Predictor of buckwheat allergy in children based on challenge test results: a retrospective observational study in Japan.

Summary: Background. Buckwheat (BW) is a major food allergen and one of the leading causes of food-induced anaphylaxis in Japan. The standard method of diagnosing food allergy is the oral food challenge (OFC). The BW-specific IgE (BW-sIgE) value is used to assess BW allergy but its utility is limited. Aim. The aim of the present study was to identify factors with predictive value for the diagnosis of BW allergy using the OFC. Methods. We evaluated 37 patients who were classified into the positive or negative group according to their OFC results. Results. Ten patients (27.0%) showed objective or persistent, moderate, subjective symptoms during the OFC. The positive group had a significantly higher BW-sIgE/total IgE ratio than the negative group (p less than 0.001), but the total IgE (p = 0.139) and BW-sIgE (p = 0.130) did not differ significantly. Receiver operator characteristic (ROC) analysis showed that the BW-sIgE/total IgE ratio had a larger area under the curve (AUC, 0.885) than BW-sIgE (AUC, 0.667). The statistically optimal cut-off was 0.0058 for the BW-sIgE/total IgE ratio, which corresponded to a clinical sensitivity and specificity of 90.0% and 81.5%, respectively. Conclusions. BW-sIgE/total IgE ratio may be more useful predictor of BW OFC results than BWs-IgE.

NWChem: Past, present, and future.

Specialized computational chemistry packages have permanently reshaped the landscape of chemical and materials science by providing tools to support and guide experimental efforts and for the prediction of atomistic and electronic properties. In this regard, electronic structure packages have played a special role by using first-principle-driven methodologies to model complex chemical and materials processes. Over the past few decades, the rapid development of computing technologies and the tremendous increase in computational power have offered a unique chance to study complex transformations using sophisticated and predictive many-body techniques that describe correlated behavior of electrons in molecular and condensed phase systems at different levels of theory. In enabling these simulations, novel parallel algorithms have been able to take advantage of computational resources to address the polynomial scaling of electronic structure methods. In this paper, we briefly review the NWChem computational chemistry suite, including its history, design principles, parallel tools, current capabilities, outreach, and outlook.

Effects of extracellular DNA and DNA-binding protein on the development of a Streptococcus intermedius biofilm.

AIMS: The aim of this study was to clarify the effects of homologous and heterologous extracellular DNAs (eDNAs) and histone-like DNA-binding protein (HLP) on Streptococcus intermedius biofilm development and rigidity. METHODS AND RESULTS: Formed biofilm mass was measured with 0·1% crystal violet staining method and observed with a scanning electron microscope. The localizations of eDNA and extracellular HLP (eHLP) in formed biofilm were detected by staining with 7-hydoxyl-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) and anti-HLP antibody without fixation, respectively. DNase I treatment (200 U ml(-1)) markedly decreased biofilm formation and cell density in biofilms. Colocalization of eHLP and eDNA in biofilm was confirmed. The addition of eDNA (up to 1 µg ml(-1)) purified from Strep. intermedius, other Gram-positive bacteria, Gram-negative bacteria, or human KB cells into the Strep. intermedius culture increased the biofilm mass of all tested strains of Strep. intermedius, wild-type, HLP-downregulated strain and control strains. In contrast, the addition of eDNA (>1 µg ml(-1)) decreased the biofilm mass of all Strep. intermedius strains. CONCLUSIONS: These findings demonstrated that eDNA and eHLP play crucial roles in biofilm development and its rigidity. SIGNIFICANCE AND IMPACT OF THE STUDY: eDNA- and HLP-targeting strategies may be applicable to novel treatments for bacterial biofilm-related infectious diseases.

Chronic kidney disease categories and renal-cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25).

