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Biomedical subjects

Yoshiko Takahashi

Publications and source records attributed to Yoshiko Takahashi.

At least 19 recordsLinked to original sources

Cadherin is required for dendritic morphogenesis and synaptic terminal organization of retinal horizontal cells.

Dendrite morphology of neurons provides a structural basis for their physiological characteristics, and is precisely regulated in a cell type-dependent manner. Using a unique transposon-mediated gene transfer system that enables conditional and cell-type specific expression of exogenous genes, we investigated the role of cadherin on dendritic morphogenesis of horizontal cells in the developing chicken retina. We first visualized single horizontal cells by overexpressing membrane-targeted EGFP, and confirmed that there were three subtypes of horizontal cells, the dendritic terminals of which projected to distinct synaptic sites in the outer plexiform layer. Expression of a dominant-negative cadherin decreased the dendritic field size, and perturbed the termination of dendritic processes onto the photoreceptor cells. The cadherin blockade also impaired the accumulation of GluR4, a postsynaptic marker, at the cone pedicles. We thus provide in vivo evidence that cadherin is required for dendrite morphogenesis of horizontal cells and subsequent synapse formation with photoreceptor cells in the vertebrate retina.

Animals↗

Early segregation of germ and somatic lineages during gonadal regeneration in the annelid Enchytraeus japonensis.

Although regeneration studies are useful for understanding how organs renew, little information is available about regeneration of reproductive organs and germ cells. We here describe the behavior of germ-cell precursors during regeneration of the oligochaete annelid worm Enchytraeus japonensis, which has the remarkable feature of undergoing asexual (by fission) and sexual reproduction . We first found that the gonad can regenerate from any body fragment yielded by fission during asexual reproduction. We then examined behavior of germ-cell lineage during this regenerative process, by using a homolog of the Piwi gene (Ej-piwi) as a marker. We found that in asexually growing animals, specialized cells expressing Ej-piwi are distributed widely in the body as single cells. These cells seem to serve as a reservoir of germ-cell precursors because during asexual propagation these cells migrate into the regenerating tissue, where they ultimately settle in the prospective gonads, and give rise to germ cells upon sexualization. These cells are distinct from the neoblasts, thought to be stem cells in other animals. This is the first report to directly show that the germ and somatic lineages are segregated in asexually growing animals and behave differently during regeneration.

Amino Acid Sequence↗

Maintenance of a low-sodium, high-carotene and -vitamin C diet after a 1-year dietary intervention: the Hiraka dietary intervention follow-up study.

BACKGROUND: The importance of dietary modification for disease prevention is widely accepted. The difficulty of implementing and sustaining long-term changes is also well documented. Nevertheless, a few studies have attempted to achieve significant dietary change for extended periods. METHODS: The Hiraka Dietary Intervention Study was a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality for stomach cancer and stroke in 1998-2000. The main study subjects were 550 healthy volunteers, who were randomized into two groups and given tailored dietary education aimed at decreasing the intake of sodium and increasing that of carotene and vitamin C in either the first or second year. Four (first intervention group) and three (second intervention group) years after the intervention ended, 308 subjects were selected for this follow-up dietary survey. RESULTS: The low-sodium, high-vitamin C and -carotene diet was maintained with only a small, nonsignificant reversal from post-intervention to follow-up (P = 0.082-0.824). Significant changes from pre-intervention to follow-up were also maintained (P < 0.01). CONCLUSION: This dietary intervention program was maintained well over 4 years after the termination of the intervention sessions.

Ascorbic Acid↗

Level-specific role of paraxial mesoderm in regulation of Tbx5/Tbx4 expression and limb initiation.

