A5065382621- Lysosomal Storage Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Trypanosoma species research and implications
- Carbohydrate Chemistry and Synthesis
- Virus-based gene therapy research
- Cell death mechanisms and regulation
- Biomedical Research and Pathophysiology
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Liver physiology and pathology
- Biochemical and Molecular Research
- Enzyme function and inhibition
- Metabolism and Genetic Disorders
- Autoimmune and Inflammatory Disorders Research
- Hepatitis B Virus Studies
- Calcium signaling and nucleotide metabolism
- Peroxisome Proliferator-Activated Receptors
- CRISPR and Genetic Engineering
- Polyamine Metabolism and Applications
- Pancreatic function and diabetes
- Dermatological and Skeletal Disorders
- Genetics and Neurodevelopmental Disorders
- Neonatal Health and Biochemistry
Saitama Medical University
2022-2024
National Center For Child Health and Development
2015-2024
Tokyo Metropolitan Children's Medical Center
1998-2005
Keio University Hospital
2005
Institute for Molecular Science
2004
National Institutes of Health
2003
Keio University
1990-2003
Tokyo National Hospital
2002
Fujita Health University
1999-2001
Tohoku University
2001
Signal transducer and activator of transcription-3 (Stat3) is one the most important molecules involved in initiation liver development regeneration. In order to investigate hepatoprotective effects Stat3, we examined whether Stat3 protects against Fas-mediated injury mouse. A constitutively activated form (Stat3-C) was adenovirally overexpressed mouse by intravenous injection, then a nonlethal dose Fas agonist (Jo2) injected intraperitoneally into (0.3 μg/g body wt). Stat3-C dramatically...
Signal transducer and activator of transcription-3 (Stat3) is one the most important molecules involved in initiation liver development regeneration. In order to investigate hepatoprotective effects Stat3, we examined whether Stat3 protects against Fas-mediated injury mouse. A constitutively activated form (Stat3-C) was adenovirally overexpressed mouse by intravenous injection, then a nonlethal dose Fas agonist (Jo2) injected intraperitoneally into (0.3 μg/g body wt). Stat3-C dramatically...
In this study, we aimed to describe the natural history of mucopolysaccharidosis I.Data from 1,046 patients who enrolled in MPS I Registry as August 2013 were available for descriptive analysis. Only data untreated and prior treatment received considered. Age at symptom onset, diagnosis, initiation examined by geographic region phenotype (from most least severe: Hurler, Hurler-Scheie, Scheie). For each symptom, frequency age onset examined.Natural 987 patients. Most Europe (45.5%), followed...
Hunter syndrome (mucopolysaccharidosis II [MPS II]), a deficiency of iduronate-2-sulfatase (IDS), causes an accumulation glycosaminoglycans, giving rise to multiple systemic and CNS symptoms. The currently available therapies, idursulfase beta, are ineffective against the symptoms because they cannot pass blood-brain barrier (BBB). A novel IDS fused with anti-human transferrin receptor antibody (JR-141) has been shown penetrate BBB ameliorate learning deficits in model mice. This...
Pabinafusp alfa (JR-141) is a novel enzyme drug that crosses the blood-brain barrier by transcytosis via transferrin receptors. In order to establish its efficacy and safety, multicenter, single-arm, open-label phase 2/3 clinical trial was conducted in 28 Japanese patients with mucopolysaccharidosis II (MPS-II, Hunter syndrome) intravenous administrations of 2.0 mg/kg pabinafusp for 52 weeks. The primary endpoint changes heparan sulfate (HS) concentrations cerebrospinal fluid (CSF)....
Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs degradation keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations MPS present numerous challenges for management necessitate need individualised treatment. Although treatment guidelines are available, methodology used to develop this guidance has come under...
Abstract We report on molecular and clinical findings in 10 Japanese patients (four males six females) from eight families (two pairs of siblings isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H Y578C), a 24-bp deletion mutation resulting loss nine amino acids creation one acid (L612_W620delinsR),...