AIMS/HYPOTHESIS: In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients. METHODS: This 4 year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8 µmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml min(-1) 1.73 m(-2)). Association of progression from 'no CKD' stage (ACR <3.5 mg/mmol and eGFR ≥ 90 ml min(-1) 1.73 m(-2)) with risk for CVD onset was also evaluated. RESULTS: During follow-up (median 3.8 years), 89 CVD events occurred. Compared with patients with 'no CKD' as reference, those with ACR ≥ 35.0 mg/mmol with co-existing eGFR 60-89 ml min(-1) 1.73 m(-2) or <60 ml min(-1) 1.73 m(-2) showed increased risk for CVD onset, whereas those with eGFR ≥ 90 ml min(-1) 1.73 m(-2) did not. Those with ACR <3.5 mg/mmol and eGFR <60 ml min(-1) 1.73 m(-2) did not show any increased risk. Among patients with 'no CKD' stage at baseline, those who progressed to ACR ≥ 3.5 mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR <90 ml min(-1) 1.73 m(-2) did not have increased risk. CONCLUSIONS/INTERPRETATION: The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.

Bactericidal activity and oral pathogen inactivation by electromagnetic wave irradiation.

AIMS: The aim of this work was to clarify the effects of electromagnetic wave irradiation (EMWI) on oral bacterial pathogens. METHODS AND RESULTS: A Gram-negative (Porphyromonas gingivalis) or Gram-positive (Streptococcus mutans, S. intermedius, Enterococcus faecalis) bacterial suspension was irradiated by EMW apparatus (500-1000 kHz, 5-15 times, 1 s time(-1) ). Quantification of survival bacteria by CFU counting revealed that EMWI exhibited marked bactericidal activity against all tested bacteria and bactericidal activity at 500 kHz increased in an irradiation number-dependent manner. After EMWI at 500 kHz, scanning electron microscopic observations showed that the chain of S. mutans cells was shortened after 5 irradiations and the outlines of bacterial cells (S. mutans and P. gingivalis) were unclear after 5-10 irradiations. EMWI inhibited the inductive effect of S. mutans on pro-inflammatory cytokine production in human monocytes and this inhibitory effect was comparable with that of heat-killed bacteria. Furthermore, using an enzyme activity assay, EMWI partially inactivated the activities of gingipains from P. gingivalis. CONCLUSIONS: These findings demonstrated that EMWI has inactivation and bactericidal activities against single microbial species among four kinds of oral pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Electromagnetic wave irradiation may be applicable for medical disinfection and sterilization, such as refractory periapical periodontitis.

Low incidence of cardiovascular events in Japanese patients with Type 2 diabetes in primary care settings: a prospective cohort study (JDDM 20).

AIMS: To investigate whether a reduced incidence of cardiovascular disease in Type 2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. METHODS: A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type 2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. RESULTS: There were 90 cardiovascular events over 10,827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P < 0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA(1c), HDL cholesterol and urinary albumin. CONCLUSION: The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type 2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors.

Influence of BMI, Age and duration of diabetes mellitus on glycaemic control with twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart (JDDM 18): retrospective reanalysis of a 6-month, randomized, open-label, multicentre trial in Japan.

BACKGROUND AND OBJECTIVE: Good glycaemic control in patients with diabetes mellitus often requires insulin supplementation therapy. Recent developments of analogue insulin and premixed formulations have increased the therapeutic options for patients who need such therapy. This study aimed to retrospectively clarify appropriate treatment regimens according to age, body mass index (BMI) and duration of diabetes in Japanese patients with type 2 diabetes previously entered in an open-label, randomized trial that compared convenience-oriented biphasic insulin aspart 30 versus multiple injections of insulin aspart with or without NPH insulin. METHODS: Japanese insulin-naïve patients were randomized to receive either biphasic insulin aspart 30 twice daily or insulin aspart three times daily with or without multiple injections of NPH insulin for a treatment period lasting 6 months. RESULTS: Reduction of glycosylated haemoglobin (HbA(1c)) at the end of 6 months was not different in the two treatment groups irrespective of BMI, age and duration of diabetes. However, the achievement rate of HbA(1c) <7.0% was significantly higher in patients with a BMI <25 kg/m2 in the multiple-injection group and tended to be higher in patients with a diabetes duration <10 years in the twice-daily injection group. CONCLUSION: Twice-daily injections of biphasic insulin aspart 30 may be more suitable for obese patients whereas multiple injections of insulin aspart with or without NPH insulin may be preferable for those with a longer duration of diabetes.

