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Biomedical subjects

Yuki Sato

Publications and source records attributed to Yuki Sato.

At least 19 recordsLinked to original sources
PubMed2026

Differential regulation of CYP46A1 in ischemic core and peri-infarct regions of male mouse brain after permanent middle cerebral artery occlusion.

Cholesterol 24-hydroxylase (CYP46A1) regulates brain cholesterol homeostasis and synaptic plasticity, playing a crucial role in ischemic stroke. Although previous studies have reported post-ischemic CYP46A1 upregulation, its spatiotemporal dynamics remain poorly defined. To elucidate these dynamics, we investigated the expression of CYP46A1 and other essential cholesterol homeostasis-related genes from 6 h to 3 days after permanent middle cerebral artery occlusion (pMCAO) in CB-17 mice. We utilized single-cell and single-nucleus transcriptomics, regional quantitative PCR, and high-resolution immunohistochemistry. CYP46A1 is predominantly expressed in neurons. Following ischemia, the cholesterol network exhibited a dynamic spatiotemporal divergence. Acutely (6 h post-ischemia), surviving regions transiently upregulated cell-autonomous cholesterol synthesis genes and CYP46A1. Subacutely (3 days), this response shifted toward a widespread upregulation of glia-dependent cholesterol transport genes and general CYP46A1 downregulation. At 24 h, CYP46A1 protein was substantially reduced in the necrotic core and superficial layer II/III of the peri-infarct cortex, but upregulated in deeper layer V, hippocampus, and lateral striatum. Notably, this localized upregulation spatially coincided with reactive microglial hypertrophy. These findings indicate that CYP46A1 is dynamically modulated in viable tissues following ischemic stress. This spatial divergence likely reflects a synergistic interaction between inflammatory propagation and neural circuit-mediated oxidative stress. Resolving these spatiotemporal profiles provides a rigorous foundation for evaluating CYP46A1 functionality and developing stage-specific therapeutic interventions.

Cholesterol 24-hydroxylase↗
PubMed2026

Lymphocyte-C-Reactive Protein Ratio as Promising New Marker for Predicting Surgical Site Infection in Children With Ulcerative Colitis.

BACKGROUND: Surgical site infection (SSI) is a major complication after ileal pouch-anal anastomosis (IPAA) in pediatric ulcerative colitis (UC), significantly impairing quality of life. The lymphocyte-to-C-reactive protein ratio (LCR), a composite marker of systemic inflammation and immune/nutritional status, has emerged as a potential predictor of postoperative outcomes. This study assessed the utility of preoperative LCR in predicting SSI in pediatric UC. METHODS: We retrospectively reviewed pediatric UC patients who underwent IPAA at Mie University Hospital between 2000 and 2024. Preoperative LCR values were analyzed, and the optimal cutoff for SSI prediction was determined using receiver operating characteristic (ROC) analysis. Multivariate logistic regression was performed to identify independent risk factors. SSI was defined according to CDC criteria within 30&#x2009;days postoperatively. RESULTS: Among 57 patients, 11 (19.3%) developed SSI. The incidence was higher in three-stage procedures than in two-stage procedures (22.7% vs. 17.1%). In both groups, preoperative LCR was significantly lower in SSI-positive patients. ROC analysis demonstrated good discrimination (AUC: 0.80), with an optimal cutoff of LCR <&#x2009;5000 (sensitivity: 90.9%, specificity: 71.7%). Multivariate analysis confirmed LCR <&#x2009;5000 as an independent predictor of SSI (odds ratio [OR]: 6.34, 95% CI: 1.23-48.2, p&#x2009;=&#x2009;0.027). CONCLUSION: Preoperative LCR is a simple, objective biomarker that reliably predicts SSI risk in pediatric UC patients undergoing IPAA. Incorporating LCR into preoperative risk stratification may enable personalized interventions, including nutritional optimization and tailored prophylaxis, to improve surgical outcomes.

inflammatory bowel disease↗
PubMed2025

A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET).

INTRODUCTION: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period. METHODS: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C-mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086). RESULTS: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%-94.8%, 95% CI: 70.8%-97.6%), median PFS was 6.6 months (95% CI: 5.3-16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo-not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance. CONCLUSIONS: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity.

Humans↗
PubMed2024

Dynamic Pathology of Enteric Neural Network Using Curcumin-assisted Multiphoton Laser Imaging in Hirschsprung Disease.

