Changes in urinary output due to concomitant administration of sacubitril/valsartan and atrial natriuretic peptide in patients with heart failure: a multicenter retrospective cohort study.

Background: Sacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure.

Change in fatty acid composition of plasma triglyceride caused by a 2 week comprehensive risk management for diabetes: A prospective observational study of type 2 diabetes patients with supercritical fluid chromatography/mass spectrometry-based semi-target lipidomic analysis.

Aims/introduction: Hypertriglyceridemia is common in patients with diabetes. Although the fatty acid (FA) composition of triglycerides (TGs) is suggested to be related to the pathology of diabetes and its complications, changes in the fatty acid composition caused by diabetes treatment remain unclear. This study aimed to identify short-term changes in the fatty acid composition of plasma triglycerides after diabetes treatment.

Characteristic changes in plasma glutamate levels and free amino acid profiles in Japanese patients with type 1 diabetes mellitus.

Aims/introduction: In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon.

Development of potent non-acylhydrazone inhibitors of intestinal sodium-dependent phosphate transport protein 2b (NaPi2b).

Inhibition of intestinal sodium-dependent phosphate transport protein 2b (NaPi2b), responsible for intestinal phosphate absorption, is considered to reduce serum phosphate levels, making it a promising therapeutic approach for hyperphosphatemia. Previously, we aimed to identify new drugs for hyperphosphatemia treatment and obtained zwitterionic compound 3 (IC = 64 nM) as a potent selective inhibitor of intestinal NaPi2b. This small-molecule compound is gut-restricted owing to its almost membrane-impermeable property.

Discovery of Gut-Restricted Small-Molecule Inhibitors of Intestinal Sodium-Dependent Phosphate Transport Protein 2b (NaPi2b) for the Treatment of Hyperphosphatemia.

NaPi2b is primarily expressed in the small intestine, lungs, and testes and plays an important role in phosphate homeostasis. The inhibition of NaPi2b, responsible for intestinal phosphate absorption, is considered to reduce serum phosphate levels, making it a promising therapeutic approach for hyperphosphatemia. Using a novel phosphate uptake inhibitor (IC = 87 nM), identified from an in-house compound collection in human NaPi2b-transfected cells as a prototype compound, we conducted its derivatization based on a Ro5-deviated strategy to develop orally administrable small-molecule NaPi2b inhibitors with nonsystemic exposure.

Evaluation of change in metabolome caused by comprehensive diabetes treatment: A prospective observational study of diabetes inpatients with gas chromatography/mass spectrometry-based non-target metabolomic analysis.

Aims/introduction: Diabetes patients develop a variety of metabolic abnormalities in addition to hyperglycemia. However, details regarding change in various metabolites after comprehensive diabetes treatment remain unknown. This study aimed to identify the short-term change in metabolome in inpatients who were subject to comprehensive diabetes treatment, using gas chromatography/mass spectrometry-based non-target metabolomics techniques.

Development of a novel class of peroxisome proliferator-activated receptor (PPAR) gamma ligands as an anticancer agent with a unique binding mode based on a non-thiazolidinedione scaffold.

We previously identified dibenzooxepine derivative 1 as a potent PPARγ ligand with a unique binding mode owing to its non-thiazolidinedione scaffold. However, while 1 showed remarkably potent MKN-45 gastric cancer cell aggregation activity, an indicator of cancer differentiation-inducing activity induced by PPARγ activation, we recognized that 1 was metabolically unstable. In the present study, we identified a metabolically soft spot, and successfully discovered 3-fluoro dibenzooxepine derivative 9 with better metabolic stability.

Changes in oxidized LDL during a half marathon in athletes with spinal cord injuries.

Introduction: We reported previously that exercise significantly increases plasma adrenaline and oxidized low-density lipoprotein (oxLDL) in healthy subjects but not in persons with spinal cord injury (SCI). Since oxLDL and adrenaline levels are associated with oxidant/antioxidant balance, and exercise training elicits production of reactive oxygen species, we elucidated the effects of exercise on adrenaline, oxidant/antioxidant balance and oxLDL in individuals with SCI.

