Sphingosine-1-phosphate augments agonist-mediated contraction in the bronchial smooth muscles of mice.

The effects of sphingosine-1-phosphate (S1P) on bronchial smooth muscle (BSM) contractility were investigated in naive mice. S1P had no effect on the basal tone of the isolated BSM tissues. However, in the presence of S1P (10(-6) M), the BSM contractions induced by acetylcholine (ACh) and endothelin-1 (ET-1) were significantly augmented: both the ACh and ET-1 concentration-response curves were significantly shifted to the left.

Lattice Boltzmann simulation on continuously regenerating diesel filter.

To reduce particulate matter (PM) including soot in diesel exhaust gas, a diesel particulate filter (DPF) has been developed. Since it is difficult to observe the phenomena in a DPF experimentally, we have conducted a lattice Boltzmann simulation. In this study, we simulated the flow in a metallic filter.

Vascular pattern classification of colorectal lesions with narrow band imaging magnifying endoscopy.

Magnifying narrow band imaging (NBI) has enabled to observe the vascular pattern of colorectal lesions. Their broad findings have been divided into six groups according to endoscopical vascular features: normal, faint, network, dense, irregular and sparse. Most hyperplastic polyps show a faint pattern.

Antigen challenge influences various transcription factors of rat bronchus: protein/DNA array study.

Although the transcription factors are required for expression of the proinflammatory cytokines and immune proteins which are involved in airway hyperresponsiveness and inflammation of bronchial asthma, the antigen-induced alterations of the transcription factors in bronchi have not yet been revealed. Therefore, in order to profile the alteration pattern of the transcription factors after antigen challenge in bronchi, we used protein/DNA arrays. Rats were sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen.

Generation of reactive oxygen species induced by gold nanoparticles under x-ray and UV Irradiations.

The radiosensitizing effect of 5-250 nm diameter Au nanoparticles (AuNPs) in water was investigated under irradiations of diagnostic x-ray and UV light. Enhanced generations of hydroxyl radical ((·)OH) and superoxide anion (O(2)(-)) were confirmed from their dependencies on the absorbed energy, ethanol concentration and AuNPs' concentration. Two kinds of fluorescent probes revealed that the reactive oxygen species (ROS) generation rate under x-ray irradiation was enhanced by factors of 1.

A new, convenient cell-based screening method for small-molecule glycolytic inhibitors.

To counteract active glycolysis in tumors, we developed a new, convenient cell-based screening system to identify an inhibitor of glycolysis. Using this system, we searched for an inhibitor in the synthetic Carbasugar library and found two candidates. It was found that both inhibited glycolysis by suppressing the glucose uptake step in tumor cells.

Sphingosine-1-phosphate aggravates antigen-induced airway inflammation in mice.

Unlabelled: Recent investigations suggest an involvement of sphingosine-1-phosphate (S1P) in the pathogenesis of allergic bronchial asthma. However, the role of S1P in the development of asthma is still controversial. Our aim was to investigate the effects of intranasal application of S1P on antigen-induced airway inflammation in a mouse model of allergic bronchial asthma.

Augmented PDBu-mediated contraction of bronchial smooth muscle of mice with antigen-induced airway hyperresponsiveness.

To explore the role of protein kinase C (PKC) in the augmented bronchial smooth muscle (BSM) contraction observed in the antigen-induced airway hyperresponsive (AHR) mice, the effects of a PKC activator, phorbol 12,13-dibutylate (PDBu), on BSM contraction were compared between the AHR and control mice. Actively sensitized mice were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge the isometrical contractions of the BSMs were measured.

Involvement of multiple PKC isoforms in phorbol 12,13-dibutyrate-induced contraction during high K(+) depolarization in bronchial smooth muscle of mice.

In airway smooth muscle, protein kinase C (PKC) has been implicated in a number of functional responses including the regulation of contractility. However, the exact role of PKC on bronchial smooth muscle (BSM) contraction is still unclear. In the present study, to determine the role of PKC activation in the BSM contraction, the effects of phorbol 12,13-dibutyrate (PDBu, a direct PKC activator) on BSM tone were examined in the absence and presence of K(+)-induced depolarization stimulation.

