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35 results on '"Osamu Sakamoto"'

1. Immunological assay using a solid-state pore with a low limit of detection

Author

Hiroyasu Takei, Tomoko Nakada, lat Wai Leong, Atsuki Ito, Kakeru Hanada, Hinako Maeda, Muhammad Shan Sohail, Kazuhiko Tomiyasu, Osamu Sakamoto, Norihiko Naono, and Masateru Taniguchi

Subjects
Medicine, Science
Abstract

Abstract Emerging infectious diseases, cancer, and other diseases are quickly tested mainly via immune reactions based on specific molecular recognition between antigens and antibodies. By changing the diameter of solid-state pores, biomolecules of various sizes can be rapidly detected at the single-molecule level. The combination of immunoreactions and solid-state pores paves the way for an efficient testing method with high specificity and sensitivity. The challenge in developing this method is achieving quantitative analysis using solid-state pores. Here, we demonstrate a method with a low limit of detection for testing tumor markers using a combination of immunoreactions and solid-state pore technology. Quantitative analysis of the mixing ratio of two and three beads with different diameters was achieved with an error rate of up to 4.7%. The hybrid solid-state pore and immunoreaction methods with prostate-specific antigen (PSA) and anti-PSA antibody-modified beads achieved a detection limit of 24.9 fM PSA in 30 min. The hybrid solid-state pore and immunoreaction enabled the rapid development of easy-to-use tests with lower limit of detection and greater throughput than commercially available immunoassay for point-of-care testing.

Published
2024
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2. Using novel micropore technology combined with artificial intelligence to differentiate Staphylococcus aureus and Staphylococcus epidermidis

Author

Ayumi Morimura, Masateru Taniguchi, Hiroyasu Takei, Osamu Sakamoto, Norihiko Naono, Yukihiro Akeda, Daisuke Onozuka, Jumpei Yoshimura, Kazunori Tomono, Satoshi Kutsuna, and Shigeto Hamaguchi

Subjects
Medicine, Science
Abstract

Abstract Methods for identifying bacterial pathogens are broadly categorised into conventional culture-based microbiology, nucleic acid-based tests, and mass spectrometry. The conventional method requires several days to isolate and identify bacteria. Nucleic acid-based tests and mass spectrometry are relatively rapid and reliable, but they require trained technicians. Moreover, mass spectrometry requires expensive equipment. The development of a novel, inexpensive, and simple technique for identifying bacterial pathogens is needed. Through combining micropore technology and assembly machine learning, we developed a novel classifier whose receiver operating characteristic (ROC) curve showed an area under the ROC curve of 0.94, which rapidly differentiated between Staphylococcus aureus and Staphylococcus epidermidis in this proof-of-concept study. Morphologically similar bacteria belonging to an identical genus can be distinguished using our method, which requires no specific training, and may facilitate the diagnosis and treatment of patients with bacterial infections in remote areas and in developing countries.

Published
2024
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3. Combining machine learning and nanopore construction creates an artificial intelligence nanopore for coronavirus detection

Author

Masateru Taniguchi, Shohei Minami, Chikako Ono, Rina Hamajima, Ayumi Morimura, Shigeto Hamaguchi, Yukihiro Akeda, Yuta Kanai, Takeshi Kobayashi, Wataru Kamitani, Yutaka Terada, Koichiro Suzuki, Nobuaki Hatori, Yoshiaki Yamagishi, Nobuei Washizu, Hiroyasu Takei, Osamu Sakamoto, Norihiko Naono, Kenji Tatematsu, Takashi Washio, Yoshiharu Matsuura, and Kazunori Tomono

Subjects
Science
Abstract

Rapid, accurate and specific point-of-care diagnostics can help manage and contain fast-spreading infections. Here, the authors present a nanopore-based system that uses artificial intelligence to discriminate between four coronaviruses in saliva, with little need for sample pre-processing.

Published
2021
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4. Hypoketotic hypoglycemia in citrin deficiency: a case report

Author

Yoichi Wada, Natsuko Arai-Ichinoi, Atsuo Kikuchi, Osamu Sakamoto, and Shigeo Kure

Subjects
Citrin deficiency, Hypoketotic hypoglycemia, Medium-chain triglyceride, Starvation test, SLC25A13, Pediatrics, RJ1-570
Abstract

Abstract Background Citrin deficiency (CD) is a recessive metabolic disease caused by biallelic pathogenic variants in SLC25A13. Although previous studies have reported ketosis in CD, it was observed at the time of euglycemia or mild hypoglycemia. Blood ketone levels concomitant with symptomatic or severe hypoglycemia in CD have not been a topic of focus despite its importance in identifying the etiology of hypoglycemia and assessing the ability of fatty acid utilization. Herein, we describe a patient with CD who had repeated episodes of hypoglycemia with insufficient ketosis. Case presentation A 1-year-old boy with repetitive hypoglycemia was referred to us to investigate its etiology. The fasting load for 13 h led to hypoketotic hypoglycemia, indicating the possibility of partial β-oxidation dysfunction. A genetic test led to the diagnosis of CD. The hypoglycemic episodes disappeared after switching to a medium-chain triglyceride-containing formula. Conclusions This case report suggests that symptomatic or severe hypoglycemia in patients with CD could be associated with relatively low levels of ketone bodies, implying that β-oxidation in these patients might possibly be partially disrupted. When encountering a patient with hypoglycemia, clinicians should check blood ketone levels and bear in mind the possibility of CD because excessive intravenous administration of glucose can cause decompensated symptoms in patients with CD as opposed to other disorders presenting with hypoketotic hypoglycemia, such as fatty acid oxidation disorders. Further studies in a large-scale cohort are warranted to confirm our speculation.

Published
2020
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5. Isovaleric acidemia: Therapeutic response to supplementation with glycine, l-carnitine, or both in combination and a 10-year follow-up case study

Author

Yasutsugu Chinen, Sadao Nakamura, Kunihito Tamashiro, Osamu Sakamoto, Kyoko Tashiro, Takahiro Inokuchi, and Koichi Nakanishi

Subjects
Isovaleric acidemia, Glycine, l-carnitine, Isovalerylcarnitine, Isovalerylglycine, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Isovaleric acidemia (IVA) is an organic acid disease caused by a deficiency of isovaleryl-CoA dehydrogenase. Deficiency of this enzyme leads to accumulation of organic acids, such as isovalerylcarnitine and isovalerylglycine. The proposed IVA treatments include leucine restriction and l-carnitine and/or glycine supplementation, which convert isovaleric acid into non-toxic isovalerylcarnitine and isovalerylglycine, respectively. We examined the therapeutic response using the leucine load test and performed a 10-year follow-up in the patient. Methods: We evaluated the patient with IVA beginning at 5 years of age, when he presented with a mild to intermediate metabolic phenotype. Ammonia, free carnitine, isovalerylcarnitine, and isovalerylglycine were analyzed in the urine and blood after a meal consisting of 1600 mg leucine with glycine alone (250 mg/kg/day), l-carnitine alone (100 mg/kg/day), or both glycine and l-carnitine for four days each. Results: (Leucine load test) Three hours after the meal, serum ammonia levels increased most dramatically with glycine treatment alone, then with both in combination, and least with l-carnitine alone. Urinary isovalerylglycine levels increased 2-fold more with glycine supplementation than those following supplementation with both agents or with l-carnitine alone. Treatment with both agents resulted in a gradual increase in urinary acylcarnitine levels during the 6-h period following the leucine load, reaching concentrations comparable to those observed with l-carnitine alone. (Clinical course) After initiation of both glycine (200 mg/kg/day) and l-carnitine (100 mg/kg/day) supplementation at 5 years of age, doses were gradually reduced to 111.7 mg/kg/day and 55.8 mg/kg/day, respectively, at 15 years of age. His mind and body had developed without any sequelae. Discussion: We concluded that l-carnitine conjugated isovaleric acid earlier than glycine. Additionally, during the 10-year follow-up period, the patient displayed no clinical deterioration.

