bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of cholinergic dysfunction in rabbits following recurrent aspiration of cow's milk*
Authors: Larsen Gary L. , Loader Joan , Nguyen Dee Dee , Colasurdo Giuseppe N. 
Published: August 2002

AbstractRecurrent aspiration of cow's milk has been shown to alter neural control of airways in young rabbits (Gelfand et al., 1997). The purpose of this study was to define the mechanisms responsible for in vitro cholinergic hyperresponsiveness in this model. Beginning at 1 week of age, rabbits received either 0.5 mL/kg whole cow's milk or sterile saline intranasally while under light anesthesia. This was repeated each weekday for 2 weeks. At 8 weeks of age, rabbits were sacrificed. Portions of lungs underwent lavage with sterile saline. Tracheal smooth muscle (TSM) segments were also removed. Segments were assessed for acetylcholine (ACh) release by high‐performance liquid chromatography ( HPLC) with electrochemical detection or acetylcholinesterase (AChE) kinetic activity by spectrophotometry. Substance P (SP), a neuropeptide that can increase ACh release from nerves, was also assessed using an enzyme immunoassay to define the content in lavage and TSM segments. Immunohistochemistry for SP within airways was also assessed.We found that recurrent aspiration of milk led to statistically significant alterations in many parameters. Acetylcholine release was significantly greater in segments of airways from rabbits that had aspirated cow's milk (27.5 ± 1.7 vs. 20.1 ± 1.6 pmol/min/g tissue) than saline. At the same time, AChE activity was less in the group that aspirated milk (8.7 ± 0.4 vs. 10.2 ± 0.5 nmol/min/mg protein) compared to saline. The amount of SP within both lavage as well as tissue homogenates was greater in the group that had aspirated the foreign protein (159.1 ± 28.9 vs. 41.9 ± 5.2 pmol/mg protein in lavage; 158.7 ± 31.9 vs. 80.5 ± 7.8 pmol/mg protein in tissues) than saline controls. While total cholinergic nerve density as assessed by choline acetyltransferase was not significantly different between groups, SP‐positive immunoreactive nerves were easily identified in the group that aspirated cow's milk.This study suggests that cholinergic hyperresponsiveness caused by repeated aspiration of milk is due to several abnormalities, including prejunctional (increase in ACh release) as well as junctional (decrease in AChE) mechanisms within the airways. In addition, an upregulation of SP within airways is part of this process. Pediatr Pulmonol. 2001; 32:409–417. © 2001 Wiley‐Liss, Inc.
Oxygen saturation in adult cystic fibrosis patients during exercise at high altitude
Authors: Ryujin Darin T. , Mannebach Steven C. , Samuelson Wayne M. , Marshall Bruce C. 
Published: August 2002

AbstractThe objective of this study was to determine the frequency and severity of decreased arterial oxy‐hemoglobin saturation during exercise in adults with cystic fibrosis at 1,500 m above sea level. A convenience sample of 50 adults with cystic fibrosis who did not have hypoxemia (oxygen saturation, < 90%) at rest were evaluated. Spirometry was performed according to American Thoracic Society standards, and maximal exercise tests were performed on an electronically braked cycle ergometer using a ramp protocol individualized for each patient. Pulse oximetry was measured every 2 min.When exercising at high altitude, 45 of 50 patients had a decrease in arterial oxy‐hemoglobin saturation from baseline to some degree. In 29 patients, oxy‐hemoglobin saturation fell below 90%; in 14 patients, it fell below 85%; and in 4 patients, it fell below 80%. Oxy‐hemoglobin saturation decreased to < 90% in 12 of 14 patients with severe pulmonary disease (FEV1 < 40% predicted), in 15 of 26 patients with moderate disease (40% less than or equal to FEV1 < 70% predicted), in 2 of 6 patients with mild disease (70% less than or equal to FEV1 < 90% predicted), and in 0 of 4 with normal pulmonary function (FEV1 greater than or equal to 90%). Percent predicted FEV1 (r = 0.57; P < 0.0001) and FEV1/FVC ratio (r = 0.52; P < 0.0001) most highly correlated with arterial oxy‐hemoglobin saturation at peak exercise.We conclude that at 1,500 m above sea level, adult CF patients with obstructive airways disease are at significant risk for decreased arterial oxy‐hemoglobin saturation during exercise. A supervised exercise test should be considered prior to recommending an exercise program for such patients. Pediatr Pulmonol. 2001; 32:437–441. © 2001 Wiley‐Liss, Inc.
Quantitative analysis of end‐tidal carbon dioxide during mechanical and spontaneous ventilation in infants and young children
Authors: Hsieh Kai‐Sheng , Lee Cheng‐Liang , Lin Chu‐Chuan , Wu Sheng‐Nan , Ko Fang‐Yuan , Huang Yung‐Feng , Huang Ta‐Cheng 
Published: August 2002

