Plasmodium berghei infection ameliorates atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Atopic diseases are more prevalent in industrialized countries than in developing countries. In addition, significant differences in the prevalence of allergic diseases are observed between rural and urban areas within the same country. This difference in prevalence has been attributed to what is called the 'hygiene hypothesis'. Although parasitic infections are known to protect against allergic reactions, the mechanism is still unknown. The aim of this study was to investigate whether or not malarial infections can inhibit atopic dermatitis (AD)-like skin lesions in a mouse model of AD. METHODS: We used NC/Nga mice which are a model for AD. The NC/Nga mice were intraperitoneally infected with 1 × 10(5) Plasmoduim berghei (Pb) XAT-infected erythrocytes. RESULTS: Malarial infections ameliorated AD-like skin lesions in the NC/Nga mice. This improvement was blocked by the administration of anti-asialo GM1 antibodies, which are anti-natural killer (NK) cells. Additionally, adoptive transfer of NK cells markedly improved AD-like skin lesions in conventional NC/Nga mice; these suggest that the novel protective mechanism associated with malaria parasitic infections is at least, in part, dependent on NK cells. CONCLUSIONS: We have experimentally demonstrated for the first time that malarial infections ameliorated AD-like skin lesions in a mouse model of AD. Our study could explain in part the mechanism of the 'hygiene hypothesis', which states that parasitic infections can inhibit the development of allergic diseases.

Antibody against chromatin assembly factor-1 is a novel autoantibody specifically recognized in systemic lupus erythematosus.

Autoantibodies to proliferating cell nuclear antigen (PCNA) are specifically, if rarely, present in systemic lupus erythematosus (SLE) patient sera. Even SLE patients lacking PCNA reactivity often show reaction to PCNA-binding protein. Here, immunoreactivity to chromatin assembly factor-1 (CAF-1), an essential molecule for DNA replication and a PCNA-binding protein, was compared for the sera of SLE patients, normal healthy controls (NHCs) and other disease controls, and in autoimmune sera reactive to standard autoantigens, by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence, and immunoblotting. CAF1 and IRF1 expression in SLE and NHC peripheral mononuclear cells were compared by quantitative real-time polymerase chain reaction. Serum interferon-γ-inducing protein-10 and anti-double-stranded (ds)DNA antibody levels were measured by ELISA. Increased CAF-1 autoimmune reactivity was recognized in SLE or serum anti-dsDNA antibody-positive patients. Significantly greater central nervous system (CNS) involvement (aseptic meningitis) and serum anti-dsDNA antibody titers were present more often in anti-CAF-1 antibody-positive than antibody-negative SLE patients. IFN-γ positively regulated CAF-1 expression in vitro and was associated with anti-CAF-1 antibody production in SLE. Thus, a novel anti-CAF-1 autoantibody is frequently found in patients with SLE and is a useful biomarker for diagnosis, especially in cases with CNS involvement. Aberrant IFN-γ regulation appears to play an important role in anti-CAF-1 antibody production in SLE.

Atom probe tomography study of Mg-doped GaN layers.

Atom probe tomography studies on highly Mg-doped homoepitaxial GaN (0001) layers with concentrations of 5 × 10(19) cm(-3) and 1 × 10(20) cm(-3) were performed. Mg cluster formation was observed only in the higher doped sample whereas in the lower doped sample the Mg distribution was homogeneous. CL measurements have shown that the emission normally attributed to stacking faults was only present in the lower doped layers (with Mg concentration of ∼5 × 10(19) cm(-3) or less), but absent in the higher doped layer, where Mg clusters were detected. Mg clusters are proposed to produce a screening effect, thereby destroying the exciton binding on the SFs and thus rendering them optically inactive.

Multiple vitellogenins and product yolk proteins in striped bass, Morone saxatilis: molecular characterization and processing during oocyte growth and maturation.

