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Abstract:Guanosine 5′-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding assays were established and utilized as a reliable and high-capacity functional assay for determining antagonist and inverse agonist pharmacological parameters of novel histamine H3ligands, at the recombinant human H3receptor. [35S]GTPγS binding assays were performed with membranes prepared from human embryonic kidney 293 cells stably expressing the full-length (445 amino acids) human H3receptor isoform, at approximately 1 pmol/mg of protein. Utilizing robotic liquid handling, assay filtration, and scintillation counting in a 96-well format, concentration–response curves were determined for up to 40 compounds per assay. The imidazole-containing H3receptor antagonist ciproxifan and the non-imidazole antagonist ABT-239 inhibited (R)-α-methylhistamine (RAMH)-stimulated [35S]GTPγS binding in a competitive manner, and negative logarithm of the dissociation equilibrium constant (pKb) values determined for nearly 200 structurally diverse H3antagonists were very similar to the respective negative logarithm of the equilibrium inhibition constant values from N-α-[3H]methylhistamine competition binding assays. H3antagonists also concentration-dependently decreased basal [35S]GTPγS binding, thereby displaying inverse agonism at the constitutively active H3receptor. At maximally effective concentrations, non-imidazole H3antagonists inhibited basal [35S]GTPγS binding by approximately 20. For over 100 of these antagonists, negative logarithm of the 50 effective concentration values for inverse agonism were very similar to the respective pKbvalues. Both H3receptor agonist-dependent and -independent (constitutive) [35S]GTPγS binding were sensitive to changes in assay concentrations of sodium, magnesium, and the guanine nucleotide GDP; however, the potency of ABT-239 for inhibition of RAMH-stimulated [35S]GTPγS binding was not significantly affected. These robust and reliable [35S]GTPγS binding assays have become one of the important tools in our pharmacological analysis and development of novel histamine H3receptor antagonists/inverse agonists. [ABSTRACT FROM AUTHOR]

AbstractLet Tbe a bounded operator on a complex Banach space X. Let Vbe an open subset of the complex plane. We give a condition sufficient for the mapping f(z)(T?z)f(z) to have closed range in the Fr?chet space H(V, X) of analytic X-valued functions on V. Moreover, we show that there is a largest open set Ufor which the map f(z)(T?z)f(z) has closed range in H(V, X) for all VU. Finally, we establish analogous results in the setting of the weak?* topology on H(V, X*). [ABSTRACT FROM AUTHOR]

Telehealth technology for application in home healthcare for adult persons with developmentaldisabilities was examined. Utilization of telehealth by clinicians, including the physician,nurse and physician assistant, physical therapist, occupational therapist, speech languagepathologist, the dietitian, and psychologist for the healthcare needs of adults with developmentaldisabilities is discussed. Such utilization results in improved access to needed healthservices by reducing time and distance for this population. A telehealth model is offered, asare shifts in healthcare using telehealth technology in home health. [ABSTRACT FROM AUTHOR]

The model presented used available data to predict whether or not a student will drop out at some time during his or her college career. The model successfully identified students who would or would not drop out approximately 80% of the time. Logistic regression analysis was employed to predict chances of attrition for matriculating freshmen soon after freshman orientation. The dependent variable was the probability a student would, at some time in their college experience, drop out of college. The independent or predictor variables included demographics, high school experiences and factor scores based on a survey of attitudes, opinions and values. A two-stage procedure consisting of factor analysis in the first stage and logistic regression in the second stage provided model parameter estimates for each cohort of matriculating freshman in years 2000 to 2003. Empirical tests revealed the model was fully configural invariant in the first stage and partially configural invariant in the second stage. [ABSTRACT FROM AUTHOR]

The model presented used available data to predict whether or not a student will drop out at some time during his or her college career. The model successfully identified students who would or would not drop out approximately 80% of the time. Logistic regression analysis was employed to predict chances of attrition for matriculating freshmen soon after freshman orientation. The dependent variable was the probability a student would, at some time in their college experience, drop out of college. The independent or predictor variables included demographics, high school experiences and factor scores based on a survey of attitudes, opinions and values. A two-stage procedure consisting of factor analysis in the first stage and logistic regression in the second stage provided model parameter estimates for each cohort of matriculating freshman in years 2000 to 2003. Empirical tests revealed the model was fully configural invariant in the first stage and partially configural invariant in the second stage. [ABSTRACT FROM AUTHOR]

This study was undertaken to define the role that apoptosis may play in inducing cellular injury and death in gastric mucosa exposed to aspirin. Apoptosis was characterized by DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and DNA–histone-associated complex formation. A human gastric cell line (AGS) was exposed to physiologic concentrations (3 to 50 mM) of aspirin. Both time- and concentration-dependent effects on apoptosis were noted, which were effectively prevented by the caspase inhibitor z-VAD-fmk. Accordingly, the role of caspases in aspirin-induced apoptosis was also evaluated. Early activation of caspase-8 and caspase-9 was demonstrated, indicating a role for both receptor and mitochondrial pathways, respectively, in the apoptotic process. Corresponding activation of effector caspases-3, -6, and -7 was also evident, as was cleavage of PARP. We conclude that physiologically relevant concentrations of aspirin induces apoptosis in human gastric cells through a caspase-mediated mechanism. [ABSTRACT FROM AUTHOR]