Tetrapod limbs, forelimbs and hindlimbs, emerge as limb buds during development from appropriate positions along the rostro-caudal axis of the main body. In this study, tissue interactions by which rostro-caudal level-specific limb initiation is established were analyzed. The limb bud originates from the lateral plate located laterally to the paraxial mesoderm, and we obtained evidence that level-specific tissue interactions between the paraxial mesoderm and the lateral plate mesoderm are important for the determination of the limb-type-specific gene expression and limb outgrowth. When the wing-level paraxial mesoderm was transplanted into the presumptive leg region, the wing-level paraxial mesoderm upregulated the expression of Tbx5, a wing marker gene, and down regulated the expression of Tbx4 and Pitx1, leg marker genes, in the leg-level lateral plate. The wing-level paraxial mesoderm relocated into the leg level also inhibited outgrowth of the hindlimb bud and down regulated Fgf10 and Fgf8 expression, demonstrating that the wing-level paraxial mesoderm cannot substitute for the function of the leg-level paraxial mesoderm in initiation and outgrowth of the hindlimb. The paraxial mesoderm taken from the neck- and flank-level regions also had effects on Tbx5/Tbx4 expression with different efficiencies. These findings suggest that the paraxial mesoderm has level-specific abilities along the rostro-caudal axis in the limb-type-specific mechanism for limb initiation.

Animals↗

Epimorphin acts extracellularly to promote cell sorting and aggregation during the condensation of vertebral cartilage.

Formation of vertebrae occurs via endochondral ossification, a process involving condensation of precartilaginous cells. Here, we provide the first molecular evidence of mechanism that underlies initiation of this process by showing that the extracellular factor, Epimorphin, plays a role during early steps in vertebral cartilage condensation. Epimorphin mRNA is predominantly localized in the vertebral primordium. When provided exogenously in ovo, it causes precocious differentiation of chondrocytes, resulting in the formation of supernumerary vertebral cartilage in chicken embryos. To further analyze its mode of action, we used an in vitro co-culture system in which labeled 10T1/2 or sclerotomal prechondrogenic cells were co-cultured with unlabeled Epimorphin-producing cells. In the presence of Epimorphin, the labeled cells formed tightly packed aggregates, and sclerotomal cells displayed augmented accumulation of NCAM and other early markers of chondrocyte differentiation. Finally, we found that the Epimorphin expression is initiated during vertebrogenesis by Sonic hedgehog from the notochord mediated by Sox 9. We present a model in which successive action of Epimorphin in recruiting and stacking sclerotomal cells leads to a sequential elongation of a vertebral primordium.

Amino Acid Sequence↗

Which landmark results in a more consistent diagnosis of Barrett's esophagus, the gastric folds or the palisade vessels?

BACKGROUND: The endoscopic landmark used to diagnose Barrett's esophagus differs between Japanese and Western endoscopists. OBJECTIVE: To compare the degree of diagnostic variation in results achieved by Japanese endoscopists when using the palisade vessels as a landmark of the distal esophagus and when using the gastric folds; interobserver diagnostic concordance was evaluated. DESIGN: Eighty-four endoscopists classified 30 patients with Barrett's esophagus by viewing projected endoscopic photographs. The endoscopists were asked to identify the distal end of the esophagus, first by using the Japanese criteria and later by using the gastric folds after an explanation of the Prague C&M Criteria. Endoscopists were divided into groups according to years in practice as an endoscopist, presence or absence of board certification from the Japan Gastroenterological Endoscopy Society, and whether they had taken any special endoscopic training courses on GERD. The kappa coefficient of reliability was calculated for each group. RESULTS: The initial overall kappa value for all the endoscopists for the identification of the distal end of the esophagus was only 0.14, an unacceptably low value of concordance over and above chance agreement. The length of experience with diagnostic endoscopy, board license, or special training had no impact on the level of concordance. After an explanation of the C&M Criteria, however, there was a statistically significant improvement in the diagnostic concordance. CONCLUSIONS: The upper end of the gastric folds, as used in C&M Criteria, may be a more suitable landmark than the palisade vessels for identifying the distal end of the esophagus by endoscopy.

Barrett Esophagus↗

Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype.