Published
2017
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6. Mortality in rheumatoid arthritis patients with pulmonary nontuberculous mycobacterial disease: A retrospective cohort study.

Author

Shunsuke Mori, Yukinori Koga, Kazuyoshi Nakamura, Sayuri Hirooka, Takako Matsuoka, Hideshi Uramoto, Osamu Sakamoto, and Yukitaka Ueki

Subjects
Medicine, Science
Abstract

ObjectiveThe aim of this study was to compare long-term mortality following diagnosis of pulmonary nontuberculous mycobacterial (NTM) disease between patients with and without rheumatoid arthritis (RA) and to evaluate predictive factors for death outcomes.MethodsWe reviewed the electronic medical records of all patients who were newly diagnosed with pulmonary NTM disease at participating institutions between August 2009 and December 2018. Patients were followed until death, loss to follow-up, or the end of the study. Taking into consideration the presence of competing risks, we used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis.ResultsA total of 225 patients (34 RA patients and 191 non-RA controls) were followed, with a mean time of 47.5 months. Death occurred in 35.3% of RA patients and 25.7% of non-RA patients. An exacerbation of pulmonary NTM disease represented the major cause of death. The estimated cumulative incidence of all-cause death at 5 years was 24% for RA patients and 23% for non-RA patients. For NTM-related death, the 5-year cumulative incidence rate was estimated to be 11% for RA patients and 18% for non-RA patients. Gray's test revealed that long-term mortality estimates were not significantly different between patient groups. Fine-Gray regression analysis showed that the predictive factors for NTM-related death were advanced age (adjusted hazards ratio 7.28 [95% confidence interval 2.91-18.20] for ≥80 years and 3.68 [1.46-9.26] for 70-80 years vs. ConclusionsRA patients with pulmonary NTM disease were not at greater risk of long-term mortality compared with non-RA patients. Rather, advanced age, male sex, causative NTM species, and cavitary NTM disease should be considered when predicting the outcomes of RA patients with pulmonary NTM disease.

Published
2020
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8. Central Venous Catheter-Related Bloodstream Infection with Kocuria kristinae in a Patient with Propionic Acidemia

Author

Masato Kimura, Eichiro Kawai, Hisao Yaoita, Natsuko Ichinoi, Osamu Sakamoto, and Shigeo Kure

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Kocuria kristinae is a catalase-positive, coagulase-negative, Gram-positive coccus found in the environment and in normal skin and mucosa in humans; however, it is rarely isolated from clinical specimens and is considered a nonpathogenic bacterium. We describe a case of catheter-related bacteremia due to K. kristinae in a young adult with propionic acidemia undergoing periodic hemodialysis. The patient had a central venous catheter implanted for total parenteral nutrition approximately 6 months prior to the onset of symptoms because of repeated acute pancreatitis. K. kristinae was isolated from two sets of blood cultures collected from the catheter. Vancomycin followed by cefazolin for 16 days and 5-day ethanol lock therapy successfully eradicated the K. kristinae bacteremia. Although human infections with this organism appear to be rare and are sometimes considered to result from contamination, physicians should not underestimate its significance when it is isolated in clinical specimens.

Published
2017
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10. Methodology to Detect Biological Particles Using a Biosensing Surface Integrated in Resistive Pulse Sensing

Author

Yukichi Horiguchi, Norihiko Naono, Osamu Sakamoto, Hiroaki Takeuchi, Shoji Yamaoka, and Yuji Miyahara

Subjects
Influenza A Virus, H1N1 Subtype, Humans, General Materials Science, Biosensing Techniques
Abstract

Resistive pulse sensing (RPS) is an analytical method that can be used to individually count particles from a small sample. RPS simply monitors the physical characteristics of particles, such as size, shape, and charge density, and the integration of RPS with biosensing is an attractive theme to detect biological particles such as virus and bacteria. In this report, a methodology of biosensing on RPS was investigated. Polydopamine (PD), an adhesive component of mussels, was used as the base material to create a sensing surface. PD adheres to most materials, such as noble metals, metal oxides, semiconductors, and polymers; as a result, PD is a versatile intermediate layer for the fabrication of a biosensing surface. As an example of a biological particle, human influenza A virus (H1N1 subtype) was used to monitor translocation of particles through the pore membrane. When virus-specific ligands (6'-sialyllactose) were immobilized on the pore surface, the translocation time of the virus particles was considerably extended. The detailed translocation data suggest that the viral particles were trapped on the sensing surface by specific interactions. In addition, virus translocation processes on different pore surfaces were distinguished using machine learning. The result shows that the simple and versatile PD-based biosensor surface design was effective. This advanced RPS measurement system could be a promising analytical technique.

Published
2022
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11. Lung Adenocarcinoma with Chronic Lymphocytic Leukemia Mimicking Bone Metastasis: A Case Report

Author

Takako, Matsuoka, Aoi, Miyazaki, Sachiyo, Kosai, Kazuyoshi, Nakamura, Hideshi, Uramoto, Hironori, Kobayashi, and Osamu, Sakamoto

Subjects
Internal Medicine, General Medicine
Abstract

A 77-year-old man was referred to our hospital for abnormal thoracic radiographs. Computed tomography (CT) revealed a 20-mm subpleural ground-glass opacity in the right S

Published
2023
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13. Effect of a Psychiatric Department Liaison Team on Patient Treatment and Outcomes

Author

Osamu Sakamoto, Kousuke Hino, Emi Endo, Atsuhiko Watanabe, Yuichi Takahashi, and Munetaka Nomoto

Subjects
Psychiatry and Mental health, medicine.medical_specialty, business.industry, Family medicine, medicine, Patient treatment, business
Abstract

The objective of this study was to determine whether implementation of a psychiatric liaison team is effective for early intervention in patients who have risk factors and improvement of their outcomes. To accomplish this, the medical records of 1,263 inpatients undergoing psychiatric consultation before and after implementation of the liaison team were retrospectively compared. Comparison results showed increases in consultation requests, mainly due to increased referrals at the cardiovascular center (19.8% vs 33.3%), patients with delirium (44.5% vs 51.8%), and frequency of nurses' referrals (0% vs 26.7%); but significant decreases in waiting time before consultation request (11 vs 9 days), duration of hospital stay (36 vs 30 days), and incidents (number of falls and inadvertent tube removal) in patients with delirium before treatment (35.8% vs 26%) were also observed. A significant increase in the use of physical restraint (36.6% to 44.8%) was noted. The results of this study show that implementation of the psychiatric liaison team enabled early intervention and a reduction in delirium-associated incidents. [ Psychiatr Ann . 2020;50(8):355–363.]

