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Biomedical subjects

A Sato

Publications and source records attributed to A Sato.

At least 19 recordsLinked to original sources

Aberrant DNA methylation of imprinted loci in superovulated oocytes.

BACKGROUND: There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The sex-specific epigenetic modifications that are imposed during gametogenesis act as a primary imprint to distinguish maternal and paternal alleles. The most likely candidate for the gametic mark is DNA methylation. However, the timing of DNA methylation acquisition in adult oocytogenesis and the effects of superovulation are unknown. METHODS: We examined the maternal methylation of PEG1(MEST), LIT1(KCNQ1OT1) and ZAC(PLAGL1) and the paternal methylation of H19 in adult growing oocytes of humans and mice and compared them with the methylation status of mouse neonatal growing oocytes by using bisulphite sequencing. Furthermore, we examined the effects of superovulation in the human and mouse. RESULTS: Maternal methylation of these genes has already been initiated to some extent in adult human and mouse non-growing oocytes but not in mouse neonates. In addition, the methylation dynamics during adult human and mouse oocyte development changed more gradually than those during neonatal oocyte development. Furthermore, we found the demethylation of PEG1 in growing oocytes from some ART-treated infertile women and a gain in the methylation of H19. We also detected methylation changes in superovulated mice. CONCLUSION: Our studies in the human and mouse suggest that superovulation can lead to the production of oocytes without their correct primary imprint and highlight the need for more research into ARTs.

Adult↗

Clinical outcome and risk factors for recurrence in borderline ovarian tumours.

We investigated the long-term prognosis of borderline ovarian tumours and determined risk factors for recurrence. One hundred and twenty-one borderline ovarian tumours treated between 1994 and 2003 at the participating institutions in the Tohoku Gynecologic Cancer Unit were retrospectively investigated for clinical stage, histopathological subtype, surgical technique, postoperative chemotherapy, the presence or absence of recurrence, and prognosis. The median follow-up period was 57 months (1-126 months). One hundred and nine cases (90.6%) were at clinical stage I. The histopathological subtypes consisted of 91 cases of mucinous tumour (75.2%), 27 cases of serous tumour (22.3%), and three cases of endometrioid tumour. Conservative surgery was used in 53 cases (43.8%), radical surgery in 68 cases (56.2%), a staging laparotomy in 43 cases (35.5%), and postoperative adjuvant therapy in 30 cases (24.8%). Recurrence was found in eight cases, but no tumour-related deaths were reported. Although no significant difference in disease-free survival rate was seen between different clinical stages, the difference in disease-free survival rate between serous and non-serous (mucinous and endometrioid) types was significant (P<0.05). The 10-year disease-free survival rate was 89.1% for the radical surgery group and 57.4% for the conservative surgery group -- this difference was significant (P<0.05). In the conservative surgery group, cystectomy and serous tumour were independent risk factors for recurrence. Although recurrence was observed, the long-term prognosis of borderline ovarian tumour was favourable, without tumour-related deaths. Considering the favourable prognosis, conservative surgery can be chosen as far as the patient has a non-serous tumour and receive adnexectomy. However, in cases of serous type and/or receiving cystectomy special care should be given as relative risk rates of recurrence elevate by 2-4-folds.

Adult↗

Adenosine A2A receptor mediated protective effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on retinal ischaemia/reperfusion damage in rats.

AIMS: To determine the effect of 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado), an adenosine A2A receptor agonist, on retinal ischaemia/reperfusion damage in rats. METHODS: Retinal ischaemia/reperfusion damage was induced by elevating the intraocular pressure of one eye to 130 mm Hg for 60 minutes and returning it to normal. 7 days later, retinal ischaemia/reperfusion damage was histologically quantified by measuring the thickness of retinal layers. Intraocular pressure was measured by pressure transducer. RESULTS: Retinal ischaemia/reperfusion caused cell loss in the ganglion cell layer and thinning of the inner plexiform and nuclear layer. Both ocular topical and intravenous administration of 2-CN-Ado caused a reduction of retinal ischaemia/reperfusion damage. A selective A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine (CSC), but not a selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a selective A2B receptor antagonist, alloxazine, reduced the protective effect of 2-CN-Ado. While ocular topical administration of 2-CN-Ado caused a sustained reduction of intraocular pressure, intravenous administration of 2-CN-Ado showed a transient ocular hypotensive effect. CONCLUSIONS: These results suggest that 2-CN-Ado attenuates retinal ischaemia/reperfusion damage, and at least some of this protective effect of 2-CN-Ado might be mediated via activation of the adenosine A2A receptor.

