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Interstitial lung diseases (ILDs) are associated with an increased risk of lung cancer, and pulmonary resection is well known to be associated with high postoperative morbidity and mortality in lung cancer patients. Postoperative mortality rate of acute exacerbation( AE) was reported 33.3~100%. Sex, CRP, KL-6, %vital capacity( VC), forced expiratory volume in 1 second( FEV1.0), history of AE, preoperative steroid use, and surgical procedures were identified as possible risk factors of AE in the univariate analyses by the data obtained from patients with non-small cell lung cancer who had undergone pulmonary resection and presented with a clinical diagnosis of ILD between January 2000 and December 2009 at 64 institutions throughout Japan. Multivariate analysis using these factors identified surgical procedures except for wedge resection, history of AE, KL-6, %VC, and male sex as independent risk factors. A score by risk prediction for AE was 5 X (history of AE)+4 X (CT:UIP pattern)+3 X (gender:male)+3 X (preoperative steroid use)+2 X (KL-6>1,000 U/ml)+1 X (VC≤80%). The predicted probability of risk score 15~22 is>0.25, and risk score 11~14 is 0.1~0.25. We can use a simple risk scoring system comprising seven parameters to identify high risk patients for AE, and provide essential information to support fair and objective clinical decision-making by thoracic surgeons.

In contemporary Japan, there is a polarizing trend in children who exercise more than 1,800 minutes a week and those who exercise less than 60 minutes a week. Quite a lot of girls in particular hate exercise,and therefore they don't get enough of it. Osteoporosis is a preventable disease from childhood. It is crucial for girls to exercise and to provide appropriate stimulation to bones before menarche, which increases bone mineral content. Exercise and sports in childhood are characterized as the ways to the lifelong prevention strategies against osteoporosis and fractures. It is hoped that all children practice appropriate exercise program based on scientific evidence to promote bone health. In this review article, the effects of exercising in childhood on bone health, and the points to be noted regarding childhood sports are described.

It is routine to search for and recognized genetic defects in human disorders to provide knowledge for diagnosis, treatment, and protection against diseases. It is also important to investigate and demonstrate the cause of a disease from the proteomic perspective, because intracellular signaling systems depend on protein dynamics. Demonstrating changes in protein levels enables us to understand biochemical events during the initiation and progression of a disease. To understand changes in protein levels in tissues and cells, we have developed a novel proteomics approach, FD-LC-MS/ MS. This consists of fluorogenic derivatization (FD), HPLC separation and detection/quantification of proteins in a biological sample, followed by the isolation and tryptic digestion of target proteins, and then their identification using HPLC and tandem mass spectrometry (MS/MS) with a database-searching algorithm. The method is highly sensitive (femtomole-level detection) through the use of less noisy fluorogenic rather than fluorescence derivatization, and enables precise and comprehensive relative quantitation of protein levels (between-day relative standard deviation of peak heights of ca. 20%) by combining FD with HPLC separation. In this paper, after a simple review of differential profiling using FD-LC-MS/MS, for example the analysis of stimulated vs. unstimulated samples, we introduce the development and application of the FD-LC-MS/MS method for comprehensive differential proteomics of several tissues, including mouse liver, mouse brain, and breast cancer cell lines, to reveal protein levels and biochemical events in tissues and cells.

Since locally advanced non-small-cell lung cancer(NSCLC)treated by surgical therapy alone has a poor prognosis, the efficacy of preoperative chemotherapy for improving postoperative survival in patients with NSCLC is controversial. A 69-year-old female was referred to our hospital for Stage IIIA(cT3bulkyN2M0)adenocarcinoma of the right lung. Computed tomography(CT)revealed a small nodule, 21mm in diameter, in the right S6, with isolated pulmonary metastasis in the same lobe and bulky subcarinal lymph node swelling. She received two courses of a combination of carboplatin(CBDCA AUC5), paclitaxel(PTX 200mg/m2)and bevacizumab(15mg/kg)as induction therapy, and showed no serious adverse effects. CT after induction therapy revealed a minor radiographic response. She underwent right lower lobectomy with node dissection 2a in 2011. An intercostal muscle flap was used for the bronchial stump. Histopathological examination revealed adenocarcinoma pT1aN0M0 of Stage I A, and showed that the pulmonary metastasis had disappeared even though the effect of induction chemotherapy was Ef2. Induction chemotherapy with carboplatin, paclitaxel and bevacizumab may be useful for treatment of locally advanced lung cancer.

Clinically available methods for estimating bone strength include bone densitometry techniques such as dual energy X-ray absorptiometry and quantitative computed tomography, and other diagnostic imaging procedures such as radiographic imaging. These techniques evaluate regional bone density and morphology, which are partly related to fracture risk, but are of limited value for quantifying structural strength. Therefore, it is necessary to develop a noninvasive method for accurate quantitative structural analysis that incorporates information on both morphology and bone density in a three-dimensional distribution. Computed tomography-based finite element method (CT/FEM), which incorporates information on both the three-dimensional architecture and bone density distribution, could possibly achieve precise assessment of the strength of the bone. We focused on a CT/FEM to quantify structural strength, developing a nonlinear CT/FEM to achieve accurate assessment of strength in the proximal femur and lumbar vertebrae. Here, we describe the CT/FEM.

