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Biomedical subjects

M Nagahama

Publications and source records attributed to M Nagahama.

At least 19 recordsLinked to original sources
PubMed2006

Down-regulation of an inhibitor of cell growth, transmembrane protein 34 (TMEM34), in anaplastic thyroid cancer.

PURPOSE: Ansaplastic thyroid cancer (ATC) is one of the most lethal malignancies, but the carcinogenic mechanism of ATC has not been clarified. Recently, we performed a cDNA microarray analysis and identified transmembrane protein 34 (TMEM34) that down-regulated in anaplastic thyroid cancer cell lines (ACL)s as compared to normal thyroid tissues. METHODS: To investigate the role of TMEM34 in ATC carcinogenesis, we examined expression levels of TMEM34 in ACLs as well as differentiated thyroid cancers (DTC)s and normal human tissues. To explore the effect of TMEM34 in ATC development, cell-growth assays with KTA2 cells were performed. RESULTS: Expression of TMEM34 was down-regulated in all 11 ACLs, as compared to either normal thyroid tissues or cell lines derived from papillary or follicular thyroid cancers. TMEM34 was expressed ubiquitously in normal human tissues tested. Transfection of TMEM34 into KTA2 cells led to inhibition of cell growth. CONCLUSIONS: Our findings suggest that TMEM34 might be a tumor suppressor gene, associated with the development of ATC from DTC.

Carcinoma↗
PubMed2005

Chemical evolution of RNA under hydrothermal conditions and the role of thermal copolymers of amino acids for the prebiotic degradation and formation of RNA.

The roles of thermal copolymers of amino acids (TCAA) were studied for the prebiotic degradation of RNA. A weak catalytic ability of TCAA consisted of Glu, L-Ala, L-Val, L-Glu, L-Asp, and optionally L-His was detected for the cleavage of the ribose phosphodiester bond of a tetranucleotide (5'-dCrCdGdG) in aqueous solution at 80 degees C. The rate constants of the disappearance of 5'-dCrCdGdG were determined in aqueous solutions using different pH buffer and TCAA. The degradation rates were enhanced 1.3-3.0 times in the presence of TCAA at pH 7.5 and 8.0 at 80 degrees C, while the hydrolysis of oligoguanylate (oligo(G)) was accelerated about 1.6 times at pH 8.0. A weak inhibitory activity for the cleavage of oligo(G) was detected in the presence of 0.055 M TCAA-Std. On the other hand, our recent study on the influences of TCAA for the template-directed reaction of oligo(G) on a polycytidylic acid template showed that TCAA has an acceleration activity for the degradation of the activated nucleotide monomer and an acceleration activity for the formation of G5' ppG capped oligo(G). This series of studies suggest that efficient and selective catalytic or inhibitory activities for either the degradation or formation of RNA under hydrothermal conditions could have hardly emerged from the simple thermal condensation products of amino acids. A scenario is going to be deduced on the chemical evolution of enzymatic activities and RNA molecules concerning hydrothermal earth conditions.

Amino Acids↗
PubMed2004

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

Biomarkers, Tumor↗
PubMed2002

Male siblings with dyserythropoiesis, microcephaly and intrauterine growth retardation.

Male siblings with intrauterine growth retardation, hydrops, mild liver dysfunction, chronic diarrhoea, failure to thrive and microcephaly are reported. In both patients, the intrauterine growth retardation was detected in the second trimester of pregnancy. Relatively severe early onset neonatal jaundice, microcytosis, anisocytosis and abnormal iron metabolism were also seen. Bone marrow examination in the second sibling showed marked ringed sideroblasts and multilobulated erythroblasts in late developmental stages. The brain was very small with enlarged cerebrospinal fluid space, a reduced number of gyri and a thin cortex. The clinical and laboratory findings in these patients appear to be unique.

Anemia, Dyserythropoietic, Congenital↗
PubMed2001

The first direct oxidative conversion of a selenol to a stable selenenic acid: experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase.

