bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels
Authors: Lienicke Uta , Hammer Hannes , Schneider Martin , Heling Kai , Wauer Roland R. , Mau Harald , Vogel Martin 
Published: October 2002

AbstractInterstitial proliferation of striated muscle in the lung is extremely rare. Most cases are associated with other congenital malformations, such as lung sequestration, diaphragmatic hernia, or cardiac malformations. We describe a newborn with rhabdomyomatous dysplasia of the lung associated with multiple congenital malformations of the heart and great vessels.The female neonate was born at 37 weeks of gestation as the second child to a 31‐year‐old woman without relevant previous medical or family history. In week 26 of gestation, a complex heart malformation and polyhydramnion were diagnosed by ultrasound. Postnatally, right lung hypoplasia, a bilobar right and left lung, anomalous drainage of the pulmonary veins, atrial and ventricular septal defects, and double‐outlet right‐ventricle and multiple aortopulmonary collaterals were described. Histological examination of a biopsy of the right lung demonstrated the presence of numerous bundles of striated muscle fibers arranged randomly in the pulmonary interstitium.Unilateral resection of the right lung was not a therapeutic option, because the left lung had developed bronchopulmonary dysplasia with severe reduction in gas exchange as a consequence of long‐term mechanical ventilation. Symptomatic relief and palliative cardiac surgery were offered. At age 5 months, the infant died of a pulmonary hemorrhage following cardiac surgery. Pediatr Pulmonol. 2002; 34:222–225. © 2002 Wiley‐Liss, Inc.
Progressive prostate hyperplasia in adult prolactin transgenic mice is not dependent on elevated serum androgen levels
Authors: Kindblom Jon , Dillner Karin , Ling Charlotte , Törnell Jan , Wennbo Håkan 
Published: October 2002

AbstractBACKGROUNDTransgenic mice overexpressing the rat prolactin (PRL) gene under control of the metallothionein‐1 promoter (Mt‐1) develop a dramatic prostatic enlargement. These animals also display significantly elevated testosterone serum levels. In this study, we aim to clarify the role of circulating androgen levels in the promotion of abnormal prostate growth in the adult PRL transgenic mouse prostate.METHODSProstate morphology and androgen‐receptor distribution patterns were analyzed in castrated and testosterone substituted adult PRL transgenic and in wild‐type males.RESULTSProgressive prostatic hyperplasia in adult PRL transgenic males was not affected by substitution to serum testosterone levels corresponding to wild‐type. Furthermore, prolonged testosterone treatment in adult wild‐type males did not produce any significant changes in prostate growth or morphology compared with wild‐type controls. Immunohistochemical studies revealed a significantly increased proportion of androgen receptor positive epithelial cells in all lobes of the PRL transgenic prostate versus wild‐type.CONCLUSIONThe present study demonstrates that progressive prostate hyperplasia in adult PRL transgenic mice is not dependent on elevated serum androgen levels. Furthermore, prolonged androgen treatment in adult wild‐type male mice appears to have no significant effect on prostate growth. In addition, our results suggest that prolonged hyperprolactinemia results in changes in prostate epithelial and stromal cell androgen receptor distribution. Prostate 53: 24–33, 2002. © 2002 Wiley‐Liss, Inc.
Androgens block interleukin‐1β–induced promatrilysin expression in prostate carcinoma cells
Authors: Stratton M. Suzanne , Greenstein Benjamin , Udayakumar Thirupandiyur S. , Nagle Raymond B. , Bowden G. Timothy 
Published: October 2002

