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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 847 records · Page 47Linked to original sources

Phospholipase C activity in egg yolk sac of Japanese quail during embryonic development.

1. The amount of lipid decreased markedly at the later stage of embryonic development, coinciding with the remarkable decrease in yolk weight. 2. Phospholipase C activity in the yolk sac appeared on the 6th day of incubation and increased markedly as incubation proceeded. 3. The enzyme showed its optimum activity at pH 9.5 and at 40 degrees C. 4. The activity was enhanced 2-fold by 20 mM CaCl2 and by 40% by 4 mM deoxycholate but inhibited by 2 mM ZnCl2 and CuSO4.

Animals↗

Cytochemical studies of LDH isoenzymes in experimental bladder tumors.

Cytomorphologic or histologic changes in the tumorigenic process of the urinary bladder epithelium and the corresponding cytochemical alteration of lactate dehydrogenase (LDH) isoenzymes were studied in rats given a bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). All the rats given BBN as drinking water for about 8 weeks showed hyperplasia of the bladder epithelium and all the rats given BBN for about 16 weeks developed papillomas. Carcinomas were noticed in 81 per cent of the animals given the carcinogen for 20 weeks. Urinary cytology showed no malignant cells before the 12th week but detected exfoliated malignant cells in 14 per cent of the rats given the carcinogen for 16 weeks. Malignant cells were found in 57 and 95 per cent of animals sacrificed at the 20th and 24th week respectively. Alteration of LDH isoenzyme pattern of cell extracts from the bladder epithelium that is characterized by shift to LDH4 and LDH5 from the preponderance of LDH1 and LDH2 in normal epithelium preceded the morphologic change; it appeared as early as the 8th week. A reversion of M/H ratio of the isoenzyme pattern could be proved cytochemically by means of urea inhibition that inactivates the LDH M-subunit.

Animals↗

Transformation of Bacillus stearothermophilus with plasmid DNA and characterization of shuttle vector plasmids between Bacillus stearothermophilus and Bacillus subtilis.

A thermophilic bacterium Bacillus stearothermophilus IFO 12550 (ATCC 12980) was transformed with each of the following plasmids, pUB110 (kanamycin resistance, Kmr), pTB19 (Kmr and tetracycline resistance [Tcr]), and its derivative pTB90 (Kmr Tcr), by the protoplast procedure in the presence of polyethylene glycol at 48 degrees C. The transformation frequencies per regenerant for pUB110, pTB19, and pTB90 were 5.9 x 10(-3), 5.5 x 10(-3), and 2.0 x 10(-1), respectively. Among these plasmids, pTB90 was newly derived, and the restriction endonuclease cleavage map was constructed. When tetracycline (5 micrograms/ml) was added into the culture medium, the copy number of pTB90 in B. stearothermophilus was about fourfold higher than that when kanamycin (5 micrograms/ml) was added instead of tetracycline. Bacillus subtilis could also be transformed with the plasmids extracted from B. stearothermophilus and vice versa. Accordingly, pUB110, pTB19, and pTB90 served as shuttle vectors between B. stearothermophilus and B. subtilis. The requirements for replication of pTB19 in B. subtilis and B. stearothermophilus appear to be different, because some deletion plasmids (pTB51, pTB52, and pTB53) derived from pTB19 could replicate only in B. subtilis, whereas another deletion plasmid pTB92 could replicate solely in B. stearothermophilus. Plasmids pTB19 and pTB90 could be maintained and expressed in B. stearothermophilus up to 65 degrees C, whereas the expression of pUB110 in the same strain was up to 55 degrees C.

Bacillus subtilis↗

Cyto- and myeloarchitectural studies on the lateral tuberal nucleus in simian Callithricidae and Prosimiae.

The cytoarchitecture and myeloarchitecture of the lateral tuberal nucleus (LTN) were examined in five species of Callithricidae and in 21 species of Prosimiae. In this study, the LTN of the Callithricidae is described in detail and the LTN of prosimian Lemuriformes is clearly demonstrated for the first time. The LTN could not be detected in other prosimians, Lorisiformes, Tarsiformes and Tupaiiformes. In coronal sections, the LTN of Callithricidae is a round nucleus embedded within the longitudinal fiber bundles in the lateral hypothalamic area. The cytological characteristics and the rostracaudal extent of the nucleus are the same as in the LTN of higher primates and man. In prosimian Lemuriformes (Daubentonia madagascariensis, all Indrioidea examined and some Lemuroidea), the LTN is similar to that of the Callithricidae, although it is smaller and less prominent.

Animals↗

Proteolytic enzymes and gonadal hormones of the ovarian follicle wall during ovulation in the domestic fowl (Gallus domesticus).

There were no significant changes in the activities of collagenase, acid and neutral protease up to ovulation. Neutral protease activity increased significantly in the post-ovulatory follicle obtained immediately after ovulation. Acid protease and collagenase showed an increasing activity with time after ovulation. The progesterone concentration of the follicle wall rose 3 h before ovulation, peaked 1 h before ovulation and remained high until ovulation. Plasma progesterone values were high but decreased before those in the follicle. Follicular progesterone concentrations decreased markedly soon after rupture, but oestradiol values then increased.

Animals↗

Motor endplate cholinesterase in human skeletal muscle.

