Pre-movement gating of somatosensory evoked potentials in Segawa disease.

PubMed

Kimura, Kazue; Nagao, Yuri; Hachimori, Kei; Hayashi, Masaharu; Nomura, Yoshiko; Segawa, Masaya

2016-01-01

Segawa disease (SD), an autosomal dominant dopa-responsive dystonia with marked diurnal fluctuation, can be clinically classified into the postural dystonia type (SD-P) and action dystonia type (SD-A). Compared to SD-A, SD-P has an earlier onset and is characterized by postural dystonia. In SD-A, along with postural dystonia, dystonic movements appear in late childhood. To evaluate the differences between these two types of SD, we studied the gating of SEPs, which is useful to investigate sensory-motor integration and might be one of the methods to detect the thalamo-cortical involvement. Fourteen patients with SD (11-63 years) and 18 age-matched normal subjects (11-51 years) were studied. Among the 14 patients with SD, 8 patients had SD-P and 6 had SD-A. Using median nerve stimulation at the wrist, the amplitude of the frontal N30 (FrN30) was compared between pre-movement and rest conditions. We found that the amplitude of the contralateral FrN30 was attenuated before movement in normal controls and in the majority of both SD types. On the other hand, the pre-movement-rest amplitude ratio in patients with SD-A was significantly larger than in patients with SD-P (P=0.0025). No significant differences were observed in the pre-movement-rest ratio between SD-P and normal subjects. The preservation or impairment of pre-movement gating shown here suggests a physiological difference between the two types of SD. More specifically, sensorimotor integration of the basal ganglia-thalamo-cortical circuits may be intact in SD-P, but are affected in SD-A. We discuss the different pathophysiology seen in the different phenotype of SD based on the different developmental involvement in the basal ganglia. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Influence of two cultivars of persimmon on atherosclerosis indices in rats fed cholesterol-containing diets: Investigation in vitro and in vivo.

PubMed

Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria; Jesion, Iwona; Namiesnik, Jacek; Drzewiecki, Jerzy; Park, Yong-Seo; Ham, Kyung-Sik; Giordani, Edgardo; Trakhtenberg, Simon

2011-01-01

To assess the influence of two persimmon cultivars on some atherosclerosis indices in rats fed cholesterol (Chol)-containing diets. Persimmon cultivars "Fuyu" and "Jiro" as supplementation to rats' diets were investigated in vitro to compare the contents of their bioactive compounds (polyphenols, flavonoids, flavanols, tannins, carotenoids, and ascorbic acid) and antioxidant potentials. In the in vivo investigation, 36 male Wistar rats were randomly divided into six diet groups, each with six rats: control, control/Fuyu, control/Jiro, Chol, Chol/Fuyu, and Chol/Jiro. During a period of 47 d (42 d of feeding and 5-d adaptation before the experiment) of the trial, rats in the control group were fed a basal diet and two additional control groups (control/Fuyu and control/Jiro) a basal diet plus 5% of lyophilized Fuyu and Jiro, respectively. The Chol, Chol/Fuyu, and Chol/Jiro rat groups were fed a basal diet supplemented with 1% Chol (Chol group) and 1% Chol plus 5% lyophilized Fuyu (Chol/Fuyu group) and plus 5% lyophilized Jiro (Chol/Jiro group), respectively. After completion of the experiment, the rats were anesthetized using Narcotan (halothane) and sacrificed and the atherosclerotic lesions in the aorta were assessed. The obtained results of the investigation of all six groups were compared. Testing of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, total cholesterol in the liver, electrophoretic patterns of liver tissue, and three-dimensional fluorescence of serum protein fractions was performed. The polyphenols and tannins were significantly higher in the Fuyu cultivar (P<0.05). The antioxidant potential of persimmon Fuyu was higher than in the Jiro cultivar, but the difference was significant only according to the 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay (P<0.05). Supplementation of diets with 5% of the lyophilized Fuyu and Jiro hindered the increase in plasma lipids versus

ARC-1965-A-34401

NASA Image and Video Library

1965-04-22

Vance I. Oyama at the Gas Chromatograph in Ames' life detection laboratory, Vance and his brother Jiro both pioneered new areas of life sciences research at Ames. Publication: Ames History; Atmosphere of Freedom; 60 yrs at NASA Ames NASA SP-2000-4314

Expanding Possibilities of Periodicals for Children in Asia and the Pacific. Report of the 1997 Training Course on Production of Periodicals for Children (Tokyo, October 1-15, 1997).

