Characteristics of the glycometabolic categories based on the oral glucose tolerance test results in Japanese adults without diabetes.

OBJECTIVE: We aimed to classify Japanese adults without diabetes into different categories based on the oral glucose tolerance test (OGTT) and characterize their insulin sensitivity and insulin secretion. PATIENTS AND METHODS: The OGTT was performed on 1,085 Japanese individuals without diabetes (aged 20-64 years); blood glucose and insulin levels were measured at 0, 30-, 60-, 90-, and 120-min. Fasting blood chemistry, hematology, and urine were analyzed. The participants were classified into four categories based on the following: (A) 30 min post-load plasma glucose levels < 157 mg/dL and/or (B) 120 min post-load plasma glucose levels < 126 mg/dL and Matsuda index > 4.97. Category 1 satisfied both conditions, category 2 satisfied condition A but not B, category 3 satisfied condition B but not A, and category 4 satisfied neither condition. RESULTS: Overall, 46%, 21%, 13%, and 20% of the participants were classified into categories 1, 2, 3, and 4, respectively. Compared with category 1, the characteristics of the other categories were: 2, low insulin sensitivity and high blood glucose levels during the later period; 3, low insulin secretion and a rapid increase in blood glucose levels; and 4, combined characteristics of categories 2 and 3. Most blood test values besides glucose metabolism in category 4 were also worse than those in category 1. Categories 1 and 2 had a high proportion of females, whereas categories 3 and 4 had a low proportion. CONCLUSIONS: Japanese adults without diabetes are classified into four categories with different insulin sensitivities and insulin secretion using OGTT results. Each category has different characteristics of age and sex distribution and clinical values besides glucose metabolism.

Basic studies toward ultrafast soft x-ray photoelectron diffraction; its application to probing local structure in iodobenzene molecules.

Ultrafast x-ray photoelectron diffraction (UXPD) for free molecules has a promising potential to probe the local structures of the molecules in an element-specific fashion. Our UXPD scheme consists of three steps: (1) near-infrared laser (NIR) with ns pulse duration aligns sample molecules, (2) ultra-violet laser with fs pulse duration pumps the aligned molecules, and (3) soft x-ray free-electron laser (SXFEL) with fs pulse duration probes the molecules by measuring x-ray photoelectron diffraction (XPD) profiles. Employing steps of (1) and (3), we have measured I 3d XPD profiles from ground state iodobenzene aligned by the NIR laser with the SXFEL. Then, we have intensively calculated I 3d XPD profiles with density functional theory, taking degrees of alignments of the molecules into account, to extract a distance between C and I atoms in iodobenzene from the experimental I 3d XPD profiles. Although we have failed to determine the distance from the comparison between the experimental and theoretical results, we have succeeded in concluding that the degeneracies of the initial state eliminate the sensitivity on molecular structure in the I 3d XPD profiles. Thus, the observation of fine structures in the XPD profiles could be expected, if a nondegenerate molecular orbital is selected for a probe of UXPD. Finally, we have summarized our criteria to perform UXPD successfully: (1) to use SXFEL, (2) to prepare sample molecules with the degree of alignment higher than 0.8, and (3) to select a photoemission process from a nondegenerate inner-shell orbital of sample molecules.

Randomized, double-blind, crossover, placebo-controlled clinical trial to evaluate the effects of chicken hot water extract on insulin secretion.

OBJECTIVE: Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC. PATIENTS AND METHODS: Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design. RESULTS: The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p < 0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL. CONCLUSIONS: Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.

Intra- and Extra-Articular Deformity of Lower Limb: Tibial Condylar Valgus Osteotomy (TCVO) and Distal Tibial Oblique Osteotomy (DTOO) for Reconstruction of Joint Congruency.

