Biomedical subjects

Yasunori Yoshimura

Publications and source records attributed to Yasunori Yoshimura.

At least 37 records · Page 2Linked to original sources

PubMed2005

Carbon monoxide as a guardian against hepatobiliary dysfunction.

Carbon monoxide (CO) generated through the reaction of heme oxygenase (HO) has attracted great interest in regulation of hepatobiliary homeostasis. The gas generated by HO-2 in the hepatic parenchyma can modestly activate soluble guanylate cyclase (sGC) expressed in hepatic stellate cells in a paracrine manner and thereby constitutively relax sinusoids. Kupffer cells express HO-1, the inducible isozyme, even under normal unstimulated conditions and constitutes approximately 30% of the total HO activity in this organ. Upon exposure to a variety of stressors such as cytokines, endotoxin, hypoxia and oxidative stress, the liver induces HO-1 and over-produces CO. The stress-inducible CO has been shown to guarantee ample blood supply during detoxification of heme and thus to play a protective role in the liver. However, molecular mechanisms by which CO serves as a protectant for hepatocytes, the cells expressing little sGC, remain to be solved. Previous observation suggested that CO modulates intracellular calcium mobilization through inhibiting cytochrome P-450 activities and thereby maintain stroke volume of bile canalicular contraction in cultured hepatocytes. CO also stimulates mrp2-dependent excretion of bilirubin-IXalpha and helps heme catabolism. Although a direct molecular target responsible for the latter event remains unknown, such properties of CO could support xenobiotic metabolism through its actions on sinusoidal hemodynamics and hepatobiliary systems.

Carbon Monoxide↗

PubMed2005

Follicle stimulating hormone-secreting pituitary microadenoma with fluctuating levels of ovarian hyperstimulation.

BACKGROUND: Enlarged multicystic ovaries and an elevated estradiol (E2) concentration have been reported as characteristics of follicle stimulating hormone (FSH)-secreting adenomas in reproductive-aged women. The natural course of the hormone in relationship to the microadenoma and ovarian findings, however, remains largely unknown. CASE: A 40-year-old woman with enlarged multicystic ovaries was nonsurgically diagnosed with an FSH-producing pituitary microadenoma. During her subsequent 12-month follow-up, the serum concentration of E2, but not FSH, and the size of the multicystic ovaries fluctuated dramatically. Both the E2 level and ovarian size were transiently normalized. CONCLUSION: Because of disease-related fluctuations, a reproductive-aged woman with an FSH-producing adenoma did not always present with laboratory values characteristic of ovarian hyperstimulation. This finding points out a possible pitfall in diagnosis and clinical management.

Adenoma↗

PubMed2005

Case of iatrogenic dysmenorrhea in non-communicating rudimentary uterine horn and its laparoscopic resection.

Abstract A case of non-communicating rudimentary uterine horn is presented and is a characteristic example of the way that surgical treatment can exacerbate dysmenorrhea by blocking retrograde menstruation. There is always some risk of missing the true diagnosis in cases of uterine abnormalities, even by direct inspection, but intraoperative laparoscopic ultrasonography can be an invaluable tool in defining anatomy. As laparoscopic resection has become the standard procedure for the treatment of unicornuate uterus, laparoscopic ultrasonography can be a useful tool for providing anatomical information to the operating surgeon about the patient.

Adult↗

PubMed2005

Melatonin as a local regulator of human placental function.

Melatonin plays a critical role in a variety of mammalian reproductive processes not only acting on the central nervous system but also behaving as a peripheral physiologic regulator. To address the relevance of melatonin to the maintenance of pregnancy at the feto-maternal interface, we investigated the expression of two types of membrane melatonin receptors, MT1 and MT2, as well as arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), the two enzymes required for the conversion of serotonin to melatonin, in the human placenta and the effect of melatonin on the release of human chorionic gonadotropin (hCG) from cultured human trophoblast cells. RT-PCR analysis and DNA sequencing revealed that transcripts of MT1, MT2, AA-NAT, and HIOMT were present in the first-trimester human placenta. We also found that melatonin significantly potentiated hCG secretion at optimal concentrations. These results suggest that melatonin may regulate human placental function in a paracrine/autocrine manner, providing evidence for a novel role in human reproduction.

