditis elegans using the mRNA-tagging method, in which poly(A) RNA was co-immunoprecipitated with an epitope-tagged poly(A)-binding protein specifically expressed in sensory neurons. Subsequent cDNA microarray analyses led to the identification of a panel of sensory neuron-expressed genes.
Phase I Trial of Capecitabine and Weekly Irinotecan in Combination With Radiotherapy for Neoadjuvant Therapy of Rectal Cancer
Authors: Hofheinz Ralf-Dieter , von Gerstenberg-Helldorf Bolko , Wenz Frederik , Gnad Ulrike , Kraus-Tiefenbacher Uta , Müldner Albrecht , Hehlmann Rüdiger , Post Stefan , Hochhaus Andreas , Willeke Frank
Published: February 2005

Purpose

To establish the feasibility and efficacy of capecitabine in combination with weekly irinotecan (CAPIRI) with concurrent pelvic radiotherapy (RT) in patients with locally advanced rectal cancer.

Patients and Methods

Nineteen patients with rectal cancer clinical stage T3-4, Nx received weekly irinotecan 50 mg/m2 (days 1, 8, 15, 22, 29) and two doses of capecitabine (days 1 through 38; dose level [DL] I, 500 mg/m2 bid; DL II, 625 mg/m2 bid) according to phase I methodology. Three-dimensional conformal RT was given to a dose of 50.4 Gy (45 Gy + 5.4 Gy).

Results

On DL I, no dose-limiting toxicities occurred, whereas diarrhea grade 3 affected three of seven patients on DL II. Twelve patients were treated on DL I and received a median relative dose-intensity of 100% for both drugs. Grade 3 or 4 adverse events were observed in only one of these patients (asthenia grade 3). All patients underwent surgery and R0 resection was achieved in all patients. Pathologic complete remission was observed in four patients and another five patients had only microfoci of residual tumor.

Conclusion

Preoperative chemoradiotherapy with CAPIRI is feasible and well tolerated. The preliminary efficacy is good, and the tolerability is at least comparable with data for fluorouracil plus irinotecan chemoradiotherapy. Larger phase II trials of the CAPIRI-RT schedule clearly are warranted.
Newcomers in the process of mitochondrial permeabilization
Authors: Lucken-Ardjomande Safa , Martinou Jean-Claude
Published: January 2005

Under stress conditions, apoptogenic factors normally sequestered in the mitochondrial intermembrane space are released into the cytosol, caspases are activated and cells die by apoptosis. Although the precise mechanism that leads to the permeabilization of mitochondria is still unclear, the activation of multidomain pro-apoptotic proteins of the Bcl-2 family, such as Bax and Bak, is evidently crucial. Regulation of Bax and Bak by other members of the family has been known for a long time, but recent evidence suggests that additional unrelated proteins participate in the process, both as inhibitors and activators. The important rearrangements mitochondrial lipids undergo during apoptosis play a role in the permeabilization process and this role is probably more central than first envisioned.
The influence of interface effects on the rocking behaviour of graphite blocks
Authors: Holmes C , Drinkwater B. W , Payne J. F. B
Published: January 2005

Large assemblies of blocks are common in many civil engineering structures such as dams, costal defences and ancient buildings. Such assemblies are also found in graphite cored nuclear reactors. These consist of large graphite bricks, which are used to moderate the reaction and are assembled in arrays up to 10m in height and 10m in diameter. In this paper, the bricks considered are 200mm x 200mm x 800mm. The seismic response of such a structure is dependent on both the properties of the bulk material and the nature of the interface between individual bricks. The bricks are in dry contact with those above and below, and it is this contacting interface that governs the rocking behaviour, which is therefore an important factor in assessing the response of the columns to vibration or a seismic event.