ERIC Educational Resources Information Center

Asia/Pacific Cultural Centre for UNESCO, Tokyo (Japan).

Following the proceedings of the training course on children's periodicals held in 1997 in Tokyo, this report contains the following articles: (1) "Children's Life and Magazines" (Jiro Saito); (2) "Periodical Picture Books to Develop Reading Skills of Children" (Tadashi Matsui); (3) "How to Produce Attractive Educational…

Successful treatment of childhood onset symptomatic dystonia with levodopa.

PubMed Central

Fletcher, N A; Thompson, P D; Scadding, J W; Marsden, C D

1993-01-01

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms. PMID:8350101

Record of Operations Against Soviet Russia on Northern and Western Fronts of Manchuria, and in Northern Korea (August 1945)

DTIC Science & Technology

1954-09-01

Col Masao Segawa Col Kaoru Okano Col Shigeru Imada - Maj Akizo Yokoyama Capt Toyonobu Kondo Maj Toru Mi tano - Lt Col Sen Nagai - 1st Lt Ichiro...nchurians, and its commander, 1st Lieutenant Ishikawa , was killed. The only unit of the division to engage in action--the 5th Company of the 24lst...Lieutenant: 161 Irie, Major: 43 Ishikawa , 1st Lt: 160 Itung River: 15, 37, 42-43 Iwai, Lt Gen, Torajiro (Cmdr lOath Div): 143, 147-48, 154 Japanese

[Today and tomorrow in child neurology at a neurological clinic for children--the importance of child neurology as the life-long neurology].

PubMed

Nomura, Yoshiko

2005-05-01

Segawa Neurological Clinic for Children was founded in 1973, and specializes in neurological disorders that start in childhood. In thirty-one years since the foundation, about 16,000 patients visited this clinic. The ages of the first visit to this clinic of the patients are mostly below 15 years. The main diseases are epilepsy, autism, mental retardation with various etiologies, Tourette syndrome, and other neurological disorders. Most of the diseases follow a chronic course and require long term follow-up. In this clinic those patients who need the continuous follow-up are seen even after reaching to adulthood. The average age of patients who were seen in the clinic during 2003 was about 21 years of age (20.77 +/- 14.28), suggesting that many of the patients are followed in this clinic for 20-30 years. The etiologies and pathophysiologies of most of these diseases are not fully understood. Therefore, the treatments based on the causes are difficult. The pathophysiologies of these diseases are modified by the ages. For example, some patients with epilepsy develop psychiatric symptoms in adulthood, and require the consultation by psychiatrists. The long-term follow up of certain disorders and evaluations of the disorders at different ages up to the adulthood have lead to new scientific discoveries. Examples include age-dependent symptoms observed in Segawa disease, psychiatric symptoms developing in frontal lobe epilepsy cases, alterations of behaviors in autism and Tourette syndrome. This knowledge suggests insights for the early prevention of later adverse outcomes. Social awareness and understanding of these neurological problems occurring in childhood are essential. The medical economic base for child neurology is another challenging and urgent issue to be solved. The importance of child neurology in the life-long neurology is stressed.

Transcultural stress factors of Japanese mothers living in the United Kingdom.

PubMed

Ozeki, Nobuko

2008-01-01

The aim of this study was to describe the stressors experienced by Japanese mothers living in the United Kingdom. An ethnomethodological design was used by means of an openended, in-depth interview. Semistructured interviews were conducted with 10 Japanese mothers living in the United Kingdom. Analysis was performed using the KJ (Kawakito Jiro) method, equivalent to content analysis and data reduction. The main stressors were participation in the small hierarchical society of the Japanese business climate, isolation, language and cultural barriers, and raising Japanese children in a British cultural context. Unsatisfactory experiences of childbirth, child rearing, and contacts with medical services were reported. Recognizing cultural differences and the difficulties that may be experienced by Japanese clients is a first step. Resources may be provided to help these clients widen their social contacts and improve communication with providers of health care and education for their children.

[Molecular mechanisms of neurotransmission].