BACKGROUND: In living tissue, it has been difficult to make microscopic-level observations without damaging the tissue. We have invented a novel intravital fluorescent observation method (IFOM) for real-time tissue observation, combining multiphoton laser scanning microscopy with curcumin vital staining (CVS-IFOM). The aim of this study was to use CVS-IFOM to analyze the enteric nervous system (ENS) in mice and human patients with hypoganglionosis and Hirschsprung disease (HSCR). METHODS: In an initial viability study, we compared live ENS images from nonfluorescent C57BL6 mice stained with curcumin (n = 5) and green fluorescent protein mice (n = 5) using multiphoton laser scanning microscopy. We then explored CVS-IFOM for the live examination of resected colon tissues from 1 patient with hypoganglionosis and 3 patients with HSCR. RESULTS: In the viability study, detailed ENS histologic features were only observed in the curcumin-stained mice. In the patient with hypoganglionosis, CVS-IFOM provided ENS details that were not visualized under hematoxylin and eosin staining or calretinin immunohistochemistry, allowing the analysis of ENS size, neural bundle number, and neural cell number per plexus. In patients with HSCR, CVS-IFOM showed a gradual hypoplastic change in the ENS from the oral edge to the anal edge, detecting disproportionate changes in the ENS within the same intestinal level, supporting a circumferentially uneven distribution of the intestinal ENS. CONCLUSIONS: CVS-IFOM may be supportive for intraoperative pathologic diagnosis during surgeries for HSCR.

Hirschsprung Disease↗
PubMed2006

A transgenic rat with the human ATTR V30M: a novel tool for analyses of ATTR metabolisms.

Amyloidogenic transthyretin (ATTR) is the pathogenic protein of familial amyloidotic polyneuropathy (FAP). To establish a tool for analyses of ATTR metabolisms including after liver transplantations, we developed a transgenic rat model expressing human ATTR V30M and confirmed expressions of human ATTR V30M in various tissues. Mass spectrometry for purified TTR revealed that rat intrinsic TTR and human ATTR V30M formed tetramers. Congo red staining and immunohistochemistry revealed that nonfibrillar deposits of human ATTR V30M, but not amyloid deposits, were detected in the gastrointestinal tracts of the transgenic rats. At 24h after liver transplantation, serum human ATTR V30M levels in transgenic rats that received livers from normal rats became lower than detectable levels. These results thus suggest that this transgenic rat may be a useful animal model which analyzes the metabolism of human ATTR V30M including liver transplantation studies.

Amyloid Neuropathies, Familial↗
PubMed2006

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↗
PubMed2006

Transcriptomic analysis indicates putative metabolic changes caused by manipulation of phosphorus availability in rice leaves.

Plants have developed several strategies for coping with phosphorus (P) deficiency. However, the details of the regulation of gene expression of adaptations to low P are still unclear. Using a cDNA microarray, transcriptomic analyses were carried out of the rice genes regulated by P deficiency and P re-supply to P-deficient plants. The OsPI1 gene, which was isolated as the most significant up-regulated gene under -P conditions, was also the most significant down-regulated gene following P re-supply. Many starch metabolism-related genes, as well as several genes for P(i)-liberating enzymes, were up-regulated by -P treatment, suggesting a homeostatic contribution to the P(i) concentration in leaf tissues. mRNAs for glucanases were also induced by P re-supply: these are suspected to play a role in loosening the cell wall compounds. Most of the genes up-regulated by -P treatment were down-regulated by P re-supply, suggesting that their responses were specific to -P conditions. Conversely, the number of genes up-regulated by P re-supply was also larger following P re-supply than in the -P condition. It is proposed that the genes up-regulated by P re-supply play an important role in P acquisition by P-deficient plants.

Gene Expression Profiling↗
PubMed2006

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↗
PubMed2006

Briarane-type diterpenoids from the Okinawan soft coral Pachyclavularia violacea.

Four new briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and D (4), were isolated from the Okinawan soft coral Pachyclavularia violacea. The structures of these compounds were elucidated on the basis of the results of spectroscopic analysis. The absolute configuration of pachyclavulide A (1) was determined by the X-ray crystallographic analysis of its p-bromobenzoyl ester.

Animals↗
PubMed2006

Meat consumption and risk of colorectal cancer in Japan: the Miyagi Cohort Study.

The association between meat consumption and risk of colorectal cancer has been controversial. We examined this question in a large prospective cohort study in Japan. From June through August 1990, 47,605 residents, aged 40-64 years, of Miyagi Prefecture in northern Japan completed a self-administered questionnaire, including a food frequency questionnaire. In the study population, we observed 474 incident cases of colorectal cancer during 11 years of follow-up, to March 2001. We used the Cox proportional hazards model to estimate the relative risk of colorectal cancer (colorectum, colon, rectum and proximal colon and distal colon) according to each of the categories of meat intake (total meat, beef, pork, ham or sausage, chicken and liver), with adjustment for sex, age and other potentially confounding variables. The multivariate relative risk of colorectal cancer in the highest category of total meat consumption compared with the lowest was 1.14 [95% confidence interval (CI)=0.85-1.53; P-trend=0.22]. We also found no significant association between total meat consumption and the risk of sub-site of colorectal cancer. In conclusion, our data do not support the hypothesis that meat consumption is a risk factor for colorectal cancer.

Cohort Studies↗
PubMed2006

Ethanol-induced hypnotic tolerance is absent in N-methyl-D-aspartate receptor epsilon 1 subunit knockout mice.

