[Steroid resistance of severe asthma - mechanisms and therapeutic targets].

Asthma therapy in general has improved a lot in recent years, but it is still a major problem that severe asthma, which accounts for 10 to 20%, still suffers from strong symptoms on a daily basis despite all therapeutic agents used in combination. American SARP and European ENFUMOSA started in 2000 to advance pathophysiological insights of severe asthma. Clinical usage of antibodies and inhibitors against IgE, TNF, IL-5, IL-4, IL-13, and TSLP are also accumulating.

[Usefulness of an anti-mouse cerebellar tissue-derived antigen antibody test in predicting immunotherapy efficacy in patients with idiopathic cerebellar ataxia].

Background: Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia.

Identification of acyl-CoA thioesterase in mouse mesenteric lymph nodes.

Acyl-CoA thioesterases (ACOTs) are a group of enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and CoA, with the potential to regulate the intracellular levels of these molecules. In this study, we show that a cytosolic isoform, ACOT7, is expressed at a significant level in the mesenteric lymph nodes (MLNs) of mice. While crude preparations of the mesenteric visceral fat contained significant levels of palmitoyl-CoA thioesterase activity, enzyme activity was concentrated 6.

Expression and distribution of acyl-CoA thioesterases in the white adipose tissue of rats.

Acyl-CoA thioesterases (Acots) are enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and coenzyme A, and have the potential to regulate the intracellular levels of these molecules. In this study, we show that a cytosolic isoform, Acot1, is expressed and distributed in immature adipocytes located in the perivascular region of the white adipose tissue (WAT) of rats. Immunoblot analyses detected Acot1 in all of the WATs examined, while immunohistochemistry revealed positively stained layered structures surrounding the adventitia of blood vessels in the subcutaneous WAT.

Analysis of molecular dynamics of colloidal particles in transported dilute samples by self-mixing laser Doppler velocimetry.

Colloidal particles in a liquid medium are transported with constant velocity, and dynamic light scattering experiments are performed on the samples by self-mixing laser Doppler velocimetry. The power spectrum of the modulated wave induced by the motion of the colloidal particles cannot be described by the well-known formula for flowing Brownian motion systems, i.e.

Hypoglycemic effects of clove (Syzygium aromaticum flower buds) on genetically diabetic KK-Ay mice and identification of the active ingredients.

Clove (Syzygium aromaticum flower buds) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In-vitro evaluation showed the extract had human peroxisome proliferator-activated receptor (PPAR)-γ ligand-binding activity in a GAL4-PPAR-γ chimera assay. Bioassay-guided fractionation of the EtOH extract resulted in the isolation of eight compounds, of which dehydrodieugenol (2) and dehydrodieugenol B (3) had potent PPAR-γ ligand-binding activities, whereas oleanolic acid (4), a major constituent in the EtOH extract, had moderate activity.

CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1, cells induced by antigen challenge in mice.

CD44 is a cell adhesion molecule involved in lymphocyte infiltration of inflamed tissues. We previously demonstrated that CD44 plays an important role in the development of airway inflammation in a murine model of allergic asthma. In this study, we investigated the role of CD44 expressed on CD4(+) T cells in the accumulation of T-helper type 2 (Th2) cells in the airway using CD44-deficient mice and anti-CD44 monoclonal antibodies.

Comparative analysis of steroid sensitivity of T helper cells in vitro and in vivo.

Background: Glucocorticoid (GC) action on asthma has been partly explained by the inhibition of T cell activation. We analyzed the steroid sensitivity of ovalbumin (OVA) reactive helper T (Th) cell clones both in vitro and in vivo.

Method: For in vitro experiments, Th clones were cultured with antigen-presenting cells, OVA, and various concentrations of dexamethasone (DEX).

Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression.

This study tested the feasibility of oral immunotherapy for bronchial asthma using a newly developed subunit vaccine in which a fragment (p45-145) of mite allergen (Der p 1) containing immunodominant human and mouse T cell epitopes was encapsulated in endoplasmic reticulum-derived protein bodies of transgenic (Tg) rice seed. Allergen-specific serum immunoglobulin responses, T cell proliferation, Th1/Th2 cytokine production, airway inflammatory cell infiltration, bronchial hyper-responsiveness (BHR) and lung histology were investigated in allergen-immunized and -challenged mice. Prophylactic oral vaccination with the Tg rice seeds clearly reduced the serum levels of allergen-specific IgE and IgG.

