The Immune System

Modern biotherapy has been in use for some 30 years. The first types of biotherapy were nonspecific stimulators of the immune response, but advances in genetic engineering are allowing the mass production of pure biological products which are now being tested as pharmaceutical agents. Biotherapy connotes the administration of products (1) that are coded by the mammalian genome; (2) that modify the expression of mammalian genes; or (3) that stimulate the immune system. In this chapter the discussion of the immune system will be limited primarily to topics relevant to cancer or autoimmune diseases. Because understanding the new biological agents requires an understanding of both the immune response and the molecular basis of oncogenesis, this chapter first presents a summary of the structure and function of the immune system. Following a discussion of immune responses, and the cells involved in these responses, will be a discussion on the current concepts of oncogenesis, particularly oncogenes and growth factors. Because research efforts are beginning to identify many biological proteins as having a role in autoimmune and other diseases, a brief introduction to autoimmune diseases is also included at the end of the chapter

An Exploratory Study Of Socially Responsibleprocurement Activitiesin The Expenditure Of Public Fundsat The State And Local Level

The aggregate annual expenditures of federal, state and local governments, in concert with universities and school districts represents incredible purchasing power and requires great prowess in its expenditure. Over the course of centuries, procurement has been used as a policy tool to improve society. This research delved into defining and determining the involvement of state and local governments in socially responsible activities related to the expenditure of public funds. Data collected in 2005 by the National Institute of Governmental Purchasing, Inc., was reviewed to determine if the expectations set for the private sector known as corporate social responsibility could be applied to the public sector. The study found that the definition as established for the private sector with regard to procurement social responsibility may also be employed in the public sector. A composite index of Public Procurement Social Responsibility (PPSR) was created as a benchmark for future comparison. Further, the presence of top-down management support for socially responsible initiatives in procurement in the areas of formal policies, goals and objectives and performance tracking mechanisms dictated higher PPSR scores for agencies. Mean Scores for PPSR were reviewed using independent variables of agency type, location, population served, procurement volume, and budget size. While top-down support of PPSR initiatives dictated strong involvement of an agency, there was no correlation between agency type, size, procurement spend, or population size on the mean score of a governmental entity, with or without the presence of PPSR drivers. The variables that influence the PPSR activities of an agency are similar across all demographics. What appears to drive the participation in socially responsible initiatives of government is the buy-in and mandate through regulation, policy and example set by management. This posture is emulated not only professionally, but the data indicates that it influences personal behavior as well. In order to bring about societal change, results are best achieved through the creation of policy for participation, establishing benchmarks for measuring success and integrating performance review milestones for achievement of goals and objectives related to PPSR

Dog Models of Naturally Occurring Cancer

Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics. Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here, we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer

Using Osteological Evidence to Assess Biological Affinity: A Re-evaluation of Selected Sites in East Tennessee

TVA/WPA excavations in East Tennessee in the 1930s uncovered archaeological sites critical for shaping theories about the prehistory of the region. Based on the archaeology of three of these sites, Hixon (AD 1155-1285), Dallas (AD 1350-1450), and Rymer (AD 1400-1600) in the Chickamauga Basin, early researchers concluded that each settlement resulted from migrations of biologically unrelated people into the area (Lewis and Lewis, 1941, 1946). Testing of this supposition using biological distance analysis (Weston, 2005) suggested that the sites instead represented biological continuity in the Chickamauga Basin. In this study, cranial and postcranial non-metric traits are used to examine biological distance between the three Chickamauga Basin sites and an extra-regional site from the Watts Bar Basin, using Mahalanobis D2 with a tetrachoric correlation matrix. Results of this four-group study differed dramatically from the expected structure of biological relationships between the sites, suggesting that the Hixon population was completely unrelated biologically to the populations in both the Chickamauga and Watts Bar Basins. In fact, these results combined with ceramic decorative styles present at the Hixon site suggest the population may have immigrated from Etowah in Bartow County, Georgia, with a continued shared cultural identity with Etowah providing sufficient barrier to mate exchange with the other East Tennessee sites examined here. Results of both cranial and postcranial non-metric biological distance analyses indicate the strongest genetic affiliations for all four sites to be between Dallas in the Chickamauga Basin and DeArmond in Watts Bar, despite great geographical separation of the settlements. In addition, an introduction to the skeletal biology of Watts Bar is presented via osteological examination of pathology and trauma of the DeArmond site. Smith (2003) recorded low levels of interpersonal and high levels of intrapersonal violence during the Dallas phase in the Chickamauga Basin. Results from DeArmond demonstrate similar rates and patterns, most likely reflecting a temporal trend in the region. The DeArmond skeletal remains exhibit low levels of metabolic stress but remarkably high levels of infectious disease. It appears that while all of the DeArmond individuals had access to high protein food resources regardless of status, status had little effect on preventing the spread of infection at the site

Feasibility of Hair Collection for Cortisol Measurement in Population Research on Adolescent Health

