bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spirometry in an unselected group of 6‐year‐old children: The DARC birth cohort study
Authors: Kjaer Henrik Fomsgaard , Eller Esben , Bindslev‐Jensen Carsten , Høst Arne 
Published: July 2008

AbstractThis study presents reference equations for spirometric parameters in 6‐year‐old children and evaluates the ability of spirometry to discriminate healthy children from children with asthma. Baseline spirometry and respiratory symptoms were assessed in 404 children participating in a longitudinal birth cohort study. Children with known asthma, possible asthma and a control group also performed bronchodilator measurements. At least two acceptable flow‐volume curves at baseline were obtained by 368/404 children (91%). The two best values for FEV1 and FVC were within 5% of each other in 88% and 83% of children, respectively. Linear regression analyses for 242 children included in the reference population demonstrated height to be the main predictor of all spirometric indices except FEV1/FVC. FEV1, FEV75, and FVC correlated reasonably to anthropometric data in contrast to flow parameters. Gender differences were found for FEV1, FVC, and FEV75, but not for flow parameters. Asthma was diagnosed in 25/404 children. Baseline lung function in healthy children and children with asthma overlapped, although asthmatic children could be discriminated to some extent. Bronchodilator tests showed a difference in ΔFEV1(mean) between healthy children and children with asthma (3.1% vs. 6.1%, P < 0.05). At a cut‐off point of ΔFEV1 = 7.8%, bronchodilator tests had a sensitivity of 46% and a specificity of 92% for current asthma. Spirometry including bronchodilator measurements was demonstrated to be feasible in 6‐year‐old children and reference values were determined. Spirometry aids the diagnosis of asthma in young children, but knowledge on sensitivity and specificity of these measurements is a prerequisite. Pediatr Pulmonol. 2008; 43:806–814. © 2008 Wiley‐Liss, Inc.
Clinical application of antibody microarray in chronic kidney disease: How far to go?
Authors: Lv Lin‐Li , Liu Bi‐Cheng 
Published: July 2008

AbstractChronic kidney disease (CKD) that affects about 10% of the adult population has been shown as a worldwide public health problem in recent years. Both basic and clinical investigations have identified complex disease‐associated protein networks involved in the pathophysiologic processes of CKD. The traditional single‐assay approach and proteomic analysis of those related proteins have given birth to a steadily increasing panel of molecules that may have the potential to serve as biomarkers for CKD. However, both approaches suffered from some shortcomings from a technological point of view. Antibody microarray (AbM) is characterized by high sensitivity, specificity, and quantitative ability for a particular set of known proteins. However, its application in CKD has been very limited so far. The objective of this review, therefore, is to address the potential applications of AbM in studying of CKD. We will briefly discuss the proteins involved in the development of CKD, future directions in which AbM approaches would probably display its potential and also some key issues that need to be considered in application of this novel technique.
Analysis of molecular forms of albumin in urine
Authors: Hortin Glen L. , Sviridov Denis 
Published: July 2008

AbstractAlbumin is not only one of the most abundant urinary protein components and one of the most widely used clinical markers for kidney disease, it also is a significant source of molecular complexity of the urinary proteome and peptidome. Urine contains multiple fragments and modified forms of albumin. Analysis of molecular forms of albumin in urine is of fundamental importance for understanding clinical assays for albumin quantification, specimen stability, and proteomic and peptidomic analysis of urine.
Proteomic strategies in bladder cancer: From tissue to fluid and back
Authors: Gromov Pavel , Moreira José M. A. , Gromova Irina , Celis Julio E. 
Published: July 2008

