Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

The CD40-CD154 system in anti-infective host defense

Research in the past few years has documented significant advances in our understanding of the CD40-CD40 ligand (CD154) system in diverse immune functions. This system influences many T cell mediated inflammatory immune responses and effector functions, unmasking a previously unexpected role for CD40-CD154 in cell mediated immunity. Manipulation of CD154 in animal models of infection by the use of CD154-deficient mice or anti-CD154 antibodies has shown the importance of this system in the initiation of the inflammatory response, in the activation of antigen-presenting cells and in resistance to infections.     

Synergistic interactions of etoposide and interleukin-1 alpha are not due to DNA damage in human melanoma cells

Family nursing, always a component of nursing, has been recently receiving increased attention through publications, educational programs, clinical practice settings and family nursing research. Nurses are in the best position to assist families experiencing the illness of a loved one, but often lack the skills and confidence necessary to assist with the psychosocial needs. The purpose of this paper is to describe the development and implementation of a family nursing program within a large, tertiary care facility. The program's evaluation is ongoing but early outcomes indicate that day-to-day nursing practice has been positively influenced and improved job satisfaction may result.     

Prediction of necking of high strength steel tubes during hydroforming—multi-axial loading

This article studies tubular hydroforming of high strength low alloy (HSLA) and dual phase (DP600) straight tubes under the action of end feeding loads. Experiments demonstrate that higher end feed loads enhance the formability of the tubes and increase the internal fluid pressure for onset of necking and bursting. Because of the action of the internal pressure and the axial compressive load, the onset of localization (necking) is due to a complex three-dimensional state of stress. Using free expansion experiments, approximate upper and lower bound strain-based forming limit curves are determined for the tube materials. These limit curves, in turn, are used to derive upper and lower bound extended stress-based forming limit curves [Simha et al., Prediction of necking in tubular hydroforming using an extended stress-based FLC. Transactions of the ASME Journal of Engineering Materials and Technology 2007;129(1): 36-47]. In conjunction with finite element computations that use solid elements to model the tube, these stress-based limit curves are used to predict upper and lower bound necking pressures under the action of end feed loading. These predictions of necking pressures, when an appropriate coefficient of tube-die friction is used, are found to bracket the experimentally measured necking pressures. Computations using plane stress shell elements to model the tubes are shown to give erroneous results, since the plane stress approximation is not valid when tubes are hydroformed in a die.     

Genetic marking shows that Ph+ cells present in autologous transplants of chronic myelogenous leukemia (CML) contribute to relapse after autologous bone marrow in CML

Relapse after autologous bone marrow transplantation for chronic myelogenous leukemia (CML) can be due either to the persistence of leukemia cells in systemic tissues following preparative therapy, or due to the persistence of leukemia cells in the autologous marrow used to restore marrow function after intensive therapy. To help distinguish between these two possible causes of relapse, we used safety-modified retroviruses, which contain the bacterial resistance gene NEO, to mark autologous marrow cells that had been collected from patients early in the phase of hematopoietic recovery after in vivo chemotherapy. The cells were then subjected to ex vivo CD34 selection following collection and 30% of the bone marrow were exposed to a safety-modified virus. This marrow was infused after delivery of systemic therapy, which consisted of total body irradiation (1,020 cGy), cyclophosphamide (120 mg/kg), and VP-16 (750 mg/m2). RT PCR assays specific for the bacterial NEO mRNA, which was coded for by the virus, and the bcr-abl mRNA showed that in two evaluable CML patients transplanted with marked cells, sufficient numbers of leukemia cells remained in the infused marrow to contribute to systemic relapse. In addition, both normal and leukemic cells positive for the retroviral transgenome persisted in the systemic circulation of the patients for at least 280 days posttransplant showing that the infused marrow was responsible for the return of hematopoiesis following the preparative therapy. This observation shows that it is possible to use a replication-incompetent safety-modified retrovirus in order to introduce DNA sequences into the hematopoietic cells of patients undergoing autologous bone marrow transplantation. Moreover, this data suggested that additional fractionation procedures will be necessary to reduce the probability of relapse after bone marrow transplantation in at least the advanced stages of the disease in CML patients undergoing autologous bone marrow transplantation procedures.     

LP-BM5 virus causes changes in lactic dehydrogenase and oxygen radical production in splenocytes of C57BL/6J mice

The LP-BM5 murine leukemia virus causes acquired immunodeficiency syndrome in C57BL/6J mice (MAIDS), similar to that of AIDS in humans. The objective of this study was to determine the effect of LP-BM5 viral infection on cellular activation and membrane integrity of splenocytes. Oxidative burst in splenocytes in response to exposure to PMA (20 microg/ml) was significantly higher (p<.02) in infected than in control mice at two weeks post-infection using luminol-enhanced chemiluminescence. By 13 weeks post-infection superoxide anion production in infected mice was significantly lower when compared to controls coinciding with decreased proliferative response to mitogens. The extent of cell membrane damage as indicated by lactic dehydrogenase (LDH) activity in serum was significantly higher in infected than in control mice (p<.001). The results from this study suggests that LP-BM5 virus causes an initial stimulation of cellular activity followed by a decreased cell activation characterized by decreased proliferation of splenocytes and decreased oxygen radical production. Decreased cell membrane integrity indicated by increased LDH activity may partly be responsible for these changes.     

Microscopical imaging of hydroxyapatite/mica composite and packed hydroxyapatite structure--an atomic force microscopy investigation

A focus on the importance of leisure in the development of student nurses has been neglected in the 1990s. This study considers 444 prospective nurses on conventional, diploma and degree courses in two areas of England. It examines their activities associated with socializing, their social support networks and their use of clubs, sports and hobbies before entering nursing. It is evident that students enter nurse training with a wide variety of leisure experiences. Changing recruitment patterns and the structure of nurse training has an effect on the leisure needs of prospective nurses which must be addressed.     

Infectious disease mortality among adults by race and socioeconomic status: metropolitan Ohio, 1989-1991

The data presented here are part of an on-going longitudinal study of the relationship between socioeconomic status and mortality in the major metropolitan centers of Ohio. Using a Standardized Mortality Ratio, we find that mortality in the seven-city urban aggregate exceeds that of the rest of the state by 39 per cent for the nonwhite population and only 1 per cent for the white population. Further, for the nonwhite population, living in a high income area has no discernible health benefit for nonwhites as compared to whites. On the other hand, for the AIDS virus, there is a clear inverse association between economic status and mortality from AIDS. It is clear that the interrelationship among race, economic status, and health continues to be a complex one on which further research is needed.