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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 667 records · Page 37Linked to original sources
PubMed1988

Difluoro-phenyl-ethyl(4-aminopropylamidinohydrazone): an irreversible inhibitor for both ornithine and S-adenosylmethionine decarboxylases and its effect on human lymphoid leukemia Molt 4B cells.

Difluoro-phenyl-ethyl(4-aminopropylamidinohydrazone) (DFPA) was synthesized as an irreversible inhibitor of ornithine and S-adenosylmethionine decarboxylases and analyzed for antiproliferative effects on leukemia cells. The compound irreversibly inhibited ornithine and S-adenosylmethione decarboxylases. This inhibition could not be reversed by dialysis or chromatography on Sephadex G-50. When human lymphoid leukemia Molt 4B cells were cultured in the presence of the inhibitor, the intracellular levels of polyamines (putrescine, spermidine and spermine) and the rate of cell proliferation were markedly depressed. In these polyamine-depleted and growth-retarded cells, the synthesis of protein, but not of DNA or RNA, was observed to be significantly inhibited.

Adenosylmethionine Decarboxylase↗
PubMed1988

Phorbol esters potentiate glucocorticoid-induced cytotoxicity in CEM-C7 human T-leukemia cell line.

Phorbol ester tumor promoter, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), is synergistic with dexamethasone to cause growth inhibition of CEM-C7 human T-leukemia cell line. A specific saturable binding component which may mediate the phorbol ester effects has been identified by using [20-(3)H]phorbol 12,13-dibutyrate in a whole cell binding assay. Saturation of the specific binding occurs at a concentration (approx. 100 nM) consistent with causing maximal cytotoxicity. Scatchard analysis of the binding after 15 min at 37 degrees C demonstrates a single class of binding sites. The number is 194,000 sites per cell. Other phorbol esters are also cytotoxic to CEM-C7 cell in the presence of 30 nM dexamethasone in an approximate proportion to their activity in competing for [20-(3)H]phorbol 12,13-dibutyrate binding. Phorbol 12, 13-didecanoate, 4-O-methyl PMA, 4-beta-phorbol do not compete for specific binding. The synergism of phorbol esters and dexamethasone on CEM-C7 cells is reversible by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7). However, by treating CEM-C7 cells with TPA for 48 h there is not any increase in the affinity or levels of glucocorticoid receptor. It is tentatively concluded that phorbol esters may play an important role linked to the glucocorticoid-induced growth inhibition in CEM-C7 human T-leukemic cell.

Binding, Competitive↗
PubMed1988

B-cell-specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQB gene.

A 95-base-pair immediate upstream sequence of the human class II major histocompatibility complex DQB gene containing the conserved X and Y elements showed enhancer activity in a transient expression assay. An "enhancer test plasmid" harboring the bacterial chloramphenicol acetyltransferase gene under the control of a truncated simian virus 40 enhancerless early promoter was employed. The DQB sequence inserted into this plasmid was active as an enhancer in Raji cells (human Burkitt lymphoma cells) but not active in Jurkat cells (human T-cell leukemia cells) or in HeLa cells (human cervical carcinoma cells). This cell-type specificity suggests that this enhancer activity may be involved in the tissue specificity of the DQB gene that is normally expressed only in mature B cells, macrophages, and thymic epithelial cells. Deletion analysis showed that both X and Y box sequences are essential for the full activity of the enhancer sequence and that these two sequences may function in a cooperative manner as cis-acting elements. Further deletions were used to define the 5' border of the X element. These results suggest that previously characterized protein factors that bind to X and Y include transcription factors involved in the cell-type specificity of this enhancer activity.

Acetyltransferases↗
PubMed1988

Inhibition of mouse skin tumor promotion and of promoter-induced epidermal polyamine biosynthesis by methylglyoxal bis(butylamidinohydrazone).