Published
2020
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14. An Artificial Intelligence Nanopore Platform Detects Omicron SARS-CoV-2 in Clinical Samples

Author

Kaoru Murakami, Shimpei I. Kubota, Kumiko Tanaka, Keiichiro Akabane, Rigel Suzuki, Yuta Shinohara, Hiroyasu Takei, Shigeru Hashimoto, Yuki Tanaka, Shintaro Hojyo, Osamu Sakamoto, Norihiko Naono, Takayui Takaai, Kazuki Sato, Yuichi Kojima, Toshiyuki Harada, Takeshi Hattori, Satoshi Fuke, Isao Yokota, Satoshi Konno, Takashi Washio, Takasuke Fukuhara, Takanori Teshima, Masateru Taniguchi, and Masaki Murakami

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2022
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15. Hypoglycemic attacks and growth failure are the most common manifestations of citrin deficiency after 1 year of age

Author

Shigeo Kure, Natsuko Arai-Ichinoi, Yoichi Wada, Atsuo Kikuchi, and Osamu Sakamoto

Subjects
Male, Pediatrics, medicine.medical_specialty, Adolescent, Encephalopathy, Jaundice, Mitochondrial Membrane Transport Proteins, Food Preferences, Japan, Genetics, medicine, Humans, Child, Genetics (clinical), Mass screening, Growth Disorders, Dyslipidemias, Citrullinemia, business.industry, Liver Diseases, Infant, Hyperammonemia, medicine.disease, Hypoglycemia, Failure to Thrive, Low birth weight, Child, Preschool, Failure to thrive, Mutation, Female, medicine.symptom, business, Dyslipidemia
Abstract

Citrin deficiency develops in different symptomatic periods from the neonatal period to adulthood. Some infantile patients are diagnosed by newborn mass screening or symptoms of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), some patients in childhood may develop hepatopathy or dyslipidemia as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some adults are diagnosed after developing adult-onset type 2 citrullinemia (CTLN2) with hyperammonemia or encephalopathy. A diagnosis is needed before the development of severe phenotypic CTLN2 but is often difficult to obtain because newborn mass screening cannot detect all patients with citrin deficiency, and undiagnosed patients often appear healthy in childhood. There are only a few reports that have described patients in childhood. To explore the clinical features of undiagnosed patients with citrin deficiency in childhood, we studied 20 patients who were diagnosed after the first year of life. Of these patients, 45% experienced hypoglycemic attacks in childhood. The acetoacetic acid level during hypoglycemic attacks was lower than expected. Growth failure at diagnosis (45%) was also noted. From the patients' history, fat- and protein-rich food preferences (80%), a low birth weight (70%), and prolonged jaundice or infantile hepatopathy (40%), were identified. To diagnose citrin deficiency in childhood, we should ask about food preferences and a history of infantile hepatopathy for all children with severe hypoglycemia or growth failure and consider the genetic test for citrin deficiency if the patient has characteristic food preferences or a history of infantile hepatopathy. This article is protected by copyright. All rights reserved.

Published
2021

16. An artificial intelligence nanopore platform for SARS-CoV-2 virus detection

Author

Kazunori Tomono, Yoshiharu Matsuura, Osamu Sakamoto, Kenji Tatematsu, Hiroyasu Takei, Rina Hamajima, Nobuaki Hatori, Yutaka Terada, Takeshi Kobayashi, Shohei Minami, Norihiko Naono, Yuta Kanai, Ayumi Morimura, Yoshiaki Yamagishi, Taniguchi Masateru, Nobuei Washizu, Yukihiro Akeda, Wataru Kamitani, Shigeto Hamaguchi, Chikako Ono, Takashi Washio, and Koichiro Suzuki

Subjects
Nanopore, Computer science, viruses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Virology, Virus detection
Abstract

High-throughput, high-accuracy detection of emerging viruses allows for pandemic prevention and control. Currently, reverse transcription-polymerase chain reaction (RT-PCR) is used to diagnose the presence of SARS-CoV-2. The principle of the test is to detect RNA in the virus using a pair of primers that specifically binds to the base sequence of the viral RNA. However, RT-PCR is a sophisticated technique requiring a time-consuming pretreatment procedure for extracting viral RNA from clinical specimens and to obtain high sensitivity. Here, we report a method for detecting novel coronaviruses with high sensitivity using artificial intelligent nanopores utilizing a simple procedure that does not require RNA extraction. Artificial intelligent nanopore platform consists of machine learning software on the servers, portable high-speed and high-precision current measuring instrument, and scalable, cost-effective semiconducting nanopore modules. Here we show that the artificial intelligent nanopores are successful in accurate identification of four types of coronaviruses, HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2, which are usually extremely difficult to detect. The positive/negative diagnostics of the new coronavirus is achieved with a sensitivity of 95 % and specificity of 92 % with a 5-minute diagnosis. The platform enables high throughput diagnostics with low false negatives for the novel coronavirus.

Published
2020
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17. Benralizumab for the Prevention of COPD Exacerbations

