Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration.

An important aspect in optimizing DNA vaccination is antigen delivery to the site of action. In this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. The novel nanoparticle, pDNA/PEI/γ-PGA complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency.

Discovery of GAMA, a Plasmodium falciparum merozoite micronemal protein, as a novel blood-stage vaccine candidate antigen.

One of the solutions for reducing the global mortality and morbidity due to malaria is multivalent vaccines comprising antigens of several life cycle stages of the malarial parasite. Hence, there is a need for supplementing the current set of malaria vaccine candidate antigens. Here, we aimed to characterize glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by the PF08_0008 gene in Plasmodium falciparum.

Conjugated asymmetric donor-substituted 1,3,5-triazines: new host materials for blue phosphorescent organic light-emitting diodes.

Conjugated asymmetric donor-substituted 1,3,5-triazines (ADTs) have been synthesized by nucleophilic substitution of organolithium catalyzed by [Pd(PPh(3))(4)]. Theoretical and experimental investigations show that ADTs possess high solubility and thermostability, high fluorescent quantum yield (35%), low HOMO (-6.0 eV) and LUMO (-2.

Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development.

The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker.

Release of TNF-α from macrophages is mediated by small GTPase Rab37.

Activated macrophages at wound sites release many cytokines which positively affect skin wound healing. However, the molecular mechanisms controlling cytokine secretion from macrophages have not been elucidated. In the present study, we performed an RT-PCR analysis and found that 19 small GTPase Rab isoforms were expressed at skin wound sites, with six of them (i.

Plasmodium vivax: comparison of immunogenicity among proteins expressed in the cell-free systems of Escherichia coli and wheat germ by suspension array assays.

Background: In vitro cell-free systems for protein expression with extracts from prokaryotic (Escherichia coli) or eukaryotic (wheat germ) cells coupled to solid matrices have offered a valid approach for antigen discovery in malaria research. However, no comparative analysis of both systems is presently available nor the usage of suspension array technologies, which offer nearly solution phase kinetics.

Methods: Five Plasmodium vivax antigens representing leading vaccine candidates were expressed in the E.

N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity.

The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein.

A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum.

Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P.

[Pneumonitis induced by rifampicin].

An 86-year-old male with pulmonary tuberculosis developed fever, rash, and interstitial pneumonia 3 weeks after the beginning of treatment with isoniazid (INH), rifampicin (RFP), and ethambutol (EB). Chest CT showed new infiltration shadows that were diffuse bilateral ground-glass opacities mixed with dense consolidation and septal thickening, accompanied by a small amount of pleural effusion. Drug-induced pneumonitis was suspected, and therefore the antituberculous regimen was discontinued.

Efficacy of blood-patch pleurodesis for secondary spontaneous pneumothorax in interstitial lung disease.

Objective: We identified the prognostic relevance of pneumothorax in interstitial lung disease (ILD) patients and evaluated the efficacy and safety of autologous blood-patch pleurodesis.

Methods: We retrospectively reviewed 59 occurrences of pneumothorax in 34 ILD patients identified over a 12-year period.

Results: Air leakage ceased in 16 of 22 (72.

Analysis of anatomical and functional determinants of obstructive sleep apnea.

Purpose: Craniofacial abnormalities have an important role in the occurrence of obstructive sleep apnea (OSA) and may be particularly significant in Asian patients, although obesity and functional abnormalities such as reduced lung volume and increased airway resistance also may be important. We conducted simultaneous analyses of their interrelationships to evaluate the relative contributions of obesity, craniofacial structure, pulmonary function, and airway resistance to the severity of Japanese OSA because there are little data in this area.

Methods: A cross-sectional observational study was performed on 134 consecutive Japanese male patients.

Worldwide sequence conservation of transmission-blocking vaccine candidate Pvs230 in Plasmodium vivax.

Pfs230, surface protein of gametocyte/gamete of the human malaria parasite, Plasmodium falciparum, is a prime candidate of malaria transmission-blocking vaccine. Plasmodium vivax has an ortholog of Pfs230 (Pvs230), however, there has been no study in any aspects on Pvs230 to date. To investigate whether Pvs230 can be a vivax malaria transmission-blocking vaccine, we performed evolutionary and population genetic analysis of the Pvs230 gene (pvs230: PVX_003905).

Measurement of naturally acquired humoral immune responses against the C-terminal region of the Plasmodium vivax MSP1 protein using protein arrays.

Protein arrays are powerful tools for antibody profiling and vaccine development against infectious agents. In the previous report, we successfully applied an antibody-based protein array for immunoprofiling of Plasmodium vivax infection. Herein, we developed a Ni-NTA surface based protein array to detect immune responses against the recombinant C-terminal region (19 and 42 kDa) of the P.

Amino acid taste receptor regulates insulin secretion in pancreatic β-cell line MIN6 cells.

