γ-SNAP stimulates disassembly of endosomal SNARE complexes and regulates endocytic trafficking pathways.

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) that reside in the target membranes and transport vesicles assemble into specific SNARE complexes to drive membrane fusion. N-ethylmaleimide-sensitive factor (NSF) and its attachment protein, α-SNAP (encoded by NAPA), catalyze disassembly of the SNARE complexes in the secretory and endocytic pathways to recycle them for the next round of fusion events. γ-SNAP (encoded by NAPG) is a SNAP isoform, but its function in SNARE-mediated membrane trafficking remains unknown. Here, we show that γ-SNAP regulates the endosomal trafficking of epidermal growth factor (EGF) receptor (EGFR) and transferrin. Immunoprecipitation and mass spectrometry analyses revealed that γ-SNAP interacts with a limited range of SNAREs, including endosomal ones. γ-SNAP, as well as α-SNAP, mediated the disassembly of endosomal syntaxin-7-containing SNARE complexes. Overexpression and small interfering (si)RNA-mediated depletion of γ-SNAP changed the morphologies and intracellular distributions of endosomes. Moreover, the depletion partially suppressed the exit of EGFR and transferrin from EEA1-positive early endosomes to delay their degradation and uptake. Taken together, our findings suggest that γ-SNAP is a unique SNAP that functions in a limited range of organelles - including endosomes - and their trafficking pathways.

Association between intention to stay on the job and job satisfaction among Japanese nurses in small and medium-sized private hospitals.

In order to examine the relationship between the intention to stay on the job and job satisfaction among Japanese nurses, and to obtain clues for preventing turnover, we conducted a questionnaire survey. The subjects involved in the survey included 625 female nurses (registered nurses, licensed practical nurses and assistant nurses) working in 4 small and medium-sized private hospitals, excluding directors of nursing. Of the 625 questionnaires distributed, 556 (89.0%) were returned. After excluding the questionnaires with missing values, 480 questionnaires were analyzed (effective response rate, 76.8%). The average age of the respondents was 32.8 yr (range: 20-65). The content of the questionnaire was nurse attributes, job satisfaction (30 items) and intention to stay on the job. For job satisfaction, factor analysis (principal factor method and promax rotation) was performed, and factors with an eigenvalue of > or =1 were extracted. Six factors were extracted by factor analysis. These factors were interpreted as "Work as specialists" (1st factor), "Relationship with superiors" (2nd factor), "Comfortable life" (3rd factor), "Relationship among nurses" (4th factor), "Communication with physicians" (5th factor) and "Working conditions" (6th factor). The factor scores were calculated and used as a scale for the evaluation of job satisfaction. To investigate the factors associated with intention to stay on the job among nurses, the standard partial regression coefficient was computed by multiple linear regression analysis, with intention to stay on the job as the dependent variable, and nurse attributes and job satisfaction (factor scores) as independent variables. Various factors including the organizational culture of each hospital may affect the relationship between job satisfaction and the intention to stay on the job. In order to adjust for these factors, differences among hospitals were included in the statistical model as independent variables. The result of the multiple regression analysis suggests that the intention to stay on the job was higher among nurses who were older and more satisfied with work as specialists (1st factor) and working conditions (6th factor).

Pharmacokinetics of beclomethasone dipropionate in an hydrofluoroalkane-134a propellant system in Japanese children with bronchial asthma.

BACKGROUND: Hydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma. METHODS: Plasma concentrations of beclomethasone 17-monopropionate (17-BMP),a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 microg as four inhalations from 50 microg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters. RESULTS: The area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t)) was 1659 +/- 850 pg x h/mL (arithmetic mean +/- standard deviation (SD)), the maximum concentration observed (C(max)) was 825 +/- 453 pg/mL and the apparent elimination half-life (t(1/2)) was 2.1 +/- 0.7 hours. The time to reach Cmax Tmax was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC(0-t), 1.04 for Cmax and 1.4 for t(1/2). The median of Tmax was 0.5 hours in American patients as well as Japanese patients. CONCLUSIONS: The pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested.