Adenosine↗

Continuous low-dose human atrial natriuretic peptide promotes diuresis in oliguric patients after living donor liver transplantation.

Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute renal failure (ARF) after liver transplantation (OLT). We evaluated renal function in OLT patients with or without ARF, describing cases unresponsive to loop diuretics successfully treated with continuous low-dose ANP infusion without hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver transplantations (LDLTs) were performed in 26 patients. One case was excluded due to the need for continuous hemodialysis (HD) during the operation. Of the 26 cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other 20 were ARF-free (group 1). The median follow-up was 24 months. No patient required either continuous or intermittent HD. Only one patient died due to multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and intraoperative blood loss in group 2 were significantly higher than those in group 1. Three cases in group 2 failed to improve on high-dose loop diuretics with low-dose dopamine, exhibiting fluid overload. The remaining three cases in group 2 responded to conventional diuretic treatments. Continuous low-dose ANP was started 2, 4, or 5 days after LDLT, and urine output significantly increased after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1 month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss during the operation caused ARF, but did not affect renal function after LDLT. Continuous low-dose ANP improved renal function and diuresis for oliguric ARF patients, preventing the need for HD or continuous venovenous hemodialysis.

Adult↗

Successful pregnancy after ICSI with strontium oocyte activation in low rates of fertilization.

Fertilization failure (complete fertilization failure or low fertilization rates) after intracytoplasmic sperm injection (ICSI) can occur in rare cases. In the majority of these cases, the unfertilized oocytes are inactivated. Assisted oocyte activation was applied as a treatment option for a case of low fertilization rate as a clinical trial. A patient with a low fertilization rate (ranging from 0% to 33.3%; mean = 17.0%) after eight previous ICSI cycles at another hospital, was diagnosed with fertilization failure. The most likely cause of fertilization failure was failure of oocyte activation. Therefore, artificial oocyte activation by strontium treatment was combined with ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with strontium (10 mM SrCl(2), 60 min) approximately 30 min after ICSl. Six injected oocytes were stimulated and all were then successfully fertilized. Two blastocysts were transferred into the uterus, resulting in a pregnancy and birth. A second pregnancy was achieved following implantation of two cryopreserved embryos (one blastocyst and one morula). In conclusion, strontium treatment was found to be an effective method for artificial oocyte activation in a case with a low fertilization rate after ICSI.

Adult↗

Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction.

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

Adult↗

Left ventricular hypertrophy in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for myocardial ischaemia, cardiac arrhythmia, sudden death, and heart failure, all common findings in patients with type 2 diabetes. AIM: To determine the prevalence of, and risk factors for, LVH in normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. DESIGN: Cross-sectional study. METHODS: From 1994 to 1998, M-mode echocardiography was performed by one experienced examiner in 262 consecutive, normoalbuminuric Caucasian type 2 diabetic patients, all with blood pressure <160/95 mmHg and not taking antihypertensive medication. Mean +/- SD age was 54 +/- 10 years, 109 were women, and median known duration of diabetes was 4 (range 1-28) years. Body mass index (BMI) was 28 +/- 5 kg/m(2), and blood pressure 134 +/- 13/79 +/- 8 mmHg, all means +/- SD. Median urinary albumin excretion rate was 9 (range 2-30) mg/24 h. RESULTS: The prevalence of LVH indexed to height(2.7) was 43% (95%CI 38-50%), and was similar in men and women. BMI, HbA(1c) and log urinary albumin excretion were significantly associated with left ventricular hypertrophy in a logistic regression model, whereas sex, age, known duration of diabetes and blood pressure were not. Similar results were obtained for left ventricular mass index. DISCUSSION: LVH was frequent in our normoalbuminuric type 2 diabetic patients not taking antihypertensive treatment. Several potentially modifiable risk factors, such as raised BMI, poor glycaemic control and elevated urinary albumin excretion rate, were associated with LVH.

Adult↗

Nitric oxide donor-induced inhibition of pregnant rat uterine spontaneous contractile activity and release of nitric oxide from uterus measured by microdialysis.

