bluuebunny/crossref_metadata_2025 huggingface dataset:
Caspase activation pathways induced by staurosporine and low potassium: Role of caspase‐2
Authors: Caballero‐Benítez Andrea , Morán Julio
Published: January 2003

Apoptotic death is a physiological process with regulatory mechanisms that are under the control of different molecules such as caspases. These are classified as initiators, such as caspases‐8 and ‐9, and effectors, such as caspases‐3 and ‐7. The participation of caspase‐2 in the effector phase of apoptosis has been commonly observed in many cell types; however, it is able to act as an initiator caspase, depending on the apoptotic stimulus. Cerebellar granule cells (CGCs) undergo apoptosis when they are transferred from high potassium (K25) to low potassium (K5); this process seems to be mediated by caspase‐3 activation. Staurosporine (STS), a full strength inhibitor of kinase proteins, also induces apoptosis in these cells. To characterize the caspase cascade induced by two stimuli in the same cell type we studied the activation of different caspases in CGCs treated with STS or K5. We found that both K5 and STS induce the activation of caspase‐3. This result was confirmed by the proteolytic cleavage of poly (ADP‐ribose) polymerase (PARP), an endogenous caspase‐3 substrate. Caspase‐2 was activated preferentially by STS, which showed a temporal course suggesting that this caspase was induced before caspase‐3. The initiator caspase‐9 was also activated by both K5 and STS, as well as cytochrome‐c release. The results obtained in this study suggest that STS and K5 induced different activation caspase pathways for apoptotic cell death of CGCs. © 2002 Wiley‐Liss, Inc.
Nitrergic dendrites in the superficial layers of the rat superior colliculus: Retinal afferents and alternatively spliced isoforms in normal and deafferented animals
Authors: Batista Claudia M. C. , Carneiro Kátia , Ernesto de Bittencourt‐Navarrete Ruben , Soares‐Mota Marcia , Cavalcante Leny A. , Mendez‐Otero Rosalia
Published: January 2003

The superficial layers of the rat superior colliculus (sSC) receive innervation from the retina and include nitrergic neurons. We have shown previously that in sSC, eye enucleation reduces NADPH diaphorase staining considerably in all but the most proximal dendrites of nitrergic neurons. We have used immunocytochemistry for neuronal nitric oxide synthase (nNOS) at light and electron microscopic levels and bilateral eye enucleation with varied survival times to determine the regulatory changes imposed by the direct and indirect loss of retinal input on apparent nNOS amount and subcellular distribution. In addition, we have used SDS‐PAGE and immunoblotting to test alternatively spliced isoforms in normal and deafferented animals. Our results show that unambiguously identified retinal terminals contact nitrergic neurons. In normal dendrites, nNOS immunoreactivity was distributed almost completely within the cytoplasm of the dendrite and along the postsynaptic membrane at synaptic junctions, in association with endoplasmic reticulum, ribosomes and external mitochondrial membranes. In contrast, nNOS labeling was greatly reduced in sSC deprived of retinal projections, and could only be observed in association with mitochondrial membranes and postsynaptic densities. Immunoblots of the soluble fraction from sSC revealed a surprisingly high proportion of the β isoform with respect to the α counterpart in normal colliculi, suggesting an increase in isoform proportion after enucleation, or at least maintenance of the same proportion. It is suggested that ultrastructural alterations observed in sSC cells of enucleated animals may be consequent to plastic reactions of the sSC cells in response to the removal of retinal afferents. © 2002 Wiley‐Liss, Inc.
Distinct protein kinases regulate SNAP‐25 expression in chromaffin cells
Authors: Montiel Carmen , Mendoza Isabel , García Carlos J. , Awad Yusfeye , García‐Olivares Jennie , Solís‐Garrido Luisa M. , Lara Hernan , García Antonio G. , Cárdenas Ana M.
Published: January 2003

The contribution of distinct Ca2+‐sensitive protein kinases to the regulation of the expression of the synaptosomal‐associated protein SNAP‐25 was examined in bovine chromaffin cells. Prolonged incubation with high K+(38 mM) or 1,1‐dimethyl‐4‐phenyl‐piperazinium (DMPP), a nicotinic receptor agonist, significantly increased SNAP‐25 protein and mRNA expression, as assessed by immunoblotting and semi‐quantitative RT‐PCR analysis. Both stimuli preferentially enhanced mRNA coding for the SNAP‐25a isoform. Increase of SNAP‐25 expression induced by K+or DMPP was inhibited over 70% by KN‐62 and KN‐93, two Ca2+/calmodulin‐dependent protein kinase (CaMK) inhibitors, whereas the inactive analogue KN‐92 only reduced the expression by 34%. The three compounds also inhibited the high K+‐elicited [Ca2+]isignal by 40%, suggesting that the effect of KN‐62 and KN‐93 was a combination of CaMK/ Ca2+influx inhibitory actions. Incubation of the cells with mitogen‐activated protein kinase (MAPK) inhibitors PD98059 and U0126 reduced protein expression elicited by high K+by 50%, but did not modify the response to DMPP. Interestingly, although protein kinase A (PKA) inhibition by H‐89 did not affect the high K+or DMPP‐induced SNAP‐25 expression, basal protein levels were significantly modified upon activation or inhibition of this pathway. Basal expression of SNAP‐25 was also modified by the protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate, but not by Gö6976, a PKC‐α inhibitor, suggesting that the Ca2+‐insensitive PKC‐ϵ isoform control basal expression of SNAP‐25 in these cells. Taken together, these results provide the first evidence that diverse protein kinases might converge in the induction of SNAP‐25 expression in chromaffin cells. The preferential contribution of one or another kinase would depend on the physiological or experimental conditions. © 2002 Wiley‐Liss, Inc.
Studies on protein and its high‐molecular‐weight subunit composition in relation to chapati‐making quality of Indian wheat cultivars
Authors: Srivastava Alok K , Prasada Rao Ummiti J S , Haridas Rao Punaroor
Published: January 2003

