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Biomedical subjects

Y Moriyama

Publications and source records attributed to Y Moriyama.

At least 217 records · Page 12Linked to original sources

Microvesicles isolated from bovine posterior pituitary accumulate norepinephrine.

Histochemical study indicated that the posterior pituitary possesses numerous microvesicles (MVs) containing synaptophysin, a marker protein specific for brain synaptic vesicles (Navone, F., Di Gioia, G., Jahn, R., Browning, M., Greengard, P., and De Camilli, P. (1989) J. Cell Biol. 109, 3425-2433). By monitoring cross-reactivity with anti-synaptophysin antibody, the MVs were highly purified from bovine posterior pituitaries by a combination of differential and sucrose density gradient centrifugations. The purified MVs had an average diameter of about 60 nm and were associated with synaptophysin as revealed by immunoelectron microscopy. The vesicles contained ATPase activity partially sensitive to bafilomycin A1 and to vanadate. The membrane fraction immunoisolated with anti-synaptophysin antibody also exhibited similar ATPase activity. The two ATPases could be purified separately; the vandate-sensitive enzyme was identified as a 115-kDa polypeptide immunochemically similar to chromaffin granule P-ATPase (forming phosphoenzyme intermediate), and the bafilomycin A1-sensitive ATPase showed essentially the same properties as those of vacuolar type H(+)-ATPases. Upon addition of ATP, the MVs formed an electrochemical gradient of protons and took up norepinephrine in a reserpine-sensitive manner, indicating the presence of secondary monoamine transporter coupled with vacuolar type H(+)-ATPase. No uptake of L-glutamate, gamma-aminobutyrate, glycine, or acetylcholine was observed. The identification of MVs as organelles responsible for storage of monoamines is important for understanding the physiological function of the posterior pituitary.

Acetylcholine↗

Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H(+)-ATPase and F0F1-ATP synthase.

Various lipophilic cations, such as quinacrine mustard and dequalinium, which are known to inhibit mitochondrial F1-ATPase, strongly inhibited vacuolar H(+)-ATPase purified from bovine adrenal chromaffin granules. Quinacrine mustard bound irreversibly to vacuolar H(+)-ATPase subunit A, and the 115 kDa accessory polypeptide and dithiothreitol had no effect. The binding was competitively inhibited by chlorpromazine and quinacrine, and these compounds specifically reduced the amount of labeling of subunit A. Quinacrine mustard also prevented the binding of [alpha-32P]ATP to subunit A but had no effect on the binding of [3H]N-ethylmaleimide to either subunit A or the 115 kDa accessory polypeptide. These results suggest that the binding site of quinacrine mustard in subunit A is not related to the N-ethylmaleimide-binding site(s), which is important for activity.

Amino Acid Sequence↗

Intermediate TCR cells with self-reactive clones are effector cells which induce syngeneic graft-versus-host disease in mice.

It has been established that, even after syngeneic bone marrow transplantation, animals treated with immunosuppressive drugs may suffer from graft-versus-host disease, showing autoimmune-like symptoms. Although the major effector cells are known to be T-cell subsets, detailed characterization of such T cells remains to be investigated. In the present study, we characterized them, especially as to whether they are thymus-derived T cells or extrathymic T cells, and how self-reactive clones were distributed among the above T-cell subsets. BALB/c mice (Mls-1b2a) were irradiated (9 Gy), subjected to bone marrow transplantation, and then treated with cyclosporin A (CsA) for 6 weeks. From 2 weeks after the cessation of CsA, these mice displayed signs of GVH disease. The major target organs included the liver and colon. Two-color staining for CD3 and IL-2R beta was applied to identify CD3-IL-2R beta+ NK cells, CD3-intermediate +IL-2R beta+ cells (i.e., intermediate CD3 or TCR cells of extrathymic origin) and CD3-high+IL-2R beta- cells (i.e., high CD3 cells of thymic origin). It was demonstrated that the major expanding lymphocytes were intermediate TCR cells and that self-reactive clones (V beta 3+ and V beta 11+ cells in this strain of mice) were confined to this population. Interestingly, these self-reactive clones had ability to respond to immobilized anti-V beta 3 and anti-V beta 11 mAbs. Liver MNC in mice with GVH disease which contained the highest proportion of intermediate TCR cells were able to mediate the adoptive transfer of GVH disease to other irradiated (6.5 Gy) mice. Intermediate TCR cells also showed potent cytotoxic activity against syngeneic leukemia cells. These results suggest that intermediate TCR cells are the major effector cells for the induction of syngeneic GVH disease.