AbstractCapnography provides a substitute for monitoring of arterial carbon dioxide tension (PCO2). We performed a prospective study to evaluate a new application of capnography, using quantitative curve analysis in the pediatric ICU. Twenty‐five infants and children admitted to the pediatric ICU after cardiovascular surgery for congenital heart diseases were included in the study. Capnographic curves were recorded during 3 phases of mechanical and spontaneous ventilation: phase 1, immediate postoperative period; phase 3, preextubation period; and phase 2, period between phases 1 and 3. Each recording included 17 sec of capnographic tracings from consecutive spontaneous and/or ventilator‐driven breaths. Quantitative curve analysis was made to define parameters including peak value of exhaled PCO2 (P), mean rate of rise of PCO2 (R), and area under each capnographic curve (A).Qualitative inspection of the wave contour showed no obvious difference in phase 3 during spontaneous and mechanically assisted ventilator breaths. However, an obvious difference existed between spontaneous and mechanically assisted breaths in phase 2. For each parameter (P, R, and A), there was a significant difference in phases 2 and 3 from spontaneous breaths. However, there was no significant difference in phases 2 and 3 from ventilator‐assisted breaths. We further calculated the ratio of parameters of spontaneous breaths (S) and ventilator‐assisted breaths (V) in phase 2 and phase 3. The ratio of S/V for P, R, and A showed significant differences between phase 2 and phase 3.We conclude that quantitative analysis of exhaled end‐tidal PCO2 curves revealed significant changes of specific parameters during the transition from the ventilator‐dependent state to the spontaneously breathing ventilator‐independent state. This new approach provides a new way to estimate respiratory status in infants and children receiving ventilator therapy. Through quantitative capnographic curve analysis, if P, R, and A from spontaneous breaths approached those of ventilator‐assisted breaths, patients have resumed reasonable pulmonary mechanics, and extubation may then be considered. Pediatr Pulmonol. 2001; 32:453–458. © 2001 Wiley‐Liss, Inc.
Congenital cystic adenomatoid malformation type 4
Authors: van Koningsbruggen Silke , Ahrens F. , Brockmann M. , Michalk D. , Rietschel E. 
Published: August 2002

AbstractA 9‐day‐old boy presented in respiratory distress and with failure to thrive. The chest X‐ray showed a hyperlucent area of the left lung. A resection of the markedly emphysematous segment 2 of the left upper lobe was performed assuming the emphysematous tissue was due to congenital lobar emphysema (CLE). Histological examination of the lung tissue, however, revealed a pattern consistent with congenital cystic adenomatoid malformation (CCAM) type 4.The therapy for CLE as well as for CCAM is similar, i.e., resection of the emphysematous tissue. As far as the prognosis is concerned, it is important to diagnose the exact type of malformation in order to exclude associated anomalies, as well as the risk of development of malignancies in later life.The frequency of associated malformations of CCAM type 4 is unknown. Although the risk for development of malignancies from CCAM type 4 is not clear at the moment, the possible development of malignancies justifies prompt resection shortly after diagnosis, even in asymptomatic patients. A life‐long follow‐up in those patients who had a resection of CCAM in early childhood is recommended. Pediatr Pulmonol. 2001; 32:471–475. © 2001 Wiley‐Liss, Inc.
Down‐regulation of the human kallikrein gene 5 (KLK5) in prostate cancer tissues
Authors: Yousef George M. , Scorilas Andreas , Chang Albert , Rendl Laura , Diamandis Maria , Jung Klaus , Diamandis Eleftherios P. 
Published: August 2002

