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Biomedical subjects

Y Moriyama

Publications and source records attributed to Y Moriyama.

At least 199 records · Page 11Linked to original sources
PubMed1996

Membrane energization by proton pumps is important for compartmentalization of drugs and toxins: a new type of active transport.

Many organelles are energized by proton pumps: mitochondria form an inside-negative membrane potential by means of the respiratory chain and endomembrane structures, such as lysosomes and synaptic vesicles, establish an internal acidic pH by means of a vacuolar-type H(+)-ATPase (V-ATPase). Various amphipathic drugs such as local anesthetics and neuron blockers are accumulated in acidic organelles upon energization by proton pumps. However, this process does not require any transporters specific for the drugs: these drugs penetrate through the lipid bilayer against a concentration gradient so as to accumulate inside the energized organelles. Essentially the same transport process takes place in liposomes that have been reconstituted with purified V- or F-ATPase. Various hydrophobic cations are also accumulated in mitochondria by a similar mechanism. The energy-dependent but transporter-independent accumulation does not belong to the known transport categories and seems to represent a new type of transport which may be important for understanding the mode of action of drugs and toxins.

Anesthetics, Local↗
PubMed1996

Role of endocrine cell microvesicles in intercellular chemical transduction.

Microvesicles (MVs) in endocrine cells are morphologically similar to neuronal synaptic vesicles. MVs were shown to contain proteins involved in neurotransmitter storage such as vacuolar H(+)-ATPase and neurotransmitter transporters, and ones in vesicular trafficking such as synaptobrevins and N-ethylmaleimide-sensitive fusion protein. Isolated MVs accumulate cell-specific neurotransmitters in an energy-dependent manner. Upon stimulation, the MVs may fuse with the plasma membrane and secrete the internal neurotransmitters. Thus, endocrine cells possess an MV-mediated secretion system as an intercellular signal transducing system.

Animals↗
PubMed1996

Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line.

Two mutations of c-kit receptor tyrosine kinase (KIT), valine-559 to glycine (G559) and aspartic acid-814 to valine (V814), resulted in its constitutive activation. To examine the transforming and differentiation-inducing potential of the mutant KIT, we used the murine interleukin-3-dependent IC-2 mast cell line as a transfectant. The IC-2 cells contained few basophilic granules and did not express KIT on the surface. The KITG559 or KITV814 gene was introduced into IC-2 cells using a retroviral vector. KITG559 and KITV814 expressed in IC-2 cells were constitutively phosphorylated on tyrosine and demonstrated kinase activity in the absence of stem cell factor, which is a ligand for KIT. IC-2 cells expressing either KITG559 or KITV814 (IC-2G559 or IC-2V814 cells) showed factor-independent growth in suspension culture and produced tumors in nude athymic mice. In addition, IC-2G559 and IC-2V814 cells showed a more mature phenotype compared with the phenotype of the original IC-2 cells, especially after transplantation into nude mice. The number of basophilic granules and the content of histamine increased remarkably. KITG559 and KITV814 also influenced the transcriptional phenotype of mouse mast cell proteases (MMCP) in IC-2 cells. The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells. The results indicated that constitutively activated KIT had not only oncogenic activity but also differentiation-inducing activity in mast cells.

Animals↗
PubMed1996

[Use of the omentum for infected sternal dehiscence after aortic valve replacement--a case report].

A 68-year-old man had prosthetic valve replacement for aortic stenosis. Unfortunately, sternal dehiscence with osteomyelitis occurred on the fifth postoperative day. Implantation of the pedicled omentum to the wound was carried out three days later. The result was excellent. This is the worthy method to try to such wound of infected sternum with dehiscence. From the point of view of anatomy and physiology, the omentum has a great benefit to repair the infected space and promote the wound healing process.

Aged↗
PubMed1996

[Open heart surgery in patients with chronic dialysis].

