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Biomedical subjects

S Yamanaka

Publications and source records attributed to S Yamanaka.

At least 37 records · Page 2Linked to original sources

Hexosaminidase-altered aberrant crypts, carrying decreased hexosaminidase alpha and beta subunit mRNAs, in colon of 1,2-dimethylhydrazine-treated rats.

Aberrant crypt foci (ACF), consisting of morphologically irregular crypts, are thought to be precancerous lesions for colon cancers. For their molecular analysis, it is necessary to avoid contamination with adjacent normal crypts and stromal cells. Decreased hexosaminidase activity in ACF, which has been histochemically demonstrated, was used in the present study to classify isolated crypts in combination with morphological changes. The length, rim diameter, and width (average SD, microm) of hexosaminidase-positive (Hex + ) crypts were 238.6 +/- 40.4, 89.5 +/- 22.9, and 57.6 +/- 14.0, respectively. For hexosaminidase-negative (Hex - ) crypts, the values were 314.4 +/- 77.8, 140.3 +/- 45.7, and 97.3 +/- 34.7, the width being 1.69 times greater (P < 0.0001). Crypts wider than 115 microm (approximately 2 times the average size of Hex + crypts) were all from ACF, judging from hexosaminidase staining. To analyze transcription levels of Hex alpha and beta subunits (Hexa and Hexb, respectively), real-time relative quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed using the LightCycler system. In aberrant crypts, both Hexa and Hexb were significantly down-regulated to 0.266 (P < 0.002) and 0.131 (P < 0.001) units, respectively, compared with those in morphologically normal crypts, with beta-actin as the internal standard. This decrease could be a molecular marker for precancerous enzyme-altered ACF.

1,2-Dimethylhydrazine↗

Important role of energy-dependent mitochondrial pathways in cultured rat cardiac myocyte apoptosis.

Recent studies have suggested that apoptosis and necrosis share common features in their signaling pathway and that apoptosis requires intracellular ATP for its mitochondrial/apoptotic protease-activating factor-1 suicide cascade. The present study was, therefore, designed to examine the role of intracellular energy levels in determining the form of cell death in cardiac myocytes. Neonatal rat cardiac myocytes were first incubated for 1 h in glucose-free medium containing oligomycin to achieve metabolic inhibition. The cells were then incubated for another 4 h in similar medium containing staurosporine and graded concentrations of glucose to manipulate intracellular ATP levels. Under ATP-depleting conditions, the cell death caused by staurosporine was primarily necrotic, as determined by creatine kinase release and nuclear staining with ethidium homodimer-1. However, under ATP-replenishing conditions, staurosporine increased the percentage of apoptotic cells, as determined by nuclear morphology and DNA fragmentation. Caspase-3 activation by staurosporine was also ATP dependent. However, loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bax translocation, and cytochrome c release were observed in both apoptotic and necrotic cells. Moreover, cyclosporin A, an inhibitor of mitochondrial permeability transition, attenuated staurosporine-induced apoptosis and necrosis through the inhibition of DeltaPsi(m) reduction, cytochrome c release, and caspase-3 activation. Our data therefore suggest that staurosporine induces cell demise through a mitochondrial death signaling pathway and that the presence of intracellular ATP favors a shift from necrosis to apoptosis through caspase activation.

Adenosine Triphosphate↗

Diesel exhaust particle-induced cell death of human leukemic promyelocytic cells HL-60 and their variant cells HL-NR6.

The cytotoxicity of diesel exhaust particles (DEPs) toward human leukemic promyelocytic cells HL-60 was examined. DEPs were toxic and cytotoxicity increased in a dose-dependent manner. All cells died with 750 microg/ml DEPs in culture media. Apoptosis occurred in HL-60 cells exposed to DEPs. The cytotoxicity of DEP extracts with organic solvents was much lower than those of DEPs and organic solvent-washed residual DEPs. HL-NR6 cells, an HL-60 variant cell line, having higher superoxide dismutase and catalase activities than HL-60 cells, were more resistant to DEP cytotoxicity. When preincubated with the fluorescent probe diacetoxymethyl 6-carboxy-2',7'-dichlorodihydrofluorescinate diacetate and then exposed to DEPs, HL-60 cells emitted green fluorescence under blue illumination, indicating that reactive oxygen species were generated within the cells. The DEP cytotoxicity correlated inversely with the cellular concentration of reduced glutathione (GSH), which had been attenuated with L-buthionine-(R,S)-sulfoximine, a gamma-glutamylcysteine synthetase inhibitor, and was lowered with ethyl reduced glutathionate, a GSH carrier across biomembranes. Further, DEPs themselves decreased the cellular concentration of GSH in a dose-dependent manner. The alpha-tocopherol model compound 2,2,5,7,8-pentamethylchroman-6-ol decreased DEP cytotoxicity, while alpha-tocopherol had no effect. In addition, quinacrine, an endocytosis inhibitor, decreased DEP cytotoxicity. These results show that DEPs are cytotoxic and suggest that the cytotoxicity results from generation of reactive oxygen species by DEPs which have been incorporated into cells.