Periodic metallo-dielectric structure in diamond.

Intense ultrashort light pulses induce three dimensional localized phase transformation of diamond. Photoinduced amorphous structures have electrical conducting properties of a maximum of 64 S/m based on a localized transition from sp(3) to sp(2) in diamond. The laser parameters of fluence and scanning speed affect the resultant electrical conductivities due to recrystallization and multi-filamentation phenomena. We demonstrate that the laser-processed diamond with the periodic cylinder arrays have the characteristic transmission properties in terahertz region, which are good agreement with theoretical calculations. The fabricated periodic structures act as metallo-dielectric photonic crystal.

Binding of neuroligins to PSD-95.

PSD-95 is a component of postsynaptic densities in central synapses. It contains three PDZ domains that localize N-methyl-D-aspartate receptor subunit 2 (NMDA2 receptor) and K+ channels to synapses. In mouse forebrain, PSD-95 bound to the cytoplasmic COOH-termini of neuroligins, which are neuronal cell adhesion molecules that interact with beta-neurexins and form intercellular junctions. Neuroligins bind to the third PDZ domain of PSD-95, whereas NMDA2 receptors and K+ channels interact with the first and second PDZ domains. Thus different PDZ domains of PSD-95 are specialized for distinct functions. PSD-95 may recruit ion channels and neurotransmitter receptors to intercellular junctions formed between neurons by neuroligins and beta-neurexins.

Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease.

BACKGROUND AND PURPOSE: To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS: We compared the time from the first visit to endpoints (discontinuation of visits because of admission, death, or institutionalization) between 56 patients with DLB and 111 patients with AD. Mini-Mental State Examination (MMSE) scores of patients were every 12 months examined up to 60 months. RESULTS: Dementia with Lewy bodies had a significantly shorter time to reaching endpoints than those with AD (median time; 40 months vs. 52 months, P < 0.0001). The proportion of admission (or death) was significantly higher in DLB than in AD (30% vs. 14%, P < 0.05), while the difference in institutionalization in nursing homes did not reach statistical significance (25% vs. 17%). Rates of longitudinal MMSE score decline for DLB and AD groups were equivalent. CONCLUSION: Dementia with Lewy bodies had a greater risk of admission (or death) because of most commonly fall-related injuries and bronchopneumonia than AD, but the two groups did not differ in rate of cognitive decline.

Attenuated radial augmentation index is associated with successful long-term antihypertensive treatment.

Pulse wave analysis was performed in apparently normal volunteers (n=164) and in essentially hypertensive patients without cardiovascular complications (n=171) using a newly developed non-invasive pulse wave measurement device (HEM-9010AI). Our results suggest that early wave reflections measured by radial augmentation index (AIr) are enhanced in volunteers with systolic blood pressure (SBP) >or= 160 mm Hg compared with the volunteers with their SBP<160 mmHg (98+/-18 vs 88+/-12, P<0.05). Furthermore, AIr is lower in hypertensive patients with long-term antihypertensive treatment than in those with short-term treatment (84+/-10 vs 89+/-13, P<0.01).

Observation of pressure wave generated by focusing a femtosecond laser pulse inside a glass.

The pressure (or stress) wave generated by focusing a femtosecond laser pulse inside a glass has been considered one of the important factors in determining structures created in the laser focal region. In this paper, a method of the transient lens (TrL) analysis was proposed to characterize the pressure wave. Experimentally, the TrL signal exhibited damping oscillation within 2 ns. Simulations of the TrL signal showed that the shape of the oscillating signal depended on the width and amplitude of the pressure wave. Comparing the observed TrL signal with the simulated one, we estimated these properties of the pressure wave generated after femtosecond laser focusing inside a soda-lime glass.

Heating and rapid cooling of bulk glass after photoexcitation by a focused femtosecond laser pulse.