The multiple vitellogenin (Vtg) system of striped bass, a perciform species spawning nearly neutrally buoyant eggs in freshwater, was investigated. Vitellogenin cDNA cloning, Western blotting of yolk proteins (YPs) using Vtg and YP type-specific antisera, and tandem mass spectrometry (MS/MS) of the YPs revealed the complex mechanisms of yolk formation and maturation in this species. It was discovered that striped bass possesses a tripartite Vtg system (VtgAa, VtgAb, and VtgC) in which all three forms of Vtg make a substantial contribution to the yolk. The production of Vtg-derived YPs is generally similar to that described for other perciforms. However, novel amino-terminal labeling of oocyte YPs prior to MS/MS identified multiple alternative sites for cleavage of these proteins from their parent Vtg, revealing a YP mixture far more complex than reported previously. This approach also revealed that the major YP product of each form of striped bass Vtg, lipovitellin heavy chain (LvH), undergoes limited degradation to smaller polypeptides during oocyte maturation, unlike the case in marine fishes spawning buoyant eggs in which LvHAa undergoes extensive proteolysis to osmotically active free amino acids. These differences likely reflect the lesser need for hydration of pelagic eggs spawned in freshwater. The detailed characterization of Vtgs and their proteolytic fate(s) during oocyte growth and maturation establishes striped bass as a freshwater model for investigating teleost multiple Vtg systems.

Comparative analyses of paediatric dental measurements using plaster and three-dimensional digital models.

AIM: Recent advances in three-dimensional imaging have led to an increased interest in the application of computer-models in paediatric dentistry. However, in evidence-based paediatric dentistry the accuracy of new methods must be validated before they are introduced to clinical practice. We aimed to compare the accuracy of measurements of digital models obtained using a non-contact 3D measuring system, with direct measurements made on plaster models (gold standard) from children. MATERIALS AND METHODS: Twelve pairs of plaster models were obtained from children with deciduous dentition; tooth size, arch width, and arch length were examined. The same parts on each cast were measured twice with at least a 2-week interval between measurements with each method by four examiners. Linear mixed-effects model analyses were performed for comparison of values from the 2 different measurement methods. RESULTS: The average difference between the 2 methods in measured values, derived from the final model, was <0.2 mm. Random effect of examiners was always the smallest component of variance, and frequently negligible. STATISTICS: Intraclass correlation coefficients were typically >90%. CONCLUSION: These results suggest that primary dentition analysis of digital models has a high accuracy level, comparable to that of direct measurement of plaster models by digital calipers.

Application of three-dimensional digital models for the morphometric analysis of predentition plasters: accuracy and precision.

AIM: This study aimed to test the accuracy and precision of measurements of three-dimensional (3D) digital models from the pre-dentition period using a noncontact 3D measurement system (3D scanner) versus the gold standard method of direct measurements using a digital caliper on plaster models. MATERIALS AND METHODS: Ten pairs of plaster models were obtained from children during the predentition period. Linear measurements were performed using both methods. Three operators were trained in the use of both methods for this study. Measurements were performed with a minimum 2-week interval between measurements in a randomly chosen order. RESULTS: The mean difference between the measured values using the two methods was <0.2 mm for each measurement. There was no linearity in the measurements using pre-dentition digital models. An ANOVA Gage R&R analysis revealed that there was no significant operator difference (P < 0.307). The rate of variation of the 3D scanner over the total variation was 2.8%. The ICC was 0.982 (P< 0.001), suggesting excellent interoperator agreement. CONCLUSION: The results suggest that measurements of digital 3D pre-dentition models are highly accurate and precise, and also comparable to measurements using the gold standard method.

Cross-Sectional and Longitudinal Associations of Creatinine-to-Cystatin C Ratio with Sarcopenia Parameters in Older Adults.

OBJECTIVES: Accumulating evidence from cross-sectional studies suggests that the serum creatinine-to-cystatin C ratio (CCR) may be a useful biomarker for sarcopenia. This study aimed to assess the cross-sectional and longitudinal associations of CCR with sarcopenia and its parameters in community-dwelling older adults. DESIGN: Cross-sectional and longitudinal study. SETTING AND PARTICIPANTS: This 6-year prospective cohort study included the repeated measurement data from 1,253 Japanese residents (662 males and 591 females) aged ≥65 years who underwent medical checkups in Kusatsu and Hatoyama, Japan. A total of 4,421 observations were collected. MEASUREMENTS: The CCR was grouped into quartiles by sex (Q1-Q4) using Q4 as the reference category. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Skeletal muscle mass index (SMI) measured using segmental multifrequency bioelectrical impedance analysis, handgrip strength (HGS), usual gait speed (UGS), and maximal gait speed (MGS) were measured repeatedly as sarcopenia parameters. The association of the CCR with changes in sarcopenia, SMI, HGS, UGS, and MGS during the 6-year period were analyzed using a generalized linear mixed-effects model. RESULTS: The prevalence of sarcopenia at baseline was 13.1% (11.9% in males and 14.5% in females). In a cross-sectional analysis, the CCR quartile was inversely associated with sarcopenia and was positively associated with SMI, HGS, and MGS (P for trend < 0.001). In a longitudinal analysis during the 6 years, a significant increase in sarcopenia in Q2 (B = 1.1% point/year; P = 0.026 for group-by-time interaction) and significant declines in SMI (B = -0.01 kg/m2/year; P = 0.044 for group-by-time interaction) and MGS (B = -0.008 m/sec/year; P = 0.041 for group-by-time interaction) in Q1 were observed compared with Q4. However, the dose-response relationship was significant only for MGS (P = 0.033 for trend). No significant group-by-time interaction was observed for HGS. CCR was not significantly associated with UGS either cross-sectionally or longitudinally. CONCLUSIONS: CCR is a useful biomarker regarding the status of sarcopenia. It may be used for sarcopenia screening even in older adults whose physical function is difficult to assess. However, further longitudinal studies are needed to determine whether CCR can be a predictor of future sarcopenia.