From January, 1986 to May, 1995, twelve patients with dialysis (11 hemodialysis; HD, and one continuous ambulatory peritoneal dialysis; CAPD) received open heart surgery. They consist of 10 males and two females aged between 35 and 66 with a mean of 58.8. The duration of dialysis was 6.8 years in a mean (the shortest for 2 months and the longest for 16 years). They classified into an equal number of four in NYHA class II, III and IV. Two of them had isolated coronary artery bypass grafting, four had aortic valve replacement (AVR) and two had mitral valve replacement (MVR). Others were each one of AVR and MVR, AVR plus MVR with tricuspid annuloplasty (TAP), AVR plus TAP, and removal of left atrial myxoma. All patients except for one of CAPD were dialysed daily 2 or 3 days before operation. Three patients were managed postoperatively with HD, one with PD, six with continuous hemodiafiltration, and two with continuous hemofiltration. The operative mortality was 25% (3/12). The causes of death were left ventricular rupture, bronchospasm, and respiratory failure. All patients who died were in class in III and IV. For the improvement of the results we emphasize the necessity of early operation that should be scheduled in class II period.

Adult↗
PubMed1996

[Coronary arterial bypass grafting for angina pectoris suspected with aortitis syndrome: a case report].

We report herein the case of a 56-year-old man with angina pectoris suspected to be accompanied with aortitis syndrome who underwent coronary artery bypass grafting (CABG). His cerebral blood flow consisted of only that of the right vertebralartery, and the marked collaterals of the bronchial artery anastomosing to the coronary artery. CABG was performed under combined with electrical fibrillation and systemic deep hypothermia, for fear of a bad influence on the cerebral tissue by the influx of high potassium cardioplegic solution. The postoperative course was uneventful and the coronary angiography revealed that the all graft were patent.

Angina Pectoris↗
PubMed1996

[A case of acute thrombosed aortic dissection (Stanford type A) in association with a true aortic arch aneurysm].

We have experienced a rare case of Stanford type A thrombosed aortic dissection in association with true aortic arch aneurysm. A 73-year-old male with asymptomatic true aortic arch aneurysm had sudden onset of severe back pain. A through examination clarified that he had Stanford type A aortic dissection coexisting with true aneurysm. In operation, we found a tear on intima of the proxymal-part of the true aneurysm. Pathologically, dissection confined to the ascending aorta did not involve the true aneurysm. The replacement of ascending aorta and aortic arch was successfully accomplished. The combination of true aortic arch aneurysm and Stanford type A aortic dissection is rare bibliographically.

Acute Disease↗
PubMed1996

[Surgical results of valve replacement with porcine bioprostheses].

We evaluated the 80 cases of porcine valve replacement, accomplished between April 1975 and December 1980. There were 48 males and 32 females aged between 16 and 60 years old with a mean of 37.4 +/- 11.4. Ten patients underwent aortic valve replacement (AVR), 63 mitral valve (MVR), and 7 AVR plus MVR. Twenty-seven Hancock valves (H) were implanted in aortic (3) and mitral (24) position and 61 Carpentier-Edwards valves (CE) were used in aortic (14), mitral (46), and tricuspid (1) position. The mean duration of follow-up was 9.3 years (0.2-19.2 years) and cumulative follow-up was 747.2 patient years (py). The late mortality was 3.3%/py (25 patients). Actuarial survival rates for all patients at 10 and 15 years were 67%, and 49% respectively. The linearized rates (LR) of structural valve deterioration (SVD) was 7.0%/py. The freedom from SVD for all patients at 10, and 15 years were 47.1%, and 12.4% respectively. There were no differences of free rates of SVD between H and CE. between valve sites implated, and among age at operation. The incidence of occurrence of SVD was gradually increased 6 years after operation. The LR of thromboembolism (TE), anticoagulant-related hemorrhage (ACH), prosthetic valve endocarditis (PVE), nonfunctional valve dysfunction (NVD), and reoperation (RO) were 0.7%/py, 0.1%/py, 0.3%/py, 0.1%/py and 7.4%/py, respectively. The freedom from TE, ACH, PVE, NVD, and RO for all patients at 15 years were 91.3%, 98.1%, 95.6%, 80%, and 6.5%, respectively. The surgical results of glutaraldehyde-preserved porcine bioprostheses was excellent during the first 5 years after operation. A high incidence of SVD has been occurred thereafter. According the indication for valve replacement with bioprotheses is now strictly limited for elderly, child bearing female case, contraindition for therapy of anticoagulants, and some social condition.