Case Presentation: Eight subjects with cervical spinal cord injury (CSCI) and nine subjects with lower lesion of SCI (lower SCI (LSCI)) participated in a wheelchair half marathon race, and blood samples were collected before (pre), immediately after (post) and 1 h after the race (post 1 h).

Efficacy, toxicity and cost analysis for non-platinum triplet (gemcitabine and vinorelbine, followed by docetaxel) vs. platinum-based chemotherapy in IIIB/IV non-small-cell lung cancer: single-institution experience.

A new non-platinum sequential triplet combination chemotherapy regimen, comprising gemcitabine (1000 mg/m(2)) and vinorelbine (25 mg/m(2)), followed by docetaxel (60 mg/m(2)), was compared in terms of efficacy, toxicity and cost with platinum-based chemotherapy regimens (comprising cisplatin plus one or more other anti-tumour drugs) for the treatment of advanced non-small-cell lung cancer in a matched, small-sample size, case-control study. Patients were selected from a single institution. Patients in the platinum and non-platinum groups were matched for clinical stage (IIIB/IV), performance status (0/1), age and sex.

[Diffuse alveolar hemorrhage after allogeneic bone marrow transplantation].

A 34-year-old woman with chronic myeloid leukemia underwent allogeneic bone marrow transplantation (BMT) after receiving high-dose chemotherapy and total body irradiation. She experienced progressively dry cough 51 days after BMT, and chest X-ray films showed patchy infiltrations in the lower fields of both lungs on the 66th day after BMT. The symptoms of cough, fever, and hypoxemia worsened.

Motor training in the manipulation of flexible objects in haptic environments.

A system with interchangeable constraints for studying skillful human movements via haptic displays is presented. It is shown how this system can be applied to the analysis of reaching movements in the manipulation of flexible objects. In the experiment, progress in arm motor training is considered for several subjects.

Characterization of preexisting humoral immunity specific for two cancer-testis antigens overexpressed at the mRNA level in non-small cell lung cancer.

In order to establish a rationale for immunotherapy for lung cancer, we have investigated immunological characteristics of tumor-associated antigens (TAAs) discovered through molecular approaches. Preexisting Abs specific to these predicted TAAs were examined using specimens of lung pleural effusions (LPEs) and sera in non-small cell lung cancer (NSCLC) patients. The novel cancer-testis (CT) antigens L514S and L552S were highly expressed in approximately half of the NSCLC tissues and established cell lines examined.

First synthesis of (+/-)-robinlin.

The first synthesis of (+/-)-robinlin (1), a novel homo-monoterpene with strong bioactivity in the brine shrimp lethality test, was achieved by starting from 3-isobutyloxy-2,6,6-trimethyl-2-cyclohexen-1-one (2).

Optimal trajectory formation of constrained human arm reaching movements.

Opening a door, turning a steering wheel, and rotating a coffee mill are typical examples of human movements that are constrained by the physical environment. The constraints decrease the mobility of the human arm and lead to redundancy in the distribution of actuator forces (either joint torques or muscle forces). Due to this actuator redundancy, there is an infinite number of ways to form a specific arm trajectory.

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02).

To evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC), we conducted the multiinstitutional phase II study. A total of 44 chemotherapy-naive patients with advanced NSCLC were treated with GEM 1000 mg m(-2) and VNR 25 mg m(-2) intravenously on days 1 and 8 every 3 weeks for three cycles. DOC 60 mg m(-2) was then administrated intravenously at 3-week intervals for three cycles.

Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer.

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.

A feasibility study of paclitaxel 225 mg/m(2) and carboplatin AUC = 6 in untreated advanced non-small cell lung cancer patients in Japan.

Background: The combination of paclitaxel (225 mg/m(2), 3 h infusion) and carboplatin [area under the curve (AUC) 6 mg/ml x min] is used widely for non-small cell lung cancer in the USA and is one of the standard regimens in the Southwest Oncology Group. In Japan, however, the upper limit of the approved dose for single-use paclitaxel is 210 mg/m(2) and the optimum dose of this agent in combination with carboplatin has not yet been established. This study was designated to determine whether the paclitaxel dose of 225 mg/m(2 ) plus carboplatin (AUC = 6) is tolerable for Japanese patients with untreated advanced non-small cell lung cancer.