Acetylserotonin O-Methyltransferase↗

PubMed2005

Association of common LH variant with hyperfunctional promoter in a Japanese infertile woman.

A common LH variant (V-LH) with Trp8Arg and Ile15Thr is often associated with ovarian dysfunction primarily in the Japanese population, and the LHB gene encoding V-LH is linked with a hyperfunctional promoter that could partly compensate for the somewhat weak biological effect of the V-LH in the Finnish and other several populations. We analyzed the promoter region in a Japanese infertile woman homozygous for the V-LH, to examine whether the hyperfunctional promoter is present or absent in the Japanese V-LH carriers with ovarian dysfunction. Direct sequencing was performed for a 661 bp promoter region from -8 to -668 bp of LHB, revealing homozygosity for eight nucleotide substitutions (-238A>G, -276G>A, -489C>A, -490T>A, -504T>A, -506T>C, -525T>G, and -552C>T) that are identical to those found in the hyperfunctional promoter. The results suggest that ovarian dysfunction frequently observed in the Japanese V-LH carriers would be due to some population-specific genetic and/or environmental factor(s) rather than to the lack of the hyperfunctional promoter and the resultant low biological effect of the V-LH. In addition, the tight linkage between the two missense substitutions in the coding region and the eight nucleotide substitutions in the promoter region of LHB appears to be common to various ethnic groups.

Adult↗

PubMed2005

Prenatal diagnosis of hemifacial microsomia by magnetic resonance imaging.

We present a case of hemifacial microsomia, first detected by prenatal sonography and confirmed by ultrafast magnetic resonance (MR) imaging. A 26-year-old patient was referred to our hospital at 20 weeks of gestation because of unilateral right-sided ventriculomegaly and of a possible ventriculoseptal defect (VSD). Our sonographic examination suggested a right orbital hypoplasia and a hemiatrophy of the nose. The ultrafast T2-weighted single-shot fast-spin echo MR imaging, demonstrated a right ear hypoplasia (microtia), a right orbital hypoplasia, and a right renal hypoplasia. Epibulbar dermoid or conjunctival lipodermoid were not recognized. The fetus was prenatally diagnosed as hemifacial microsomia. Termination of pregnancy was performed at 21 weeks gestation, and a male baby weighing 342g was stillborn. The baby showed facial asymmetry, including hemiatrophy of the right nose, and right ear hypoplasia. Autopsy revealed a 2mm area of VSD, agenesis of the right kidney and ureter, pancreatic and renal aberration into right adrenal gland, thymus hypoplasia and an unfixed ascending colon without intestinal malrotation. To the best of our knowledge, this is the first report of prenatal diagnosis for hemifacial microsomia using fetal MR imaging. In our case, fetal MR imaging has evolved into a powerful diagnostic tool, for the accurate prenatal diagnosis.

Adult↗

PubMed2004

Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality.

We report a family in which a healthy, unrelated couple had a male fetus with bilateral ventriculomegaly, a normal liveborn girl, a hydatidiform molar pregnancy, a female fetus with ventriculomegaly and situs abnormalities, and a male fetus with hydrocephalus, a three-lobed left lung, and defective tracheal cilia with absent inner dynein arms and a single centriole. A mutation analysis of FOXJ1 and POLL in the last fetus with ciliary defect revealed no mutation within their coding regions. The presence of three affected fetuses of both sexes in a family with phenotypically normal parents suggests that the condition was inherited as an autosomal recessive trait. A thorough evaluation of the thoracic and abdominal situs is recommended before counseling a family of a child with hydrocephalus, because the recognition of situs defects may point to the diagnosis of primary ciliary defect and recurrence risk of 25% for siblings. This figure is much higher than the general risk of 1-2% for siblings of a patient with isolated hydrocephalus.