Animals↗

Conformational changes of alpha-lactalbumin induced by the stepwise reduction of its disulfide bridges: the effect of the disulfide bridges on the structural stability of the protein in sodium dodecyl sulfate solution.

Four disulfide bridges of bovine alpha-lactalbumin (alpha-lact) were selectively reduced to obtain its derivatives with three, two, and zero disulfide bridges (designated as 3SS, 2SS, and 0SS alpha-lact, respectively). The original helicity was almost maintained in 3SS alpha-lact missing only the Cys6-Cys120 bridge. Upon the reduction of both Cys28-Cys111 and Cys6-Cys120 bridges, various changes occurred in the protein. In particular, the maximum fluorescence of 1-anilinonaphthalene-8-sulfonic acid was observed in this stage. Upon the reduction of all disulfide bridges, the hydrophobic box of the protein, formed by Trp60, Ile95, Tyr103, and Trp104, was disrupted and an internal helical structure was destroyed. The conformation of each derivative was examined mainly in a solution of sodium dodecyl sulfate. In the surfactant solution, the helicity increased from 33% to 37% in 3SS alpha-lact, from 26% to 31% in 2SS alpha-lact, and from 18% to 37% in 0SS alpha-lact, as against from 34% to 44% in intact alpha-lact. On the other hand, the tryptophan fluorescence of each derivative was affected in very low surfactant concentrations, suggesting that the tertiary structure considerably changed prior to the secondary structural change in the surfactant solution.

Anilino Naphthalenesulfonates↗

Acute aortic dissection in a patient with osteogenesis imperfecta.

A case of osteogenesis imperfecta complicated with acute type A aortic dissection is presented. Emergency graft replacement of the ascending aorta was performed successfully despite the anticipated difficulties with tissue friability. Therefore, such an operation is suggested to be worthy of consideration and feasible in patients with osteogenesis imperfecta.

Acute Disease↗

Infective mitral valve endocarditis after percutaneous transvenous mitral commissurotomy.

Infective mitral valve endocarditis developed in a 40-year-old female patient after a percutaneous transvenous mitral commissurotomy (PTMC). The echocardiogram demonstrated a vegetation in the anterior leadflet of the mitral valve and moderate aortic insufficiency. The patient underwent replacement of the infected mitral and incompetent aortic valves. Infective mitral valve endocarditis should be recognized as a potentially lethal complication after PTMC. The important measures to prevent bacteremia during PTMC and the appropriate role of operation are discussed.

Adult↗

Effects of long-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome.

We examined the effects of long-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in 61 patients with myelodysplastic syndrome (MDS). Patients were randomly assigned to receive daily subcutaneous injection of 60 micrograms/m2, 125 micrograms/m2 or 250 micrograms/m2 for 8 weeks. A significant increase in granulocyte counts including neutrophils and eosinophils was shown from one week after the start of the treatment in all three dose groups. The increase in granulocyte counts reached a plateau at the 4th week and was sustained during the treatment period. However, no consistent change in other cell lineages including monocytes, lymphocytes, reticulocytes and platelets were observed. Nevertheless peak-levels of these cells were significantly higher than the pre-treatment levels. In higher dose groups, the number of patients developing infections was reduced. There was no significant difference in the incidence of adverse events among the 3 dose groups, and the toxicity was generally well-tolerated. These observations indicate that treatment with rhGM-CSF can be of potential therapeutic benefit to patients with MDS.

Adolescent↗

Concanamycin B inhibits the expression of newly-synthesized MHC class II molecules on the cell surface.

We screened natural chemical compounds which inhibit the expression of newly-synthesized MHC class II molecules on the cell surface. IFN-gamma stimulates Colo 205 adenocarcinoma cells to induce the expression of MHC class I, MHC class II, and ICAM-1 molecules on the cell surface. We show here that concanamycin B inhibits the expression of MHC class II molecules on Colo 205 cells, whereas it does not affect the expression of MHC class I and ICAM-1 molecules. Concanamycin B also abrogates the enhancement of the MHC class II expression by IL-4 on mouse lymphocytes. Furthermore, concanamycin B suppresses the antigen presentation by MHC class II molecules.