AbstractWe have applied protein expression profiling technologies in combination with immunohistochemistry, using fresh tissue and urine samples, to assess bladder cancer heterogeneity and prognosis as well as to generate protein markers for tumor progression and early diagnosis of the disease. Here, we review some selected lines of investigation and approaches undertaken by our laboratory, drawing on more than 15 years of experience in bladder cancer proteomics, to highlight a number of issues that may be useful for researchers entering the field. In particular, we address the identification of markers for bladder cancer progression and exemplify the potential of gel‐based proteomic profiling of urine samples for the early detection of urothelial carcinomas. In addition, we provide a brief description of a novel and highly promising source of biomarkers, the tumor interstitial fluid (TIF) that perfuses the tumor microenvironment.
Analysis of the urine proteome in patients with pancreatic ductal adenocarcinoma
Authors: Weeks Mark E. , Hariharan Deepak , Petronijevic Ljiljana , Radon Tomasz P. , Whiteman Hannah J. , Kocher Hemant M. , Timms John F. , Lemoine Nicholas R. , Crnogorac‐Jurcevic Tatjana 
Published: July 2008

AbstractPancreatic ductal adenocarcinoma (PDAC) accounts for over 213 000 deaths worldwide each year, largely due to late diagnosis. One of the risk factors for the development of PDAC is chronic pancreatitis (CP); the intense desmoplastic reaction makes differentiation between the two conditions extremely difficult. In order to identify biomarkers for noninvasive diagnosis, we performed 2‐D DIGE analysis of urine samples from healthy individuals and patients with PDAC and CP. Despite considerable intersample heterogeneity, a total of 127 statistically valid (p<0.05), differentially expressed protein spots were detected, 101 of which were identified using MALDI‐TOF MS. A number of these, including annexin A2, gelsolin and CD59 have already been associated with PDAC, however, their validation using immunoblotting proved challenging. This is probably due to extensive PTMs and processing thus indicating the need for raising specific antibodies for urinary proteins. Despite this, our study clearly demonstrates that urine is a valid source of noninvasive biomarkers in patients with pancreatic diseases.
The urinary proteome in diabetes and diabetes‐associated complications: New ways to assess disease progression and evaluate therapy
Authors: Rossing Kasper , Mischak Harald , Rossing Peter , Schanstra Joost P. , Wiseman Alex , Maahs David M. 
Published: July 2008

AbstractDiabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes‐associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen‐derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen‐derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention.
Identification of phosphoproteins in kidney tissues from patients with autosomal dominant polycystic kidney disease
Authors: Liu Yawei , Dai Bing , Mei Changlin , Zhang Yan , Xiong Xishan , Sandford Richard 
Published: July 2008

AbstractProtein phosphorylation is a very important PTM. Phosphorylation/dephosphorylation of a protein can alter its behavior in almost every conceivable way. Previous studies indicate that abnormal phosphorylation is involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, large‐scale proteomic analysis of altered phosphoproteins in ADPKD has not been reported. In this study, total proteins from ADPKD cystic kidney tissues (n = 5) and normal kidney tissues (n = 5) were extracted and phosphoproteins were enriched by phosphate metal affinity chromatography, then separated by 2‐DE and identified by LC‐MS/MS. Between the two groups, 48 protein spots showing more than a twofold difference were detected. Among them, 28 spots were up‐regulated and 20 down‐regulated in ADPKD kidney tissues. Of these, 38 different proteins were identified including cell signaling proteins, cytoskeleton proteins, mitochondria metabolic enzymes, antioxidant proteins, molecular chaperones, transcription factors and regulators. Two differential phosphoproteins, annexin II and tropomyosin, were further confirmed by immunoprecipitation and Western blot analysis. The results show that there are many kinds of abnormal phosphoproteins in ADPKD cystic kidney tissues. More studies on the functions of the differential phosphoproteins may provide us new clues for ADPKD pathogenesis and treatment.
Proteomic analysis of a podocyte vesicle‐enriched fraction from human normal and pathological urine samples
Authors: Lescuyer Pierre , Pernin Agnès , Hainard Alexandre , Bigeire Caty , Burgess Jennifer A. , Zimmermann‐Ivol Catherine , Sanchez Jean‐Charles , Schifferli Jürg A. , Hochstrasser Denis F. , Moll Solange 
Published: July 2008

