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Biomedical subjects

Y Moriyama

Publications and source records attributed to Y Moriyama.

At least 307 records · Page 17Linked to original sources

Surgical treatment of abdominal aortic aneurysm in the high-risk patient.

In an attempt to define the preoperative risk factors that predictably influence mortality after aneurysmectomy, this study reviews the surgical management of abdominal aortic aneurysms in a series of 110 consecutive patients who underwent elective resection. The preoperative risks to be added to the present study included pulmonary insufficiency, renal dysfunction, advanced age of over 80 years, ischemic heart disease, and associated other diseases such as thoracic aneurysms, atherosclerosis of the limbs and malignant tumors. Forty-six patients had one of these risk factors (one-risk group), 17 had two (two-risk group), and 9 had three (three-risk group). The operative mortality rates were 4.2 per cent for the high-risk patients and 0 per cent for the patients at no risk. As the number of risk factors increased, aneurysm repair was associated with an increased operative mortality; being 2.2 per cent in the one-risk group, 5.9 per cent in the two-risk group and 11.1 per cent in the three-risk group. The common risk factor in patients who died after aneurysmectomy was pulmonary insufficiency which induced prolonged periods of assisted ventilation. Thus, the optimal management of high-risk patients, particularly those with pulmonary insufficiency, may reduce the mortality after aneurysmectomy.

Aged↗

Vanadate-sensitive ATPase from chromaffin granule membranes formed a phosphoenzyme intermediate and was activated by phosphatidylserine.

Vanadate-sensitive ATPase (115 kDa molecular weight) in adrenal chromaffin granules is an intrinsic membrane enzyme with its catalytic site located at the outer surface of the granules. Upon incubation with [gamma-32P]ATP, the purified ATPase formed an alkaline-labile phosphoenzyme intermediate, which was inhibited by vanadate but not by Na+ or K+. Ratio of ATPase or phosphatase activity and formation of phosphoenzyme intermediate was constant during purification after the first glycerol density gradient centrifugation. Phosphatidylserine specifically activated the enzyme about three-fold by increasing the Vmax value without changing the Km for ATP. Other phospholipids, including phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, as well as lysophospholipids and detergents, had no effect. These results indicated that the vanadate-sensitive ATPase belongs to the P-type ATPases, which differ from known cation-translocating P-type ATPases.

Adenosine Triphosphatases↗

Inhibition of neurotransmitter and hormone transport into secretory vesicles by 2-(4-phenylpiperidino)cyclohexanol and 2-bromo-alpha-ergocryptine: both compounds act as uncouplers and dissipate the electrochemical gradient of protons.

2-(4-Phenylpiperidino)cyclohexanol (AH-5183) and 2-bromo-alpha-ergocryptine, known inhibitors of the transport of acetylcholine and L-glutamate, respectively, into synaptic vesicles, inhibited the ATP-dependent uptake of dopamine in parallel with the dissipation of the electrochemical gradient of protons in chromaffin granule membrane vesicles. These compounds induced the release of accumulated dopamine from the vesicles. They also inhibited the ATP-dependent formation of the electrochemical gradient of protons in liposomes reconstituted with chromaffin H(+)-ATPase without affecting the activities for ATP hydrolysis, and ATP-dependent uptakes of dopamine, gamma-aminobutyrate, and glutamate into synaptic vesicles. These results indicated that 2-(4-phenylpiperidino)cyclohexanol and 2-bromo-alpha-ergocryptine acted as uncouplers in the secretory vesicles.

Animals↗

Gene transfer into human leukemia cell lines by electroporation: experience with exponentially decaying and square wave pulse.

The efficiency of gene transfer into human leukemia cell lines by electroporation was investigated. For both transient expression (beta-galactosidase gene) and stable transformation (neomycin resistance gene), the transfer efficiency into leukemia cell lines using a square wave pulse was superior to that using an exponentially decaying wave. The transfer rate of pMoZtk (containing beta-galactosidase gene) into K562 by electroporation using a square wave was approximately 5%, compared with 1% by an exponentially decaying pulse. Whereas the transfer rate of pMAM-neo into K562 by electroporation using an exponentially decaying pulse was less than 10(-5), a square wave generated much more efficient introduction rate of nearly 10(-3). In the other leukemia cell lines also, some square wave yields were better than exponential yields and all square wave yields were at least as good as the exponential yields.

Blotting, Southern↗

N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden.