A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non-small cell lung cancer.

The split-course concurrent thoracic radiation therapy (TRT) and full-dose chemotherapy for unresectable stage III non-small cell lung cancer (NSCLC) has produced promising results by comparison with the sequential approach. Instead of split-course radiation, we conducted a phase II study to investigate the feasibility of continuous concurrent TRT and chemotherapy. Twenty-two patients with unresectable NSCLC were enrolled onto a phase II study of continuous concurrent radiotherapy and chemotherapy.

Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours.

Previously we analysed overlapping homozygous deletions in lung and breast tumours/tumour lines and defined a small region of 120 kb (part of LCTSGR1) at 3p21.3 that contained putative lung and breast cancer tumour suppressor gene(s) (TSG). Eight genes including RASSF1 were isolated from the minimal region.

[Autopsy case of adenoid cystic carcinoma of the trachea: endobronchial treatment improves quality of life].

A 67-year-old man presented with dyspnea on exertion. Bronchoscopic examination revealed a tumor arising from the middle portion of the trachea and extending to the right main bronchus. The pathological diagnosis was adenoid cystic carcinoma.

Increased serum levels of basic fibroblast growth factor in lung cancer patients: relevance to response of therapy and prognosis.

Angiogenesis is controlled by inhibitors and angiogenic factors. Among these, basic fibroblast growth factor (bFGF) is closely involved in cancer proliferation and has been related to progression and prognosis of various cancers, including lung cancer. To evaluate the role of bFGF, we measured serum levels of bFGF from healthy controls (Ctrl) and 106 patients with lung cancer, including 31 adenocarcinomas (AD), 29 squamous cell carcinomas (SQ), and 46 small cell carcinomas (SCLC), by enzyme-linked immunosorbent assays.

Immunohistochemical analysis of Bcl-2 protein in early squamous cell carcinoma of the bronchus treated with photodynamic therapy.

Photodynamic therapy (PDT) in early squamous cell carcinoma of the bronchus has been shown to result in complete response (CR) and cure. However, local recurrence after PDT develops frequently even after complete remission. Because the effect of PDT had been reported to depend on apoptosis, and apoptosis is inhibited by bcl-2 protein, the relationship between the expression of bcl-2 protein and local recurrence after PDT was examined immunohistochemically.

Solitary squamous papilloma of the bronchus associated with human papilloma virus type 11.

A 79-year-old female presented with persistent dry cough, and a chest radiograph showed a mass shadow in the right upper lung. Bronchoscopic examination revealed that the right main bronchus was severely obstructed by a polypoid tumor, which was diagnosed pathologically as squamous papilloma. After the failure of the attempted endobronchial snare to remove the tumor, right upper lobectomy was performed.

Functional evidence for involvement of multiple putative tumor suppressor genes on the short arm of chromosome 3 in human oral squamous cell carcinogenesis.

Cytogenetic and restriction fragment length polymorphism (RFLP) analyses have suggested that a putative tumor suppressor genes(s), which may play an important role in the development of human oral squamous cell carcinoma (SCC), is located on the short arm of chromosome 3 (3p). We previously reported that introducing in intact human chromosome 3 into three different oral SCC tumorigenic cell lines completely suppresses the tumorigenicity of each cell line with significant decrease in the in vitro growth rate and morphological changes. To map the tumor suppressor gene(s) on 3p, we have now examined the tumorigenicity of microcell hybrid clones containing various fragments derived from 3p that were introduced by microcell-mediated chromosome transfer.

Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer.

Previously, we have reported that the inactivation of putative tumor-suppressor gene(s) on chromosome 5q21-22 may play an important role in the progression of lung cancer. Here, we describe the establishment of a yeast artificial chromosome (YAC) contig that spans 8-10 Mb at the 5q21-22 region. Six cosmid contigs have also been established in this YAC contig.