In order to predict the suitability of wheat for chapati making, 15 Indian wheat cultivars were studied for various protein characteristics in relation to chapati‐making quality. The cultivars varied considerably in their protein characteristics and chapati‐making potential. Results clearly indicated that both quantitative and qualitative characteristics of proteins influenced the chapati‐making potential of cultivars. Puffed height, the important qualitative parameter of chapati, was positively correlated with protein content (r = 0.62, p < 0.05), gluten content (r = 0.79, p < 0.01), sodium dodecyl sulphate (SDS) sedimentation value (r = 0.57, p < 0.05) and Glu‐1 quality scores of high‐molecular‐weight (HMW) subunits (r = 0.66, p < 0.01). Overall quality score of chapati was positively correlated with gluten content (r = 0.64, p < 0.01), SDS sedimentation value (r = 0.60, p < 0.05) and Glu‐1 score (r = 0.58, p < 0.05). HMW subunit composition varied considerably among cultivars. Cultivars having 5 + 10 subunits at the Glu‐1D chromosome, a protein content of about 130 g kg−1 and SDS sedimentation value around 75 ml yielded excellent chapatis, while those having 2 + 12 subunits, a protein content of about 115 g kg−1 and SDS sedimentation value around 55 ml resulted in poor chapatis. Interestingly, the presence of the 1BL/1RS chromosome in cultivars had no adverse effect on chapati quality.

© 2003 Society of Chemical Industry
Kinetic behaviour and stability of Escherichia coli ATCC27257 alkaline phosphatase immobilised in soil humates
Authors: Pilar María C , Ortega Natividad , Perez‐Mateos Manuel , Busto María D
Published: January 2003

Alkaline phosphatase (EC 3.1.3.1) extracted from Escherichia coli ATCC27257 was immobilised by co‐flocculation with soil humates in the presence of Ca2+. The effects of time, temperature, pH and concentration of enzyme and support on immobilisation were studied. Between 58 and 92% of the added phosphatase was strongly bound to the humates, depending on the conditions of immobilisation used. Some characteristics of the humate–phosphatase complexes and of the free enzyme were compared. The enzymatic complexes showed values of Km (2.22 mM) and activation energy (33.4 kJ mol−1) similar to those of the free enzyme (2.00 mM and 27.6 kJ mol−1). The pH/activity profiles revealed no change in terms of shape or optimum pH (10.5) upon immobilisation of alkaline phosphatase. However, the immobilised enzyme showed maximal activity in the range of 80–100 °C, while the free enzyme had its highest activity at 60 °C. The thermal stability of alkaline phosphatase was enhanced by complexation to the soil humates.

© 2003 Society of Chemical Industry
Use of neural networks for the prediction of frictional drag and transmission of axial load in horizontal wellbores
Authors: Sadiq Tanvir , B. Gharbi Ridha , C. Juvkam‐Wold Hans
Published: January 2003

The use of mud motors and other tools to accomplish forward motion of the bit in extended reach and horizontal wells allows avoiding large amounts of torque caused by rotation of the whole drill string. The forward motion of the drill string, however, is resisted by excessive amount of friction. In the presence of large compressive axial loads, the drill pipe or coiled tubing tends to buckle into a helix in horizontal boreholes. This causes additional frictional drag resisting the transmission of axial load (resulting from surface slack‐off force) to the bit. As the magnitude of the frictional drag increases, a buckled pipe may become ‘locked‐up’ making it almost impossible to drill further. In case of packers, the frictional drag may inhibit the transmission of set‐up load to the packer. A prior knowledge of the magnitude of frictional drag for a given axial load and radial clearance can help avoid lock‐up conditions and costly failure of the tubular.

In this study a neural network model, for the prediction of frictional drag and axial load transmission in horizontal wellbores, is presented. Several neural network architectures were designed and tested to obtain the most accurate prediction. After cross‐validation of the Back Propagation Neural Network (BPNN) algorithm, a two‐hidden layer model was chosen for simultaneous prediction of frictional drag and axial load transmission. A comparison of results obtained from BPNN and General Regression Neural Network (GRNN) algorithms is also presented. Copyright © 2002 John Wiley & Sons, Ltd.
A simulation using a hybrid method for predicting fault zones ahead of a tunnel face
Authors: Lee In‐Mo , Kim Don‐Hee
Published: January 2003

By monitoring and analysing three‐dimensional absolute displacement during tunnel excavation, it is possible to predict discontinuity zones ahead of tunnel face. This paper presents results of the three‐dimensional displacement obtained from three‐dimensional simulations using hybrid method for assessing the effect of discontinuity zones on monitoring data. The influence of fault zones and in situ initial stresses on the three‐dimensional tunnel movement is evaluated. Copyright © 2002 John Wiley & Sons, Ltd.
Determination of burn‐in parameters and residual life for highly reliable products
Authors: Tseng Sheng‐Tsaing , Tang Jen , Ku In‐Hong
Published: January 2003

