bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic plasticity of neural stem cells: Fact or fancy?
Authors: Greco Beatrice , Recht Lawrence 
Published: December 2002

AbstractSeveral studies have described the potential for embryonic and adult neural stem cells to differentiate into non‐neural cells such as muscle and blood, tissues that are derived from non‐neuroectodermal germ layers. This raised the exciting possibility that these cells possessed a broader range of differentiation potential than originally thought and raised interesting prospects for possible transplantation utilization. However, a number of recent reports have raised questions about whether the phenomena observed actually represented true somatic plasticity. In this review, we critically analyze these studies with the aim of providing some criteria by which future studies that address this important problem may be evaluated. © 2002 Wiley‐Liss, Inc.
Induction of senescence‐associated growth inhibitors in the tumor‐suppressive function of retinoids
Authors: Roninson Igor B. , Dokmanovic Milos 
Published: December 2002

AbstractRetinoids, physiological regulators of cell growth and differentiation, are used in the treatment or chemoprevention of several malignant diseases. This class of compounds can induce growth arrest or apoptosis in tumor cells. Permanent growth arrest of retinoid‐treated cells is often assumed to result from retinoid‐induced differentiation. Recent studies in breast carcinoma and neuroblastoma cells demonstrated that retinoids can stop tumor cell growth through the program of senescence rather than differentiation. Retinoid‐induced tumor suppression is associated with the induction of multiple intracellular and secreted growth‐inhibitory proteins. Most of these proteins were also found to be upregulated in senescent cells. The induction of senescence‐associated growth inhibitors appears to be an indirect effect of retinoids. Elucidation of the mechanisms responsible for the induction of growth‐inhibitory genes in retinoid‐treated cells should help in developing agents that would mimic the antiproliferative effect of retinoids in retinoid‐insensitive cancers. © 2002 Wiley‐Liss, Inc.
Retinal neuroprotection by growth factors: A mechanistic perspective
Authors: Chaum Edward 
Published: December 2002

AbstractFor more than a decade it has been known that certain growth factors inhibit apoptosis in genetically determined and experimental models of inner and outer retinal degeneration. The molecular mechanisms underlying these protective effects and the signaling that supports the survival of photoreceptors and retinal ganglion cells in these models have recently come under more in depth investigation. This paper reviews our current understanding of the balance of pro‐ and antiapoptotic signals that determine cell fate in the retina and how the activation of key signal transduction pathways by specific classes of neurotrophins protects retinal neurons. © 2002 Wiley‐Liss, Inc.
Induction of p202, a modulator of apoptosis, during oncogenic transformation of NIH 3T3 cells by activated H‐Ras (Q61L) contributes to cell survival
Authors: Xin Hong , Geng Yanbiao , Pramanik Rocky , Choubey Divaker 
Published: December 2002

AbstractPrevious studies have revealed that p202 (52 kDa), an interferon (IFN) and differentiation‐inducible protein, negatively regulates cell proliferation and modulates cell survival. However, the role of p202 in transformed cells remains to be investigated. Here we report that constitutive expression of oncogenic H‐Ras (Q61L) in NIH 3T3 cells, which resulted in cell transformation, was associated with increases in the steady‐state levels of 202 RNA and protein. Interestingly, the increase in p202 levels in transformed cells correlated with increases in the activity of the transcription factor c‐Jun/AP‐1, which bound to the two potential AP‐1 DNA binding sites (the AP‐1CS1 and AP‐1CS2) in the 5′‐regulatory region of the 202 gene in gel mobility shift assays. Furthermore, the site‐directed mutagenesis, coupled with promoter‐reporter analyses, revealed that these two AP‐1 DNA binding sites contribute to the regulation of the 202 gene in Ras transformed cells. Because treatment of transformed cells with a specific inhibitor of MEK (PD 98059) resulted in significant decreases in the levels of p202, these observations raise the possibility that in transformed cells Ras/Raf/MEK pathway regulates the transcriptional activation of the 202 gene. Significantly, decreases in the levels of p202 in Ras transformed NIH 3T3 cells under reduced serum conditions increased the susceptibility to apoptosis. Collectively, our observations support the idea that the transcriptional increases in the levels of p202 by oncogenic H‐Ras in NIH 3T3 cells are needed for cell survival. © 2002 Wiley‐Liss, Inc.
Microsatellite DNA analyses support an east‐west phylogeographic split of American alligator populations
Authors: Davis Lisa M. , Glenn Travis C. , Strickland Denise C. , Guillette Louis J. , Elsey Ruth M. , Rhodes Walter E. , Dessauer Herbert C. , Sawyer Roger H. 
Published: December 2002

