Biomedical subjects

S Adachi

Publications and source records attributed to S Adachi.

At least 19 recordsLinked to original sources

PubMed2006

Thyroid hormone receptor beta is widely expressed in the brain and pituitary of the Japanese eel, Anguilla japonica.

In a previous study, we cloned the thyroid hormone receptor betaB (TRbetaB) from a teleostean fish, the Japanese conger eel (Conger myriaster). The gene encoding this receptor is expressed in the brain and pituitary. In this study, we cloned TRbetaB from the brain of the Japanese eel (Anguilla japonica) to extend our studies into thyroid hormone function in fish. RT-PCR analysis demonstrated that the TRbetaB transcripts were abundant in both the brain and pituitary. The TRbetaB cDNA encoded a 379 amino acid protein with much higher homology to the conger eel TRbetaB than to other fish TRs, supporting the existence of a TRbetaB isoform, at least in anguilliforms. In a transiently transfected Japanese eel cell line, Hepa-E1, TRbetaB and its splice variants in the ligand-binding domain (TRbetaBL) showed thyroid hormone (TH)-dependent activation of transcription from the TH-responsive promoter. In situ hybridization studies revealed the presence of TRbetaB transcripts in the pars distalis of the pituitary.

Amino Acid Sequence↗

PubMed2006

A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours.

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study.

Adult↗

PubMed2005

Portal venous tumor thrombus associated with hepatic metastasis of renal cell carcinoma: case report.

We report a case of liver metastasis of renal cell carcinoma with portal venous tumor thrombus. Abdominal computed tomographic images showed a large hepatic mass that enhanced slightly during arterial phase. Multiple hypoattenuating lesions were seen in the intrahepatic portal venous branches and were traced directly from the mass. The histologic specimen confirmed metastatic liver tumor of renal cell carcinoma with portal venous tumor thrombus.

Adult↗

PubMed2005

Bisphenol A in ambient air particulates responsible for the proliferation of MCF-7 human breast cancer cells and Its concentration changes over 6 months.

To survey the estrogenic activity of the organic extracts from particulate matter of urban ambient outdoor air, samples were collected on glass fiber filters using a high-volume air sampler on the rooftop of our institute for 6 months (six filters/month). After extracting the organic materials and separating them into three fractions, i.e., acidic, neutral, and basic, we applied a cell-growth assay using MCF-7 human breast cancer cells to the original extract and the extracts of the fractions. Only the extract in the acidic fraction showed cell proliferation activity in a dose-response manner. To survey the chemical(s) responsible for the activity, a gas chromatography/mass spectrometry (GC/MS) analysis was conducted after silylating the extract. The presence of bisphenol A (BPA) was confirmed, because the retention times and the MS fragment patterns between the silylated derivative of a component in the sample and that of BPA itself were the same. By using a GC/MS-SIM (selective ion monitoring) technique, the average value was found to be 0.51 ng/m(3) of air (range: 0.02 approximately 1.92 ng/m(3) of air). The trend of the residual levels in air particulates showed seasonal variation, increasing from autumn to winter and decreasing from winter to spring. The only exception was that the value in January was lower than those in December and February. Considering the content of BPA in the extract of the acidic fraction and the strength of the activities with the extract and BPA itself, the estrogenic activity due to BPA in the fraction seemed to decrease. In spite of this decline, the possibility remains that the estrogenic activity mainly originated from BPA.

Air Pollutants↗

PubMed2005

[Sandwich technique for closing of the large muscular Swiss-cheese type ventricular septal defects].

A 9-year-old girl, who has had a diagnosis as a Taussig-Bing anomary, underwent an original Jatene procedure (o-J) 2 months after birth. This time, she had a diagnosis of the muscular multiple ventricular septal defects (mVSD) and pulmonary stenosis after o-J. The mVSD was Swiss-cheese type and was large from the proximal of the infundibular septum to the apex and posterior of the septum. It was closed by the sandwich technique using a pair of felt patches, which of one was placed at right ventricular side and the other was at left ventricular side, slightly larger than the whole area of the mVSD. The patch fixation was placed with 1 stitch at the center between the patches and a few stitches around the right ventricular side patch to the ventricular septum. Postoperative cardiac function was uneventful regardless of the very large patches placed at the ventricular septum and the cardiac catheterization after 1 year postoperatively showed the pulmonary/systemic blood flow ratio was 1.0. This technique for the closure of the large Swiss-cheese type mVSD can be considered to be very effective.