A 63-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination revealed moderately-differentiated adenocarcinoma (pT2N2M0, pStage III A). She received one course of a combination of etoposide (ETP) and cisplatin(CDDP)as adjuvant therapy, followed by oral intake of UFT. At 9 months post-operatively, she received radiation therapy for lymph node recurrence, at which time new multiple lung metastases were found. After receiving 3 courses of a combination of vinorelbine (VNR) and CDDP, a complete response (CR) of all metastatic lesions was achieved. Three years after the original surgery, metastatic lesions recurred, and a total of 9 courses of a combination of VNR and carboplatin (CBDCA) and partial resection of the right lung for pulmonary metastasis were performed in succession. Following this therapy, treatment with gefitinib was initiated for about 6 months, and computed tomography (CT) showed progressive disease. For 8 years following the original operation, the patient received oral chemotherapy using S-1 and has maintained CR on CT. We conclude that oral administration of S-1 is useful as palliative chemotherapy without serious adverse events or worsening of quality of life. Patients like this case are thus able to continue chemotherapy for a long time.

Osteoporosis is a systemic skeletal disease characterized by bone fragility and susceptibility to fracture risk. Bone fragility and fracture risk primarily reflect the integration of bone density and bone quality. Micro-computed tomography (CT) and clinical CT are useful techniques for assessing osteoporosis and predicting fracture risk. Micro-CT is useful for assessing 3D trabecular bone structure. Quantitative CT (QCT) and peripheral QCT (pQCT) are promising tools for the measurements of the bone density. CT-based finite element method (FEM) may provide some useful information about bone mechanics and predict bone strength and fracture site. The usefulness and the limitations of these techniques are reviewed in this paper.

A method has been proposed for determining the detection limit (L(D)) from the slope of a semilogarithmic plot of a B/B(0) curve in competitive enzyme linked immunosorbent assay (ELISA). As an application, this paper describes a graphic determination of L(D) from analogue data in the literature. The L(D) obtained corresponds to the concentration at which the relative standard deviation of concentration estimates is 30%.

In order to understand the mechanism for maintaining life of animals based on the search of dynamics of biomolecules, I have developed several sensitive and selective methods for their quantification. Using the methods of derivatization with the developed benzofurazan fluorogenic reagents (4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), ammonium 7-fluoro-2,1,3-benzoxadiazole 4-sulfonate (SBD-F) and etc.) followed by high-performance liquid chromatography (HPLC)--fluorescence detection, a certain kind of biological and clinical importance was demonstrated of chiral bio-molecules (D-amino acids, D-lactic acid and so on), peptides and proteins. The proposed method (derivatization with SBD-F, isolation of the fluorescent proteins by two-dimensional HPLC, enzymatic digestion and identification of the altered proteins by HPLC-mass spectrometry (MS)/MS with database-searching algorithm) for proteomics studies revealed the changed proteins in the islets of Langerhans of the dexamethazone-induced diabetic rats. An importance of catecholamine metabolism on the blood pressure regulation was also suggested by the method of HPLC-chemiluminescence detection of catecholamines and their 3-O-methylmetabolites. A new field of Analytical Chemistry, i.e., Bio-Analytical Chemistry, was also proposed.

The internal standard methods are known to compensate for the errors from sample preparation and injection into an analytical instrument. However, recent HPLC apparatuses have injectors of excellent repeatability and it is dubious whether the cancellation of injection error can lead to substantial improvement in the precision of analysis. This paper answers the above question experimentally and theoretically. The HPLC analysis of butylscopolamine bromide is taken as an example. The relative standard deviations (RSD) of measurements in the internal standard method and absolute calibration curve method are compared and the advantages of these methods are discussed. The measurement RSD is shown to be well estimated by the (function of mutual information) (FUMI) theory without repeating measurements. This report also demonstrates simple equations for calculating the measurement RSD at an arbitrary concentration of analyte and for selecting the better method between the internal standard method and absolute calibration curve method under specific experimental conditions.

In system suitability tests, the daily conditions of an analytical instrument are checked with the standard deviation (SD) of measurements as a criterion. This paper examines how exactly the SD values obtained from the measurements can indicate instrumental conditions. The HPLC measurement for acetaminophen is repeated six times daily to obtain an SD estimate, and these procedures are repeated for seven days. The degree of scattering of the seven SD values corresponds well to the 95% confidence intervals calculated from the chi-square distribution (n = 6). Therefore it is concluded that the variability of the daily conditions of the HPLC system used in this study is too small to detect by referring to the SD estimates (n = 6) and the daily change in the SD estimates only represents the error of the SD estimation itself. However, if the repetition number is 40 (n = 40), the SD estimates will be a good indicator. Forty measurements are practically impossible for a slow analysis like HPLC, and this paper recommends the function of mutual information theory as a substitute for repetitive measurement.