[structure: see text]. A stable selenenic acid was synthesized by direct oxidation of a selenol bearing a novel bowl-type substituent with H2O2, and its structure was established by X-ray crystallographic analysis. Selenenyl sulfides obtained by the reaction of the selenenic acid with 1,4-dithiols were reduced to the corresponding selenol by treatment with a tertiary amine, thus achieving the experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase.

Catalysis↗
PubMed2001

Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver.

PURPOSE: Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. MATERIALS AND METHODS: The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. RESULTS: The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3+/-12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2+/-107 IU/l), than in group 1 (672.3+/-160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. CONCLUSION: These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.

Animals↗
PubMed2001

Distribution of peripheral nerve terminals in the small and large intestine of congenital aganglionosis rats (Hirschsprung's disease rats).

The congenital aganglionosis rat is considered to be an animal model of Hirschsprung's disease. The mutants had a long constricted segment (from distal ileum to rectum) below the dilated distal ileum. In the dilated region, synaptophysin-immunoreactivity (IR) was almost preserved in all layers of the intestinal wall. In the constricted distal ileum and oral proximal colon, synaptophysin-IR was scarce in all layers, including the circular and longitudinal muscle layers. In the anal proximal and distal colon, synaptophysin-IR was almost scarce in the circular muscle layer (CML). An ultrastructural study confirmed that almost no terminals were found in the CML of any regions of constricted intestine. Therefore, the CML in any region of a constricted segment, is presumed to be poor innervation. However, a few synaptophysin-IR were found in the longitudinal muscle layer (LML) of an anal part of a constricted segment. An ultrastructural study also confirmed that some terminals were observed in the LML of this segment. The present study suggested that denervated CML is related to the production of constricted segment, irrespective of the presence or absence of terminals in the LML.

Animals↗
PubMed2001

Cellular localization of group IIA phospholipase A2 in rats.

It has been known that group II phospholipase A2 (PLA2) mRNA and protein are present in the homogenates of the spleen, lung, liver, and kidney in normal rats, but the cellular origin of this enzyme has not been yet identified. At present, five subtypes of group II PLA2 have been identified in mammals. Antibodies or mRNA probes previously used for detecting group II PLA2 need to be evaluated to identify the subtypes of group II PLA2. In this study we tried to identify group IIA PLA2-producing cells in normal rat tissues by in situ hybridization (ISH) using an almost full-length RNA probe for rat group IIA enzyme. Group IIA PLA2 mRNA was detected in megakaryocytes in the spleen and Paneth cells in the intestine by ISH. These cells were also immunopositive for an antibody raised against group IIA PLA(2) isolated from rat platelets. Group IIA PLA2 mRNA-positive cells were not detected in lung, liver, kidney, and pancreas. Under normal conditions, group IIA PLA2-producing cells are splenic megakaryocytes and intestinal Paneth cells in rats.

Animals↗
PubMed2001

Effect of bezafibrate on soluble adhesion molecules and platelet activation markers in patients with connective tissue diseases and secondary hyperlipidemia.

We evaluated the plasma concentrations of soluble adhesion molecules, platelet activation markers, and platelet-derived microparticles (PMPs) in patients with connective tissue diseases who had secondary hyperlipidemia caused by long-term steroid administration (n = 22) before and after treatment with bezafibrate. There were differences in levels of platelet activation markers both before and after treatment (platelet CD62p: 15.11+/-2.03 vs 10.38+/-8.53%, P < 0.05; platelet CD63: 12.12+/-9.17 vs 9.90+/-7.20%, P < 0.05). There were also differences in the levels of PMPs and soluble adhesion molecules both before and after treatment (PMP: 514+/-273 vs 401+/-201 /10(4) platelet. P < 0.05; soluble vascular cell adhesion molecule-1: 724+/-191 vs 666+/-157 ng/mL, P < 0.01). After 6 months of treatment, serum lipid concentrations were reduced by 9% for total cholesterol (TC) and 32% for triglyceride (TG). The level of PMPs, activated platelets, and soluble adhesion molecules were all significantly decreased after treatment with bezafibrate. These findings suggest that bezafibrate may be useful for inhibiting both PMP-dependent and -independent vascular damage in patients with connective tissue diseases complaining of secondary hyperlipidemia.