To investigate the energy dissipation process after focusing a femtosecond laser pulse inside a zinc borosilicate glass, the time-dependent lens effect in the laser focal region was observed by a transient lens (TrL) method. We found that the TrL signal after 100 ns can be explained clearly by thermal diffusion. By fitting the observed signal, we obtained the phase change due to temperature increase, the initial diameter of the heated volume and the thermal diffusivity. On the basis of the results, the temperature increase and the cooling rate were estimated to be about 1800 K and 1.7X10(8) Ks(-1), respectively. We have also observed the signal change on a 100 ns scale, which can not be explained by the thermal diffusion model. This change was attributed to the relaxation of the heated material.

Caries-related bacteria and cytokines induce CXCL10 in dental pulp.

UNLABELLED: Marked infiltration of inflammatory cells, such as activated T-cells, is observed in the progression of pulpitis; however, little is known about the mechanism of their recruitment into pulpal lesions. It has been recently demonstrated that CXC chemokine ligand 10 (CXCL10) chemoattracts CXC chemokine receptor 3 (CXCR3)-positive activated T-cells. We therefore examined whether CXCL10 is involved in the pathogenesis of pulpitis. CXCL10 mRNA expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Immunostaining results revealed that CXCL10 was detected in macrophages, endothelial cells, and fibroblasts in inflamed dental pulp, and that CXCR3 expression was observed mainly on T-cells. Moreover, cultured dental pulp fibroblasts produced CXCL10 after stimulation with live caries-related bacteria, peptidoglycans, and pro-inflammatory cytokines. In contrast, heat-killed bacteria did not induce CXCL10 secretion. These findings suggest that CXCL10-CXCR3 may play an important role in the pulpal immune response to caries-related bacterial invasion. ABBREVIATIONS: CXCL10, CXC chemokine ligand 10; CXCR3, CXC chemokine receptor 3; IFN, interferon; FBS, fetal bovine serum; LTA, lipoteichoic acid; PGN, peptidoglycan; IL, interleukin; TNF, tumor necrosis factor; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay; CCL, C-C chemokine ligand; TLR, Toll-like receptor; NOD, nucleotide oligomerization domain; HDPF, human dental pulp fibroblasts.

Deep gray matter hyperperfusion with occipital hypoperfusion in dementia with Lewy bodies.

Although decreased occipital perfusion is a characteristic feature of dementia with Lewy bodies (DLB), not all patients with DLB show a significant decreased perfusion in the occipital lobe. We explored characteristics of perfusion changes to improve the identification of DLB, in addition to occipital hypoperfusion. Statistical image analysis of single photon emission computed tomography data was performed on 22 patients with DLB and 25 patients with Alzheimer's disease (AD). A significant decreased perfusion in the occipital lobe was found in 16 patients with DLB (72%) and three patients with AD (12%), while a significant increased perfusion in the deep gray matter (striatum and/or thalamus) was found in 18 patients with DLB (81%) and eight patients with AD (31%), respectively. Either occipital hypoperfusion or deep gray matter hyperperfusion was found in 21 patients with DLB (95%), while in nine patients with AD (35%), indicating a sensitivity of 95% and a specificity of 65% in discriminating DLB from AD. Our results suggest that the addition of deep gray matter hyperperfusion to occipital hypoperfusion may be useful in the clinical differentiation of DLB and AD.

Tumorigenic effect of 3-amino-1H-1,2,4-triazole on rat thyroid.

Six groups of female outbred Wistar rats were subjected to the following treatments: 2,500 ppm 3-amino-1H-1,2,4-triazole (amitrole) administered in the drinking water (group I); partial thyroidectomy and administration of amitrole in the drinking water (group II); partial thyroidectomy plus autoimplantation of resected thyroid tissue plus administration of amitrole in the drinking water (group III); no treatment (control of group I) (group IV); partial thyroidectomy without amitrole administration (control of group II) (group V); or partial thyroidectomy plus autoimplantation of resected thyroid tissue without amitrole administration (control of group III) (group VI). Goiters developed in all rats given amitrole (groups I-III). Invasive growth of the proliferating follicular tissue through the capsule into adjacent fatty tissue and of pericapsular blood vessels was frequent in these groups (P less than 0.001); invasive lesions were more frequent in the lobectomized thyroid glands of rats (groups II and III). Seven papillary adenomas composed of atypical cells with hyperchromatic nuclei and many mitoses were found in the thyroid glands and grafts in amitrole-treated groups I-II. No invasive growth or adenomas appeared in the control rats of groups IV-VI. Cholangiofibrosis developed in 5 of 100 rats in groups I-III.