Abnormalities, Multiple↗

PubMed2004

Rapid replacement of somatic linker histones with the oocyte-specific linker histone H1foo in nuclear transfer.

The most distinctive feature of oocyte-specific linker histones is the specific timing of their expression during embryonic development. In Xenopus nuclear transfer, somatic linker histones in the donor nucleus are replaced with oocyte-specific linker histone B4, leading to the involvement of oocyte-specific linker histones in nuclear reprogramming. We recently have discovered a mouse oocyte-specific linker histone, named H1foo, and demonstrated its expression pattern in normal preimplantation embryos. The present study was undertaken to determine whether the replacement of somatic linker histones with H1foo occurs during the process of mouse nuclear transfer. H1foo was detected in the donor nucleus soon after transplantation. Thereafter, H1foo was restricted to the chromatin in up to two-cell stage embryos. After fusion of an oocyte with a cell expressing GFP (green fluorescent protein)-tagged somatic linker histone H1c, immediate release of H1c in the donor nucleus was observed. In addition, we used fluorescence recovery after photobleaching (FRAP), and found that H1foo is more mobile than H1c in living cells. The greater mobility of H1foo may contribute to its rapid replacement and decreased stability of the embryonic chromatin structure. These results suggest that rapid replacement of H1c with H1foo may play an important role in nuclear remodeling.

Animals↗

PubMed2004

Kupffer cells alter organic anion transport through multidrug resistance protein 2 in the post-cold ischemic rat liver.

Although Kupffer cells (KCs) may play a crucial role in post-cold ischemic hepatocellular injury, their role in nonnecrotic graft dysfunction remains unknown. This study examined reveal the role of KC in post-cold ischemic liver grafts. Rat livers treated with or without liposome-encapsulated dichloromethylene diphosphonate, a KC-depleting reagent, were stored in University of Wisconsin (UW) solution at 4 degrees C for 8 to 24 hours and reperfused while monitoring biliary output and constituents. The ability of hepatocytes to excrete bile was assessed through laser-confocal microfluorography in situ. Cold ischemia-reperfused grafts decreased their bile output significantly at 8 hours without any notable cell injury. This event coincided with impaired excretion of glutathione and bilirubin-IXalpha (BR-IXalpha), suggesting delayed transport of these organic anions. We examined whether intracellular relocalization of multidrug resistance protein-2 (Mrp2) occurred. Kinetic analyses for biliary excretion of carboxyfluorescein, a fluoroprobe excreted through this transporter, revealed significant delay of dye excretion from hepatocytes into bile canaliculi. The KC-depleting treatment significantly attenuated this decline in biliary anion transport mediated through Mrp2 in the 8-hour cold ischemic grafts via redistribution of Mrp2 from the cytoplasm to the canalicular membrane. Furthermore, thromboxane A(2) (TXA(2)) synthase in KC appeared involved as blocking this enzyme improved 5-carboxyfluorescein excretion while cytoplasmic internalization of Mrp2 disappeared in the KC-depleting grafts. In conclusion, KC activation is an important determinant of nonnecrotic hepatocellular dysfunction, jeopardizing homeostasis of the detoxification capacity and organic anion metabolism of the post-cold ischemic grafts.

ATP-Binding Cassette Transporters↗

PubMed2004

Hypertensive disorders in Japanese women with gestational glucose intolerance.

