Biomedical subjects

Yoriko Watanabe

Publications and source records attributed to Yoriko Watanabe.

10 recordsLinked to original sources

PubMed2006

Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

Activin Receptors, Type I↗

PubMed2006

Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile.

BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis. RESULTS: The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity. CONCLUSION: The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.

Adolescent↗

PubMed2005

Medical sequencing of candidate genes for nonsyndromic cleft lip and palate.

Nonsyndromic or isolated cleft lip with or without cleft palate (CL/P) occurs in wide geographic distribution with an average birth prevalence of 1/700. We used direct sequencing as an approach to study candidate genes for CL/P. We report here the results of sequencing on 20 candidate genes for clefts in 184 cases with CL/P selected with an emphasis on severity and positive family history. Genes were selected based on expression patterns, animal models, and/or role in known human clefting syndromes. For seven genes with identified coding mutations that are potentially etiologic, we performed linkage disequilibrium studies as well in 501 family triads (affected child/mother/father). The recently reported MSX1 P147Q mutation was also studied in an additional 1,098 cleft cases. Selected missense mutations were screened in 1,064 controls from unrelated individuals on the Centre d'Etude du Polymorphisme Humain (CEPH) diversity cell line panel. Our aggregate data suggest that point mutations in these candidate genes are likely to contribute to 6% of isolated clefts, particularly those with more severe phenotypes (bilateral cleft of the lip with cleft palate). Additional cases, possibly due to microdeletions or isodisomy, were also detected and may contribute to clefts as well. Sequence analysis alone suggests that point mutations in FOXE1, GLI2, JAG2, LHX8, MSX1, MSX2, SATB2, SKI, SPRY2, and TBX10 may be rare causes of isolated cleft lip with or without cleft palate, and the linkage disequilibrium data support a larger, as yet unspecified, role for variants in or near MSX2, JAG2, and SKI. This study also illustrates the need to test large numbers of controls to distinguish rare polymorphic variants and prioritize functional studies for rare point mutations.

Cleft Lip↗

PubMed2005

Alternations of static cerebral and systemic circulation in normal humans during 14-day head-down bed rest.

BACKGROUND: There have so far been few reports on the static regulations of cerebral and systemic circulation during prolonged head-down bed rest (HDBR). Our aim was to investigate the time course changes in static cerebral and systemic circulation during 14 days of 6 degrees HDBR. MATERIAL/METHODS: Sixteen subjects participated in the HDBR study. The systolic, mean, and diastolic cerebral blood flow velocities (CBFVs) of the middle cerebral artery were measured using a transcranial Doppler technique. Cerebrovascular bed resistance indices, i.e., resistance index (RI), pulsatility index (PI), and estimated regional cerebrovascular resistance (CVRest) were calculated. The systemic cardiovascular functions, i.e, heart rate (HR), mean arterial pressure (MAP), left ventricular ejection time (LVET), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were measured or calculated. RESULTS: All CBFVs consistently showed significant decreases from the 2nd day to the last day of the HDBR. The RI and PI showed a rising tendency throughout the HDBR. The CVRest showed significantly higher levels in the later half of the HDBR. The HR and MAP did not change during the HDBR. CONCLUSIONS: The adaptive process of cerebral circulation triggered by HDBR begins very early and leads to a new equilibrium within few days after the onset of HDBR. The alteration of static cerebral circulation with prolonged HDBR, i.e., lowered CBFVs and somewhat higher cerebrovascular bed resistance implies a reduction in the cerebral circulation, but it does not necessarily imply the impaired regulation of cerebral circulation.

Adult↗

PubMed2005

Intensive cycle training with artificial gravity maintains muscle size during bed rest.

INTRODUCTION: The present study aimed to investigate the effect of intensive cycle training with short-arm centrifuge-induced hypergravity during bed rest on muscle size and function. METHODS: This study involved 10 healthy men who were divided into 2 groups: a countermeasure group, BR-CM (n = 5); and a control group, BR-Cont (n = 5). The BR-CM subjects partook in intensive cycle training (to 90% of maximum HR) with short-arm centrifuge-induced artificial gravity on alternate days during 20-d bed rest. Muscle volume of the thigh and maximum voluntary contraction (MVC) during isometric knee extensions was measured before and after bed rest. Muscle functional magnetic resonance imaging (mfMRI) and electromyogram (EMG) of the quadriceps femoris were obtained during submaximal knee extension exercises at a load of 30% MVC. RESULTS: The volume of the total thigh muscles was maintained in the BR-CM group (-1%), whereas it was not in the BR-Cont group (-9%, p < 0.05). MVC decreased in the BR-CM (7%) and BR-Cont groups (23%). EMG activity in the BR-CM group after bed rest was significantly lower than that of before; however, no significant change was found in the BR-Cont group. There were no significant changes in the resting and exercised mfMRI signals in either the BR-CM or BR-Cont groups. CONCLUSION: These results suggest that intensive cycle training with hypergravity maintained the size of human skeletal muscles during bed rest.