Today, many products are designed and manufactured to function for a long period of time before they fail. Determining product reliability is a great challenge to manufacturers of highly reliable products with only a relatively short period of time available for internal life testing. In particular, it may be difficult to determine optimal burn‐in parameters and characterize the residual life distribution. A promising alternative is to use data on a quality characteristic (QC) whose degradation over time can be related to product failure. Typically, product failure corresponds to the first passage time of the degradation path beyond a critical value. If degradation paths can be modeled properly, one can predict failure time and determine the life distribution without actually observing failures. In this paper, we first use a Wiener process to describe the continuous degradation path of the quality characteristic of the product. A Wiener process allows nonconstant variance and nonzero correlation among data collected at different time points. We propose a decision rule for classifying a unit as normal or weak, and give an economic model for determining the optimal termination time and other parameters of a burn‐in test. Next, we propose a method for assessing the product's lifetime distribution of the passed units. The proposed methodologies are all based only on the product's initial observed degradation data. Finally, an example of an electronic product, namely contact image scanner (CIS), is used to illustrate the proposed procedure. © 2002 Wiley Periodicals, Inc. Naval Research Logistics, 2003
Scheduling with tool changes to minimize total completion time: A study of heuristics and their performance
Authors: Akturk M. Selim , Ghosh Jay B. , Gunes Evrim D.
Published: January 2003

The machine scheduling literature does not consider the issue of tool change. The parallel literature on tool management addresses this issue but assumes that the change is due only to part mix. In practice, however, a tool change is caused most frequently by tool wear. That is why we consider here the problem of scheduling a set of jobs on a single CNC machine where the cutting tool is subject to wear; our objective is to minimize the total completion time. We first describe the problem and discuss its peculiarities. After briefly reviewing available theoretical results, we then go on to provide a mixed 0–1 linear programming model for the exact solution of the problem; this is useful in solving problem instances with up to 20 jobs and has been used in our computational study. As our main contribution, we next propose a number of heuristic algorithms based on simple dispatch rules and generic search. We then discuss the results of a computational study where the performance of the various heuristics is tested; we note that the well‐known SPT rule remains good when the tool change time is small but deteriorates as this time increases and further that the proposed algorithms promise significant improvement over the SPT rule. © 2002 Wiley Periodicals, Inc. Naval Research Logistics, 2003
Optimal stopping in software testing
Authors: Morali Nilgun , Soyer Refik
Published: January 2003

In this paper we address the problem of how to decide when to terminate the testing/modification process and to release the software during the development phase. We present a Bayesian decision theoretic approach by formulating the optimal release problem as a sequential decision problem. By using a non‐Gaussian Kalman filter type model, proposed by Chen and Singpurwalla (1994), to track software reliability, we are able to obtain tractable expressions for inference and determine a one‐stage look ahead stopping rule under reasonable conditions and a class of loss functions. © 2002 Wiley Periodicals, Inc. Naval Research Logistics, 2003
Transient analysis of electro‐osmotic transport by a reduced‐order modelling approach
Authors: Qiao R. , Aluru N. R.
Published: January 2003

Transient behaviour of electro‐osmotic transport in typical electrokinetic channels is studied in this paper. The time needed for the electro‐osmotic flow to reach steady‐state exhibits multiple time scales depending on whether the flow is governed by either a viscous force, electrokinetic force or by a combination of both. When an intersection is present in the electrokinetic channel, such as in a cross or a T‐channel, the flow in the main channel and in the intersection gets to steady‐state at different times.

A weighted Karhunen–Loève (KL) decomposition method is proposed in this paper to generate the global basis function for reduced‐order simulation. The key idea in a weighted KL approach is that, instead of minimizing a least‐squares measure of ‘error’ between the linear subspace spanned by the basis functions and the observation space, we minimize the weighted ‘error’ between the two spaces. The global basis functions in a weighted KL approach can be generated by computing the singular value decomposition (SVD) of the matrix containing the weighted snapshots. We show that the weighted KL decomposition based reduced‐order model is computationally more efficient and can capture the multiple time scales encountered in electro‐osmotic transport much more effectively compared to the classical KL decomposition based reduced‐order model. Copyright © 2003 John Wiley & Sons, Ltd.
Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community‐acquired pneumonia in children
Authors: Kogan Ricardo , Martínez M. Angélica , Rubilar Lilian , Payá Ernesto , Quevedo Ilsa , Puppo Homero , Girardi Guido , Castro‐Rodriguez José A.
Published: January 2003

Our objective was to compare the clinical efficacy of azithromycin vs. erythromycin and amoxicillin in the treatment of presumed bacterial community‐acquired pneumonia in ambulatory children, and to evaluate the etiologies of these illnesses. One hundred and ten children, aged 1 month to 14 years, were enrolled between January 1996–January 1999. Children were distributed into two groups according to clinical and radiological patterns: classic or atypical pneumonia. Patients with classic pneumonia were randomly assigned to receive oral amoxicillin 75 mg/kg/day for 7 days, or azithromycin 10 mg/kg/day for 3 days; patients with atypical pneumonia received azithromycin 10 mg/kg/day for 3 days, or erythromycin 50 mg/kg/day for 14 days. Chest X‐ray, clinical, and laboratory parameters were obtained on enrollment. Clinic visits were performed on days 3, 7, and 14, and chest X‐ray follow‐up on days 7 and 14. Microbiological diagnosis of classic pathogens was based on blood and bronchial secretion cultures. The diagnosis of atypical pathogens C. pneumoniae, C. trachomatis, and M. pneumoniae was based on PCR and serologic tests.