Bezafibrate↗
PubMed2001

Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus.

We assessed the role of platelet activation markers (PMPs, Annexin V and CD62P on activated platelets), cytokines (IL-1 beta, IL-4, IL-6, IFN- gamma, GM-CSF, and TNF alpha ), and soluble factors (sIL-2R, TM, sHLA-1, beta(2) -m, sVCAM-1, sPECAM-1, sP-selectin and sE-selectin) in vascular damage related to SLE. There were differences in the levels of PMPs and platelet activation markers between the SLE patients and controls (PMPs: 493+/-82 vs. 328+/-36, p<0.05; plt-CD62P; 8.5%+/-1.2 % vs. 4.6%+/-0.7 %, p<0.05; plt-Annexin V: 11.3%+/-2.1 % vs. 4.9%+/-0.6 %, p<0.01). There were no differences in the levels of IFN- gamma between the groups. However, the levels of IL-1 beta, IL-4, IL-6, GM-CSF, TNF alpha, and soluble factors were higher in the SLE patients than in the controls. The levels of IL-4, IL-6, beta2 -m, sIL-2R, sVCAM-1, sP-selectin, and sE-selectin in SLE patients with elevated sTM levels were higher than those in the SLE patients without elevated sTM levels. On the other hand, elevations of sIL-2R, sVCAM-1, and sP-selectin were not found in patients with Behçet disease or rheumatoid arthritis. The levels of platelet CD62P, platelet annexin V, and PMP were significantly elevated in high-sTM patients. These findings suggest the possibility that activated platelets and cytokines participate in the pathogenesis of SLE in patients with elevated sTM levels.

Adult↗
PubMed2001

[Systemic inflammatory response syndrome triggered by necrotizing cholecystitis after treatment of underlying low titer cold agglutinin disease].

In April 1996, a 77-year-old man initially presented with fever, rash and polyarthralgia, and was diagnosed as having low titer cold agglutinin disease with acute hemolytic anemia. The patient's condition and laboratory findings improved after administration of corticosteroid (prednisolone 60 mg). In June 1996, however, he developed acute cholecystitis and died due to sepsis, disseminated intravascular coagulation and multiple organ failure. During the course, the levels of inflammatory cytokines such as TNF-alpha and IL-6 were correlated with the pathology, and the disease was diagnosed as systemic inflammatory response syndrome (SIRS). Autopsy revealed necrotizing cholecystitis, erythrophagocytosis in the liver, and cytomegalovirus infection in the lung and gall bladder. This was considered to be a rare case of low titer cold agglutinin disease complicated by SIRS.

Aged↗
PubMed2000

Determination of functional regions of p125, a novel mammalian Sec23p-interacting protein.

The Sec23p-Sec24p complex is a component of coat protein II-coated vesicles involved in protein export from the endoplasmic reticulum. We previously identified a novel Sec23p-interacting protein, p125, which consists of 1000 amino acids and comprises a proline-rich region and a phospholipase A(1) homology region. p125, when ectopically expressed in cultured cells, localizes to endoplasmic reticulum-Golgi intermediate regions. In the present study we showed that expressed p125 principally colocalizes with p115 and GM130, both of which are involved in vesicle tethering to Golgi membranes. Next, we determined the functional regions of p125 by expressing a p125 series with deletions. The results showed that the proline-rich region (residues 135-259) is responsible for the binding to Sec23p. For the correct localization of p125, a region (residues 135-1000) comprising both the proline-rich and phospholipase A(1) homology regions was required.

Animals↗
PubMed2000

N-ethylmaleimide-sensitive factor is associated with the nuclear envelope.