Human papillomavirus type 56-associated Bowen disease.

BACKGROUND: Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear. OBJECTIVE: To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations. METHODS: Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease. RESULTS: Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types. CONCLUSIONS: This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.

Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption.

We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF-induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.

Study of charged particle activation analysis (II): Determination of boron concentration in human blood samples.

Boron Neutron Capture Therapy (BNCT) is a radiotherapy for the treatment of intractable cancer. In BNCT precise determination of 10B concentration in whole blood sample before neutron irradiation of the patient, as well as accurate neutron dosimetry, is crucial for control of the neutron irradiation time. For this purpose ICP-AES and neutron induced prompt γ-ray analysis are generally used. In Ibaraki Neutron Medical Research Center (iNMRC), an intense proton beam will be accelerated up to 8 MeV, which can also be used for Charged Particle Activation Analysis (CPAA). Thus, in this study, we apply the CPAA utilizing the proton beam to non-destructive and accurate determination of 10B concentration in whole blood sample. A CPAA experiment is performed by utilizing an 8 MeV proton beam from the tandem accelerator of Nuclear Science Research Institute in Japan Atomic Energy Agency. The 478 keV γ-ray of 7Be produced by the 10B(p, α)7Be reaction is used to quantify the 10B in human blood. The 478 keV γ-ray intensity is normalized by the intensities of the 847 keV and 1238 keV γ-rays of 56Co originating from Fe in blood. The normalization methods were found to be linear in the range of 3.27 µg 10B/g to 322 µg 10B/g with correlation coefficients of better than 0.9999.

Persistent urticaria characterized by recurrent lasting urticarial erythema with histological features of prominent perivascular eosinophilic infiltration.

We report a 29-year-old woman with a 15-year history of recurrent pruritic urticarial erythemas. The individual lesions lasted for > 24 h, and antihistaminic agents were not effective. Histological examination of a skin biopsy revealed interstitial oedema of the dermis and perivascular infiltration of numerous eosinophils without vasculitis. No internal organ involvement or peripheral blood eosinophilia was present. A diagnosis of persistent urticaria was made and the patient was successfully treated with oral corticosteroid therapy. Persistent urticaria has been described as an unusual reaction that lasts longer than typical urticaria. It is effectively treated with corticosteroids, but not with antihistaminic agents. In order to choose the most effective treatment, persistent urticaria should be recognized as a different clinical condition from typical urticaria.

Score-Based and Nutrient-Derived Dietary Patterns Are Associated with Depressive Symptoms in Community-Dwelling Older Japanese: A Cross-Sectional Study.

OBJECTIVES: This study evaluated associations of score-based and nutrient-derived dietary patterns with depressive symptoms in community-dwelling older Japanese. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: 982 community-dwelling adults aged 65 years or older. MEASUREMENTS: Score-based pattern was assessed by using dietary variety score (DVS), which covers 10 food group items in Japanese meals. Nutrient-derived dietary patterns were identified by using reduced rank regression (RRR), with folate, vitamin C, magnesium, calcium, iron, and zinc intakes as response variables. Depressive symptoms were assessed with the Geriatric Depression Scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for these dietary patterns in multivariate logistic regression analyses with potential confounders. The lowest consumption category was used as the reference group. RESULTS: The prevalence of depressive symptoms was 13.5%. Higher DVS was associated with fewer depressive symptoms (OR=0.52, 95% CI=0.27-1.03 for the highest vs the lowest DVS; P for trend=0.031). The first RRR dietary pattern score was characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruits, and green tea and a low intake of rice and was inversely associated with the prevalence of depressive symptoms (OR=0.53, 95% CI=0.30-0.92; P for trend=0.030). CONCLUSION: Greater dietary variety and a dietary pattern characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruit, and green tea and a low intake of rice were consistently associated with lower prevalence of depressive symptoms in community-dwelling older Japanese. Therefore, both patterns identified the components of dietary habits essential to depression prevention.