This paper describes an investigation into the effect of microscopic and macroscopic surface features on the rocking behaviour of a single graphite brick. Typical real surfaces exhibit some form of macroscopic waviness in addition to the microscopic roughness and therefore only a small fraction of the surfaces are in contact. A number of analytical models are used to compare the effects of specific surface features with experimental data from real bricks. These models are compared with experimental results to assess their importance in explaining the rocking behaviour observed experimentally. Factors such as surface curvature, contact size and position are shown to be particularly important to the rocking stiffness of a brick. In most cases, the reduction in the rocking stiffness compared to perfectly flat surfaces is due to both the reduced moment arm of the contact forces and the increased strain at the contact region due to the high stress caused by the small area of contact.
An ultrasonic approach for contact stress mapping in machine joints and concentrated contacts
Authors: Marshall M B , Lewis R , Drinkwater B. W , Dwyer-Joyce R. S
Published: January 2005

The measurement of pressure at a contact in a machine part is important because contact stresses frequently lead to failure by seizure, wear or fatigue. While the interface might appear smooth on a macroscale, it consists of regions of asperity contact and air gaps on a microscale. The reflection of an ultrasonic pulse at such a rough contact can be used to give information about the contact conditions. The more conformal the contact, the smaller is the proportion of an incident wave amplitude that will be reflected. In this paper, this phenomenon has been used to produce maps of contact pressure at machine element interfaces. An ultrasonic pulse is generated and reflected at the interface, to be received by the same piezoelectric transducer. The transducer is scanned across the interface and a map of reflected ultrasound (a c-scan) is recorded. The proportion of the wave reflected can be used to determine the stiffness of the interface. Stiffness correlates qualitatively with contact pressure, but unfortunately there is no unique relationship. In this work, two approaches have been used to obtain contact pressure: firstly by using an independent calibration experiment, and secondly by using experimental observations that stiffness and pressure are linearly related. The approach has been used in three example cases: a series of press fitted joints, a wheel/rail contact and a bolted joint.
Effect of alpha irradiation on UO2 surface reactivity in aqueous media
Authors: Jégou Christophe , Muzeau B. , Broudic V. , Poulesquen A. , Roudil Danièle , Jorion F. , Corbel C.
Published: February 2005

The option of direct disposal of spent nuclear fuel in a deep geological formation raises the need to investigate the long-term behavior of the UO2 matrix in aqueous media subjected to α-β-γ radiation. The β-γ emitters account for most of the activity of spent fuel at the moment it is removed from the reactor, but diminish within a millennial time frame by over three orders of magnitude to less than the long-term activity. The latter persists over much longer time periods and must therefore be taken into account over a geological disposal time scale. Leaching experiments with solution renewal were carried out on UO2 pellets doped with alpha emitters (238Pu and 239Pu) to quantify the impact of alpha irradiation on UO2 matrix alteration. Three batches of doped UO2 pellets with different alpha flux levels (3.30×104, 3.30×105, and 3.2×106 α cm-2 s-1) were studied. The results obtained in aerated and deaerated media immediately after sample annealing or interim storage in air provide a better understanding of the UO2 matrix alteration mechanisms under alpha irradiation.

Interim storage in air of UO2 pellets doped with alpha emitters results in variations of the UO2 surface reactivity, which depends on the alpha particle flux at the interface and on the interim storage duration. The variation in the surface reactivity and the greater uranium release following interim storage cannot be attributed to the effect of alpha radiolysis in aerated media since the uranium release tends toward the same value after several leaching cycles for the doped UO2 pellet batches and spent fuel. Oxygen diffusion enhanced by alpha irradiation of the extreme surface layer and/or radiolysis of the air could account for the oxidation of the surface UO2 to UO2+x. However, leaching experiments performed in deaerated media after annealing the samples and preleaching the surface suggest that alpha radiolysis does indeed affect the dissolution, which varies with the flux at the UO2/water interface.
Drosophila couch potato Mutants Exhibit Complex Neurological Abnormalities Including Epilepsy Phenotypes
Authors: Glasscock Edward , Tanouye Mark A
Published: February 2005