Antioxidants↗

Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium. 1. Fermentation and biological characteristics.

Haliangicin, a novel beta-methoxyacrylate antibiotic with a conjugated tetraene moiety, was isolated from the culture broth of a marine myxobacterium. A bacterium tentatively named as Haliangium luteum required 2-3% NaCl for the growth and production of haliangicin. Haliangicin inhibits the growth of a wide spectrum of fungi but was inactive against bacteria. In mitochondrial respiratory chains, haliangicin interfered the electron flow within the cytochrome b-c1 segment.

Antifungal Agents↗

[Gross spreading multiple extramedullary plasmacytomas to the skin in the terminal stage of multiple myeloma].

A 71-year-old woman with an 8-year history of IgG-kappa type multiple myeloma was admitted because of severe lumbago and bone destruction. Her serum IgG level was elevated to 5,565 mg/dl at admission. Despite treatment with doxorubicin, vincristine, dexamethasone, melphalan and interferon-alpha, the response was transient. Nine months later, multiple skin nodules appeared on her chest, abdominal wall and right thigh accompanied by elevation of the serum IgG level. Response to combination chemotherapy with cyclophosphamide, ranimustine, vincristine and prednisolone was also transient. The skin tumors on the bilateral thighs, especially on the left side, acquired chemotherapy resistance and gradually enlarged. Although the serum IgG level was maintained by chemotherapy within the range 1, 790-2,676 mg/dl, the skin tumors on the left thigh had spread very rapidly and appeared "rock-like". The enlarged tumors caused necrosis with erosions and oozing hemorrhage. A skin biopsy from the tumors on the left thigh showed plasmacytoma in which infiltration of large anaplastic plasma cells was observed. The patient died of sepsis 8 months after the skin tumors initially developed. This is a very rare case of multiple myeloma in which multiple large plasmacytomas of the skin developed and grew aggressively at the terminal stage after a long-term indolent course.

Aged↗

Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway.

NAT1/p97/DAP5 is a newly identified protein that shares homology with the translation initiation factor eIF4G. Studies in vitro and in transfected cells indicated that NAT1 might suppress global translation, thereby repressing cellular proliferation. Here we studied the functions of NAT1 in vivo by disrupting its gene in mice. NAT1(-/-) embryos died during gastrulation, indicating a crucial role for NAT1 in embryogenesis. Undifferentiated NAT1(-/-) embryonic stem cells were normal in morphology, proliferation, global translation and gene expression profile. However, NAT1(-/-) cells exhibited an impaired ability to differentiate: they were resistant to differentiation induced by retinoic acid, and teratomas derived from them consisted of undifferentiated and poorly differentiated tissues. The expression of retinoic acid-responsive genes, such as the cell-cycle inhibitor p21(WAF1), was selectively impaired in NAT1(-/-) cells. Transcription from synthetic retinoic acid-responsive elements was also impaired. These data demonstrated that this translation initiation factor homolog controls specific gene expression pathways required for cellular differentiation.

Animals↗

Evolution, structure, and expression of GNPI/Oscillin orthologous genes.

Oscillin was identified from hamster sperm as a factor responsible for oocyte calcium oscillations. However, its high level of homology with the bacterial glucosamine-6-phosphate isomerase suggests that it may play more fundamental roles. In the current study, we identified Oscillin orthologs from Caenorhabditis elegans, Drosophila melanogaster, mouse, and human. Their amino acid identities with hamster oscillin were 67.0, 72.3, 97.6, and 95.5%, respectively. No Oscillin orthologs were found in Saccharomyces cerevisiae. The human Oscillin gene (HGMW-approved symbol GNPI) spans 12.4 kb and consists of eight exons. The position of the fourth intron was conserved in other species. The human Oscillin promoter has features characteristic of housekeeping genes, including a GC-rich content, multiple SP1 binding sites, and the absence of a TATA motif. Human and mouse Oscillin genes were ubiquitously expressed in all tissues examined. These data showed that Oscillin is a housekeeping gene conserved throughout evolution and do not support the notion that Oscillin is the sperm-specific factor responsible for calcium oscillations.

Aldose-Ketose Isomerases↗

Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth.

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting MKN45 cells with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector alone. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase. This was accompanied by overexpression of p21 protein. Tumorigenicity in the nude mice injected with antisense GLUT1 expressing cells was significantly slower than in those with wild-type MKN45 cells. These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and that expression of antisense GLUT1 mRNA via gene therapy can be used as a tool in the treatment of cancer.

Adenocarcinoma↗

High-pressure synthesis of the polymorph of layer structured compounds MNX (M = Zr, Hf; X = Cl, Br, I).