Differential corticosterone responses to stress in the lung in two strains of Flinders rats.

BACKGROUND: Acute stress affects a variety of organs and cellular systems. These include the hypothalamic-pituitary-adrenal (HPA) axis, corticotropin-releasing factor (CRF), mast cells and nerves. Flinders-sensitive (FSL) rat strains have hypercholinergic responses and are more sensitive than Flinders-resistant rats (FRL) to anaphylaxis. OBJECTIVE: To investigate the effects of acute water avoidance stress (1 h) on FSL and FRL tracheal epithelial tissue. METHODS: We measured short circuit current (I(sc)) as a measure of tracheal response, and the effect of substance P (SP) on tracheal epithelium in Ussing chambers. Electron microscopy was performed to assess mast cell activation. RESULTS: Both strains showed increased I(sc) responses to stress, inhibited by prior injection of the CRF receptor 1 and 2 antagonist, alpha-helical CRF-(9-41). No increases in conductance were seen. Stress responses were accompanied by electron microscopic morphologic evidence for mast cell degranulation, which was not completely inhibited by alpha-helical CRF-(9-41) pre-treatment. Stress primed the epithelium for an enhanced response to SP in FSL, but this again was not inhibited by alpha-helical CRF-(9-41). FRL had 2.5 times the corticosterone response of FSL. CONCLUSION: Acute stress affects the tracheal epithelium, not accompanied by changes in ion permeability, but associated with mast cell degranulation. Because blunted HPA axis responses are associated with vulnerability to inflammation, this may partially explain the findings. These stress effects on the lung have a genetic basis associated with relative corticosterone responses, are complex and only in part mediated by CRF.

Role of pathogenic auto-antibody production by Toll-like receptor 9 of B cells in active systemic lupus erythematosus.

OBJECTIVES: Toll-like receptor 9 (TLR9) is a pattern-associated receptor functioning in innate immunity that may be involved in the recognition of self-antigens and the production of pathogenic auto-antibodies. Therefore, we examined the expression of TLR9 in systemic lupus erythematosus (SLE) to determine whether TLR9 is involved in the production of pathogenic auto-antibodies. METHODS: B cells were collected from patients with active SLE, and subjected to analysis of the TLR9 molecule using flow cytometry fluorescence activated cell sorting (FACS) and TLR9 mRNA by reverse-transcriptase polymerase chain reaction. SLE B cells were stimulated with CpG-ODN, and subsequent cytokine and anti-dsDNA antibody production was measured by enzyme-linked immunosorbent assay. RESULTS: The expression and mRNA level of TLR9 on B cells was up-regulated in SLE patients, and SLE disease activity index (SLEDAI) and CH50 were correlated with TLR9 expression on CD20+ B cells. Moreover, TLR9-CpG interaction enhanced the production of anti-dsDNA antibody and IL-10. CONCLUSIONS: The present study demonstrated that higher expression of TLR9 on peripheral blood B cells from patients with active SLE was significantly correlated with CH50 and SLEDAI to TLR9, and induced the production of anti-dsDNA antibody and IL-10 by TLR9-CpG ligation. These results suggest that an abnormality of innate immunity plays a crucial role in the pathology of SLE, and that blockade of CpG-TLR9 interaction may be a new therapeutic approach for SLE.

Prostaglandin F(2alpha) negatively regulates bone resorption in murine osteoclast development.

Prostaglandin (PG) E(2) promotes osteoclastic cell differentiation, but the physiological function of PGF(2alpha) remains unclear. We examined the physiological effects of PGF(2alpha) on osteoclast differentiation using a murine cell line, RAW264, and the column-purified murine bone marrow cells, both of which are differentiable into osteoclast-like multi-nuclear cells. Although PGF(2alpha) did not affect the number of differentiated osteoclasts, PGF(2alpha) reduced the bone resorption activity of osteoclasts developed from both cell types in a pit formation assay. Thus, PGF(2alpha) inhibits bone resorption without affecting the number of osteoclasts, providing a novel molecular mechanism underlying bone metabolism.