Adolescent↗
PubMed1996

[Surgical results of valve replacement with the Björk-Shiley tilting disc valves].

We evaluated the Björk-Shiley tilting-disc (BS) valve replacement up to the longest duration for about 12 years. The study was started in November 1982 and ended in September 1991. There were total number of 206 with 117 males and 89 females aged between 18 and 71 with a mean of 51.6. Eighty three patients had isolated aortic valve replacement (AVR), 92 had isolated mitral valve replacement (MVR), and 31 had AVR plus MVR. One hundred and fourteen spherical-disc valves were replaced in the aortic, 112 spherical and 11 monostrut in the mitral position. The mean duration of follow up was 6.5 years for a total of 1330.6 patient years (PY). Forty-one patients (3.8%/PY) died later, and 14 out of 41 died of valve-related complications. Actuarial survival rates for all, AVR, MVR and DVR at 10 years after operation were 71.2%, 73.5%, 73.9% and 55.4%, respectively. The linearized rates of thromboembolism (TE), thrombosed valve (TV), anticoagulant-related hemorrhage (ACH), prosthetic valve endocarditis (PVE), hemolysis (H), and reoperation (RO) were 1.2%/PY, 0.2%/PY, 0.7%/PY, 0.2%/PY, 0.1%/PY, and 0.2%/PY, respectively. The rates of freedom from TE, TV, ACH, PVE, H, and RO and 10 years after operation were 83.5%, 98.5%, 94.0%, 98.4%, 99.0% and 95.6%, respectively. The major causes of postoperative mortality and morbidity were TE, TV, and ACH. One hundred and fifty-six out of 161 patients showed an improvement in NYHA functional class post operatively. The surgical results of valve replacement with the BS valve was excellent and acceptable one. Intensive management with a special reference of anticoagulant therapy is necessary for a long-term management of the patients with mechanical valve replacement.

Adolescent↗
PubMed1996

[A case of ASD with SLE treated with Carmeda BioActive surface circuit in cardiopulmonary bypass system].

A 61-year-old woman of ASD complicated with SLE was operated on. We used a heparin coating Carmeda BioActive Surface (CBS) in cardiopulmonary bypass circuit for the purpose to prevent the postoperative complications due to the reduced complement activation by SLE. This system could prevent the decline of the reduced complement activation during cardiopulmonary bypass and after operation. The management of steroid therapy for SLE patient, usefulness of heparin coating CBS system for hypocomplement disease were discussed.

Anti-Inflammatory Agents↗
PubMed1995

Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation.

Mutant mice with splenomegaly and nonspherocytic hemolytic anemia were found in an inbred colony of the CBA/N (hereafter CBA) strain maintained in the Japan SLC Haruno farm (Shuchi-gun, Shizuoka, Japan). The activity of pyruvate kinase (PK) in red blood cells (RBCs) of the anemic mutants decreased to 16.2% of normal (+/+) CBA mice. Because the mutant CBA mice showed a remarkable reticulocytosis (41.6%) and because the PK activity of reticulocytes is much higher than that of mature RBCs, the PK activity in mature RBCs of the mutant CBA mice was calculated to be 2.8% that of mature RBCs of CBA-(+/+) mice. Because RBC type PK is encoded by the Pk-1 locus of the mouse (chromosome 3), we designated the mutant locus as Pk-1slc. The anemia and PK deficiency of CBA-Pk-1slc/Pk-1slc mice were cured by bone marrow transplantation (BMT) from CBA-(+/+) mice. Prior irradiation was not necessary for the curative BMT. On the other hand, the BMT from CBA-Pk-1slc/Pk-1slc mice to nonirradiated CBA-(+/+) mice did not result in the decrease of RBCs and the reduction of PK activity. The present results indicate that CBA-Pk-1slc/Pk-1slc mice are a potentially useful animal model for studying pathophysiology of PK deficiency and for developing new therapeutic methods to correct PK deficiency.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1995

Reconstitution of the metal-tetracycline/H+ antiporter of Escherichia coli in proteoliposomes including F0F1-ATPase.

