[From a Ph.D. Thesis: Understanding the Past, Predicting the Future].

　Posey et al. have reported multiple molecular diagnoses in 4.5% of cases (101/2076) in which whole-exome sequencing was informative.

Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1 gene copy number variations.

CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay.

A Mouse Model for Oral Mucositis Induced by Cancer Chemotherapy.

Background: Oral mucositis (OM), one of the side-effects induced by chemotherapy, has 40% incidence and the incidence rate increases to approximately 100% in combination with radiotherapy. We describe OM in ICR mice induced using 5-fluorouracil (5-FU) and 20% acetic acid.

Materials And Methods: We optimized the dose of 5-FU and 20% acetic acid and validated the efficacy of standard therapies for OM.

Fatty Acids as Useful Serological Markers for Crohn's Disease.

Background: We have previously reported that patients with Crohn's disease (CD) have a very specific erythrocyte membrane phospholipid fatty acid profile. The findings of this study suggest that the activities of enzymes involved in the metabolism of linoleic acid (LA), that is, delta-6 desaturase, are higher in CD patients than in healthy individuals.

Methods: We evaluated the utilities of various fatty acid compositions of the plasma (p-) as new serological markers for CD compared to those of erythrocyte membranes (e-).

Isolation of 2-deoxy-scyllo-inosose (DOI)-assimilating yeasts and cloning and characterization of the DOI reductase gene of Cryptococcus podzolicus ND1.

2-Deoxy-scyllo-inosose (DOI) is the first intermediate in the 2-deoxystreptamine-containing aminoglycoside antibiotic biosynthesis pathway and has a six-membered carbocycle structure. DOI is a valuable material because it is easily converted to aromatic compounds and carbasugar derivatives. In this study, we isolated yeast strains capable of assimilating DOI as a carbon source.

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats.

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats.

Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism in rats.

Long-term treatment with antiepileptic drugs (AED) is associated with an elevated risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has been shown to affect bone metabolism adversely, whereas newly developed AEDs have not been studied. This study evaluated the effects of topiramate and lamotrigine on bone metabolism in rats.

Effects of different heat-moisture treatments on the physicochemical properties of brown rice flour.

We evaluated the effect of heat-moisture treatment (HMT) on the main chemical components, physical properties, and enzyme activities of two types of brown rice flour: high-amylose Koshinokaori and normal-quality Koshiibuki. Five different HMTs using brown rice (moisture content was 12.0%) were assessed: 0.

PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus infection via interaction with LGP2.

Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of Cardiovirus-infected cells and activate innate immune responses. Here, we evaluated whether the double-stranded RNA-binding protein PACT plays a role in this anti-viral response to further elucidate the mechanism. Immunoprecipitation experiments demonstrated that PACT interacts with LGP2 and that this interaction is enhanced by encephalomyocarditis virus (EMCV) infection.

Natural Killer T Cell-Targeted Immunotherapy Mediating Long-term Memory Responses and Strong Antitumor Activity.

Current tumor therapies, including immunotherapies, focus on passive eradication or at least reduction of the tumor mass. However, cancer patients quite often suffer from tumor relapse or metastasis after such treatments. To overcome these problems, we have developed a natural killer T (NKT) cell-targeted immunotherapy focusing on active engagement of the patient's immune system, but not directly targeting the tumor cells themselves.

Pork Loin Treated with High Hydrostatic Pressure as a Food Processing Technology: Subacute Toxicity of the Freeze-Dried Powder and Cytotoxicity of the Methanol Extracts.

High hydrostatic pressure (HP) treatment is used in food processing owing to its sterilization effect. Meat or meat products are sterilized and become tender by HP processing. Therefore, the variety of HP-processed meat products has increased worldwide.

Effect of the antidiabetic agent pioglitazone on bone metabolism in rats.

Thiazolidinediones (TZDs) are synthetic peroxisome proliferator-activated receptor gamma (PPARγ) agonists used as therapy for type 2 diabetes. However, clinical studies reported that the therapeutic modulation of PPARγ activity using TZDs may induce negative effects on bone metabolism. This study aimed to evaluate the effect of the TZD pioglitazone on bone metabolism in rats.

Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome: A case report and literature review.

Rationale: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy.

[Peripheral T-cell lymphoma, not otherwise specified: a retrospective single-center analysis].

