The role of Mycoplasma pneumoniae infection in the initial onset and exacerbations of asthma.

Asthma is a disease in which airway hyperresponsiveness, increased airway contraction, and airway secretion occur as a result of allergic airway inflammation. Mycoplasma infections are well known to exacerbate asthma pathology as well as to cause the onset of asthma itself. Mechanisms of airway epithelial injury, activation of innate immunity, or increased Th2-dominant immune responses caused by community-acquired distress syndrome toxin (CARDSTx) or diacylated lipoprotein have been reported in exacerbations or the onset of asthma because of Mycoplasma infections.

AP-VAS 2012 case report: an atypical case of microscopic polyangiitis presenting with acute tubulointerstitial nephritis without glomerular change.

Renal involvement in myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis is frequently characterized by focal segmental crescentic and/or necrotizing glomerulonephritis. However, a few cases of only tubulointerstitial nephritis (TIN) involvement without any apparent glomerular lesions have been reported. Here we report just such a case.

Prognostic value of vascular endothelial growth factors A and C in oral squamous cell carcinoma.

Background: Vascular endothelial growth factor (VEGF) family members play a major role in angiogenesis and vascularization. VEGF-A promotes tumor angiogenesis by stimulating the growth of tumor vascular endothelial cells. In addition, VEGF-C has been identified as a potent inducer of lymphangiogenesis in tumor and lymph node metastasis.

Regulation of alkaline ceramidase activity by the c-Src-mediated pathway.

Ceramidase hydrolyzes ceramide to fatty acids and sphingosine, and sphingosine is then converted to sphingosine-1-phosphate. Ceramide and sphingosine-1-phosphate act as signaling molecules. Although stimuli coupling to protein kinases-dependent systems have been shown to regulate ceramidase activity, the exact role of c-Src-mediated signal has not been elucidated.

Amphiphilic COSAN and I2-COSAN crossing synthetic lipid membranes: planar bilayers and liposomes.

The boron-rich cobaltabisdicarbollide (COSAN) and its 8,8'-I2 derivative (I2-COSAN), both of purely inorganic nature, are shown to cross through synthetic lipid membranes. These results reveal unexpected properties at the interface of biological and synthetic membranes.

Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies.

Objective: To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).

Methods: Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC.

Targeted activation of PKA and Epac promotes glioblastoma regression .

Ras-p44/42 mitogen-activated protein kinase (MAPK) and Akt signaling are the key pathways involved in the promotion of glioblastoma formation. Notably, phosphodiesterase 4 (PDE4) is widely expressed in brain tumors and promotes their growth. PDE4 inhibitors have been reported to suppress glioblastoma growth and .

Long-term heat exposure prevents hypoxia-induced apoptosis in mouse fibroblast cells.

Long-term continuous exposure to high ambient temperatures induces complete heat acclimation in humans and animals. However, to date, the effects of long-term exposure to heat stress on cells have not been fully evaluated. In this study, we investigated an adaptive physiological process induced in culture cells by continuous exposure to mild heat stress for 60 days.

A novel photodynamic therapy for drug-resistant prostate cancer cells using porphyrus envelope as a novel photosensitizer.

Background: In the clinic, it is often very difficult to treat drug-resistant advanced prostate cancer by conventional treatments. Photodynamic therapy (PDT) is a minimally invasive treatment that takes advantage of photochemical reactions between a photosensitizer and light. On the basis of several of its key characteristics, PDT is considered to be a promising novel method for treating drug-resistant prostate cancer.

Role of sphingolipids in arachidonic acid metabolism.

The arachidonic acid (AA) cascade is regulated mainly by the actions of two rate-limiting enzymes, phospholipase A₂ (PLA₂) and inducible cyclooxygenase-2 (COX-2). PLA₂ acts to generate AA, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to prostaglandin production. Amongst more than 30 members of the PLA₂ family, cytosolic PLA₂α (cPLA₂α, group IVA) plays a major role in releasing AA from cellular membranes.

Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial.

Importance: No highly effective interventions to prevent delirium have been identified.

Objective: To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium.

Design, Setting, And Participants: A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital.

Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus: a modest but significant effect of aldosterone synthase.

Recent genome-wide association studies have identified multiple variants that confer risk of type 2 diabetes mellitus (DM). However, established associations explain only a part of the heritability. Thus, even at the genome-wide association studies era, candidate gene approach should be still useful.

Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B.

Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. We previously showed that methylxanthines, including caffeine and theophylline, have antitumor and antiinflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE). A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor.

A murine model of airway fibrosis induced by repeated naphthalene exposure.

The airway epithelium serves as a biological barrier essential for host defense against inhaled pollutants. While chronic epithelial injury, commonly associated with chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome, often results in airway fibrosis, limited animal models of airway fibrosis have been established. Club cells (Clara cells) in the small airways represent an important population of epithelial progenitor cells and also the principal site of localization of the cytochrome P-450 monooxygenase system, which metabolically activates xenobiotic chemicals such as naphthalene by converting them to toxic epoxide intermediates.

