Sapporo City Institute of Public Health

Sapporo, Japan

Sapporo City Institute of Public Health

Sapporo, Japan
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Tajima T.,Hokkaido University | Fujikura K.,Sapporo City Institute of Public Health | Fukushi M.,Sapporo Immunodiagnostic Laboratory | Hotsubo T.,Nippon Telegraph and Telephone | Mitsuhashi Y.,Sapporo City Institute of Public Health
Pediatric Endocrinology Reviews | Year: 2012

A nationwide screening test for congenital adrenal hyperplasia (CAH) was first initiated in Japan in 1989, over 20 years ago, and it is now 30 years since a pilot study was initiated in Sapporo in 1982. The incidence of 21-hydroxylase deficiency in Japan is about 1/18,000 persons, which is similar to that in other countries. The effectiveness of early detection and treatment of CAH in Japan has been demonstrated by costbenefit analyses. However, the false-positive rate of CAH screening in preterm infants remains high compared to screening tests for term infants. To improve the positive predictive value, we have employed 21-hydroxylase gene (CYP21A2) analysis on dried blood spots and high performance liquid chromatography (HPLC) to measure 17-hydroxyprogesterone, and currently use tandem mass spectrometry (LC-MS/MS) as a screening technique. We suggest that LC-MS/MS should be used in the future to improve the accuracy of CAH screening in Japan.

Oda E.,Tokyo Women's Medical University | Fukushi M.,Sapporo City Institute of Public Health | Okumiya T.,Kumamoto University | Osawa M.,Tokyo Women's Medical University
Molecular Genetics and Metabolism | Year: 2011

Pompe disease is caused by a deficiency of acid alpha-glucosidase (GAA) that results in glycogen accumulation, primarily in muscle. Newborn screening (NBS) for Pompe disease has been initiated in Taiwan and is reportedly successful. However, the comparatively high frequency of pseudodeficiency allele makes NBS for Pompe disease complicated in Taiwan. To investigate the feasibility of NBS for Pompe disease in Japan, we obtained dried blood spots (DBSs) from 496 healthy Japanese controls, 29 Japanese patients with Pompe disease, and five obligate carriers, and assayed GAA activity under the following conditions: (1) total GAA measured at pH 3.8, (2) GAA measured at pH 3.8 in the presence of acarbose, and (3) neutral glucosidase activity (NAG) measured at pH 7.0 without acarbose. The % inhibition and NAG/GAA ratio were calculated. For screening, samples with GAA < 8% of the normal mean, % inhibition > 60%, and NAG/GAA ratio > 30 were considered to be positive. Two false positive cases (0.3%) were found, one was a healthy homozygote of pseudodeficiency allele (c.1726G>A). The low false-positive rate suggests that NBS for Pompe disease is feasible in Japan. © 2011 Elsevier Inc.

PubMed | Universitats Kinderklinik, Programme Quebecois de Depistage Neonatal Sanguin, Instituto Naciional Of Perinatologia, National Institute for Public Health and the Environment RIVM and 12 more.
Type: Journal Article | Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2014

Because of lack of worldwide standardization of influenza virus surveillance, comparison between countries of impact of a pandemic is challenging. For that, other approaches to allow internationally comparative serosurveys are welcome.Here we explore the use of neonatal screening dried blood spots to monitor the trends of the 2009 influenza A (H1N1) pdm virus by the use of a protein microarray.We contacted colleagues from neonatal screening laboratories and asked for their willingness to participate in a study by testing anonymized neonatal screening bloodspots collected during the course of the pandemic. In total, 7749 dried blood spots from 13 countries in 5 continents where analyzed by using a protein microarray containing HA1 recombinant proteins derived from pandemic influenza A (H1N1) 2009 as well as seasonal influenza viruses.Results confirm the early start of the pandemic with extensive circulation in the US and Canada, when circulation of the new virus was limited in other parts of the world. The data collected from sites in Mexico suggested limited circulation of the virus during the early pandemic phase in this country. In contrast and to our surprise, an increase in seroprevalence early in 2009 was noted in the dataset from Argentina, suggestive of much more widespread circulation of the novel virus in this country than in Mexico.We conclude that this uniform serological testing of samples from a highly standardized screening system offers an interesting opportunity for monitoring population level attack rates of widespread diseases outbreaks and pandemics.