Effects of methylglyoxal bis(butylamidinohydrazone) (MGBB), a reversible inhibitor of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases of ODC and AdoMetDC activities, ODC and mRNA level and polyamine contents in mouse skin were investigated in connection with tumor formation. Formation of papillomas by applications of TPA to 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin was effectively inhibited by simultaneous topical applications of MGBB, MGBB also dose-dependently inhibited the ability of TPA to induce increases of ODC activity, ODC mRNA level and the accumulation of putrescine and spermidine in mouse skin. Induction of AdoMetDC activity was not affected by the drug. These inhibitory effects of MGBB on ODC induction and tumor promotion were more evident in multiple application experiments than with a single application of the drug.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Phase II study of carboplatin in small cell lung cancer.

Carboplatin (CBDCA; cis-diammine-1, 1-cyclobutane dicarboxylate platinum II), a new platinum analogue, was administered to 18 patients with small cell lung cancer (SCLC) at a dose of 300-450 mg/m2 intravenously every four weeks, in a phase II study. All patients could be evaluated to assess response and 17 for toxicity. The overall response rate was 28% (5/18), including one complete response. Of eight patients previously untreated, four (50%) showed a response, including one complete response. The response rate in patients with no previous cisplatin-treatment was 50% (5/10). Response durations in five responders were 2, 3, greater than 4, greater than 10 and 11 months. Toxicity was primarily hematologic, with thrombocytopenia being dose-limiting. Thrombocytopenia (less than 75,000/mm3) was observed in 12 patients (71%), six requiring platelet transfusion. Leukopenia (less than 3,000/mm3) was observed in 11 patients (65%). There were no episodes of serious infection or bleeding, however. Myelosuppression was more severe in heavily pretreated patients than in patients previously untreated. Dose reductions were required following multiple treatments for cumulative myelotoxicity. Mild to moderate nausea and vomiting occurred in seven patients (44%). Nephrotoxicity and ototoxicity were not observed. Carboplatin was demonstrated to be an active agent against SCLC. Further investigation into dose and schedule of CBDCA in combination chemotherapy is warranted.

Aged↗
PubMed1988

Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level.

Recombinant human interleukin-2 (rIL-2) was administered to 34 patients with advanced malignancy. Three schedules of rIL-2 administration employed were as follows: (A) 2-hr iv infusion of 6.7 X 10(5) U/m2/day (A1, 6 cases) or 2.2 X 10(6) U/m2/day (A2, 8 cases) for five consecutive days; (B) 24-hr continuous iv infusion of 3.3 X 10(5) U/m2/day (B1, 3 cases), 6.7 X 10(5) U/m2/day (B2, 7 cases) or 1.1 X 10(6) U/m2/day (B3, 5 cases) for 28 consecutive days; and (C) 24-hr continuous iv infusion of 6.7 X 10(5) U/m2/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose-limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2-hr iv infusion, rIL-2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24-hr continuous infusion, more than 1 U/ml serum IL-2 activity was maintained for 14 days in group B3. Natural killer (NK) and lymphokine-activated killer (LAK) activities were augmented by rIL-2 administration in patients of groups A, B3 and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL-2 administration, and recovered by day 3. The percentage of IL-2 receptor and Leu HLA-DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA-DR positive cells as well as NK and LAK activities increased upon rIL-2 administration and decreased during an intermission of two days. However, the percentage of rIL-2 receptor positive cells increased during the intermission of rIL-2. The most effective schedule of rIL-2 administration was considered to be the schedule of group C on the basis of this study.

Adult↗
PubMed1988

Induction of differentiation of mouse myeloid leukemia M1 cells by serum of patients with chronic myeloid leukemia.