AbstractPodocytes (glomerular visceral epithelial cells) release vesicles into urine. Podocyte vesicle‐enriched fractions from normal and pathological human urine samples were prepared for proteomic analysis. An immunoadsorption method was applied and enrichment of podocyte vesicles was assessed. We identified 76 unique proteins. One protein, serum paraoxonase/arylesterase 1 (PON‐1), was newly identified in normal human urine sample. We confirmed this result and showed PON‐1 expression in normal human kidney. These results demonstrated the potential for using the urine samples enriched in podocyte vesicles as a starting material in studies aimed at discovery of biomarkers for diseases.
The ratio of matrix metalloproteinase to E‐cadherin expression: A pilot study to assess mRNA and protein expression among African American prostate cancer patients
Authors: Pettaway Curtis A. , Song Renduo , Wang Xuemei , Sanchez‐Ortiz Ricardo , Spiess Philippe E. , Strom Sara , Troncoso Patricia 
Published: July 2008

AbstractBACKGROUNDWe assessed the expression of Matrix Metalloproteinase (MMP) to E‐cadherin (M/E ratio) to determine the correlation of gene expression with pathologic variables and outcome in a cohort of African American (AA) prostate cancer patients.METHODSTumors from formalin‐fixed, paraffin embedded RP specimens were examined. Gleason scores were 6, 7, and ≥8 in 7, 16, 13 tumors, respectively. Pathologic stage was organ confined (pT2) in 18 and advanced (>pT2) in 18 tumors. A colorimetric mRNA in situ hybridization (ISH) assay was performed using biotinylated anti‐sense oligonucleotide probes for MMP 2 and 9, as well as for E‐cadherin gene transcripts. Immunohistochemistry (IHC) was performed utilizing specific monoclonal antibodies to detect the above genes. Image analysis was performed to determine the intensity of both mRNA and protein expression. Two reviewers analyzed ISH gene expression independently.RESULTSThe M/E expression ratio was significantly increased at the invasive edge (but not the center) of tumors of higher Gleason score (P = 0.02 and 0.0008) and pathologic stage (P = 0.0001 and <0.0001) when examined by both ISH and IHC. Significant variability in ISH staining interpretation was noted within and among the two study reviewers. An M/E ratio >2.5 was associated with biochemical recurrence after radical prostatectomy in addition to tumor pathologic stage subsequent to univariate statistical analysis.CONCLUSIONSThe M/E ratio characterizes an important aspect of the molecular phenotype associated with the histologic progression of prostate cancer among African American prostate cancer patients. A larger comparative study is required to determine potential racial variation and prognostic significance of gene expression. Prostate 68: 1467–1476, 2008. © 2008 Wiley‐Liss, Inc.
Phase II study of fulvestrant (faslodex®) in castration resistant prostate cancer
Authors: Chadha Manpreet K. , Ashraf Umeer , Lawrence David , Tian Lili , Levine Ellis , Silliman Carrie , Escott Paul , Payne Valencia , Trump Donald L. 
Published: July 2008

AbstractBACKGROUNDPreclinical evidence supports the role of estrogen receptor signaling in prostate cancer. In this trial we investigated the tolerability and efficacy of fulvestrant, a pure estrogen receptor antagonist, in the treatment of castration resistant prostate cancer (CRPC).METHODSPatients with CRPC were enrolled after written informed consent. Fulvestrant was administered by intramuscular injection at a dose of 500 mg on day 0, then 250 mg on day 14, day 28 and monthly thereafter. History, physical examination, serum prostate specific antigen (PSA) levels and toxicity was evaluated monthly. Radiographic studies were repeated every 3 months to assess disease. Treatment was continued until disease progression, unacceptable toxicity, non‐compliance or consent withdrawal.RESULTSTwenty patients were enrolled over a period of six months. All patients were Caucasians with median age of 69.5 years [range: 47–85 years]. Sixteen patients (80%) had radiological evidence of metastasis and four patients (20%) had rising PSA as the only evidence of progressive disease. Patients received a median of three treatment cycles of fulvestrant [range: 1–11]. Median time to progression was 4.3 months (95% confidence interval of 3–5.7 months) and median overall survival was 19.4 months (range: 9.9–19.4 months) after a median follow‐up of 16 months. No patient showed ≥50% reduction in PSA or radiologic improvement. Few adverse events were noted, none of which were attributed directly to fulvestrant.CONCLUSIONFulvestrant was well tolerated but failed to produce clinical or PSA response in men with CRPC. Prostate 68: 1461–1466, 2008. © 2008 Wiley‐Liss, Inc.
Insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial
Authors: Neuhouser Marian L. , Schenk Jeannette , Song Yoon Ju , Tangen Catherine M. , Goodman Phyllis J. , Pollak Michael , Penson David F. , Thompson Ian M. , Kristal Alan R. 
Published: July 2008

