Illness experiences of patients with ischemic heart disease during their transitional phase from hospitalization to discharge in Japan

The purpose of this study was to explore the experience of patients with ischemic heart disease (IHD) during the transitional phase from hospitalization to discharge. Twenty-four patients who experienced IHD for the first time comprised the sample of the study. Semi-structured interviews were conducted during the transitional phase. The results of the qualitative inductive analysis showed two categories of illness experience : (i) the connection of heart attack experience with the self, and (ii) the instability of the self as a patient with heart disease. The participants were found to vacillate between the self as patient with a heart disease and the typical self before the disease onset. The transitional phase is the time when patients experience changes in their symptoms and physical conditions rather than a condition of stability signifying recovery. Patients are expected to manage the symptoms of their heart disease by themselves ; however the participants showed signs and symptoms of confusion and anxiety about facilitating their own care. These findings suggest the importance of outpatient nursing practice focusing on the support and emphasis on nursing interventions for patient anxiety and alleviation of confusion through the management of symptoms of heart disease after discharge

Illness experiences of patients with ischemic heart disease during their transitional phase from hospitalization to discharge in Japan

The purpose of this study was to explore the experience of patients with ischemic heart disease (IHD) during the transitional phase from hospitalization to discharge. Twenty-four patients who experienced IHD for the first time comprised the sample of the study. Semi-structured interviews were conducted during the transitional phase. The results of the qualitative inductive analysis showed two categories of illness experience : (i) the connection of heart attack experience with the self, and (ii) the instability of the self as a patient with heart disease. The participants were found to vacillate between the self as patient with a heart disease and the typical self before the disease onset. The transitional phase is the time when patients experience changes in their symptoms and physical conditions rather than a condition of stability signifying recovery. Patients are expected to manage the symptoms of their heart disease by themselves ; however the participants showed signs and symptoms of confusion and anxiety about facilitating their own care. These findings suggest the importance of outpatient nursing practice focusing on the support and emphasis on nursing interventions for patient anxiety and alleviation of confusion through the management of symptoms of heart disease after discharge

Pronuclear injection-based mouse targeted transgenesis for reproducible and highly efficient transgene expression

Mouse transgenesis has proven invaluable for analysis of gene function and generation of human disease models. We describe here the development of a pronuclear injection-based targeted transgenesis (PITT) system, involving site-specific integration in fertilized eggs. The system was applied to two different genomic target loci to generate a series of transgenic lines including fluorescent mice, which reproducibly displayed strong, ubiquitous and stable transgene expression. We also demonstrated that knockdown mice could be readily generated by PITT by taking advantage of the reproducible and highly efficient expression system. The PITT system, which circumvents the problem of unpredictable and unstable transgene expression of conventional random-integration transgenic mice, reduces the time, cost and effort needed to generate transgenic mice, and is potentially applicable to both in vivo ‘gain-of-function’ and ‘loss-of-function’ studies

Phosphorylation of p27Kip1 by Epstein-Barr Virus Protein Kinase Induces Its Degradation through SCFSkp2 Ubiquitin Ligase Actions during Viral Lytic Replication*

Epstein-Barr virus (EBV) productive replication occurs in an S-phase-like cellular environment with high cyclin-dependent kinase (CDK) activity. The EBV protein kinase (PK), encoded by the viral BGLF4 gene, is a Ser/Thr protein kinase, which phosphorylates both viral and cellular proteins, modifying the cellular environment for efficient viral productive replication. We here provide evidence that the EBV PK phosphorylates the CDK inhibitor p27Kip1, resulting in ubiquitination and degradation in a proteasome-dependent manner during EBV productive replication. Experiments with BGLF4 knockdown by small interfering RNA and BGLF4 knock-out viruses clarified that EBV PK is involved in p27Kip1 degradation upon lytic replication. Transfection of the BGLF4 expression vector revealed that EBV PK alone could phosphorylate the Thr-187 residue of p27Kip1 and that the ubiquitination and degradation of p27Kip1 occurred in an SCFSkp2 ubiquitin ligase-dependent manner. In vitro, EBV PK proved capable of phosphorylating p27Kip1 at Thr-187. Unlike cyclin E-CDK2 activity, the EBV PK activity was not inhibited by p27Kip1. Overall, EBV PK enhances p27Kip1 degradation effectively upon EBV productive replication, contributing to establishment of an S-phase-like cellular environment with high CDK activity

TORC2, a Coactivator of cAMP-response Element-binding Protein, Promotes Epstein-Barr Virus Reactivation from Latency through Interaction with Viral BZLF1 Protein*S⃞

Reactivation of the Epstein-Barr virus from latency is dependent on expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical inducers such as 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. We found here that Transducer of Regulated cAMP-response Element-binding Protein (CREB) (TORC) 2 enhances Zp activity 10-fold and more than 100-fold with co-expression of the BZLF1 protein. Mutational analysis of Zp revealed that the activation by TORC is dependent on ZII and ZIII cis elements, binding sites for CREB family transcriptional factors and the BZLF1 protein, respectively. Immunoprecipitation, chromatin immunoprecipitation, and reporter assay using Gal4-luc and Gal4BD-BZLF1 fusion protein indicate that TORC2 interacts with BZLF1, and that the complex is efficiently recruited onto Zp. These observations clearly indicate that TORC2 activates the promoter through interaction with the BZLF1 protein as well as CREB family transcriptional factors. Induction of the lytic replication resulted in the translocation of TORC2 from cytoplasm to viral replication compartments in nuclei, and furthermore, activation of Zp by TORC2 was augmented by calcium-regulated phosphatase, calcineurin. Silencing of endogenous TORC2 gene expression by RNA interference decreased the levels of the BZLF1 protein in response to 12-O-tetradecanoylphorbol-13-acetate/ionophore. Based on these results, we conclude that Epstein-Barr virus exploits the calcineurin-TORC signaling pathway through interactions between TORC and the BZLF1 protein in reactivation from latency