|
| ||
|
|
||
Biological Outcomes (biological + outcome)
Selected AbstractsTopical dose delivery in the reptilian egg treatment modelENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2007Jennifer K. Muller Abstract Developing assays to detect endocrine-mediated toxicity from in ovo or in utero exposure is a current challenge in regulatory toxicology. Some species of reptiles exhibiting a unique mode of sex determination, in which the incubation temperature during a critical period determines gonadal sex, have been explored as an in ovo model to screen environmental contaminants for endocrine effects. We critically review published egg-exposure studies and conclude that data regarding the pharmacokinetics of topically applied substances are insufficient to validate dose,response relationships for the effects of chemicals on in ovo endocrine function or gender determination in reptiles. The insufficiencies in these data largely result from methodological failures, including lack of measurement verification, failure to investigate and control extraneous factors affecting the measurements, and lack of independent replication of results. Considerable additional research will be necessary to alleviate these methodological inadequacies. Given the current status of the data, topical treatment of reptilian eggs cannot be considered to be a valid means of establishing causal relationships between chemical treatment and biological outcome. [source] Blockade of B-cell-activating factor suppresses lupus-like syndrome in autoimmune BXSB miceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Hanlu Ding Abstract B-cell-activating factor (BAFF), a member of the tumour necrosis factor superfamily, plays a critical role in the maturation, homeostasis and function of B cells. In this study, we demonstrated the biological outcome of BAFF blockade in BXSB murine lupus model, using a soluble fusion protein consisting of human BAFF-R and human mutant IgG4 Fc. Mutation of Leu235 to Glu in IgG4 Fc eliminated antibody-dependent cell cytotoxicity (ADCC) and complement lysis activity, and generated a protein devoid of immune effector functions. Treatment of BXSB mice with BAFF-R-IgG4mut fusion protein for 5 weeks resulted in significant B-cell reduction in both the peripheral blood and spleen. Treated mice developed lower proteinuria, reduced glomerulonephritis and much delayed host death than untreated animals. Thus, BAFF blockade with BAFF-R-IgG4mut protein is an effective strategy to treat B-cell-mediated lupus-like pathology. Moreover, compared with other IgG isotypes with undesired effector functions, mutant IgG4 Fc should prove useful in constructing novel therapeutic reagents to block immune molecule signalling in various diseases. [source] Role of gp130-mediated signalling pathways in the heart and its impact on potential therapeutic aspectsBRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2008P Fischer IL-6-type cytokines bind to plasma membrane receptor complexes containing the common signal transducing receptor chain gp130 that is ubiquitously expressed in most tissues including the heart. The two major signalling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, have been demonstrated to play important roles in cardiac development, hypertrophy, protection and remodelling in response to physiological and pathophysiological stimuli. Experimental data, both in vivo and in vitro, imply beneficial effects of gp130 signalling on cardiomyocytes in terms of growth and survival. In contrast, it has been reported that elevated serum levels of IL-6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. Moreover, it has been shown that the local gp130 receptor system is altered in failing human hearts. In the present review, we summarize the basic principles of gp130 signalling, which requires simultaneous activation of STAT and ERK pathways under the tight control of positive and negative intracellular signalling modulators to provide a balanced biological outcome. Furthermore, we highlight the key role of the gp130 receptor and its major downstream effectors in the heart in terms of development and regeneration and in response to various physiological and pathophysiological stress situations. Finally, we comment on tissue-specific diversity and challenges in targeted pharmacological interference with components of the gp130 receptor system. British Journal of Pharmacology (2008) 153, S414,S427; doi:10.1038/bjp.2008.1; published online 4 February 2008 [source] The Role of Functional Parameters for Topographical Characterization of Bone-Anchored ImplantsCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2 2006Anna Arvidsson MSc ABSTRACT Background, The surface topographical characterization of bone-anchored implants has been recommended to be based on amplitude, spatial, and hybrid parameters. There are also functional parameters that have the potential to describe characteristics important for a specific application. Purpose, The aim of the present study was to evaluate if parameters that have been described as functional in engineering applications are also relevant in the topographical characterization of bone-anchored implants. Materials and Methods, The surface topography of threaded titanium implants with different surface roughness (Sa, Sds, and Sdr) was analyzed with an optical interferometer, and five candidating functional parameters (Sbi, Sci, Svi, Sm, and Sc) were calculated. Examples of the same parameters for five commercially available dental implants were also calculated. Results, The highest core fluid retention index (Sci) was displayed by the turned implants, followed by fixtures blasted with 250- and 25-,m particles, respectively. Fixtures blasted with 75-,m Al2O3 particles displayed the lowest Sci value. This is the inverse order of the bone biological ranking based on earlier in vivo studies with the experimental surfaces included in the present study. Conclusion, A low core fluid retention index (Sci) seems favorable for bone-anchored implants. Therefore, it is suggested to include Sci to the set of topographical parameters for bone-anchored implants to possibly predict the biological outcome. [source] Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviewsADDICTION, Issue 5 2010Norah Palmateer ABSTRACT Aims To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes. Methods Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta-analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality (,core') or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements. Results Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self-reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes. Conclusions The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis-à-vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood-borne virus transmission. [source] Non-malignant clonal expansions of CD8+ memory T cells in aged individualsIMMUNOLOGICAL REVIEWS, Issue 1 2005Eric T. Clambey Summary:, CD8+ T cells provide a major line of defense against intracellular pathogens. Upon encounter with antigen, CD8+ T cells go through three distinct phases involving proliferation, contraction, and differentiation to become eventually long-lived CD8+ memory T cells. CD8+ memory T cells provide long-term protection against infection by intracellular pathogens. CD8+ memory T-cell proliferation and survival are regulated by many factors, including cytokines, and CD8+ memory T cells are stably maintained over a period of months to years. In aged humans and mice, however, there are significant alterations to the CD8+ memory T-cell compartment with frequent development of monoclonal expansions of CD8+ memory T cells in healthy individuals. Interestingly, CD8+ clonal expansions are not malignant and do not progress to lymphomas, suggesting that these cells must still be under certain constraints. In this review, we discuss our current understanding of factors that contribute to and regulate these CD8+ clonal expansions as well as the impact of CD8+ clonal expansions on immune function of the aged. In addition, we discuss similarities and differences between CD8+ clonal expansions observed in humans and mice, and we postulate that CD8+ clonal expansions represent a spectrum of biological outcomes ranging from antigen-driven to antigen-independent phenomena. [source] Developmental adaptation: Where we go from here,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2009A. Roberto Frisancho The concept of developmental adaptation is a powerful framework that can be used for understanding the origin of population differences in phenotypic and genotypic biological traits. There is great deal of information describing how developmental responses can shape adult biological outcomes. Specifically, current research suggest that individuals developing in stressful environments such as high altitude will attain an adult enlarged residual lung volume that contribute to the successful cardiovascular adaptation of the high-altitude Andean native. Likewise, studies on the etiology of the metabolic syndrome indicate that development under poor nutritional environments elicit efficient physiological and metabolic responses for the utilization of nutrients and energy, which become disadvantageous when the adult environmental conditions provide abundant access to food and low energy expenditure. Epigenetic research in experimental animals and retrospective research in humans confirm that environmental influences during developmental period have profound consequences on the phenotypic expression of biological and behavioral traits during adulthood. Research on epigenetics is a productive direction for human biologists concerned with understanding the origins of human biological variability. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source] REVIEW ARTICLE: How to make a melanoma: what do we know of the primary clonal events?PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008Dorothy C. Bennett Summary Rapid advances have been made in our knowledge of the commonest genetic and epigenetic alterations found in human sporadic melanomas. Valuable recent contributions came from analyses of gene copy number by comparative genome hybridization, and from large-scale gene expression profiling. All of the commonest affected genes encode regulatory components. Loci with established importance in melanoma, like CDKN2A, BRAF and PTEN, have been joined by some less familiar genes including transcription factor sequences TBX2 and STK11 (LKB). This knowledge is reviewed in relation to the cellular signaling pathways affected by these molecules, their biological outcomes, and the implications as to what changes are required overall to generate a melanoma. The data support a model in which genesis of melanoma requires changes that (1) initiate clonal expansion, (2) overcome cell senescence, and (3) reduce apoptosis. [source] Economic intensification and degenerative joint disease: Life and labor on the postcontact north coast of PeruAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009Haagen D. Klaus Abstract This study tests the hypothesis that the colonial economy of the Lambayeque region of northern coastal Peru was associated with a mechanically strenuous lifestyle among the indigenous Mochica population. To test the hypothesis, we documented the changes in the prevalence of degenerative joint disease (or DJD) in human remains from the late pre-Hispanic and colonial Lambayeque Valley Complex. Comparisons were made using multivariate odds ratios calculated across four age classes and 11 principle joint systems corresponding to 113 late pre-Hispanic and 139 postcontact adult Mochica individuals. Statistically significant patterns of elevated postcontact DJD prevalence are observed in the joint systems of the shoulder, elbow, wrist, and knee. More finely grained comparison between temporal phases indicates that increases in prevalence were focused immediately following contact in the Early/Middle Colonial period. Analysis of DJD by sex indicates postcontact males experienced greater DJD prevalence than females. Also, trends between pre- and postcontact females indicate nearly universally elevated DJD prevalence among native colonial women. Inferred altered behavioral uses of the upper body and knee are contextualized within ecological, ethnohistoric, and ethnoarchaeological frameworks and appear highly consistent with descriptions of the local postcontact economy. These patterns of DJD appear to stem from a synergism of broad, hemispheric level sociopolitical alterations, specific changes to Mochica activity and behavior, regional economic intensification, and local microenvironmental characteristics, which were all focused into these biological outcomes by the operation of a colonial Spanish political economy on the north coast of Peru from A.D. 1536 to 1751. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source] How race becomes biology: Embodiment of social inequalityAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2009Clarence C. Gravlee Abstract The current debate over racial inequalities in health is arguably the most important venue for advancing both scientific and public understanding of race, racism, and human biological variation. In the United States and elsewhere, there are well-defined inequalities between racially defined groups for a range of biological outcomes,cardiovascular disease, diabetes, stroke, certain cancers, low birth weight, preterm delivery, and others. Among biomedical researchers, these patterns are often taken as evidence of fundamental genetic differences between alleged races. However, a growing body of evidence establishes the primacy of social inequalities in the origin and persistence of racial health disparities. Here, I summarize this evidence and argue that the debate over racial inequalities in health presents an opportunity to refine the critique of race in three ways: 1) to reiterate why the race concept is inconsistent with patterns of global human genetic diversity; 2) to refocus attention on the complex, environmental influences on human biology at multiple levels of analysis and across the lifecourse; and 3) to revise the claim that race is a cultural construct and expand research on the sociocultural reality of race and racism. Drawing on recent developments in neighboring disciplines, I present a model for explaining how racial inequality becomes embodied,literally,in the biological well-being of racialized groups and individuals. This model requires a shift in the way we articulate the critique of race as bad biology. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||