Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein

Here, we describe the folding/unfolding kinetics of alpha3D, a small designed three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing methods reveal a single-exponential process consistent with a minimal folding time of 3.2 +/- 1.2 micros (at approximately 50 degrees C), indicating that a protein can fold on the 1- to 5-micros time scale. Furthermore, the single-exponential nature of the relaxation indicates that the prefactor for transition state (TS)-folding models is probably >or=1 (micros)-1 for a protein of this size and topology. Molecular dynamics simulations and IR spectroscopy provide a molecular rationale for the rapid, single-exponential folding of this protein. alpha3D shows a significant bias toward local helical structure in the thermally denatured state. The molecular dynamics-simulated TS ensemble is highly heterogeneous and dynamic, allowing access to the TS via multiple pathways.     

Multiple bone fractures found in a young sarcoidosis patient with long stable disease

A 22-year-old Japanese man was found to have bilateral hilar lymphadenopathy (BHL), and was diagnosed with sarcoidosis in 1995. He was followed without treatment until 2002, when a bone fracture due to osseous sarcoidosis was found in his left thumb. Despite systemic treatment with corticosteroid and methotrexate, a new bone lesion developed in his right foot and his right middle finger was fractured. The patient also suffered multiple organ involvements including brain and muscle lesions. This is the first report of a sarcoidosis patient who presented with BHL, and developed bone fractures after a long stable period of more than 5 years.     

The predictive role of infiltrative growth pattern in early pharyngeal cancers

Conclusion: The infiltrative growth pattern may predict tumor depth and lymph node metastasis. INF-a seems to fall into a low-risk category, and no additional treatment may be required immediately. Objectives: Tumor depth is a predictor of lymph node metastasis in early pharyngeal cancers. An infiltrative growth pattern is also a prognostic factor in other cancers. This study aimed to elucidate the predictive role of infiltrative growth pattern in early pharyngeal cancers. Methods: Thirty-eight lesions from 37 patients who had undergone trans-oral resection of pharyngeal cancers were included. According to the Japanese Classification of Esophageal Cancer, infiltrative growth pattern was classified into three groups; INF-a, INF-b, and INF-c. The correlation between infiltrative growth pattern and tumor depth, cervical lymph node metastasis was analyzed. Results: Of the 38 lesions, 25 were INF-a, nine were INF-b, and four were INF-c lesions. Lymph node metastasis was observed in three INF-b and one INF-c lesions. In contrast, no INF-a had lymph node metastasis. All INF-a lesions showed shallow invasion of the sub-epithelium; INF-b and INF-c lesions had significantly greater depth than INF-a.     

Effects of Hangeshashinto on the nasal physiological function: An in vitro study.

ObjectiveHangeshashinto is a Japanese Kampo medicine applied for the treatment of oral mucositis and gastroenteritis. Hangeshashinto exhibits broad-spectrum antibacterial activity and suppresses prostaglandin (PG)E2 production in the mucosa and has the ability to improve the inflammatory condition. In addition to these effects, because cAMP, a composition of Hangeshashinto, facilitates ciliary beat, Hangeshashinto could also improve the physiological function of the nasal mucosa, consist of ciliated epithelium, but details were unknown.MethodsThis study was aimed to investigate the effects of Hangeshashinto on the nasal mucosa. Healthy nasal mucosal sections were collected from the nasal septum of ten Japanese white rabbits, placed in a collagen dish for tissue culture, and rinsed with two different concentrations of Hangeshashinto solution (1.0%, n = 10 and 2.5%, n = 10) and cAMP solution (50µM, n=10 and 100 µM, n=10) or saline (control, n = 10). Ciliary beat frequency (CBF) as a physiological function of the nasal mucosa was recorded at 1, 3 and 7 days after rinsing, and histological evaluation of epithelial damage was performed at 7 days after rinsing.ResultsCBF in the 1.0% but not in the 2.5% Hangeshashinto group, increased at 3 and 7 days compared with that in the control group (p < 0.05). This trend was also observed in the CBF in the 100 µM cAMP group, significant difference was not observed between the CBF of the 1.0% Hangeshashinto group and the 100 µM cAMP group at 1, 3 and 7 days after rinsing (p > 0.05). Histological score only in the 2.5% Hangeshashinto group was lower than that in the control group (p < 0.05), while a significant decline was not observed in the other groups compared to that in the control group (p > 0.05).ConclusionOur results suggest that 1.0% Hangeshashinto solution facilitates the physiological function of the nasal mucosa by promoting ciliary functions without histological damage of cilia epithelium. When applied with the appropriate concentration, Hangeshashinto could have ability to improve the physiological functions of the nasal mucosal epithelium.     

Job Demands,Job Resources,and Job Performance in Japanese Workers: A Cross-sectional Study

This study investigated the cross-sectional association of job demands (i.e., psychological demands) and job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward) with job performance. A total of 1,198 workers (458 males and 740 females) from a manufacturing company in Japan completed a self-administered questionnaire that included the Job Content Questionnaire, Effort-Reward Imbalance Questionnaire, World Health Organization Health and Work Performance Questionnaire, and demographic survey. Hierarchical multiple regression analyses were conducted. After adjusting for demographic characteristics, decision latitude (β=0.107, p=0.001) and extrinsic reward (β=0.158, p<0.001) were positively and significantly associated with job performance while supervisor support (β=−0.102, p=0.002) was negatively and significantly associated with job performance. On the other hand, psychological demands or co-worker support was not significantly associated with job performance. These findings suggest that higher decision latitude and extrinsic reward enhance job performance among Japanese employees.     

Free air on CT and the risk of peritonitis in peritoneal dialysis patients: a retrospective study

Background: Intra-abdominal free air is found frequently in patients undergoing peritoneal dialysis (PD). Some studies have investigated an association between intra-abdominal free air and peritonitis in PD patients. However, most used chest X-rays, which are of limited sensitivity, and the association was not made clear. We conducted a retrospective study of the association between peritonitis and intra-abdominal free air using computed tomography. Methods: The presence and volume of free air, and its relationship with other variables, were assessed on review of routine examinations in 108 patients. Correlations between the presence of free air and age, duration of PD, continuous ambulatory versus automated PD, presence or absence of a person who assisted in bag changes, exit-site infection, tunnel infection and peritonitis were assessed. Results: Free air was detected in 29 patients (27.1%). The prevalence of peritonitis was higher in the free air (+) group than in the free air (?) group: 1/40.2 patient-months for free air (+) versus 1/96.9 patient-months for free air (?). The risk ratio of free air for peritonitis was 2.41 (95% confidence interval: 2.28–2.55) and was similar when corrected for age, gender, albumin, diabetes mellitus and body mass index. Conclusion: Free air is an independent risk factor for peritonitis in PD patients. This suggests that bag change procedures should be re-evaluated, and patients re-educated, when necessary.     

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between “precursor-like” and “regular type” lesions

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically “regular type” IDC-P and “precursor-like” IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.