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Biomedical subjects

T Saito

Publications and source records attributed to T Saito.

At least 37 records · Page 2Linked to original sources

Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer.

Human chromosomal region 11p15.5, which is homologous to mouse chromosome region 7F5, is a well-known imprinted region. The CDKN1C/KCNQ1OT1 imprinted domain, which is one of two imprinted domains at 11p15.5, includes nine imprinted genes regulated by an imprinting center (IC). The CDKN1C/KCNQ1OT1 IC is a differentially methylated region of KCNQ1OT1(KCNQ1OT-DMR) with DNA methylation on the maternal allele and no methylation on the paternal allele. CDKN1C (alias p57KIP2), an imprinted gene with maternal expression, encoding a cyclin-dependent kinase inhibitor, is a critical gene within the CDKN1C/KCNQ1OT1 domain. In Beckwith-Wiedemann syndrome (BWS), approximately 50% of patients show loss of DNA methylation accompanied by loss of histone H3 Lys9 dimethylation on maternal KCNQ1OT-DMR, namely an imprinting disruption, leading to diminished expression of CDKN1C. In cancer, at least three molecular mechanisms--imprinting disruption, aberrant DNA methylations at the CDKN1C promoter, and loss of heterozygosity (LOH) of the maternal allele--are seen and all three result in diminished expression of CDKN1C. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain is involved in the development of both BWS and cancer and it changes the maternal epigenotype to the paternal type, leading to diminished CDKN1C expression. In this review, we describe recent advances in epigenetic control of the CDKN1C/KCNQ1OT1 imprinted domain in both humans and mice.

Animals↗

Genomic structure of swine taste receptor family 1 member 3, TAS1R3, and its expression in tissues.

Taste receptor family 1 member 3, TAS1R3, is shown to be involved in sweet and umami tastes in mouse, and the nucleotide sequence of the gene has been reported in rat, gorilla, and human. Pigs are frequently used as models for human diseases, and are also considered to be source animals for xenotransplantation to humans due to their anatomical and physiological similarities to humans. Therefore, in the present study, the genomic structure of the swine TAS1R3 gene was determined, and TAS1R3 expression was studied in various swine tissues. The gene was shown to reside on swine chromosome 6q22-->q23, from which three types of mRNAs were generated: 3,752 bp derived from six exons in tongue, 3,704 bp from six exons and 3,630 bp from seven exons in testis. The 6 exons/5 introns were structurally similar to those of humans and mice, but the 7 exons/6 introns structure of TAS1R3 was first observed in swine. High expressions of TAS1R3 were revealed in tongue, kidney, and testis by real-time PCR. The expression profile of the tissues except for kidney was similar to that of mouse. When in situ hybridization using an RNA probe for TAS1R3 was performed on swine tongue and testis tissues, TAS1R3 expressions were revealed in tongue circumvallate papillae, fungiform papillae, mucosal epithelium, follicular B lymphocytes, lymphocytes in submucosal tissues of lingual tonsil, and spermatogenic cells. Using peripheral mature B lymphocytes, the expression of TAS1R3 in B lymphocytes was further confirmed by real-time PCR and sequencing of the real-time PCR product.

Animals↗

The extent of alveolar bone loss is associated with impaired glucose tolerance in Japanese men.

BACKGROUND: The treatment of periodontal disease in diabetic patients is reported to have a beneficial effect on their glucose control. A recent study indicated that having deep pockets is significantly associated with past development of glucose intolerance in non-diabetic individuals using an oral glucose tolerance test (OGTT). These findings suggest that periodontal disease is a risk factor for diabetes, although more evidence is needed. METHODS: A total of 193 Japanese men aged 50 to 54 years with at least 10 teeth were examined as part of a comprehensive health examination before retirement from the Japan Self-Defense Force. Alveolar bone loss of the posterior teeth was measured on a panoramic x-ray film. An OGTT was administered and impaired glucose tolerance (IGT) and diabetes were defined. The relationships between the mean ratio of alveolar bone loss to root length and OGTT results were analyzed after adjusting for known risk factors for diabetes. RESULTS: The proportion of subjects with IGT increased significantly in the subjects with higher tertiles of alveolar bone loss (P<0.05). In the multivariate logistic regression analysis excluding diabetic subjects, the adjusted OR for IGT to normal glucose tolerance (NGT) increased in subjects with higher tertiles of alveolar bone loss (P for trend=0.03). In the subjects with the highest tertile of alveolar bone loss, the adjusted OR for IGT to NGT was 4.27 (95% confidence interval [CI]: 1.41 to 12.9; P=0.01). CONCLUSION: The degree of alveolar bone loss is significantly associated with IGT, suggesting that periodontitis with alveolar bone loss is associated with impaired glucose tolerance.