AbstractBACKGROUNDWe have shown previously that interleukin (IL) ‐1β– and IL‐6–induced promatrilysin expression is mediated by an indirect pathway that requires NFκB‐dependent synthesis of IL‐6 and STAT3 signaling. We now demonstrate that IL‐1β–induced but not IL‐6–induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node–derived carcinoma cells of the prostate).METHODSBy using enzyme‐linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL‐1β or IL‐6 LNCaP‐treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL‐6–treated cells pretreated with testosterone.RESULTSIn LNCaP treated with testosterone before IL‐1β stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NFκB transactivation activity and induction of IL‐6 protein expression and mRNA. Testosterone and 5α‐dihydrotestosterone did not have an inhibitory effect on IL‐6–induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NFκB transactivation activity.CONCLUSIONFrom these data, we conclude that testosterone blocks IL‐1β–induced promatrilysin expression by inhibition of NFκB transactivation activity, which in turn, blocks IL‐6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL‐1β and IL‐6 may provide alternative drug targets for inhibiting prostate cancer progression. Prostate 53: 1–8, 2002. © 2002 Wiley‐Liss, Inc.
Both retinoids and androgens are required to maintain or promote functional differentiation in reaggregation cultures of human prostate epithelial cells
Authors: Goossens Karine , Deboel Ludo , Swinnen Johannes V. , Roskams Tania , Manin Michèle , Rombauts Wilfried , Verhoeven Guido 
Published: October 2002

AbstractBACKGROUNDPrimary cultures and subcultures of prostate epithelial cells (PEC) proliferate markedly, but rapidly loose secretory differentiated function and androgen responsiveness. Here, we investigated whether differentiation could be restored or preserved by using three‐dimensional reaggregation cultures treated with retinoids and/or androgens.METHODSPEC were cultured as monolayers or as reaggregation cultures on a rotatory shaker. Reaggregation cultures were also developed from freshly isolated cells. Morphology was evaluated microscopically. Expression of cytokeratins (CKbasal for basal cells and CK18 for luminal cells), E‐cadherin, α‐ and β‐catenin, androgen receptor (AR), and prostate specific antigen (PSA) was evaluated by immunohistochemistry and/or Western blotting. Differentiated function was further evaluated by measurements of PSA in the medium and by reverse transcriptase‐polymerase chain reactions for AR, PSA, prostate specific membrane antigen, β‐microseminoprotein, and zinc‐α2‐glycoprotein. Proliferation was evaluated by immunohistochemical staining for Ki‐67.RESULTSMonolayer cultures of PEC expressed CKbasal as well as CK18, a combination compatible with an intermediary amplifying population of epithelial cells. No expression of PSA could be detected, and all attempts to re‐induce differentiation of PEC in classic two‐dimensional culture systems failed. In reaggregation cultures of subcultured PEC, retinoids proved essential to maintain a compact three‐dimensional structure. This effect was accompanied by increased levels of E‐cadherin and of the catenins and by a shift in the cytokeratin expression pattern toward that typical for secretory differentiated cells (CK18 only). Even in the presence of androgens, however, PSA remained undetectable. Similar effects of retinoids were observed in reaggregation cultures of freshly prepared PEC, and in the latter cultures, the combination of androgens and retinoids maintained a low level of PSA secretion for at least 40 days.CONCLUSIONSA combination of retinoids and androgens is able to preserve, for a prolonged period of time, some degree of secretory differentiation in freshly isolated PEC maintained in reaggregation culture. The same combination is unable to restore secretory differentiation in subcultured PEC. Prostate 53: 34–49, 2002. © 2002 Wiley‐Liss, Inc.
Fas‐Fas ligand signaling pathway mediates an interleukin‐12–induced rejection of a murine prostate tumor system
Authors: Zhang Shaobo , Zeng Guangyuan , Kao Chinghai , Gardner Thomas , Sweeney Christopher , Yang Ning‐Sun , Eble John N. , Cheng Liang 
Published: October 2002