Cardiac Surgical Procedures↗

PubMed2005

[Papillary fibroelastoma of the right atrium; report of a case].

Papillary fibroelastoma is a rare benign tumor commonly arising from a heart valve. We describe an unusual papillary fibroelastoma that arose from the right side of the interatrial septum. An intracardiac tumor was discovered by routine echocardiography in an asymptomatic 68-year-old woman. The echocardiographic examination revealed a 20 mm mobile tumor in the right atrium. Tricuspid obstruction was not observed, nor was regurgitation. The tumor was resected through a right atriotomy. It had multiple papillary fronds and arose from the interatrial septum. Pathologic examination confirmed papillary fibroelastoma. The postoperative course was uneventful, and the patient was discharged on postoperative day 13.

Aged↗

PubMed2004

Deduced primary structure of two forms of vitellogenin in Japanese common goby (Acanthogobius flavimanus).

Complete nucleotide sequences of two forms of vitellogenin (Vg) cDNA in Japanese common goby were determined from a liver cDNA library of E(2)-treated male fish. These two Vg cDNAs contained complete open reading frames encoding 1664 and 1238 amino acid residues including signal peptides, respectively. From comparison of the deduced amino acid sequences of both Vgs and the partial amino acid sequences of the yolk proteins, the longer sequence was concluded to be cDNA of the Vg-530 and the shorter one was that of the Vg-320 of the Japanese common goby which were reported in our previous paper. The deduced sequence of Vg-530 without signal peptide was arranged by lipovitellin heavy-chain (LvH), phosvitin (Pv), lipovitellin light-chain (LvL), and beta'-component beta'-c) domains from the N-terminus, and showed a range of 40-45% sequence identity to those of other fish. Furthermore, the deduced sequence of Vg-320 showed no obvious Pv domain, has a shortened C-terminal coding region after the LvH domain, and showed a close similarity to the phosvitin-less Vg of zebrafish. Moreover, biochemical analysis of the yolk proteins verified that Vg-530 cleaves into the Lv-Pv complex (molecular mass: 470 kDa) and beta'-c (33 kDa), while Vg-320 showed no change when incorporated into oocytes. The present study demonstrated the existence of the two different forms of Vgs at both the cDNA and protein level, and showed molecular alteration of the two Vgs during vitellogenesis. Two Vg sequence data will aid in designing nucleotide probes for detecting Vg gene expressions as a biomarker of environmental estrogens.

Amino Acid Sequence↗

PubMed2004

Role of IL-18 in pathogenesis of endometriosis.

BACKGROUND: Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal fluid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis. METHODS: IL-18 and IL-1beta concentrations were measured in the peritoneal fluid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor alpha-chain (IL-18Ralpha) was analysed in endometriotic tissues immunohistochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal fluid monocytes and endometriotic cells of endometriosis patients. RESULTS: IL-18 concentrations in the peritoneal fluid of endometriosis patients averaged 592.57 +/- 108.27 pg/ml, significantly higher than 260.50 +/- 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ significantly between endometriosis and control patients. Similarly, no significant differences were observed in IL-1beta concentrations in either the peritoneal fluid or the serum. IL-18 and IL-18Ralpha were expressed in endometriotic tissues. IL-18Ralpha expression was also observed in cells infiltrating into the inflammatory area of the endometriosis patients. COX-II was induced in peritoneal fluid monocytes and in endometriotic cells in response to IL-18 stimulation. CONCLUSIONS: The elevation of IL-18 in the peritoneal fluid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.

Adult↗

PubMed2004

Transgenerational transmission of radiation- and chemically induced tumors and congenital anomalies in mice: studies of their possible relationship to induced chromosomal and molecular changes.