Autologous peripheral blood stem cell transplantation in a patient with relapsed pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare and aggressive primary intrathoracic neoplasma of children. The prognosis is extremely poor with frequent metastasis to the brain and bone. We present a 4-year-old girl with a tumor mass in the right hemithorax initially diagnosed as pneumoniae. Tumor resection was performed and the histologic report indicated the diagnosis of PPB. The patient received chemotherapy comprising vincristine, actinomycin D, doxorubicin, cisplatin, and cyclophosphamide. Irradiation was performed with total 45 Gy at the right lower pulmonary lobe. She relapsed 29 months later at the pleura between the right middle and lower pulmonary lobe. Tumor resection and total 45 Gy of irradiation were performed again. High-dose chemotherapy comprising cisplatin, adriamycin, and cyclophosphamide was performed followed by autologous peripheral blood stem cell transplantation (PBSCT). The patient achieved complete hematologic recovery. Thirty-one months after PBSCT, no signs of relapse have been observed. Although it might be that the patient could have been cured with second surgery alone or by the surgery and subsequent chemotherapy, high-dose chemotherapy and PBSCT should be considered for the treatment of relapsed PPB.

Factors associated with turnover interntion among nurses in small and medium-sized medical institutions.

OBJECTIVES: The objective of this study was to evaluate factors associated with turnover intention among nurses in small and medium-sized medical institutions. METHODS: A self-administered questionaire survey was performed in 293 registered nurses, licensed practical nurses, and assistant nurses working full-time in various medical institutions. Multiple linear regression analysis was conducted, with turnover intention as the dependent variable, and nurses' basic attributes and job satisfaction as independent variables. RESULTS: As for nurses' basic attributes, turnover intention was significantly associated with registered nurses, younger nurses and those with low satisfaction with sleep. As for nurses' job satisfaction, the number of nurses with turnover intention was significantly higher for those with low satisfaction with salary, low satisfaction with welfare, poor implementation of fair salary raise and poor cooperation among nurses. CONCLUSION: Turnover intention may be reduced by the enhancement of trust in the organization, giving appropriate advice to young nurses and registered nurses, and developing measures for addressing sleep disorders.

Behavior of new type of rock wool (HT wool) in lungs after exposure by nasal inhalation in rats.

OBJECTIVES: Previous types of rock wool has been recently replaced with high-temperature wool (HT wool). HT wool is characterized by a chemical composition with a higher concentration of Al(2)O(3) and a lower concentration of SiO(2), lower biopersistence, and a higher melting point than previous types of rock wool. To evaluate the safety of HT wool, an asbestos substitute, we examined the biopersistence of HT wool in the lungs, based on changes in fiber count according to the length and fiber size (length and width), by performing a nose-only inhalation exposure study in rats. METHODS: Male Fischer 344 rats were exposed to fibers at the target exposure concentration of 30 mg/m(3) continuously for 3 hours daily for 5 consecutive days. Rats were sacrificed shortly after exposure, and 1, 2, and 4 weeks after exposure, and their lung tissues were incinerated at a low temperature. Then, fiber counts and sizes in the lungs were analyzed using a phase contrast microscope. RESULTS: The fiber count in the lungs 4 weeks after exposure significantly decreased from the baseline value (shortly after exposure). The half-life of fibers calculated from the approximation curve was 34 days for all fibers and 11 days for fibers longer than 20 µm. CONCLUSIONS: Both the length and width significantly decreased 4 weeks after exposure, probably because fibers were ingested by alveolar macrophages, discharged to outside of the body by mucociliary movement, or lysed by body fluid. In future studies, it is necessary to examine the long-term persistence of fibers in the lungs.

Factors associated with satisfaction among participants in a periodical worksite health check-up in Japan.

To improve the satisfaction of people who had periodical worksite health check-ups, we conducted a questionnaire survey. It is possible that a portion of the health check-up participants who have a medical history of serious disease may have different expectations of periodical health check-ups compared to healthy individuals. We conducted the analysis by dividing the participants into three groups: those with a medical history of serious disease, those without a medical history of serious disease, and the whole group of those with and without a medical history of serious disease. There were 50 individuals with a medical history of serious disease and 226 without a medical history of serious disease. There were 231 males and 45 females. The average age was 40.3 yr (range: 21-64). To investigate the factors that influence overall satisfaction, we conducted multiple linear regression analysis by a stepwise method, with overall satisfaction as a dependent variable, and attributes of health check-up participants, factors related to the physician, factors related to the examination, and indirect factors such as waiting time as independent variables. The selective criterion for the variables was that the p value was less than 0.05, but sex and age were always included in the final model as independent variables because they might be confounding factors. In the whole group of those with and without a medical history of serious disease, overall satisfaction was significantly associated with the technical level of the person in charge of the examinations, the explanation of the person in charge of the examinations, the time spent for examination, the content of the interview with physicians and interview time with physicians. In the group with a serious disease medical history, overall satisfaction was significantly associated with the explanation of the person in charge of the examinations and interview time with physicians. In the group without a serious disease medical history, overall satisfaction was significantly associated with age, the technical level of the person in charge of the examinations, the time spent for examinations, the content of the interview with physicians and interview time with physicians.