AbstractBACKGROUNDRecent data suggest that anti‐tumor activities of interleukin‐12 (IL‐12) involve the induction of apoptosis. Fas (APO‐1/CD95) is a type I membrane protein that is capable of initiating an apoptosis signaling pathway when bound to its ligand (FasL). We undertook this study to test the hypothesis that Fas‐FasL–mediated apoptosis plays a role in IL‐12–induced tumor regression.METHODSAn mIL‐12 expression vector driven by cytomegalovirus promoter was used to express murine IL‐12 cDNA in the RM‐9 murine prostate carcinoma cell line. Control RM‐9 cells and RM‐9 cells stably transfected with IL‐12 gene (RM‐9‐IL12) were inoculated subcutaneously in 4‐ to 6‐week‐old male C57BL/J6 mice. Tumor size was measured every 3 days. Western blot and immunohistochemical assays were used to evaluate Fas and FasL protein expression. In situ fluorescent end labeling was used to label apoptotic cells.RESULTSIL‐12–expressing RM‐9 prostate carcinoma cells transplanted into C57BL/J6 mice grew more slowly than control RM‐9 cells and vector control RM‐9‐Luc cells. The average survival time of the RM‐9‐IL12 mice was longer than 53 days, whereas the mean survival for mice transplanted with control RM‐9 cells was only 16 days. Apoptotic cells were more numerous in RM‐9‐IL12 tumors: 10.3% vs. 1.5% in control (P = 0.001). Fas and FasL proteins were increased approximately twofold in the RM‐9‐IL12 tumors compared with the RM‐9 control tumors as determined by Western blot and immunohistochemical analyses (P < 0.05).CONCLUSIONThe Fas‐FasL–mediated apoptosis pathway may contribute to the IL‐12–induced rejection of prostate carcinoma. Prostate 53: 69–76, 2002. © 2002 Wiley‐Liss, Inc.
Towards atomic resolution with crystals grown in gel: The case of thaumatin seen at room temperature
Authors: Sauter Claude , Lorber Bernard , Giegé Richard 
Published: October 2002

AbstractOne reason for introducing a gel in the crystallization medium of proteins is its ability to reduce convection in solution. This can lead to better nucleation and growth conditions, and to crystals having enhanced diffraction properties. We report here the X‐ray characterization at room temperature of high‐quality crystals of the intensely sweet thaumatin prepared in a sodium tartrate solution gelified with 0.15% (m/v) agarose. Using a synchrotron radiation, these crystals diffracted to a previously unachieved resolution. A diffraction dataset was collected from four crystals at a resolution of 1.2 Å with a Rsym of 3.6% and a completeness of 99%. Refinement was carried out to a final crystallographic R‐factor of 12.0%. The quality of the electron density map allowed for the observation of fine structural details in the protein and its solvation shell. Crystallization in gel might be used more generally to improve the quality of macromolecular crystals. Advantages provided by the gelified medium in the frame of structural studies are emphasized. Proteins 2002;48:146–150. © 2002 Wiley‐Liss, Inc.
Model of the αLβ2 integrin I‐domain/ICAM‐1 DI interface suggests that subtle changes in loop orientation determine ligand specificity
Authors: Legge Glen B. , Morris Garrett M. , Sanner Michel F. , Takada Yoshikazu , Olson Arthur J. , Grynszpan Flavio 
Published: October 2002

AbstractThe interaction of the αLβ2 integrin with its cellular ligand the intercellular adhesion molecule‐1 (ICAM‐1) is critical for the tight binding interaction between most leukocytes and the vascular endothelium before transendothelial migration to the sites of inflammation. In this article we have modeled the αL subunit I‐domain in its active form, which was computationally docked with the D1 domain of the ICAM‐1 to probe potential protein‐protein interactions. The experimentally observed key interaction between the carboxylate of Glu 34 in the ICAM‐1 D1 domain and the metal ion‐dependent adhesion site (MIDAS) in the open αL I‐domain was consistently reproduced by our calculations. The calculations reveal the nature of the αLβ2/ICAM‐1 interaction and suggest an explanation for the increased ligand‐binding affinity in the “open” versus the “closed” conformation of the αL I‐domain. A mechanism for substrate selectivity among αL, αM, and α2 I‐domains is suggested whereby the orientation of the loops within the I‐domain is critical in mediating the interaction of the Glu 34 carboxylate of ICAM‐1 D1 with the MIDAS. Proteins 2002;48:151–160. © 2002 Wiley‐Liss, Inc.
Normal mode analysis of macromolecular motions in a database framework: Developing mode concentration as a useful classifying statistic
Authors: Krebs W. G. , Alexandrov Vadim , Wilson Cyrus A. , Echols Nathaniel , Yu Haiyuan , Gerstein Mark 
Published: October 2002

