LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25

Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes autosomal-dominant familial Parkinson's disease (PD). Yeast two-hybrid screening revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein, interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is phosphorylated by LRRK2. A glutathione-S-transferase (GST) pull-down assay showed that LRRK2 may interact with Snapin via its Ras-of-complex (ROC) and N-terminal domains, with no significant difference on interaction of Snapin with LRRK2 wild type (WT) or its pathogenic mutants. Further analysis by mutation study revealed that Threonine 117 of Snapin is one of the sites phosphorylated by LRRK2. Furthermore, a Snapin T117D phosphomimetic mutant decreased its interaction with SNAP-25 in the GST pull-down assay. SNAP-25 is a component of the SNARE (Soluble NSF Attachment protein REceptor) complex and is critical for the exocytosis of synaptic vesicles. Incubation of rat brain lysate with recombinant Snapin T117D, but not WT, protein caused decreased interaction of synaptotagmin with the SNARE complex based on a co-immunoprecipitation assay. We further found that LRRK2-dependent phosphorylation of Snapin in the hippocampal neurons resulted in a decrease in the number of readily releasable vesicles and the extent of exocytotic release. Combined, these data suggest that LRRK2 may regulate neurotransmitter release via control of Snapin function by inhibitory phosphorylation.

A Study on Factors and Correlations of Burnout and Job Satisfaction of Dietitians in Hospitals

This study aimed to examine factors and the correlations of burnout and job satisfaction in hospital dietitians. Burnout was classified into three sub-concepts: emotional exhaustion, depersonalization, and reduced personal accomplishment. Job satisfaction was also classified into three sub-concepts, including relationships, self-realization, and advancement opportunities. A survey was conducted with dietitians working in general hospitals of over 400 beds, in the Seoul metropolitan area. The factors that significantly influenced emotional exhaustion were health, work hours, number of intern dietitians, self-esteem, level of responsibility, while the factors that influenced depersonalization were relationships with coworkers, and role ambiguity. Personal accomplishment was influenced by age, the number of staff dietitians, the general number of managed workers, and self-esteem. In terms of job satisfaction, relationship was affected by age and relationships with supervisors, while self-realization was influenced by work hours, health, the number of patient meals, and role ambiguity. Age, job regularity, business management, role ambiguity, and relationships with supervisors also affected advancement opportunities. Emotional exhaustion, depersonalization, and reduced personal accomplishments, which represented burnout, had negative relationships with satisfaction with relationships, self-realization and advancement opportunities. Dietitians with low job satisfaction were likely to experience burnout. These results suggest that burnout and job satisfaction are influenced by internal and external factors that are individual or organizational problems encountered by hospital dietitians. Therefore, managers as well as dietitians need to understand these factors and overcome them through communication and mutual support.

A Study on Factors of Job Satisfaction and Burnout of Hospital Dietitians / 대한지역사회영양학회지

This research aims to examine the experiences of hospital dietitians' burnout and the factors of their burnout, such as demographic factors, unique characteristics of hospitals, their self-respect, and organizational factors. In order for this, a questionnaire survey was conducted with hospital dietitians working in general hospitals of over 400 beds in the Seoul Metropolitan area. The average point of self-respect of dietitians is 3.67 out of 5.00. Their experience of burnout turned out to be 3.17 out of 7, the extent of job satisfaction is high, that is 3.35 out of 5.00. The decrease of personal accomplishment is shown to be closely related to the burnout of dietitians. The emotional exhaustion in burnout at the significant level 0.001 is increasing as the annual gross salary is low, their age is young, extra-working hours are long, and is high to the dietitians serving meals and working at entrusted companies. The factors affected by burnout experience vary with individual circumstances. So, to prevent the emotional exhaustion, depersonalization, and reduced personal accomplishment, hospital dietitians' spiritual and physical health needs to be kept up by their self-development and investment.