Forty‐seven children met the criteria for classic pneumonia (23 children received azithromycin, and 24 received amoxicillin), and 59 children had atypical pneumonia (33 children were treated with azithromycin, and 26 with erythromycin). Demographic characteristics at enrollment were similar between children with classic pneumonia treated with azithromycin and erythromycin and children treated with azithromycin and erythromycin for atypical pneumonia. However, on day 7, children with classic pneumonia who received azithromycin normalized their chest X‐ray more often than those who received amoxicillin (81.0% vs. 60.9%, respectively, P = 0.009). The same was true for children with atypical pneumonia; their chest X‐rays had normalized by day 14 (100% in those with azithromycin vs. 81% in those with erythromycin, P = 0.059). Also, children with atypical pneumonia treated with azithromycin had earlier cessation of cough than children treated with erythromycin (3.6 ± 1.9 vs. 5.5 ± 3.6 days respectively, P = 0.02). There were only three children with side effects (mild diarrhea, all in the erythromycin group). Etiological agents were identified in 41% of children.

In conclusion, azithromycin is an effective therapeutic option for the treatment of community‐acquired classic and atypical pneumonia in children. Pediatr Pulmonol. 2003; 35:91–98. © 2003 Wiley‐Liss, Inc.
Role of viruses and atypical bacteria in exacerbations of asthma in hospitalized children: A prospective study in the Nord‐Pas de Calais region (France)
Authors: Thumerelle C. , Deschildre A. , Bouquillon C. , Santos C. , Sardet A. , Scalbert M. , Delbecque L. , Debray P. , Dewilde A. , Turck D. , Leclerc F.
Published: January 2003

We studied the role of viruses and atypical bacteria in children hospitalized with exacerbated asthma by a prospective study of children with acute asthma admitted to the Department of Pediatrics in Lille, and to 15 hospitals in the Nord‐Pas de Calais region, from October 1, 1998–June 30, 1999. We included children aged 2–16 years with active asthma, defined as three or more recurrent episodes of reversible wheezing. The severity of asthma and of asthmatic exacerbations was recorded. Immunofluorescence assays (IFA) on nasopharyngeal secretions (NPS), serological tests, or both, were used for detection of influenza virus, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and coronavirus. Polymerase chain reaction (PCR) assays on NPS were used for rhinovirus and enterovirus. Serological tests for Chlamydia pneumoniae and Mycoplasma pneumoniae were performed. A control group of asymptomatic asthmatic outpatients was examined for respiratory viruses (using IFA and PCR). Eighty‐two symptomatic children (mean age, 7.9 years) were examined. Viruses were detected in 38% (enterovirus, 15.8%; rhinovirus, 12%; RSV, 7.3%). Serological tests for atypical bacteria were positive in 10% of patients (C. pneumoniae, 5%; M. pneumoniae, 5%). Among the 27 control subjects (mean age, 7.9 years), one PCR was positive for enterovirus. There was no correlation between severity of chronic asthma or asthmatic exacerbations and the diagnosis of infection. Atypical bacterial pathogen infections were linked with prolonged asthmatic symptoms. In conclusion, we confirmed the high incidence of viral infection in acute exacerbations of asthma, especially enteroviruses or rhinoviruses. Persistent clinical features were more frequently associated with atypical bacterial infections, suggesting that these infections should be investigated and treated in cases of persistent asthmatic symptoms. Pediatr Pulmonol. 2003; 35:75–82. © 2003 Wiley‐Liss, Inc.
Asthma‐specific quality of life questionnaires in children: Are they useful and feasible in routine clinical practice?
Authors: Williams Jeff , Williams Kate
Published: January 2003

This study used well‐validated quality of life (QOL) instruments to compare the QOL scores achieved by children aged 7–17 years with the views of their parents of the effects of their child's asthma on family life. Also, a comparison was made between the child's QOL scores and the judgment of the clinician in charge in regard to asthma control.

There was poor correlation between the overall scores of the children and the overall caregiver's score (r = 0.19, P = 0.18), and no correlation between the child's score and assessment of control given by the clinician in charge of the case (r = 0.02, P = 0.98).

It is important to recognize that there may be little relationship between the concerns of the child regarding his or her asthma, the effects on the family as reported by a parent, and the clinician's view of asthma control. This recognition may significantly affect treatment planning with the family. The administration of the QOL instrument used in this study was straightforward and quite quick, with a mean time to completion of about 8 min. Pediatr Pulmonol. 2003; 35:114–118. © 2003 Wiley‐Liss, Inc.
Three‐minute step test to assess exercise capacity in children with cystic fibrosis with mild lung disease
Authors: Narang I. , Pike S. , Rosenthal M. , Balfour‐Lynn I.M. , Bush A.
Published: January 2003

The information obtained from a simple submaximal test (the 3‐min step test) was compared with that from a maximal cycle ergometry study, in a group of children with CF with relatively mild abnormalities of lung function (FEV1 > 50% predicted). Nineteen subjects with CF undertook both exercise tests on the same day. Measurements included heart rate (HR), oxygen saturations (SaO2), visual analogue score of perceived breathlessness (VAS), 15‐count breathlessness score (15c), and peak oxygen consumption (VO2). There were significant differences in the median changes in HR and VAS during the cycle test compared to the step test, 78 vs. 46 beats per minute (P < 0.05) and 51 mm vs. 42 mm (P < 0.05), respectively. There were no differences between median changes in 15c and SaO2, but 3 subjects had significant desaturations (>4%) during the cycle test only. Significant exercise desaturations may occur in mild CF lung disease and will not be detected by a 3‐min step test. The 15c did not discriminate between a maximal and a submaximal test, and was less useful than VAS. Important information may be missed by the step test which is detected by more complex exercise tests. Pediatr Pulmonol. 2003; 35:108–113. © 2003 Wiley‐Liss, Inc.
Antimicrobial susceptibility profile of molecular typed cystic fibrosis Stenotrophomonas maltophilia isolates and differences with noncystic fibrosis isolates
Authors: Cantón Rafael , Valdezate Sylvia , Vindel Ana , Sánchez Del Saz Begoña , Maíz Luis , Baquero Fernando
Published: January 2003