Sustained downregulation of YY1-associated protein-related protein gene expression in rat hippocampus induced by repeated electroconvulsive shock.

YY1AP-related protein (YARP) is a structural homolog of YY1-associated protein (YY1AP), which has a YY1-binding domain. During perinatal development, YARP mRNA expression is increased at a late stage of embryonic neurogenesis. It is not known whether YARP expression is regulated during adult neurogenesis.

Neuronal expression, cytosolic localization, and developmental regulation of the organic solute carrier partner 1 in the mouse brain.

Organic solute carrier partner 1 (OSCP1) is a mammalian, transporter-related protein that is able to facilitate the uptake of structurally diverse organic compounds into the cell when expressed in Xenopus laevis oocytes. This protein has been implicated in testicular handling of organic solutes because its mRNA expression is almost exclusive in the testis. However, in this study, we demonstrated significant expression of OSCP1 protein in mouse brain, the level of which was rather higher than that in the testis, although the corresponding mRNA expression was one-tenth of the testicular level.

Regulated expression of acyl-CoA thioesterases in the differentiation of cultured rat brown adipocytes.

Acyl-CoA thioesterases (ACOTs) are enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. In this study, we show that the expression profile of the ACOT isoforms changes remarkably during the differentiation of cultured rat brown adipocytes. Immunocytochemistry suggested that cytosolic ACOT1 was present in the preadipocytes, while mitochondrial ACOT2 was additionally expressed as the cells differentiated, concurrent with the accumulation of lipid droplets in the cytoplasm.

Eosinophils are required for the induction of bronchial hyperresponsiveness in a Th transfer model of BALB/c background.

Background: Helper T (Th) cells are deeply involved in the pathophysiology of bronchial asthma, such as eosinophilic inflammation, bronchial hyperresponsiveness (BHR), airflow limitation and remodeling. It is still unclear whether Th cells contribute to BHR independently of eosinophilic inflammation. The double GATA (dblGATA) site is a high-affinity GATA-binding site in the GATA-1 promoter.

Evaluation of cysteinyl leukotriene-induced contraction of human cultured bronchial smooth muscle cells.

Background: Cysteinyl leukotrienes (cysLTs) are major mediators involved in bronchial asthma, particularly bronchial constriction. However, a contractile response of human bronchial smooth muscle cells (hBSMCs) to cysLTs has not been well characterized at cellular level.

Methods: A contraction assay using collagen gel embedded with cultured hBSMCs was established to analyze contractile responses at cellular level.

Murine Th clones confer late asthmatic response upon antigen challenge.

Background: Helper T (Th) cells are deeply involved in the pathophysiology of bronchial asthma, such as eosinophilic inflammation, bronchial hyperresponsiveness and remodeling. However, it is still unclear how Th cells contribute to airflow limitation, another cardinal feature of bronchial asthma.

Method: Unprimed BALB/c mice were transferred with ovalbumin (OVA)-reactive Th clones.

Airway eosinophilic inflammation is attenuated in conserved noncoding sequence-1-deficient mice.

Background: Conserved noncoding sequence-1 (CNS-1) is an important regulatory element for T helper 2 cytokine expression. IL-4, IL-5 and IL-13 expression as well as serum IgE level were attenuated in CNS-1-/- mice.

Method: CNS-1-/- and CNS-1+/+ mice were sensitized with ovalbumin (OVA) followed by antigen challenge.

Generation of vortex beams from lasers with controlled Hermite- and Ince-Gaussian modes.

We report selective excitations of higher-order Hermite-Gaussian and Ince-Gaussian (IG) modes in a laser-diode-pumped microchip solidstate laser and controlled generation of corresponding higher-order and multiple optical vortex beams of different shapes using an astigmatic mode converter (AMC). Simply changing the pump-beam diameter, shape, and lateral off-axis position of the tight pump beam focus on the laser crystal within a microchip semispherical cavity can produce the desired optical vortex beams in a well controlled manner. Pattern changes featuring different IG and HG modes obtained by rotating the AMC are also demonstrated.