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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 163 records · Page 9Linked to original sources

A new ceramide with a novel branched-chain fatty acid isolated from the epiphytic dinoflagellate coolia monotis

From the dinoflagellate Coolia monotis, a new ceramide (1) bearing a 2-hydroxy-15-methyl-3-octadecenoyl moiety was isolated as a cellular constituent. The structure, including the partial absolute configuration, was elucidated as 1 on the basis of the 2D NMR of 1, and chiral HPLC and CD examinations with benzoyl derivatives of its degradation products. To our knowledge, this is the first example, from natural sources, of a C18 fatty acid with a methyl group substituted at a C15 carbon.

Journal Article↗

Biphasic expression of CD4 in acute myelocytic leukemia (AML) cells: AML of monocyte origin and hematopoietic precursor cell origin.

In 227 of 495 (45.9%) Japanese adult patients with acute myelocytic leukemia (AML), leukemic cells expressed CD4. Incidence of CD4 expression in each FAB subtype was as follows: M1 37.4%, M2 33.7%, M3 35.4%, M4 65.0%, and M5 78.3%. The typical expression pattern of myelomonocytic differentiation antigens and cytokine receptors in CD4+ AML was CD34lowCD33high CD11bhighGM-CSFRhigh. AML cases with 11q23 abnormalities and with inv(16) were frequently CD4-positive. These data collectively indicate that CD4 expression in AML cells is associated with monocytic characteristics. However, CD4+CD34high AML cases appear to have unique immature characteristics including low expression of myelomonocytic differentiation antigens (ie CD33 and CD11b), and accumulation of chromosome abnormalities (ie t(8;21) in CD4lowCD34high AML and chromosome 7 abnormalities in CD4highCD34high AML). We speculate that these leukemia subsets originate from CD4+ hematopoietic precursor cells, therefore then should be considered separately from most of the CD4+ AML as represented by CD34lowCD33high CD11bhighGM-CSFRhigh. Overall survival of patients with CD4+ AML in our series was worse than that of those with CD4 AML (P = 0.0202).

Adult↗

Molecular genetic and immunohistochemical study of autosomal recessive Alport's syndrome.

A DNA analysis of autosomal type IV collagen alpha3 and alpha4 chain genes (COL4A3 and COL4A4) and an immunohistochemical study of type IV collagen alpha1 to alpha6 chains were performed in an inbred family with autosomal recessive Alport's syndrome (AS). A linkage study using polymorphic markers around the COL4A3/COL4A4 genes clearly differentiated the affected patients from healthy individuals. These patients were homozygous for all markers analyzed, whereas their parents were heterozygotes. Because of the large size of both the genes and the heterogeneous range of the mutations of these genes, linkage analysis by using highly polymorphic markers is still the method of choice in genetic counseling for autosomal recessive AS, as well as for the X-linked form. Although the distribution of alpha1 and alpha2 chains in the index patient and her affected sister were normal, the alpha3 and alpha4 chains were completely defective in the renal basement membrane (BM). The alpha5 chain could be found in Bowman's capsular basement membrane (BCBM) but not in the glomerular basement membrane (GBM). In addition, our study showed, for the first time, that the alpha6 chain in BCBM is spared in this form of AS. This abnormal pattern of type IV collagen could be a useful tool for differentiation of the autosomal recessive type from the X-linked type of AS.

Adolescent↗

Endoscopic treatment of refractory filarial chyluria: a preliminary report.

PURPOSE: We report our experiences treating 5 patients who had filarial chyluria using an endoscopic approach. MATERIALS AND METHODS: Two men and 3 women 47 to 83 years old with chyluria were treated with endoscopic coagulation using guide tube methods. Intrarenal pelvic instillation of silver nitrate was not effective in 4 patients and catheterization was impossible in 1. RESULTS: The responsible lesion was successfully coagulated in all 5 patients. Because the lesion was in the ruptured portion of the caliceal fornix, we thought that chyluria had arisen in the fragile portion of the fornix (fistulization). After endoscopic treatment there was no recurrence in any patient. CONCLUSIONS: Endoscopy is effective and minimally invasive therapy for filarial chyluria.

