Kanuma

Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1α release and iBALT formation, even long after particulate instillation...

Sebelipase alfa (Kanuma®, Kanuma™), the first commercially available recombinant human lysosomal acid lipase (LAL), is approved in various countries worldwide, including those of the EU, the USA and Japan, as a long-term enzyme replacement therapy for patients diagnosed with LAL deficiency (LAL-D), an ultra-rare, autosomal recessive, progressive metabolic liver disease. In an ongoing study in nine infants presenting with early-onset LAL-D (Wolman disease), open-label treatment with sebelipase alfa significantly improved 1-year survival compared with historical controls...

Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis...

OBJECTIVE: We retrospectively elucidated the oncological outcomes, prognostic factors and toxicities of proton beam therapy in trimodal bladder-preserving therapy for muscle-invasive bladder cancer at our institution. METHODS: From 1990 to 2015, 70 patients with cT2-3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal transurethral resection of the bladder tumor, small pelvis photon irradiation, intra-arterial chemotherapy and proton beam therapy...

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No abstract text is available yet for this article.

Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12...

CpG oligodeoxynucleotide (ODN) is one of promising nucleic acid-based adjuvants. We recently improved its ability to enhance CD8(+) T-cell responses to coadministered protein antigen without conjugation or emulsion, by forming a nanoparticulate complex between CpG ODN (K3) and mushroom-derived β-glucan schizophyllan (SPG), namely K3-SPG. Here, we sought to elucidate the cellular immunological mechanisms by which K3-SPG induce such potent CD8(+) T-cell responses to coadministered antigen. By focusing on two DC subsets, plasmacytoid DCs and CD8α(+) DCs, as well as the secreted cytokines, IFN-α and IL-12, we found that K3-SPG strongly activates mouse plasmacytoid DCs to secrete IFN-α and CD8α(+) DCs to secrete IL-12, respectively...

Sebelipase alfa (Kanuma™) is a recombinant human lysosomal acid lipase (LAL) developed by Synageva BioPharma Corp. (now Alexion Pharmaceuticals, Inc.) for long-term enzyme replacement therapy in patients with LAL deficiency. The agent, administered by intravenous infusion once weekly or once every other week, acts to replace the deficient enzyme activity in patients with LAL deficiency, reducing lysosomal lipid accumulation, and thereby improving disease-related abnormalities such as dyslipidaemia and liver abnormalities...

Melanin-concentrating hormone receptor 1 (MCH1 receptor) is known to be involved in the control of mood and stress, in addition to the regulation of feeding. Here, we report further evidence that the blockade of the MCH1 receptor exhibits antidepressant and anxiolytic-like effects in a variety of animal models using TASP0382650 and TASP0489838, newly synthesized MCH1 receptor antagonists, with different scaffolds. Both TASP0382650 and TASP0489838 exhibited high affinities for human MCH1 receptor with IC50 values of 7...

STATEMENT OF PROBLEM: Controlling tooth reduction for porcelain laminate veneers (PLVs) in fractions of millimeters is challenging. PURPOSE: The purpose of this study was to assess an automated robotic tooth preparation system for PLVs for accuracy and precision compared with conventional freehand tooth preparation. MATERIAL AND METHODS: Twenty maxillary central incisor tooth models were divided into 2 groups. Ten were assigned to a veneer preparation with a robotic arm according to preoperative preparation design-specific guidelines (experimental group)...

In the present study, a novel tablet porous material (TPM) was developed from Kanuma clay (K-clay), corn starch, and calcium oxide. Laboratory-scale batch experiments were conducted to evaluate the phosphate adsorption capacity of TPM from aqueous solution. The adsorption isotherms, adsorption kinetics, phosphate recycling, and major factors such as temperature, pH, and dosage were investigated. The phosphate adsorption results fitted the Freundlich isotherm model very well, and the adsorption process was an endothermic and spontaneous reaction which could be described by a pseudo second-order kinetic model...

A novel ceramic adsorbent was developed to adsorb ammonium from high concentration ammonium contaminated wastewater. Typical gardening cultivation mediums in Japan-Kanuma clay and Akadama clay were used to synthesize the ceramic adsorbent. Static batch experiments were conducted to investigate the effect of various parameters such as contact time, initial ammonium concentration, adsorbent dosage, and competing cations during the ammonium adsorption process. The results revealed that the Freundlich isotherm model fitted better with the adsorption process than the Langmuir model, and the adsorption process was well described by pseudo-second-order kinetic model...

OBJECTIVE: This study evaluated the usefulness of p16(INK4a)/Ki-67 as a new biomarker in the diagnosis of human papillomavirus (HPV)-related cervical lesions. STUDY DESIGN: From 69 women with previous positive cytology, clinician-collected (CC) samples were obtained using a Cervex-Brush®. One month later, self-collected (SC) material was acquired using a Rovers® Viba-Brush. Liquid-based cytology specimens were prepared from both samples, and then the grades of squamous intraepithelial lesions (SIL) were determined; following immunostaining with CINtec® PLUS, HPV status was analyzed using a linear array...

OBJECTIVE: This study compared the usefulness of self-collected (SC) and clinician-collected (CC) materials for cervical cytology and human papillomavirus (HPV) genotyping. STUDY DESIGN: Fifty women with previous positive cytology and who were undergoing regular checkups were included in the study. CC samples were collected using a Cervex-Brush Combi with liquid-based cytology. One month later, SC material was acquired using the Rovers Viba-brush vaginal sampler, and fixed at home...

Kanuma mud, a geomaterial, is used as an adsorbent for the removal of fluoride from water. The influences of contact time, solution pH, adsorbent dosage, initial fluoride concentration and co-existing ions were investigated by batch equilibration studies. The rate of adsorption was rapid with equilibrium being attained after about 2 h, and the maximum removal of fluoride was obtained at pH 5.0-8.0. The Freundlich isotherm model was found to represent the measured adsorption data well. The negative value of the thermodynamic parameter ΔG suggests the adsorption of fluoride by Kanuma mud was spontaneous, the endothermic nature of adsorption was confirmed by the positive ΔH value...

The clinical use of gene therapy requires tight regulation of the gene of interest and functional expression only when it is needed. Thus, it is necessary to develop ways of regulating functional gene expression with exogenous stimuli. Many regulatable systems are currently under development. For example, the tetracycline-dependent transcriptional switch has been successfully employed for in vivo preclinical applications. However, there are no examples of regulatable systems that have been employed in human clinical trials...

Overexpression of clusterin, an antiapoptotic molecule, has been reported to induce resistance to chemotherapy in a variety of cancer cell types. The aim of this study was to evaluate the significance of clusterin expression to predict response to platinum-based neoadjuvant chemotherapy and survival of patients with invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy specimens of invasive cervical cancer before neoadjuvant chemotherapy were obtained from 46 patients who subsequently underwent radical hysterectomy at Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007...

The glutamate hypothesis of schizophrenia suggests that hypofunction of N-methyl-D-aspartate (NMDA) receptors may be critical for schizophrenic symptoms; therefore, pharmacological approaches that enhance NMDA function may be beneficial for the treatment of schizophrenia. Several lines of evidence indicate that NMDA and metabotropic glutamate (mGlu) 5 receptors are closely associated signaling partners and that a selective mGlu5 receptor agonist might provide a viable approach for increasing NMDA receptor function in the treatment of schizophrenia...

A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1...