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Biomedical subjects

K Tago

Publications and source records attributed to K Tago.

At least 37 records · Page 2Linked to original sources
PubMed1999

Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM.

A novel variant cDNA from the human ST2 gene other than ST2 or ST2L was identified and tentatively named ST2V. Alternative splicing inserts a new exon which leads to a change in the C-terminal portion of ST2, causing it to gain a hydrophobic tail instead of losing the third immunoglobulin-like domain. ST2V is expressed in human leukemic cell line UT-7 and its sublines UT-7/GM, UT-7/EPO, and UT-7/TPO, in addition to human helper T cell line 5C10. The amount of ST2V mRNA is greatly diminished when UT-7/GM cells are induced to differentiate into either erythroblastic or megakaryoblastic phenotypes. The possible roles of the ST2V in growth and differentiation are intriguing.

Alternative Splicing↗
PubMed1999

Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy.

A novel insulin sensitizing agent, thiazolidine, has been demonstrated to inhibit the growth of cultured vascular smooth muscle cells (VSMC) in vitro. This study was undertaken to examine the in vivo effects of the thiazolidine compound pioglitazone (PIO) on carotid neointimal thickening, after endothelial injury in Wistar rats and vascular hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). PIO treatment (3 mg/kg/day for 1 week prior to endothelial injury and 2 weeks postendothelial injury) remarkably decreased neointimal cross-sectional areas in treated animals (63.8 +/- 4.9 x 10(3) microm2) versus controls (196 +/- 7.6 x 10(3) microm2, P < 0.05). Bromodeoxyuridine uptake in the neointima, a marker of DNA synthesis, was also decreased after treatment compared with controls. In SHR-SP/Izm but not in Wistar rats, PIO treatment decreased blood pressure and plasma insulin levels. PIO treatment in SHR-SP/Izm (3 mg/kg/day from 4 weeks of age for 7 weeks) significantly decreased the medial wall thickness of the mesenteric artery (10.4 +/- 1.2 x 10(3) microm2 versus control, 21.2 +/- 2.4 x 10(3) microm2, P < 0.05). In addition, PIO treatment significantly decreased the expression of EIIIA fibronectin both in the carotid neointima of Wistar rats and the media of the mesenteric artery in SHR-SP/Izm compared with their respective controls (P < 0.05). These results suggest that PIO has vasculo-protective effects in both acute and chronic vascular injury in vivo through inhibition of VSMC proliferation.

Animals↗
PubMed1999

Induction of heme oxygenase produces load-independent cardioprotective effects in hypertensive rats.

Although heme oxygenase (HO) has been suggested to be involved in the regulation of cardiovascular function through production of carbon monoxide (CO), the pathophysiological significance of HO in hypertensive organ damage remains unknown. We examined the effects of inducing HO-1 mRNA by stannous chloride (SnCl2) on cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Chronic administration of SnCl2 resulted in a significant decrease in left ventricular (LV) weight/body weight ratio and LV brain natriuretic peptide (BNP) mRNA levels as a marker of cardiac hypertrophy and a significant increase in LV HO-1 mRNA levels and LV cGMP contents in SHR-SP/Izm, while there was no significant change in systemic blood pressure. These results provide the first evidence that induction of HO in the heart attenuates cardiac hypertrophy in load-independent mechanism in genetically hypertensive rats.

Animals↗
PubMed1999

Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells.

The ST2 gene encodes receptor-like molecules that are very similar to the type I interleukin-1 receptor. Two distinct types of the ST2 gene products, ST2 (a soluble secreted form) and ST2L (a transmembrane form) are produced by alternative splicing. Here we demonstrate that the human ST2 gene has two alternative promoters followed by distinct noncoding first exons, which are located more than 8 kb apart and are spliced to the common exon 2 containing the translation initiation site. Within 1001 bp upstream of the transcription initiation site of the cloned distal promoter, there are four GATA-1. The main promoter used for the expression of the ST2 gene in UT-7, a human leukaemic cell line, is distinct from that in TM12, a human fibroblastic cell line. Although UT-7 cells use both distal and proximal promoters, the distal promoter is used dominantly for expression of both ST2 and ST2L mRNA. On the other hand, almost all transcription in TM12 cells starts from the proximal promoter. These results contrast with those of former studies on the rat system, in which ST2 and ST2L mRNA were generated by use of the proximal and distal promoters, respectively. Furthermore, UT-7 cells use multiple transcription initiation sites in both the proximal and distal promoters, whereas the transcription of the ST2 gene in TM12 cells starts at a unique site. Intriguingly, these results suggest that ST2 and ST2L proteins have distinct functions in different cells within different biological systems, such as those of growth control, differentiation and immunological responses.

