Increasing Incidence and Age at Onset of Amyotrophic Lateral Sclerosis in Nagano Prefecture, Japan

Article信州医学雑誌 64(5): 239-246(2016)journal articl

Calciphylaxis as a Catastrophic Complication in a Patient with POEMS Syndrome

Calciphylaxis is a vascular calcification-cutaneous necrosis syndrome, usually seen in patients with end-stage renal disease and secondary hyperparathyroidism. We report a 57-year-old polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome patient complicated with extensive skin ulcers due to calciphylaxis. He first noted a painful cutaneous ulcer on his left thigh, and then skin lesions rapidly worsened, resulting in multiple intractable ulcers with gangrene on his legs and trunk in a few months. Serum vascular endothelial growth factor (VEGF) was markedly elevated. Biopsy samples from his skin ulcers showed the deposition of calcium in the medial layer of cutaneous vessels, this finding being compatible with calciphylaxis. This is the second reported case with POEMS syndrome complicated with calciphylaxis. Both patients had no evidence of renal failure, hyperparathyroidism, or clotting disorders. The pathogenic link between POEMS syndrome and calciphylaxis is still unclear, but VEGF is known to regulate vascular calcification, in cooperation with bone morphogenetic proteins. Further, corticosteroid and several proinflammatory cytokines activate nuclear factor-κB pathway, known as the final common pathway leading to vascular calcification. Taken together, we consider that POEMS syndrome can be an independent risk condition for calciphylaxis

Bir kırmızı, bir sarı gül ve Gülbaba

Taha Toros Arşivi, Dosya Adı: Galatasarayİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Marked intrafamilial phenotypic variation in a family with SOD1 C111Y mutation

Our objectives were to identify the disease-causing mutation in, and report on the clinical features of, a Japanese family that had coexisting phenotypes of amyotrophic lateral sclerosis and spinal muscular atrophy. The family comprised nine patients (six men and three women). We reviewed their clinical records and performed mutation analysis of the copper/zinc superoxide dismutase (SOD1) gene in some of these patients. The patients either had a rapid (n = 7) or an extremely long (n = 2) clinical course. The mean age at onset was 39.0 +/- 13.7 years (range 20-68 years). The initial symptoms were bulbar palsy (n = 2), upper (n = 4) or lower (n = 2) limb muscle weakness, or leg cramps (n = 1). The total disease duration varied widely, ranging from one year to >69 years. We identified a SOD1 C111Y mutation among patients in this family. In conclusion, the family showed a marked intrafamilial phenotypic variation associated with the SOD1 C111Y mutation. Elucidating the biological basis of disease expression in patients with the SOD1 C111Y mutation may provide us with useful information to develop therapeutic approaches and to prevent disease progression.ArticleAMYOTROPHIC LATERAL SCLEROSIS. 13(5):479-486 (2012)journal articl

Long-lived neutral-kaon flux measurement for the KOTO experiment

The KOTO ($K^0$ at Tokai) experiment aims to observe the CP-violating rare decay $K_L \rightarrow \pi^0 \nu \bar{\nu}$ by using a long-lived neutral-kaon beam produced by the 30 GeV proton beam at the Japan Proton Accelerator Research Complex. The $K_L$ flux is an essential parameter for the measurement of the branching fraction. Three $K_L$ neutral decay modes, $K_L \rightarrow 3\pi^0$, $K_L \rightarrow 2\pi^0$, and $K_L \rightarrow 2\gamma$ were used to measure the $K_L$ flux in the beam line in the 2013 KOTO engineering run. A Monte Carlo simulation was used to estimate the detector acceptance for these decays. Agreement was found between the simulation model and the experimental data, and the remaining systematic uncertainty was estimated at the 1.4\% level. The $K_L$ flux was measured as $(4.183 \pm 0.017_{\mathrm{stat.}} \pm 0.059_{\mathrm{sys.}}) \times 10^7$ $K_L$ per $2\times 10^{14}$ protons on a 66-mm-long Au target.Comment: 27 pages, 16 figures. To be appeared in Progress of Theoretical and Experimental Physic

A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline

Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs

Ceruloplasmin Protects Against Rotenone-Induced Oxidative Stress and Neurotoxicity