Author

Criner, G. J., Celli, B. R., Brightling, C. E., Agusti, A., Papi, A., Singh, D., Sin, D. D., Vogelmeier, C. F., Sciurba, F. C., Bafadhel, M., Backer, V., Kato, M., Ramirez-Venegas, A., Wei, Y. -F., Bjermer, L., Shih, V. H., Jison, M., O'Quinn, S., Makulova, N., Newbold, P., Goldman, M., Martin, U. J., GALATHEA Study Investigators, TERRANOVA Study Investigators, Otto, Burghuber, Bernhard, Forstner, Gerhard, Köberl, Bernd, Lamprecht, Judith, Löffler-Ragg, Horst, Olschewski, Michael, Studnicka, Francois, Beaucage, Guy, Chouinard, Anthony, Dechant, Anthony, Dowell, Jacques, Hebert, Sohail, Khattak, Kieran, Killian, William, Killorn, Andy, Lam, Francois, Maltais, Darcy, Marciniuk, Lyle, Melenka, Bonavuth, Pek, Jeremy, Road, Donald, Sin, Alain, Vaugeois, Brandie, Walker, Tomas, Dvorak, Stanislav, Holub, Otakar, Hokynar, Vitezslav, Kolek, Daniela, Kopecka, Jan, Krepelka, Jaroslav, Mares, Josef, Veverka, Vladimir, Zindr, Sabine, Ballenberger, Rolf, Dichmann, Christian, Geßner, Margret, Jandl, Claus, Keller, Joachim, Kirschner, Marc, Kornmann, Petra, Mikloweit, Ingomar, Naudts, Axel, Overlack, Isabelle, Schenkenberger, Volker, Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan, Zielen, István, Albert, Beatrix, Bálint, Mária Csilla Hangonyi, Teréz, Kecskés, Anikó, Kurucz, Balázs, Medgyasszay, Lajos, Molnár, János, Mucsi, Márta, Papp, Magdolna, Póczi, Éva, Radeczky, Zsolt Pápai Székely, Csilla, Szabó, Gyöngyi, Szabó, Melinda, Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio, Donazzan, Federica, Meloni, Elisabetta, Pace, Pierluigi, Paggiaro, Alberto, Papi, Ricciardolo, Fabio Luigi Massimo, Antonio, Spanevello, Fumiaki, Aoki, Ryosuke, Eda, Takeo, Endo, Yasushi, Fukushima, Kenichi, Gemba, Naoki, Hagimoto, Hiromasa, Harada, Yasuko, Harada, Norihiko, Hata, Osamu, Hataji, Nobuo, Hatakeyama, Takahiko, Horiguchi, Gen, Ideura, Motoyasu, Iikura, Azusa, Ikegami, Shirou, Imokawa, Yoshikazu, Inoue, Takeshi, Isobe, Ryoji, Ito, Susumu, Iwata, Tadashi, Kamei, Motokazu, Kato, Hideki, Katsura, Yuji, Kawarada, Norio, Kihara, Masaharu, Kinoshita, Takashi, Kinoshita, Tomoo, Kishaba, Hideo, Kita, Arihiro, Kiyosue, Shigeru, Komatsu, Kazuki, Konishi, Sekiya, Koyama, Makoto, Kudo, Kazuhiko, Machida, Hironi, Makita, Hiroto, Matsuse, Naoki, Miyazawa, Hiroyuki, Nakamura, Yuji, Nakatani, Kazuyuki, Nishimura, Takashi, Nishimura, Junichi, Ogawa, Hiroyuki, Ohbayashi, Tetsuro, Ohdaira, Tsukasa, Ohnishi, Kazuhiko, Oki, Masahiko, Saito, Kenji, Sakamoto, Osamu, Sakamoto, Hisakuni, Sekino, Noriharu, Shijubo, Masaharu, Shinkai, Hideo, Soto, Yoshitaka, Sugawara, Noriaki, Suko, Hisaho, Takahashi, Masamitsu, Takahashi, Tsuneyuki, Takahashi, Hiroshi, Tanaka, Hiroyuki, Taniguchi, Tadayuki, Terada, Takao, Tochigi, Kazuyo, Tohyama, Hirokazu, Tokuyasu, Keisuke, Tomii, Tomomasa, Tsuboi, Mitsuyoshi, Utsugi, Katsumaru, Yamamoto, Michiko, Yamamoto, Shuichi, Yano, Makoto, Yoshida, Frank, Custers, Richard, Dekhuijzen, Remco, Djamin, Jan Willem Van Dan Berg, Lowie, Vanfleteren, Pascal, Wielders, Bogusława, Cimoszko, Anna, Doboszyńska, Andrzej, Dyczek, Andrzej, Fal, Krystyna, Folcik, Łukasz, Goliński, Marek, Jutel, Andrzej, Kolczyński, Piotr, Kuna, Ewa, Łączyńska, Wojciech, Machowiak, Maciej, Marczak, Joanna, Markiewicz, Janusz, Milanowski, Grzegorz, Mincewicz, Maria, Nittner-Marszalska, Wojciech, Papiewski, Małgorzata, Pawlukiewicz, Witold, Pomiećko, Barbara, Rewerska, Cezary, Rybacki, Wojciech, Skucha, Ewa, Trębas-Pietraś, Ewa, Uhryn, Małgorzata, Żurowska-Gębala, Laurentia, Andrei, Traian, Mihaescu, Stefan, Mihaicuta, Eniko Vera Pall, Ioan, Petrui, Angelica, Savu, Claudia, Toma, Ana, Trailescu, Vladimir, Abrosimov, Nataliya, Astafyeva, Evgenyi, Bazdyrev, Nadezhda, Berdnikova, Laura, Bolieva, Ekaterina, Bukreeva, Valery, Chistyakov, Anna, Galustyan, Halida, Gantseva, Svetlana, Goncharova, Sergey, Grigoriev, Galina, Ignatova, Inna, Ilyashevich, Nadezhda, Izmozherova, Magomed, Kamalov, Yaroslava, Khovaeva, Natalia, Kuzubova, Lyudmila, Kvitkova, Liudmila, Lenskaya, Igor, Leshchenko, Olga, Magnitskaya, Boris, Molotilov, Artem, Molotkov, Svetlana, Myasoedova, Sergey, Nedogoda, Vladimir, Nosov, Marina, Osipenko, Andrey, Peskov, Veronika, Popova, Oksana, Ratushnay, Irina, Ryzhova, Olga, Shangina, Natalia, Shaporova, Evgeny, Shmelev, Lybov, Shpagina, Alexander, Shutkin, Yuri, Shvarts, Mikhail, Smirnov, Irina, Stitsenko, Maksim, Vasilev, Arkadiy, Vertkin, Elena, Vishneva, Alexander, Vizel, Anna, Zateyschikova, Mohamed, Abdool-Gaffar, Ismail, Abdullah, Axel, Bruning, Nyda, Fourie, Michael, Greenblatt, Mohammed, Tayob, Venter, K, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin, Brutsche, Michael, Grob, Jörg, Leuppi, Daiana, Stolz, Alexander, Turk, Nawar, Bakerley, Mona, Bafadhel, Christopher, Brightling, Rekha, Chaudhuri, Gourab, Choudhury, Graham, Devereux, Imran, Hussain, Kai, Lee, William, Macnee, Ravindran, Mahadeva, Matthew, Masoli, Monica, Nordstrom, Manish, Patel, Allan, Reid, Dinesh, Saralaya, Tariq, Sethi, Sukh Dave Singh, Anthony, G de Soyza, Tom, Wilkinson, Alice, Turner, Helen, Ward, Chandar, Abboy, Ivan, Ackerman, Idalia, Acosta, Arun, Adlakha, Bassil, Aish, Mohamed, Ali, Charles, Andrews, Robby, Ayoub, Anil, Badhwar, Dennis, Bassetti, Sherif El Bayadi, Richard, Beasley, Shashi, Bellam, Jonathan, Bernstein, Maria, Blahey, Scott, Bloom, Eugene, Bleecker, Wesley, Bray, Johnathan, Brewer, Robert, Buynak, William, Calhoun, Edward, Campbell, Anthony, Captain, Birjis, Chinoy, Kenneth, Chinsky, Geoffrey, Chupp, Arsenio, Columbie, Clinton, Corder, Gerard, Criner, Humberto, Cruz, Edward, Cullen, Kevin, Deboer, Michael, Denenberg, Mark, Dransfield, Leonard, Dunn, Miles, Elmore, David, Erb, Faisal, Fakih, Gary, Ferguson, Charles, Fogarty, Mark, Freed, Stephen, Fritz, David, Fuentes, Shariar, Cohen-Gadol, Robert, Garver, John, Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert, Gordon, Gregory, Gottschlich, Donald, Graham, David, Grant, Gary, Greenwald, James, Greenwald, Kenneth, Haft, Gregory, Hammond, Nadia, Hansel, Jeffrey, Harris, Humberto, Hernandez, Marvin, Heuer, Albrecht, Heyder, David, Hill, Willis, Holloway, Octavian, Ioachimescu, Richard, Jackson, Ajay, Jain, Nan, Jiang, Thomas, Kaelin, Adolfo, Kaplan, Mitchell, Kaye, Akram, Khan, Yekaterina, Khronusova, Ryan, Klein, Joel, Kline, Firas, Koura, Ritsu, Kuno, Ware, Kuschner, Jean Claude Labissiere, David Laman Jr, John, Lee, Mitchell, Lee, Lawrence, Levinson, Njira, Lugogo, Mador, M, Nathaniel, Marchetti, Rafael, Martinez, Richard, Martinez, Peter, Mattar, David, Maybee, Dennis, Mcgraw, Michael, Mcguire, Curtis, Mello, Aaron, Milstone, John, Mitchell, Wendy, Moore, Timothy, Moriarty, Cheta, Nand, Brooke, Nevins, Ikeadi, Ndukwu, Rachel, Nisbet, David, Nyanjom, Maria, Nualart, Thomas, O'Brien, Mikhail, Palatnik, Gnyandev, Patel, Amit, Patel, Guido, Perez, Christopher, Perry, Michael, Pfeffer, Krishna, Pudi, Marina, Raikhel, Murali, Ramaswamy, Joe, Ramsdell, Donato, 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Filiz Kosar, Hakan Gunen, Ismail Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel Nayci, Serir Aktogu Ozkan, Abdullah Sayiner, Esra Uzaslan, Viktor Blazhko, Volodymyr Gavrysyuk, Olena Golub, Liudmyla Iashyna, Tetiana Ilashchuk, Volodymyr Koshlia, Olena Krakhmalova, Vitali Kryvenko, Lesia Kuryk, Olena Levchenko, Yuriy Mostovoy, Mykola Ostrovskyy, Tetyana Pertseva, Olena Piura, Nadiya Rudnytska, Ganna Stupnytska, Nataliia Velychko, Oleh Yakovenko, Lilia Rodriguez Ables, Roger Abrahams, Bassil Aish, Jose Alvarez, Fernando Arencibia, Chander Arora, Samir Arora, Francis Averill, Kwabena Ayesu, Stephen Basheda, Steven Bauer, Jose Bautista, Matthew Beacom, Richard Beasley, Hernando Bernal, Subodh Bhuchar, J'Cinda Bitters, John Burk, Elizabeth Burkett, James Cain, Robert Call, Christopher Chappel, Bartolome Celli, Tom Christensen, Jeremy Cole, Jerome Daniel, Nguyen Dang, Enrique Davis, Samuel Deleon, Robert DeLuca, Ernesto Diaz, Anthony DiMarco, Calvin Dixon, Ankur Doshi, Hugh Durrence, Alain Eid, John Elsen, Herbon Fleming, May Flores, Charles Fogarty, Scott Franczek, Stephen Fritz, Gregory Funk, Stuart Garay, Bernard Garcia, Luis Ramos Gonez, Gregory Gottschlich, Joseph Graif, Carl Griffin, Yamirka Duardo Guerra, David Headley, Mitzie Hewitt, Susan Hole, Robert Holladay, Ira Horowitz, Yu-Luen Hsu, Jonathan Ilowite, Stephen Jones, Ravindra Kashyap, Edward Kerwin, Ahtaram Khan, Nicole Kimzey, James Krainson, Flory Kreutter, Kannappan Krishnaswamy, Shahrukh Kureishy, Albert Lai, Alex Lechin, Daria Lee, Marcus Lee, Williams Leeds, Joseph Lillo, Edward Lisberg, Lawrence Madoff, Narendra Maheskwari, Mujibur Majumder, Sashi Makam, Douglas Mapel, Matthew Mardiney, Jennifer Martin, David Maybee, Isaac Melamed, Elvin Mendez, Stuart Millstone, Joseph Montes, Lee Morrow, Frank Murphy, Dany Obeid, France Occy, Godson Oguchi, Juan Ortiz, Francisco Padron, Ward Paine, James Pearle, Enrique Pelayo, Vandely Perez, David Pham, Carlos Piniella, Kevin Pritchett, Padmashri Rastogi, Stephen Ryan, Syed Rehman, Jackson Rhudy, Eustace Riley, James Riser, Clifford Risk, Emory Robinette, Christopher Roney, Gary Ruoff, David Russian, Mercedes Samson, Jay Sandberg, Jose Santiago, William Sargeant, Alan Schecter, Frank Sciurba, Jeffrey Scott, Ilia Segal, Sudhir Sehgal, Frederic Seifer, Sudhir Sekhsaria, Richard Sellman, Paul Shapero, Jeffrey Shea, Lawrence Sher, John Sibille, Jawed Siddiqui, William Sims, Toniya Singh, Deren Sinkowitz, Denise Smyth, Daniel Soteres, Daniel Sousa, Ralph Steele, Thomas Stern, Jose Suarez, Sever Surdulescu, Ricardo Tan, Tonny Tanus, Raymond Tidman, Aurelio Torres-Consuegra, Barry Troyan, John Updegrove, Sanjay Vadgama, Armando Pineda-Velez, Eduardo Viera, Andrew Wachtel, Ralph Wade, Jimin Wang, Dave Webster, Paul Weinberg, Terry Wells, Jeffrey White, Bram Wieskopf, Hugh Windom, Patrick Wright, David Wyatt, Bassam Yousef, Zahid Zafar, Chau Ngo, Huong Le, Lan Nguyen, Thanh Nguyen, Nhung Nguyen

