Varying-coefficient modeling via regularized basis functions

We address the problem of constructing varying-coefficient models based on basis expansions along with the technique of regularization. A crucial point in our modeling procedure is the selection of smoothing parameters in the regularization method. In order to choose the parameters objectively, we derive model selection criteria from the viewpoints of information-theoretic and Bayesian approach. We demonstrate the effectiveness of proposed modeling strategy through Monte Carlo simulations and analyzing a real data set.Comment: 10 pages, 4 figure

Urinary adiponectin as a biomarker for DKD

We previously developed two immune complex transfer enzyme immunoassays (ICT-EIA) to measure total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) in urine and have verified their usefulness as biomarkers for diabetic kidney disease. In this study, we developed T-AN and H-AN assays using the sandwich EIA (Sand-EIA). The reactivities of Sand-EIAs were compared with ICT-EIAs by measuring size exclusion chromatography (SEC) fractions of urine and adiponectin standard. As a result, ICT-EIAs showed higher macromolecular specificity. We then analyzed the molecular profile of adiponectin in the urine of 5 patients with different eGFR stages by measuring SEC fractions of urine. The results showed that smaller adiponectin correlated relatively well with eGFR stage. Finally, because SEC is time-consuming, we investigated that the ratio of T-ANs by Sand-EIA and ICT-EIA could be a good indicator of the monomer adiponectin. The ratio was evaluated using 77 urine samples from patients with diabetes and showed a significant decrease at an earlier stage compared with other biomarkers. In conclusion, we demonstrated a new index to estimate monomer adiponectin in urine by using Sand-EIA and ICT-EIA, and urinary monomer adiponectin can be a good early indicator of deterioration of renal function in diabetic patients

Factors Predicting a Favorable Disease Course Without Anti-TNF Therapy in Crohn’s Disease Patients

Determining factors that predict a favorable disease course without anti-tumor necrosis factor (TNF) agents would help establish a more cost-effective strategy for Crohn’s disease (CD). A retrospective chart review was performed for CD patients with disease durations > 10 years who had not received anti-TNF agents as first-line therapy. Patients were divided into 2 groups: those who received neither anti-TNF agents nor bowel resection (G1), and those who had received an anti-TNF agent and/or bowel resection (G2). The patient backgrounds, therapies and clinical courses were compared between the groups. A total of 62 CD patients met the inclusion criteria (males: 71%; median duration of follow-up: 19 years). Six patients were included in G1; they were significantly less likely to have upper gastrointestinal lesions than G2 (p=0.007). A multivariate analysis revealed that the significant factors for avoidance of bowel resection without anti-TNF treatment were non-stricturing and non-penetrating behaviors, and absence of upper gastrointestinal lesions at the diagnosis (hazard ratios 0.41 and 0.52; p=0.004 and 0.04, respectively). In consideration of the long treatment course of CD, patients with non-stricturing and non-penetrating behaviors and no upper gastrointestinal lesions should not be treated with anti-TNF agents as first-line therapy

Marylosides A-G, Norcycloartane Glycosides from Leaves of Cymbidium Great Flower ‘Marylaurencin’

Seven novel norcycloartane glycosides, maryloside A–G (1–7), were isolated from the leaves of Cymbidium Great Flower ‘Marylaurencin’, along with a known norcycloartane glycoside, cymbidoside (8). These structures were determined on the basis of mainly NMR experiments as well as chemical degradation and X-ray crystallographic analysis. The isolated compounds (1–6 and 8) were evaluated for the inhibitory activity on lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Consequently, 1 and 3 exhibited moderate activity

Atomic Bomb Fallout and “Black rain” at Manose District (Hirama-cho) Located Northeast of Nagasaki City