Transition metal nitride halides MNX (M = Zr, Hf; X = Cl, Br, I) have two types of layer structured polymorphs, the alpha-form with the FeOCl type and the beta-form with the SmSI type. Both polymorphs consist of corrugated double M-N layers sandwiched between halogen layers, but with different atomic arrangements within the layers. The beta-form had been considered to be a high-temperature polymorph, because some beta-forms were obtained by thermal treatment of the corresponding alpha-forms. Here, the alpha-form was successfully transformed into the beta-form under high-pressure and high-temperature conditions; the new members of the beta-form were prepared for the first time from alpha-HfNBr, alpha-ZrNI, and alpha-HfNI using a high pressure of 3-5 GPa at 900 degrees C. The beta-form should be characterized as the high-pressure form rather than the corresponding high-temperature polymorph. This is the first high-pressure study on the polymorphs of metal nitride systems.

Journal Article↗

High-pressure synthesis of a new silicon clathrate superconductor, Ba8Si46.

A new silicon clathrate compound with a composition of Ba8Si46 was prepared under high-pressure and high-temperature conditions. The compound was isomorphous with Na8Si46 and became a superconductor with a transition temperature of 8.0 K. Barium atoms occupy all of the Si20 and Si24 cages of the clathrate structure. This is the first clathrate superconductor obtained as a bulk phase.

Journal Article↗

Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes.

Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process.

Adult↗

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Adult↗

Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations in systemic hemodynamics in rats.

The present experiments were conducted to clarify the mode of cardiovascular action of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a nitric oxide (NO) scavenger, during rat endotoxic shock by determining cardiac output and systemic arterial tone simultaneously. Lipopolysaccharide (LPS) (10 mg/kg, i.v.) decreased systemic blood pressure and cardiac output with transient increases in hematocrit and total vascular resistance. Administration of carboxy-PTIO (1.7 mg x kg(-1) x min(-1), i.v. for 60 min) at 90 min after LPS attenuated further decline in blood pressure and cardiac output without affecting changes in hematocrit or total vascular resistance. It is concluded that carboxy-PTIO attenuates endotoxin-induced hypotension predominantly by maintaining cardiac output in rat experimental endotoxic shock.

Animals↗

Purification and characterization of novel transglutaminase from Bacillus subtilis spores.

Transglutaminase activity was detected in suspensions of purified spores prepared from lysozyme-treated sporulating cells of Bacillus subtilis AJ 1307. The enzyme was easily solubilized from the spores upon incubation at pH 10.5 at 37 degrees C. The transglutaminase activity was separated into two fractions upon purification by hydrophobic interaction chromatography (TG1 and TG2). Each enzyme was purified to electrophoretic homogeneity (about 1,000-fold). Both enzymes had the same molecular weight of 29,000 as estimated by SDS-PAGE, had the same N-terminal 30 amino acid sequence, and also showed the same optimal temperature (60 degrees C) and pH (8.2). The purified enzyme catalyzed formation of cross-linked epsilon-(gamma-glutamyl)lysine isopeptides, resulting in the gel-formation of protein solutions such as alphas-casein and BSA.

Amino Acid Sequence↗

Chromosome 22q11 deletion complicated by dissecting pulmonary arterial aneurysm and jejunal atresia in an infant.

We present an autopsy case of a 46-day-old male infant with chromosome 22q11 deletion, which is considered the primary cause of several diseases, including DiGeorge syndrome and velocardiofacial syndrome. The patient had 2 notable congenital abnormalities: multiple dissecting pulmonary arterial aneurysms distributed in both lungs and multiple jejunal atresia with apple-peel deformity. The former, a very rare pathologic condition especially in infancy, was found incidentally at autopsy and was the primary cause of death. To our knowledge, neither of these lesions has been reported previously in a patient with chromosome 22q11 deletion.

Aortic Dissection↗

[A case of synchronous ipsilateral renal cell carcinoma and ureteral transitional cell carcinoma].

A 62-year-old man was admitted to our hospital with the chief complaint of right flank pain. Abdominal computed tomographic scan revealed a right hydronephrosis and intrapelvic tumor. Ultrasound revealed a renal mass lesion. Ultrasound guided renal biopsy and laparotomy of intrapelvic tumor was performed. The histopathological diagnosis was renal cell carcinoma and ureteral transitional cell carcinoma.

Biopsy↗

[Cracks of polycarbonate three-way stopcock are caused by fat emulsion not by propofol].

We found fine cracks in a three-way stopcock after continuous infusion of propofol (Diprivan, Astra-Zeneca, UK). In this paper the possible mechanism was investigated. At first we checked various three-way stopcocks of various manufactures, such as JMS, Terumo, Nipro and Top. All of them were made with polycarbonate. Fine cracks were observed in all stopcocks after 6 hours of liquid contact with propofol between the three-way stopcock and male connector. Based on the mechanical stretch tests of polycarbonate plastic strips with saline, 10% fat emulsion (Intralipid, Otsuka, Japan), or 1% propofol in 10% fat emulsion (Diprivan), significantly greater cracks were observed in both fat group and propofol group, compared with the saline group. But there was no significant difference in cracks between fat and propofol groups. The size of crack increased in a time and strength dependent manner. We conclude that the cause of cracks in three-way stopcock is fat emulsion as a vehicle of propofol not propofol itself.

Anesthesiology↗