Animals↗

[Isolated aortic valve regurgitation due to degeneration of the valve leaflet--a clinical study].

From 1989 through 1993 thirty-eight patients underwent aortic valve replacement at our institution for isolated aortic regurgitation (AR) caused by idiopathic degeneration of the valve. There were 32 male and 6 female patients aged between 33 and 74 years with a mean of 59 years. Preoperative New York Heart Association functional class, cardiothoracic ratio, cardiac index, and left ventricular end-diastolic pressure were 2.6, 57%, 3.1 L/min/m2, and 18 mmHg, respectively. Cross-sectional echocardiography clarified aortic valve prolapse in seven patients. Excised valvular cusps were thin, redundant and translucent in association with cuspal fenestration in 9 cases and idiopathic commissural disruption in 2 cases. Histological study revealed significant disruption of the fibrosa and cystic degeneration of the spongiosa layer filled with mucopolysaccharide. Actuarial survival rate, including 3 operative deaths, was 89% at 3 years after AVR with no apparent valve related complications. Idiopathic degeneration of the aortic valve is a common cause of AR, occurring in half of the surgically treated patients. We emphasize the importance of this lesion as a cause of AR.

Adult↗

[Significance of combined use of anticoagulants and antiplatelet agents in the early stage after prosthetic valve replacement].

Patients who had undergone prosthetic valve replacement were treated with warfarin (anticoagulant) alone or in combination of ticlopidine (200 mg/day) or aspirin (81 mg/day) (anti-platelet agents). The study of blood coagulation factors and platelet aggregation were carried out with these cases. 1) The patients (n = 24) receiving warfarin for 21 days after prosthetic valve replacement revealed marked increases in PIVKA-II and vitamin K1-epoxide. The protein C activity was significantly lower than that before the operation. High levels of more than 5 ng/ml of TAT were found before operation and after warfarin administration for 21 days. 2) Warfarin did not affect platelet aggregation, whereas ticlopidine inhibited ADP-induced platelet aggregation and aspirin inhibited both collagen-induced and arachidonic acid-induced aggregation. In conclusion, combined use of anticoagulants and antiplatelet agents after prosthetic valve replacement will suppress not only the blood coagulation but also the platelet aggregation systems.

Adult↗

FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group.

A phase II study of the efficacy and safety of FK506, a new potent immunosuppressant, has been conducted in 49 patients with GVHD after allogeneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study. FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had become uncontrollable with cyclosporin and/or other immunosuppressants. The response to FK506 was evaluated in 13 patients with acute and 26 with chronic GVHD. A marked response was observed in 5 and a good response in 2 of 13 patients with acute GVHD. For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8. The most common adverse effects were renal toxicity (53.1%), followed by nausea and vomiting (30.6%) and a feeding of warmth (18.4%). There was a correlation between renal toxicity and whole blood levels of FK506. The dose should be adjusted to keep a trough level between 15 and 25 ng/ml. FK506 is promising in the treatment of both acute and chronic GVHD, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.

Acute Disease↗

[Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father].

We report a case of a 19-year-old male with congenital aplastic anemia and multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and mental retardation. He was admitted to our hospital because of severe pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42% myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and underwent allo-BMT from an HLA-identical father. The conditioning regimen consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total body irradiation. Severe toxicity associated with the conditioning regimen was not observed. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is well and free of disease for 15 months since BMT. Very few cases of Fanconi's anemia with leukemic transformation treated by BMT have been reported. Long-term observation will be necessary to evaluate our conditioning regimen for Fanconi's anemia with leukemic transformation.

Adult↗

Enhanced elimination of Ph+ chromosome cells in vitro by combined hyperthermia and other drugs (AZT, IFN-alpha, TNF, and quercetin): its application to autologous bone marrow transplantation for CML.

