TYPE VI COLLAGEN STIMULATES MACROPHAGES TO PROMOTE INFLAMMATION

poster abstractCollagen VI (COL6), an extracellular matrix protein (ECM), is important in maintaining the integrity of the tissue. Our recent findings have demonstrat-ed that excess COL6 is present in the lungs of comorbid patients with em-physema and adenocarcinoma. COL6 localized in the pulmonary interstitium is likely to interact with endothelial, epithelial and infiltrated pulmonary mac-rophages. The hypothesis is that excessive COL6 activates macrophages to promote inflammation, which may exacerbate pulmonary diseases. To test our hypothesis, bone marrow derived macrophages or macrophage cell lines were stimulated with soluble COL6 followed by analysis of activation markers and pro inflammatory cytokines. And results showed an increase in the number of CD86 positive cells and the levels of IL-12 and IFNγ production following stimulation. Taken together, our data have provided a link between increased amounts of COL6 and subsequent immune responses, which may play a role in the pathogenesis of pulmonary inflammatory diseases

ENHANCING THE TUMOR FIGHTING CAPACITY OF NK CELLS THROUGH THE USE OF SOYPEPTIDE

poster abstractNatural killer or (NK) cells are important components of the innate immune system, which play a major role in the rejection of tumors, and virally in-fected cells. By producing pro-inflammatory cytokines such as IFN-gamma, NK cells are able to exert immunoregulatory functions that influence the adaptive immunity of other immune cells. Due to its critical role in tumor inhibition, researchers, utilizing various cytokines, including IL-12 and IL-2, have fervently pursued the manipulation of NK activity. NK cells respond to cytokines in a dose-dependent manner; however, the toxicity of certain cy-tokines (like IL-2) in high doses prohibits their widespread clinical use. Therefore, efforts to activate NK cells without requiring high doses of cyto-kines is warranted. We recently exploited a soy derived dietary peptide called lunasin to improve the immune functions. The hypothesis was that the lunasin peptide has stimulatory effects on immune cells. To test this hy-pothesis, human peripheral blood mononuclear cells (PBMCs) of healthy do-nors were stimulated with and without lunasin in combination with cytokines IL-12 or IL-2. Our results showed that the lunasin peptide exerts a robust synergistic effect when combined with the selected cytokines. This effect ap-pears to regulate the expression of a number of genes that are important for NK activity. Our findings support the potential clinical use of lunasin in com-bination with cytokine to enhance the tumor fighting capacity of NK cells

Accuracy of ICD-9-CM Codes by Hospital Characteristics and Stroke Severity: Paul Coverdell National Acute Stroke Program

Background—Epidemiological and health services research often use International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) codes to identify patients with clinical conditions in administrative databases. We determined whether there are systematic variations between stroke patient clinical diagnoses and ICD‐9‐CM codes, stratified by hospital characteristics and stroke severity. Methods and Results—We used the records of patients discharged from hospitals participating in the Paul Coverdell National Acute Stroke Program in 2013. Within this stroke‐enriched cohort, we compared agreement between the attending physician\u27s clinical diagnosis and principal ICD‐9‐CM code and determined whether disagreements varied by hospital characteristics (presence of a stroke unit, stroke team, number of hospital beds, and hospital location). For patients with a documented National Institutes of Health Stroke Scale score at admission, we assessed whether diagnostic agreement varied by stroke severity. Agreement was generally high (\u3e 89%); differences between the physician diagnosis and ICD‐9‐CM codes were primarily attributed to discordance between ischemic stroke and transient ischemic attack (TIA), and subarachnoid and intracerebral hemorrhage. Agreement was higher for patients in metropolitan hospitals with stroke units, stroke teams, and \u3e 200 beds (all P \u3c 0.001). Agreement was lowest (60.3%) for rural hospitals with ≤ 200 beds and without stroke units or teams. Agreement was also lower for milder (94.9%) versus more‐severe (96.4%) ischemic strokes (P \u3c 0.001). Conclusions—We identified disagreements in stroke/TIA coding by hospital characteristics and stroke severity, particularly for milder ischemic strokes. Such systematic variations in ICD‐9‐CM coding practices can affect stroke case identification in epidemiological studies and may have implications for hospital‐level quality metric