Our aim was to study whether nitric oxide (NO) donor-induced inhibition of pregnant rat myometrium contractility correlates with the release of NO. Uterine rings from mid-pregnant and late pregnant Sprague-Dawley rats were used for isometric tension recording. Concentration-response relationships to sodium nitroprusside (SNP), nitroglycerine (NTG) and diethylamine (DEA)/NO were assessed. The time course of NO release after addition to the organ chambers of the 3 NO-donors was assessed by the detection of NO products NOx (NO3+NO2) using the microdialysis probe by a HPLC-NO detector system. DEA/ NO induced greater inhibition of the spontaneous contractile activity of uterine rings from mid-pregnant rats than SNP or NTG. In uterine rings from late pregnant rats, however, the maximal inhibition of the contractility by all 3 NO-donors were significantly less. The NOx levels measured in the uterine ring walls from either mid-pregnant or late pregnant rats significantly increased after DEA/ NO as compared to the basal levels or the levels after NTG or SNP. The decrease of NO-donor-induced inhibition of rat myometrium contractility, with unchanged formation of NOx, at term, suggests that the changes in NO signaling are responsible for gestational age-dependent attenuation of the inhibitory effect.

Animals↗

Effects of sex steroids on expression of adenylyl cyclase messenger RNA in rat uterus.

The aim of our study was to investigate the effects of estradiol (E2) and/or progesterone (P4) bilateral ovariectomized rats on gene expressions of adenylyl cyclases (AC2, AC4, AC6, AC9). Non-pregnant (NP) Wister rats (between post-natal 10 and 12 weeks) and normal pregnant rats (between postnatal 10 and 14 weeks) were used. NP rats were divided into five groups: 1) control NP rats, 2) ovariectomy rats (OVX), 3) OVX injected with E2 (6 microg) for 4 days (E2), 4) OVX injected with P4 (5 mg) for 4 days (P4), 5) ovariectomy rats injected with E2 (6 microg) and P4 (5 mg) for 4 days (E2/P4). The ovariectomized rats were sacrificed by anesthesia of diethyl ether after 24 h from the last injection. The pregnant group was sacrificed in the same way on 14 (P14), 17 (P17) and 21 (P21) of pregnancy, because the days between P14 and P17 were the second trimester of pregnancy and P21 was the third trimester. Total RNA were prepared from the uteri of each subject, and expression of ACs was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Expression of mRNAs for AC2, AC4, AC6 and AC9 were maximally increased on P17 and then decreased on P21. In OVX rats, expression of mRNAs for AC2, AC4, and AC9 were decreased as compared to NP. AC2 mRNA was significantly increased by E2 treatment. AC4 and AC9 mRNA was significantly increased by injection of E2 or P4. AC6 mRNA level was not affected by E2 and/or P4. In conclusion, AC2, AC4 and AC9 gene expression is affected by estrogen and/or P4. On the contrary, AC6 gene expression was not changed by OVX or hormone treatment. Since, all ACs mRNA examined here are increased during pregnancy, AC6 may be affected by other factor(s) other than estrogen and P4.

Adenylyl Cyclases↗

Peyer's patch dendritic cells as regulators of mucosal adaptive immunity.

The mucosal immune system maintains a delicate balance between providing robust defense against infectious pathogens and, at the same time, regulating responses toward innocuous environmental and food antigens and commensal microbes. The Peyer's patch (PP) has been studied in detail as a major inductive site for mucosal immunity within the small intestine. While the mechanisms responsible for the induction of mucosal immunity versus tolerance are not yet fully understood, recent studies have highlighted mucosal dendritic cells (DCs) as regulators of the immune responses to orally administered antigens. Here we discuss recent studies that describe the role of PP DCs in immune induction and speculate on the mechanism by which the resident DCs regulate T cell and immunoglobulin A (IgA) responses in the gastrointestinal mucosa.

Animals↗

Experience with recipient's superficial femoral vein as conduit for middle hepatic vein reconstruction in a right-lobe living donor liver transplant procedure.