PubMed

Nagatsu, T

2000-12-01

of the developmental compensation. Thus conditional knockout of a specific type of neurons at a definite time after birth is required. Immunotoxin mediated conditional cell targeting (IMCT) (Kobayashi et al, Proc Natl Acad Sci 92, 1132-1136, 1995) is a novel transgenic technique for elucidating the function of a neuron in a neuronal circuit. Human molecular genetics of genetic neurological diseases are also useful for elucidating molecular mechanisms of neurotransmission. Autosomal dominant dopa-responsive dystonia (DRD) (Segawa's disease) with mutations of GTP cyclohydrolase I (Ichinose et al, Nature Genet 8, 236-242, 1994) causes a partial decrease in dopamine in the nigrostriatal dopamine neurons and produces a dystonia phenotype (Segawa's syndrome). In contrast, autosomal recessive GTP cyclohydrolase I deficiency with complete loss of the enzyme activity produces deficiencies of dopamine, norepinephrine, and serotonin and complex phenotypes with severe neurological symptoms (Ichinose et al, J Biol Chem 270, 10062-10071, 1995).

A qualitative study on the attributes of nurses' workplace social capital in Japan.

PubMed

Norikoshi, Kensuke; Kobayashi, Toshio; Tabuchi, Keiji

2018-01-01

To identify attributes of nurses' workplace social capital in Japan. Much attention has been paid to nurses' workplace social capital to improve the quality of the work environment; however, few studies are available on the attributes of nurses' workplace social capital. Semi-structured interviews were conducted with 32 nurses at seven hospitals. Nurses reported on the attributes of workplace social capital, such as characteristics facilitating individual positive action in an organisation, which were qualitatively analysed using the Kawakita Jiro method. The attributes of nurses' workplace social capital were organised into six groups: affirmation; exchange of appreciation; unrestricted information sharing; ability to trust; access to the strength; and altruistic reciprocity. The attributes of nurses' workplace social capital included a social structure that allowed nurses to make full use of their abilities both vertically and horizontally and were supported by a sense of security. In particular, newly emerged exchange of appreciation and altruistic reciprocity were important for nurses in Japan in building cooperative relationships with others. Managing human relationships, such as exchange of appreciation and altruistic reciprocity, in clinical settings based on nurses' workplace social capital may promote positive emotions in the organisation, positive ideas among staff and cooperative teamwork, which may lead to high-quality patient care. © 2017 John Wiley & Sons Ltd.

The degree of social difficulties experienced by cancer patients and their spouses.

PubMed

Takeuchi, Takashi; Ichikura, Kanako; Amano, Kanako; Takeshita, Wakana; Hisamura, Kazuho

2018-06-08

Although recent studies have increasingly reported physical and psychological problems associated with cancer and its treatment, social problems of cancer patients and their families have not been sufficiently elucidated. The present study aimed to identify cancer-associated social problems from the perspectives of both patients and their spouses and to compare and analyze differences in their problems. This was a cross-sectional internet-based study. Subjects were 259 patients who developed cancer within the previous five years and 259 patients' spouses; the data were derived from two surveys in 2010 (patients) and 2016 (spouses) whose participants were not part of the same dyad but matched by propensity scores, estimated for age, sex, and the presence or absence of recurrence. We investigated the social difficulties of cancer patients and patients' spouses. Regarding social difficulties experienced by cancer patients and spouses, the 60 patient survey items were categorized into 14 labels by the Jiro Kawakita (KJ) method, which is a qualitative synthesis method developed by Kawakita to classify categorical data. Although patients had higher scores on most subcategories, young spouses aged 39 or younger and female spouses had difficulty scores as high as the corresponding patients on many subcategories. Health care providers should show sufficient concern for both patients and their spouses, particularly young and female spouses.

A numerical analysis of plasma non-uniformity in the parallel plate VHF-CCP and the comparison among various model

NASA Astrophysics Data System (ADS)

Sawada, Ikuo

2012-10-01

We measured the radial distribution of electron density in a 200 mm parallel plate CCP and compared it with results from numerical simulations. The experiments were conducted with pure Ar gas with pressures ranging from 15 to 100 mTorr and 60 MHz applied at the top electrode with powers from 500 to 2000W. The measured electron profile is peaked in the center, and the relative non-uniformity is higher at 100 mTorr than at 15 mTorr. We compare the experimental results with simulations with both HPEM and Monte-Carlo/PIC codes. In HPEM simulations, we used either fluid or electron Monte-Carlo module, and the Poisson or the Electromagnetic solver. None of the models were able to duplicate the experimental results quantitatively. However, HPEM with the electron Monte-Carlo module and PIC qualitatively matched the experimental results. We will discuss the results from these models and how they illuminate the mechanism of enhanced electron central peak.[4pt] [1] T. Oshita, M. Matsukuma, S.Y. Kang, I. Sawada: The effect of non-uniform RF voltage in a CCP discharge, The 57^th JSAP Spring Meeting 2010[4pt] [2] I. Sawada, K. Matsuzaki, S.Y. Kang, T. Ohshita, M. Kawakami, S. Segawa: 1-st IC-PLANTS, 2008

Transverse relaxation of scalar-coupled protons.