Multiresistance in Stenotrophomonas maltophilia limits the effectiveness of antimicrobial therapy for infections due to this organism. It can be of special concern in cystic fibrosis (CF) patients due to frequent antimicrobial administration. The in vitro activity of 41 antimicrobial agents against 76 epidemiologically defined CF S. maltophilia isolates by pulsed‐field‐gel electrophoresis (PFGE) technique under XbaI and SpeI restriction was compared with that obtained with 51 non‐CF strains recovered from respiratory sources. Minimal inhibitory concentrations (MICs) were determined with the standard National Committee for Clinical Laboratory Standards agar dilution technique, but with 24‐hr incubation. Forty‐seven different PFGE profiles were observed within 76 S. maltophilia CF isolates. Minocycline (resistance rate, 0%; MIC90, 1 μg/ml), doxycycline (6.4%; 8 μg/ml), trovafloxacin (4.2%; 2 μg/ml), moxifloxacin (6.3%; 2 μg/ml), clinafloxacin (6.3%; 2 g/ml), and moxalactam (17.0%; 64 g/ml) displayed low resistance rates. On the contrary, resistance rates were higher with ceftazidime (70.0%; 256 μg/ml), cefepime (83.0%; 128 μg/ml), piperacillin (87.2%; >1,024 μg/ml), ticarcillin (87.2%; >512 μg/ml), and aztreonam (95.7%; >1,024 μg/ml). Clavulanate reverted resistance to ticarcillin and aztreonam in 40.4% and 31.7% of strains, respectively. Aminoglycosides displayed reduced activities with susceptibility rates lower than 20% and MIC90 higher than 128 μg/ml. With the exception of trimethoprim‐sulfamethoxazole (25.4 vs. 31.3%), CF isolates were more resistant than non‐CF isolates. Remarkably, resistance was enhanced in S. maltophilia isolates persistently recovered in chronically colonized patients. Susceptibility analysis demonstrated higher resistance rates among CF S. maltophilia isolates when compared with respiratory isolates from non‐CF patients. Moreover, persistently recovered CF S. maltophilia isolates were more resistant than sporadic non‐CF isolates. Pediatr Pulmonol. 2003; 35:99–107. © 2003 Wiley‐Liss, Inc.
Effects of bracing on lung function in idiopathic juvenile kyphosis
Authors: Priftis Kostas N. , Hager John , Vlachou Maria , Anthracopoulos Michael B.
Published: January 2003

Although considerable information is available on the effects of bracing on lung function in kyphoscoliosis, there is a paucity of data on idiopathic juvenile kyphosis (IJK). The present study was designed to investigate the immediate effect of bracing on lung function in children and adolescents with mild‐to‐moderate IJK. Spirometry, measurement of lung volumes, and arterial oxyhemoglobin saturation (SaO2) were performed in 24 patients, 9–17 years of age, who were treated with a corrective brace for mild‐to‐moderate IJK (Cobb angle, 46–75°). Children were studied when braced and unbraced.

When children were unbraced, mean percent predicted values (±standard deviation) for total lung capacity (TLC), vital capacity (VC), functional residual capacity (FRC), and forced expiratory volume in 1 sec (FEV1) were 100.0% (±13.0%), 92.7% (±14.2%), 108.2% (±20.4%), and 95.0% (±16.3%), respectively. With the brace on, significant reductions occurred in all lung function measurements: TLC decreased by 9.5% (P < 0.001), VC by 9.3% (P = 0.001), FRC by 14.2% (P = 0.005), and FEV1 by 8.9% (P = 0.009). SaO2 decreased from 96.2% (±1.6%) to 95.2% (±1.4%) (P = 0.027). An inverse relationship was observed between pre‐ and postbracing change in TLC and Cobb angle children (P = 0.021).

Our findings indicate that corrective bracing in mild‐to‐moderate IJK results in mild lung restriction and a clinically insignificant drop in SaO2. The effect of bracing on TLC decreases as the severity of kyphosis increases in these patients. Pediatr Pulmonol. 2003; 35:83–86. © 2003 Wiley‐Liss, Inc.
Long‐term noninvasive mechanical ventilation for children at home: A national survey
Authors: Fauroux B. , Boffa C. , Desguerre I. , Estournet B. , Trang H.
Published: January 2003

Experience with domiciliary noninvasive mechanical ventilation (NIMV) in children is limited. The aim of this study was to determine the number of patients and categorize the use of domiciliary NIMV in children in France.

An anonymous cross‐sectional national study was performed, using a postal questionnaire sent to all specialist centers utilizing domiciliary NIMV for chronic respiratory failure. Patients aged <18 years and receiving home NIMV were included in the study.