Middle hepatic vein reconstruction during the right-lobe living donor liver transplant procedure has been recognized to be a significant factor. We initially reconstructed only a single middle hepatic vein orifice draining into segment 8. In cases where the right-lobe liver graft has several major middle hepatic vein tributaries, including veins draining segment 5 that are remote from the right hepatic vein orifice, a long and thick interposition conduit is necessary for reconstruction. Among 11 consecutive adult patients who received a right-lobe liver graft without a middle hepatic vein at our institution, 8 underwent reconstruction of all major middle hepatic vein tributaries using a vein graft from the recipient's superficial femoral vein. The remaining 3 patients had no major middle hepatic vein tributaries. Posttransplant-computed tomography imagings showed increased liver mass with a patent superficial femoral vein graft in 8 patients. In the absence of a venous system from a deceased donor, a recipient superficial femoral vein offers an excellent size match to maintain the venous outflow of middle hepatic vein tributaries. Reconstruction with recipient superficial femoral vein plays an important role in maximizing liver function and minimizing morbidity in the early posttransplant period.

Adult↗

PGE1 inhibits the expression of PAI-1 mRNA induced by TNF-alpha in human mesangial cells.

We examined the effect of PGE1 on the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA induced by tumor necrosis factor-alpha (TNF-alpha) in human mesangial cells, because PAI-1 is one of major factors for the progression of glomerulosclerosis. The expression of PAI-1 mRNA was increased after stimulation with TNF-alpha, and it was diminished by pre-incubation with PGE1. Next, we examined the effect of PGE1 on the phosphorylation of mitogen activated protein kinase (MAPK) family and Akt. TNF-alpha activated the phosphorylation of p44/42 MAPK, p38 MAPK, SAPK/JNK and Akt in mesangial cells. PGE1 inhibited the TNF-alpha induced phosphorylation of SAPK/JNK and Akt, but not p44/42 MAPK and p38 MAPK. The TNF-alpha induced expression of PAI-1 mRNA was not affected by PD98059, an inhibitor of MEK, SB203580, an inhibitor of p38 MAPK, nor LY294002, an inhibitor of PI3 K. However, DMAP, an inhibitor of SAPK/JNK, inhibited the expression of PAI-1 mRNA, suggesting that the TNF-alpha induced expression of PAI-1 mRNA is regulated by the SAPK/JNK dependent pathway in human mesangial cells. By the incubation with H8, an inhibitor of PKA, the inhibitory effect of PGE1 on the expression of PAI-1 mRNA was abolished, suggesting that PGE1 inhibited the PAI-1 mRNA expression via the PKA pathway. Our results suggest that the inhibition of PAI-1 synthesis by PGE1 in human mesangial cells may have therapeutic implications for glomerulosclerosis such as occurs in diabetic nephropathy.

Alprostadil↗

Milk/dairy products consumption, galactose metabolism and ovarian cancer: meta-analysis of epidemiological studies.

Ovarian cancer is the fifth most common cause of cancer death among women and the leading cause of gynaecological cancer death in the United States. Milk/dairy products consumption was considered to be a risk factor for ovarian cancer mainly because milk carbohydrate-lactose and galactose metabolism is toxic to oocytes. However, recent evidence does not support this hypothesis completely. We collected epidemiological studies related to the association between milk/dairy products consumption or galactose metabolism (lactose, galactose, galactose-1-phosphate uridyltransferase, lactose/transferase) and ovarian cancer published between January 1966 and August 2003 and found 27 items from 22 independent studies. Twenty studies were case-control studies and the other two were cohort studies. A meta-analysis method was conducted to estimate relative risk combining all relative data. In general, we did not find any association between milk/dairy products or galactose metabolism and ovarian cancer risk in this meta-analysis. The consumption of whole milk and butter, which contain relatively high amounts of fat, was positively (relative risk > 1.2), but not significantly, associated with an increased risk.

Case-Control Studies↗

Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance and pulmonary complication in thoracic esophagectomy patients.

SUMMARY: In spite of improvements in surgical technique and perioperative care, severe lung complication remains as the leading cause of morbidity in thoracic esophageal cancer patients who undergo esophagectomy. The purpose of this study was to evaluate the safety and effectiveness of postoperative drug therapy using low dose dopamine, gabexate mesilate, and ulinastatin on postoperative lung complication in esophageal cancer patients. Sixty-one patients operated for esophageal cancer from 1996 to 2000 were treated postoperatively with low dose dopamine (300 microg/kg/h), gabexate mesilate (80 mg/h), and ulinastatin (300 000 unit/day) as a study group. Seventy-four patients operated from 1987 to 1994 served as an historical control group. Various preoperative and perioperative medical parameters and water balance were analyzed. Postoperative pulmonary complications were observed in 26 patients (35.1%) in the control group and three patients (4.9%) in the study group, respectively (P < 0.0001). Preoperative and perioperative variables were not significantly different between the groups. Water balance from operation to postoperative day 3 in the study group was significantly lower than the control group. Postoperative use of low dose dopamine, gabexate mesilate, and ulinastatin significantly reduced pulmonary complications after esophagectomy. This may be partly attributable to negative water balance during the early postoperative days.

