Amano N.,Keio University |
Mukai T.,Asahikawa Kosei General Hospital |
Ito Y.,Japanese Red Cross Hokkaido College of Nursing |
Narumi S.,Keio University |
And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: C-type natriuretic peptide-natriuretic peptide receptor B (NPR-B) signaling is critical for endochondral ossification, which is responsible for longitudinal growth in limbs and vertebrae. Biallelic NPR2 mutations cause acromesomelic dysplasia, type Maroteaux, which is bone dysplasia characterized by severe short stature and short limbs. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. Objective: The goal of this study was to identify and characterize NPR2 mutations among Japanese patients with short stature. Subjects and Methods: We enrolled 101 unrelated Japanese patients with short stature. NPR2 and NPPC were sequenced, and the identified variants were characterized in vitro. Results: In two subjects,weidentified two novel heterozygous NPR2 mutations (R110C and Q417E) causing a loss of C-type natriuretic peptide-dependent cGMP generation capacities and having dominant-negative effects. R110C was defective in trafficking from the endoplasmic reticulum to the Golgi apparatus. In contrast, Q417E showed clear cell surface expression. Conclusions: We identified heterozygous NPR2 mutations in 2% of Japanese patients with short stature. Our in vitro findings indicate that NPR2 mutations have a dominant negative effect, and their dominant-negative mechanisms vary corresponding to the molecular pathogenesis of the mutations. Copyright © 2014 by the Endocrine Society. Source
Doi A.,Iwate Prefectural University |
Noguchi K.,Iwate Prefectural University |
Katamachi K.,Iwate Prefectural University |
Ishii T.,Japanese Red Cross Hokkaido College of Nursing |
And 3 more authors.
International Journal of Design and Nature and Ecodynamics | Year: 2010
For obstetricians and midwives, 'internal examination' refers to an important diagnostic technique in which the progress of labor is examined using the index and middle fingers inserted into the vagina or rectum. Training of this internal examination technique has been commonly performed using a model of the human body (manikin). However, with this method, it was impossible to determine visually where and how the examining fingers are touching, making it difficult for trainers to teach advanced examination skills efficiently and evaluate training achievements. Against this background, we have developed a training system for internal examination that enables simulation of normal and abnormal conditions of labor by detecting the position and direction of the examining fingers in real-time via tactile and visual perceptions using anatomical and virtual models. This system allows trainees to experience both normal and abnormal fetal descent into the pelvis. In addition to support the abnormal conditions, we propose the unique measurements function using magnetic sensors, in order to estimate the precise baby status, such as a gap of the uterine ostium or baby head. We conducted a survey of eight students at our university, and made inquiries for our system, and evaluated it for understanding where the position of ischiatic thor (spinal ischium), baby head, and uterine ostium. The result of the several questions shows that the understanding of all students is improved by using our system. © 2010 WIT Press. Source
Konno R.,Jichi Medical University |
Sagae S.,JR Sapporo Railway Hospital |
Yoshikawa H.,University of Tsukuba |
Basu P.S.,Chittaranjan National Cancer Institute |
And 3 more authors.
Japanese Journal of Clinical Oncology | Year: 2010
Disease burden of cervical cancer in Asia was summarized. Human papillomavirus 16 is the most oncogenic human papillomavirus type. Korea's national cervical cancer screening program targets women aged 30 or over, with coverage of almost 80%. Japan has a long history (50 years) of cervical cancer screening, and cytological screening programs have reduced the incidence/mortality of cervical cancer by 70%. But, recent cervical cancer screening coverage is ~24%. Modeling suggested that vaccination of all 12-year-old girls would reduce cervical cancer cases by 73% in Japan. India has no cervical cancer screening program, as well as a serious lack of awareness in the general population, medical professionals and policy-makers. A realistic, affordable approach would be a low-volume, once-in-a-lifetime human papillomavirus-based screening program. In Australia, the national cervical cancer program has been very successful in reducing the incidence and mortality of cervical cancer. Australia was the first country to implement free, national human papillomavirus immunization (April 2007), expected to reduce human papillomavirus 16 infections by 56% in 2010 and 92% in 2050. A comparison of the UK and Japan was demonstrated that in the UK, cervical cancer screening and human papillomavirus vaccination uptakes are high because the government provides adequate education/funding. The Japanese government needs to put more emphasis on women's health and preventative medicine. Our conclusion and recommendations are that heightened public awareness of cervical cancer prevention, focusing on screening and vaccination will lead to improved survival and a better quality of life. © The Author (2010). Published by Oxford University Press. All rights reserved. Source
Nagasaka M.,Kobe University |
Morioka I.,Kobe University |
Yokota T.,Kobe University |
Fujita K.,Kobe University |
And 8 more authors.