AbstractBACKGROUNDWe investigated whether peptides involved in cellular proliferation and apoptosis, [insulin‐like growth factor I (IGFI) and its major binding protein (insulin‐like growth factor binding protein 3)], predicted risk of benign prostate hyperplasia (BPH).METHODSWe conducted a nested‐case–control study in the placebo arm of the prostate cancer prevention trial (PCPT). Cases (n = 727) were men with surgical or medical treatment for BPH; two or more IPSS scores >14; or two scores of at least five points over baseline one of which was ≥12. Controls (n = 727) were frequency matched by age to cases, reported no BPH treatment, and no IPSS score >8. Cases and controls remained on the PCPT placebo and were followed closely until their 7‐year PCPT anniversary. Baseline serum was analyzed for IGFI and IGFBP3. Unconditional logistic regression and polytomous regression estimated the multivariate‐adjusted odds ratio (OR) for BPH risk.RESULTSIGFBP3 was inversely and the IGFI:IGFBP3 ratio was positively associated with BPH risk, but findings were statistically significant only for men with severe symptoms (OR = 0.60, 95% CI = 0.40–0.90 for the fifth vs. first quintile of IGFBP3, P‐trend = 0.01). Associations did not differ by age (<65 or ≥65 years), and there was a suggestion that the IGFI:IGFBP3 – BPH risk association may be stronger among overweight men.CONCLUSIONSA high IGFI:IGFBP3 ratio was associated with increased BPH risk, and high serum IGFBP3 was associated with decreased BPH risk among men with severe symptoms. These results confirm findings from other recent studies. Prostate 68: 1477–1486, 2008. © 2008 Wiley‐Liss, Inc.
Signaling pathways of PDZ2 domain: A molecular dynamics interaction correlation analysis
Authors: Kong Yifei , Karplus Martin 
Published: July 2008

AbstractPDZ domains are found in many signaling proteins. One of their functions is to provide scaffolds for forming membrane‐associated protein complexes by binding to the carboxyl termini of their partners. PDZ domains are thought also to play a signal transduction role by propagating the information that binding has occurred to remote sites. In this study, a molecular dynamics (MD) simulation‐based approach, referred to as an interaction correlation analysis, is applied to the PDZ2 domain to identify the possible signal transduction pathways. A residue correlation matrix is constructed from the interaction energy correlations between all residue pairs obtained from the MD simulations. Two continuous interaction pathways, starting at the ligand binding pocket, are identified by a hierarchical clustering analysis of the residue correlation matrix. One pathway is mainly localized at the N‐terminal side of helix α1 and the adjacent C‐terminus of loop β1‐β2. The other pathway is perpendicular to the central β‐sheet and extends toward the side of PDZ2 domain opposite to the ligand binding pocket. The results complement previous studies based on multiple sequence analysis, NMR, and MD simulations. Importantly, they reveal the energetic origin of the long‐range coupling. The PDZ2 results, as well as the earlier rhodopsin analysis, show that the interaction correlation analysis is a robust approach for determining pathways of intramolecular signal transduction. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Rapid comparison of properties on protein surface
Authors: Sael Lee , La David , Li Bin , Rustamov Raif , Kihara Daisuke 
Published: July 2008