Osteotomies are the established surgical procedure for the deformity of the lower limb induced by osteoarthritis (OA) of the knee and ankle. Closed-wedge (CW) and open-wedge (OW) high tibial osteotomy (HTO) are extra-articular surgery, which aim to shift the mechanical axis from medial to slightly lateral and reduce the overload in the medial compartment of the varus deformed knee by extra-articular correction. However, varus deformity of the knee with the teeter effect, which could be accompanied with subluxation and thrust due to the medial-lateral soft tissue imbalance, is not resolved only by the shift of mechanical axis. The depression of the medial tibia plateau, so-called pagoda deformity, is the intra-articular deformity, which could potentially cause the teeter effect and involves intra-articular incongruency. In such case, the osteotomy with novel concept should be developed to overcome the issues, both the imbalance of soft tissue and intra-articular deformity. Tibial condylar valgus osteotomy (TCVO) is an intra-articular osteotomy, which improves the joint congruency of the medial-compartment knee OA with subluxation and/or intra-articular deformity and also provides better joint stability. A similar argument is raised in the treatment of the ankle OA. Low tibial osteotomy (LTO) is an extra-articular surgery to correct malalignment of lower leg. Distal tibial oblique osteotomy (DTOO) is a novel surgery to improve the bony congruency of the ankle OA. In DTOO, the distal tibia is cut obliquely from the proximal medial to the distal lateral in the coronal plane and towards the center of the tibiofibular joint to improve the bony congruency of the ankle joint. Tibial condylar valgus osteotomy (TCVO) and distal tibial oblique osteotomy (DTOO) can correct intra-articular deformity of knee and ankle, respectively. The rationale and indication of TCVO and DTOO for the treatment of the lower limb by reconstructing the joint congruency are discussed.

Initial dissolution of D2O at the gas-liquid interface of the ionic liquid [C4min][NTf2] associated with hydrogen-bond network formation.

We have studied the initial dissolution of D2O at the interfacial surface of the flowing jet sheet beam of the ionic liquid (IL) [C4min][NTf2] using the King and Wells method as a function of both the temperature and collision energy of the IL. The initial dissolution probability of D2O into the IL [C4min][NTf2] was found to follow the general propensity that the solubility of gases into a liquid decreases with temperature. However, a large partial molar enthalpy and entropy for the initial dissolution of D2O in the IL [C4min][NTf2] were observed from the temperature dependence of the initial dissolution probability: ΔHl = -53 ± 8 kJ mol-1, ΔSl = -210 ± 30 J mol-1 K-1. In addition, it was found that the collision energy significantly reduced the initial dissolution probability. We propose that the associated D2O molecules at the interface of the IL [C4min][NTf2] make a hydrogen-bond network around the [NTf2]- anion before dissolution into the deeper portion of the interface layer.

Risk factors for infantile atopic dermatitis and recurrent wheezing.

BACKGROUND: The pathogenic mechanisms of atopic dermatitis (AD) and recurrent wheezing (RW) during infancy are not fully understood. OBJECTIVE: We evaluated immunological markers associated with AD and RW during infancy. METHODS: We followed a cohort (n = 314) from birth to 14 months of age. Some of the participants underwent a physical examination and blood test at 6 and 14 months of age. Univariate and multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to find which immunological markers could be risk factors for AD and RW. RESULTS: Of 16 immunological markers found in cord blood, only immunoglobulin (Ig) E was associated with AD at 6 months of age (adjusted OR [aOR], 1.607). None of the markers was associated with AD or RW at 14 months of age. Of 23 immunological markers at 6 months of age, total IgE (aOR, 1.018) and sensitization to egg white (aOR, 23.246) were associated with AD at 14 months of age. Phytohemagglutinin (PHA)-induced production of interleukin (IL) 4 from peripheral blood mononuclear cells (PBMCs) (aOR, 1.043) was associated with RW at 14 months of age. CONCLUSION: Cord blood IgE was a risk factor for AD at 6 months of age. Total IgE and sensitization to egg white at 6 months of age were risk factors for AD at 14 months of age. PHA-induced IL-4 production in PBMCs at 6 months of age was a risk factor for RW at 14 months of age.

Blood pressure control status and effects of pravastatin on cardiovascular events occurrence in patients with dyslipidaemia.