AbstractBACKGROUNDKallikreins are a subgroup of serine proteases with diverse physiological functions. Many kallikrein genes are differentially expressed in various malignancies and prostate specific antigen (PSA; encoded by the KLK3 gene) is the best tumor marker for prostate cancer. Human glandular kallikrein (hK2; encoded by the KLK2 gene) is an emerging tumor marker for prostate cancer. KLK5 is a newly discovered human kallikrein gene which shares a high degree of homology and is located adjacent to KLK2 and KLK3 genes on chromosome 19q13.4. Like KLK2 and KLK3, the KLK5 gene is regulated by steroid hormones in the BT‐474 breast cancer cell line. We have previously shown that KLK5 is differentially expressed in ovarian and breast cancer.METHODSWe compared the expression of KLK5 in 29 pairs of histologically confirmed normal and prostate cancer tissues by quantitative RT‐PCR using the LightCycler technology.RESULTSKLK5 expression was significantly lower in cancer tissues compared to their normal counterparts. Lowest levels of expression were found in T3 stage tumors compared with T1 and T2. Also, a significant negative correlation was found between Gleason score and KLK5 expression.CONCLUSIONSKLK5 should be further studied as a potential new prognostic marker in prostate cancer, whose expression is negatively correlated with cancer aggressiveness. Prostate 51: 126–132, 2002. © 2002 Wiley‐Liss, Inc.
Alternative splicing isoforms of hippostasin (PRSS20/KLK11) in prostate cancer cell lines
Authors: Nakamura Terukazu , Mitsui Shinichi , Okui Akira , Kominami Katsuya , Nomoto Takeshi , Ukimura Osamu , Kawauchi Akihiro , Miki Tsuneharu , Yamaguchi Nozomi 
Published: August 2002

AbstractBACKGROUNDHippostasin is a kallikrein‐like protease (PRSS20/KLK11), which is expressed preferentially in the hippocampus and prostate. We have reported that alternative splicing variants of human hippostasin are regulated in a tissue‐specific manner. Brain‐type hippostasin consists of 250 amino acids including a typical signal sequence, and is expressed in the brain and prostate. The prostate‐type hippostasin, which has 32 extra amino acids at the N‐terminal end, is expressed only in the prostate.METHODSWe analyzed the expression and localization of hippostasin in normal prostate tissue, BPH tissue, and prostate cancer cell lines. We performed northern blotting, in situ hybridization, immunohistochemistry, and RT‐PCR.RESULTSHippostasin mRNA is expressed preferentially in the normal prostate and weakly in the testis. It was detected in prostate secretory epithelium. Hippostasin protein was localized in the prostate secretory epithelium, and western blotting showed that hippostasin was present in semen. All tested prostate cancer cell lines, including PSA‐negative cell lines, expressed hippostasin. Interestingly, all the prostate cancer cell lines expressed only brain‐type but not prostate‐type hippostasin, while normal prostate and BPH expressed both types of hippostasinCONCLUSIONSOur results suggest the possibility that hippostasin may be a useful marker by which prostate cancer and BPH can be distinguished Prostate 49:72–78, 2001. © 2001 Wiley‐Liss, Inc.
Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma
Authors: Szende B. , Romics I. , Minik K. , Szabó J. , Torda I. , Lovász S. , Szomor L. , Tóth L. , Bély M. , Kerényi T. , Bartók K. , Végh A. 
Published: August 2002

AbstractBackgroundApoptosis is one of the major events following total androgen blockade (TAB). The aim of this study was to determine the predictive value of some histological parameters including apoptosis and gene products which influence apoptosis, based on repeated biopsies taken from the same patients.MethodsAt the time of diagnosis by needle biopsy TNM stage, serum PSA, Gleason's grade, apoptotic and mitotic index, Ki67, p53, and bcl2 expression were investigated in 60 prostate carcinoma patients. Antiandrogen therapy supplemented with surgical or chemical castration was administered. Serum PSA‐test and needle biopsy were repeated 13–14 weeks after starting the therapy, simultaneously with determination of the apoptotic and mitotic index, Ki67, p53, and bcl2 expression.ResultsForty‐seven patients were alive at the end of the study, 13 patients died. Decrease in mitotic, increase in apoptotic index predicted favourable long‐term response to antiandrogen therapy. Lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to favourable effect of antiandrogen treatment. Since the ratio between Ki67 and apoptotic index strongly decreased in the survivors upon therapy, changes in Ki67/apoptosis ratio is recommended as a histologically detectable predictive factor. bcl2 expression did not show significant correlation with the outcome of the disease.ConclusionsHistological evaluation of mitotic and apoptotic index, Ki67, and p53 expression in repeated biopsies contributes to predicting the value of the actual treatment and may be useful to institute alterations in therapy. Prostate 49:93–100, 2001. © 2001 Wiley‐Liss, Inc.
Relationship of p21WAF‐I protein expression with prognosis in advanced prostate cancer treated by androgen ablation
Authors: Omar Eltaher A. , Behlouli Hassan , Chevalier Simone , Aprikian Armen G. 
Published: August 2002

