The 2.3A crystal structure of the antibody Fab HPC-4 in complex with calcium and the epitope peptide.

The murine monoclonal antibody HPC-4, directed against the activation region of the human anticoagulant zymogen protein C (PC), is one of the few immunoglobulins known to display calcium-dependent antigen binding. Unlike the more common class of antibodies that merely recognize a calcium-bound conformation of their antigen, HPC-4 interacts directly with calcium in the high affinity PC-HPC-4 complex.Metal ions can have considerable affinities for proteins, and give rise to geometric constraints that are often taken advantage of in protein-protein interactions. The coordination shell of metal ions can be filled by atoms provided by two different proteins, resulting in a high affinity protein complex. Surprisingly, this highly efficient binding strategy is rarely observed in immunoglobulins, despite the great number of known antibody structures determined in complex with their protein antigens.The structure reveals a mode of calcium binding which underlies a novel mechanism of metal aided antigen recognition. The ion is located at the antibodyantigen interface, where it functions both as an electrostatic bridge and as a conformational effector of the antibody. The antigen is further stabilized by an extensive and diverse array of interactions spanning a large surface area of contact. Our results provide a structural explanation for many of the observed characteristics of HPC-4, the first member of a unique class of calcium binding antibodies. As such, it represents a significant contribution to the study of interfacial metals and the structural biology of antibodies.To provide a structural understanding of HPC-4 function and of the particular antibody class to which it belongs, we have solved the X-ray crystal structure of the HPC-4 Fab fragment in ternary complex with its epitope peptide in the presence of calcium at a resolution of 2.3A. Within the crystal, the antigen-binding region is undistorted by crystalline lattice contacts. All complementarity-determining regions and the peptide antigen have well-defined electron density

Is MR Spectroscopy Really the Best MR-Based Method for the Evaluation of Fatty Liver in Diabetic Patients in Clinical Practice?

Objective: To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification.Methods: Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 5469 years) underwent MRI and MRS at 3.0 T. the liver fat fraction was calculated from triple-and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. the accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman's correlation coefficients.Results: the prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. the thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis.Conclusions: Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.D'Or Institute for Research and EducationFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)DOr Inst Res & Educ, Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Estado Rio de Janeiro, Rio de Janeiro, BrazilUniv São Paulo, Inst Phys Sao Carlos, Sao Carlos, SP, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniv Paris Diderot Sorbonne, Paris, FranceUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Quantitative diagnostics of soft tissue through viscoelastic characterization using time-based instrumented palpation

AbstractAlthough palpation has been successfully employed for centuries to assess soft tissue quality, it is a subjective test, and is therefore qualitative and depends on the experience of the practitioner. To reproduce what the medical practitioner feels needs more than a simple quasi-static stiffness measurement. This paper assesses the capacity of dynamic mechanical palpation to measure the changes in viscoelastic properties that soft tissue can exhibit under certain pathological conditions. A diagnostic framework is proposed to measure elastic and viscous behaviors simultaneously using a reduced set of viscoelastic parameters, giving a reliable index for quantitative assessment of tissue quality. The approach is illustrated on prostate models reconstructed from prostate MRI scans. The examples show that the change in viscoelastic time constant between healthy and cancerous tissue is a key index for quantitative diagnostics using point probing. The method is not limited to any particular tissue or material and is therefore useful for tissue where defining a unique time constant is not trivial. The proposed framework of quantitative assessment could become a useful tool in clinical diagnostics for soft tissue

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

A preliminary examination of variables which influence the public acceptance of potable water reuse applications

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.Issued also on microfiche from Lange Micrographics.Water resource management in Texas is maturing from an era of project development to one of water supply management through conservation, reallocation, and reuse as a means of meeting water supply needs. As opportunities for conventional water supply development dwindle and costs for wastewater disposal climb, the role water reuse plays in water resource management increases significantly. Both potable and nonpotable applications of reclaimed water offer a means to extend and maximize the utility of limited water resources. The literature on barriers to water reuse has primarily focused on public acceptance of nonpotable uses of the water. Very little research exists on the variables influencing public acceptance of water reuse for potable or nonpotable uses. Studies conducted by Bruvold (1972) revealed positive correlations between public acceptance of reuse and beliefs in water scarcity, pollution of existing supplies, perceived economic benefit, health official approval, and technological ability to purify water and wastewater. Bruvold (1980) also identified five factors which affected public acceptance of both potable and nonpotable uses. No further studies have been conducted to examine specific variables which influence public acceptance of potable water reuse. The purpose of this exploratory study was to identify the critical variables which influence public acceptance of potable water reuse or reuse in recreational settings where direct contact is likely. The study also sought to assess whether public preferences for reuse practices prescribed a hierarchy of acceptable applications. These research questions were answered through personal interviews followed by a brief questionnaire. The respondents in this study expressed four primary concerns about using recycled water for potable purposes: (1) short-and long-term health impacts; (2) reduction in the quality of the water supply; (3) mistrust of the reliability of treatment and distribution systems; and (4)possible pollution of water supplies. Of these variables, significant public concerns regarding the acceptance of potable water reuse are primarily limited to health and water quality issues. Results also indicated that the public is more willing to support nonpotable uses of recycled water, supporting some of the earlier research findings in the field

Emil and Fina Garteiser reading in their living room, Hondo, Texas

Photograph shows Emil and Euphrosina ''Fina'' Fohn Garteiser seated in chairs. Emil is looking up; Fina is looking at magazine.Information from lenders: Couple were photographed by their son, who took picture from window. The couple read COUNTRY GENTLEMEN and PATHFINDER. House was at 1910 22nd Street