Carbonic anhydrase IV (CA IV) is a membrane-bound form of carbonic anhydrase. We have characterized the catalytic activity and inhibition recombinant human CA IV. high-activity isozyme in CO2 hydration with pH-independent kcat value (1.1 × 106 s-1) comparable to that II (8 105 s-1). Furthermore, more active HCO3- dehydration than as illustrated by nearly 3-fold increase kcat/KM 3 107 M-1 s-1. However, esterase decreased 150-fold compared II. The mechanisms are identical. Both isozymes show...
It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which same catalytic properties as membrane-associated purified from tissues. We have determined three-dimensional structure by x-ray crystallographic methods to resolution 2.8 Å. Although zinc binding site and hydrophobic substrate pocket are generally similar those other...
Our objective was to assess how the diagnosis and treatment of mucopolysaccharidosis I (MPS I) have changed over time. We used data from 891 patients in MPS Registry, an international observational database, analyze ages at symptom onset, diagnosis, initiation, allocation (hematopoietic stem cell transplantation, enzyme replacement therapy with laronidase, both, or neither) time for all disease phenotypes (Hurler, Hurler–Scheie, Scheie syndromes). The interval between has become shorter...
Abstract Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder resulting from pathogenic variants in the α‐L‐iduronidase ( IDUA ) gene. Clinical phenotypes range severe (Hurler syndrome) to attenuated (Hurler‐Scheie and Scheie syndromes) vary age of onset, severity, rate progression. Defining phenotype at diagnosis essential for disease management. To date, no systematic analysis genotype‐phenotype correlation large MPS cohorts have been performed. Understanding...
For many metabolic diseases, early correction of the inherited deficiency is required to prevent long-term sequelae. We examined ability adeno-associated virus (AAV) mediate efficient gene transfer during neonatal period in mice with lysosomal storage disease mucopolysaccharidosis type VII (MPS VII). Quadriceps newborn MPS were injected an AAV vector containing human beta-glucuronidase (GUSB) cDNA. High-level intramuscular GUSB expression was seen as 2 weeks age, and persisted for at least...
Abstract We report on clinical and molecular findings in five karyotypic males (cases 1–5) one female (case 6) with distal 9p monosomy. Cases 1–3 6 had external genitalia, case 4 showed ambiguous 5 exhibited male genitalia left cryptorchidism right intrascrotal testis. Gonadal explorations at gonadectomy cases 3 revealed that streak gonad agonadism, bilateral hypoplastic testes. Endocrine studies 1–4 1, 3, definite primary hypogonadism, basal FSH levels of 54, 39, 41 IU/L, respectively,...
Abstract We report on PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11) mutation analysis and clinical assessment in 45 patients with Noonan syndrome. Sequence was performed for all of the coding exons 1–15 PTPN11, revealing a novel 3-bp deletion 10 recurrent missense mutations 18 patients. Clinical showed that 1) growth pattern similar mutation-positive mutation-negative patients, no significant difference birth length [−0.6 ± 2.2 sd (n = 10) vs. −0.6 1.4 21); P 0.95], childhood...
After a Pompe disease diagnosis is confirmed in infants identified through newborn screening (NBS), when and if to start treatment with enzyme replacement therapy (ERT) alglucosidase alfa must be determined. In classic infantile-onset disease, ERT should as soon possible. Once started, regular, routine follow-up necessary monitor for effects, progression, adverse effects. Decision-making or late-onset (LOPD) more challenging because patients typically have no measurable signs symptoms...
Pompe disease is an autosomal recessive disorder caused by acid α-glucosidase (GAA) deficiency, which results in the accumulation of glycogen lysosomes multiple tissues, including cardiac, skeletal, and smooth muscle cells. Thus far, 558 sequence variants GAA gene have been published Disease Mutation Database, some mutations appear with considerable frequency particular ethnic groups, such as Caucasians, Taiwanese, Chinese, Koreans. However, mutation pattern Japanese patients remains poorly...