This article provides a broad overview of our earlier studies on the induction of tumors and congenital anomalies in the progeny of X-irradiated or chemically treated mice and our subsequent (published, hitherto unpublished and on-going) investigations aimed at identifying potential relationships between genetic changes induced in germ cells and the adverse effects manifest as tumors and congenital anomalies using cytogenetic and molecular approaches. The earlier studies document the fact that tumors and congenital anomalies can be induced by irradiation or treatment with certain chemicals such as urethane and that these phenotypes are heritable i.e., transmitted to generations beyond the first generation. These findings support the view that transmissible induced genetic changes are involved. The induced rates of congenital abnormalities and tumors are about two orders of magnitude higher than those recorded in the literature from classical mutation studies with specific locus mutations. The cytogenetic studies addressed the question of whether there were any relationships between induced translocations and induced tumors. The available data permit the inference that gross chromosomal changes may not be involved but do not exclude smaller induced genetic changes that are beyond the resolution of the techniques used in these studies. Other work on possible relationship between visible chromosomal anomalies (in bone marrow preparations) and tumors were likewise negative. However, there were indications that some induced cytogenetic changes might underlie induced congenital anomalies, i.e., trisomies, deletions and inversions were observed in induced and transmissible congenital anomalies (such as dwarfs, tail anomalies). Studies that explored possible relationships between induction of minisatellite mutations at the Pc-3 locus and tumors were negative. However, gene expression analysis of tumor (hepatoma)-susceptible offspring of progeny descended from irradiated male mice showed abnormal expression of many genes. Of these, only very few were oncogenes. This lends some support to our hypothesis that cumulative changes in gene expression of many genes, which perform normal cellular functions, may contribute to the occurrence of tumors in the offspring of irradiated or chemically treated mice.

4-Nitroquinoline-1-oxide↗

PubMed2004

[Valvuloplasty for mitral regurgitation immediately following Kawasaki disease without abnormal coronary arteries lesion; report of a case].

It is not uncommon that valve disease is complicated with Kawasaki disease (KD). However, it is rare to show normal coronary arteries simultaneously. We experienced a case of valvuloplasty towards the mitral regurgitation (MR) followed immediately after KD showing normal coronary arteries. A 3 year-old-female, with a diagnosis of KD at 4 months after birth, was referred to our hospital 5 months after birth. The echocardiography detected a moderate MR. The preoperative catheterization at 2.5 years old showed grade III MR, enlargement of left atrium and left ventricle, pulmonary capillary wedge pressure (PCWP) = 12 mmHg, left ventricular ejection fraction (LVEF) = 675, and normal coronary arteries. Pulmonary hypertention was not revealed. The operative findings showed mitral valve prolapse due to the elongation of the chordae of the anterior leaflet. She underwent artificial chordal reconstruction using expanded polytetrafluoroethylene sutures and mitral annuloplasty by Kay-Reed method. The postoperative course was uneventful, and she was discharged on postoperative day 19.

Artificial Organs↗

PubMed2003

Successful T-cell-replete peripheral blood stem cell transplantation from HLA-haploidentical microchimeric mother to daughter with refractory acute lymphoblastic leukemia using reduced-intensity conditioning.

A 16-year-old girl with refractory acute lymphoblastic leukemia underwent reduced-intensity hematopoietic stem cell transplantation from her two-locus-mismatched haploidentical mother, who was microchimeric for the patient's hematopoietic cells. The conditioning regimen comprised melphalan, fludarabine, and low-dose total body irradiation. Non-T-cell-depleted peripheral blood stem cells were infused with graft-versus-host disease (GVHD) prophylaxis consisting of tacrolimus, prednisolone, and short-course methotrexate. Complete donor-type engraftment without evidence of residual leukemia was confirmed on day 22. Severe GVHD was not observed despite rapid cessation of immunosuppression. The patient remains well in continuous remission 15 months after transplant. This successful experience suggests that maternal hematopoietic stem cell transplants for children, in the presence of microchimerism, may be associated with hyporesponsiveness to the inherited paternal HLA antigens (IPA); preventing severe GVHD.