AbstractWe examined the population genetic structure of American alligators (Alligator mississippiensis) sampled from 12 localities across the southeastern United States. The primary goal of this study was to determine the extent of population differentiation among alligators from four Florida lakes using eight microsatellite loci and compare the results to additional sites located at varying distances from them. Analyses of population structure revealed little differentiation (FST=0.039; Rho=0.012) among the four Florida lakes, Apopka, Griffin, Orange and Woodruff, which are all located in the St. John&&apos;s River watershed in north‐central Florida. Further, there was little differentiation among these samples and samples collected from the Everglades National Park (FST=0.044; Rho=0.009) and south Georgia (FST=0.045; Rho=0.032). Therefore, these six samples were pooled together as a “FL/sGA group.” Similarly, samples collected in the western extent of the range, Anahuac National Wildlife Refuge in Texas and Salvador Wildlife Management Area, Marsh Island Wildlife Refuge and Rockefeller Wildlife Refuge in Louisiana, also lacked population structure (FST=0.024; RST=0.040). These four populations were pooled into the “TX/LA group.” Comparisons of these two groups with samples taken from the Santee Coastal Reserve in South Carolina and Mobile, Alabama yielded three to four times more differentiation among groups (FST=0.131; Rho=0.187). These and other analyses support the hypothesis of an east‐west phylogeographic split in American alligator populations and are consistent with studies of many freshwater fish and aquatic and terrestrial turtles distributed throughout this same geographic region. J. Exp. Zool. (Mol. Dev. Evol.) 294:352–372, 2002. © 2002 Wiley‐Liss, Inc.
Serum procalcitonin concentrations in bacterial pneumonia in children: A negative result in primary healthcare settings
Authors: Korppi Matti , Remes Sami , Heiskanen‐Kosma Tarja 
Published: December 2002

AbstractA microbe‐specific diagnosis in community‐acquired pneumonia (CAP) is difficult in children, and studies on nonspecific chest radiographic and host response markers have been inconsistent. Serum procalcitonin (PCT) is a newly recognized, promising marker for differentiating between bacterial and viral infections. Serum PCT was measured by a luminometric assay in 190 children with CAP diagnosed in the primary healthcare setting during a population‐based study in a geographically defined population. The pneumococcal, mycoplasma, chlamydia, and viral etiology of infections was studied by an extensive serologic test panel.The median PCT concentrations were 0.47, 0.46, and 0.35 ng/mL in children aged <5 years, 5–9 years, and ≥10 years (P = 0.004). An elevated PCT >1.0 ng/mL was seen in 12.1% and >2.0 ng/mL in only 2.1% of the children. No association was seen between severity (inpatient vs. outpatient care) and etiology of CAP (evidence for pneumococcal, mycoplasma, or chlamydia, vs. viral infection).We conclude that serum PCT measurements have no role in the diagnosis of bacterial CAP in children in primary healthcare settings. Pediatr Pulmonol. 2003; 35:56–61. © 2003 Wiley‐Liss, Inc.
Influence of maturation on infant diaphragm function assessed by magnetic stimulation of phrenic nerves
Authors: Dimitriou Gabriel , Greenough Anne , Moxham John , Rafferty Gerrard F. 
Published: December 2002