Dyslipidaemia is often associated with hypertension, and many clinical trials have shown that lipid-lowering therapy and strict blood pressure (BP) control are important for preventing cardiovascular disease (CVD). However, few reports describe the effect of statins on CVD occurrence in relation to long-term BP control. In the present analysis, we investigated the effects of baseline BP and follow-up BP control on the occurrence of CVD in patients enrolled in the MEGA Study. We investigated whether BP values provide more accurate prediction of the occurrence of CVD, including cerebrovascular disease/transischemic attack (CVA/TIA), and the effect of pravastatin on CVA/TIA. The risk for CVA/TIA and other CVD increased significantly (P≤0.001) as the severity of hypertension increased. In contrast, pravastatin reduced the onset of CVA/TIA, regardless of the BP controlled. The mean BP was a more accurate predictor of CVD than a one-time BP value. In patients with mild-to-moderate dyslipidaemia, elevated BP increases the risk for CVA/TIA and other CVD, and rigorous BP control was important for preventing CVD, in particular CVA/TIA. The 12-month mean BP is useful to avoid attenuation to determine the association between CVD and BP. Pravastatin prevented CVA/TIA, regardless of BP controlled.

Protein-losing enteropathy associated with egg allergy in a 5-month-old boy.

Protein-losing enteropathy (PLE), the manifestation of a diverse set of disorders, is characterized by excessive loss of plasma proteins into the affected portions of the gastrointestinal tract, and this results in hypoalbuminemia. A 5-month-old breastfed boy presented severe PLE with hypogammaglobulinemia, hypocalcemia, and hypomagnesemia induced by an egg allergy. He developed hypocalcemic convulsions. The diagnosis of PLE was confirmed by elevated fecal alpha1-antitrypsin clearance and a positive finding on a protein-losing scintigram. His allergy to egg delivered through maternal milk was confirmed as the cause of PLE, since the mother's elimination of egg from her diet improved his condition and maternal egg challenge provoked symptoms of diarrhea, vomiting, and elevated alpha1-antitrypsin clearance. At the time of writing, he is 22 months old and has experienced no further episodes after the elimination of egg-containing food.

Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats.

In adult hippocampus, neural progenitor cells give rise to neurons throughout life, and the neurogenesis is modulated by various intrinsic and extrinsic factors. Recent reports showed that lesion of septal cholinergic nuclei projecting to hippocampus suppressed the survival of newborn cells in the dentate gyrus (DG) of hippocampus. Here, we studied whether pharmacological treatment to activate or inhibit the cholinergic system could modulate adult hippocampal neurogenesis. 5'-Bromo-2'-deoxyuridine (BrdU) was injected to label dividing cells before the drug treatment. Immunohistochemical analysis was performed in normal rats chronically treated with an acetylcholinesterase inhibitor donepezil or a muscarinic acetylcholine receptor blocker scopolamine for four weeks. Donepezil increased, but scopolamine decreased, the number of BrdU-positive cells in the DG as compared with the control. Neither drug altered the percentage of BrdU-positive cells that were also positive for a neuronal marker neuronal nuclei, nor net population of proliferative cells labeled with proliferating cell nuclear antigen. We also found that donepezil enhanced, and scopolamine suppressed, the expression level of phosphorylated cAMP response element binding protein (CREB), which is related to cell survival, in the DG. These results indicate that donepezil enhances and scopolamine suppresses the survival of newborn cells in the DG via CREB signaling without affecting neural progenitor cell proliferation and the neuronal differentiation. This is the first evidence that pharmacological manipulation of the cholinergic system can modulate adult hippocampal neurogenesis.

Multiple enzyme activities of flavivirus proteins.

Dengue viruses (DENV) have 5'-capped RNA genomes of (+) polarity and encode a single polyprotein precursor that is processed into mature viral proteins. NS2B, NS3 and NS5 proteins catalyse/activate enzyme activities that are required for key processes in the virus life cycle. The heterodimeric NS2B/NS3 is a serine protease required for processing. Using a high-throughput protease assay, we screened a small molecule chemical library and identified -200 compounds having > or = 50% inhibition. Moreover, NS3 exhibits RNA-stimulated NTPase, RNA helicase and the 5'-RNA triphosphatase activities. The NTPase and the 5'-RTPase activities of NS3 are stimulated by interaction with NS5. Moreover, the conserved, positively charged motif in DENV-2 NS3, 184RKRK, is required for RNA binding and modulates the RNA-dependent enzyme activities of NS3. To study viral replication, a variety of methods are used such as the in vitro RNA-dependent RNA polymerase assays that utilize lysates from DENV-2-infected mosquito or mammalian cells or the purified NS5 along with exogenous short subgenomic viral RNAs or the replicative intracellular membrane-bound viral RNAs as templates. In addition, a cell-based DENV-2 replicon RNA encoding a luciferase reporter is also used to examine the role of cis-acting elements within the 3' UTR and the RKRK motif in viral replication.

