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Members of the protein family having similarity to BPI (bactericidal/permeability increasing protein) (the BPI-like proteins), also known as the PLUNC (palate, lung and nasal epithelium clone) family, have been found in a range of mammals; however, those in species other than human or mouse have been relatively little characterized. Analysis of the BPI-like proteins in cattle presents unique opportunities to investigate the function of these proteins, as well as address their evolution and contribution to the distinct physiology of ruminants. The present review summarizes the current understanding of the nature of the BPI-like locus in cattle, including the duplications giving rise to the multiple BSP30 (bovine salivary protein 30 kDa) genes from an ancestral gene in common with the single PSP (parotid secretory protein) gene found in monogastric species. Current knowledge of the expression of the BPI-like proteins in cattle is also presented, including their pattern of expression among tissues, which illustrate their independent regulation at sites of high pathogen exposure, and the abundance of the BSP30 proteins in saliva and salivary tissues. Finally, investigations of the function of the BSP30 proteins are presented, including their antimicrobial, lipopolysaccharide-binding and bacterial aggregation activities. These results are discussed in relation to hypotheses regarding the physiological role of the BPI-like proteins in cattle, including the role they may play in host defence and the unique aspects of digestion in ruminants. [ABSTRACT FROM AUTHOR]

Abstract  To determine whether participants in the behavior enhances drug reduction of incontinence (BE-DRI) trial experienced reduction in the frequency of nocturia and/or nocturnal leakage during treatment with antimuscarinic phamacotherapy with or without additional behavioral therapy. We analyzed urinary diary data relating to nocturia and nocturnal incontinence before and after 8 weeks of study treatment in the BE-DRI trial, in which patients were randomly assigned to receive drug therapy with tolterodine tartrate extended-release capsules 4 mg alone or in combination with behavioral training. Chi-square tests assessed whether nocturia and nocturnal incontinence prevalence varied by treatment arm and paired t tests assessed the change in mean frequency of nocturia and nocturnal leakage. Among 305 women, 210 (69%) had an average of at least one nocturia episode at baseline. There were small but statistically significant differences (p  [ABSTRACT FROM AUTHOR]

Starting with the conformal symmetries of Euclidean space, we construct a manifold where time manifests as a part of the geometry. Though there is no matter present in the geometry studied here, geometric terms analogous to dark energy and dark matter appear when we write down the Einstein tensor. Specifically, the quotient of the conformal group of Euclidean four-space by its Weyl subgroup results in a geometry possessing many of the properties of relativistic phase space, including both a natural symplectic form and non-degenerate Killing metric. We show that the general solution posesses orthogonal Lagrangian submanifolds, with the induced metric and the spin connection on the submanifolds necessarily Lorentzian, despite the Euclidean starting point. Using an orthonormal frame adapted to the phase space properties, we also find two new tensor fields not present in Riemannian geometry. The first is a combination of the Weyl vector with the scale factor on the metric, and determines the timelike directions on the submanifolds. The second comes from the components of the spin connection, symmetric with respect to the new metric. Though this field comes from the spin connection, it transforms homogeneously. Finally, we show that in the absence of Cartan curvature and sources, the configuration space has geometric terms equivalent to a perfect fluid and a cosmological constant. [ABSTRACT FROM AUTHOR]

Particle shape plays a crucial role in the design of novel reinforced composites. We introduce the notion of a geometrical anisotropy index A to characterize the particle shape and establish its relationship with the effective elastic constants of biphase composite materials. Our analysis identifies three distinct regions of A: (i) By using ovoidal particles with small A, the effective stiffness scales linearly with A for a given volume fraction a; (ii) for intermediate values of A, the use of prolate particles yield better elastic properties; and (iii) for large A, the use of oblate particles result in higher effective stiffliess. Interestingly, the transition from (ii) to (iii) occurs at a critical anisotropy AC~ and is independent of a. [ABSTRACT FROM AUTHOR]

AbstractObjective:To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally.Methods:This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected.Results:Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10  g/dL. At week 9, 426 (33%) patients had a Hb level of 10––12  g/dL, 165 (13%) of >12  g/dL, 226 (18%) of <10  g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10––12  g/dL. For patients with a baseline Hb of <10  g/dL, the Kaplan––Meier (K––M) percentage of patients with Hb levels ≥10  g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K––M% of patients with Hb levels >13  g/dL from week 1 to EOTP was 10%. The K––M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses.Conclusions:This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13  g/dL were infrequent. Limitations are related to the observational nature of this study. [ABSTRACT FROM AUTHOR]

AbstractObjective:To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally.Methods:This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected.Results:Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10  g/dL. At week 9, 426 (33%) patients had a Hb level of 10––12  g/dL, 165 (13%) of >12  g/dL, 226 (18%) of <10  g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10––12  g/dL. For patients with a baseline Hb of <10  g/dL, the Kaplan––Meier (K––M) percentage of patients with Hb levels ≥10  g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K––M% of patients with Hb levels >13  g/dL from week 1 to EOTP was 10%. The K––M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses.Conclusions:This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13  g/dL were infrequent. Limitations are related to the observational nature of this study. [ABSTRACT FROM AUTHOR]

A series of fluorine-containing benzamide analogs was synthesized and evaluated as candidate ligands for positron emission tomography (PET) imaging of the sigma-2 (2) receptor status of solid tumors. Four compounds having a moderate to high affinity for 2receptors and a moderate to low affinity for sigma-1 (1) receptors were radiolabeled with fluorine-18 via displacement of the corresponding mesylate precursor with 18Ffluoride. Biodistribution studies in female Balb/c mice bearing EMT-6 tumor allografts demonstrated that all four F-18-labeled compounds had a high tumor uptake (2.5−3.7% ID/g) and acceptable tumor/normal tissue ratios at 1 and 2 h post-i.v. injection. An analysis of the chemistry and biodistribution data suggested that N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F3c)and N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-iodo-3-methoxybenzamide (18F3f)are acceptable compounds for imaging the 2receptor status of solid tumors. [ABSTRACT FROM AUTHOR]

The mechanisms regulating involution of mammary glands after weaning are not clear, but engorgement with milk is a key trigger. Many cell types require to be anchored to an extracellular matrix (ECM) as a prerequisite for survival and this is achieved via intregrins binding to specific motifs and signalling their attachment, intracellularly, via focal adhesion kinase (FAK). We sought to determine firstly, if expression of β1-integrin and FAK is reduced during the first stage of involution. Expression of β1-integrin and FAK was significantly reduced at 6 h after sealing teats and this was accompanied with a decreased abundance of cytochrome C in mitochondria. Secondly, we sought to determine if expression of β1-integrin and FAK was restored during the first, partially reversible stage of involution (at 24 h), but not during the second irreversible stage, which occurs after 72 h. Re-suckling restored full expression of the 80 kDa fragment of FAK, but not of the 125 kDa protein or β1-integrin at 24 h after weaning. Re-suckling did not restore expression of either peptide after 72 h. Changes in expression of cytochrome C and pro-caspase-3 (apoptotic markers) were similar to that of the 80 kDa fragment of FAK. These data suggest that epithelial cells can restore partial contact with their basement membrane during the first, reversible stage, but not during the second irreversible stage of involution. We speculate that decreased contact between epithelial cells and their basement membrane initiates apoptosis in mammary glands at weaning. This process begins within 6 h of pup withdrawal. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]