AbstractInfant diaphragm function may be adversely affected in a variety of disorders and conditions. Key to establishing an accurate diagnosis are appropriate control data. The aim of this study was to determine the effect of maturation on diaphragm function, using a nonvolitional test. Diaphragm function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated by magnetic stimulation of the phrenic nerves. Ballon catheters were positioned in the lower third of the esophagus and stomach. Esophageal (Pes) and gastric (Pgas) pressure changes were measured using differential pressure transducers. The pressure signals were amplified and displayed in real time on a computer (running Labview™ software) and Pdi derived by online subtraction of Pes from Pgas.Twenty‐nine infants (14 born preterm), at a median gestational age of 37 (range, 25–42) weeks, were studied at a median postconceptional age (PCA) of 39 (range, 32–44) weeks. At time of measurement, none had respiratory problems or were hyperinflated (functional residual capacity ranged from 23–35 mL/kg). The preterm infants had significantly lower transdiaphragmatic pressures responses following median left (4.0, range 2.5–6.8 cmH2O vs. 4.8, range 2.8–7.2 cmH2O) and median right phrenic nerve stimulation (3.6, range 2.6–4.8 cmH2O vs. 4.3, range 2.7–6.8 cmH2O) (P < 0.05) than term infants. Following left and right phrenic nerve stimulation, Pdi correlated significantly with gestational age (r = 0.4, P < 0.05, and r = 0.4, P < 0.05, respectively) and PCA (r = 0.37, P = 0.05, and r = 0.56, P < 0.01, respectively).We conclude that gestational age at birth and postconceptional age at time of measurements must be taken into account when interpreting the results of infant diaphragm function tests. Pediatr Pulmonol. 2003; 35:17–22. © 2003 Wiley‐Liss, Inc.
Lung function and symptom perception in children with asthma and their parents
Authors: Horak Elisabeth , Grässl Gerhard , Skladal Daniela , Ulmer Hanno 
Published: December 2002

AbstractA large proportion of children with asthma are managed without recourse to specialized care, and treatment decisions are based solely on symptoms as reported by the children and their parents. We investigated 90 school‐age children with the diagnosis of asthma and their accompanying parent to evaluate whether we can obtain better information by using three different means of asking for asthma symptoms: a questionnaire for children (QSRchildren), “smilies,” and a visual analogue scale for children (VASchildren). Furthermore, we analyzed the relationship between these symptom reports and lung function results. Finally, we attempted to determine whether performing a lung function test contributes relevant information toward improving asthma management.Multiple linear regression adjusted for age and gender showed a significant relationship between VAS for children and forced expiratory volume in 1 sec (FEV1) (P = 0.047) and maximal expiratory flow at 50% of forced vital capacity (MEF50) (P = 0.037). Neither age, gender, QSR for children, “smilies for children” nor all the parents' scores showed a significant association with lung function measurement in the regression model. Subgroup analysis with Spearman's rank correlation coefficients by age group revealed significant correlation in children <10 years between VAS for children, QSR for parents, smilies for parents, and the lung function parameters FEV1, and MEF50. Above age 10 years there was no correlation at all, with the accuracy correlation ranging from −0.04 to +0.21.Our data demonstrate that reported symptoms do not reliably correlate with lung function results in asthmatic children and the childrens' parents, and correlation is dependent on the instrument used for symptom evaluation. In children, the VAS, and in parents, the QSR were the most valuable means of obtaining best information on asthma symptoms. This underlines the importance of supplementing information on asthma symptoms with lung function measurements to more reliably assess the severity of asthma. Pediatr Pulmonol. 2003; 35:23–28. © 2003 Wiley‐Liss, Inc.
Thrombin contributes to bronchoalveolar lavage fluid mitogenicity in lung disease of the premature infant
Authors: Dik Willem A. , Zimmermann Luc J.I. , Naber Brigitta A. , Janssen Daphne J. , van Kaam Anton H.L.C. , Versnel Marjan A. 
Published: December 2002