We investigated the relationship between gestational glucose intolerance and the development of pregnancy-induced hypertension including gestational hypertension (GH) and preeclampsia. Consecutive Japanese women with singleton pregnancies underwent a standard 1h, 50g oral glucose challenge test (GCT) at 24-27 weeks of gestation, followed by a 75g, 2h oral glucose tolerance test (OGTT) if the GCT result exceeded 130mg/dl. Using criteria of the Japan Society of Obstetrics and Gynecology, gestational diabetes mellitus (GDM) was defined by two or more abnormal OGTT values and mild glucose intolerance by one abnormal value. The normal glucose tolerance group included women with GCT results below 130mg/dl or normal OGTT values. GH was defined as blood pressure of at least 140/90mmHg occurring for the first time after mid-pregnancy, without proteinuria. Preeclampsia was determined as GH with proteinuria. Of 2651 consecutive patients, 49 women were found to have GDM, and 139 showed mild glucose intolerance. Sixty patients showed GH, and 58 developed preeclampsia. The frequency of GH in mild glucose intolerance or GDM was 5.8% or 8.2%, respectively, significantly greater than in normal glucose tolerance (P<0.01). Incidence of preeclampsia was not significantly increased in women with mild glucose intolerance or GDM (2.2% or 4.1%, respectively, compared to those with normal glucose tolerance). Japanese women with gestational glucose intolerance therefore have an increased risk of developing GH.

Adult↗

PubMed2004

Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins.

OBJECTIVE: To examine whether Arg554Lys polymorphism in the gene for aryl hydrocarbon receptor (AHR) and/or Pro185Ala polymorphism in the gene for aryl hydrocarbon receptor repressor (AHRR) constitutes a susceptibility locus for dioxin-related male infertility. DESIGN: Association study of male infertility with polymorphisms. SETTING: National research institute and university hospitals. PATIENT(S): 123 Japanese men with azoospermia or severe oligozoospermia and 112 men with proven fertility. INTERVENTION(S): Polymorphism analysis. MAIN OUTCOME MEASURE(S): The allele and genotype frequencies between infertile men and controls. RESULT(S): The allele and genotype frequencies of the AHR polymorphism were comparable between infertile men and controls. By contrast, although the difference in the allele frequency of the AHRR polymorphism did not reach a significant level, the genotype frequency was statistically significantly different between the two groups of men. Furthermore, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. CONCLUSION(S): The Pro185Ala polymorphism in AHRR may constitute a susceptibility locus for dioxin-related male infertility. It appears that the negative feedback effect of AHRR on dioxin-related signaling is weaker for the proline allele than for the alanine allele, and that the hypomorphic function of the proline allele exerts a recessive adverse effect on male fertility.

Adult↗

PubMed2004

Pulmonary hypoplasia: prediction with use of ratio of MR imaging-measured fetal lung volume to US-estimated fetal body weight.

PURPOSE: To determine the ratio of fetal lung volume (FLV) to fetal body weight (FBW) by using ultrasonography (US) and magnetic resonance (MR) imaging and to evaluate the usefulness of this ratio in predicting pulmonary hypoplasia (PH) in fetuses at high risk. MATERIALS AND METHODS: MR imaging lung volumetry and US biometry were performed in 90 fetuses at 25-39 weeks gestation. In the control group of 73 fetuses, normal lung development was confirmed at neonatal follow-up and the normative ratio of MR imaging-measured FLV to US-estimated FBW (FLV/FBW) was determined. The high-risk group included 17 fetuses at risk for PH. The FLV/FBW was compared between the control and high-risk groups and with US parameters for predicting the development of PH in the high-risk group. Measurements 2 or more standard deviations below the mean control group measurement were considered abnormal. Comparisons of the FLV/FBW between groups were made by using the Student t test. The association between development of PH and measurement of each parameter was analyzed by using the Fisher exact probability test. RESULTS: In the control group, the FLV/FBW decreased with gestational age during the third trimester and had a normal distribution (mean ratio, 0.028 mL/g; range, 0.015-0.444 mL/g). The mean FLV/FBW for the nine fetuses with PH (0.012 mL/g +/- 0.008) was significantly lower (P <.001) than that for the control group (0.028 mL/g +/- 0.007). Fetuses with abnormal FLV/FBW values were at significantly greater risk (P <.05) for PH development. Abnormal FLV/FBW values had higher diagnostic accuracy than abnormal US parameters. Sensitivity of the FLV/FBW was 89% (eight of nine fetuses); specificity, 88% (seven of eight fetuses); positive predictive value, 89% (eight of nine fetuses); negative predictive value, 88% (seven of eight fetuses); and accuracy, 88% (15 of 17 fetuses). CONCLUSION: The FLV/FBW reflects the adequacy of intrauterine lung growth and can help predict PH.