Adolescent↗

PubMed2002

Ovarian mitochondrial cytochrome b mRNA levels increase with sexual maturity in freshwater eels (Anguilla spp.).

Differential display of mRNA was used to identify an upregulated gene in ovaries of artificially maturing Japanese eels (Anguilla japonica). Accordingly, mitochondrial (mt) cytochrome b, whose transcript levels increased from early to late vitellogenesis, was isolated, cloned and sequenced. Temporal trends in artificially maturing eels were compared with those in naturally and artificially maturing New Zealand eels (longfinned eel, Anguilla dieffenbachii; shortfinned eel, Anguilla australis) by Northern blot and in situ hybridization analysis to rule out any experimental artifacts. An increase in ovarian mt cytochrome b signals was seen when comparing immature and midvitellogenic longfinned eels, but not immature and early vitellogenic shortfinned eels, from the wild. Long-term captivity yielded reduced target mRNA levels, but abundance increased after hormonal induction of vitellogenesis. These results imply that the increase in mt cytochrome b mRNA levels during artificial maturation reflects natural development, although its onset appears to be brought forward during artificial maturation in the Japanese eel. It is suggested that increased mt cytochrome b mRNA levels result from both mitochondrial replication and increased transcription, and that they reflect the build-up of machinery for enhanced ATP-synthesis at some stage of oogenesis and/or early zygote development.

Animals↗

PubMed2002

Malignant epithelial tumor of unknown origin of the broad ligament.

Malignant epithelial tumor of the broad ligament is rare and to our knowledge only 17 cases have been reported. We report a 54-year-old Japanese woman in whom transvaginal sonography (TVS) and magnetic resonance imaging (MRI) showed a left adnexal tumor. Serum CA125 was elevated to 10,000 U/ml. Preoperatively, we diagnosed this tumor was a left ovarian malignant tumor though, it was confirmed a the 47x57 mm tumor in the left broad ligament at laparotomy. Histologically most of the tumor showed serous papillary adenocarcinoma with changes similar to poorly differentiated carcinoma and as seen in transitional cell carcinoma on hematoxylin-eosin staining. After three courses of platinum based adjuvant chemotherapy, the patient is alive with no recurrence at 18 months postoperatively.

Broad Ligament↗

PubMed2002

Successful hematopoietic stem cell transplantation for aplastic anemia following living-related liver transplantation.

A 1-year-old boy received a living-related liver transplantation (LRLT) from his HLA-haploidentical father to treat acute liver failure following non-A, non-B, non-C hepatitis. He subsequently developed pancytopenia and was diagnosed with aplastic anemia (AA). He was platelet transfusion dependent and developed two episodes of life-threatening intracranial hemorrhage despite immuno-suppressive therapy consisting of cyclosporin A, antithymocyte globulin, and anabolic steroids. He received combined hematopoietic stem cell transplantation (hSCT) with cord blood and bone marrow from an HLA-matched sibling. Conditioning consisted of cyclophosphamide (CY) 200 mg/kg and 7 Gy total lymphoid irradiation (TLI). Marrow engraftment was prompt and there was no significant graft-versus-host disease (GVHD).

Anemia, Aplastic↗

PubMed2001

Activation of lectin-like oxidized low-density lipoprotein receptor-1 induces apoptosis in cultured neonatal rat cardiac myocytes.