Kaneko H.,Fukushima Medical University | Aoki K.,Hokkaido University | Ohno S.,Hokkaido University | Ishiko H.,Mitsubishi Group | And 7 more authors.
Journal of Clinical Microbiology | Year: 2011

For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Tomatsu S.,Saint Louis University | Montano A.M.,Saint Louis University | Oguma T.,Daiichi Sankyo | Dung V.C.,Saint Louis University | And 9 more authors.
Molecular Genetics and Metabolism | Year: 2010

Glycosaminoglycans (GAGs) are accumulated in various organs in both mucopolysaccharidoses (MPS) and mucolipidoses II and III (ML II and III). MPS and ML II and III patients can not properly degrade dermatan sulfate (DS) and/or heparan sulfate (HS). HS storage occurs in the brain leading to neurological signs while DS storage involves mainly visceral and skeletal manifestations. Excessive DS and HS released into circulation and thus blood levels of both are elevated, therefore, DS and HS in blood could be critical biomarkers for MPS and ML. Such measurement can provide a potential early screening, assessment of the clinical course and efficacy of therapies. We here assay DS and HS levels in MPS and ML patients using liquid chromatography tandem mass spectrometry (LC/MS/MS). Plasma samples were digested by heparitinase and chondroitinase B to obtain disaccharides of DS and HS, followed by LC/MS/MS analysis. One hundred-twenty samples from patients and 112 control samples were analyzed. We found that all MPS I, II, III and VI patients had a significant elevation of all DS + HS compositions analyzed in plasma, compared with the controls (P < 0.0001). Specificity and sensitivity was 100% if the cut off value is 800 ng/ml between control and these types of MPS group. All MPS I, II and III patients also had a significant elevation of plasma HS, compared with the controls (P < 0.0001). All MPS VI patients had a significant elevation of plasma DS, compared with the controls (P < 0.0001). These findings suggest measurement of DS and/or HS levels by LC/MS/MS is applicable to the screening for MPS I, II, III and VI patients. © 2009.

Katsumata N.,National Health Research Institute | Ogawa E.,Tohoku University | Fujiwara I.,Tohoku University | Fujikura K.,Sapporo City Institute of Public Health
Metabolism: Clinical and Experimental | Year: 2010

Combined 17α-hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 that catalyzes both 17α-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads. In the present study, we analyzed the CYP17A1 gene in a Japanese girl with 17α-hydroxylase/17,20-lyase deficiency. The patient was referred to us for clitoromegaly at the age of 3 years. The karyotype was 46,XY. The patient was diagnosed as having 17α-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17A1 gene revealed a compound heterozygous mutation. One mutation was a deletion of codon 53 or 54 encoding Phe (TTC) in exon 1 (ΔF54) on a maternal allele, which has been previously shown to partially abolish both 17α-hydroxylase and 17,20-lyase activities. The other was a novel missense mutation resulting in a substitution of Asn (AAC) for His (CAC) at codon 373 in exon 6 (H373N) on a paternal allele. Functional expression study demonstrated that the H373N mutation almost completely eliminates enzymatic activity. Previous studies have demonstrated that replacement of histidine by leucine at position 373 causes complete loss of both 17α-hydroxylase and 17,20-lyase activities with a defect in heme binding due to a global alteration of P450c17 structure, indicating the importance of H373 for P450c17 structure and function. Together, these results indicate that the patient is a compound heterozygote for the ΔF54 and H383N mutations and that these mutations inactivate both 17α-hydroxylase and 17,20-lyase activities and give rise to clinically manifest combined 17α-hydroxylase/17,20-lyase deficiency. © 2010 Elsevier Inc. All rights reserved.