Alternative Splicing↗
PubMed1999

Cooperation of six and eya in activation of their target genes through nuclear translocation of Eya.

Drosophila sine oculis and eyes absent genes synergize in compound-eye formation. The murine homologues of these genes, Six and Eya, respectively, show overlapping expression patterns during development. We hypothesized that Six and Eya proteins cooperate to regulate their target genes. Cotransfection assays were performed with various combinations of Six and Eya to assess their effects on a potential natural target, myogenin promoter, and on a synthetic promoter, the thymidine kinase gene promoter fused to multimerized Six4 binding sites. A clear synergistic activation of these promoters was observed in certain combinations of Six and Eya. To investigate the molecular basis for the cooperation, we first examined the intracellular distribution of Six and Eya proteins in transfected COS7 cells. Coexpression of Six2, Six4, or Six5 induced nuclear translocation of Eya1, Eya2, and Eya3, which were otherwise distributed in the cytoplasm. In contrast, coexpression of Six3 did not result in nuclear localization of any Eya proteins. Six and Eya proteins were coimmunoprecipitated from nuclear extracts prepared from cotransfected COS7 cells and from rat liver. Six domain and homeodomain, two evolutionarily conserved domains among various Six proteins, were necessary and sufficient for the nuclear translocation of Eya. In contrast, the Eya domain, a conserved domain among Eya proteins, was not sufficient for the translocation. A specific interaction between the Six domain and homeodomain of Six4 and Eya2 was observed by yeast two-hybrid analysis. Our results suggest that transcription regulation of certain target genes by Six proteins requires cooperative interaction with Eya proteins: complex formation through direct interaction and nuclear translocation of Eya proteins. This implies that the synergistic action of Six and Eya is conserved in the mouse and is mediated through cooperative activation of their target genes.

Amino Acid Sequence↗
PubMed1999

[Renin-angiotensin-aldosterone system in the reproductive system].

Besides the circulating renin-angiotensin-aldosterone (R-A-A) system, the tissue R-A-A system has been elucidated to play important roles as autocrines and/or paracrines. The components of R-A-A system are expressed in the ovary, uterus and placenta, indicating the existence of the tissue R-A-A system in these organs. The data indicating the involvement of R-A-A system of these tissues into reproduction have been accumulated. AT2 receptors might modulate the initiation and progression of follicle atresia involving granulosa cell apoptosis. AT2 receptors are expressed abundantly in the uterus and decreased during pregnancy. The placental renin are shown to be secreted into the maternal circulation and elevate blood pressure. It is expected to elucidate the significance of the R-A-A system in the reproductive system.

Animals↗
PubMed1998

Functional involvement of mSos in interleukin-3 and thrombin stimulation of the Ras, mitogen-activated protein kinase pathway in BaF3 murine hematopoietic cells.

Stimulation of the interleukin (IL)-3 receptor provokes rapid activation of the Ras pathway in various hematopoietic cell lines. Also, a wide range of G-protein-coupled receptors induce Ras activation following ligand stimulation. In this report, we investigate the mechanism underlying Ras activation upon stimulation of these two types of receptors in hematopoietic cells. Thrombin, a G-protein-coupled receptor ligand, was found to stimulate extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) in IL-3-dependent BaF3 cells, suggesting a significant function of thrombin receptor-mediated signaling. We show that the Ras-guanine nucleotide exchange factor mSos is indispensable for activation of the Ras pathway in IL-3- or thrombin-stimulated BaF3 cells. The activation of Ras in response to IL-3 as defined by accumulation of the GTP-bound form was impaired by conditional overexpression of a dominant-negative mutant of mSos (DeltamSos1). Furthermore, following induction of DeltamSos1, IL-3 enhancement of the kinase activities of c-Raf-1, ERK2, and JNK1 downstream of Ras was almost completely blocked. Similarly, thrombin-induced Ras-dependent ERK2 activation was diminished by DeltamSos1. However, the tyrosine phosphorylation pattern of cellular substrates upon thrombin stimulation was entirely different from the pattern of IL-3-induced tyrosine phosphorylation. Collectively, these results provide evidence that mSos plays a crucial role in both IL-3 and thrombin activation of the Ras pathway in hematopoietic cells, although molecules (including tyrosine kinases) mediating the signal to mSos are likely to be different between the two types of receptors.