Detailed information was obtained from 102 patients from 15 centers: 4/15 centers cared for 84% of patients; 7% of patients were under 3 years old; 35% were between 4–11 years old; and 58% were older than 12 years. Underlying diagnoses included neuromuscular disease (34%), obstructive sleep apnea (OSA) and/or cranio‐facial abnormalities (30%), cystic fibrosis (17%), congenital hypoventilation (9%), scoliosis (8%), and other disorders (2%). NIMV was started because of nocturnal hypoventilation (67%), acute exacerbation (28%), and/or failure to thrive (21%). Volume‐targeted ventilation was preferred in restrictive disorders (56%) and central hypoventilation (56%), while pressure support ventilation (PSV) was preferred in cystic fibrosis (71%). Patients with OSA and/or cranio‐facial abnormalities were ventilated with continuous positive airway pressure (45%) or bilevel PSV (52%).

In conclusion, NIMV is currently used in France for the domiciliary management of children with a variety of conditions causing chronic respiratory failure. However, NIMV in children is still performed on a small scale, and combined with the heterogeneity of the patient population, its application would best be served by centers specializing in the initiation and long‐term follow‐up of these patients. Pediatr Pulmonol. 2003; 35:119–125. © 2003 Wiley‐Liss, Inc.
Mechanistic investigation of the adrenergic induction of ventral prostate hyperplasia in mice
Authors: Marinese Dorene , Patel Rupa , Walden Paul D.
Published: January 2003

Background

The norepinephrine (NE) analog phenylephrine has previously been shown to induce atypical prostate hyperplasia in rats. The objective of the present study was to provide further insight into the mechanism of phenylephrine‐induced prostate growth.

Methods

Adult male C57/BL6 mice were given daily subcutaneous injection of phenylephrine, isoproterenol, or phenylephrine in combination with BMY7378, cyclazosin, RS100329, or yohimbine, and the effects on ventral prostate histology, and proliferative and apoptotic indices determined. Phenylephrine was also administered in combination with testosterone in castrated mice.

Results

Atypical prostatic hyperplasia characterized by piling up and/or papillary infolding of epithelial cells with concomitant stromal smooth muscle hyperplasia was seen in adult mice given subcutaneous injection of phenylephrine daily for 26 days. Phenylephrine induced hyperplasia was more severe proximally and was associated with significantly reduced rates of apoptosis (but no change in cell proliferation) in both stromal and epithelial compartments. Only the α1A‐adrenoceptor selective subtype antagonist RS100329 abrogated the phenylephrine‐induced hyperplasia. Using selective antibodies, the α1A−1‐adrenoceptor subtype was predominantly localized to the stromal compartments of the mouse and rat ventral prostates. The effects of phenylephrine were mediated independent of testicular androgens.

Conclusions

Prostatic hyperplasia in mice occurs as a consequence of subchronic administration of the sympathomimetic phenylephrine. Response to phenylephrine is mediated by the α1A‐adrenoceptor, which predominates in the stroma of the rodent ventral prostate. Conceivably, therefore, phenylephrine could directly modulate prostate stromal growth, and indirectly modulate epithelial growth in a paracrine fashion. We cannot, however, rule out the contribution of other indirect effects such as hypoxia/reperfusion or effects on intermediary metabolism. Prostate 54: 230–237, 2003. © 2002 Wiley‐Liss, Inc.
Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells
Authors: Yeh Jiun‐Yih , Huang William J. , Kan Shu‐Fen , Wang Paulus S.
Published: January 2003

Background

Cardiac glycosides may induce oncolytic effects in cancers. This study was to evaluate bufalin and cinobufagin effects on the proliferation of prostate cancer cell lines named LNCaP, DU145, and PC3.

Methods

Cell proliferation was measured by MTT assay. The cytotoxic effects were determined by lactate dehydrogenase measurements. The intracellular calcium concentration ([Ca2+]i) was measured by a dual‐wavelength spectrometer system. TUNEL assay and flow cytometry were performed to measure percentage of apoptotic cells. A colorimetric assay was to measure caspases activities.

Results

Bufalin and cinobufagin inhibited proliferation of cancer cells at doses of 0.1, 1, or 10 μM after 2–4 days of culture. Cytotoxicity of bufalin and cinobufagin on the DU145 and LNCaP cells was dose‐dependent. Bufalin or cinobufagin increased [Ca2+]i and apoptosis in cancer cells after a 24‐hr culture as well as caspase 3 activities in DU145 and PC3 cells and caspase 9 activities in LNCaP cells.

Conclusions

Bufalin and cinobufagin may inhibit the proliferation of prostate cancer cell lines associated with sustained elevation of the [Ca2+]i and that of apoptosis. Prostate 54: 112–124, 2003. © 2002 Wiley‐Liss, Inc.
TERE1, a novel gene affecting growth regulation in prostate carcinoma
Authors: McGarvey Terence W. , Nguyen Trang , Puthiyaveettil Raghunath , Tomaszewski John E. , Malkowicz S. Bruce
Published: January 2003