Alveolar Bone Loss↗

The effect of nitrite on aerobic phosphate uptake and denitrifying activity of phosphate-accumulating organisms.

An anaerobic/aerobic/anoxic/aerobic sequencing batch reactor (SBR) was operated with municipal wastewater to investigate the effect of nitrite on biological phosphorus removal (BPR). When nitrite accumulated, aerobic phosphate uptake activity significantly decreased and, in case of hard exposure to nitrite, BPR severely deteriorated. The interesting observation was that the relative anoxic activity of phosphate accumulating organisms (PAOs) increased after nitrite exposure. Moreover batch tests of aerobic phosphate uptake in the presence/absence of nitrite indicated that PAOs with the higher relative anoxic activity are less sensitive to nitrite exposure. From these results, we concluded that BPR is sensitive to nitrite exposure, but BPR containing PAOs with the higher relative anoxic activity is possibly more stable against nitrite than BPR containing PAOs with the lower relative anoxic activity.

Bacteria, Anaerobic↗

Immunomodulatory effects of polysaccharides produced by Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.

The extracellular polysaccharides (EPS) produced by lactic acid bacteria (LAB) are associated with the rheology, texture, and mouthfeel of fermented milk products, including yogurt. This study investigated the immunomodulatory effects of EPS purified from the culture supernatant of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1. The crude EPS were prepared from the culture supernatant of L. bulgaricus OLL1073R-1 by standard chromatographic methods, and were fractionated into neutral EPS and acidic EPS (APS). Acidic EPS were further fractionated into high molecular weight APS (H-APS) and low molecular weight APS (L-APS). High molecular weight APS were shown to be phosphopolysaccharides containing D-glucose, D-galactose, and phosphorus. Stimulation of mouse splenocytes by H-APS significantly increased interferon-gamma production, and, moreover, orally administered H-APS augmented natural killer cell activity. Oral administration of yogurt fermented with L. bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059 to mice showed a similar level of immunomodulation as H-APS. However, these effects were not detected following administration of yogurt fermented with the starter combination of L. bulgaricus OLL1256 and S. thermophilus OLS3295. We conclude from these findings that yogurt fermented with L. bulgaricus OLL1073R-1, containing immunostimulative EPS, would have an immunomodulatory effect on the human body.

Animals↗

[Patient-prosthesis mismatch after aortic valve replacement; tolerable lower limit of indexed effective orifice area].

This study was aimed at determining the tolerable lower limit of the indexed effective orifice area (EOAI) to prevent patient-prosthesis mismatch (PPM). Echocardiography was performed in 87 consecutive patients who underwent aortic valve replacement (AVR). EOAI was estimated for each type and size of prosthesis and used to define PPM as moderate if >0.65 cm2/ m2 and < or = 0.85 cm2/m2, and severe if < or = 0.65 cm/m2. Aortic valve pressure gradients, left ventricular dimensions, and outcome (in-hospital and 1-year) were analyzed in the presence or absence of abnormal gradients (> or = 40 mmHg) to assess the influence of a small valve (19 mm or less labeled size). Severe PPM was found in 23% of all patients, and 50% of the severe PPM patients had an abnormal gradient. There was 1 death and 1 brain damage from ventricular fibrillation because of severe PPM in the abnormal gradient group with a small valve. In PPM patients with a small valve, EOAI (0.61 +/- 0.04 vs 0.69 +/- 0.07) and preoperative interventricular septal thickness (IVST : 16.4 +/- 2.6 mm vs 13.5 +/- 1.5 mm) were significantly different between abnormal and normal gradient groups. An EOAI > or = 0.69 appeared to be tolerable in patients with a lower level of hypertrophy (IVST < 16 mm).