OBJECTIVE: Barrett's esophagus with the intestinal predominant mucin phenotype is considered to have a higher malignant potential than that with the gastric predominant mucin phenotype. The purpose of this prospective study was to investigate the prevalence of and risk factors for Barrett's esophagus with the intestinal predominant mucin phenotype in patients undergoing endoscopy. MATERIAL AND METHODS: A total of 1699 consecutive patients undergoing esophagogastroduodenoscopy were enrolled in the study. A targeted biopsy was performed when endoscopically observed columnar-appearing esophagus was stained with crystal violet. The sample, histologically evidenced as Barrett's esophagus, was immunohistochemically evaluated and categorized as of either gastric or intestinal predominant mucin phenotype. All the patients were requested to complete the structured questionnaire indicating their symptoms and food consumption patterns. Prevalence of and risk factors for Barrett's esophagus with and without the intestinal predominant mucin phenotype were investigated. RESULTS: Out of 1668 patients, 629 (37.7%) were found to have endoscopic Barrett's esophagus. In 333 out of 1668 patients (19.9%), histological studies were diagnostic of Barrett's esophagus. One hundred and six of these 333 patients (31.8%) had the intestinal predominant mucin phenotype. Age, male gender and the presence of hiatal hernia were confirmed by multivariate analysis as the independent predictors for the presence of Barrett's esophagus with the intestinal predominant mucin phenotype. CONCLUSIONS: Barrett's esophagus with the intestinal predominant mucin phenotype was immunohistochemically found in 6.4% of all study patients. Older age, male gender and the presence of hiatal hernia were the risk factors for the presence of Barrett's esophagus with the intestinal predominant mucin phenotype.

Adolescent↗

Dietary glycemic index and load in relation to metabolic risk factors in Japanese female farmers with traditional dietary habits.

BACKGROUND: Little is known about the relation of dietary glycemic index (GI) and glycemic load (GL) to metabolic risk factors, particularly in non-Western populations. OBJECTIVE: We examined the cross-sectional associations between dietary GI and GL and several metabolic risk factors in healthy Japanese women with traditional dietary habits. DESIGN: The subjects were 1354 Japanese female farmers aged 20-78 y from 5 regions of Japan. Dietary GI and GL were assessed with a self-administered diet-history questionnaire. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). Fasting blood samples were collected for biochemical measurements. RESULTS: The mean dietary GI was 67, and the mean dietary GL (/1000 kcal) was 88 (GI for glucose = 100). White rice (GI = 77) was the major contributor to dietary GI and GL (58.5%). After adjustment for potential dietary and nondietary confounding factors, dietary GI was positively correlated with BMI (n = 1354; P for trend = 0.017), fasting triacylglycerol (n = 1349; P for trend = 0.001), fasting glucose (n = 764; P for trend = 0.022), and glycated hemoglobin (n = 845; P for trend = 0.038). Dietary GL was independently negatively correlated with HDL cholesterol (n = 1354; P for trend = 0.004) and positively correlated with fasting triacylglycerol (P for trend = 0.047) and fasting glucose (P for trend = 0.012). CONCLUSIONS: Both dietary GI and GL are independently correlated with several metabolic risk factors in subjects whose dietary GI and GL were primarily determined on the basis of the GI of white rice.

Adult↗

Blood pressure change in a free-living population-based dietary modification study in Japan.

OBJECTIVE: To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels. DESIGN: Open randomised, controlled trial. SETTING: Free-living healthy subjects in two rural villages in north-eastern Japan. PARTICIPANTS: Five hundred and fifty healthy volunteers aged 40-69 years. INTERVENTIONS: Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene, and of fruit and vegetables. MAIN OUTCOME MEASURES: Blood pressure, dietary intake and urinary excretion of sodium, dietary carotene and vitamin C, and fruit and vegetable intake data were collected at 1 year after the start of the intervention. RESULTS: During the first year, changes differed significantly between the intervention and control groups for dietary (P = 0.002) and urinary excretion (P < 0.001) of sodium and dietary vitamin C and carotene (P = 0.003). Systolic blood pressure decreased from 127.9 to 125.2 mmHg (2.7 mmHg decrease; 95% confidence interval, -4.6 to -0.8) in the intervention group, whereas it increased from 128.0 to 128.5 mmHg (0.5 increase; -1.3 to 2.3) in the control group. This change was statistically significant (P = 0.007). In contrast, the change in diastolic blood pressure did not significantly differ between the groups. In hypertensive subjects, a significant difference in systolic blood pressure reduction was seen between the groups (P = 0.032). CONCLUSION: Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes, which resulted in a significant decrease in systolic blood pressure.