Subjects
Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Anti-asthmatic Agent, law.invention, Pulmonary Disease, Chronic Obstructive, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Humanized, COPD Exacerbations, benralizumab, clinical trials, COPD, Subcutaneous, General Medicine, Middle Aged, anti–IL-5Rα, Benralizumab, Pulmonary Disease, Chronic Obstructive/drug therapy, [SDV] Life Sciences [q-bio], Female, Antibodies, Monoclonal, Humanized/administration & dosage, Chronic Obstructive, Benralizumab COPD exacerbations, Injections, Subcutaneous, Socio-culturale, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Eosinophils, Humans, Patient Acuity, Receptors, Interleukin-5, Antibodies, chronic obstructive pulmonary disease, Injections, Pulmonary Disease, 03 medical and health sciences, Phase III, Anti-Asthmatic Agents/administration & dosage, In patient, business.industry, Eosinophils/metabolism, medicine.disease, Clinical trial, Receptors, Interleukin-5/antagonists & inhibitors, chemistry, Multicenter study, randomized controlled trial, Immunology, Interleukin-5, business
Abstract

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Published
2019
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18. Isovaleric acidemia: Therapeutic response to supplementation with glycine, l-carnitine, or both in combination and a 10-year follow-up case study

Author

Kunihito Tamashiro, Yasutsugu Chinen, Osamu Sakamoto, Kyoko Tashiro, Sadao Nakamura, Takahiro Inokuchi, and Koichi Nakanishi

Subjects
0301 basic medicine, medicine.medical_specialty, Urinary system, Glycine, Urine, Isovalerylcarnitine, 03 medical and health sciences, Endocrinology, Internal medicine, Genetics, medicine, Carnitine, Molecular Biology, lcsh:QH301-705.5, chemistry.chemical_classification, Meal, lcsh:R5-920, Chemistry, Isovalerylglycine, Isovaleric acidemia, Isovaleric Acidemia, l-carnitine, 030104 developmental biology, Enzyme, lcsh:Biology (General), Leucine, lcsh:Medicine (General), medicine.drug, Research Paper
Abstract

Isovaleric acidemia (IVA) is an organic acid disease caused by a deficiency of isovaleryl-CoA dehydrogenase. Deficiency of this enzyme leads to accumulation of organic acids, such as isovalerylcarnitine and isovalerylglycine. The proposed IVA treatments include leucine restriction and l-carnitine and/or glycine supplementation, which convert isovaleric acid into non-toxic isovalerylcarnitine and isovalerylglycine, respectively. We examined the therapeutic response using the leucine load test and performed a 10-year follow-up in the patient. Methods:We evaluated the patient with IVA beginning at 5 years of age, when he presented with a mild to intermediate metabolic phenotype. Ammonia, free carnitine, isovalerylcarnitine, and isovalerylglycine were analyzed in the urine and blood after a meal consisting of 1600 mg leucine with glycine alone (250 mg/kg/day), l-carnitine alone (100 mg/kg/day), or both glycine and l-carnitine for four days each. Results:(Leucine load test) Three hours after the meal, serum ammonia levels increased most dramatically with glycine treatment alone, then with both in combination, and least with l-carnitine alone. Urinary isovalerylglycine levels increased 2-fold more with glycine supplementation than those following supplementation with both agents or with l-carnitine alone. Treatment with both agents resulted in a gradual increase in urinary acylcarnitine levels during the 6-h period following the leucine load, reaching concentrations comparable to those observed with l-carnitine alone. (Clinical course) After initiation of both glycine (200 mg/kg/day) and l-carnitine (100 mg/kg/day) supplementation at 5 years of age, doses were gradually reduced to 111.7 mg/kg/day and 55.8 mg/kg/day, respectively, at 15 years of age. His mind and body had developed without any sequelae. Discussion:We concluded that l-carnitine conjugated isovaleric acid earlier than glycine. Additionally, during the 10-year follow-up period, the patient displayed no clinical deterioration., 論文

Published
2017

19. Reversible brain atrophy in glutaric aciduria type 1

Author

Yukimune Okubo, Shigeo Kure, Yoshitsugu Oikawa, Yurika Numata-Uematsu, Yosuke Kakisaka, Mitsugu Uematsu, Natsuko Arai-Ichinoi, and Osamu Sakamoto

Subjects
0301 basic medicine, medicine.medical_specialty, Glutaric aciduria type 1, Lesion, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Developmental Neuroscience, Internal medicine, medicine, Humans, Carnitine, Amino Acids, Dried blood, Operculum (brain), Amino Acid Metabolism, Inborn Errors, Glutaryl-CoA Dehydrogenase, Brain Diseases, Metabolic, business.industry, Metabolic disorder, Brain, General Medicine, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), medicine.symptom, Dietary modifications, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. The typical clinical onset features an acute encephalopathic crisis developed in early childhood, causing irreversible striatal injury. Recently, tandem mass spectrometry of spots of dried blood has allowed pre-symptomatic detection of GA1 in newborns. Early treatment can prevent irreversible neurological injury. We report the case of a girl with GA1 who exhibited a characteristic reversible change upon brain magnetic resonance imaging (MRI). She was diagnosed with GA1 as a newborn. She commenced dietary carnitine and her intake of lysine and tryptophan were reduced at the age of 4weeks. After treatment commenced, her mean glutarylcarnitine level was lower than that in the previous reports. The plasma lysine and tryptophan levels were maintained below the normal ranges. At 4months, brain MRI revealed a widened operculum with dilatation of the subarachnoid spaces surrounding the atrophic bilateral frontotemporal lobes; this is typical of GA1 patients. However, at 17months, MRI revealed that the atrophic lesion had disappeared and she subsequently underwent normal maturation. She has never suffered a metabolic decompensation episode. At 26months, her development and brain MRI were normal. The present reversible brain atrophy in a patient with GA1 indicates that early dietary modifications with a lower level of glutarylcarnitine and administration of carnitine can lead to normal development.