Plutonium atomic bomb (A-bomb) was exploded at 503 meters height above Nagasaki City on August 9, 1945. Many studies on radioactive contamination, radiation dose, effect to people and so on have been conducted until now. Local fallout from the A-bomb mainly spread a lot in the east direction centering on Nishiyama area located about 4 km east of the hypocenter. Like the Hiroshima A-bomb, black rain accompanied by radioactive materials fell shortly after the explosion, but relationship between local fallout fall zone and black rain fall area has not been sufficiently elucidated, which has enhanced the concerns on radiation exposure to the A-bomb survivor. Concerning the black rain due to the Nagasaki A-bomb, it has been said that black rain did not fall across a wide area in a comprehensive way, except for the heavily contaminated Nishiyama area, but fell at various areas with conditions of light rain and/or soaking after the explosion. Among many villages or towns, especially in the Manose District where is a small intermountain village about 7.5 km northeast of the hypocenter, it had always been heard and known that the residents living there encountered black rain and experienced hair loss. In this district, the hair loss of inhabitants occurred actually with high probability, but its reason has not been elucidated well. Therefore, in order to reevaluate the local fallout level in the Manose District by the A-bomb, residual long-lived radionuclides 137Cs and Pu isotopes were measured for soil samples collected at the Manose District including the surrounding areas in July, 2011. As a result, accumulated levels of 137Cs and 239,240Pu in the Manose District were not so high, each being nearly background (BG) level. The dispersion of local fallout Pu from the A-bomb was reconfirmed by 240Pu/239Pu atomic ratios measured in soil samples at the same time, and was found to be primarily limited in the east direction, especially around the Nishiyama area. Those results were consistent with results obtained so far. Further researches are needed for understanding scientifically the cause of the high incidence rate of hair loss in this district.This research was supported by JSPS KAKENHI Grants Numbers 23406002 (April 2011-March 2014) and 26257501 (April 2014-March 2018)

Development of fully automated and ultrasensitive assays for urinary adiponectin and their application as novel biomarkers for diabetic kidney disease

Glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) are used to diagnose and classify the severity of chronic kidney disease. Total adiponectin (T-AN) and high molecular weight adiponectin (H-AN) assays were developed using the fully automated immunoassay system, HI-1000 and their significance over conventional biomarkers were investigated. The T-AN and H-AN assays had high reproducibility, good linearity, and sufficient sensitivity to detect trace amounts of adiponectin in the urine. Urine samples after gel filtration were analyzed for the presence of different molecular isoforms. Low molecular weight (LMW) forms and monomers were the major components (93%) of adiponectin in the urine from a diabetic patient with normoalbuminuria. Urine from a microalbuminuria patient contained both high molecular weight (HMW) (11%) and middle molecular weight (MMW) (28%) adiponectin, although the LMW level was still high (52%). The amount of HMW (32%) and MMW (42%) were more abundant than that of LMW (24%) in a diabetic patient with macroalbuminuria. T-AN (r = − 0.43) and H-AN (r = − 0.38) levels showed higher correlation with estimated GFR (eGFR) than UAER (r = − 0.23). Urinary levels of both T-AN and H-AN negatively correlated with renal function in diabetic patients and they may serve as new biomarkers for diabetic kidney disease

Current status of hematopoietic stem cell transplantation and umbilical cord blood bank in Chugoku-Shikoku area

The hematopoietic stem cell transplantation (HSCT) is rapidly and widely spreading in the treatment strategy of various types of cancers, since peripheral and umbilical cord blood (CB) have been introduced as new sources of transplantable cells in addition to ordinary bone marrow cells. In this report, the current status of HSCT was reviewed. CB is rich in hematopoietic stem/progenitor cells, which have high proliferative potential. T cells in CB are speculated to be immature and immune-tolerable cells with less potential to cause acute or chronic graft versus host disease (GVHD), which are directly related with transplant-related morbidity and mortality. Furthermore, transplants with CB are not strictly restricted by a HLA-disparity. On the other hand, the less number of collected cells from CB is a major problem when the cells are applied for clinical transplantation, because the lower number of infused cells often result in engraftment failure. Further, we have no data of the viability after long term cryopreservation. We must carefully judge the usefulness of CB as a cell source for transplantation, but the benefits of CB may have a possibility to overcome these disadvantage in the near future. Finally, the activity of cord blood bank in Chugoku-Shikoku area, which was started from August 1998, was also introduced

Observation of the Pharynx to the Cervical Esophagus Using Transnasal Endoscopy with Blue Laser Imaging