Kinetic pathway to double-gyroid structure.

We have investigated the structural development during order-order transitions to the double-gyroid (DG) phase of nonionic surfactant/water systems based on two-dimensional small-angle x-ray scattering patterns from highly oriented ordered mesophases. The lamellar (L) to DG transition proceeds through two intermediate structures, a fluctuating perforated layer structure having ABAB stacking and a hexagonal perforated lamellar structure with ABCABC stacking (HPLABC). For a hexagonally packed cylinder (H) to DG transition, we also observed the HPLABC structure as the intermediate phase, thus the HPLABC is an entrance structure for the DG phase. The hexagonal perforated lamellar (HPL) structure consists of hexagonally packed holes surrounded by the planar tripods, and the transition from HPL structure to the DG phase proceeds by rotation of the dihedral angle of connected tripods. A geometrical consideration shows that large deformations of HPL planes are necessary to form the DG structure from the HPLABC structure, whereas the transition from a HPL structure with ABAB stacking (HPLAB) to the DG structure is straightforward. In spite of the topological constraints, the HPLABC structure is observed in the kinetic pathway to the DG structure.

Leaky phenotype of X-linked agammaglobulinaemia in a Japanese family.

X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency that is caused by a block in early B-cell differentiation. Whereas early B precursors in the bone marrow are present in substantial numbers, XLA-affected individuals have dramatically reduced numbers of circulating mature B cells, plasma cells and immunoglobulins of all isotypes. We report on a Japanese family with 3 XLA patients, in whom the serum immunoglobulin levels and number of B cells showed a significant difference among them in spite of harbouring the same splice donor site mutation in the BTK gene. We developed concise method for detection of this mutation, which is helpful for discovering the carrier. Patient 2 showed a significant serum immunoglobulin levels of all isotypes, including allergen-specific IgE. Expression of a normal and truncated size BTK gene was detected in patient 2's peripheral blood mononuclear cells (PBMCs). Expression of BTK protein was also detected in some B cells. These results suggest that the leaky phenotype in patient 2 was caused in part by the expression of a normal BTK gene transcript. The increased frequency of infection with age expanded the number of B cells with normal BTK gene expression and produced the serum immunoglobulin, including IgE.

[Mitral valve replacement for mitral regurgitation caused by papillary muscle head rupture complicating acute myocardial infarction: report of a case].

A 71-year-old female was admitted for acute posterolateral infarction. On the next day of the successful emergency perctaneous coronary intervention, she developed severe dyspnea and was intubated at intensive care unit. Massive mitral regurgitation was detected on color Doppler imaging and left ventricular cardiac failure was increasingly developed. The urgent operation was performed for papillary muscle rupture 18 days after first episode. Head rupture of the posterior papillary muscle was found during surgery and the mitral valve was replaced by a prosthetic valve (SJM # 25). The postoperative course was uneventful and she discharged on 52 days after surgery.

Review of efficacy of rosuvastatin 5 mg.

The prevalence of coronary heart disease (CHD) has been increasing in the past few decades in Japan, as it has in industrialised countries worldwide. CHD risk can be substantially reduced by lowering low-density lipoprotein cholesterol (LDL-C) in patients with dyslipidaemia. Statins are highly effective for this indication, but many patients treated with these drugs still do not meet their treatment goals, often because clinicians fail to titrate these patients to a higher, potentially more effective, dose. Thus, there is a need for more effective agents that can help patients reach their goals at starting doses. This paper reviews key clinical results for a new agent, rosuvastatin. The data show that rosuvastatin 5 mg is highly effective in lowering LDL-C to recommended levels for most patients (mean reductions ranging from 42 to 52%). In addition, rosuvastatin 5 mg effectively lowers triglycerides (-16%), total cholesterol (-30%), non-high-density lipoprotein cholesterol (non-HDL-C; -38%) and apolipoprotein (apo) B levels (-33%) and increases HDL-C (+8.2-13%) in a wide range of patients with hypercholesterolaemia, including the elderly, obese patients, postmenopausal women and patients with hypertension, CHD, diabetes and metabolic syndrome. The 5-mg dose of rosuvastatin dose also produces greater reductions in LDL-C and larger increases in HDL-C than recommended initial doses of atorvastatin, simvastatin or pravastatin (for LDL-C reductions, p <0.001 vs. atorvastatin 10 mg, simvastatin 20 mg and pravastatin 20 mg; for HDL-C elevations, p <0.01 vs. atorvastatin 10 mg). These results demonstrate that rosuvastatin 5 mg produces favourable effects on the lipid profile and helps more patients achieve LDL-C goals than comparator statins.