Aged↗

[Ascending aortic aneurysm following aortic valve replacement due to aortitis syndrome; report of a case].

A 60-year-old woman had previously undergone aortic valve replacement for aortic regurgitation. As the aortic wall was elastic hard, inflammatory change was suspected; therefore, we undertook a partial biopsy of the ascending aortic wall and the intraoperative pathological specimens were compatible with aortitis syndrome. As there was no active inflammatory change, she was diagnosed as inactive aortitis syndrome and steroid therapy was not applied. Seven years later, a follow-up computed tomography (CT) showed an ascending aortic aneurysm of 65 mm in diameter. Aortic root replacement was planned based on a clinical diagnosis of an aneurysm of the ascending aorta. The patient was discharged without complication 21 days after surgery. It is possible that an inactive stage of aortitis may lead to late dilatation of the ascending aorta; therefore, careful postoperative follow-up is necessary in such cases.

Aorta↗

[Re-translocation method using bilateral internal thoracic arteries; report of a case].

A 43-year-old male was admitted to our hospital with a peri-graft pseudoaneurysm and an aorto-left ventricle communication, following Danielson translocation for infective endocarditis 5 years earlier. He underwent the re-translocation using bilateral internal thoracic arteries (ITAs). The postoperative course was quite reasonable and the patient was discharged. In spite of usefulness for severe infective endocarditis, the translocation might develop several complications, such as pseudoaneurysms and troubles with bypass grafts. This technique requires close observation postoperatively. Using ITAs at the initial translocation method might be a wise option.

Adult↗

Resolving the discrepancy of 135 MeV pd elastic scattering cross sections and relativistic effects.

Three precise measurements for elastic pd scattering at 135 MeV/A have been performed with the three different experimental setups. The cross sections are described well by the theoretical predictions based on modern nucleon-nucleon forces combined with three-nucleon forces. Relativistic Faddeev calculations show that relativistic effects are restricted to backward angles. This result supports the two measurements recently reported by RIKEN and contradicts the KVI data.

Journal Article↗

Elevation of both cyclooxygenase-2 and prostaglandin E2 receptor EP3 expressions in rat placenta after uterine artery ischemia-reperfusion.

Intrauterine growth restriction (IUGR) has a multifactorial pathogenesis and is an important cause of perinatal mortality. The relationship between fetal weight and placental blood flow in an animal model of IUGR has been investigated, showing that fetal growth is regulated by placental blood flow. The aim of the present study was to determine whether ischemia-reperfusion (I/R) injury stimulates the prostaglandin E2 (PGE2) system or the vascular endothelial growth factor (VEGF) system in the placenta of a rat IUGR model. COX-2 is reported to be involved in ischemic damage in many organs. There are 4 types of PGE2 receptor (EP1, EP2, EP3 and EP4). It is well known that EP1 and EP3 is associated with vasoconstriction. In the present study, vessels were occluded in the right uterine horn on day 17 of pregnancy in rats, and the clamps were removed after 30 min of ischemia. At 24h, 48 h, and 5 days after I/R injury, the live fetuses and placentas were obtained by cesarean section. This study revealed that I/R injury caused IUGR 5 days after the treatment. COX-2 expression and EP3 receptor expression were significantly elevated at 24h after I/R injury, but VEGF mRNA expression was not altered in the placenta from the ischemic horn compared with the non-ischemic horn. These results suggested that induction of the COX-2-EP3 system in the placenta may be one of the causes of IUGR induced by uterine ischemia, because the EP3 receptor and PGE2 are well known to mediate vasoconstriction in many organs.

Animals↗

Implication of increased NRSF/REST binding activity in the mechanism of ethanol inhibition of neuronal differentiation.

The neuron-restrictive silencer factor (NRSF), or repressor element-1 silencing transcription factor (REST), is a transcription factor that mediates negative regulation of neuronal genes. NRSF represses multiple neuronal target genes in non-neuronal and neuronal precursor cells to regulate the proper timing of neuronal gene expression during neurogenesis. In the present study, we investigated the effects of ethanol and MEK inhibitor U0126 on the DNA binding activity of NRSF in neural stem cells prepared from rat embryos. Both ethanol and U0126 enhanced NRSF binding activity measured by the method based on the principal of electrophoretic mobility shift assay (EMSA) and decreased neuronal differentiation in a concentration dependent manner. Western blot analysis revealed that ethanol suppressed phosphorylation of extracellular signal-regulated kinase (ERK) without affecting expression of total ERK. These results suggest that ethanol-induced potentiation of NRSF binding activity underlies the mechanism of ethanol inhibition of neuronal differentiation and decreased neurogenesis.