Carcinogenic activity of quinoline on rat liver.

The effects of prolonged p.o. administration of quinoline or 2-chloroquinoline on rat liver were examined histologically. Hepatocellular carcinomas and hemangioendotheliomas were observed in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% quinoline for about 16 to 40 weeks. However, no neoplastic changes were seen in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% 2-chloroquinoline for 40 weeks. In groups that received low concentrations of quinoline, the incidences of hepatocellular carcinomas were higher and the incidences of hemangioendotheliomas were lower than in the group that received a high concentretion of quinoline. The liver tumors induced by quinoline were classified histologically as hemangioendotheliomas or hemangiosarcomas and trabecular hepatocellular carcinomas. Typical nodular hyperplasias were occasionally seen in the livers of rats treated with quinoline. 2-Chloroquinoline did not induce any nodular hyperplasia or other neoplastic changes, but it caused diffuse fatty changes of parenchymal cells. Oval cell infiltration and bile duct proliferation were slight or moderate. Cirrhotic changes were rare in the livers of rats treated with either quinoline or 2-chloroquinoline. The serum levels of glutamic oxaloacetic transaminase and alkaline phosphatase were slightly changed in groups treated with quinoline, but no other remarkable changes were detected.

Urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.

Clinicopathological, radiological, and histological studies were performed on urinary bladder neoplasia induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five adult beagle dogs and in ten adult mongrel dogs. Tumors of the urinary bladder developed in dogs given various daily doses of BBN p.o. for different periods. The latent period of tumor induction was 4 years in dogs receiving a daily dose of 80 mg of BBN, 2 to 2.5 years in dogs receiving a daily dose of 160 mg of BBN, and 1.5 years in dogs receiving a daily dose of 240 mg of BBN. The total dose of BBN ingested by the dogs until the first tumors were observed by urological examinations was nearly the same in all groups, 100 to 140 g. These results suggest that there is a correlation between dose and induction time, but further dose-response studies are required. Histologically, tumors of the urinary bladder were transitional cell papillomas or transitional cell carcinomas resembling morphologically those found in human cases. It is possible to observe the process of development of urinary bladder tumors from initial lesions to invasive tumors using routine urological examinations. We believe that this experimental model is valuable for clinicopathological studies of urinary bladder tumors.

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.

In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.

Localization of membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 at tight junctions of epithelial cells.

Membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 and Synapse-associated protein (SAP) 97/human Discs-large tumor suppressor gene (hDLG) are ubiquitous isoforms of synaptic scaffolding molecule (S-SCAM) and Postsynaptic density (PSD)-95/SAP90, both of which are implicated in the structures of synapses, respectively. SAP97/hDLG is localized at epithelial junctions and may function as a scaffolding protein, but the subcellular localization or the function of MAGI-1/BAP1 has not been clarified. In intestinal epithelial cells, MAGI-1/BAP1 was localized at tight junctions, whereas SAP97/hDLG was localized diffusely at cell - cell junctions. In Madine Darby canine kidney (MDCK) cells, MAGI-1/BAP1 was colocalized with ZO-1, whereas SAP97/hDLG was colocalized with E-cadherin. In MDCK cells, dominant active and negative mutants of Rac1 small G protein changed the amounts of SAP97/hDLG at cell - cell junctions, but not that of MAGI-1/BAP1. When MDCK cells were switched to a low Ca2+ medium, E-cadherin disappeared from the plasma membrane, and cells were dissociated. The phorbol 12-myristate 13-acetate-treatment after the low Ca2+ switch induced a tight junction-like structure. MAGI-1/BAP1 was recruited with ZO-1 to this structure, but SAP97/hDLG or E-cadherin was not. These findings suggest that MAGI-1/BAP1 is a component of tight junctions of epithelial cells, and that its role is different from that of SAP97/hDLG.