Aged↗

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells.

Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately 70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function.

Adrenomedullin↗

Regulation of endothelial production of C-type natriuretic peptide by interaction between endothelial cells and macrophages.

We demonstrated endothelial production of C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, and its regulation by cytokines, including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can control vascular tone and growth as an endothelium-derived relaxing peptide. We also revealed the marked elevation of plasma CNP concentration in patients with septic shock, in which TNF alpha plays a significant part. As the interaction between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in the pathogenesis of atherosclerosis, we investigated the effect of coculture of EC and macrophages on endothelial production of CNP. We used a human monocytic leukemia cell line, THP-1, which differentiates into macrophages when treated with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived macrophages enhanced CNP secretion by more than 10-fold compared with the single culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13-acetate treatment. Prevention of direct contact between EC and THP-1-derived macrophages did not attenuate the increase in CNP secretion. Northern blotting revealed the augmentation of CNP messenger RNA expression in EC in the coculture. We detected TNF alpha in the conditioned medium from the coculture of EC and THP-1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated cGMP production significantly in vascular smooth muscle cells. These results indicate that endothelial production of CNP is stimulated mainly by TNF alpha released from THP-1-derived macrophages in the coculture. Endothelial CNP at the enhanced level may be one of the vascular mediators to regulate local vascular tone and growth through cGMP production by vascular smooth muscle cells, suggesting the potential significance of endothelial CNP in atherosclerosis.

Animals↗

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidino-benzoyloxy)phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats.

The effect of methylcarbonylmethyl 2(S)-14-(4-guanidino-benzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on experimental pancreatitis in rats was examined in comparison with that of camostat. TT-S24 showed a preventive effect on increases in plasma amylase activity and pancreatic weight induced by cerulein injection. TT-S24 also reduced an increase in plasma amylase activity induced by taurocholate. TT-S24 effectively prevented the mortality induced by an injection of a mixture of trypsin and taurocholate. TT-S24 showed no effect on an increase in amylase activity 6 h after duodenum ligation (closed duodenal loop pancreatitis), indicating that the drug had no effect on the initiation and propagation step of closed duodenal loop pancreatitis. On the other hand, TT-S24 reduced an increase in amylase activity 6 h after release of the duodenum ligation. TT-S24 showed anti-trypsin, anti-kallikrein, anti-thrombin and anti-plasmin activities. The effect of TT-S24 on some experimental pancreatitis models was nearly equal to or somewhat more potent in most instances to that of camostat. Therefore, TT-S24 should be useful in the clinical treatment of pancreatitis.

Amylases↗

Effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24) on pancreatic secretion in rats.

The effect of methylcarbonylmethyl 2(S)-[4-(4-guanidinobenzoyloxy) phenyl] propionate methanesulfonate (TT-S24), a newly synthesized trypsin inhibitor, on exocrine pancreatic secretion was examined and compared with that of camostat in rats. Intraduodenal (i.d.) administration of TT-S24 and camostat resulted in an increase in volume, amylase concentration and amylase output of pancreatic juice. Although i.v. injection of TT-S24 and camostat (3 mg/kg) had no effect on the pancreatic juice volume, TT-S24 (i.v.) dose-dependently increased pancreatic juice volume under acetylcholine (10 micrograms/kg/min) infusion. In addition, the weight of pancreases from WBN rats was significantly increased by 28 day oral administration of TT-S24 (100 mg/kg) with a potency similar to that observed with camostat.

Acetylcholine↗

Fiber numbers per unit weight of JFM standard reference samples determined with a scanning electron microscope. Japan Fibrous Material.