Animals↗
PubMed1998

Morphological studies of glomeruli in obstructive kidneys by confocal laser scanning microscopy and quick-freezing replica method.

Morphological changes of glomeruli in obstructive kidneys were studied by using confocal laser scanning microscopy (CLSM), and quick-freezing and deep-etching (QF-DE) method. Twenty-one rabbits were divided into three groups, consisting of control, 6-hr bilateral ureteral obstruction (BUO) and 24-hr BUO. In the experimental groups, the attenuation of cell bodies, the lengthening and stretching of major processes, the cystic formation in the cytoplasm and the fusion of foot processes were observed on conventional ultrathin sections. These changes in the 24-hr BUO group were more clearly observed than those in the 6-hr BUO group. By the CLSM, cell bodies and foot processes of podocytes in the experimental groups were more intensely immunostained with anti-alpha-tubulin antibody and phalloidin-FITC. By the QF-DE method, cytoskeletons in the podocyte cell bodies and major processes were composed of numerous intermediate filaments, but distinct changes of actin filaments and microtubules were not observed in the control and experimental groups. Considering the physiological changes in BUO, the mechanical stress appeared to be brought about by hemodynamic factors rather than the change of intratubular pressure, resembling the morphological changes in experimental animals with hyperfiltration and the homeostatic adaptation of podocytes under the BUO condition.

Animals↗
PubMed1997

[Hemobilia after percutaneous transhepatic gallbladder drainage for cholecystitis in a patient undergoing aortic valve replacement].

A 50-year-old man with hemobilia after percutaneous transhepatic gallbladder drainage (PTGBD) for cholecystitis is presented. PTGBD had been performed for acute cholecystitis following aortic valve replacement. A combination of aspirin and warfarin as anticoagulant therapy had been administrated with the prothrombin time of approximate 40%. Six months later, the patient was again admitted to our hospital because of jaundice, high fever and digestive bleeding. PTGBD was again attempted under the diagnosis of acute cholecystitis. Endoscopic retrograde cholangiopancreatography revealed coagula which were excreted from the papilla of Vater, thus followed by a cholecystectomy accompanying with a choledochotomy. Three ulcers were observed in the cut surface of the resected gallbladder. Microscopic examinations of the gallbladder showed hemorrhage and inflammation. We reported out patient because hemobilia in the chronic phase after aortic valve replacement is rare.

Acute Disease↗
PubMed1997

[Mitral valve prolapse associated with severe pulmonary hypertension: a case report].

Severe (110/50 mmHg) pulmonary hypertension (PH) secondary to mitral valve prolapse is rare. We reported herein severe PH secondary to mitral valve prolapse in a 65-year-old female. The patient underwent mitral valve replacement and tricuspid annuloplasty. The pulmonary artery pressure after the operation decreased to 69/20 mmHg. Prostagrandin E1 was effective for residual PH compared with nicardipine hydrochloride.

Aged↗
PubMed1996

Augmentation by calmodulin of ADP-ribosylation factor-stimulated phospholipase D activity in permeabilized rabbit peritoneal neutrophils.

Activation of the membrane-bound phospholipase D (PLD) requires cytosolic factor(s), and ADP-ribosylation factor (ARF) has been identified as a cytosolic PLD activator. In the present study, we demonstrate that calmodulin (CaM) and ARF are both involved in PLD activation in rabbit peritoneal neutrophils. The PLD activity of streptolysin O-permeabilized, cytosol-depleted rabbit neutrophils was significantly enhanced when the permeabilized cells were reconstituted with bovine brain cytosol in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), whereas there was little activation of the enzyme in the absence of cytosol. The GTP gamma S-stimulated PLD activity in the presence of cytosol was augmented on increasing the concentration of free Ca2+. The PLD activity stimulated by GTP gamma S and Ca2+ in this system was inhibited by the calmodulin inhibitor W-7. These findings suggest that CaM plays a role as a cytosolic PLD activator. Moreover, highly purified CaM alone, as well as partially purified ARF alone, promoted a slight stimulation of the PLD activity in permeabilized neutrophils. Interestingly, ARF-stimulated PLD activity was augmented by CaM in the presence of GTP gamma S and Ca2+. This augmentation was again inhibited by W-7, as well as by the structurally unrelated CaM inhibitor trifluoperazine. These data imply that CaM stimulates the PLD activity of rabbit neutrophils in concert with ARF.