PubMed

Segawa, Takuya F; Baishya, Bikash; Bodenhausen, Geoffrey

2010-10-25

In a preliminary communication (B. Baishya, T. F. Segawa, G. Bodenhausen, J. Am. Chem. Soc. 2009, 131, 17538-17539), we recently demonstrated that it is possible to obtain clean echo decays of protons in biomolecules despite the presence of homonuclear scalar couplings. These unmodulated decays allow one to determine apparent transverse relaxation rates R(2) (app) of individual protons. Herein, we report the observation of R(2) (app) for three methyl protons, four amide H(N) protons, and all 11 backbone H(α) protons in cyclosporin A. If the proton resonances overlap, their R(2) (app) rates can be measured by transferring their magnetization to neighboring (13)C nuclei, which are less prone to overlap. The R(2) (app) rates of protons attached to (13)C are faster than those attached to (12)C because of (13)C-(1)H dipolar interactions. The differences of these rates allow the determination of local correlation functions. Backbone H(N) and H(α) protons that have fast decay rates R(2) (app) also feature fast longitudinal relaxation rates R(1) and intense NOESY cross peaks that are typical of crowded environments. Variations of R(2) (app) rates of backbone H(α) protons in similar amino acids reflect differences in local environments.

Simultaneous measurement of monoamine metabolites and 5-methyltetrahydrofolate in the cerebrospinal fluid of children.

PubMed

Akiyama, Tomoyuki; Hayashi, Yumiko; Hanaoka, Yoshiyuki; Shibata, Takashi; Akiyama, Mari; Nakamura, Kazuyuki; Tsuyusaki, Yu; Kubota, Masaya; Yoshinaga, Harumi; Kobayashi, Katsuhiro

2017-02-01

We describe a new method for simultaneous measurement of monoamine metabolites (3-O-methyldopa [3-OMD], 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], 5-hydroxyindoleacetic acid [5-HIAA], and homovanillic acid [HVA]) and 5-methyltetrahydrofolate (5-MTHF) and its use on cerebrospinal fluid (CSF) samples from pediatric patients. Monoamine metabolites and 5-MTHF were measured by high-performance liquid chromatography with fluorescence detection. CSF samples were prospectively collected from children according to a standardized collection protocol in which the first 1-ml fraction was used for analysis. Monoamine metabolites and 5-MTHF were separated within 10min. They showed linearity from the limit of detection to 1024nmol/l. The limit of quantification of each metabolite was sufficiently low for the CSF sample assay. In 42 CSF samples after excluding cases with possibly altered neurotransmitter profiles, the concentrations of 3-OMD, MHPG, 5-HIAA, HVA, and 5-MTHF showed significant age dependence and their ranges were comparable with the reference values in the literature. The metabolite profiles of aromatic l-amino acid decarboxylase deficiency, Segawa disease, and folate receptor α defect by this method were compatible with those in the literature. This method is a simple means of measuring CSF monoamine metabolites and 5-MTHF, and is especially useful for laboratories not equipped with electrochemical detectors. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring Attractiveness of the Basic Sciences for Female Physicians.

PubMed

Yamazaki, Yuka; Fukushima, Shinji; Kozono, Yuki; Uka, Takanori; Marui, Eiji

2018-01-01

In Japan, traditional gender roles of women, especially the role of motherhood, may cause early career resignations in female physicians and a shortage of female researchers. Besides this gender issue, a general physician shortage is affecting basic science fields. Our previous study suggested that female physicians could be good candidates for the basic sciences because such work offers good work-life balance. However, the attractiveness for female physicians of working in the basic sciences, including work-life balance, is not known. In a 2012 nationwide cross-sectional questionnaire survey, female physicians holding tenured positions in the basic sciences at Japan's medical schools were asked an open-ended question about positive aspects of basic sciences that clinical medicine lacks, and we analyzed 58 respondents' comments. Qualitative analysis using the Kawakita Jiro method revealed four positive aspects: research attractiveness, priority on research productivity, a healthy work-life balance, and exemption from clinical duties. The most consistent positive aspect was research attractiveness, which was heightened by medical knowledge and clinical experience. The other aspects were double-edged swords; for example, while the priority on research productivity resulted in less gender segregation, it sometimes created tough competition, and while exemption from clinical duties contributed to a healthy work-life balance, it sometimes lowered motivation as a physician and provided unstable income. Overall, if female physicians lack an intrinsic interest in research and seek good work-life balance, they may drop out of research fields. Respecting and cultivating students' research interest is critical to alleviating the physician shortage in the basic sciences.