Published
2017
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20. Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2

Author

Toshihiro Ohura, Yoshiyuki Okano, Osamu Sakamoto, and Ayano Inui

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Diet therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Organic Anion Transporters, 030105 genetics & heredity, Hypoglycemia, Liver transplantation, Biochemistry, Gastroenterology, Mitochondrial Membrane Transport Proteins, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Cholestasis, Internal medicine, Genetics, Medicine, Humans, Molecular Biology, Triglycerides, Citrullinemia, biology, business.industry, Fatty liver, Calcium-Binding Proteins, Infant, Newborn, Vitamins, medicine.disease, Liver Transplantation, Fatty Liver, Citrin, Failure to thrive, biology.protein, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Identification of the genes responsible for adult-onset type II citrullinemia (CTLN2) and citrin protein function have enhanced our understanding of citrin deficiency. Citrin deficiency is characterized by 1) neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD); 2) adaptation/compensation stage with unique food preference from childhood to adulthood; and 3) CTLN2. The treatment of NICCD aims to prevent the progression of cholestasis, and it includes medium chain triglycerides (MCT) milk and lactose-free milk, in addition to medications (e.g., vitamin K2, lipid-soluble vitamins and ursodeoxycholic acid). Spontaneous remission around the age of one is common in NICCD, though prolonged cholestasis can lead to irreversible liver failure and may require liver transplantation. The adaptation/compensation stage (after one year of age) is characterized by the various signs and symptoms such as hypoglycemia, fatty liver, easy fatigability, weight loss, and neuropsychiatric symptoms. Some poorly-controlled patients show failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). Diet therapy is the key in the adaptation/compensation stage. Protein- and fat-rich diet with a protein: fat: carbohydrate ratio being 15-25%: 40-50%: 30-40% along with the appropriate energy intake is recommended. The use of MCT oil and sodium pyruvate is also effective. The toxicity of carbohydrate is well known in the progression to CTLN2 if the consumption is over a long term or intense. Alcohol can also trigger CTLN2. Continuous intravenous hyperalimentation with high glucose concentration needs to be avoided. Administration of Glyceol® (an osmotic agent containing glycerol and fructose) is contraindicated. Because the intense treatment such as liver transplantation may become necessary to cure CTLN2, the effective preventative treatment during the adaptation/compensation stage is very important. At present, there is no report of a case with patients reported having the onset of CTLN2 who are on the diet therapy and under the appropriate medical support during the adaptation/compensation stage.

Published
2019

22. Seventeen Novel Mutations in PCCA and PCCB Genes in Indian Propionic Acidemia Patients, and Their Outcomes

Author

Renu Saxena, Roumi Deb, Sunita Bijarnia-Mahay, Neerja Gupta, Yosuke Shigematsu, Ishwar Chander Verma, Deepti Gupta, Madhulika Kabra, Seiji Yamaguchi, Ratna Dua Puri, Osamu Sakamoto, Sudha Kohli, and Seema Thakur

Subjects
Male, 0301 basic medicine, Methylmalonyl-CoA Decarboxylase, Propionic Acidemia, India, 030105 genetics & heredity, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, 03 medical and health sciences, symbols.namesake, Asian People, Polymorphism (computer science), medicine, Humans, Genetic Predisposition to Disease, Propionic acidemia, Allele, Gene, Alleles, Genetics (clinical), Sequence Deletion, G alpha subunit, Genetics, Sanger sequencing, Mutation, Infant, Newborn, Infant, General Medicine, medicine.disease, Protein Subunits, 030104 developmental biology, Child, Preschool, symbols, Female, Methylmalonyl-CoA decarboxylase
Abstract

The goal of this study was to identify mutations in the propionyl-CoA carboxylase alpha subunit (PCCA) and propionyl-CoA carboxylase beta subunit (PCCB) genes, and to assess their effects on propionic academia (PA) patients.Twenty-five Indian children with PA were enrolled in this study. Bidirectional Sanger sequencing was performed on both the coding and flanking regions of the PCCA and PCCB genes and the chromatograms were analyzed. Bioinformatic tools were used to classify novel variations into pathogenic or benign.The majority of the cases (19/25, 76%) were of the early-onset (90 days of age) type and 5 were of the late-onset type. The majority of patients had mutations in the PCCA gene (18/25). A total of 26 mutations were noted: 20 in the PCCA gene and 6 in PCCB gene. Seventeen mutations were novel (14 in PCCA and 3 in PCCB). The SNP c.937CT (p.Arg313Ter), was noted in 9/36 (25%) alleles in the PCCA gene. All of the children were symptomatic and only three survived who are doing well with no major disabilities.The spectrum of mutations in the PCCA and PCCB genes among Indians is distinct from other populations. The absence of a common mutation signifies the heterogeneity and admixture of various subpopulations. These findings also suggest that individuals of Indian origin may not benefit from the mutation-based "carrier screening panels" offered by many genetic laboratories.

Published
2016
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23. Correction: Biallelic GALM pathogenic variants cause a novel type of galactosemia

Author

Matsuyuki Shirota, Natsuko Arai-Ichinoi, Erika Ogawa, Osamu Ohara, Keiko Nakayama, Toshiyuki Fukao, Yoko Nakajima, Masayuki Yamamoto, Hideo Sasai, Osamu Sakamoto, Yoichi Wada, Hiromi Nyuzuki, Ryoji Fujiki, Atsuo Kikuchi, Mika Ishige, Yusuke Takezawa, Hiroki Hirai, Shinya Iwasawa, Ryo Funayama, Yoko Aoki, Tetsuya Ito, Shigeo Kure, Tetsuya Niihori, and Seizo Koshiba

Subjects
Genetics, business.industry, Galactosemia, medicine, medicine.disease, business, Genetics (clinical)
Published
2020
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24. Biallelic GALM pathogenic variants cause a novel type of galactosemia

Author

Hideo Sasai, Yoichi Wada, Matsuyuki Shirota, Osamu Ohara, Ryo Funayama, Atsuo Kikuchi, Hiromi Nyuzuki, Ryoji Fujiki, Toshiyuki Fukao, Osamu Sakamoto, Mika Ishige, Yusuke Takezawa, Shigeo Kure, Tetsuya Niihori, Hiroki Hirai, Yoko Aoki, Tetsuya Ito, Shinya Iwasawa, Seizo Koshiba, Erika Ogawa, Natsuko Arai-Ichinoi, Masayuki Yamamoto, Keiko Nakayama, and Yoko Nakajima

Subjects
0301 basic medicine, Galactosemias, Male, Biology, Peripheral blood mononuclear cell, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, education, Genetics (clinical), Exome sequencing, Alleles, Sanger sequencing, chemistry.chemical_classification, education.field_of_study, Base Sequence, Galactosemia, Galactose, Genetic Variation, Infant, medicine.disease, Molecular biology, eye diseases, Leloir pathway, 030104 developmental biology, Enzyme, chemistry, Child, Preschool, symbols, Female, Galactose mutarotase, Carbohydrate Epimerases, 030217 neurology & neurosurgery
Abstract