Nicotinamide methyltransferase (Nmd CH3transferase) activity increased in the liver of mice after i.p. transplantation of Ehrlich ascites tumor (ascitic form), but not in the liver of mice with acute inflammation induced by the i.p. administration of D-galactosamine, and it rather showed a decrease together with necrosis after carbon tetrachloride administration. When Nmd CH3transferase activity of rat hepatocytes in primary culture was investigated with the addition of dexamethasone, epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha and N1-methylnicotinamide (1-CH3Nmd), changes in activity were not correlated with DNA synthesis, suggesting that the increase of this enzyme activity in the tumor host liver was not directly related to liver cell proliferation. Thus, in order to make use of the increase of this enzyme activity as a tumor burden marker, a procedure for its estimation by measuring the blood level of 1-CH3Nmd, a metabolite of Nmd produced by Nmd CH3transferase, was established. The 1-CH3Nmd level in the blood of mice bearing Ehrlich ascites tumor 4 h after s.c. loading of Nmd (500 mg/kg body weight) was closely correlated with this enzyme activity in the liver (r = 0.835, P less than 0.00001) from the early to the terminal stage of tumor development. Furthermore, similar correlations were seen in the animal groups bearing various other tumors, such as s.c. implanted Ehrlich ascites tumor (solid form) and i.p. implanted sarcoma S-180, hepatoma MH-134, Yoshida ascites sarcoma and leukemia L-1210, but not solid tumors such as Lewis lung carcinoma and melanoma B-16, although almost all of the animals bearing these tumors showed a higher enzyme activity than their control normal animals.

Animals↗

Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient.

A protein factor which stimulated [3H]thymidine uptake into free hepatocytes prepared from normal mouse liver was detected in the ascitic fluid of gynecological cancer patients. The factor was subsequently further purified from the ascitic fluid of an endometrial cancer patient by DEAE-Sephacel, Sephadex G-150 and Phenyl-Sepharose CL-4B column chromatographies, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a single protein band of 54,000 Da, designated tentatively as 54K ascitic protein (54K-AP). 54K-AP was similar to human alpha 1-antitrypsin (alpha 1-AT) in terms of SDS-PAGE and immunological behavior, but was slightly different in terms of amino acid sequence and isoelectric point. Although 54K-AP inhibited the activities of bovine trypsin and alpha-chymotrypsin as did human alpha 1-AT, 54K-AP inhibited the plasminogen activator released from human endometrial cancer Ishikawa cells more efficiently than alpha 1-AT. Because, in contrast to normal serum, the serum from the endometrial cancer patients stimulated [3H]thymidine uptake into hepatocytes, the possibility arises that 54K-AP could be produced by the cancer host as a defence mechanism against the cancer.

Amino Acid Sequence↗

Hematopoietic recovery in a patient with acute lymphoblastic leukemia after an autologous marrow graft purged by combined hyperthermia and interferon in vitro.

We describe a patient with acute lymphoblastic leukemia (ALL) in whom hemopoiesis recovered after an autologous marrow graft purged by in vitro hyperthermia. A 17-year-old woman was diagnosed as having ALL in April 1985. After clinical remission was induced, marrow cells were harvested. The marrow cells were treated with hyperthermia at 42.0 degrees C for 1 h in the presence of alpha-interferon to eliminate residual leukemic cells, and then cryopreserved. In January 1990, during her fourth remission she was treated with busulfan and cyclophosphamide, and then received the thawed autologous marrow. Her hematopoietic recovery was prompt with normal trilineage regeneration without any life-threatening complications. She is in good health without evidence of a leukemic relapse at 6 months after autologous bone marrow transplantation. This case suggests that human multilineage progenitor cells retain self-renewal capacity in vivo even after treatment with heat and alpha-interferon in vitro followed by the freezing and thawing procedures.

Adolescent↗

Alpha-interferon broadens the difference between surviving fractions of normal and leukemic progenitor cells in vitro by heat: its application to marrow purging.

Alpha-interferon (IFN) may inhibit the proliferation of human leukemic progenitor cells (L-CFU) in vitro and enhance the anti-tumor effects by heat. In this study, the combined effects of IFN and hyperthermia on the growth of L-CFU and human granulocyte-macrophage progenitors (CFU-GM) were examined to determine if this combination resulted in a greater selective killing of L-CFU than that obtained by heat treatment alone. The survival of normal CFU-GM without IFN decreased at elevated temperatures (42-44 degrees C). However, IFN added during heating (42 and 43 degrees C) appeared significantly to protect against the hyperthermic killing of CFU-GM in vitro leaving over 50% of CFU-GM surviving. The optimal dose to protect CFU-GM in vitro dropped to a rather low dose (100 U/ml). On the other hand, the addition of IFN to leukemic cell suspensions enhanced the hyperthermic killing of myeloid leukemic cell lines (HEL and KG-1) as well as a T lymphoblastic cell line (CEM) in a dose-related manner. In addition, similar results were observed in the study of L-CFU from patients with acute myelogenous leukemia. These results suggest that IFN can be used to broaden the difference between surviving fractions of CFU-GM and L-CFU by heat. Thus, this combination could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous remission marrow graft before autologous bone marrow transplantation.