ADP-Ribosylation Factors↗
PubMed1996

Nail regeneration in digits replanted after amputation through the distal phalanx.

Nail regeneration was studied in 48 digits replanted after amputation through the distal phalanx. Twenty-seven were amputated through Tamai's zone I, at the nailbed level, and 21 digits were amputated through zone II, proximal to the nail. The nails of 9 digits in zone I and 14 in zone II showed almost normal nail regeneration. We observed that replantation after amputations distal to the lunula will show near normal nail regeneration if there is minimal postoperative circulatory disturbance. Amputations proximal to the lunula, however, have a greater chance of causing damage to the germinal matrix, which results in more problems with nail growth.

Adolescent↗
PubMed1996

[Comparison of hormone therapy alone and in combination with chemotherapy of cisplatin and methotrexate in newly diagnosed patients with stage D2 prostatic cancer].

BACKGROUND: Prognosis of hormone-refractory prostatic cancer is dismal. We evaluated the efficacy of cytotoxic chemotherapy in combination with hormone therapy in patients with newly diagnosed metastatic prostatic cancer. METHODS: From February 1984 to March 1992, 39 newly diagnosed patients with stage D2 prostatic cancer were randomized to orchiectomy plus diethylistilbestrol diphosphate or orchiectomy plus diethylstilbestrol diphosphate plus combination chemotherapy with cisplatin and methotrexate. RESULTS: There was not significant difference in survival or progression-free survival between the two groups. CONCLUSION: Chemotherapy has not been proved to prolong survival or progression-free survival in patients who received hormone therapy.

Adenocarcinoma↗
PubMed1996

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.

Alkyl and Aryl Transferases↗
PubMed1996

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. II. Structure elucidation and total synthesis.

Schizostatin (1) has been isolated as a potent and selective inhibitor of squalene synthase. Its structure has been determined using spectroscopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) was achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper reagent to acetylenedicarboxylate.

Enzyme Inhibitors↗
PubMed1995

Synergistic activation of rat brain phospholipase D by ADP-ribosylation factor and rhoA p21, and its inhibition by Clostridium botulinum C3 exoenzyme.

An activator of rat brain phospholipase D (PLD) that is distinct from the already identified PLD activator, ADP-ribosylation factor (ARF), was partially purified from bovine brain cytosol by a series of chromatographic steps. The partially purified preparation contained a 22-kDa substrate for Clostridium botulinum C3 exoenzyme ADP-ribosyltransferase, which strongly reacted with anti-rhoA p21 antibody, but not with anti-rac1 p21 or anti-cdc42Hs p21 antibody. Treatment of the partially purified PLD-activating factor with both C3 exoenzyme and NAD significantly inhibited the PLD-stimulating activity. These results suggest that rhoA p21 is, at least in part, responsible for the PLD-stimulating activity in the preparation. Recombinant isoprenylated rhoA p21 expressed in and purified from Sf9 cells activated rat brain PLD in a concentration- and GTP gamma S (guanosine 5'-O-(3-thiotriphosphate))-dependent manner. In contrast, recombinant non-isoprenylated rhoA p21 (fused to glutathione S-transferase) expressed in Escherichia coli failed to activate the PLD. This difference cannot be explained by a lower affinity of non-isoprenylated rhoA p21 for GTP gamma S, as the rates of [35S]GTP gamma S binding were very similar for both recombinant preparations and the GTP gamma S-bound form of non-isoprenylated rhoA p21 did not induce PLD activation. Interestingly, recombinant isoprenylated rhoA p21 and ARF synergistically activated rat brain PLD; a similar pattern was seen with the partially purified PLD-activating factor. The synergistic activation was inhibited by C3 exoenzyme-catalyzed ADP-ribosylation of recombinant isoprenylated rhoA p21 in a NAD-dependent manner. Inhibition correlated with the extent of ADP-ribosylation. These findings suggest that rhoA p21 regulates rat brain PLD in concert with ARF, and that isoprenylation of rhoA p21 is essential for PLD regulation in vitro.

ADP Ribose Transferases↗