Carcinoma, Squamous Cell↗

A case of gain-of-function mutation in calcium-sensing receptor: supplemental hydration is required for renal protection.

AIMS: The calcium-sensing receptor (CaSR) regulates the extracellular calcium level, mainly by controlling parathyroid hormon secretion and renal calcium reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities increase CaSR activity leading to the development of such clinical manifestations as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case of CaSR gain-of-function mutation and represent a therapeutic intervention based on the functional characteristics of CaSR in renal tubule. METHODS AND RESULTS (CASE): DNA sequence analysis revealed a heterozygous G to T mutation identified in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal extracellular domain of the CaSR gene, one of the most important parts for the three-dimensional construction of the receptor, resulting in the substitution of phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide administration and supplemental hydration were started in addition to calcium supplementation. The combination therapy of thiazide and supplemental hydration markedly reduced both renal calcium excretion and urinary calcium concentration from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from 10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy stopped the progression of renal calcification during the follow-up period. CONCLUSION: Supplemental hydration should be considered essential for the following reasons: (1) calcium supplementation activates the CaSR in the kidney and suppresses renal urinary concentrating ability, (2) the thiazide has a diuretic effect, (3) as calcium supplementation increases renal calcium excretion, the supplemental hydration decreases urinary calcium concentration by increasing urinary volume, thereby diminishing the risk of intratubular crystallization of calcium ion.

Administration, Oral↗

Significantly reduced spontaneous thrombolytic activity in older men: a possible explanation for the gender differences in risk of acute coronary syndromes.

BACKGROUND: Although incidence of arterial thrombotic events increases with advancing age, the mechanism of such increased risk is poorly understood. There is also a gender difference; coronary heart disease is more common in men than women. The aim of the present study was to investigate the possible contribution from platelet reactivity and spontaneous thrombolysis, determinants of arterial thrombosis, to the increased risk of thromboembolism in aging, but otherwise healthy subjects. METHOD: One hundred and forty-five normal subjects (61 men, 82 women) of age between 19 and 77 years were grouped into groups of young (<30 years); middle aged (31-50 years), and older (>51 years), according to their gender and body mass index (BMI). A new in vitro test [Gorog Thrombosis Test (GTT)] was used to measure in sequence both platelet reactivity [occlusion time (OT)] and spontaneous thrombolysis [lysis time (LT)] from one non-anticoagulated blood sample. RESULT: OT in all women was 315+/-9.2 s (mean+/-S.E.M.), in all men OT was 300+/-10.6 s. The mean LT in all women was 2557+/-201.5 s, and in all men LT was 2493+/-198.6 s. Advanced age did not enhance platelet reactivity (OT), but increased BMI did (P=0.039). Spontaneous thrombolysis (LT) was impaired in older men but not in women (difference between young vs. middle age: P=0.019; young vs. older: P=0.0002). CONCLUSION: Our findings suggest that in men, spontaneous thrombolytic activity is reduced with age, and this may explain the increased frequency and severity of thromboembolic events. Interestingly, in women, spontaneous thrombolytic activity did not change after menopause.

Acute Disease↗

Is the degree of fetal hepatosplenomegaly with transient abnormal myelopoiesis closely related to the postnatal severity of hematological abnormalities in Down syndrome?

We present three cases of transient abnormal myelopoiesis associated with trisomy 21 in which hepatomegaly was apparent during the fetal period. In the first case, the fetal hepatosplenomegaly was severe, multiple organ failure occurred in the neonatal period and death ensued at 4 weeks of age. In the second case, the hepatomegaly was moderate, and with conservative treatment in the neonatal period the outcome was good. In the third case, hepatomegaly was mild and improved spontaneously, and the hematological abnormalities required only conservative treatment in the neonatal period. Our experience raises the question of whether fetal hepatosplenomegaly is a predictor of transient myeloproliferative disorder with trisomy 21 and whether the degree of fetal hepatomegaly is a marker for the neonatal severity of hematological abnormalities.

Adult↗