We examined the capacities of sera from patients with myeloid leukemia to induce differentiation in mouse myeloid leukemic M1 cells. Higher differentiation-inducing activity (D-activity) was detected in sera of patients with chronic myelomonocytic leukemia or chronic myeloid leukemia (CML) than in sera of patients with acute myeloid leukemia and normal volunteers. The D-activity in the sera was lost on heating the sera at 56 degrees for 30 min. The major peak of D-activity on Sephadex G-200 gel filtration had an apparent molecular weight of 160,000. The origin of the D-activity in sera of patients with CML was studied by culturing fractions of peripheral blood cells of patients with D-activity for 3 days and then measuring the ability of the conditioned medium (CM) to induce differentiation of M1 cells. The cells in the myeloblast and promyelocyte fraction differentiated spontaneously into macrophage-like cells during culture for 3 days and the cells in the late granulopoietic cell fraction differentiated into neutrophil-like cells. Higher D-activity was present in CM of cells in the myeloblast and promyelocyte fraction than in CMs of late granulopoietic cell fractions. These results suggest that human leukemic cells produce D-activity for M1 cells during their differentiation into macrophage-like cells.

Animals↗
PubMed1988

Carcinoid tumor of the middle ear. An immunohistochemical and electron microscopic study. Report of a case.

A primary tumor of the middle ear was examined histologically, histochemically, immunohistochemically and ultrastructurally. Neuroendocrine cell differentiation, a carcinoid feature, was demonstrated by the presence of numerous argyrophil granules, as well as positive serotonin, glicentin, glucagon, and human pancreatic polypeptide (hPP) granules in some of the Grimelium-positive cells. Chromogranin A was also detected in the cells, but much less frequently than Grimelius-positive staining. Neither neuron-specific enolase (NSE) nor epithelial membrane antigen (EMA) was demonstrated in the tumor. Mucin was demonstrated only intraluminally. Electron microscopy revealed many typical neurosecretory granules in tumor cells, but no apical mucin granules. The tumor appeared to be benign, and there has been no sign of recurrence during a postoperative period of one year.

Adult↗
PubMed1988

Necrosis of portal tumor embolus of hepatocellular carcinoma by lipiodol transcatheter chemo-embolization. A case report.

We describe a case of hepatocellular carcinoma in which a tumor embolus in the portal vein and 3 of 4 intrahepatic metastases were necrosed completely by Lipiodol transcatheter chemo-embolization (Lipiodol-TCE). Tumor emboli in the portal vein and intrahepatic metastases usually cannot be necrosed by conventional transcatheter chemo-embolization alone, because small nodules such as intrahepatic metastases and tumor emboli in the portal vein are supplied blood from the portal vein. However, in this case, Lipiodol-TCE was effective against tumor emboli in the portal vein and intrahepatic metastases.

Aged↗
PubMed1988

Mechanisms of chronic recurrent idiopathic ventricular tachycardia.

In 24 patients with idiopathic ventricular tachycardia (VT), mechanisms of VT and the effects of antiarrhythmic drugs after induction were studied electrophysiologically, and by exercise testing. VT was induced electrophysiologically in 14 patients. Class 1 antiarrhythmic drugs were effective in 7 of them, which implied that one of the mechanisms of idiopathic VT was reentry related to the depressed channel dependent slow conduction. In 6 of the 14 patients, the QRS morphology of VT showed a complete RBBB with axis deviation pattern and the tachycardia was responsive to verapamil. In 2 of them, induction of VT was facilitated at low plasma verapamil concentrations. In the other 2 patients, left ventricular mapping showed that a notched potential preceding each QRS complex and the retrograde His bundle deflection with a short interval were recorded during VT. These findings suggested that the mechanism of this type of VT was reentry, mediated by Ca dependent slow conduction and located within the left bundle branch network. Exercise testing provoked VT in eight. Beta-blockers and Ca-antagonists were effective in 6 and in 4, respectively. These findings indicate the possibility that in addition to enhanced automaticity or reentry, triggered activity could play a role in the genesis of exercise related VT.

Adolescent↗
PubMed1988

[Pharmacological comparison of the CNS effects of propentofylline and caffeine].

The CNS effects of propentofylline and caffeine, methylxanthine derivatives, were compared. In mice, caffeine antagonized diazepam-induced muscle relaxation and the inhibitory effect of diazepam against pentylenetetrazole-induced convulsions, but propentofylline did not. In spinal cats, the dorsal root reflex potentials were inhibited by caffeine but not affected by propentofylline, and the monosynaptic reflex potentials were increased by propentofylline but not influenced by caffeine. The results indicate that propentofylline differs from caffeine in that it neither antagonizes diazepam nor affects the GABA system.