Higashi T.,University of Shizuoka | Suzuki M.,University of Shizuoka | Hanai J.,Sapporo City Institute of Public Health | Inagaki S.,University of Shizuoka | And 3 more authors.
Journal of Separation Science | Year: 2011

Vitamin D deficiency in an infant is associated with a wide range of adverse health outcomes in later life. A method for the quantification of 25-hydroxyvitamin D3 [25(OH)D3, the best-established indicator of vitamin D status] in neonatal dried blood spots (DBSs) using LC/ESI-MS/MS has been developed and validated. The method employed two steps of derivatization, a Diels-Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione followed by acetylation, to enhance the detectability of 25(OH)D3 in ESI-MS/MS and to separate 25(OH)D3 from 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], a potent interfering metabolite. 25(OH)D3 was extracted from two DBS punches (3 mm in diameter, equivalent to 5.3μL of whole blood), purified using an Oasis HLB® cartridge, and subjected to derivatization prior to analysis with LC/ESI-MS/MS. 25-Hydroxyvitamin D4 was used as the internal standard. This method was reproducible (intra- and inter-assay RSDs, <6.9%) and accurate (analytical recovery, 95.2-102.7%), and the LOQ was 3.0 ng/mL. The developed method enabled specific quantification of 25(OH)D3 in neonatal DBSs and detection of vitamin D deficiency without interference from 3-epi-25(OH)D3. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Katsumata N.,National Health Research Institute | Shinagawa T.,National Health Research Institute | Horikawa R.,National Center for Child Health and Development | Fujikura K.,Sapporo City Institute of Public Health
Metabolism: Clinical and Experimental | Year: 2010

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder caused by the defective CYP21A2 gene that leads to various degrees of impaired secretion of both cortisol and aldosterone. In the present study, we analyzed the CYP21A2 gene in a Japanese male patient with 21-OHD and functionally characterized the mutant CYP21A2 gene. The patient presented with hypoglycemia and a salt-losing crisis during the neonatal period, and was diagnosed as having the salt-wasting form of 21-OHD based on the clinical and laboratory findings. Analysis of the CYP21A2 gene revealed that the patient is homozygous for a novel C to A conversion at -9 position of intron 9 (IVS9-9C>A) and that his parents are heterozygous for the IVS9-9C>A mutation. Transient expression of the IVS9-9C>A mutant CYP21A2 gene in COS-1 cells demonstrated that the mutation creates an aberrant splice acceptor site at -7 position of intron 9 and totally inactivates the authentic splice acceptor site of intron 9, which results in complete deficiency of 21-hydroxylase activity and loss of immunoreactive 21-hydroxylase protein. Clinical presentations of the patient as the severe salt-wasting form of 21-OHD are in good agreement with these results of the expression study. In conclusion, the patient is a homozygote for the novel intronic IVS9-9C>A mutation, which affects messenger RNA splicing and totally inactivates 21-hydroxylase to give rise to clinically manifest classic salt-wasting 21-OHD. © 2010 Elsevier Inc.

Takashita E.,Japan National Institute of Infectious Diseases | Ejima M.,Japan National Institute of Infectious Diseases | Itoh R.,Japan National Institute of Infectious Diseases | Miura M.,Japan National Institute of Infectious Diseases | And 4 more authors.
Eurosurveillance | Year: 2014

Six influenza A(H1N1)pdm09 viruses were detected in Sapporo, Japan, between November and December 2013. All six viruses possessed an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir. No epidemiological link among the six cases could be identified; none of them had received neuraminidase inhibitors before specimen collection. The haemagglutinin and neuraminidase genes of the six viruses were closely related to one another, suggesting clonal spread of a single resistant virus.

Miyoshi M.,Hokkaido Institute of Public Health | Komagome R.,Hokkaido Institute of Public Health | Ishida S.,Hokkaido Institute of Public Health | Kikuchi M.,Sapporo City Institute of Public Health | And 4 more authors.
Japanese Journal of Infectious Diseases | Year: 2014

Laboratory diagnoses for measles were performed in a total of 97 cases in Hokkaido, Japan, during 2011-2012. Two patients were confirmed to be positive for measles virus (MV), both of whom lived in the Iburi district of Hokkaido. Molecular analysis of the nucleotide sequences of the nucleoprotein (N) gene revealed that these 2 strains had high homology with each other and belonged to the genotype D8. The onset interval of these cases and epidemiological data suggested that MV transmission had occurred between them and then terminated. Phylogenetic analysis of the N gene revealed that the strains identified in Hokkaido were classified into a cluster that contained many genotype D8 strains that were detected within a large area of Japan. Eventually, 9 cases were officially reported as measles. However, other than the abovementioned 2 cases, no genetic information regarding MV was obtained. In future, further active surveillance combined with the genetic investigation should be required in all suspected measles cases to verify the elimination status.

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