Transcriptional targeting of gene expression in breast cancer by the promoters of protein regulator of cytokinesis 1 and ribonuclease reductase 2

For cancer gene therapy, cancer-specific over-expression of a therapeutic gene is required to reduce side effects derived from expression of the gene in normal cells. To develop such an expression vector, we searched for genes over-expressed and/or specifically expressed in cancer cells using bioinformatics and have selected genes coding for protein regulator of cytokinesis 1 (PRC1) and ribonuclease reductase 2 (RRM2) as candidates. Their cancer-specific expressions were confirmed in both breast cancer cell lines and patient tissues. We compared each promoter's cancer-specific activity in the breast normal and cancer cell lines using the luciferase gene as a reporter and confirmed cancer-specific expression of both PRC1 and RRM2 promoters. To test activities of these promoters in viral vectors, the promoters were also cloned into an adeno-associated viral (AAV) vector containing green fluorescence protein (GFP) as the reporter. The GFP expression levels by these promoters were various depending on cell lines tested and, in MDA-MB-231 cells, GFP activities derived from the PRC1 and RRM2 promoters were as strong as that from the cytomegalovirus (CMV) promoter. Our result showed that a vector containing the PRC1 or RRM2 promoter could be used for breast cancer specific overexpression in gene therapy.

Analysis of Linear Growth in Children after Living-related Liver Transplantation / 대한소아소화기영양학회지

PURPOSE: The aim of this study is to evaluate the effective role of living-related liver transplantation (LRLT) on posttransplant linear growth in children. METHODS: Thirty six children were enrolled who received LRLT at Asan Medical Center from December, 1994 to February, 1999 and showed more than one-year postoperative survival. Mean height standard deviation score (zH) was analyzed according to medical records including heights during pretransplant and posttransplant follow-up periods. RESULTS: zH of total children showed significant linear growth after LRLT from -1.58 to 0.33 at 24 posttransplant month (p<0.05). zH in children under 6 years of age, to exclude the effect of adolescent linear growth spurt, showed increment in height (p<0.05). Linear growth of children with liver cirrhosis improved and that with fulminant hepatitis was matained same. While stunted children (mean zH=-2.30) achieved good catch-up growth after transplantation, children with normal growth remained same. Children with significant hepatic dysfunction after LRLT such as chronic rejection or posttransplant lymphoproliferative disorder showed retarded posttrasplant linear growth. There was no statistical difference according to the type of immunosuppressants. CONCLUSION: LRLT resulted in adequate or catch-up linear growth in children with acute, chronic and metabolic liver disease. Successful LRLT suggested to be a promising option not only in long term survival but also in normal linear growth.

The Usefulness of the Head-up Tilt Test for Diagnosis of Syncope in Pediatric Patients

PURPOSE: The purpose of this study is to examine the usefulness of the head-up tilt test for diagnosis of unexplained syncope in children. METHODS: Head-up tilt test results and clinical features of 41 children with unexplained syncope, presyncope, dizziness and seizure were studied from January, 1997 through January, 2001 at Asan Medical Center. Medical records of children were reviewed retrospectively. The children were evaluated with an 80 degrees head-up tilt test for 15 minutes with or without intravenous infusion of isoproterenol(0.05-0.1 ng/kg/min). RESULTS: 41 children made up the study population, of whom 23(56%) had a positive head-up tilt test and 21(60%) of 35 patients with a history of syncope or presyncope had a positive head-up tilt test. Isoproterenol infusion provoked the more positive head-up tilt test. The patients with positive test results showed three patterns of response to tilting. 16 patients had a predominantly vasodepressor response; three patients had a cardioinhibitory response; and four patients had a mixed response. The patients had an average of five studies performed per patient, including chest radiograph, electrocardiogram, 24 hour Holter monitoring, treadmil test, head computed tomographic scan or magnetic resonance imaging, and echocardiography. The head-up tilt test was most effective for evaluation of unexplained syncope in children. CONCLUSION: Head-up tilt testing performed early in the evaluation will increase the probability of a diagnosis, and will often prevent the need for further extensive, expensive, anxiety-producing tests in children. More controlled studies and a standardization of degree and duration of tilting are necessary to validate the head-up tilt test as a useful diagnostic tool in children with unexplained syncope.

A Case of Acute Necrotizing Encephalopathy

Acute necrotizing encephalopathy is a recently established disease entity, proposed by Mizuguchi et al in 1995, that shows a characteristic symmetric and multifocal involvement of both thalamus, brainstem tegmentum, cerebral periventricular white matter, and cerebellar medulla. It is known to be prevalent in Japan and other Far Ease countries. The etiology of the acute necrotizing encephalopathy remains unknown. The typical course of acute necrotizing encephalopathy is the development of the irreversible neurologic symptoms related to brain lesions. The diagnosis can be made on the basis of the combination of a typical clinical profile and characteristic radiologic findings. We experienced a first case of acute necrotizing encephalopathy in a 9 month old boy in Korea. We report this case with the brief review of related literatures.