Adult↗

PubMed2004

Acceleration with exercise during head-down bed rest preserves upright exercise responses.

INTRODUCTION: This study was designed to elucidate the effect of short-arm centrifuge-induced artificial gravity with exercise training during ground-based simulated spaceflight, i.e., prolonged head-down bed rest (HDBR), on respiratory and cardiovascular responses to upright exercise. METHODS: There were 10 healthy men who underwent 20 d of -6 degrees HDBR, and were assigned to either a countermeasure (CM) group (n = 5) or a no countermeasure (No-CM) group (n = 5). The subjects in the CM group performed two sessions (20 min each session, 40 min total) of short-arm centrifuge-induced artificial gravity with exercise training in a supine position on alternate days (10 d total) during HDBR. The first session was set at 0.8-1.4 G load at heart level with a constant exercise intensity (60 W), and the second session began with a 0.3 G load at heart level with an interval exercise protocol (40-80% peak oxygen uptake; VO2peak). The measurements of respiratory and cardiovascular responses to incremental exercise were performed pre- and post-HDBR. RESULTS: The 20 d of HDBR increased minute expired ventilation, heart rate, and respiratory exchange ratio and decreased stroke volume during submaximal exercise in the No-CM group, whereas these parameters were unchanged in the CM group. In the No-CM group, VO2peak decreased significantly (47.0 +/- 8.6 to 34.8 +/- 6.8 ml x kg(-1) x min(-1), p < 0.05), whereas VO2peak in the CM group did not show a significant decrease following 20 d of HDBR (47.7 +/- 10.0 to 43.9 +/- 8.9 ml x kg(-1) x min(-1)). These results suggest that short-arm centrifuge-induced artificial gravity with exercise training is effective in maintaining respiratory and cardiovascular responses to upright exercise.

Adolescent↗

PubMed2004

Effect of centrifuge-induced artificial gravity and ergometric exercise on cardiovascular deconditioning, myatrophy, and osteoporosis induced by a -6 degrees head-down bedrest.

We have reported that centrifuge-induced artificial gravity with ergometric exercise could reduce developing cardiovascular deconditioning in humans. In the present study, we examined this load could prevent the myatrophy and osteoporosis induced by head-down bedrest for 20 days. Subjects were ten healthy male volunteers with informed consent. They were requested to lie down at -6 degrees for 20 days, and evaluation for cardiovascular deconditioning, myatrophy, and osteoporosis. As the result, high G-load with low intensity exercise suppressed the orthostatic intolerance and increase in serum osteoporotic marker, whereas low G-load with high intensity ergometric exercise maintained the maximal oxygen intake, heart dimension, and prevented myatrophy. The combination of high/low G-load with low/high intensity exercise will determine the optimal protocol for prevention of cardiovascular deconditioning, myatrophy, and osteoporosis.

Adult↗

PubMed2003

Effect of supplementation with L-carnitine at a small dose on acylcarnitine profiles in serum and urine and the renal handling of acylcarnitines in a patient with multiple acyl-coenzyme A dehydrogenation defect.

We studied the effects of L-carnitine supplementation at a small dose on the profiles of acylcarnitines in serum and urine, as well as the renal handling of acylcarnitines, in a patient with multiple acyl-coenzyme A dehydrogenation defect. After supplementation with L-carnitine at a dose of 20 mg/kg/day, the concentration of each acylcarnitine measured both in the serum and in the urine had increased significantly, with the exception of that of an acylcarnitine with a carbon chain length (C) of 8 (C8 acylcarnitine). The magnitude of increase in the concentrations of the acylcarnitines in the serum was not associated with chain length, whereas in the urine, the magnitude tended to be greater in proportion to the shortness of the chain length. The fractional excretions of C2-C5 acylcarnitines exceeded 100%, indicating that they were produced in, or transported across, renal tubular epithelial cells and secreted into the urine. These results indicate that supplementation with a relatively small amount of L-carnitine can enhance the renal excretion of accumulated short-chain-length acylcarnitines through tubular excretion, in addition to basic glomerular filtration.

Acyl-CoA Dehydrogenase↗

PubMed2002

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies. Phenotypic overlap and linkage data suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

Animals↗

PubMedDate not supplied

In a Vietnamese population, MSX1 variants contribute to cleft lip and palate.

PURPOSE: To identify causes of nonsyndromic cleft lip and palate in a Vietnamese population. METHODS: In this study, 175 families with at least one case of cleft lip and/or palate were studied using the candidate genes TGFA, MSX1, and TGFB3. RESULTS: Transmission distortion for alleles of MSX1 were demonstrated for the whole population and two missense mutations were identified, including one (P147Q) that is found in approximately 2% of the population. The P147Q appears to arise from a founder individual based on shared haplotypes in unrelated families. CONCLUSIONS: MSX1 contributes to nonsyndromic clefting in a Vietnamese population, and consistent with other studies, identifiable mutations in this gene cause about 2% of cases of nonsyndromic clefting.

Alleles↗