[Studies Using Text Mining on the Differences in Learning Effects between the KJ and World Café Method as Learning Strategies].

PubMed

Yasuhara, Tomohisa; Sone, Tomomichi; Konishi, Motomi; Kushihata, Taro; Nishikawa, Tomoe; Yamamoto, Yumi; Kurio, Wasako; Kohno, Takeyuki

2015-01-01

The KJ method (named for developer Jiro Kawakita; also known as affinity diagramming) is widely used in participatory learning as a means to collect and organize information. In addition, the World Café (WC) has recently become popular. However, differences in the information obtained using each method have not been studied comprehensively. To determine the appropriate information selection criteria, we analyzed differences in the information generated by the WC and KJ methods. Two groups engaged in sessions to collect and organize information using either the WC or KJ method and small group discussions were held to create "proposals to improve first-year education". Both groups answered two pre- and post- session questionnaires that asked for free descriptions. Key words were extracted from the results of the two questionnaires and categorized using text mining. In the responses to questionnaire 1, which was directly related to the session theme, a significant increase in the number of key words was observed in the WC group (p=0.0050, Fisher's exact test). However, there was no significant increase in the number of key words in the responses to questionnaire 2, which was not directly related to the session theme (p=0.8347, Fisher's exact test). In the KJ method, participants extracted the most notable issues and progressed to a detailed discussion, whereas in the WC method, various information and problems were spread among the participants. The choice between the WC and KJ method should be made to reflect the educational objective and desired direction of discussion.

The difficulty of professional continuation among female doctors in Japan: a qualitative study of alumnae of 13 medical schools in Japan

PubMed Central

Nomura, Kyoko; Yamazaki, Yuka; Gruppen, Larry D; Horie, Saki; Takeuchi, Masumi; Illing, Jan

2015-01-01

Objectives To investigate the difficulties Japanese female doctors face in continuing professional practice. Design A qualitative study using the Kawakita Jiro method. Setting A survey conducted in 2011 of 13 private Japanese medical school alumni associations. Participants 359 female doctors. Primary outcome measures Barriers of balancing work and gender role. Results The female doctors reported that professional practice was a struggle with long working hours due to a current shortage of doctors in Japan. There was also a severe shortage of childcare facilities in the workplace. Some women appeared to have low confidence in balancing the physician's job and personal life, resulting in low levels of professional pursuit. There appeared to be two types of stereotypical gender roles, including one expected from society, stating that “child rearing is a woman's job”, and the other perceived by the women themselves, that some women had a very strong desire to raise their own children. Male doctors and some female doctors who were single or older were perceived to be less enthusiastic about supporting women who worked while raising children because these coworkers feared that they would have to perform additional work as a result of the women taking long periods of leave. Conclusions Important factors identified for promoting the continuation of professional practice among female doctors in Japan were the need to improve working conditions, including cutting back on long working hours, a solution to the shortage of nurseries, a need for the introduction of educational interventions to clarify professional responsibilities, and redefinition of the gender division of labour for male and female doctors. In addition, we identified a need to modernise current employment practices by introducing temporary posts to cover maternity leave and introducing flexible working hours during specialist training, thus supporting and encouraging more women to continue their medical

Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency.

PubMed

Ichinose, H; Ohye, T; Matsuda, Y; Hori, T; Blau, N; Burlina, A; Rouse, B; Matalon, R; Fujita, K; Nagatsu, T

1995-04-28

GTP cyclohydrolase I is the first and rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin in mammals. Previously, we reported three species of human GTP cyclohydrolase I cDNA in a human liver cDNA library (Togari, A., Ichinose, H., Matsumoto, S., Fujita, K., and Nagatsu, T. (1992) Biochem. Biophys. Res. Commun. 187, 359-365). Furthermore, very recently, we found that the GTP cyclohydrolase I gene is causative for hereditary progressive dystonia with marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242). To clarify the mechanisms that regulate transcription of the GTP cyclohydrolase I gene and to generate multiple species of mRNA, we isolated genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is encoded by a single copy gene and is composed of six exons spanning approximately 30 kilobases. We sequenced all exon/intron boundaries of the human and mouse genes. Structural analysis also demonstrated that the heterogeneity of GTP cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor site at the sixth exon. The transcription start site of the mouse GTP cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes were determined. We performed regional mapping of the mouse gene by fluorescence in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to region C2-3 of mouse chromosome 14. We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity.