Alcohol-Induced Disorders, Nervous System↗

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗

Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.

To identify clinical and electrophysiologic features related to IV immunoglobulin (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199 responders and 113 nonresponders). Muscle atrophy and decreased compound muscle action potential were pronounced in nonresponders of IVIg. Male gender, longer disease duration, and slow progression of symptoms were also associated with IVIg unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves indicated IVIg unresponsiveness in CIDP.

Adult↗

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

Journal Article↗

The start of an islet transplantation program in Japan.

In Japan, pancreas donation had become possible from cadaveric donor sources, both heart-beating or non-heart-beating (NHB). Pancreas allografts have been distributed in the organ allocation system of the Japan Organ Transplant Network. Meanwhile, islet transplantation has been categorized as a tissue transplantation; it is free from legal restraints. Thus, pancreata for islet isolation must be obtained from NHB donors. Herein we report the starting program and preliminary results of islet transplantation in Japan. Selection and listing criteria for transplantation include regional priority, ABO blood type, previous islet transplant status with insulin independence, and a longer waiting time. Five institutes in Japan (Fukushima, Chiba, Kyoto, Kobe, and Fukuoka) are prepared to start programs. A two-layer cold storage method using perfluorocarbons and UW solution is recommended for pancreas preservation. Islet isolation and purification procedures are performed according to institute-specific protocol. Immunosuppression is based on sirolimus/tacrolimus combined with basiliximab induction. Two or three consecutive infusions of >5000 IE/kg are planned for each recipient until achieving insulin independence. Twenty-seven isolations and 14 transplants were performed in eight non-insulin-dependent diabetes mellitus (IDDM) recipients. Almost all (26 of 27) were NHB donors. All recipients are free from hypoglycemic episode after transplantation. One of these recipients is insulin independent; the others are currently on minimal doses of exogenous insulin. The feasibility of islet transplantation using NHB donors was confirmed using a two-layer cold storage method and a steroid-free immunosuppressive protocol, with a high rate of graft function.

Aged↗

Treatment of external iliac artery dissection with endovascular stent placement in a patient with simultaneous pancreas and kidney transplantation.

Dissection of the external iliac artery is a rare but serious complication after transplantation, leading to graft loss. Stent angioplasty has been accepted for iliac artery dissection, but the safety and benefits of this procedure in transplantation are unclear. We report a case of right external iliac artery dissection with simultaneous kidney and pancreas transplantation, which was noticed during the operation. A self-expandable metallic stent was inserted from the right femoral artery to the dissected area and arterial blood flow was immediately restored. The postoperative clinical course was uneventful and soon after transplantation both the kidney and pancreas graft functioned well. Together with a previously reported six cases of stent replacement with transplantation and our case, no complication related to this procedure was reported, and in six cases the arterial flow was restored and graft function was improved. Endovascular stent replacement may be a safe and effective procedure for iliac artery dissection in transplantation.

Adult↗

Evaluation of energy state of islet independent of size using a newly developed ATP bioluminescence assay.

ATP content or energy charge (EC) of islets may be a good parameter to assess viability. In this study, we examined adenine nucleotides and EC of freshly isolated or 24-hour cultured rat islets of various diameters using a novel bioluminescent enzymatic cycling assay system. For freshly isolated islets, ATP content and islet diameter showed a high correlation (r = 0.842, P < .001), but a significant correlation was not observed for cultured islets (r = 0.284) when all islets were included for the analysis. When only the cultured islets with a diameter <350 microm were included for analysis, a significant correlation was observed (r = 0.719). EC of freshly isolated islets fluctuated widely irrespective of diameter, in contrast with results of 24-hour cultured islets, which showed a stable, high EC, regardless of diameter. These data suggest that the ATP content of islets correlates with the islet size and that EC of islets widely fluctuates following isolation, indicating a significant role of monitoring ATP and EC of islets before transplantation.

Adenosine Triphosphate↗