Archives of Disease in Childhood | Year: 2015
Objectives: This study aimed to investigate the incidence of short stature at 3 years of age in a Japanese cohort of late preterm infants who were born at 34-36 weeks' gestational age (GA). We compared these late preterm infants with term infants (37-41 weeks' GA), and evaluated the effect of birth weight on the incidence of short stature. Methods: A longitudinal population-based study of 26 970 neonates who were born between 34 weeks' and 41 weeks' GA in 2006-2008 was conducted in Kobe, Japan. Of these neonates, 1414 were late preterm and 25 556 were term infants. The late preterm infants were then divided into three subgroups based on birth weight as determined by Japanese neonatal anthropometric charts for GA at birth: large-for-GA (n=140), appropriate-for-GA (AGA, n=1083), and small-for-GA (SGA, n=191). The incidence of short stature at 3 years of age was calculated in the late preterm group and compared with that in the term group, and between the AGA and SGA groups with late preterm birth. Results: The incidence of short stature in the late preterm group was 2.9%, which was significantly higher than that in the term group (1.4%). Late preterm SGA infants developed short stature with a significantly higher (9.4%) incidence than that of late preterm AGA infants (2.1%). Conclusions: The incidence of short stature in 3-year-old children who were late preterm infants has a 2-fold higher risk than that in term infants. The risk of developing short stature is increased 4.5-fold if they are SGA. © 2015, BMJ Publishing Group. All rights reserved. Source
Inoue H.,Diabetes Therapeutics and Research Center |
Inoue H.,Tokushima University |
Mukai T.,Asahikawa University |
Sakamoto Y.,Tokushima University |
And 7 more authors.
Clinical Endocrinology | Year: 2012
Context To date, approximately 35 different POU1F1 mutations have been described in patients with familial and sporadic combined pituitary hormone deficiency (CPHD) from different ethnic backgrounds. The majority are missense mutations clustered within the conserved POU-specific and POU-homeo domains, encoded by exons 4 and 6, respectively. Objectives This study aimed to identify the molecular basis and clinical characteristics of a Japanese CPHD family with a novel POU1F1 mutation. Design The POU1F1 gene was sequenced in identical twin brothers with mild CPHD. The mutation identified was also evaluated in family members as well as 188 Japanese controls and then examined in functional studies. Results A novel heterozygous splice site mutation (Ex2 + 1G>T; c.214 + 1G>T) was detected. This mutation was also present in their undiagnosed mother, but not in any of the controls. In vitro splicing studies suggested this mutation to result in an in-frame skipping of exon 2, thus producing an internally deleted protein lacking most of the R2 transactivation subdomain (TAD-R2). Heterologous expression studies of the mutated POU1F1 protein showed only modest reductions in its transactivation activities in HEK293T cells, while acting as a dominant-negative inhibitor of the endogenous activities of POU1F1 in pituitary GH3 cells. Conclusions This is the first report of a mutation at the exon 2 donor splice site of POU1F1, affecting TAD-R2. The addition of this mutation to the growing list of pathological POU1F1 mutations may provide deeper insights into clinical heterogeneity in the expressions of individual mutations and a better understanding of the structure-function relationships of POU1F1. © 2011 Blackwell Publishing Ltd. Source