Adult↗

Influence of acid suppressants on gastric emptying: cross-over analysis in healthy volunteers.

BACKGROUND: Gastric emptying plays an important role in gastroesophageal reflux disease. Acid suppressants such as H2 receptor antagonists and/or proton pump inhibitors are often used in patients with gastroesophageal reflux disease. However, it remains controversial whether H2 receptor antagonists and proton pump inhibitors delay or accelerate gastric emptying. Here, the influence of acid suppressants on gastric emptying was evaluated via a cross-over study using the [13C]-labeled acetate breath test. METHODS: Twenty normal male subjects without gastroesophageal reflux disease symptoms were enrolled. Gastric emptying was investigated five times in every subject by the [13C]-labeled acetate breath test with oral administration of the vehicle, domperidone, and three acid suppressants: ranitidine, famotidine and rabeprazole. Gastric emptying was estimated by the values of T(max-calc), T(1/2) and %dose/2 h calculated from the 13CO2 breath excretion curve. RESULTS: Using the T(max-calc) values, rabeprazole, ranitidine and famotidine did not influence gastric emptying time in comparison with vehicle administration. Using the T(1/2) and %dose/2 h values, rabeprazole tended to delay gastric emptying. Domperidone produced a statistically significant acceleration of gastric emptying for all three variables (P < 0.05). CONCLUSION: Oral dosage of the H2 receptor antagonists, ranitidine and famotidine, has no significant effect on gastric emptying. However, rabeprazole may delay gastric emptying more strongly than H2 receptor antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Kinetics of indocyanine green removal from blood can be used to predict the size of the area removed by radiofrequency ablation of hepatic nodules.

BACKGROUND AND AIM: The size of radiofrequency ablation (RFA) in the liver can be negatively influenced by the surrounding blood flow. The indocyanine green (ICG) test can be used to evaluate the effective blood flow in the liver, and distance from the hilus can affect local blood flow. The aim of this study was to assess whether the ICG test or distance from the hilus could be used to predict the size of the ablated area in liver by RFA treatment of hepatocellular carcinoma (HCC) nodules. METHODS: The RFA measurements of 44 HCC nodules in 39 patients were retrospectively studied. Cases were included if they met the following criteria: (i) no catheter treatment before RFA; (ii) no movement of the RFA device; (iii) strict ablation time; and (iv) only one ablation. In all patients, ICG-R15 testing was done immediately before RFA and the initial therapeutic efficacy was evaluated by dynamic computed tomography scanning 2-5 days after RFA. The correlation between the maximum size of the RFA area and the ICG test results or the distance of the target area from the hilus (site of first portal vein divergence) were analyzed statistically. RESULTS: The ICG-R15 result was significantly correlated with the maximum diameter of the ablated area both in 2 cm-electrode tip length (R2 = 0.35, P = 0.0012), and in 3 cm-tip length (R2 = 0.26, P = 0.0377). Multiple-regression analysis showed that the electrode tip length (P = 0.0010) and ICG-R15 (P = 0.0046) were independent factors that could predict the maximum diameter of the RFA area. CONCLUSION: The results of ICG testing can be used to predict the size of the area that will be ablated at a target liver site before RFA treatment.

Aged↗

Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo.

A culture system to generate eye-like structures consisting of lens, neural retina, and retinal pigmented epithelium (RPE) cells from undifferentiated embryonic stem cells has been established. Precursors of RPE cells that differentiated in the cultures were responsive to Wnt2b signaling and identified retrospectively to form secondary colonies consisting of only RPE-like cells in eye-like structures. These transplanted eye-like structures were capable of populating the developing chick eye as neuronal retina and RPE cells. The outgrowth of a single cell layer of mature RPE cells from the grafted eye-like structures confirmed the existence of precursors for RPE cells. These results suggest that the eye-like structures resulted from the normal developmental pathway responsible for generating eyes in vivo. If a functional effect of these cells can be established, such eye-like structures may be potentially used to establish therapy models for various eye diseases.