A standard reference 10 sample-set of fibrous minerals were prepared by the Japan Fibrous Material Research Association (JFMRA) under the name of JMF standard reference samples. In this paper, the fiber number per unit weight of JFM standard reference samples was determined with a scanning electron microscope. Fiber numbers per unit weight (f/microgram) and standard deviations observed in this experiment were as follows: glass wool (GW1) 7.0 +/- 0.1 x 10(2), rock wool (RW1) 1.7 +/- 0.2 x 10(3), micro glass fiber (MG1) 6.5 +/- 0.4 x 10(4), refractory ceramic fibers; (RF1) 8.8 +/- 0.7 x 10(3), (RF2) 8.7 +/- 0.8 x 10(3), mullite fibers (RF3) 3.5 +/- 0.7 x 10(3), potassium titanate whisker (PT1) 5.9 +/- 0.3 x 10(5), silicon carbide whisker (SC1) 4.1 +/- 0.4 x 10(5), titanium oxide whisker (rutile) (TO1) 6.4 +/- 0.6 x 10(5), and wollastonite (WO1) 2.4 +/- 0.1 x 10(4). Fiber numbers per unit weight would change in proportion to the cube or cube root of the fiber size if the fibers have the same density and the same aspect ratio. JFM standard reference samples should be used taking into consideration the difference in fiber number per unit weight when users conduct in vitro and/or in vivo (injection) biological experiments using these samples.

Humans↗

[Successful syngeneic peripheral blood stem cell transplantation for protracted myelosuppression after chemotherapy in a patient with acute myelogenous leukemia].

Acute myelogenous leukemia (M2) with translocation of 8;21. Was diagnosed in 61-year-old man. He was successfully treated and obtained complete remission. After consolidation therapy, myeloid suppression and maturation arrest at the myelocyte level were recognized. Following intensive chemotherapy, he received rhG-CSF-mobilized peripheral blood stem cell transplantation (PBSCT) from an identical twin because he had life threatening infectious events and protracted myelosuppression. Transplantation of 2.5 x 10(6)/kg CD34+ cells resulted in a rapid normal tri-lineage hematologic reconstitution. Syngeneic PBSCT appears to be a substitute for syngeneic bone marrow transplantation in certain situations.

Antineoplastic Combined Chemotherapy Protocols↗

[Adrenomedullin receptors].

Adrenomedullin(AM) is a potent hypotensive peptide originally isolated from human pheochromocytoma. AM exerts various biological actions such as vasodilation, bronchodilation and natriuresis, by stimulating cAMP production and increasing free Ca2+ levels through the specific receptors. Although an orphan receptor cloned from rat lung, which contained seven transmembrane domains, was proved to be one of the AM receptors, it is now considered by many studies that other receptor subtypes should be present. The precise signal transduction mechanism for the AM receptor is not fully elucidated yet, but it is supposed that AM acts against proliferative changes of vascular and mesangial cells as seen in hypertensive states, at least partly by inhibiting the MAP kinase pathway. Further studies on the AM receptor subtypes and their intracellular signaling mechanisms are needed to clarify the role of AM in various pathophysiological conditions.

Adrenomedullin↗

[Successful emergency operation for massive hemorrhage due to jejunal angiodysplasia after intensive chemotherapy in a patient with refractory anemia with excess of blasts].

A 59-year-old man was referred to our hospital because of pancytopenia. Peripheral blood examination showed a WBC of 1,500/microliters with 2% blasts, Hb 8.1 g/dl and a platelet count of 4.1 x 10(4)/microliters. A bone marrow aspiration revealed hyperplasia with proliferation of blasts (15.7%) and myelodysplasia. Chromosome analysis revealed multiple aberrations, including -5, -7, +8. The patient was given a diagnosis of refractory anemia with excess of blasts (RAEB) and treated with combination chemotherapy. Agranulocytosis and high fever remained after chemotherapy, and abdominal pain and diarrhea developed. An abdominal X-ray film and computed tomography scan demonstrated dilated small bowel, thickness of the bowel wall, and ascites. A diagnosis of neutropenic enterocolitis was given. During the WBC recovery period from nadir, massive hematochezia developed in the patient. Angiography detected the leakage of contrast medium from a peripheral region of the first jejunal artery into the jejunal lumen. A partial resection of the jejunum was thus performed, and a histological examination revealed the presence of irregularly dilated blood vessels in the submucosal layer. These findings were consistent with the features of angiodysplasia, and indicate that angiodysplasia should be considered one cause of intestinal hemorrhage in elderly patients during intensive chemotherapy.