Involvement of K(+) channels in the augmented nasal venous responsiveness to nitric oxide in rat model of allergic rhinitis.

Objective: one of the factors of nasal obstruction observed in allergic rhinitis is thought to be a dilatation of microveins in nasal mucosa, although the exact mechanism(s) is not fully understood. In nasal mucosae of repeatedly antigen challenged rats, NO-induced venodilatation itself is augmented. In the present study, the roles of K(+) channels in sodium nitroprusside (NO donor; SNP)-induced venodilatation of nasal mucosae in antigen-challenged rats were investigated.

A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer.

In 2005, we initiated a clinical trial that examined the efficacy of the oncolytic virus HF10 to treat pancreatic cancer. Pancreatic cancer continues to have a high mortality rate, despite multimodal treatments for patients, and new therapeutic methods are greatly needed. The current mainstream methods for cancer treatment include biological therapeutics such as trastuzumab (Herceptin) for breast cancer or erlotinib (Tarceva) for non-small cell lung cancer.

A novel glycosylation signal regulates transforming growth factor beta receptors as evidenced by endo-beta-galactosidase C expression in rodent cells.

The αGal (Galα1-3Gal) epitope is a xenoantigen that is responsible for hyperacute rejection in xenotransplantation. This epitope is expressed on the cell surface in the cells of all mammals except humans and Old World monkeys. It can be digested by the enzyme endo-β-galactosidase C (EndoGalC), which is derived from Clostridium perfringens.

High therapeutic potential for systemic delivery of a liposome-conjugated herpes simplex virus.

Purpose: Oncolytic viral therapy is a newly developed modality to treat tumors. Many clinical trials worldwide have examined the efficacy of locally injected oncolytic viruses. However, systemic intravascular injections are limited by the humoral immune response, which dramatically decreases the level of infection.

MicroRNAs and their therapeutic potential for human diseases: MiR-133a and bronchial smooth muscle hyperresponsiveness in asthma.

MicroRNAs (miRNAs) play important roles in normal and diseased cell functions. The small-GTPase RhoA is one of the key proteins of bronchial smooth muscle (BSM) contraction, and an upregulation of RhoA has been demonstrated in BSMs of experimental asthma. Although the mechanism of RhoA upregulation in the diseased BSMs is not fully understood, recent observations suggest that RhoA translation is controlled by a miRNA, miR-133a, in cardiomyocytes.

SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness, but not airway inflammation, in mice.

To determine if endogenously generated sphingosine-1-phosphate (S1P) is involved in the development of allergic bronchial asthma, the effects of systemic treatments with SKI-II, a specific inhibitor of sphingosine kinase, on antigen-induced bronchial smooth muscle (BSM) hyperresponsiveness and airway inflammation were examined in mice. Male BALB/c mice were actively sensitized with ovalbumin (OA) antigen and were repeatedly challenged with aerosolized antigen. Animals also received intraperitoneal injections with SKI-II (50 mg/kg) 1 h prior to each antigen challenge.

RhoA, a possible target for treatment of airway hyperresponsiveness in bronchial asthma.

Airway hyperresponsiveness to nonspecific stimuli is one of the characteristic features of allergic bronchial asthma. An elevated contractility of bronchial smooth muscle has been considered as one of the causes of the airway hyperresponsiveness. The contraction of smooth muscles including airway smooth muscles is mediated by both Ca²+-dependent and Ca²+-independent pathways.

A case of asthma-complicated influenza myocarditis.

A 36-year-old man with a history of asthma visited an outpatient clinic complaining of high fever and general fatigue, and was diagnosed as having influenza type A by influenza antigen test. Laboratory findings revealed mild inflammation, mild acidemia, and hypercapnea with radiologic infiltrations in the right lung, and remarkable wheezes in both lungs were heard on auscultation. He was diagnosed with asthma exacerbation and having influenza pneumonia, and was referred to us.