Background In 2014, the new transnasal endoscopy with Blue laser Imaging (BLI) has been developed. Aim We present the usefulness of the observation of from the pharynx to the cervical esophagus using transnasal endoscopy with BLI. Patients and Methods This study was conducted between June 2014 and October 2014. During this period, 70 consecutive patients (60 men, 10 women; mean age 67.9 years old) with esophageal or head and neck cancer underwent endoscopic screening at the oropharynx and hypopharynx by transnasal endoscopy with BLI system We performed this endoscopic observation from oral cavity to pharynx before inserting into the cervical esophagus.The visibility of subsites of the hypopharynx and the orifice of the esophagus was evaluated. The extent of the view of hypopharyngeal opening was classified into 3 categories (excellent, good, poor). Then, the diagnostic accuracy of transnasal endoscopy with BLI system was estimated. Our screening is as follows. First, the patient is asked to bow their head deeply in the left lateral position. We put a hand on the back of the patient’s head and push it forward. The patient is then asked to lift the chin as far as possible. In order to inspect the oral cavity, we insert an endoscope without a mouthpiece. After observation of the oral cavity, the endoscope was inserted through the nose. When the tip of the endoscope reached caudal to the uvula, the patient opened his mouth wide, stuck his tongue forward as much as possible and made a vocal sound like “ayyy”. The endoscopist caused the endoscope to U-turn and observed the oropharynx, in particular the radix linguae (Intra-oropharyngeal U-turn method). For examination of the hypopharynx and the orifice of the esophagus, the patient is asked to blow hard and puff their cheeks while the mouth remains closed (Trumpet maneuver). Results 8 elderly cases were excluded because they could not perform the adequate ballooning. Finally, 62 cases were investigated. The ballooning the pyriform sinus and posterior wall not only allows accurate assessment of the stretched pharyngeal mucosa but also gives a view of postcricoid subsite and the orifice of the esophagus. The wide endoscopic view of the pharynx was obtained in a series of the procedures (excellent=53/62, 85.4%; good=7/52, 4.5%; and poor=2/62, 7.6%). Among 70 patients, 6 superficial lesions (8.6%) at the oropharynx(n=1) and hypopharynx (n=5) were discovered with BLI system. Mucosal redness, a pale thickened mucosa, white deposits or loss of a normal vascular pattern, well demarcated areas covered with scattered dots are important characteristics to diagnose superficial carcinoma. Conclusion The more progress achieved in transnasal endoscopy rapidly in the last few years, it can improve for observing the blind area using trans-oral endoscopy, therefore the trans-nasal endoscope will be a standard tool for the screening of the upper gastrointestinal tract in the near future

A case of sagittal splitting ramus osteotomy and genioplasty in a patient with congenital factor VII deficiency

Blood coagulation factor VII is involved in the extrinsic clotting system, and congenital defects or deficiencies affecting blood coagulation factor VII are rare. We report the case of a patient who was diagnosed with factor VII deficiency based on a preoperative examination and then underwent factor VII replacement therapy and orthognathic surgery, together with a brief discussion of the literature.The patient was a 25-year-old woman. She presented to our hospital after being diagnosed with jaw deformity and underwent sagittal splitting ramus osteotomy and genioplasty under general anesthesia. Preoperative tests revealed an abnormally short prothrombin time. Blood tests detected very low coagulation factor VII activity (33%), and so the patient was diagnosed with factor VII deficiency.We conducted preoperative factor VII replacement therapy to inhibit bleeding, and then the abovementioned surgical procedure was performed safely. The operative time was 1 hour 30 minutes, and little intraoperative blood loss occurred. The patient\u27s postoperative course was good, e.g., no abnormal bleeding occurred, and she was discharged on postoperative day 7

A comprehensive study on the immunological reactivity of the Hsp90 molecular chaperone.

Periodontitis is a chronic infectious disease, Porphyromonas gingivalis being the most implicated pathogen. In the present study, we investigated the role of P. gingivalis HtpG (PgHtpG), a bacterial ortholog of mammalian Hsp90, in the growth of P. gingivalis and also assessed the immunological cross-reactivity of the members of the Hsp90 family. Antiserum against rat liver Hsp90 potently reacted with yeast Hsp90, called Hsc82, and also weakly with human Hsp90 (hHsp90) and human mitochondrial paralog Trap1, but did not react with PgHtpG, Escherichia coli HtpG, or human endoplasmic reticulum paralog Grp94. Moreover, among 19 monoclonal antibodies raised against hHsp90, nine cross-reacted with yeast Hsc82, and one with human Grp94, but none bound to PgHtpG or E. coli HtpG. Among them, three mAbs that strongly reacted with yeast Hsc82 recognized Asn(291)-Ile(304), a conserved region of the family protein. The polyclonal antibody raised against a peptide, Met(315)-Glu(328), of human Grp94, which corresponded to the conserved region of hHsp90, cross-reacted with hHsp90, but not with other Hsp90-family members. Thus, although mammalian Hsp90 shares some immunological reactivity with yeast Hsc82, human Grp94, and human Trap1, it is considerably distinct from its bacterial ortholog, HtpG. Disruption of the P. gingivalis htpG gene neither affected bacterial survival nor altered the sensitivity of P. gingivalis to various forms of stress