The tetracycline resistance gene (tetA) was cloned downstream of the lac promoter. When expression of the tetA gene in E. coli cells carrying the lac Iq gene was induced with isopropyl beta-D-thiogalactopyranoside, the tetracycline resistance protein (TetA) was overproduced, amounting to about 30% of the integral cytoplasmic membrane protein. Essentially pure TetA protein could be obtained by solubilization with 1.25% n-octyl-beta-D-glucopyranoside and one-step purification by DEAE Sepharose CL-6B column chromatography. The TetA protein was incorporated into proteoliposomes with F0F1-ATPase. The proteoliposomes exhibited [3H]tetracycline transport dependent on ATP hydrolysis. The specific activity was about 2 nmol/mg protein/min. The proteoliposomes also showed H+ efflux coupled with tetracycline influx. Tetracycline/H+ antiport by proteoliposomes reconstituted with the Ser-65-->Cys mutant TetA protein was inhibited by N-ethylmaleimide. These results proved for the first time that the tetracycline/H+ antiport is only mediated by the TetA protein.

Amino Acid Sequence↗
PubMed1995

Vesicular L-glutamate transporter in microvesicles from bovine pineal glands. Driving force, mechanism of chloride anion activation, and substrate specificity.

Pinealocytes, endocrine cells that synthesize and secrete melatonin, possess a large number of synaptic-like microvesicles (MVs) containing the L-glutamate transporter (Moriyama, Y., and Yamamoto, A. (1995) FEBS Lett., 367, 233-236). In this study, the L-glutamate transporter in MVs isolated from bovine pineal glands was characterized as to its driving force, requirement of anions, and substrate specificity. Upon the addition of ATP, the MVs accumulated L-glutamate. The uptake was significantly dependent on the extravesicular Cl- concentration, being negligible in the absence of Cl- and maximum at 2-5 mM and decreasing gradually at 20-100 mM. The membrane potential (inside positive) was maximum at 0-10 mM Cl- and then decreased gradually depending on the Cl- concentration, whereas a pH gradient was practically absent without Cl- and increased gradually up to 100 mM Cl-. Ammonium acetate or nigericin plus K+, a dissipator of a pH gradient, had little effect on or was slightly stimulatory toward the uptake, whereas valinomycin plus K+ inhibited both formation of the membrane potential and the glutamate uptake to similar extents. The ATP- and Cl(-)-dependent glutamate uptake was inhibited by fluoride, iodide, or thiocyanate, without vacuolar H(+)-ATPase being affected. An anion channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, similarly inhibited the glutamate uptake in a Cl- protectable manner. Furthermore, ATP- and glutamate-dependent acidification of MVs was observed when 4 mM Cl- was present. Among more than 50 kinds of glutamate analogues tested, only a few compounds, including 1-aminocyclohexane-trans-1,3-dicarboxylic acid, caused similar acidification. A good correlation was observed between the acidification and the inhibition of glutamate uptake by glutamate analogues. These results indicated that 1) the major driving force of the glutamate uptake is the membrane potential, 2) Cl- regulates the glutamate uptake, probably via anion-binding site(s) on the transporter, and 3) the transporter shows strict substrate specificity. Hence, the overall properties of the vesicular glutamate transporter in the MVs well matched those of the synaptic vesicle glutamate transporter. We concluded that the vesicular glutamate transporter, being similar if not identical to the neuronal counterpart, operates in endocrine cells.

ATP-Binding Cassette Transporters↗
PubMed1995

Localization of N-ethylmaleimide-sensitive fusion protein in pinealocytes.