A functional interaction between CPI-17 and RACK1 proteins in bronchial smooth muscle cells.

CPI-17 is a phosphorylation-dependent inhibitor of smooth muscle myosin light chain. Using yeast two-hybrid system, we have identified the receptor for activated C kinase 1 (RACK1) as a novel interaction partner of CPI-17. The direct interaction and co-localization of CPI-17 with RACK1 were confirmed by immunoprecipitation and confocal microscopy analysis, respectively.

Involvement of Src family kinase activation in angiotensin II-induced hyperresponsiveness of rat bronchial smooth muscle.

Angiotensin II (Ang II) might be an important mediator in pathogenesis of airway hyperresponsiveness (AHR) that is the asthmatic characteristic feature of asthma, although the mechanisms of AHR caused by Ang II are not yet clear. Presently, the RT-PCR analyses revealed that all the Src family kinases (SFKs), such as Fyn, Lck, Lyn, Hck, Src, Yes, Blk, Fgr and Frk, were expressed in the lungs and main bronchi of rats. The phosphorylation (activation) of SFK (Tyr416) was increased in bronchial smooth muscle (BSM) by Ang II.

Induction of RhoA gene expression by interleukin-4 in cultured human bronchial smooth muscle cells.

RhoA, a small GTPase, is one of the key proteins of smooth muscle contraction. In allergic asthma, an upregulation of RhoA in bronchial smooth muscle has been suggested. However, the mechanism of its upregulation has not yet been clarified.

[Prognostic lung abscess factors].

Background: Lung abscess, although curable when caught early and treated appropriately, still may recur repeatedly or require surgery. We retrospectively assessed prognostic lung abscess factors and predictive recurrence factors. We evaluated comorbidity using the Charson comorbidity index (CCI).

Diagnostic accuracy of pit pattern and vascular pattern analyses in colorectal lesions.

Background: The aim of this prospective study is to compare the usefulness of magnifying narrow band imaging (NBI) and magnifying chromoendoscopy in the diagnosis of colorectal lesions.

Methods: The subjects were 1185 patients who underwent a complete colonoscopic examination and endoscopic or surgical treatment, from January 2006 to February 2008. A total of 1473 lesions were evaluated (53 hyperplastic polyps, 1317 adenomas, 103 submucosally invasive cancers).

Augmented venous responsiveness to leukotriene D(4) in nasal septal mucosae of repeatedly antigen-challenged rats.

One possible mechanism of the nasal obstruction observed in allergic rhinitis is thought to be a dilatation of veins in nasal mucosa, although the exact mechanism(s) is not fully understood. An involvement of cysteinyl leukotrienes (CysLTs) in the nasal obstruction has also been suggested. In addition to the specific antigen-induced nasal symptoms, nasal hyperresponsiveness to non-specific stimuli is one of the characteristic features of patients with allergic rhinitis.

Phorbol 12,13-dibutyrate-mediated contraction of the stimulated bronchial smooth muscles of mice.

Increasing evidence suggests that protein kinase C (PKC) is involved in the Ca(2+) sensitization of various smooth muscle contractions. However, the exact role of PKC on bronchial smooth muscle (BSM) contraction is still unclear. In the present study, to determine the role of PKC activation in the BSM contraction, the effects of phorbol 12,13-dibutyrate (PDBu) on BSM tone were examined in the absence and presence of contractile stimulation.

Downregulation of sphingosine-1-phosphate receptors in bronchial smooth muscle of mouse experimental asthma.

To determine whether or not sphingosine-1-phosphate (S1P) is involved in the augmented bronchial smooth muscle (BSM) contractility, one of the causes of airway hyperresponsiveness in asthmatics, the effects of S1P on BSM tone were investigated in control and repeatedly antigen-challenged mice. Both in the control and antigen-challenged animals, S1P had no effect on basal tone of the isolated BSM tissues. However, in the BSMs pre-depolarized by 60mM K(+), S1P caused a significant increase in tension in the control mice.