Bone Marrow Purging↗

[Intermittent administration of natural interferon-alpha for over 5 years induced complete suppression of Philadelphia chromosome in a patient with myelogenous leukemia].

A 60-year-old woman was admitted to our hospital because of gastric ulcer, anemia, and leukocytosis in November 1984. Blood cell counts on admission were as follows: RBC 407 x 10(4)/microliters, Hb 9.8 g/dl, WBC 33,000/microliters (baso 8%, eo 7%, myelo 11%, meta 2%, stab 4%, seg 54%), Plt 93.7 x 10(4)/microliters. Bone marrow showed hypercellular and myeloid hyperplasia. She was diagnosed as Ph1-chromosome positive chronic myelogenous leukemia. She received natural interferon-alpha at the dosage of 600 x 10(4) IU daily for 22 days from January 14, 1985. After March 1985, she has been given intermittent administration of interferon once in 10 to 20 days, and maintained normal blood cell counts. Cytogenetic improvement was seen on 35 months after the start of IFN and complete suppression of Ph1 chromosome was observed at July 1990 (66 months after).

Drug Administration Schedule↗

No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by [11C]propyl ketene method.

This article describes the preparation of sn-1,2-[11C]diacylglycerols and sn-1,3-[11C]diacylglycerols by a no-carrier-added reaction based on a labeling method using [1-11C]propyl ketene, which is one of the most potent acylating agents. [1-11C]Propyl ketene was produced by pyrolytic decomposition of [1-11C]butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine. We adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-[1-11C]butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-[11C]Diacylglycerol was also synthesized by [1-11C]propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-[11C]diacylglycerol were higher than those of sn-1,3-[11C]diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2-[11C]diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover.

Acylation↗

Efficient introduction of a gene into hematopoietic cells in S-phase by electroporation.

Cells of the hematopoietic cell line K562 were synchronized by three different methods: single aphidicolin treatment, thymidine treatment followed by hydroxyurea exposure, and double hydroxyurea treatment. The synchronized cells were transfected via electroporation with plasmid pMoZtk, which contains the beta-galactosidase gene, using a square wave pulse immediately after synchronization or at various time points during culture. Simultaneously, synchronized cells were fluorescence-activated cell sorter (FACS) analyzed to determine their stage in the cell cycle using double staining with bromodeoxyuridine (BrdU) and propidium iodide. Highly efficient introduction of pMoZtk was observed for the cell fraction, which predominantly consisted of the cells in S-phase. These results suggest that by increasing the proportion of cells in S-phase, the efficiency of gene transfer into hematopoietic cells such as hematopoietic stem cells can be improved.

Aphidicolin↗

[Myocardial protection with verapamil in open cardiac surgery--a clinical study for the optimal use].

To determine the optimal use of Verapamil as a myocardial protective agent during open heart surgery, patients were divided into 3 groups of 15 patients each of the same severity and operative difficulty. In group I, Verapamil was added to the blood cardioplegia in a concentration of 1 mg/L. In group II, 0.2 mg/kg of verapamil was added in the pump prime and in group III, in addition to the same amount of pump prime, an additional 0.1 mg/kg of Verapamil was added to the bypass circuit at 60 minutes after the start of bypass and continuous drip of 0.5 micrograms/kg/min for 24 hours after surgery. Only group III continued to maintain an effective concentration of verapamil, that was said in a range between 15 and 100 ng/ml in the serum during and after surgery. It is suggested from the present study that recommendable verapamil administration is as in group III with no severe arrhythmias, significantly less usage of catecholamines without mortality.

Cardiac Surgical Procedures↗

[Surgical management of tricuspid regurgitation associated with acquired valvular disease].

The best means of managing tricuspid regurgitation associated with acquired valvular disease is still controversial. During the period from 1978 to 1988, 111 patients who had tricuspid regurgitation along with associated valvular dysfunction were treated in Kagoshima University Hospital. Patients with moderate to severe regurgitation underwent annuloplasty in 61 (Carpentier's in 39, DeVega's in 20, and Kay's method in 2) and valve replacement in 8. Forty-two patients were treated conservatively on the tricuspid valve because of mild regurgitation. We found the results to be less satisfactory with a high incidence of postoperative deaths and residual tricuspid regurgatation in the group treated by annuloplasty with a Carpentier ring than in the other two groups of annuloplasty or in the group of valve replacement. We conclude the modified DeVega's method is the first choice for annuloplasty in patients with mild to moderate regurgitation, and we believe it appropriate to replace the valve in an increasing number of subjects which have severe regurgitation.

Adult↗