AbstractWe investigated protein motions using normal modes within a database framework, determining on a large sample the degree to which normal modes anticipate the direction of the observed motion and were useful for motions classification. As a starting point for our analysis, we identified a large number of examples of protein flexibility from a comprehensive set of structural alignments of the proteins in the PDB. Each example consisted of a pair of proteins that were considerably different in structure given their sequence similarity. On each pair, we performed geometric comparisons and adiabatic‐mapping interpolations in a high‐throughput pipeline, arriving at a final list of 3,814 putative motions and standardized statistics for each. We then computed the normal modes of each motion in this list, determining the linear combination of modes that best approximated the direction of the observed motion. We integrated our new motions and normal mode calculations in the Macromolecular Motions Database, through a new ranking interface at http://molmovdb.org. Based on the normal mode calculations and the interpolations, we identified a new statistic, mode concentration, related to the mathematical concept of information content, which describes the degree to which the direction of the observed motion can be summarized by a few modes. Using this statistic, we were able to determine the fraction of the 3,814 motions where one could anticipate the direction of the actual motion from only a few modes. We also investigated mode concentration in comparison to related statistics on combinations of normal modes and correlated it with quantities characterizing protein flexibility (e.g., maximum backbone displacement or number of mobile atoms). Finally, we evaluated the ability of mode concentration to automatically classify motions into a variety of simple categories (e.g., whether or not they are “fragment‐like”), in comparison to motion statistics. This involved the application of decision trees and feature selection (particular machine‐learning techniques) to training and testing sets derived from merging the “list” of motions with manually classified ones. Proteins 2002;48:682–695. © 2002 Wiley‐Liss, Inc.
Protein molecular dynamics with electrostatic force entirely determined by a single Poisson‐Boltzmann calculation
Authors: Lu Ben Zhuo , Chen Wei Zu , Wang Cun Xin , Xu Xiao‐jie 
Published: October 2002

AbstractThe electrostatic force including the intramolecular Coulombic interactions and the electrostatic contribution of solvation effect were entirely calculated by using the finite difference Poisson‐Boltzmann method (FDPB), which was incorporated into the GROMOS96 force field to complete a new finite difference stochastic dynamics procedure (FDSD). Simulations were performed on an insulin dimer. Different relative dielectric constants were successively assigned to the protein interior; a value of 17 was selected as optimal for our system. The simulation data were analyzed and compared with those obtained from 500‐ps molecular dynamics (MD) simulation with explicit water and a 500‐ps conventional stochastic dynamics (SD) simulation without the mean solvent force. The results indicate that the FDSD method with GROMOS96 force field is suitable to study the dynamics and structure of proteins in solution if used with the optimal protein dielectric constant. Proteins 2002;48:497–504. © 2002 Wiley‐Liss, Inc.
Prediction of protein solvent accessibility using support vector machines
Authors: Yuan Zheng , Burrage Kevin , Mattick John S. 
Published: October 2002

AbstractA Support Vector Machine learning system has been trained to predict protein solvent accessibility from the primary structure. Different kernel functions and sliding window sizes have been explored to find how they affect the prediction performance. Using a cut‐off threshold of 15% that splits the dataset evenly (an equal number of exposed and buried residues), this method was able to achieve a prediction accuracy of 70.1% for single sequence input and 73.9% for multiple alignment sequence input, respectively. The prediction of three and more states of solvent accessibility was also studied and compared with other methods. The prediction accuracies are better than, or comparable to, those obtained by other methods such as neural networks, Bayesian classification, multiple linear regression, and information theory. In addition, our results further suggest that this system may be combined with other prediction methods to achieve more reliable results, and that the Support Vector Machine method is a very useful tool for biological sequence analysis. Proteins 2002;48:566–570. © 2002 Wiley‐Liss, Inc.
Inhibitor binding alters the directions of domain motions in HIV‐1 reverse transcriptase
Authors: Temiz N. Alpay , Bahar Ivet 
Published: October 2002

AbstractUnderstanding the molecular mechanisms of HIV‐1 reverse transcriptase (RT) action and drug inhibition is essential for designing effective antiretroviral therapies. Although comparisons of the different crystal forms of RT give insights into the flexibility of different domains, a direct computational assessment of the effect of inhibitor binding on the collective dynamics of RT is lacking. A structure‐based approach is used here for exploring the dynamics of RT in unliganded and inhibitor‐bound forms. Non‐nucleoside RT inhibitors (NNRTI) are shown to interfere directly with the global hinge‐bending mechanism that controls the cooperative motions of the p66 fingers and thumb subdomains. The net effect of nevirapine binding is to change the direction of domain movements rather than suppress their mobilities. The second generation NNRTI, efavirenz, on the other hand, shows the stronger effect of simultaneously reorienting domain motions and obstructing the p66 thumb fluctuations. A second hinge site controlling the global rotational reorientations of the RNase H domain is identified, which could serve as a target for potential inhibitors of RNase H activity. Proteins 2002;49:61–70. © 2002 Wiley‐Liss, Inc.
Risks to the aquatic ecosystem from the application of Metarhizium anisopliae for locust control in Australia
Authors: Milner Richard J , Lim Richard P , Hunter David M 
Published: October 2002