Lens and Retina Formation Require Expression of Pitx3 in Xenopus Pre-lens Ectoderm

Pitx3 is expressed in tissues fated to contribute to eye development, namely, neurula stage ectoderm and prechordal mesoderm, then presumptive lens ectoderm, placode, and finally lens. Pitx3 overexpression alters lens, optic cup, optic nerve, and diencephalon development. Many of the induced anomalies are attributable to midline deficits; however, as assessed by molecular markers, ectopic Pitx3 appears to temporarily enlarge the lens field. These changes are usually insufficient to generate either ectopic lenses to enlarge the eye that eventually differentiates. Conversely, use of a repressor chimera or of antisense morpholinos alters early expression of marker genes, and later inhibits lens development, thereby abrogating retinal induction. Reciprocal grafting experiments using wild-type and morpholino-treated tissues demonstrate that Pitx3 expression in the presumptive lens ectoderm is required for lens formation. Contradictory to recent assertions that retina can form in the absence of a lens, the expression of Pitx3 in the presumptive lens ectoderm. is critical for retina development

Assessment of RELAP5-3D for Analysis of Very High Temperature Gas-Cooled Reactors

The RELAP5-3D© computer code is being improved for the analysis of very high temperature gas-cooled reactors. Diffusion and natural circulation can be important phenomena in gas-cooled reactors following a loss-of-coolant accident. Recent improvements to the code include the addition of models that simulate pressure loss across a pebble bed and molecular diffusion. These models were assessed using experimental data. The diffusion model was assessed using data from inverted U-tube experiments. The code’s capability to simulate natural circulation of air through a pebble bed was assessed using data from the NACOK facility. The calculated results were in reasonable agreement with the measured values

Altered Plasma Pharmacokinetics of Ceftiofur Hydrochloride in Cows Affected with Severe Clinical Mastitis

Ceftiofur is the most commonly used antimicrobial in lactating dairy cows. Recently, there has been an increase in the number of violative residues of ceftiofur in the tissues of cull dairy cows. This was the first project in a series of projects we will be completing aimed at characterizing the pharmacokinetics of ceftiofur in disease challenged animals. The results of this study indicate that diseased animals have lower plasma concentrations and altered pharmacokinetics compared to healthy animals. Future work will investigate the influence of altered pharmacokinetics on the presence of violative residues

EFFECTS OF TYPE VI COLLAGEN ON MACROPHAGES

poster abstractEmphysema is an abnormal inflammatory response of the alveoli that lose their elasticity due to destruction of alveolar septi. Collagen, an extracellular matrix protein (ECM), is expressed in the lung, which is important in maintaining the integrity of the tissue. Destruction of the ECM components in the alveolar structure contributes to the development of emphysema. We have found that the gene expression of type VI collagen (COL6A1) is higher in the lungs of emphysema patients as compared to that from normal controls. Type VI collagen (COL6) is found in the pulmonary interstitial compartment where massive macrophages are infiltrated in the inflammatory environment. The hypothesis is that excessive COL6 activates macrophages to mediate inflammatory responses, which may contribute to the pathogenesis of emphysema. The goal is to define the effects of type VI collagen on macrophages. Results from murine bone marrow derived macrophages showed a marked increase in the numbers of CD86-positive cells after soluble COL6 stimulation. To further support the stimulatory function of COL6, human THP-1 cells as well as primary monocytes produced inflammatory cytokines IL-12 and IFNγ following COL6 stimulation. Taken together, our data has demonstrated the stimulatory effects on macrophages by COL6 stimulation, which may mediate the inflammatory responses in the pathogenesis of emphysema