Recent pharmacological studies suggest that N-methyl-D-aspartate (NMDA) receptors play an important role in neuroadaptive processes in the development of tolerance to addictive drugs, such as opioids, amphetamine, and cocaine. In the present study, we investigated the contribution of the NMDA receptor to ethanol-induced hypnotic tolerance using NMDA receptor epsilon1 subunit knockout mice. Hypnotic sensitivity to a single injection of 3, 3.5, and 4 g/kg ethanol was not significantly different between wild-type mice and NMDA receptor epsilon1 subunit knockout mice. In contrast, although wild-type mice displayed hypnotic tolerance after repeated administration of 4 g/kg ethanol for 4 consecutive days, no change in the duration of hypnosis was observed in knockout mice. No significant differences were observed in blood ethanol clearance between wild-type and knockout mice on day 4. Our results indicate epsilon1 subunit containing the NMDA receptor might be involved in the development of ethanol-induced hypnotic tolerance.

Animals↗
PubMed2006

Characterization of the disposition of lutein after i.v. administration to rats.

Lutein is a carotenoid that has antioxidant effects. Although lutein has received much attention recently due to its antioxidant activities, little information about the pharmacokinetic properties of lutein is available. The disposition of lutein after i.v. administration has not been investigated because lutein is now used as a supplement. The present study was undertaken to acquire additional data on the disposition of lutein after i.v. administration. After i.v. administration, lutein is preferentially distributed to the liver, spleen and lung. Intravenous administration of lutein may provide effective antioxidant activities in these tissues, not only the eye. The results of this study should provide valuable data for drug development.

Animals↗
PubMed2006

Structure-activity relationships of neuromedin U. V. study on the stability of porcine neuromedin U-8 at the C-terminal asparagine amide under mild alkaline and acidic conditions.

Porcine neuromedin U-8 (X-Asn-NH(2), X=H-Tyr-Phe-Leu-Phe-Arg-Pro-Arg) is occasionally unstable in the biological fluids used for bioassay as well as in the acidic solutions used for purification of synthetic peptides. In this study, HPLC examination of an incubate solution of X-Asn-NH(2) revealed that the main decomposition products in Tyrode's solution (pH 7.4) were either alpha- or beta-monocarboxylic acid analogs (X-Asn-OH or X-Asp-NH(2)), and that no dicarboxylic acid analog (X-Asp-OH) was produced. Further investigation, employing a model peptide (Y-Asn-NH(2), Y=Benzoyl-Pro-Arg) incubated in a 0.1 M sodium bicarbonate solution at 60 degrees C, revealed that the decomposition of C-terminal Asn-NH(2) occurred through the formation of an aminosuccinimide intermediate (Y-Asu), at a rate faster than that of Y-Asn-Ser peptide but slower than that of Y-Asn-Gly peptide. Mild acid hydrolysis of X-Asn-NH(2) examined in a 1 M HCl solution at 60 degrees C yielded X-Asn-OH and X-Asp-NH(2), which further decomposed to yield X-Asp-OH. The C-terminal degradation of X-Asn-NH(2) resulted in reduced biological and immunochemical binding activities.

Acids↗
PubMed2006

Impact of non-dietary nutrients intake on misclassification in the estimation of nutrient intake in epidemiologic study.

BACKGROUND: Few previous epidemiologic studies have evaluated the effects of non-dietary nutrient intake, such as supplements, over the counter (OTC) drugs, and prescription drugs containing vitamins or minerals, in examining the relationship between dietary factors and health outcomes. METHODS: To examine the influence of the non-dietary intake of vitamins and calcium on the estimation of nutrient intake, we conducted a cross-sectional study with 1,168 community-dwelling Japanese subjects aged 70 years or older in 2002. The subjects were asked to bring their non-dietary nutrient sources to the examining site. The dietary and non-dietary intakes of vitamins B1, C, E and calcium were obtained and the subjects were grouped into quartiles according to their dietary intake and their dietary plus non-dietary intake. The degree of agreement between these two classifications was examined to estimate the degree of misclassification. RESULTS: Among the subjects who were classified into the highest intake category for vitamin E with dietary intake plus non-dietary nutrient intake, 34.2 % were misclassified into lower category with dietary intake alone. Similarly, intake of vitamin B(1), vitamin C and calcium were misclassified 28.8%, 18.8 %, 6.2 %, respectively. CONCLUSIONS: Our data suggest that estimation of vitamin intake from dietary sources alone would yield a maximum misclassification of one-third, which would lead to misleading conclusions being drawn from epidemiologic studies. In contrast, the degree of misclassification for calcium may be relatively small.

Aged↗
PubMed2006

[Case of an elderly patient with marked hypertension following intravenous fentanyl administration during the induction of anesthesia].

A 76-year-old woman was scheduled to undergo distal gastrectomy and cholecystectomy. She had no history of illnesses including hypertension. During the induction of anesthesia, she developed hypertension just after intravenous administration of fentanyl 200 microg. The marked hypertension lasted for 30 min without any complaints and neurological symptoms, and gradually became normalized. We started the induction of anesthesia again without using fentanyl. For the maintenance of anesthesia, sevoflurane, nitrous oxide, and epidural anesthesia with intermittent administration of 0.75% ropivacaine were used. The operation was finished successfully without any complications. We consider intravenous small dose of fentanyl could be a cause of unexpected marked hypertension in this elderly patient.

Aged↗