Significant effects of diacylglycerol on body fat and lipid metabolism in patients on hemodialysis.

AIMS: The long-term effects of dietary diacylglycerol (DAG) on body fat and lipid metabolism were studied in patients undergoing hemodialysis (HD). METHODS: Ten patients (seven males, three females) ranging in age from 40 to 64 years were enrolled. During the test period, 9.8 g of DAG was ingested per day for 3 months. RESULTS: Body mass index did not change throughout the study. The abdominal fat area measured by CT scan decreased significantly at 3 months, and increased significantly 3 months after completion of the DAG ingestion period. The serum composition of very low-density lipoprotein (VLDL) decreased significantly at 3 months and high-density lipoprotein (HDL) increased significantly at 3 months; these were determined using polyacrylamide gel electrophoresis. Serum lipoprotein (a) decreased significantly at 3 months. CONCLUSIONS: Our study showed that 3-month ingestion of DAG reduced the amount of abdominal fat and improved serum lipid profiles in free-living HD patients.

[Surgical treatment for chronic hemorrhagic pyothorax].

A case of pleuro-pneumonectomy following arterial embolization for chronic hemorrhagic pyothorax occurring 40 years after artificial pneumothorax treatment was investigated. The patient was an 80-year-old male diagnosed with chronic hemorrhagic pyothorax after complaining of bloody sputum and difficulty breathing during exertion. The pyothorax space was conspicuously extended, and the mediastinal space was compressed. Although this condition was treated periodically over time by thoracentesis, pleuro-pneumonectomy was selected as a radical treatment. Since a large amount of hemorrhaging was expected during surgery, preoperative transcatheter embolization of the left lateral thoracic artery, the bronchial arteries and the left internal thoracic artery was performed. The amount of hemorrhaging during surgery from the feeding artery from the thoracic wall was 5,700 ml. There was an abundance of dilated blood vessels within the thickened pleura, and angiomatous structures were observed. Although symptoms improved following surgery, sudden massive hemorrhage was observed from the thoracic drain on the morning of the 79th postoperative day, and the patient died from hemorrhagic shock. Emergency thoracotomy was performed, and aortic rupture was observed on the origin of the left subclavian artery. Chronic hemorrhagic pyothorax has a peculiar pathology even for chronic pyothorax, and a large amount of hemorrhaging can be expected during surgery. Precaution must be taken for postoperative arterial hemorrhage caused by delayed inflammation.

Semiquantitative evaluation of mRNAs for the membranous form of immunoglobulin heavy chain is useful for investigating the etiology in CVID.

Common variable immunodeficiency (CVID) is a primary antibody deficiency syndrome characterized by defective B-cell maturation and antibody formation resulting in low serum antibody levels of all immunoglobulin (Ig) isotypes. To investigate the pathogenesis of CVID, we developed a set of competitive polymerase chain reaction for membrane-bound Ig heavy chain (mHC) mRNAs for IgM, IgG and IgA. Data on three children with CVID in group A of Bryant's classification were analysed. All the three mHC mRNA levels in Patient 1 were almost same as those in healthy controls. In Patient 2, mHC mRNA for IgM was detected at a level similar to that in controls, but mHC mRNAs for IgG and IgA heavy chains were not detected. In Patient 3, all the three mHC mRNAs were undetectable. Our data suggest that a different molecular basis exists in these patients with CVID even though all belong to group A of Bryant's classification. Use of our method facilitates a better understanding of molecular events in CVID patients and may be useful for precise classifications of CVID.