Autologous bone marrow transplantation (ABMT) for chronic myelogenous leukemia (CML) is limited because of the difficulty in purging Ph chromosome positive cells from bone marrow cells (or peripheral blood stem cells). Combining hyperthermia with certain drugs that affect Ph+ cell growth in vivo and in vitro may enhance the killing (apoptosis) of CML cells in vitro. In this study, we chose such drugs (i.e., azidothymidine [AZT], interferon-alpha [IFN-alpha], tumor necrosis factor [TNF], and quercetin) and tested this hypothesis using two CML-derived cell lines in vitro, K562 and KU812, to enhance the killing of CML cells with heat. Our results indicate that the optimal hyperthermic purging effect is achieved by heating at 42 degrees C for 1 hour with IFN-alpha (100 U/mL) and AZT (0.5 microM/L) or with quercetin (50 microM) [corrected], depending on the sensitivity of the CML cells eliminated in vitro. K562 cells were significantly eradicated by a combination of IFN-alpha and AZT, while KU812 cells were significantly inhibited by quercetin at the temperature and drug concentrations above. This combined effect may enhance apoptosis of CML cells in vitro.

Apoptosis↗

[Surgical treatment for complete rupture of anterior papillary muscle after acute myocardial infarction].

A 64-year-old male patient with postinfarction complete anterior papillary muscle rupture and massive mitral regurgitation is presented. The diagnosis was suspected clinically and confirmed by transesophageal echocardiography. One week after the episode of acute myocardial infarction (AMI) the patient had a sudden onset of severe congestive heart failure with pulmonary edema and was transferred to our hospital. The patient underwent an emergency mitral valve replacement with a SJM29M prosthetic valve. Histological examination revealed an acute coagulation necrosis of the anterior papillary muscle without specific inflammatory change. To our knowledge this is the second case with successful surgery for a complete rupture of the anterior papillary muscle following AMI in Japan.

Echocardiography, Transesophageal↗

[Valvular surgery for the patients 70 years old or older].

From January 1986 to June 1993, twenty one patients aged 70 years or older with valvular heart disease underwent open heart surgery. There were 12 males and 9 females with a mean age of 71.2 years (range 70 to 76). Eight patients were in NYHA class III, and 4 in class IV preoperatively. AVR was performed in 10 patients, MVR, MVR with TAP, OMC, AVR with MAP, DVR with TAP in 4, 4, 1, 1, and 1, respectively. Mechanical and bioprosthetic valves were replaced in 11, and 9 patients respectively. There were 6 early death (4 operative, 2 hospital). Longer duration of cardiopulmonary bypass (p < 0.05) and aortic crossclamp time (p < 0.05) were the risk factors independently for early mortality. Follow-up of 15 hospital survivors was 100% (8 months-7.7 years, mean: 3.2 years) and cumulative follow-up was 47.6 patients years (PY). There was one late death, and one prosthetic valve endocarditis (2.1%/PY). No other valve-related complications was occurred. Actuarial survival rate and freedom from valve-related morbidity at seven years were 83.3%, and 93.3%, respectively. These results show that operative mortality of valvular disease in elderly patients remains high, but the late results is acceptable one. Valve surgery for these elderly patients is reasonably acceptable.

Aged↗

[Double valve replacement with mechanical prostheses--an operative results].

From January 1980 to December 1993, sixty eight patients underwent double valve replacement with mechanical prostheses. There were forty males and twenty-eight females with a mean age of 49.6 years (ranging from 30 to 68 years). They were classified 10 of NYHA class IV, 28 of class III. Twelve patients had previous cardiac operation. TR was identified in 20 patients. DVR was performed in 53 patients, DVR + TVR in one, DVR + TAP in 13. Twenty-two had St. Jude Medical (SJM) prostheses and 46 had Björk-Shiley (BS) prostheses. Early death before 30 postoperative days occurred in 6 patients (8.8%). MOF was the most frequent cause for early death. The risk factors for early death were the NYHA class IV, infective endocarditis, longer duration of cardiopulmonary bypass, necessity of postoperative IABP support. Other factors such as emergency operation, previous operation, tricuspid valve surgery, duration of aortic cross clamp time were not the predictors for early death. Cumulative follow-up was 284.0 patient years (PY). The rate of late survival was 74.1% (40 patients). Linearized rates of thromboembolism (TE), prosthetic valve endocarditis (PVE), hemolysis (H), reoperation (RO) were 2.8%/PY, 0.7%/PY, 0.4%/PY, 1.1/PY respectively. The free rates from TE, PVE, H, RO at nine years were 75.6%, 96.2%, 93.1%, and 89.8%, respectively. The cumulative survival rates at 14 years were 53.2% in over-all patients, and 64.3% in hospital survivors. We conclude that the early surgery is recommended for the patients with multiple valvular heart disease. The late outcomes of DVR with SJM or BS mechanical prosthesis is an acceptable one.

Adult↗