Body Weight↗

PubMed2004

Massive hepatic infarction in preeclampsia: successful treatment with continuous hemodiafiltration and corticosteroid therapy.

Massive hepatic infarction associated with pregnancy is extremely rare, but is potentially fatal. A 35-year-old primigravida with mild preeclampsia developed acute right upper quadrant pain and marked elevation of liver enzymes at 26 weeks' gestation. After emergent cesarean section, her condition was complicated by oliguric renal failure and pulmonary edema with further deterioration of hepatic function (aspartate transaminase 4339 IU/L; alanine transaminase 3489 IU/L; lactate dehydrogenase 10780 IU/L). The contrast-enhanced computed tomography revealed non-enhancing low attenuation throughout the right lobe of liver, compatible with infarction. Continuous hemodiafiltration was initiated as renal support on postpartum day one. However, excessive fluid accumulation persisted, and she developed severe edema formation in both lung and systemic body surface. To ameliorate microvascular endothelial injury, corticosteroid therapy was begun on postpartum day five. Following treatment initiation, her renal and hepatic function showed steady improvement, accompanied by drastic resolution of edema formation. She was discharged five weeks postpartum with no additional treatment, and is without sequelae six months later. Massive hepatic infarction should be considered in preeclamptic patients who present acute abdominal pain and severe hepatic dysfunction, and continuous hemodiafiltration with corticosteroid therapy may improve the maternal outcome.

Abdominal Pain↗

PubMed2003

Pyrazolo pyrimidine-type inhibitors of SRC family tyrosine kinases promote ovarian steroid-induced differentiation of human endometrial stromal cells in vitro.

Reversible protein tyrosine phosphorylation, coordinately controlled by protein tyrosine kinases and phosphatases, is a critical element in signal transduction pathways regulating a wide variety of biological processes, including cell growth, differentiation, and tumorigenesis. We have previously reported that c-Src belonging to the Src family tyrosine kinase (SFK) becomes dephosphorylated at tyrosine 530 (Y530) and thereby activated during progestin-induced differentiation of human endometrial stromal cells (i.e., decidualization). In this study, to elucidate the role of decidual c-Src activation, we examined whether 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), both potent and selective SFK inhibitors, affected the ovarian steroid-induced decidualization in vitro. Unexpectedly, PP1 paradoxically increased the kinase activity of decidual c-Src together with dephosphorylation of Y530 in the presence of ovarian steroids. Concomitantly, PP1 enhanced morphological and functional decidualization, as determined by induction of decidualization markers, such as insulin-like growth factor binding protein-1 and prolactin. PP2 also advanced decidualization along with up-regulation of the active form of c-Src whose Y-530 was dephosphorylated. In contrast to PP1 and PP2, herbimycin A, a tyrosine kinase inhibitor with less specificity for SFKs, showed little enhancing effect on the expression of both IGFBP-1 and active c-Src. These results suggest that SFKs, including c-Src, may play a significant role in stromal cell differentiation, providing a clue for a possible therapeutic strategy to modulate endometrial function by targeting signaling pathway(s) involving SFKs.

Animals↗

PubMed2003

Structure and expression of the human oocyte-specific histone H1 gene elucidated by direct RT-nested PCR of a single oocyte.