Recently, we isolated a ubiquitously expressed gene designated TERE1, which has a significant effect on the growth regulation in bladder cancer. The TERE1 gene maps to chromosome 1p36.11‐1p36.33 between the micro‐satellite markers D1S2667 and D1S434, a chromosome locus that has been identified by loss of heterozygosity studies as a site of a putative tumor suppressor gene or genes for multiple tumor types including prostate carcinoma. The expression of the TERE1 transcript and protein was examined in a series of thirty microdissected prostate tumors by semi‐quantitative RT/PCR and immunohistochemistry. There was a significant 61% decrease in the TERE1 transcript in prostate carcinoma (CaP) and a distinct loss of the TERE1 protein in metstatic prostate. Though a loss of heterozygosity at chromosome 1p36 was found in 25% of these prostate tumors, there appeared to be no TERE1 mutations present in these tumor samples. Induced TERE1 expression after transduction or transfection of TERE1 constructs into two prostate carcinoma (LNCaP and PC‐3) cell lines significantly decreased proliferation up to 80% with a significant increase in the number of cells in G1. Serum factors but not DHT (dihydrotestosterone) appear to regulate the amount of TERE1 protein in the androgen responsive LNCaP cell line. Additionally, we have identified by microarray analysis various growth regulatory genes that are down‐regulated or up‐regulated in TERE1‐transduced PC‐3 cells. Altogether, these data suggest that TERE1 maybe significant in prostate cancer growth regulation and the down regulation or absence of TERE1 may be an important component of the phenotype of advanced disease. Prostate 54: 144–155, 2003. © 2002 Wiley‐Liss, Inc.
Serum insulin‐like growth factor binding protein‐3/prostate‐specific antigen ratio is a useful predictive marker in patients with advanced prostate cancer
Authors: Miyata Yasuyoshi , Sakai Hideki , Hayashi Tomayoshi , Kanetake Hiroshi
Published: January 2003

BACKGROUND

Insulin‐like growth factor‐1 (IGF‐1) and insulin‐like growth factor binding protein‐3 (IGFBP‐3) play an important role in regulation of prostate cancer cell growth. We studied the prognostic significance of serum IGF‐1 and IGFBP‐3 levels, and IGF‐1/prostate‐specific antigen (PSA) and IGFBP‐3/PSA ratios in patients with prostate cancer.

METHODS

Serum levels of IGF‐1, IGFBP‐3, and PSA were determined in 112 patients diagnosed with prostate cancer. Serum samples from 32 patients with histologically confined benign prostatatic hyperplasia (BPH) served as control.

RESULTS

Serum IGF‐1 levels were significantly higher in advanced prostate cancer (n = 84) than in BPH patients (P < 0.01). IGFBP‐3 levels were significantly lower in patients with advanced prostate cancer than in localized tumor (n = 28) or BPH (P < 0.05, each). Univariate analysis showed that serum PSA, IGF‐1/PSA ratio, IGFBP‐3/PSA ratio, T, N and M classifications correlated significantly with relapse‐free survival of advanced prostate cancer patients treated with hormonal therapy. Multivariate analysis identified IGFBP‐3/PSA ratio as the only significant variable for relapse‐free survival (odds ratio 5.81, 95% CI 1.57–21.51). IGFBP‐3/PSA ratio was also an independent predictor of cause‐specific survival (stepwise analysis, odds ratio 4.86, P < 0.01).

CONCLUSIONS

Our results suggested that IGFBP‐3/PSA ratio might be a useful prognostic marker of advanced prostate cancer. Prostate 54: 125–132, 2003. © 2002 Wiley‐Liss, Inc.
Using splines to detect changes in PSA doubling times
Authors: Guess Brad , Jennrich Robert , Johnson Henry , Redheffer Ray , Scholz Mark
Published: January 2003

BACKGROUND

PSA doubling time (PSADT) can predict the likelihood of clinical progression in patients with biochemical relapse after surgery or radiation for prostate cancer. Changes in PSA doubling time in response to therapy may be of clinical or investigational significance. How does one estimate PSADT before and after the initiation of therapy and determine if any change is statistically significant or simply the result of random variation? These are the type of questions addressed.

METHODS

Our technique uses a best‐fitting spline (i.e., a broken‐line approximation) to a graph of log PSA on time to estimate PSADTs before and after treatment initiation. A linear regression program is used to produce the fit and to evaluate the statistical significance of any change in PSADT. This method differs from previous methods in that it uses all the data, exploits the continuity of PSA at the time of treatment initiation, and allows one to make statistical significance statements about specific individuals.

RESULTS

Our technique is illustrated with data from a pilot clinical trial using a nutritional supplement in 12 men with prostate cancer. A detailed analysis of the first patient shows how the data are handled, how two lines of computer code are sufficient to fit the spline model, and how the doubling times and statistical significance of a change are read from the computer output. In the study, 9 of 12 patients had a statistically significant increase in doubling time. Because the study is preliminary and used only to illustrate our method, no medical discussion of the study is included. The last section of the study, in part expository, is devoted to explaining the underlying principles for those who may want to know not only what to do, but why it works.

CONCLUSIONS

The method presented here for determining changes in PSADT is both simple and broadly applicable. It allows the evaluation of the size and statistical significance of an observed change or increase in PSADT in response to therapy for prostate cancer. It can be done using essentially any statistical software and widely accepted statistical methods. Prostate 54: 88–94, 2003. © 2002 Wiley‐Liss, Inc.
Plasma matrix metalloproteinase 9 as biomarker of prostate cancer progression in Dunning (Copenhagen) rats
Authors: Jung Klaus , Krell Hans‐Willi , Ortel Bernhard , Hasan Tayyaba , Römer Andreas , Schnorr Dietmar , Loening Stefan A. , Lein Michael
Published: January 2003

Background

Matrix metalloproteinases (MMPs) play an important role in invasion and metastatic spread of cancer cells. The objective of this study was to assess MMPs in plasma of Dunning tumor rats as indicators of the progression of prostate cancer and follow‐up parameters after treatment.

Methods

Prostate cancer was induced in male Copenhagen rats by either subcutaneous or orthotopic implantation of R3327‐MatLyLu cells. During the development of the tumor, plasma MMP‐2, and MMP‐9 were measured by gelatin‐substrate zymography and Western blot technique with densitometry in untreated animals, rats treated with laser‐induced hyperthermia, or with the new synthetic MMP inhibitor RO 28‐2653.