Anemia, Refractory, with Excess of Blasts↗

Detection and cloning of unique integration sites of retrotransposon, intracisternal A-particle element in the genome of acute myeloid leukemia cells in mice.

We previously found retrotransposition of the intracisternal A-particle (IAP) element in the genome of acute myeloid leukemia (AML) cells induced by X-irradiation of C3H/He mice (FEBS 16333). To analyze the occurrence of the IAP-mediated retrotransposition in AML cells, we compared integration sites of the IAP element by polymerase chain reaction (PCR) in the genomes of five AML strains derived from different C3H mice. Unique PCR products were found in all of the above independent leukemia cells, whereas no such products were detected in normal cells. Results of cloning, sequencing and Southern analyses showed that the PCR products were derived from novel integration sites of the IAP element in the genome. The data suggest that IAP-mediated retrotransposition occurs frequently in radiation-induced AML cells from C3H/He mice.

Animals↗

Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes.

BACKGROUND: In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. METHODS AND RESULTS: The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC <1% of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC-conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10(-10) to 10(-6) mol/L) and transforming growth factor-beta1 (TGF-beta1) (10(-13) to 10(-9) mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-beta1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-beta1 was associated with the potentiation of ET-1 production in the MC-NMC coculture, and the effect of Ang II or TGF-beta1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. CONCLUSIONS: These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II- or TGF-beta1-induced cardiocyte hypertrophy.

Angiotensin II↗

Kidney-specific expression of a novel mouse organic cation transporter-like protein.

Using the signal sequence trap method, we have cloned a novel 12-membrane-spanning transporter-like protein, termed renal-specific transporter (RST), from the mouse kidney. RST is a 553-amino-acid protein highly homologous to recently cloned organic cation transporters, e.g. it is 30% identical to rat organic cation transporter I at the amino acid level. Northern blot analysis has revealed that the RST gene is expressed abundantly and specifically in the kidney. In situ hybridization analysis has shown that RST gene expression is restricted to the renal proximal tubule, where various organic cations such as endogenous catecholamines and choline or clinically used cationic drugs are known to be actively excreted.

Amino Acid Sequence↗

The prostaglandin E2 and F2 alpha receptor genes are expressed in human myometrium and are down-regulated during pregnancy.

Prostaglandin (PG) E2 and PGF2 alpha are believed to play important roles in the myometrial contraction and the initiation of labor. Myometrial contraction by these prostanoids is mediated mainly through EP3 and FP, which are specific receptors to PGE2 and PGF2 alpha, respectively. During normal pregnancy, uterine myometrium are relaxed until term. To explore the involvement of EP3 and FP in the myometrial relaxation during pregnancy, we examined the EP3 and FP gene expressions in nonpregnant and pregnant myometrium obtained by hysterectomy for gynecological diseases. In all samples examined, expressions of EP3 and FP genes were detected. During pregnancy, the expression of EP3 gene in human myometrium was significantly reduced, to 60% of that in nonpregnant myometrium. The expression of FP gene in human myometrium also decreased during pregnancy to 55% of that in nonpregnant myometrium. In the myometrium from the nonpregnant women taking combined oral contraceptives, the gene expressions of EP3 and FP were not significantly changed as compared to those in nonpregnant controls. The down-regulation of EP3 and FP during pregnancy may play a role in the relaxation of myometrium and thus in the maintenance of normal pregnancy in humans.

Adult↗