Molecular analysis of physiological responses to changes in nitrogen in a marine macroalga, Porphyra yezoensis (Rhodophyta).

The rhodophyte seaweed Porphyra yezoensis, known more commonly world-wide as "nori", is an important commercial crop in Japan. Cultivation of nori in Japan is often affected by outbreaks of "iroochi", a discoloration of the thalli due to a decrease in inorganic nutrients in the culture area that in turn decreases the amount of photosynthetic pigments in the thalli. Treating thalli with inorganic nitrogen can reverse iroochi. In this paper, we report on the characterization of three P. yezoensis genes, a nitrate transporter (PyNRT2) and two urea transporters (PyUT1 and PyUT2), which may be involved in reversing iroochi. The predicted length of the PyNRT2 protein was 479 amino acids (AA), while PyUT1 and PyUT2 were 740 and 680 AA, respectively. PyNRT2 was more similar to NRT2 from a chromophyte than to NRTs from Chlamydomonas and higher plants. The two P. yezoensis UTs had 56% AA identity to each other, and showed the closest relationship to higher plant and yeast DUR3 proteins which formed a subfamily of the sodium-solute symporter protein family. Hydrophobicity plots of the AA sequences showed that the PyNRT2, PyUT1, and PyUT2 included 12, 15, and 16 transmembrane domains, respectively. Southern blot analysis indicated that the P. yezoensis genome has a single NRT2-encoding gene and at least four UT-encoding genes. Expression analysis of PyNRT2 and PyUT genes showed that the messenger RNA level of the PyNRT2 gene reached a maximum after 48 h in the nitrate starvation condition and was then restored to the constitutive level, while expression of the PyUT genes was induced in proportion to treatment times in the nitrate starvation condition. These results suggest that the PyNRT2 and PyUT are responsible for the high-affinity nitrate/urea transport systems that operate under low external nitrate concentrations.

Localization and transient emission properties in InGaN/GaN quantum wells of different polarities within core-shell nanorods.

Transient photoluminescence (PL) characteristics and localization phenomena in InGaN/GaN core-shell nanorods (NRs) were investigated from 6 K up to 285 K. The NRs exhibit three well-defined PL bands in the near-UV, blue, and green range ascribed to the emission of quantum well (QW) areas situated at the (1.00) sidewalls, (10.1) top facets, and (00.1) tip, respectively. At low temperature, time-resolved PL shows a fast decay time of about 0.5 ns for the semi- and non-polar QWs, while the polar QWs exhibit at least a twice-longer time. Rapid delocalization of carriers above 50 K indicates shallow potential fluctuations in the QWs. At room temperature, the characteristic fast PL decay time of the three QW bands stabilizes around 300 ps. The slow decaying PL components have different characteristic decay times that are explained by additional localization at basal stacking faults (BSFs), taking into account the quantum confined Stark effect. In addition, narrow excitonic luminescence lines are observed in the BSF-enriched polar QWs, providing direct evidence of the impact of the BSF/QW crossings on the optical properties of the NRs. A PL rise time of about 100 ps does not show any deviation between bands. These findings are suggestive of similar transport mechanisms in temperature equilibrium without inter-facet transport between different QWs. We believe that predictable transient characteristics can play a key role in creating uniform NR ensembles for device applications.

Insight into the performance of multi-color InGaN/GaN nanorod light emitting diodes.

We report on the thorough investigation of light emitting diodes (LEDs) made of core-shell nanorods (NRs) with InGaN/GaN quantum wells (QWs) in the outer shell, which are grown on patterned substrates by metal-organic vapor phase epitaxy. The multi-bands emission of the LEDs covers nearly the whole visible region, including UV, blue, green, and orange ranges. The intensity of each emission is strongly dependent on the current density, however the LEDs demonstrate a rather low color saturation. Based on transmission electron microscopy data and comparing them with electroluminescence and photoluminescence spectra measured at different excitation powers and temperatures, we could identify the spatial origination of each of the emission bands. We show that their wavelengths and intensities are governed by different thicknesses of the QWs grown on different crystal facets of the NRs as well as corresponding polarization-induced electric fields. Also the InGaN incorporation strongly varies along the NRs, increasing at their tips and corners, which provides the red shift of emission. With increasing the current, the different QW regions are activated successively from the NR tips to the side-walls, resulting in different LED colors. Our findings can be used as a guideline to design effectively emitting multi-color NR-LEDs.