Galactosemia is caused by metabolic disturbances at various stages of galactose metabolism, including deficiencies in enzymes involved in the Leloir pathway (GALT, GALK1, and GALE). Nevertheless, the etiology of galactosemia has not been identified in a subset of patients. This study aimed to explore the causes of unexplained galactosemia. Trio-based exome sequencing and/or Sanger sequencing was performed in eight patients with unexplained congenital galactosemia. In vitro enzymatic assays and immunoblot assays were performed to confirm the pathogenicity of the variants. The highest blood galactose levels observed in each patient were 17.3–41.9 mg/dl. Bilateral cataracts were observed in two patients. In all eight patients, we identified biallelic variants (p.Arg82*, p.Ile99Leufs*46, p.Gly142Arg, p.Arg267Gly, and p.Trp311*) in the GALM encoding galactose mutarotase, which catalyzes epimerization between β- and α-D-galactose in the first step of the Leloir pathway. GALM enzyme activities were undetectable in lymphoblastoid cell lines established from two patients. Immunoblot analysis showed the absence of the GALM protein in the patients’ peripheral blood mononuclear cells. In vitro GALM expression and protein stability assays revealed altered stabilities of the variant GALM proteins. Biallelic GALM pathogenic variants cause galactosemia, suggesting the existence of type IV galactosemia.

Published
2018

25. An Invasive Lepidic Predominant Adenocarcinoma Extensively Involving the Lung with Areas of Sarcomatoid Carcinoma Containing Osteoclast-like Giant Cells

Author

Osamu Sakamoto, Kazuyoshi Nakamura, Hironori Kobayashi, Hideshi Uramoto, Fumiya Imamura, Sayuri Hirooka, Mitsuhiro Matsumoto, Hirotsugu Kohrogi, Taiyo Komatsu, Yuki Tenjin, and Takaaki Ito

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Lung Neoplasms, Osteoclasts, Adenocarcinoma, Giant Cells, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Osteoclast, Internal Medicine, medicine, Humans, Sarcomatoid carcinoma, Lung cancer, Aged, 80 and over, Lung, business.industry, Osteoclast-Like Giant Cell, Carcinoma, Giant Cell, General Medicine, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Giant cell, 030220 oncology & carcinogenesis, Female, Lepidic Predominant Adenocarcinoma, business
Abstract

Primary lung tumor tissue exhibiting numerous multinucleated osteoclast-like giant cells (OGCs) is an extremely rare histological type. In this study, we describe the case of an 82-year-old woman. Chest CT demonstrated an extensive crazy-paving appearance in both of the lung fields and a solid round mass in the right lower lobe. A pathological examination of the tumor revealed sarcomatoid carcinoma containing OGCs combined with diffused, invasive lepidic predominant adenocarcinoma. We herein present an extremely rare lung cancer, invasive lepidic predominant adenocarcinoma extensively involving the lung with areas of sarcomatoid carcinoma containing OGCs.

Published
2016
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26. First Japanese case of Zellweger syndrome with a mutation inPEX14

Author

Toshihiro Ohura, Osamu Sakamoto, Mitsugu Uematsu, Kazuhiro Haginoya, Yoichi Matsubara, Eishin Ogawa, Yuki Hasegawa, Shoko Komatsuzaki, and Nobuyuki Shimozawa

Subjects
medicine.medical_specialty, Zellweger syndrome, Psychomotor retardation, business.industry, Rickets, Disease, medicine.disease, Gastroenterology, Hypotonia, Endocrinology, Internal medicine, Pediatrics, Perinatology and Child Health, Failure to thrive, Mutation (genetic algorithm), Mutation testing, Medicine, medicine.symptom, business
Abstract

Zellweger syndrome, one of the peroxisome biogenesis disorders, is an autosomal recessive disease caused by mutations in PEX genes. It is characterized by severe hypotonia, failure to thrive, psychomotor retardation, liver dysfunction, and sensorineural hearing impairment. Most of the patients with this disease die before the age of 1 year. PEX14 is the 13th PEX gene responsible for peroxisome biogenesis disorders. Thus far, only two patients with PEX14 deficiency have been reported. Here, we report the first case of a Japanese patient with a PEX14 mutation who showed severe hypotonia, psychomotor retardation, demyelination, and developed rickets at the age of 5 months. An increased excretion of 3,6-epoxydicarboxylic acids leads to the diagnosis of Zellweger syndrome and a mutation analysis of PEX14 revealed a homozygous mutation of c.538C>T (p.Q180X). The patient survived for a prolonged period of time but died of liver failure at the age of 46 months.

Published
2015
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27. Mechanism for increased hepatic glycerol synthesis in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse: Urine glycerol and glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency

Author

Eishi Kuroda, Shigeo Kure, Osamu Sakamoto, Akio Inui, David S. Sinasac, Yoichi Nakamura, Fumio Endo, Masahide Yazaki, Takeyori Saheki, Masahisa Horiuchi, Chun-Hua Zhang, Akihiro Asakawa, Katsura Takano, Shizuka Rikimaru, Takashi Kadowaki, Shu-ichi Ikeda, Yuki Fujimoto, Mitsuaki Moriyama, Hiroshi Mitsubuchi, Yoshiyuki Okano, Kazuhiro Eto, Ken Ichi Yamamura, Yuan Zong Song, Miharu Ushikai, and Kenji Kawabe

Subjects
Glycerol, Pyruvate, Redox state, biology, Fructose, Dehydrogenase, Carbohydrate, Mitochondrial aspartate-glutamate carrier, chemistry.chemical_compound, Glycerol-3-phosphate dehydrogenase, chemistry, Biochemistry, Citrin, biology.protein, Molecular Medicine, Citrin deficiency, NAD+ kinase, Glycerol 3-phosphate, Molecular Biology
Abstract

The mitochondrial aspartate-glutamate carrier isoform 2 (citrin) and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) double-knockout mouse has been a useful model of human citrin deficiency. One of the most prominent findings has been markedly increased hepatic glycerol 3-phosphate (G3P) following oral administration of a sucrose solution. We aimed to investigate whether this change is detectable outside of the liver, and to explore the mechanism underlying the increased hepatic G3P in these mice. We measured G3P and its metabolite glycerol in plasma and urine of the mice under various conditions. Glycerol synthesis from fructose was also studied using the liver perfusion system. The citrin/mGPD double-knockout mice showed increased urine G3P and glycerol under normal, fed conditions. We also found increased plasma glycerol under fasted conditions, while oral administration of different carbohydrates or ethanol led to substantially increased plasma glycerol. Fructose infusion to the perfused liver of the double-knockout mice augmented hepatic glycerol synthesis, and was accompanied by a concomitant increase in the lactate/pyruvate (L/P) ratio. Co-infusion of either pyruvate or phenazine methosulfate, a cytosolic oxidant, with fructose corrected the high L/P ratio, leading to reduced glycerol synthesis. Overall, these findings suggest that hepatic glycerol synthesis is cytosolic NADH/NAD+ ratio-dependent and reveal a likely regulatory mechanism for hepatic glycerol synthesis following a high carbohydrate load in citrin-deficient patients. Therefore, urine G3P and glycerol may represent potential diagnostic markers for human citrin deficiency.