We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years.

Growth hormone activates hepatic and cerebral cholesterol metabolism in small-for-gestational age children without catch-up growth.

Background: Growth hormone (GH) replacement therapy improves hypercholesterolemia in patients with GH deficiency, suggesting that GH modulates cholesterol metabolism.

Objectives: We examined GH effects on lipid profiles and cholesterol-related markers reflecting hepatic and cerebral cholesterol metabolism in small-for-gestational age (SGA) children without catch-up growth.

Methods: This study examined SGA children without catch-up growth (n = 22) and healthy children (controls, n = 11).

ErbB2 signaling epigenetically suppresses microRNA-205 transcription via Ras/Raf/MEK/ERK pathway in breast cancer.

We previously reported that microRNA-205 (miR-205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR-205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR-205 downregulation. In ErbB2-overexpressing breast epithelial cells, miR-205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD98059, Raf-1 inhibitor ZM-336372, and ERK inhibitor SCH772984, but PI3K inhibitor LY294002 and p38 MAPK inhibitor SB203580 had no effect.

WP1066, a small molecule inhibitor of the JAK/STAT3 pathway, inhibits ceramide glucosyltransferase activity.

WP1066 is a well-known inhibitor of the JAK/STAT3 signaling pathway. By a screen of known small molecule inhibitors of various enzymes and protein factors, we identified WP1066 as a ceramide glucosyltransferase inhibitor. Ceramide glucosyltransferase catalyzes the first glycosylation step during glycosphingolipid synthesis.

Adsorption of Protein-Bound Uremic Toxins Through Direct Hemoperfusion With Hexadecyl-Immobilized Cellulose Beads in Patients Undergoing Hemodialysis.

An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro.

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report.

Objective: Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum.

Characterization of the O-antigen polysaccharide derived from Pantoea agglomerans IG1 lipopolysaccharide.

A polysaccharide fraction was isolated from the Pantoea agglomerans IG1 lipopolysaccharide (IP-PA1), and its O-antigenic polysaccharide was characterized by chemical analyses and 1D and 2D H and C NMR spectroscopy. The polysaccharide is composed of linear tetrasaccharide repeating units, consisting of glucose and rhamnose, where 40% of one of the rhamnose residues is substituted with glucose: →2)-α-l-Rhap-(1→6)-α-d-Glcp-(1→2)-[β-d-Glcp-(1→3)]-α-l-Rhap-(1→2)-α-l-Rhap-(1→.

Lipopolysaccharides Derived from Can Promote the Phagocytic Activity of Amyloid β in Mouse Microglial Cells.

Background/aim: Recent studies reported that lipopolysaccharide (LPS) exhibits beneficial effects on prevention of immune-related diseases by activating macrophages. We previously demonstrated that pre-treatment with LPS derived from Pantoea agglomerans (LPSp) activated amyloid β (Aβ) phagocytosis in mouse primary microglia. In the present study, we further examined the promotory effect on phagocytosis of phagocytic particles in the C8-B4 microglia cell line.

Measurement of the Phagocytic Activity of Human Peripheral Blood Using a Highly Sensitive Fluorometric Detection Device Without Hemolysis.

Background/aim: Phagocytes recognize pathogens that enter the body as well as other abnormal and foreign materials that may exist within an organism (such as dead cells, oxidized lipids, and denatured proteins), and phagocytose and eliminate them to maintain a healthy state. In a previous study a simple prototype device was used, under development by Hamamatsu Photonics (Prototype), that detects fluorescence to determine the phagocytic activity of the murine macrophage cell line J774.1.

Comparative evaluation of torasemide and spironolactone on adverse cardiac remodeling in a rat model of dilated cardiomyopathy.

Background: Chronic heart failure (CHF) involves fluid retention and volume overload, leading to impaired cardiac function. In these conditions, diuretic agents are most commonly used to treat edema and thereby reducing the volume load on the failing heart. There are several other beneficial effects of diuretics apart from their action on urinary excretion.

Microbicidal Effects of Stored Aqueous Ozone Solution Generated by Nano-bubble Technology.

Background/aim: Clinically used disinfectants are often irritating and cause skin problems. Ozone water is unique among disinfectants. It does not damage skin cells and readily decomposes to oxygen without generating harmful residues.