Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.

Previous studies have reported that ST2 is preferentially expressed on Th2 cells and plays a critical part in controlling airway inflammation in murine models of asthma. However, the clinical role of ST2 in patients with bronchial asthma remains unclear. In our study, we examined 56 patients with atopic asthma in a nonattack phase and 200 nonatopic normal volunteers for healthy control, and analyzed the relationship of their serum ST2 levels to asthma severity, pulmonary function, and laboratory data.

Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy.

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress.

Vascular endothelial growth factor (VEGF) expression in the subacromial bursa is increased in patients with impingement syndrome.

Vascular endothelial growth factor (VEGF), which is known to be an angiogenetic factor, plays an important role in the inflammation of synovial tissue. To investigate the relationships between VEGF and clinical symptoms in rotator cuff disease, VEGF expression was examined using RT-PCR and immunohistochemical analysis in 50 patients with this disease (26 with full-thickness cuff tear, 12 with partial-thickness tear, and 12 with subacromial bursitis). VEGF mRNA expression was detected in 40 out of 50 patients by RT-PCR.

Inhibitory effect of a presenilin 1 mutation on the Wnt signalling pathway by enhancement of beta-catenin phosphorylation.

Mutations in the presenilin 1 (PS1) gene are the most common genetic factor underlying the development of early onset familial Alzheimer's disease (FAD). Accumulating evidence has shown that FAD-linked mutations of PS1 enhance the generation of amyloid-beta (1-42) protein. Recently, beta-catenin has been shown to interact with PS1.

Cholesterol-dependent formation of GM1 ganglioside-bound amyloid beta-protein, an endogenous seed for Alzheimer amyloid.

GM1 ganglioside-bound amyloid beta-protein (GM1/Abeta), found in brains exhibiting early pathological changes of Alzheimer's disease (AD) including diffuse plaques, has been suggested to be involved in the initiation of amyloid fibril formation in vivo by acting as a seed. To elucidate the molecular mechanism underlying GM1/Abeta formation, the effects of lipid composition on the binding of Abeta to GM1-containing lipid bilayers were examined in detail using fluorescent dye-labeled human Abeta-(1-40). Increases in not only GM1 but also cholesterol contents in the lipid bilayers facilitated the binding of Abeta to the membranes by altering the binding capacity but not the binding affinity.

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) causes Akt phosphorylation and morphological changes in intracellular organellae in cultured rat astrocytes.

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is widely used for cell viability and cytotoxicity assays, but cell biological effects of MTT itself have not been investigated. In this paper we show that MTT induces a morphological change in an intracellular membranous compartment labeled with anti-Rab5 antibody, dissociation of early endosomal auto-antigen (EEA1) from the membrane fraction, and phosphorylation of Akt probably through a phosphatidylinositol-3-OH kinase [PI(3)K] pathway in cultured rat astrocytes. These findings suggest that MTT affects cellular functions and conditions to some extent, and such effects of MTT may cause some discrepancies of measurement of cell viability using MTT assay and other assays.

Comparative biokinetics of tritium in rats during continuous ingestion of tritiated water and tritium-labeled food.

Purpose: The biokinetics of tritium during continuous ingestion of tritiated water and tritiated wheat were investigated to estimate the radiation dose rates at the end of two modes of chronic exposure.

Materials And Methods: Wistar strain male rats continuously ingested tritiated water as drinking water and tritiated wheat as food for 14 weeks. Urine and tissue samples were obtained and total tritium in the fresh wet samples and organically bound tritium (OBT) in the freeze-dried samples were determined.

Requirement for natural killer T (NKT) cells in the induction of allograft tolerance.

In this study, we investigated the role of Valpha14 natural killer T (NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not Valpha14 NKT cell-deficient mice.

Cholesterol-dependent modulation of tau phosphorylation in cultured neurons.

One of the hallmarks of Alzheimer's disease (AD) is the abnormal state of tau. It is both highly phosphorylated and aggregated into paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). However, the mechanism underlying the hyperphosphorylation of tau in NFTs and neuronal degeneration in AD remains to be elucidated.

Site-specific phosphorylation of tau accompanied by activation of mitogen-activated protein kinase (MAPK) in brains of Niemann-Pick type C mice.

Niemann-Pick type C (NPC) disease is characterized by an accumulation of cholesterol in most tissues and progressive neurodegeneration with the formation of neurofibrillary tangles. Neurofibrillary tangles are composed of paired helical filaments (PHF), a major component of which is the hyperphosphorylated tau. In this study we used NPC heterozygous and NPC homozygous mouse brains to investigate the molecular mechanism responsible for tauopathy in NPC.

Expression and regulation of apolipoprotein E receptors in the cells of the central nervous system in culture: A review.

The importance of apolipoprotein E (apoE) in the central nervous system (CNS) became increasingly clear since the descovery that apoE ε4 allele is a major risk factor for Alzheimer's disease. ApoE is one of the major apolipoproteins that acts as a ligand for the cellular uptake of lipoproteins via apoE receptors, members of low-density lipoprotein receptor (LDLR) family, in the CNS. Recently, LDLR family has been shown to have new functions that modulate intracellular signalling and affect neuronal and glial functions, survival and regeneration.

Quantitative changes in the mRNA for contractile proteins and metabolic enzymes in masseter muscle of bite-opened rats.

To study the effects of bite opening on the fibre phenotypes of rat masseter, the mRNAs of four predominant myosin heavy-chain isoforms (MHC I, IIa, IId/x and IIb) and two alkali light-chain isoforms (LC1f and 3f) as well as those of two metabolic enzymes, carbonic anhydrase III (CAIII, oxidative enzyme) and glucose-phosphate isomerase (GPI, glycolytic enzyme), were measured in relation to the total RNA of masseter muscle by competitive, reverse transcriptase-polymerase chain reaction in control and bite-opened rats. Bite opening (2.8 mm increase in the vertical dimension for 1 week) significantly (P<0.

The cloning and nucleotide sequence of human ST2L cDNA.

The ST2 gene is a member of the IL-1 receptor family and is hypothesized to be involved in helper T cell function, but its functional ligand and physiological role remain unknown. We have cloned the human ST2L cDNA that encodes a distinct type of membrane-bound ST2 protein. The predicted 556-amino-acid sequence showed 67% identity to the mouse ST2L protein.

Construction of ELISA system to quantify human ST2 protein in sera of patients.

The human ST2 gene can be specifically induced by growth stimulation in fibroblastic cells, and can also be induced by antigen stimulation in Th2 cells. The gene encodes a soluble secreted protein, ST2, and a transmembrane protein, ST2L, which are closely related to the interleukin-1 receptor. To gain insight into the biological roles of the ST2 gene, three monoclonal antibodies (MAbs) against human ST2 gene products were obtained.

Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers.

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-beta) superfamily involved in a range of biological activities. The loss of sensitivity to TGF-beta is frequent in human lung cancers and inactivation of Smad family members are thought to play important roles in disruption of TGF-beta signaling. In the study presented here, we characterized the biological and biochemical functions of six Smad2 and Smad4 mutants, which we previously identified in human lung cancers.

The mitochondrial DNA of Dictyostelium discoideum: complete sequence, gene content and genome organization.

We present an overview of the gene content and organization of the mitochondrial genome of Dictyostelium discoideum. The mitochondria genome consists of 55,564 bp with an A + T content of 72.6%.