N-ethylmaleimide-sensitive fusion protein (NSF), a protein necessary for vesicular docking and/or fusion, was detected immunohistochemically in pinealocytes. NSF was distributed similarly to synaptophysin and vacuolar-type H(+)-ATPase (V-ATPase), marker proteins for synaptic-like microvesicles (MVs) abundantly present in pinealocytes. A subcellular fractionation study indicated that .> 95% of NSF was present as a membrane-bound form and that some NSF was associated with MVs. Like neuronal NSF, the protein was not solubilized from membranes with either 2 mM Mg-ATP or 2% sodium carbonate, suggesting that NSF was tightly bound to the membranes. NSF was also detected in purified MVs from bovine posterior pituitaries. Since MVs are the organelles in which transmitters are stored, these results suggest that NSF is involved in the MV-mediated exocytosis of transmitters from endocrine cells.

Adrenal Medulla↗
PubMed1995

Growth response of acute myeloblastic leukemia cells to recombinant human thrombopoietin.

Thrombopoietin (TPO) is a newly identified hematopoietic growth factor that stimulates both megakaryopoiesis and thrombopoiesis through its interaction with a specific cell surface receptor encoded by the c-mpl proto-oncogene. In an effort to investigate the effect of TPO on human myeloid leukemia cells, the expression of c-mpl and the proliferative response to recombinant human (rh) TPO were investigated in a series of patients with acute myeloblastic leukemia (AML). Of 50 cases of AML, the c-mpl mRNA was detectable by means of Northern blot analysis in 26 cases, and the in vitro treatment with rhTPO led to proliferation of AML cells in 22 cases. The c-mpl expression and proliferative response to rhTPO was observed in all subtypes of AML and did not correlate with French-American-British classification, whereas all cases of M7-type AML cells expressed c-mpl and proliferated in response to rhTPO. Furthermore, rhTPO-induced proliferation of AML cells was augmented with the addition of interleukin-3 (IL-3), IL-6, stem cell factor, or granulocyte-macrophage colony-stimulating factor. These results suggested that c-mpl may be functional in terms of supporting proliferation of various types of AML cells and that TPO may contribute, at least in part, to abnormal growth of the cells, especially in combination with other hematopoietic growth factors.

Acute Disease↗
PubMed1995

Syntaxin 1 (HPC-1) is associated with chromaffin granules.

Syntaxin 1 (HPC-1), a component of the receptor for SNAPs (soluble N-ethylmaleimide-sensitive factor attachment proteins), has been implicated in the docking and fusion of synaptic vesicles with the plasma membrane. It was reported that syntaxin 1 in rat brain and chromaffin cells (PC12) is exclusively located on the plasma membrane (Bennett, M. K., Calakos, N., and Scheller, R. H. (1992) Science 257, 255-259; Söllner, T., Bennett, M. K., Whiteheart, S. W., Scheller, R. H., and Rothman, J. E. (1993) Cell 75, 409-418). By means of biochemical and morphological analyses, we now show that syntaxin 1 is associated with chromaffin granules in the adrenal medulla. This finding raises the possibility that syntaxin 1 in chromaffin cells is a component of vesicle-SNAP receptor as well as one of target-SNAP receptor on the plasma membrane.

Adrenal Medulla↗
PubMed1995

Microvesicles isolated from bovine pineal gland specifically accumulate L-glutamate.

Pinealocytes, endocrine cells that synthesize and secrete melatonin, possess a large number of synaptic-like microvesicles (MVs) containing synaptophysin. By monitoring cross-reactivity with anti-synaptophysin antibody, the MVs were highly purified from bovine pineal glands. The purified MVs were morphologically similar to but distinct from neuronal synaptic vesicles by their lack of synapsin I. Immunological study indicated that the MVs contained vacuolar H(+)-ATPase, synaptotagmin and synaptobrevin 2 (VAMP2). The MVs accumulated L-glutamate at the expense of ATP hydrolysis by vacuolar H(+)-ATPase. No uptakes of melatonin, serotonin, noradrenaline, gamma-aminobutyrate or acetylcholine were observed. These results indicated that the MVs are organelles for storage of L-glutamate in pinealocytes and suggested a possibility that pinealocytes transmit glutamate signals by MVs-mediated exocytosis.

ATP-Binding Cassette Transporters↗