Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I.

Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by deficiency of alpha-L-iduronidase leading to accumulation of its catabolic substrates, dermatan sulfate (DS) and heparan sulfate (HS), in lysosomes. This results in progressive multiorgan dysfunction and death in early childhood. The recent success of enzyme replacement therapy (ERT) for MPS I highlights the need for biomarkers that reflect response to such therapy.

Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography-tandem mass spectrometry.

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A disease), a progressive lysosomal storage disease, causes skeletal chondrodysplasia through excessive storage of keratan sulfate (KS). KS is synthesized mainly in cartilage and released to the circulation. The excess storage of KS disrupts cartilage, consequently releasing more KS into circulation, which is a critical biomarker for MPS IVA.

Induced sputum concentrations of mucin in patients with asthma and chronic cough.

Background: Mucus hypersecretion is an important pathophysiologic index of airway disease. Measurement of secreted mucin in sputum has been reported in asthma, but not in chronic cough with or without increased sputum production.

Methods: We studied 49 patients with classic asthma (CA), 39 with cough-variant asthma (CVA), nine and five with chronic cough associated with sinobronchial syndrome (SBS) and gastroesophageal reflux disease (GERD), respectively, and 11 healthy controls.

Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers.

This is a clinical safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) study of a single ascending dose (SAD) and a multiple ascending dose (MAD) of the oral direct factor Xa inhibitor edoxaban in healthy males. The placebo-controlled, single-blind, randomized, 2-part study consists of a SAD arm with 85 subjects (10, 30, 60, 90, 120, 150 mg) and a MAD arm with 36 subjects (90 mg daily, 60 mg twice daily, 120 mg daily). Effects of food and formulation (tablet vs solution) are assessed in a crossover substudy.

Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008-2009 season.

Background: A substantial increase in oseltamivir-resistant A(H1N1) influenza viruses was reported in Europe in late 2007.

Objectives: To monitor the antiviral susceptibility profile of human A(H1N1) influenza viruses in Japan during the 2007-2008 and 2008-2009 seasons.

Study Design: Viruses were obtained from respiratory samples of patients with influenza collected in Japan between December 2007 and April 2008 (n=1046) and between December 2008 and April 2009 (n=1789).

Validation of disaccharide compositions derived from dermatan sulfate and heparan sulfate in mucopolysaccharidoses and mucolipidoses II and III by tandem mass spectrometry.

Glycosaminoglycans (GAGs) are accumulated in various organs in both mucopolysaccharidoses (MPS) and mucolipidoses II and III (ML II and III). MPS and ML II and III patients can not properly degrade dermatan sulfate (DS) and/or heparan sulfate (HS). HS storage occurs in the brain leading to neurological signs while DS storage involves mainly visceral and skeletal manifestations.

Epidemiology of human influenza A and B viruses in Myanmar from 2005 to 2007.

Objectives: To perform genetic analysis of influenza A and B viruses in Myanmar from 2005 to 2007 and to determine the prevalence of amantadine-resistant influenza A viruses.

Methods: Phylogenies of the HA and NA genes were analyzed and mutations in M2 that confer resistance to amantadine were screened.

Results: Influenza in Myanmar exhibited seasonality, which coincided during the rainy season from June to August.

Relationship between small airway function and health status, dyspnea and disease control in asthma.

Background: Small airways play important roles in the pathophysiology of asthma. However, relationships between small airway involvement and health status and dyspnea have not been investigated.

Objectives: It was the aim of this study to assess the relationships between proximal and peripheral airway functions and health status, dyspnea and disease control in patients with asthma, using impulse oscillometry (IOS).

Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics.

Background And Objective: Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC(4) synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known.

[Influence of black vinegar on itraconazole absorption].

Itraconazole (ITCZ), a useful oral drug effective against Aspergillus, is reported to cause insufficient blood concentration through unstable enteral absorption. Hypoacidic gastic conditions have been reported to reduce absorption, whereas acidic drinks promote it. We present a case of pulmonary aspergillosis in a subject administered ITCZ with black vinegar, a popular health food in Japan.

CD4(+)CD8(+) thymocytes are induced to cell death by a small dose of puromycin via ER stress.

When the CD4(+)CD8(+) thymic lymphoma cells were treated with puromycin, we found that most of the cells died at 0.3-1 microg/ml of puromycin within 24h. However, cell death was greatly reduced when the dose of puromycin was increased.

Emerging genotypes of human respiratory syncytial virus subgroup A among patients in Japan.

Human respiratory syncytial virus (HRSV) is a common etiological agent of acute lower respiratory tract disease in infants. We report the molecular epidemiology of HRSV in Niigata, Japan, over six successive seasons (from 2001 to 2007) and the emerging genotypes of HRSV subgroup A (HRSV-A) strains. A total of 488 HRSV samples were obtained from 1,103 screened cases in a pediatric clinic in Niigata.

Simultaneous determination by APCI-LC/MS/MS of hydroxylated and methoxylated polybrominated diphenyl ethers found in marine biota.

