bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAs 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractIt 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.