The difficulty of professional continuation among female doctors in Japan: a qualitative study of alumnae of 13 medical schools in Japan.

PubMed

Nomura, Kyoko; Yamazaki, Yuka; Gruppen, Larry D; Horie, Saki; Takeuchi, Masumi; Illing, Jan

2015-03-27

To investigate the difficulties Japanese female doctors face in continuing professional practice. A qualitative study using the Kawakita Jiro method. A survey conducted in 2011 of 13 private Japanese medical school alumni associations. 359 female doctors. Barriers of balancing work and gender role. The female doctors reported that professional practice was a struggle with long working hours due to a current shortage of doctors in Japan. There was also a severe shortage of childcare facilities in the workplace. Some women appeared to have low confidence in balancing the physician's job and personal life, resulting in low levels of professional pursuit. There appeared to be two types of stereotypical gender roles, including one expected from society, stating that "child rearing is a woman's job", and the other perceived by the women themselves, that some women had a very strong desire to raise their own children. Male doctors and some female doctors who were single or older were perceived to be less enthusiastic about supporting women who worked while raising children because these coworkers feared that they would have to perform additional work as a result of the women taking long periods of leave. Important factors identified for promoting the continuation of professional practice among female doctors in Japan were the need to improve working conditions, including cutting back on long working hours, a solution to the shortage of nurseries, a need for the introduction of educational interventions to clarify professional responsibilities, and redefinition of the gender division of labour for male and female doctors. In addition, we identified a need to modernise current employment practices by introducing temporary posts to cover maternity leave and introducing flexible working hours during specialist training, thus supporting and encouraging more women to continue their medical careers. Published by the BMJ Publishing Group Limited. For permission to use (where not

Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.

PubMed

Segawa, H; Fukasawa, Y; Miyamoto, K; Takeda, E; Endou, H; Kanai, Y

1999-07-09

We have isolated a cDNA from rat small intestine that encodes a novel Na+-independent neutral amino acid transporter with distinctive characteristics in substrate selectivity and transport property. The encoded protein, designated L-type amino acid transporter-2 (LAT-2), shows amino acid sequence similarity to the system L Na+-independent neutral amino acid transporter LAT-1 (Kanai, Y., Segawa, H., Miyamoto, K., Uchino, H., Takeda, E., and Endou, H. (1998) J. Biol. Chem. 273, 23629-23632) (50% identity) and the system y+L transporters y+LAT-1 (47%) and KIAA0245/y+LAT-2 (45%) (Torrents, D., Estevez, R., Pineda, M., Fernandez, E., Lloberas, J., Shi, Y.-B., Zorzano, A., and Palacin, M. (1998) J. Biol. Chem. 273, 32437-32445). LAT-2 is a nonglycosylated membrane protein. It requires 4F2 heavy chain, a type II membrane glycoprotein, for its functional expression in Xenopus oocytes. LAT-2-mediated transport is not dependent on Na+ or Cl- and is inhibited by a system L-specific inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), indicating that LAT-2 is a second isoform of the system L transporter. Compared with LAT-1, which prefers large neutral amino acids with branched or aromatic side chains, LAT-2 exhibits remarkably broad substrate selectivity. It transports all of the L-isomers of neutral alpha-amino acids. LAT-2 exhibits higher affinity (Km = 30-50 microM) to Tyr, Phe, Trp, Thr, Asn, Ile, Cys, Ser, Leu, Val, and Gln and relatively lower affinity (Km = 180-300 microM) to His, Ala, Met, and Gly. In addition, LAT-2 mediates facilitated diffusion of substrate amino acids, as distinct from LAT-1, which mediates amino acid exchange. LAT-2-mediated transport is increased by lowering the pH level, with peak activity at pH 6.25, because of the decrease in the Km value without changing the Vmax value. Because of these functional properties and a high level of expression of LAT-2 in the small intestine, kidney, placenta, and brain, it is suggested that the