AbstractObjectivesThe objectives of our study were (1) to characterize the expression of p21 and p53 proteins in advanced stage prostate cancer, (2) to determine the relationship between p53 and p21 protein expressions, and (3) to relate p53 and p21 expression to clinical outcome after androgen ablation.MethodsSeventy‐five patients with advanced prostate cancer (clinical stage C: 11, stage D1: 8, stage D2: 56), who all underwent androgen ablation, had tissue specimens obtained prior to hormonal therapy and studied immunohistochemicaly for p53 (Mab D07) and p21 (Mab EA10) expression. Clinical outcome was analyzed using the Kaplan–Meier method and log‐rank tests. Cox proportional hazard model was used to determine the independence of multiple variables.ResultsAbout 33.3% of cases expressed p53 and 33.3% expressed p21 positive immunoreactivity. No statistically significant correlation between p21 and p53 expression either in the entire study group (N = 75) or in stage D2 cases (N = 56) was observed (P = 0.38 and P = 0.68, respectively). Disease‐specific survival was significantly related to p21 expression (P = 0.0006 for entire study group and P = 0.01 for D2 cases). There was no statistically significant differences in disease‐specific survival between p53 positive or negative cases (P = 0.38 overall, P = 0.7 stage D2 only). p21 expression and the number of bone lesions were independently associated with shorter survival (multivariate P = 0.001, P = 0.005, respectively).ConclusionsThe data suggests that p21 expression is a strong and independent poor prognostic factor in patients with advanced stage prostate cancer treated by androgen ablation. Prostate 49:191–199, 2001. © 2001 Wiley‐Liss, Inc.
Anti‐cooperativity and cooperativity in hydrophobic interactions: Three‐body free energy landscapes and comparison with implicit‐solvent potential functions for proteins
Authors: Shimizu Seishi , Chan Hue Sun 
Published: August 2002

AbstractPotentials of mean force (PMFs) of three‐body hydrophobic association are investigated to gain insight into similar processes in protein folding. Free energy landscapes obtained from explicit simulations of three methanes in water are compared with that predicted by popular implicit‐solvent effective potentials for the study of proteins. Explicit‐water simulations show that for an extended range of three‐methane configurations, hydrophobic association at 25°C under atmospheric pressure is mostly anti‐cooperative, that is, less favorable than if the interaction free energies were pairwise additive. Effects of free energy nonadditivity on the kinetic path of association and the temperature dependence of additivity are explored by using a three‐methane system and simplified chain models. The prevalence of anti‐cooperativity under ambient conditions suggests that driving forces other than hydrophobicity also play critical roles in protein thermodynamic cooperativity. We evaluate the effectiveness of several implicit‐solvent potentials in mimicking explicit water simulated three‐body PMFs. The favorability of the contact free energy minimum is found to be drastically overestimated by solvent accessible surface area (SASA). Both the SASA and a volume‐based Gaussian solvent exclusion model fail to predict the desolvation barrier. However, this barrier is qualitatively captured by the molecular surface area model and a recent “hydrophobic force field.” None of the implicit‐solvent models tested are accurate for the entire range of three‐methane configurations and several other thermodynamic signatures considered. Proteins 2002;48:15–30. © 2002 Wiley‐Liss, Inc.
Some insights into protein structural class prediction
Authors: Zhou G.P. , Assa‐Munt Nuria 
Published: August 2002

AbstractIt has been quite clear that the success rate for predicting protein structural class can be improved significantly by using the algorithms that incorporate the coupling effect among different amino acid components of a protein. However, there is still a lot of confusion in understanding the relationship of these advanced algorithms, such as the least Mahalanobis distance algorithm, the component‐coupled algorithm, and the Bayes decision rule. In this communication, a simple, rigorous derivation is provided to prove that the Bayes decision rule introduced recently for protein structural class prediction is completely the same as the earlier component‐coupled algorithm. Meanwhile, it is also very clear from the derivative equations that the least Mahalanobis distance algorithm is an approximation of the component‐coupled algorithm, also named as the covariant‐discriminant algorithm introduced by Chou and Elrod in protein subcellular location prediction (Protein Engineering, 1999; 12:107–118). Clarification of the confusion will help use these powerful algorithms effectively and correctly interpret the results obtained by them, so as to conduce to the further development not only in the structural prediction area, but in some other relevant areas in protein science as well. Proteins 2001;44:57–59. © 2001 Wiley‐Liss, Inc.
Protochlorophyllide oxidoreductase: A homology model examined by site‐directed mutagenesis
Authors: Townley Helen E. , Sessions Richard B. , Clarke Anthony R. , Dafforn Timothy R. , Griffiths W. Trevor 
Published: August 2002