Oocyte-specific histone H1 is expressed during oogenesis and early embryogenesis. It has been described in mice and some nonmammalian species, but not in humans. Here, we identified the cDNA in unfertilized human oocytes using direct RT-nested PCR of a single cell. Sequencing of this cDNA indicated an open reading frame encoding a 347-amino acid protein. Expression was oocyte-specific. Homology was closest with the corresponding gene of mouse (H1oo; 42.3%), and, to lesser extent, with that of Xenopus laevis (B4; 25.0%). The gene, named osH1, included five exons as predicted by the NCBI annotation project of the human genome, although the actual splicing site at the 3(') end of exon 3 was different by 48 nucleotides from the prediction. The presence of polyadenylation signals and successful amplification of cDNA by RT-PCR using an oligo(dT) primer suggested that the osH1 mRNA is polyadenylated unlike somatic H1 mRNA. Our technique and findings should facilitate investigation of human fertilization and embryogenesis.

Amino Acid Sequence↗

PubMed2003

Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells.

Histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones, regulating gene transcription. Decidualization is the progestin-induced differentiation of estrogen-primed endometrial stromal cells (ESCs), which is crucial for implantation and maintenance of pregnancy. We here show that trichostatin A (TSA), a specific HDAC inhibitor, enhances the up-regulation of decidualization markers such as insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin in a dose-dependent manner that is directed by 17beta-estradiol (E(2)) plus progesterone (P(4)) in cultured ESCs, but not glandular cells, both isolated from human endometrium. Morphological changes resembling decidual transformation were also augmented by co-addition of TSA. Acid urea triton gel analysis and immunoblot using acetylated histone type-specific antibodies demonstrated that treatment with E(2) plus P(4) significantly increased the levels of acetylated H3 and H4 whose increment was augmented by co-treatment with TSA. Chromatin immunoprecipitation assay revealed that treatment with E(2) plus P(4) increased the amount of proximal progesterone-responsive region of IGFBP-1 promoter associated with acetylated H4, which was dramatically enhanced by co-addition of TSA. Taken together, our results suggest that histone acetylation is deeply involved in differentiation of human ESCs and that TSA has a potential as an enhancer of decidualization through promotion of progesterone action.

Acetylation↗

PubMed2003

Electroporation of cynomolgus monkey embryonic stem cells.

Efficient genetic modification of primate embryonic stem (ES) cells is essential for the application for both basic and preclinical research. The transfection efficiency of primate ES cells is reportedly lower than that of mouse ES cells. Cynomolgus monkey ES cells provide a powerful model for understanding human development and disease. We evaluated electroporation as a method to introduce foreign genes into cynomolgus monkey ES cells. Our examination has allowed us to establish a protocol producing about 100 stably transfected clones from 10(7) cynomolgus monkey ES cells. Differences in efficiency, however, were observed for other ES cell lines. We compared the transcriptional activities of the PGK-1, CMV, and SV40 promoters in cynomolgus monkey ES cells generating efficient G418 selection. Although the PGK-1 and SV40 promoters efficiently drove neo gene expression, the CMV promoter was significantly less transcriptionally active in cynomolgus monkey ES cells. Using this electroporation method, we established fluorescent cynomolgus monkey ES cell lines. These cells may be useful tools for tracing grafted cells in transplantation studies using a variety of functional cells derived from cynomolgus monkey ES cells.

Animals↗

PubMed2003

Cutoff value of 1 h, 50 g glucose challenge test for screening of gestational diabetes mellitus in a Japanese population.

A total of 2651 consecutive native Japanese women who underwent a glucose challenge test (GCT) were retrospectively investigated. GCT was performed between 24 and 27 weeks of gestation; each subject received a 50 g oral glucose load without regard to the fasting or fed state, followed by a determination of 1 h venous plasma glucose level. Women demonstrating GCT exceeding 130 mg/dl received a 75 g, 2 h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus (GDM). All women with GDM were treated with a strict diabetic protocol including insulin therapy. Forty-nine (1.8%) women were diagnosed to have GDM. The receiver-operator characteristic curve identified a GCT finding above 140 mg/dl as the cutoff value for detecting GDM, which showed a sensitivity and specificity of 96 and 76%, respectively. Our results suggest that the cutoff value of a 50 g GCT is 140 mg/dl to identify pregnancies with GDM in a Japanese population.

Blood Glucose↗