Background: Black–White disparities in adolescent health are widespread and thought to be explained, in part, by exposure to chronic stress. Cortisol assayed from hair is increasingly recognized as a valid and reliable measure for chronic physiological stress, but the feasibility of collecting hair among large probability samples of diverse adolescents is unknown. Purpose: The aim of the study was to investigate participation in hair collection for cortisol analyses in a probability sample of racially and socioeconomically diverse adolescents, including the extent to which sociodemographic factors and adverse exposures were associated with participation. Methods: The study included a probability sample of 516 adolescents conducted in conjunction with a prospective cohort study on adolescent health. Data were collected over 1 week via in-home interviews, ecological momentary assessment, global positioning system methods, and in-home hair collection at the end of the week. Results: Of the 516 eligible youth, 471 (91.3%) participated in the hair collection. Of the 45 youth who did not provide hair samples, 18 had insufficient hair, 25 refused, and 2 did not participate for unknown reasons. Multivariable logistic regression results indicated that non-Hispanic Black youth were less likely than their non-Hispanic White peers to participate due to insufficient hair or refusal (OR = 0.24, 95% CI [0 .09, 0.60]). Despite lower rates of participation, the proportion of Black youth in the participating sample was representative of the study area. No significant differences in participation were found by other sociodemographic characteristics or adverse exposures. Conclusions: Hair collection for cortisol measurement is feasible among a probability sample of racially and socioeconomically diverse adolescents. Hair cortisol analyses may accelerate research progress to understand the biological and psychosocial bases of health disparities

Ubiquinol Reduces Muscle Wasting but Not Fatigue in Tumor-Bearing Mice

Purpose: Fatigue is the most common and distressing symptom reported by cancer patients during and after treatment. Tumor growth increases oxidative stress and cytokine production, which causes skeletal muscle wasting and cardiac dysfunction. The purpose of this study was to determine whether treatment with the antioxidant ubiquinol improves muscle mass, cardiac function, and behavioral measures of fatigue in tumor-bearing mice. Method: Adult female mice were inoculated with colon26 tumor cells. Half the control and tumor-bearing mice were administered ubiquinol (500 mg/kg/day) in their drinking water. Voluntary wheel running (i.e., voluntary running activity [VRA]) and grip strength were measured at Days 0, 8, 14, and 17 of tumor growth. Cardiac function was measured using echocardiography on Day 18 or 19. Biomarkers of inflammation, protein degradation, and oxidative stress were measured in serum and heart and gastrocnemius tissue. Results: VRA and grip strength progressively declined in tumor-bearing mice. Muscle mass and myocardial diastolic function were decreased, and expression of proinflammatory cytokines was increased in serum and muscle and heart tissue on Day 19 of tumor growth. Oxidative stress was present only in the heart, while biomarkers of protein degradation were increased only in the gastrocnemius muscle. Ubiquinol increased muscle mass in the tumor-bearing and control animals but had no effect on the expression of biomarkers of inflammation, protein degradation, or oxidative stress or on behavioral measures of fatigue

Effect of Perceived Stress on Cytokine Production in Healthy College Students

Chronic psychological stress impairs antibody synthesis following influenza vaccination. Chronic stress also increases circulating levels of proinflammatory cytokines and glucocorticoids in elders and caregivers, which can impair antibody synthesis. The purpose of this study was to determine whether psychological stress increases ex vivo cytokine production or decreases glucocorticoid sensitivity (GCS) of peripheral blood leukocytes from healthy college students. A convenience sample of Reserve Officer Training Corps (ROTC) students completed the Perceived Stress Scale (PSS). Whole blood was incubated in the presence of influenza vaccine and dexamethasone to evaluate production of interleukin-6 (IL-6), interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). Multiple regression models controlling for age, gender, and grade point average revealed a negative relationship between PSS and GCS for vaccine-stimulated production of IL-1β, IL-6, and TNF-α. These data increase our understanding of the complex relationship between chronic stress and immune function

Piggy in the Middle: How Direct Customer Power Affects First-Tier Suppliers’ Adoption of Socially Responsible Procurement Practices and Performance

Companies are faced with a choice of which type of power to use in their efforts to persuade their first-tier suppliers to adopt socially responsible procurement practices with key second-tier suppliers. However, we know little about how first-tier suppliers will react to different types of power and which are most effective in encouraging the adoption of socially responsible procurement practices. We are also ignorant of the impact of these practices on first-tier suppliers’ performance. This paper uses bases of power theory to examine the impact of buyer companies’ power usage (non-mediated and mediated) on first-tier suppliers’ adoption of socially responsible procurement practices (process-based and market-based) with their own (second-tier) suppliers. We surveyed managers responsible for sustainable supply chain management in 156 firms and analyzed the results using structural equation modeling. Our findings show that non-mediated power use (expert and referent) influences the adoption of process-based and market-based practices, while mediated power use (coercion, legitimacy, and reward) has no significant impact on the adoption of either type of practice. Additionally, we find that the adoption of market-based socially responsible procurement practices leads to enhanced performance for first-tier suppliers who adopt these practices with their second-tier suppliers