AbstractAn homology model of protochlorophyllide reductase (POR) from Synechocystis sp. was constructed on a template from the tyrosine‐dependent oxidoreductase family. The model showed characteristics appropriate to a globular, soluble protein and was used to generate a structure of the ternary complex of POR, nicotinamide adenine dinucleotide phosphate (NADPH), and protochlorophyllide. The POR ternary model was validated by mutagenesis experiments involving predicted coenzyme‐binding residues and by chemical modification experiments. A core tryptophan residue was shown to be responsible for much of the protein's fluorescence. Both quenching of this residue by coenzyme and fluorescence resonance energy transfer (FRET) from the protein to the coenzyme allowed the binding constant of NADPH to be determined. Replacement of this residue by Tyr gave an active mutant with approximately halved fluorescence and a negligible FRET signal, consistent with the role of this residue in energy transfer to the NADPH at the active site and with the model. The mechanism of the enzyme is discussed in the context of the model and semiempirical molecular orbital calculations. Proteins 2001;44:329–335. © 2001 Wiley‐Liss, Inc.
Computation and mutagenesis suggest a right‐handed structure for the synaptobrevin transmembrane dimer
Authors: Fleming Karen G. , Engelman Donald M. 
Published: August 2002

AbstractBiological membrane fusion involves a highly precise and ordered set of protein–protein interactions. Synaptobrevin is a key player in this process. Mutagenesis studies of its single transmembrane segment suggest that it dimerizes in a sequence specific manner. Using the computational methods developed for the successful structure prediction of the glycophorin A transmembrane dimer, we have calculated a structural model for the synaptobrevin dimer. Our computational search yields a well‐populated cluster of right‐handed structures consistent with the experimentally determined dimerization motif. The three‐dimensional structure contains an interface formed primarily by leucine and isoleucine side‐chain atoms and has no interhelical hydrogen bonds. The model is the first three‐dimensional picture of the synaptobrevin transmembrane dimer and provides a basis for further focused experimentation on its structure and association thermodynamics. Proteins 2001;45:313–317. © 2001 Wiley‐Liss, Inc.
Non‐competitive GABA antagonists: probing the mechanisms of their selectivity for insect versus mammalian receptors
Authors: Ozoe Yoshihisa , Akamatsu Miki 
Published: August 2002

AbstractA great variety of non‐competitive antagonists of ionotropic γ‐aminobutyric acid (GABA) receptors have been reported. While they are structurally diverse, there are common features in their structures. Thus, it was hypothesized that they bind to an identical site in different or overlapping orientations, and this hypothesis was validated by three‐dimensional structure–activity relationship (3D‐QSAR) analysis using receptor‐binding data. Meanwhile, although most antagonists are highly toxic to both vertebrates and invertebrates, several classes of antagonists, such as nor‐diterpene lactone picrodendrins, phenyl heterocyclic compounds and disubstituted bicyclophosphorothionates, were found to exhibit selectivity for housefly versus rat GABA receptors. To probe their selectivity mechanisms, the 3D‐QSAR method was applied to the three classes of antagonists. This revealed several important differences that might be related to the selectivity of antagonists between the structures of the non‐competitive antagonist‐binding sites of housefly and rat GABA receptors.© 2001 Society of Chemical Industry
Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A
Authors: Jeschke Peter , Harder Achim , Etzel Winfried , Gau Wolfgang , Thielking Gerhard , Bonse Gerhard , Iinuma Katsuharu 
Published: August 2002

AbstractThe tetra‐ and mono‐thionated cyclic octadepsipeptides represent novel cyclic octadepsipeptide derivatives with broad‐spectrum activity against parasitic nematodes in mice and sheep. Some of these show better activity than the potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymenolepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Trichostrongylus colubriformis in sheep compared with PF1022A. Here we report on two different and simple synthetic pathways for this new class of thionated cyclic octadepsipeptides.© 2001 Society of Chemical Industry