BACKGROUND: Lectin-like oxidized LDL receptor-1 (LOX-1) was originally identified as a receptor expressed predominantly in endothelial cells. LOX-1 can also be expressed in other cell types, and the activation of the LOX-1 pathway has been implicated in apoptosis. There have been no reports, however, about LOX-1 expression in cardiac myocytes or regulation of myocardial cell apoptosis by LOX-1. METHODS AND RESULTS: In primary cardiac myocytes from neonatal rats, immunohistochemical analyses using a specific monoclonal antibody against LOX-1 demonstrated that LOX-1 expression was markedly induced by stimulation with norepinephrine and endothelin-1. LOX-1 expression was upregulated in cardiac myocytes as well as in vessel walls of failing rat hearts in vivo. In the presence of a low concentration of oxidized LDL that did not induce apoptosis by itself, artificial overexpression of LOX-1 in cardiac myocytes in culture resulted in apoptosis. LOX-1 overexpression induced activation of p38 mitogen-activated protein kinase (MAPK) and oxidative stress in cardiac myocytes, as demonstrated by an increase in positive immunostaining for 8-hydroxy-2'-deoxyguanosine. Inhibition of p38 MAPK by cotransfection of a dominant-negative form of MKK6 as well as by administration of a specific inhibitor, SB203580 or FR167653, almost completely blocked the induction of apoptosis by LOX-1 activation. Antioxidant catalase also blocked LOX-1-induced apoptosis as well as activation of p38 MAPK. CONCLUSIONS: These findings demonstrate that LOX-1 expression in cardiac myocytes is induced by neurohormonal factors activated in heart failure and that LOX-1-dependent apoptosis in these cells requires p38 MAPK, a component of oxidant stress-sensitive signaling pathways.

Animals↗

PubMed2001

Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats.

Dietary cobalamin (vitamin B12; Cbl) deficiency caused significant increases in plasma serine, threonine, glycine, alanine, tyrosine, lysine and histidine levels in rats. In particular, the serine and threonine levels were over five and eight times, respectively, higher in the Cbl-deficient rats than those in the sufficient controls. In addition, some amino acids, including serine and threonine, were excreted into urine at significantly higher levels in the deficient rats. When Cbl was supplemented into the deficient rats for 2 weeks, in coincidence with the disappearance of the urinary excretion of methylmalonic acid (an index of Cbl deficiency), the plasma serine and threonine levels were normalized. These results indicate that Cbl deficiency results in metabolic disorder of certain amino acids, including serine and threonine. The expression level of hepatic serine dehydratase (SDH), which catalyzes the conversion of serine and threonine to pyruvate and 2-oxobutyrate, respectively, was significantly lowered by Cbl deficiency, even though Cbl does not participate directly in the enzyme reaction. The SDH activity in the deficient rats was less than 20% of that in the sufficient controls, and was normalized 2 weeks after the Cbl supplementation. It is thus suggested that the decrease of the SDH expression relates closely with the abnormalities in the plasma and urinary levels of serine and threonine in the Cbl-deficient rats.

Animals↗

PubMed2001

Picometer-scale dynamical x-ray imaging of single DNA molecules.

Time-resolved dynamical x-ray imaging of individual DNA molecules with picometer-scale precision is demonstrated for the first time. Diffracted x-ray tracking (DXT), a single-molecule experiment with x rays, monitors the rotating motions, rather than the translational motions, of a labeled nanocrystal. DXT can obtain information about the dynamics of single molecules through a quantitative analysis, since the signals from DXT are independent of the chemical conditions.

DNA↗

PubMed2001

Induction of CCR7 expression in thymocytes requires both ERK signal and Ca(2+) signal.

CC chemokine receptor 7 (CCR7) expression is crucial for thymocyte trafficking across the corticomedullary junction in the thymus and for lymph node homing of naive T cells. However, the induction mechanism of CCR7 expression is vastly unknown. In isolated CD4+CD8+CCR7-thymocytes, a moderate 20-h pulse stimulation with a combination of the calcium ionophore ionomycin and the protein kinase C activator phorbol myristate acetate induced CCR7 expression and CD8 downregulation. Similar changes were induced in a CD4+CD8+CCR7- T cell line upon stimulation with the same combination of reagents, but not with either one alone. These changes were inhibited by U0126, an inhibitor of the extracellular signal-regulated kinase kinase (ERKK/MEK). The transfectants expressing a constitutively active form of the MEK kinase Raf-1 became CD4+CD8+CCR7+ upon stimulation with ionomycin alone. Thus, Raf-1-mediated signals and Ca(2+)-dependent signals are essential to induce CCR7 expression in CD4+CD8+ T cells and thymocytes as well as their differentiation.

Animals↗