RNA-binding proteins play critical roles in regulation of gene expression, and impairment can have severe phenotypic consequences on nervous system function. We report here the discovery of several complex neurological phenotypes associated with mutations of couch potato (cpo), which encodes a Drosophila RNA-binding protein. We show that mutation of cpo leads to bang-sensitive paralysis, seizure susceptibility, and synaptic transmission defects. A new cpo allele called cpoEG1 was identified on the basis of a bang-sensitive paralytic mutant phenotype in a sensitized genetic background (sda/+). In heteroallelic combinations with other cpo alleles, cpoEG1 shows an incompletely penetrant bang-sensitive phenotype with ∼30% of flies becoming paralyzed. In response to electroconvulsive shock, heteroallelic combinations with cpoEG1 exhibit seizure thresholds less than half that of wild-type flies. Finally, cpo flies display several neurocircuit abnormalities in the giant fiber (GF) system. The TTM muscles of cpo mutants exhibit long latency responses coupled with decreased following frequency. DLM muscles in cpo mutants show drastic reductions in following frequency despite exhibiting normal latency relationships. The labile sites appear to be the electrochemical GF-TTMn synapse and the chemical PSI-DLMn synapses. These complex neurological phenotypes of cpo mutants support an important role for cpo in regulating proper nervous system function, including seizure susceptibility.
Adaptive Molecular Evolution for 13,000 Phage Generations
Authors: Wichman Holly A , Millstein Jack , Bull J J
Published: February 2005

Bacteriophage φX174 was evolved on a continuous supply of sensitive hosts for 180 days (∼13,000 phage generations). The average rate of nucleotide substitution was nearly 0.2% (11 substitutions)/20 days, and, surprisingly, substitutions accumulated in a clock-like manner throughout the study, except for a low rate during the first 20 days. Rates of silent and missense substitutions varied over time and among genes. Approximately 40% of the 71 missense changes and 25% of the 58 silent changes have been observed in previous adaptations; the rate of parallel substitution was highest in the early phase of the evolution, but 7% of the later changes had evolved in previous studies of much shorter duration. Several lines of evidence suggest that most of the changes were adaptive, even many of the silent substitutions. The sustained, high rate of adaptive evolution for 180 days defies a model of adaptation to a constant environment. We instead suggest that continuing molecular evolution reflects a potentially indefinite arms race, stemming from high levels of co-infection and the resulting conflict among genomes competing within the same cell.
Suppression of an Atypically Spliced Rice CACTA Transposon Transcript in Transgenic Plants
Authors: Greco Raffaella , Ouwerkerk Pieter B F , Pereira Andy
Published: February 2005

OsES1, a rice homolog of the maize En/Spm transposon, is transcribed to produce TnpA-like and TnpD-like transcripts. However, an alternatively spliced form of the TnpA-like transcript, which was found to be suppressed in transgenic plants, was revealed to be due to atypical splicing of a Hipa-like CACTA transposon.
Genetic Architecture of Transcript-Level Variation in Differentiating Xylem of a Eucalyptus Hybrid
Authors: Kirst Matias , Basten Christopher J , Myburg Alexander A , Zeng Zhao-Bang , Sederoff Ronald R
Published: February 2005

Species diversity may have evolved by differential regulation of a similar set of genes. To analyze and compare the genetic architecture of transcript regulation in different genetic backgrounds of Eucalyptus, microarrays were used to examine variation in mRNA abundance in the differentiating xylem of a E. grandis pseudobackcross population [E. grandis × F1 hybrid (E. grandis × E. globulus)]. Least-squares mean estimates of transcript levels were generated for 2608 genes in 91 interspecific backcross progeny. The quantitative measurements of variation in transcript abundance for specific genes were mapped as expression QTL (eQTL) in two single-tree genetic linkage maps (F1 hybrid paternal and E. grandis maternal). EQTL were identified for 1067 genes in the two maps, of which 811 were located in the F1 hybrid paternal map, and 451 in the E. grandis maternal map. EQTL for 195 genes mapped to both parental maps, the majority of which localized to nonhomologous linkage groups, suggesting trans-regulation by different loci in the two genetic backgrounds. For 821 genes, a single eQTL that explained up to 70% of the transcript-level variation was identified. Hotspots with colocalized eQTL were identified in both maps and typically contained genes associated with specific metabolic and regulatory pathways, suggesting coordinated genetic regulation.