N-Ethylmaleimide-sensitive factor (NSF) is an ATPase involved in many membrane fusion events within the exocytic and endocytotic pathways. In the present study we showed that NSF is associated with the nuclear envelope. Golgi-associated NSF was released from membranes upon incubation with Mg(2+)-ATP, reflecting the disassembly of a complex consisting of NSF, soluble NSF attachment proteins (SNAPs), and SNAP receptors (SNAREs). In contrast nuclear envelope-associated NSF in interphase cells was not released by the same treatment. During mitosis, however, it was released from nuclear membranes by Mg(2+)-ATP. These results suggest that the binding mode of nuclear membrane-associated NSF changes during the cell cycle.

Adenosine Triphosphate↗
PubMed2000

Regulation of the golgi structure by the alpha subunits of heterotrimeric G proteins.

Disassembly of the Golgi apparatus is elicited by the action of nordihydroguaiaretic acid (NDGA) and this disassembly is prevented by the activation of heterotrimeric G proteins. In the present study we showed that overexpression of Galpha(z) or Galpha(i2) significantly suppresses the disassembly of the Golgi apparatus induced by NDGA. Overexpression of Gbeta(1)gamma(2), on the other hand, had no effect on NDGA-induced Golgi disassembly. Galpha(z) neither blocked Golgi disassembly induced by brefeldin A or nocodazole, nor interfered with protein transport, suggesting its specificity on the action of NDGA. Our results suggest that the alpha subunits of heterotrimeric G proteins are responsible for the maintenance of the Golgi structure.

Animals↗
PubMed2000

Serum levels of soluble CD30 in autologous peripheral blood stem cell transplantation.

High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important method of treatment for hematological and solid tumors. We examined levels of interleukin(IL)-4, interferon (IFN)gamma, soluble (s) CD30, and sIL-2 receptor (R) before and after autologous PBSCT, and compared findings for PBSCT with those for bone marrow transplantation (BMT). We found significantly higher IL-4 levels 1 and 3 weeks after PBSCT than before PBSCT, while IFNgamma levels remained almost unchanged after PBSCT. IFNgamma levels were increased 3 weeks after BMT, although no increase in IL-4 level was observed. The serum sCD30 level was significantly higher 3 weeks after PBSCT, but not following BMT. For 34 samples on days 0 and 21 from 17 patients undergoing PBSCT, a strong correlation was observed between sCD30 and sIL-2R levels (r = 0.43, P < 0.01). However, no significant correlation between sCD30 and sIL-2R levels was found for BMT patients. These findings suggest that sCD30 is a useful marker for evaluating immunological activity following autologous PBSCT, and that the immunological conditions after autologous PBSCT may be associated with helper-T-cell-2-type immune responses.

Adult↗
PubMed2000

Limitations of exogenous L-arginine in exerting a cytoprotective effect on hepatic ischemia/reperfusion injury.

To test whether or not the L-arginine/nitric oxide (NO) pathway induces a protective effect, we investigated the effect of exogenous L-arginine on hepatic ischemia/reperfusion (I/R) injury, using ex vivo perfusion of the isolated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37 degrees C. Either 600 mg/kg of L-arginine (groups 1 and 4), D-arginine (group 2), N(G)-nitro-L-arginine methyl ester (L-NAME) (group 3), or saline (group 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/kg of L-NAME was preadministered at 10 min prior to the administration of L-arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (227% +/- 70% of the pre-reperfusion levels at 5 min) after reperfusion in group 1. Pretreatment with L-NAME suppressed the elevation of the NO levels immediately after reperfusion in group 4. The lactate dehydrogenase release to the effluent perfusate significantly decreased and the histological findings showed that the sinusoidal damage observed after reperfusion was mitigated in group 1 more than in the other groups. These results thus suggest that exogenous L-arginine produced a relatively small amount of NO and therefore resulted in a slight decrease of hepatic I/R injury.

Animals↗