A method has been developed for the simultaneous analysis of hydroxylated and methoxylated analogs of tetrabromodiphenyl ethers (OH-tetraBDEs and MeO-tetraBDEs) and of hydroxylated and methoxylated analogs of tetrabromobiphenyl (diOH-tetraBB and diMeO-tetraBB) using high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (APCI-LC/MS/MS) in negative ion mode. Chromatographic separation was performed on a 150 mm ODS column with acetonitrile:water (9:1, v/v) in mobile phase. Multiple reaction monitoring (MRM) was performed using the precursor [M-H]- ion for hydroxylated analogs, and the [M-Br+O]- ion for tetraBDEs and tetraBB, and their methoxylated analogs.

Effect of inhaled corticosteroids on small airways in asthma: investigation using impulse oscillometry.

Background: Small airways appear to have an important role in asthma. Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) has ultrafine particles and accordingly greater deposition in the small airways than chlorofluorocarbon (CFC)-BDP. Impulse oscillometry systems (IOS), a new and non-invasive measure of pulmonary function, can examine the resistance of total (R5), large (R20), and small airways (R5-R20) separately, and low-frequency reactance area (AX), also considered a measure of small airways dysfunction.

Regulation of adenosine 5'-triphosphate (ATP)-gated P2X(4) receptors on tracheal smooth muscle cells.

We examined the effects of extracellular adenosine 5'-triphosphate (ATP) on single airway smooth muscle (ASM) cells from porcine trachea using a patch-clamp technique. ATP induced a sustained inward current. Phospholipase C inhibitor U-73122 failed to inhibit the current, suggesting the involvement of P2X receptor.

Specific IgE response to trichophyton and asthma severity.

Background: Sensitization to Trichophyton, a major dermatophyte, has been associated with asthma. Whether such sensitization is generally associated with the severity of asthma, like other molds such as Alternaria, is unknown.

Methods: We compared 258 patients with asthma, which was classified by severity as mild (n = 123), moderate (101), or severe (34), and 114 healthy control subjects, with regard to specific IgE titers against Trichophyton rubrum and other common allergens such as mixed molds, house-dust mite, cat dander, dog dander, Japanese cedar pollen, mixed Graminea pollens and mixed weed pollens.

Molecular evolution of human influenza A viruses in a local area during eight influenza epidemics from 2000 to 2007.

A total of 1,041 human influenza A virus isolates were collected at a clinic in Niigata, Japan, during eight influenza seasons from 2000 to 2007. The H3N2 subtype accounted for 75.4% of the isolates, and the rest were H1N1.

Role of Ca2+ mobilization and Ca2+ sensitization in 8-iso-PGF 2 alpha-induced contraction in airway smooth muscle.

Background: Isoprostanes are prostaglandin (PG)-like compounds synthesized by oxidative stress, not by cyclooxygenase, and increase in bronchoalveolar lavage fluid of patients with asthma. The airway inflammation implicated in this disease may be amplified by oxidants. Although isoprostanes are useful biomarkers for oxidative stress, the action of these agents on airways has not been fully elucidated.

Negative APCI-LC/MS/MS method for determination of natural persistent halogenated products in marine biota.

A sensitive and selective method utilizing high performance liquid chromatography coupled to negative atmospheric pressure chemical ionization tandem mass spectrometry (APCI-LC/MS/MS) was developed to enable analysis of selected natural persistent organohalogens accumulated in marine biota. The analytes were three methoxylated tetrabromodiphenyl ethers (6-MeO-BDE47, 2'-MeO-BDE68, and 2',6-diMeO-BDE68), a dimethoxylated tetrabromobiphenyl (2,2'-diMeO-BB80), and two halogenated methyl bipyrroles (Cl(7)-MBP and Br(4)Cl(2)-DBP). These products were well resolved on a 150 mm reversed-phase column with methanol as the mobile phase.

TP receptor-mediated release of eosinophil chemotactic activity from human bronchial smooth muscle cells.

There are reports indicating that thromboxane A(2) receptors (TP receptors) may stimulate the eosinophil accumulation in the lower airways of asthmatics, however, the mechanisms behind such an effect remain unknown. We quantified the synthesis of eosinophil chemotactic activity and eosinophilic CC chemokines, including CCL5, CCL7, CCL8, CCL11, CCL13, CCL24, and CCL26 in primary cultures of human bronchial smooth muscle cells (BSMC) stimulated with a prostanoid TP receptor agonist, IBOP (10(-9)-10(-7) M). The activation of prostanoid TP receptors in BSMC induced the release of potent eosinophil chemoattractant(s) in the presence of interleukin (IL)-4.

Role of prostaglandin D(2) and its receptors in the pathophysiology of asthma.

Prostaglandin D(2) (PGD(2)) is one of the most abundant lipid mediators present in the airways of asthmatics. However, little was known of the role it plays in the pathophysiology of asthma, until the identification of DP (DP1, PTGDR) and CRTH2 (DP2), two PGD(2)-specific transmembrane receptors with different distribution and intracellular signaling. Pharmacological tools, such as receptor-specific agonists and antagonists, and genetically-engineered mice, which lack either DP or CRTH2, have helped understand the complex effects of PGD(2) in allergic inflammation of the airways.

Effects of adiponectin on growth and differentiation of human keratinocytes--implication of impaired wound healing in diabetes.

Impaired wound healing is one of the most common complications associated with diabetes. Adiponectin is an abundant circulating adipocyte-derived cytokine that has beneficial effects on disorders accompanying diabetes. Herein we report that adiponectin has a regulatory effect on the growth and differentiation of HaCaT human keratinocyte cells.