AbstractChronic lung disease of prematurity (CLD) is a common consequence of neonatal respiratory distress syndrome (RDS) and is characterized by pulmonary fibrosis. Increased thrombin activity in the alveolar compartment is associated with pulmonary fibrosis in adults and animals, and contributes to bronchoalveolar lavage (BAL) fluid mitogenicity for fibroblasts. We hypothesized that BAL fluid from infants who develop CLD contains increased mitogenic activity for lung fibroblasts compared to BAL fluid from resolving RDS, and that increased thrombin levels contribute to this activity. Sequential BAL (postnatal days 2–14) was obtained from 37 premature infants who were ventilated for RDS. Twenty‐six infants developed CLD, whereas 11 resolved. BAL fluid mitogenic activity was determined in a proliferation assay, using human fetal lung fibroblasts. The contribution of thrombin to mitogenic activity was determined using the thrombin inhibitor PPACK. Furthermore, thrombin levels in BAL fluid were measured using a specific substrate to detect thrombin activity and by measuring thrombin‐antithrombin III complex (TATIII). BAL fluid mitogenic activity was comparable between CLD and RDS (CLD, 33% proliferation on day 2 to 41% on day 14; RDS, 21% on day 2 to 54% on day 7). Thrombin inactivation by PPACK completely inhibited mitogenic activity in BAL samples obtained on days 2 and 4 (CLD, P < 0.001 on days 2 and 4; RDS, P < 0.05 on day 4). From day 7 onwards, inhibition of thrombin only partly reduced (P < 0.05) CLD BAL fluid mitogenic activity, indicating that other mitogenic factors contribute as well. Suprisingly, thrombin activity and TATIII were decreased in BAL fluid from CLD compared with RDS patients on days 2 and 4. In conclusion, our study shows that BAL fluid from infants with and without CLD development is equally mitogenic for lung fibroblasts, and that thrombin is a major mitogen in these samples. This suggests that fibroproliferation may occur early in the lungs from infants with both CLD and RDS, and that thrombin contributes to this. Pediatr Pulmonol. 2003; 35:34–41. © 2003 Wiley‐Liss, Inc.
Method for assessment of volume of trapped gas in infants during multiple‐breath inert gas washout
Authors: Gustafsson Per M. , Källman Sigun , Ljungberg Henrik , Lindblad Anders 
Published: December 2002

AbstractA breath‐by‐breath inert gas washout method for assessment of the volume of trapped gas in the lungs (VTG) in sedated sleeping infants is described. It is based on washin using a gas mixture containing 4% sulfur hexafluoride (VTG,SF6) and washout with air. A mass spectrometer was used for continuous gas concentration measurements, and a Fleisch no. 0 pneumotachometer for flow measurement. When equilibration of the tracer gas was achieved with tidal breathing washin, five passive inflations with a maximum positive airway pressure of 20 cm of H2O were performed to ensure filling of lung spaces not communicating during tidal breathing. After tidal washout of the tracer gas by air until the end‐tidal concentration was 1/40th of its starting concentration, five passive inflations with air were instituted again. The VTG,SF6 was calculated from the volume of SF6 mobilized by these large breaths, and expressed as the corresponding volume of air.Triplets of VTG,SF6 determination in 8 infants aged 9–31 months with varying degrees of airway obstruction showed an average volume of 13.7 mL (range, 4.7–25.0). The average SD of the triplets was 2.1 mL (range, 0.1–5.5 mL). Subjects with high VTG,SF6/FRC results demonstrated lower maximal expiratory flow at FRC (V′maxFRC) results (Z‐scores) and greater inhomogeneity of ventilation distribution than those with low trapped gas volumes.It is concluded that gas trapping can be assessed with acceptable precision with this washout method. Further studies are needed to establish the sensitivity and usefulness of the method in infants with various types of airway pathology. Pediatr Pulmonol. 2003; 35:42–49. © 2003 Wiley‐Liss, Inc.
Nitrotyrosine and NO synthases in infants with respiratory failure: Influence of inhaled NO
Authors: Aikio Outi , Vuopala Katri , Pokela Marja‐Leena , Andersson Sture , Hallman Mikko 
Published: December 2002

AbstractInhaled nitric oxide (NO) is a selective vasodilator in pulmonary hypertension. However, the safety of inhaled NO (iNO) has not been established. Using an immunohistochemical technique, we studied the expression of NO synthase (NOS) isoforms NOS1, NOS2, NOS3, and nitrotyrosine, the marker of toxic NO‐superoxide pathway, in lung specimens from autopsies.Twelve infants dying with respiratory failure had iNO up to 60 parts per million for 0.1–15 days. Twelve control infants were matched in pairs on the basis of the diagnosis, number of gestational days at birth, age at death, and whether extracorporeal perfusion was required. In addition, 5 infants who died of SIDS or nonpulmonary trauma (healthy lungs) were compared to 8 age‐matched cases with respiratory failure. Immunostaining was graded by the intensity of the color deposit and the frequency in specific cells stained.Inhaled NO tended to increase NOS2 expression in bronchiolar epithelium and adjacent tissue. There were no other differences in the distribution of nitrotyrosine or NOS isoforms between iNO‐treated infants and the control group with respiratory failure. All NOS isoforms were evident in the lungs studied. In severe respiratory failure, nitrotyrosine was mostly detectable in the bronchiolar epithelium and alveolar exudates, whereas in healthy lungs those sites did not contain nitrotyrosine.The alveolar tissue of infants with progressive respiratory may be affected by the NO‐superoxide pathway. However, inhalation of NO was not associated with a detectable increase in oxidant stress. Pediatr Pulmonol. 2003; 35:8–16. © 2003 Wiley‐Liss, Inc.
Calcium binding to the transmembrane domain of the sarcoplasmic reticulum Ca2+‐ATPase: Insights from molecular modeling
Authors: Costa Valeria , Carloni Paolo 
Published: December 2002