Published
2015
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28. A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia

Author

Ryoko Fukai, Hiroshi Koga, Naomichi Matsumoto, Yasunari Sakai, Osamu Sakamoto, Yoshito Ishizaki, Toshiro Hara, Satoshi Akamine, Hiroyuki Torisu, Masafumi Sanefuji, Masahiko Kimura, Ayumi Sakata, Noriko Miyake, Shouichi Ohga, Hirotomo Saitsu, Seiji Yamaguchi, and Kazuhiro Ohkubo

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Adolescent, Encephalopathy, CDKL5, Methylmalonic acid, Methylmalonic acidemia, 030105 genetics & heredity, Protein Serine-Threonine Kinases, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Methionine, Internal medicine, Genetics, medicine, Humans, Amino Acid Metabolism, Inborn Errors, Genetics (clinical), Brain Diseases, business.industry, General Medicine, Syndrome, medicine.disease, Hypsarrhythmia, chemistry, CDKL5 Disorder, Concomitant, medicine.symptom, Propionates, business, 030217 neurology & neurosurgery, Methylmalonic Acid
Abstract

Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy.

Published
2017

29. AB017. Gene panel study for target metabolic diseases of newborn screening in Japan

Author

Masahisa Kobayashi, Yoko Nakajima, Osamu Sakamoto, Takashi Hamazaki, Kimitoshi Nakamura, Go Tajima, Hideo Sasai, Ryoji Fujiki, Tetsuya Ito, Toshiyuki Fukao, Osamu Ohara, Shiro Matsumoto, Hironori Kobayashi, and Yuki Hasegawa

Subjects
Newborn screening, Pediatrics, medicine.medical_specialty, business.industry, Gene panel, Newborn Screening, Inborn Errors of Metabolism, Medicine, General Medicine, business, Bioinformatics
Published
2017

30. Successful control of maternal phenylketonuria by tetrahydrobiopterin

Author

Osamu Sakamoto, Shigeo Kure, Kei Murayama, and Natsuko Arai-Ichinoi

Subjects
Adult, 0301 basic medicine, Phenylketonuria, Maternal, medicine.medical_specialty, business.industry, Phenylalanine, Tetrahydrobiopterin, 030105 genetics & heredity, Biopterin, Phenylalanine restricted diet, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pregnancy, 030225 pediatrics, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Humans, Female, Maternal phenylketonuria, business, medicine.drug
Published
2018
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31. Reappraising newborn screening for cobalamin C disorder

Author

Kei Nishiyama, Osamu Sakamoto, Fusako Sasaki, Vlad Tocan, Hidetoshi Takada, Kazuko Yoshimura, Shinichi Hirose, Kazuhiro Ohkubo, Shouichi Ohga, Naoko Toda, Kanako Higashi, Masataka Ishimura, and Kanako Kojima-Ishii

Subjects
0301 basic medicine, 03 medical and health sciences, Pediatrics, medicine.medical_specialty, Newborn screening, chemistry.chemical_compound, 030104 developmental biology, chemistry, business.industry, Pediatrics, Perinatology and Child Health, medicine, business, Cobalamin
Published
2017

32. Central Venous Catheter-Related Bloodstream Infection with Kocuria kristinae in a Patient with Propionic Acidemia

Author

Hisao Yaoita, Osamu Sakamoto, Masato Kimura, Shigeo Kure, Natsuko Ichinoi, and Eichiro Kawai

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, Coccus, Cefazolin, Case Report, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Medicine, lcsh:RC109-216, 030212 general & internal medicine, Propionic acidemia, Kocuria kristinae, biology, business.industry, General Medicine, medicine.disease, biology.organism_classification, Surgery, Catheter, Bacteremia, Vancomycin, business, Central venous catheter, medicine.drug
Abstract

Kocuria kristinae is a catalase-positive, coagulase-negative, Gram-positive coccus found in the environment and in normal skin and mucosa in humans; however, it is rarely isolated from clinical specimens and is considered a nonpathogenic bacterium. We describe a case of catheter-related bacteremia due to K. kristinae in a young adult with propionic acidemia undergoing periodic hemodialysis. The patient had a central venous catheter implanted for total parenteral nutrition approximately 6 months prior to the onset of symptoms because of repeated acute pancreatitis. K. kristinae was isolated from two sets of blood cultures collected from the catheter. Vancomycin followed by cefazolin for 16 days and 5-day ethanol lock therapy successfully eradicated the K. kristinae bacteremia. Although human infections with this organism appear to be rare and are sometimes considered to result from contamination, physicians should not underestimate its significance when it is isolated in clinical specimens.

Published
2017

33. [Collision Lung Cancer Consisting of Squamous Cell Carcinoma and Adenocarcinoma which Showed Identical Epidermal Growth Factor Receptor Mutation;Report of a Case]

Author

Yutaka, Motomura, Takeshi, Mori, Satoshi, Furuhashi, Naoko, Hayashi, Tomoko, Suzumura, Tohru, Yamanaka, Osamu, Sakamoto, Kazumi, Kuriwaki, Keiichiro, Kanemitsu, and Makoto, Suzuki

Abstract

We report a 79-year-old woman with collision cancer in the right middle lobe of the lung. She had a persistent abnormal shadow after treatment for pneumonia pointed out in right middle lung field on chest radiogram, and referred to our hospital. On examination, the chest computed tomography showed a pure-solid mass of 7.6 cm in diameter in right middle lobe of the lung which was thought to invade the superior pulmonary vein. She underwent a successful right pneumonecomty, and the postoperative course was uneventful. The tumor proved to be a collision cancer consisting of poor differentiated squamous cell carcinoma and invasive adenocarcinoma, lepidic predominanat by pathological examination. Epidermal growth factor receptor mutations (L858R) were found in both squamous cell carcinoma and adenocarcinoma of the tumor, possibly suggesting the same origin of both histological types.

Published
2015

34. Phenotypic Variability and Newly Identified Mutations of the IVD Gene in Japanese Patients with Isovaleric Acidemia

Author

Osamu, Sakamoto, Natsuko, Arai-Ichinoi, Hiroshi, Mitsubuchi, Yasutsugu, Chinen, Hidenori, Haruna, Hidehiko, Maruyama, Hidenori, Sugawara, and Shigeo, Kure

Subjects
Male, Heterozygote, Adolescent, Isovaleryl-CoA Dehydrogenase, Infant, Newborn, Mutation, Missense, Infant, Exons, Polymerase Chain Reaction, Gas Chromatography-Mass Spectrometry, Introns, Phenotype, Asian People, Leucine, Mutation, Odorants, Humans, Female, Age of Onset, Child, Pentanoic Acids, Amino Acid Metabolism, Inborn Errors
Abstract

Isovaleric acidemia (IVA) is an autosomal recessive inborn error affecting leucine metabolism. It is caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD), a mitochondrial matrix enzyme that catalyzes the oxidation of isovaleryl-CoA to 3-methylcrotonyl-CoA. IVD is a FAD-containing enzyme, consisting of four identical subunits. Clinical features of IVA include poor feeding, vomiting, lethargy, developmental delay, metabolic acidosis, and a characteristic "sweaty foot" odor. IVA is one of the target disorders for newborn screening by tandem mass spectrometry (MS/MS). The human IVD gene is located on chromosome 15q. To date, over 50 disease-causing mutations have been reported worldwide. In this study, we searched for IVD mutations in five Japanese patients with IVA (neonatal type, two patients; chronic intermittent type, two patients; and mild biochemical type, one patient). The diagnosis of IVA was confirmed by urinary organic acid analysis using gas chromatography and mass spectrometry. All coding exons and the flanking introns in the IVD gene were amplified by PCR and were directly sequenced. We thus identified six hitherto unknown mutations (p.G94D, p.E116K, p.M167T, p.L243P, p.L246P, and c.696+1GT) and four previously reported (p.R53P, p.R395C, p.Y403C, and p.E411K) pathogenic mutations. All patients were compound heterozygotes, and each mutation was identified in a single patient. Pathogenicity of newly identified mutations was validated using computational programs. Among them, the p.M167T is believed to influence FAD binding, as the position 167 is present in one of the FAD-binding sites. Our results have illustrated the heterogeneous mutation spectrum and clinical presentation of IVA in the Japanese patients.

Published
2015

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