E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts.

Cellular senescence is important for the maintenance of tissue homeostasis, and has recently been shown to pose a natural barrier to tumorigenesis. The E3 ubiquitin ligase, E6AP, has been linked to a number of protein regulators of the cell cycle as well as the cellular stress response. We therefore explored the role of E6AP in the cellular response to stress. We found that mouse embryo fibroblasts (MEFs) lacking E6AP escape replicative senescence, as well as Ras-induced senescence associated with impaired markers. E6AP-deficient MEFs exhibit a range of transformed phenotypes: these include the ability to grow under stress conditions (such as low serum and DNA damage), enhanced proliferation, anchorage independent growth and enhanced growth of xenografts in mice. The transformed phenotype of E6AP-deficient MEFs is associated with lower basal and stress-induced accumulation of p53. Overall, our study implicates E6AP as an important regulator of the cellular response to stress, in particular through the regulation of replicative and oncogene-induced senescence.

Adaptation as a mediator of intimate abuse and traumatic stress in battered women.

The purpose of this research was to test one aspect of a proposed middle-range theory synthesized from the Roy adaptation model and linked with the framework of post-traumatic stress. A predictive-correlational design was used to examine adaptation as a mediator of traumatic stress in battered women. Analysis included regression and path analytic procedures. Results indicated (a) direct relationships between the focal stimuli of abuse and the response of post-traumatic stress disorder and (b) adaptation in the physiologic, self-concept, and interdependence modes partially mediated the relationship between the focal stimuli of abuse and the response of post-traumatic stress disorder in battered women.

Prevalence and patterns of posttraumatic stress disorder in abused and postabused women.

This study examined the prevalence and patterns of posttraumatic stress disorder (PTSD) symptomatology in abused and postabused women. A convenience sample of 160 abused, postabused, and nonabused women completed measures related to physical and emotional abuse by an intimate partner, risk of homicide, and PTSD. Results indicated that PTSD symptoms were present in both the abused and postabused women and were positively correlated with the severity of abuse and risk of homicide that the women experienced. The postabused women were out of the abusive relationship an average of nine years, yet continued to experience PTSD symptoms.

CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells can be made to express recombinant CD40-ligand (CD154) by transduction with a replication-defective adenovirus vector (Ad-CD154). Ad-CD154-transduced and bystander leukemia cells become highly effective antigen-presenting cells that can induce CLL-specific autologous cytotoxic T lymphocytes in vitro. This study investigated the immunologic and clinical responses to infusion of autologous Ad-CD154-CLL cells in patients with CLL. After a one-time bolus infusion of autologous Ad-CD154-transduced leukemia cells, there was increased or de novo expression of immune accessory molecules on bystander, noninfected CLL cells in vivo. Treated patients also developed high plasma levels of interleukin-12 and interferon-gamma, the magnitudes of which corresponded to absolute blood CD4(+) T-cell counts before therapy. On average, patients experienced a greater than 240% increase in absolute blood T-cell counts within 1 to 4 weeks of treatment. Moreover, treatment increased the numbers of leukemia-specific T cells, demonstrated by autologous ELISPOT assay and mixed lymphocyte reactions. These biologic effects were associated with reductions in leukemia cell counts and lymph node size. Treatment did not induce autoimmune thrombocytopenia or hemolytic anemia and no dose-limiting toxicity was observed. This approach may provide a novel and effective form of gene therapy for patients with this disease.

Enhancing the clinical practicum experience through journal writing.

Although journaling is commonplace, its usefulness or effectiveness has been rarely supported by empirical data or examples. The purpose of this article is to highlight integration of classroom and clinical learning, decision-making skills and level of skill acquisition in the Senior Practicum experiences through student journal entry exemplars. Critical thinking, observation and description, and empathy and release of feelings will be discussed.

Posttraumatic stress in battered women: does the diagnosis fit?

Posttraumatic stress disorder (PTSD) has been recommended as an appropriate psychiatric diagnosis for battered women. The criteria for the diagnosis are reviewed along with research that supports its application in battering situations. Definitional, diagnostic, research, and treatment issues using the diagnosis with abused women also are discussed, including recommendations for future investigations and clinical application.

Meningeal macrophages reflect lymphocytic choriomeningitis virus pathogenic phenotypes.

Intracerebral (i.c.) infection of adult mice with lymphocytic choriomeningitis (LCM) virus can result in acute lethal central nervous system (CNS) disease which is the result of the host's thymus-derived lymphocyte (T cell) response against the virus. Whether the specific effector function of the T cell is that of a cytotoxic cell (Tc) or a delayed-type hypersensitivity cell (Td) is still under debate. We assumed that if Td cells were important in pathogenesis then accessory cells in the brain (specifically, glass-adherent macrophages) might vary with the outcome of i.c. infection. We found that accumulation of macrophages in the brain (washed from meninges and skull cap) appeared to be independent of the severity of the infection (controlled by the mouse strain as well as the strain and dose of virus used). However, differentiation of macrophages was clearly linked to whether or not the infection caused rapid death. In mice that were destined to survive, macrophages became large, extensively vacuolated, and phagocytically active. In lethally-infected mice macrophages were small and had poor phagocytic abilities. At present this dichotomy could be viewed as either a cause or a consequence of disease outcome. However, the data are not inconsistent with the hypothesis that Td lymphocytes may be of primary importance in pathogenesis.

Lipid in the Achilles tendon. A comparative study.

The tendo Achillis of man and its homologue from a fairly wide range of exotic animals, most of which had died in captivity from natural causes, have been examined for stainable lipid. Adiposity of the tendon was seen principally in man. Chondroid plaques, containing an abundance of intracellular triglycerides, are a normal feature in birds. Similar thickenings in the few reptiles examined were rich in phospholipids. Extracellular (perifibrous, interstitial) deposits of lipid with a high content of esterified cholesterol were found in more than 90% of human specimens, in 52% of other mammals and in 62.5% of birds included in the survey. In general, lipid insudation of tendons increased with age and was less intense in animals than man. Aetiological factors and the relationship of extracellular lipid deposits in tendons to those in the arterial wall and dura mater are considered.