AbstractSarcoplasmic reticulum Ca2+‐ ATPase pumps Ca2+ ions from muscle cells to the sarcoplasmic reticulum. Here we use molecular dynamics and electrostatic modeling to investigate structural and dynamical features of key intermediates in the Ca2+ binding process of the protein. Structural models of the protein (containing either two, one, or no calcium ions in the transmembrane domain) are constructed based on the X‐ray structure by Toyoshima et al. (Nature 2000;405:647–655). The protein is embedded in a water/octane bilayer, which mimics the water/membrane environment. Our calculations provide information on the hydration of the two Ca2+ ions, not emerging from the X‐ray structure. Furthermore, they indicate that uptake of the metal ions causes large structural rearrangements of the metal binding sites. In addition, they suggest that the two ions reach their binding sites via two specific pathways. Finally, they allow identification of residues in the outer mouth of the protein that might interact with the Ca2+ ions during the binding process. Proteins 2003;50:104–113. © 2002 Wiley‐Liss, Inc.
Protein‐based virtual screening of chemical databases. II. Are homology models of g‐protein coupled receptors suitable targets?
Authors: Bissantz Caterina , Bernard Philippe , Hibert Marcel , Rognan Didier 
Published: December 2002

AbstractThe aim of the current study is to investigate whether homology models of G‐Protein‐Coupled Receptors (GPCRs) that are based on bovine rhodopsin are reliable enough to be used for virtual screening of chemical databases. Starting from the recently described 2.8 Å‐resolution X‐ray structure of bovine rhodopsin, homology models of an “antagonist‐bound” form of three human GPCRs (dopamine D3 receptor, muscarinic M1 receptor, vasopressin V1a receptor) were constructed. The homology models were used to screen three‐dimensional databases using three different docking programs (Dock, FlexX, Gold) in combination with seven scoring functions (ChemScore, Dock, FlexX, Fresno, Gold, Pmf, Score). Rhodopsin‐based homology models turned out to be suitable, indeed, for virtual screening since known antagonists seeded in the test databases could be distinguished from randomly chosen molecules. However, such models are not accurate enough for retrieving known agonists. To generate receptor models better suited for agonist screening, we developed a new knowledge‐ and pharmacophore‐based modeling procedure that might partly simulate the conformational changes occurring in the active site during receptor activation. Receptor coordinates generated by this new procedure are now suitable for agonist screening. We thus propose two alternative strategies for the virtual screening of GPCR ligands, relying on a different set of receptor coordinates (antagonist‐bound and agonist‐bound states). Proteins 2003;50:5–25. © 2002 Wiley‐Liss, Inc.
Efficient RMSD measures for the comparison of two molecular ensembles
Authors: Brüschweiler Rafael 
Published: December 2002

AbstractQuantitative measures are presented for comparing the conformations of two molecular ensembles. The measures are based on Kabsch's formula for the root‐mean‐square deviation (RMSD) and the covariance matrix of atomic positions of isotropically distributed ensembles (IDE). By using a Taylor series expansion, it is shown that the RMSD can be expressed solely in terms of the IDE matrices. A fast approximate method is introduced for the pairwise RMSD determination whose computational cost scales linearly with the number of structures. A similarity measure for two structural ensembles that is based on the trace metric of the differences of powers of the IDE matrices is presented. The measures are illustrated for conformational ensembles generated by a molecular dynamics computer simulation of a partially folded A‐state analog of ubiquitin. Proteins 2003;50:26–34. © 2002 Wiley‐Liss, Inc.