AbstractThe mapping of physicochemical characteristics onto the surface of a protein provides crucial insights into its function and evolution. This information can be further used in the characterization and identification of similarities within protein surface regions. We propose a novel method which quantitatively compares global and local properties on the protein surface. We have tested the method on comparison of electrostatic potentials and hydrophobicity. The method is based on 3D Zernike descriptors, which provides a compact representation of a given property defined on a protein surface. Compactness and rotational invariance of this descriptor enable fast comparison suitable for database searches. The usefulness of this method is exemplified by studying several protein families including globins, thermophilic and mesophilic proteins, and active sites of TIM β/α barrel proteins. In all the cases studied, the descriptor is able to cluster proteins into functionally relevant groups. The proposed approach can also be easily extended to other surface properties. This protein surface‐based approach will add a new way of viewing and comparing proteins to conventional methods, which compare proteins in terms of their primary sequence or tertiary structure. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide
Authors: Di Fiore Anna , Monti Simona Maria , Hilvo Mika , Parkkila Seppo , Romano Vincenza , Scaloni Andrea , Pedone Carlo , Scozzafava Andrea , Supuran Claudiu T. , De Simone Giuseppina 
Published: July 2008

AbstractThe cytosolic isoform XIII is a recently discovered member of the human carbonic anhydrase (hCA, EC 4.2.1.1) family. It is selectively expressed among other tissues in the reproductive organs, where it may control pH and ion balance regulation, ensuring thus proper fertilization conditions. The authors report here the X‐ray crystallographic structure of this isozyme in the unbound state and in complex with a classical sulfonamide inhibitor, namely acetazolamide. A detailed comparison of the obtained structural data with those already reported for other CA isozymes provides novel insights into the catalytic properties of the members of this protein family. On the basis of the inhibitory properties of acetazolamide against various cytosolic/transmembrane isoforms and the structural differences detected within the active site of the various CA isoforms, further prospects for the design of isozyme‐specific CA inhibitors are here proposed. Proteins 2009. © 2008 Wiley‐Liss, Inc.
Computational protein design with side‐chain conformational entropy
Authors: Sciretti Daniele , Bruscolini Pierpaolo , Pelizzola Alessandro , Pretti Marco , Jaramillo Alfonso 
Published: July 2008

AbstractRecent advances in modeling protein structures at the atomic level have made it possible to tackle “de novo” computational protein design. Most procedures are based on combinatorial optimization using a scoring function that estimates the folding free energy of a protein sequence on a given main‐chain structure. However, the computation of the conformational entropy in the folded state is generally an intractable problem, and its contribution to the free energy is not properly evaluated. In this article, we propose a new automated protein design methodology that incorporates such conformational entropy based on statistical mechanics principles. We define the free energy of a protein sequence by the corresponding partition function over rotamer states. The free energy is written in variational form in a pairwise approximation and minimized using the Belief Propagation algorithm. In this way, a free energy is associated to each amino acid sequence: we use this insight to rescore the results obtained with a standard minimization method, with the energy as the cost function. Then, we set up a design method that directly uses the free energy as a cost function in combination with a stochastic search in the sequence space. We validate the methods on the design of three superficial sites of a small SH3 domain, and then apply them to the complete redesign of 27 proteins. Our results indicate that accounting for entropic contribution in the score function affects the outcome in a highly nontrivial way, and might improve current computational design techniques based on protein stability. Proteins 2009. © 2008 Wiley‐Liss, Inc.
MADAMM: A multistaged docking with an automated molecular modeling protocol
Authors: Cerqueira N. M. F. S. A. , Bras N. F. , Fernandes P. A. , Ramos M. J. 
Published: July 2008

AbstractDealing with receptor flexibility in docking methodology is still a problem. The main reason behind this difficulty is the large number of degrees of freedom that have to be considered in this kind of calculations. In this paper, we present an automated procedure, called MADAMM, that allows flexibilization of both the receptor and the ligand during a multistaged docking with an automated molecular modeling protocol. We show that the orientation of particular residues at the interface between the protein and the ligand have a crucial influence on the way they interact during the docking process, and the standard docking methodologies failed to predict their correct mode of binding. We present some examples that demonstrate the capabilities of this approach when compared with traditional docking methodologies. Proteins 2009. © 2008 Wiley‐Liss, Inc.