Amino acids such as L-glutamate and L-arginine are potent stimuli for insulin secretion from pancreatic β-cells. However, the precise molecular mechanisms of amino acid-induced insulin secretion have only partly understood. In this study, we show here that mouse pancreatic β-cell line MIN6 cells expressed amino acid taste receptor (heterodimer of type 1 taste G protein-coupled receptor member 1 and member 3; Tas1R1 and Tas1R3, respectively).

The new red-emitting phosphor of oxyfluoride Ca2RF4PO4:Eu3+ (R=Gd, Y) for solid state lighting applications.

The novel red-emitting phosphors of Eu3+-activated Ca2RF4PO4:Eu3+ (R=Gd, Y) prepared by a solid-state reaction have been evaluated as a candidate for white solid state lighting. The detailed luminescence properties, e.g.

PaCO2 six months after the initiation of long-term noninvasive ventilation in patients with COPD.

Background And Objective: The appropriate target level for PaCO(2) after the introduction of long-term noninvasive positive pressure ventilation (NPPV) in patients with COPD remains uncertain, and therefore must be tested.

Methods: Data on 54 patients with COPD receiving long-term domiciliary NPPV were examined retrospectively. PaCO(2) a few months after NPPV and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome.

Comparison of biomarkers of subclinical lung injury in obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate.

Methods: Subjects of the present study were 197 patients suspected to have OSA.

The thermal stabilities of luminescence and microstructures of Eu2+-doped KBaPO4 and NaSrPO4 with β-K2SO4 type structure.

Eu(2+)-doped monophosphates NaSrPO(4) and KBaPO(4) with the β-K(2)SO(4) structure were synthesized using the conventional high temperature solid state reaction. The X-ray powder diffraction, photoluminescence excitation, and emission spectra and decay curves were measured. The phosphors can be efficiently excited by UV-visible light from 220 to 430 nm to realize emission in the visible range.

Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic beta cells (MIN6).

The Forkhead box transcription factor FoxO1 regulates metabolic gene expression in mammals. FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression.

A tipping point in drug dosing in late-life schizophrenia.

Minimally effective doses of antipsychotics are likely influenced by several clinical and demographic characteristics of patients, with age being one of the most important elements. In light of age-related physiologic changes as well as interindividual differences in pharmacokinetic and pharmacodynamic systems, individualized dosing with regard to age will be critically important for safer drug treatment for older patients with schizophrenia. In the present review, we propose the following cautious psychopharmacologic interventions for this population: 1) simple regimen (avoid polypharmacy), 2) be aware of the presence of patients who are very sensitive to drugs, 3) gradual dose titration, and 4) timely and thorough assessments of therapeutic and side effects.

Adenovirus-vectored Plasmodium vivax ookinete surface protein, Pvs25, as a potential transmission-blocking vaccine.

Adjuvants or delivery vehicles are essential components to expedite malaria vaccine development. In this study, replication-defective human adenovirus serotype 5 (rAd) was genetically engineered to express the Plasmodium vivax ookinete surface protein (OSP), Pvs25 (AdPvs25). BALB/c mice immunized with the AdPvs25 through various routes including intramuscular, subcutaneous and intranasal routes were analyzed for induction of antigen-specific transmission-blocking immunity.

Genetic polymorphism of Plasmodium vivax msp1p, a paralog of merozoite surface protein 1, from worldwide isolates.

Plasmodium vivax msp1p, a paralog of the candidate vaccine antigen P. vivax merozoite surface protein 1, possesses a signal peptide at its N-terminus and two epidermal growth factor-like domains at its C-terminus with a glycosylphosphatidylinositol attachment site. The msp1p gene locus may have originated by a duplication of the msp1 gene locus in a common ancestor of the analyzed Plasmodium species and lost from P.

Immediate noninvasive ventilation may improve mortality in patients with hepatopulmonary syndrome after liver transplantation.

Hepatopulmonary syndrome (HPS) is defined as hypoxemia induced by intrapulmonary vascular dilations associated with liver disease. Although liver transplantation (LT) is the only effective therapy established for severe HPS, patients with a partial pressure of arterial oxygen (PaO(2) ) less than 60 mm Hg have a poor prognosis. We treated a 4-year-old boy with HPS whose preoperative PaO(2) level was 48.

Dual roles of Notch in regulation of apically restricted mitosis and apicobasal polarity of neuroepithelial cells.

How the mitosis of neuroepithelial stem cells is restricted to the apical ventricular area remains unclear. In zebrafish, the mosaic eyes(rw306) (moe/epb41l5(rw306)) mutation disrupts the interaction between the putative adaptor protein Moe and the apicobasal polarity regulator Crumbs (Crb), and impairs the maintenance of neuroepithelial apicobasal polarity. While Crb interacts directly with Notch and inhibits its activity, Moe reverses this inhibition.

Pyridylmethylthio derivatives as VEGF inhibitors: part 2.

Optimization of compounds 5 and 6 led to the discovery of VEGF inhibitor 10g which reduced CYP inhibition. It was highly active in vitro (VEGF induced HUVEC proliferation assay) and showed efficacies in three disease models in vivo (cancer, RA, and AMD).