AbstractLaboratory tests of Metarhizium anisopliae var acridum Driver & Milner, at a dose of 1.3 × 106 conidia ml−1, had no adverse effects on nymphs of mayfly, Ulmerophlebia sp or 8‐week‐old fry of the rainbow fish, Melanotaenia duboulayi Castelnau. This dose was toxic to the cladoceran, Ceriodaphnia dubia Richard, causing 100% mortality in 48 h. When this test was repeated at doses of up to 6.7 × 103 conidia ml−1, there was only 5% mortality after 192 h. Spraying of artificial water sources with a very high dose of the fungus as an aqueous spray resulted in 80–130 conidia ml−1 at 15 cm depth in the first 24 h after spraying. The conidia rapidly settled out and were absent from the top 15 cm layer of water after about 50 h. A similar experiment using the oil formulation as used in field control resulted in a 2‐ to 20‐fold lower level of conidia in the water. Finally, sampling actual water sources in spray areas revealed a very low level of contamination of the water, with a maximum mean level of 29 conidia ml−1 in the first 24 h after treatment. Thus the level of conidia likely to enter water during control campaigns is a small fraction of that required to kill cladocerans, the only sensitive non‐target organism tested. It is concluded that the biopesticide is very unlikely to pose any hazard to aquatic organisms.© 2002 Society of Chemical Industry
Do statisticians count? A personal view
Authors: Grieve A. P. 
Published: October 2002

AbstractThe number of statisticians working in the pharmaceutical industry has risen 50‐fold since the formation of PSI in 1977. It would be comforting to think that the influence of statisticians within their companies has increased in a parallel fashion, however I do not believe that to be the case. In this paper I look at barriers which prevent statisticians contributing as much as they should and look at potentials solutions. Copyright © 2002 John Wiley & Sons, Ltd.
Psychopharmacological studies on Tragia involucrata root extract
Authors: Dhara A. K. , Pal S. , Nag Chaudhuri A. K. 
Published: October 2002

AbstractThe methanol fraction of the root extract of Tragia involucrata was investigated for psychopharmacological activity in rodents. It produced an alteration of behavioural pattern and a reduction in spontaneous motility. A significant potentiation of pentobarbitone‐induced sleep, a decrease of body temperature, suppression of the aggressive behaviour pattern and of the conditioned avoidance response (CAR) were observed with the fraction. These suggest that the methanol fraction of the T. involucrata root extract possesses significant central nervous system depressant action. Copyright © 2002 John Wiley & Sons, Ltd.
Activity of essential oils of three Micromeria species (Lamiaceae) against micromycetes and bacteria
Authors: Marinković B. , Marin P. D. , Knez̆ević‐Vukc̆ević J. , Soković M. D. , Brkić D. 
Published: October 2002

AbstractThe chemical composition of essential oils from three Micromeria species: M. dalmatica Benth., M. albanica (Griceb. ex K. Mal) Šilić and M. thymifolia (Scop.) Fritsch were investigated by GC and GC‐MS and their antibacterial and antifungal activities against seven fungal and six bacterial species were evaluated. Biological assays showed strong fungitoxicity of oils from all three Micromeria spp., particularly M. albanica, against all fungi tested. Essential oils of these species also exerted antibacterial effect against Streptococcus aureus, Escherichia coli, Bacillus subtilis and Micrococcus luteus at low concentrations. Higher concentrations of essential oil of M. albanica and M. dalmatica were active against Gram‐negative Pseudomonas aeruginosa, which could be due to the high content of piperitenone oxide. Copyright © 2002 John Wiley & Sons, Ltd.