A novel coronary active perfusion system using a conventional intra-aortic balloon pump for off-pump coronary artery bypass grafting.

Objective: It is important for coronary active perfusion systems to avoid myocardial ischemia during off-pump coronary artery bypass grafting. We have developed a new concept for a perfusion system to pump blood based on changes in helium gas volume. This system uses a conventional intra-aortic balloon pump to activate the perfusion pump.

Acute thrombotic thrombocytopenic purpura after pneumococcal vaccination.

We report the case of a 68-year-old woman with acute thrombotic thrombocytopenic purpura (TTP) that developed after pneumococcal vaccination. She was found in a confusional state with high fever 15 days after vaccination. Laboratory data showed hemolytic anemia and thrombocytopenia, and blood smear showed fragmented erythrocytes.

Myasthenia gravis: predictive factors associated with the synchronized elevation of anti-acetylcholine receptor antibody titer in Kanazawa, Japan.

For a brief period, an increased incidence of elevated anti-acetylcholine receptor antibody titer was observed in patients with myasthenia gravis (MG) in Kanazawa, Japan. The purpose of this study was to examine the predictive factors associated with this antibody titer elevation. Decreased odds of titer elevation were seen in patients with early-onset MG than in those with late-onset MG.

Sequential treatment of oxaliplatin-containing PEGylated liposome together with S-1 improves intratumor distribution of subsequent doses of oxaliplatin-containing PEGylated liposome.

We recently reported that combination therapy with metronomic S-1 dosing and oxaliplatin (l-OHP)-containing PEGylated liposomes improved antitumor activity in a murine colorectal tumor model. However, little is known about the mechanism underlying such improved therapeutic efficacy. Here we investigated the impact of combined treatment on biodistribution, tumor accumulation and intratumor distribution of test PEGylated liposomes and on the structure of tumor vasculature in a solid tumor.

[Development of high boron content liposomes and their promising antitumor effect for neutron capture therapy].

  High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve the efficient cell-killing effect of boron neutron capture therapy (BNCT) that relies on the nuclear reaction of two essentially nontoxic species, boron-10 ((10)B) and thermal neutrons in boron-loaded tissues. Recent development of boron cluster lipids and their liposomal boron delivery system (BDS) are summarized in this article. Boron compounds that have no affinity to tumor can potentially be delivered to tumor tissues by liposomes, therefore, liposomal BDS would be one of the most attractive approaches for efficient BNCT of various cancers.

Vulnerability to traumatic stress in fibromyalgia patients: 19 month follow-up after the great East Japan disaster.

Introduction: The aim of this study was to investigate vulnerability and long-term influence of traumatic stress caused by the Great East Japan Disaster which occurred on March 11, 2011, in patients with fibromyalgia, which is a chronic pain syndrome probably involving central sensitization.

Methods: A total of 60 female patients with fibromyalgia were compared with female patients with rheumatoid arthritis (RA, n = 23) as another chronic pain disease, and with female healthy controls (HC, n = 26) in the observational study. To evaluate responses to traumatic stress, the scores of Impact of Event Scale-Revised (IES-R) were assessed one month after the disaster and every six months until 19 months after the disaster.

Diaryl-substituted ortho-carboranes as a new class of hypoxia inducible factor-1α inhibitors.

Diaryl-substituted ortho-carboranes 1 were synthesized from the corresponding alkynes by decaborane coupling under microwave-irradiated conditions with a combination of N,N-dimethylaniline and chlorobenzene. Among the compounds synthesized, 1a and 1d exhibited significant inhibition of hypoxia-induced HIF-1 transcriptional activity. Both compounds similarly suppressed hypoxia-induced HIF-1α accumulation in a concentration-dependent manner without affecting HIF-1α mRNA expression.

The highly conserved human cytomegalovirus UL136 ORF generates multiple Golgi-localizing protein isoforms through differential translation initiation.

The UL133-UL138 locus in the unique long b' (ULb') region of the human cytomegalovirus (HCMV) genome is considered to play certain roles in viral replication, dissemination and latency in a host cell type-dependent manner. Here we characterized the proteins encoded by UL136, one of the open reading frames (ORFs) in the locus. Comparative sequence analysis of UL136 among clinical isolates and laboratory strains indicates that its predicted amino-acid sequence is highly conserved.

Human cytomegalovirus induces apoptosis in neural stem/progenitor cells derived from induced pluripotent stem cells by generating mitochondrial dysfunction and endoplasmic reticulum stress.

Background: Congenital human cytomegalovirus (HCMV) infection, a leading cause of birth defects, is most often manifested as neurological disorders. The pathogenesis of HCMV-induced neurological disorders is, however, largely unresolved, primarily because of limited availability of model systems to analyze the effects of HCMV infection on neural cells.

Methods: An induced pluripotent stem cell (iPSC) line was established from the human fibroblast line MRC5 by introducing the Yamanaka's four factors and then induced to differentiate into neural stem/progenitor cells (NSPCs) by dual inhibition of the SMAD signaling pathway using Noggin and SB-431542.