Animals↗
PubMed1988

Effects of pentobarbital and cyproheptadine on brain ischemia induced by bilateral occlusions of carotid arteries and vertebral arteries of second cervical vertebra in rats.

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.

Animals↗
PubMed1988

[Comparative study on the mutagenic activity of rat liver and bladder S9 by fluctuation test].

Mutagenicity of seven aromatic amines, two heterocyclic amines, two azo compounds and one polycyclic aromatic hydrocarbon was examined with a fluctuation test modified by Gatehouse. The test was performed by using Salmonella typhimurium TA98 in the presence of liver and bladder S9 from PCB pretreated rats. Seven out of 12 compounds showed mutagenic activities with liver S9 and seven with bladder S9. Benzidine, 3-methylcholanthrene and 2-acetylaminofluorene showed a negative response with bladder S9 but a positive response with liver S9. The mutagenicity of the seven compounds observed with bladder S9 had a lower sensitivity than with liver S9. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole showed mutagenic activity at lower concentrations than the other compounds which showed mutagenic activity either with bladder S9 or liver S9. Mutagenicity of 3-methylcholanthrene was observed at high concentration only in the presence of liver S9. The findings from the present study suggested that aromatic amines, heterocyclic amines and polycyclic aromatic hydrocarbons were more likely to be activated to strong mutagens with liver S9 than with bladder S9.

Amines↗
PubMed1988

[Mutagenicity of benzene metabolites by fluctuation test].

Mutagenicity of five benzene metabolites was examined by a fluctuation test modified by Gatehouse. The test was performed by using Salmonella typhimurium TA100 with or without a metabolic activation system. Catechol showed mutagenic activity with and without a metabolic activation system in the fluctuation test. Hydroxyhydroquinone, phenol, hydroquinone and p-benzoquinone were positive only with a metabolic activation system in this test. The Ames' plate method and preincubation method are widely used as a screening test for the mutagenic compounds. However, the fluctuation test is very useful in detecting mutagenic activity of chemicals which are negative in the Ames test though being a mutagen or carcinogen.

Animals↗
PubMed1988

A case of giant mediastinal leiomyoma with long-term survival.

A 67-year-old female was emergently admitted to our hospital because of severe dyspnea with cyanosis. One month before admission, she consulted a doctor and chest x-ray disclosed a huge tumor shadow occupying most of the left hemithorax. At that time, she did not complain of any particular symptoms except slight cough. Twelve days after admission, the patient lost consciousness and an emergency operation was performed. The tumor showed severe adhesion to the aorta and the lower lobe of the left lung, but not to the esophagus. After the operation, mechanical ventilation was necessary for 13 days to recover pulmonary function. Histological diagnosis was made as leiomyoma, which is rarely seen in the mediastinal region. At present, the patient survived 10 years without any symptom of recurrence. In this paper, the authors report a case of mediastinal leiomyoma which received an emergency operation and attained long term survival. Twelve similar cases reported in the past were also reviewed.

Aged↗
PubMed1988

Differential modulation of protein kinase C by bryostatin 1 and phorbol ester.

Bryostatin 1, a macrocyclic lactone, activated protein kinase C purified from mouse brain in a dose-dependent fashion to the same degree as phorbol 12-myristate 13-acetate (PMA). There was no significant difference in calcium and phosphatidylserine requirements for activation of protein kinase C between bryostatin 1 and PMA. We also found no significant difference in the inhibitory effect between staurosporine and H-7 known to be potent inhibitors of protein kinase C. These data suggest that bryostatin 1 and PMA activate protein kinase C in a similar way. We found, however, that negative modulation of protein kinase C with bryostatin 1 was weaker than that with PMA. The reason of this difference was unclear. It may possibly suggest that there is some difference in configuration of protein kinase C after binding between these activators.

Animals↗