Results

Normal prostatic tissue of the Copenhagen rats predominantly expressed proMMP‐2 but not proMMP‐9 whereas MMP‐9 was only found in cancerous tissue. Elevated plasma MMP‐9 values were demonstrated in rats with subcutaneous or orthotopic tumors. Animals with tumors and treated with the MMP inhibitor RO 28‐2653 had both a lower tumor volume and a lower plasma MMP‐9 concentration compared with controls.

Conclusions

The determination of plasma MMP‐9 in Dunning tumor rats is a useful tool to monitor the progression of prostate cancer and to assess the efficacy of drugs like MMP inhibitors or other treatment protocols. Prostate 54: 206–211, 2003. © 2002 Wiley‐Liss, Inc.
Design of clinical trials using an adaptive test statistic
Authors: Lawrence John
Published: January 2003

Since the treatment effect of an experimental drug is generally not known at the onset of a clinical trial, it may be wise to allow for an adjustment in the sample size after an interim analysis of the unblinded data. Using a particular adaptive test statistic, a procedure is demonstrated for finding the optimal design. Both the timing of the interim analysis and the way the sample size is adjusted can influence the power of the resulting procedure. It is possible to have smaller average sample size using the adaptive test statistic, even if the initial estimate of the treatment effect is wrong, compared to the sample size needed using a standard test statistic without an interim look and assuming a correct initial estimate of the effect. Copyright © 2002 John Wiley & Sons, Ltd.
A Sequential procedure for studies comparing multiple doses
Authors: Denne Jon , Koch Gary
Published: January 2003

An attractive method of dealing with the multiplicity inherent in studies comparing multiple doses is to use a testing strategy in which hypotheses (or sets of hypotheses) are tested in a prespecified order, with rejection at each step a necessary condition for continuation to the next step. Such a strategy naturally lends itself to interim monitoring. We demonstrate how this may be achieved. Copyright © 2002 John Wiley & Sons, Ltd.
Two approaches to fractional supersymmetrical quantum mechanics
Authors: Daoud M. , Kibler M.
Published: January 2003

Two complementary approaches of 𝒩 = 2 fractional supersymmetrical quantum mechanics of order k are studied in this article. The first, based on a generalized Weyl–Heisenberg algebra Wk (which comprises the affine quantum algebra Uq(sl2) with qk = 1 as a special case), apparently contains solely one bosonic degree of freedom. The second uses generalized bosonic and k‐fermionic degrees of freedom. As an illustration, a particular emphasis is put on the fractional supersymmetrical oscillator of order k. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Numerical determination of complex resonance energies by using a superposition of δ‐potentials
Authors: Kapshai Valery , Alferova Tatjana , Elander Nils
Published: January 2003

A method using a superposition of a finite but varied number of δ‐potentials has been applied to treat the integral Schrödinger equation with three different potentials. Positions of scattering resonances are numerically determined as complex poles of the partial‐wave S‐matrix. The method, in principle, makes it possible to obtain several resonances for short‐range potentials like a square well (or barrier). The numerical method is elaborated to treat integral equations and is applicable to solve problems for which no differential equations can be derived. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Algebraic expressions of Clebsch–Gordon coefficients for the group chain O† ⊃ C
Authors: Fan Peng‐Dong
Published: January 2003

Using the algebraic expressions of the projection operators for the group chain O ⊃ C, concise algebraic expressions of the Clebsch–Gordon (CG) coefficients are derived in the group chain O ⊃ C for both single‐valued and double‐valued representations. The simplicity of the expressions is that they are merely functions of the quantum numbers of the group chain O ⊃ C. The symmetry of the CG coefficients is also derived. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Mott–Wannier excitons in the tetragonal BaTiO3 lattice
Authors: Prócel Luis Miguel , Tipán Francisco , Stashans Arvids
Published: January 2003

Structural and electronic properties of excitons in the tetragonal BaTiO3 crystal is studied using a quantum chemical method developed for crystals. The obtained defect structure corresponds to the so‐called Mott–Wannier‐type exciton having a considerable distance between the hole and electronic parts of the defect. Performed crystalline lattice relaxation shows displacements of atoms in an extensive defective region of up to 12 atoms. However, the calculated magnitudes of atomic movements are not large, normally not exceeding 0.08 Å. It is also observed that the self‐trapped exciton polarizes the lattice around it. Using the so‐called ΔSCF method, the luminescence energy due to the exciton is found to be equal to 0.94 eV. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Applications of density functional theory methods in millimeter‐wave spectroscopy
Authors: Rissi Eduardo , Rivelino Roberto , Canuto Sylvio
Published: January 2003

Density functional theory (DFT), using the most common functionals, and ab initio quantum chemistry methods are used to calculate the rotational constants and dipole moments of the astrophysically important molecules HCN, CH3CN, CH3CNH+, HCCCN, and HCCNC. As far as millimeter‐wave spectroscopy is of interest the DFT methods performed well with most functionals, giving results within ±1% of experiments for rotational constants and ±3% for dipole moments. Analyzing the results obtained with all theoretical models, it may be concluded that the Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP) and Becke's three‐parameter functional with Perdew–Wang correlational functional [B3PW91/6‐31G(d, p)] give the best performances. A detailed analysis of the electron correlation effects shows that HCCCN is more stable than is HCCNC, by 1.16 eV, with important contribution arising from triple excitations. This result is also compared with those obtained with DFT methods. Despite occasional difficulties, DFT with the currently available functionals are of great utility in quickly assessing spectroscopic parameters of astrophysical interest. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003