To clarify the neuroprotective property of ceruloplasmin and the pathogenesis of aceruloplasminemia, we generated ceruloplasmin-deficient (CP−/−) mice on the C57BL/10 genetic background and further treated them with a mitochondrial complex I inhibitor, rotenone. There was no iron accumulation in the brains of CP−/− mice at least up to 60 weeks of age. Without rotenone treatment, CP−/− mice showed slight motor dysfunction compared with CP+/+ mice, but there were no detectable differences in the levels of oxidative stress markers between these two groups. A low dose of rotenone did not affect the mitochondrial complex I activity in our mice, however, it caused a significant change in motor behavior, neuropathology, or the levels of oxidative stress markers in CP−/− mice, but not in CP+/+ mice. Our data support that ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity, probably through its antioxidant properties independently of its function of iron metabolism

Evaluasi Rantai Pasok Beras Menggunakan Metode Fuzzy Analytical Network Process (FANP) (Studi Kasus Di Perum Bulog Sub Divre Wilayah VII, Malang)

Beras merupakan makanan pokok bagi masyarakat Indonesia yang berasal dari tanaman padi. Proses tanaman padi diubah menjadi beras hingga bisa sampai ke tangan konsumen memerlukan proses yang cukup panjang. Proses tersebut dapat melalui jalur swasta yang diawali dengan pengumpul-pengumpul di desa, perusahaan–perusahaan penggilingan padi, grosir dan berakhir oleh pedagang-pedagang eceran, atau melalui jalur pemerintah (BUMN) yaitu Perum BULOG. Evaluasi terhadap rantai pasok Raskin di Perum BULOG bertujuan untuk mengidentifikasi kendala dalam sistem rantai pasok beras pada Bulog Sub Divre VII Malang, menentukan kriteria yang digunakan sebagai dasar evaluasi rantai pasok beras menggunakan Fuzzy Analytical Network Process (FANP), serta menentukan pengaruh keterkaitan antar kriteria yang digunakan dalam evaluasi rantai pasok beras menggunakan Fuzzy Analytical Network Process (FANP). Metode Fuzzy Analytical Network Process (FANP) dapat memfasilitasi ketergantungan (dependensi) antara kriteria dengan kriteria maupun ketergantungan (interdependensi) antara kriteria dengan sub kriteria dalam menentukan bobot kepentingan. Analytic Network Process (ANP) yang diperkenalkan oleh Saaty adalah teknik pengambilan keputusan yang komprehensif sesuai untuk kedua jenis data kuantitatif dan kualitatif dan mampu mengatasi masalah ketergantungan dan umpan balik antara alternatif atau kriteria sehingga memudahkan analisis yang lebih sistematis. Teori fuzzy digunakan untuk membantu pemilihan alternatif dengan ANP apabila data-data atau informasi yang diberikan, baik oleh pengambil keputusan maupun data tentang atribut suatu alternatif tidak dapat disajikan xiv dengan lengkap, mengandung ketidakpastian atau ketidakkonsistenan Permasalahan rantai pasok Raskin ditinjau dari sisi Mitra Kerja Pengadaan (MKP) yaitu adanya faktor-faktor yang mempengaruhi mitra dalam memasok beras ke BULOG sedangkan kendala dalam sistem rantai pasok Raskin ditinjau dari sisi Perum BULOG yaitu adanya tuntutan kepada Perum BULOG sebagai perusahaan logistik untuk menyalurkan Raskin yang sesuai baik dari segi kualitas, jumlah, waktu dan tempat yang dikehendaki konsumen, secara aman, efektif dan efisien. Berdasarkan hasil pembobotan terhadap 15 sub kriteria yang digunakan untuk mengevaluasi faktor-faktor yang mempengaruhi Mitra Kerja Pengadaan (MKP) dalam memasok beras ke BULOG menurut kriteria QCDFR (Quality, Cost, Delivery, Flexibility), yang paling besar pengaruhnya adalah sub kriteria kesesuaian harga dengan biaya operasional (C3) (0,23790) disusul oleh respon mitra terhadap standar yang ditetapkan perusahaan (R3) (0,12936) dan loyalitas mitra (R2) (0,06940). Berdasarkan hasil pembobotan terhadap 17 sub kriteria yang digunakan untuk mengevaluasi Perum BULOG sebagai perusahaan logistik yang ditunjuk untuk menyalurkan Raskin ditinjau dari lima proses inti pada model SCOR meliputi perencanaan (plan), pengadaan (source), penyimpanan (make), penyaluran (deliver), serta pengembalian (return), yang paling besar pengaruhnya adalah sub kriteria pemantauan kualitas (C1) (0,21363), pemantauan umur simpan (C2) (0,16615), dan kesesuaian terhadap kualitas (B1) (0,14973)