Animals↗

A novel signal induces a segmentation fissure by acting in a ventral-to-dorsal direction in the presomitic mesoderm.

We describe here a novel inductive action that operates during somitic segmentation in chicken embryos. We previously reported that the posterior border cells located at a next-forming boundary in the anterior end of the presomitic mesoderm (PSM) exhibit an inductive activity that acts on the anterior cells to cause the formation of a somitic fissure (Sato, Y., Yasuda, K., Takahashi, Y., 2002. Morphological boundary forms by a novel inductive event mediated by Lunatic fringe and Notch during somitic segmentation. Development 129, 3633-3644). In this study, we have found a second inductive action along the dorso-ventral (D-V) axis during fissure formation. When relocated into a non-segmenting region of PSM, the ventral-most cells taken from the presumptive boundary are sufficient to induce an ectopic fissure in host cells. The ventrally derived signal acts in a ventral-to-dorsal direction but not ventrally, regardless of where the ventral cells are placed. This directional signaling is governed, at least in part, by the signal-receiving cells of the PSM, which we found to be polarized along the D-V axis, and also by intimate cell-cell interactions. Finally, we have observed that morphological segmentation is able to rearrange the anterior and posterior regionalization of individual somites. These findings suggest that discrete unidirectional signals along both the antero-posterior and the D-V axes act coordinately to achieve the formation of the intersomitic fissure, and also that fissure formation is important for the fine-tuning of A-P regionalization in individual somites.

Animals↗

Mesenchymal-to-epithelial transition during somitic segmentation: a novel approach to studying the roles of Rho family GTPases in morphogenesis.

During early development in vertebrates, cells change their shapes dramatically both from epithelial to mesenchymal and also from mesenchymal to epithelial, enabling the body to form complex tissues and organs. Using somitogenesis as a novel model, Rho family GTPases have recently been shown to play essential and differential roles in individual cell behaviors in actual developing embryos. Levels of Cdc42 activity provide a binary switch wherein high Cdc42 levels allow the cells to remain mesenchymal, while low Cdc42 levels produce epithelialization. Rac1 activity needs to be precisely controlled for proper epithelialization through the bHLH transcription factor Paraxis. Somitogenesis is expected to serve as an excellent model with which one can understand how the functions of developmental genes are resolved into the morphogenetic behavior of individual cells.

Animals↗

Common mechanisms for boundary formation in somitogenesis and brain development: shaping the 'chic' chick.

When organs and tissues acquire their characteristic shapes and functions during early development, boundaries are established that distinguish between and delimit distinct areas. Such boundaries are not mere edges, but also play important roles as secondary signaling centers in subsequent morphogenesis. Following on pioneering findings provided by studies in Drosophila, the mechanisms underlying boundary formation in vertebrate embryogenesis have attracted the interest of an increasing number of researchers. Somitogenesis and brain development, in particular, serve as model systems for the study of the molecular and cellular events occurring at developing boundaries. Recent findings allow us to draw some general pictures concerning the shared mechanisms that participate in these processes of organogenesis, in which Notch, Eph/ephrin and cadherin-mediated signaling are among the main key regulators.

Animals↗

Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1.

Mesenchymal-epithelial transitions (MET) are crucial for vertebrate organogenesis. The roles of Rho family GTPases in such processes during actual development remain largely unknown. By electroporating genes into chick presomitic mesenchymal cells, we demonstrate that Cdc42 and Rac1 play important and different roles in the MET that generates the vertebrate somites. Presomitic mesenchymal cells, which normally contribute to both the epithelial and mesenchymal populations of the somite, were hyperepithelialized when Cdc42 signaling was blocked. Conversely, cells taking up genes that elevate Cdc42 levels remained mesenchymal. Thus, Cdc42 activity levels appear critical for the binary decision that defines the epithelial and mesenchymal somitic compartments. Proper levels of Rac1 are necessary for somitic epithelialization, since cells with activated or inhibited Rac1 failed to undergo correct epithelialization. Furthermore, Rac1 appears to be required for Paraxis to act as an epithelialization-promoting transcription factor during somitogenesis.

Animals↗