The activity and properties of cholinesterase (ChE) of the motor endplate and its fractions were studied in isolated human skeletal muscle. This preparation was used since the ChE activity of the membrane preparation was localized only in the motor endplate. The endplate ChE was stable in the isolated membrane for 4 weeks at 4 degrees C. The specific activity of the extracted ChE of human muscle membrane was 29.6% higher than that of the original membrane. Studies with specific substrates and ChE inhibitors indicated that most of the ChE of human muscle membrane and its fractions was acetylcholinesterase, and that the minor component was pseudocholinesterase. A Michaelis-Menten constant of 3.82 mM was estimated in the endplate ChE, and 0.88 mM in the extracted ChE of the endplate. The extracted human endplate ChE was separated into three fractions by Sephadex G-200 chromatography, and into two fractions by acrylamide gel electrophoresis.

Acetylcholinesterase↗

Inhibition of human motor endplate cholinesterase by anticholinesterase compounds.

The inhibition of human motor endplate cholinesterase by anticholinesterase compounds was studied using isolated muscle membrane preparation. Ambenonium was most potent, and edrophonium was least potent in inhibiting motor endplate cholinesterase. The slope of the regression line for inhibition of motor endplate cholinesterase was greatest for ambenonium, and smallest for neostigmine and edrophonium. These compounds were less potent inhibitors of plasma cholinesterase. Ambenonium was more specific, and other compounds were less specific inhibitors of motor endplate cholinesterase. In myasthenic patients, these compounds produced adequate inhibition of motor endplate cholinesterase even in the presence of relatively mild plasma cholinesterase inhibition.

Cholinesterase Inhibitors↗

Cholinesterase activity of the motor endplate in rat intercostal muscle.

Cholinesterase activity was localized solely in the motor endplate of the membrane in rate intercostal muscle. The diameter of rat motor endplates in the gradient dimension was 31.9 micrometers. The cholinesterase activity per unit protein of the soluble fraction of rat muscle membrane was 35.6% higher than the original membrane. From studies with specific substrates and cholinesterase inhibitors, the cholinesterase activity of rat muscle membrane and its soluble fraction consists of more than 90% acetylcholinesterase and less than 10% pseudocholinesterase.

Animals↗

Cholinesterase of skeletal muscle and its subcellular components.

The cholinesterase activity of skeletal muscle and its subcellular components, including motor endplates, was compared chemically in human, mouse and rat. The total cholinesterase activity of muscle per unit protein was in the descending order of human, mouse and rat. Cholinesterase was present in all subcellular components fractionated by differential centrifugation, and was greatest in the microsome fraction followed, in descending order, by the mitochondria, myofibril, and supernatant fractions. Each of these fractions had greater cholinesterase activity in human muscle than in mouse muscle, and in mouse muscle than in rat muscle. The ratio of the activity of the microsome fraction to the activity of muscle homogenate was 11.1 in human, 4.6 in mouse and 3.4 in rat. Because of its relatively greater proportion, the myofibril fraction seems to contribute most to the total cholinesterase activity of muscle. Muscle membrane contained high cholinesterase activity of motor endplates, and the activity was greater than the activity of the microsome fraction in rat. Cholinesterase activity per motor endplate was in the descending order of rat, human and mouse, and the variation was less than the variation in the total muscle cholinesterase activity among these species.

Cholinesterases↗

[Treatment of elderly patients with hepatocellular carcinomas with mitomycin C and 5-fluorouracil].

Twenty elderly patients with hepatocellular carcinoma were treated with 5-fluorouracil (5-FU) at a daily dose of 200-300 mg per os, and with a combination of 0.3-0.35 mg/kg of mitomycin C (MMC) iv on day 1 and 8-10 mg/kg of 5-FU iv daily starting on day 1 for 5 consecutive days, repeating at 4 week intervals. According to the Koyama-Saito's criteria, there was no response in the 5-FU treatment, while a 20% (2/10) of response rate (2 partial responses) was obtained in the combination regimen. The durations of response in 2 partial responses were 7.3 and 4.0 months, respectively. The median survival with MMC and 5-FU was 3.4 months compared with 1.5 months with 5-FU alone, and the survival was correlated with tumor response. The combination produced more gastrointestinal toxicities and myelotoxicities compared to a single drug, but they were well tolerated. These results support the superiority of the combination of MMC and 5-FU over 5-FU alone in the treatment of elderly hepatocellular carcinoma.

Aged↗

[Moderate dose methotrexate with citrovorum factor rescue therapy in the treatment of head and neck cancer].

A clinical trial of moderate dose methotrexate (MTX)-CF rescue was conducted in 12 institutions. Thirty-seven patients with head and neck carcinoma entered this trial, of which 32 were evaluable. MTX was administered 350 mg/m2 (500 mg/body) by i.v. drip over 6 hours. Three hours after completion of MTX infusion, CF rescue was started. There was no complete response in 32 patients. Nine patients showed partial response with the response rate of 28%. The response rates were 21% for the group of patients treated previously, and 75% for the group untreated previously. MTX concentration in plasma was determined at 6, 24, 48 and 72 hours after the initiation of MTX infusion, and the assay results revealed a safe range. GI disturbances were seen at the rates of 11 to 38%. Bone marrow suppression was mild and no renal toxicity was observed. We concluded that the moderate dose MTX-CF rescue therapy was useful for head and neck carcinoma. As a next step, we are planning to conduct a clinical trial of high-dose MTX.

Adult↗

[Pharmacokinetics of cis-dichlorodiammineplatinum (II)].

The pharmacokinetics of cis-dichlorodiammineplatinum (II) have been studied in 8 patients with advanced head and neck cancer. Plasma and urine platinum concentration were determined by atomic absorption spectrometry. Three different infusion methods were compared: 1) 24 hour continuous i.v. infusion; 2) 2 hour i. a. infusion and; 3) equally divided 5 daily i. a. infusion. In 4 patients receiving the 24 hour infusion, plasma platinum level had declined with second peak, which appeared 0.5-6 hours after end of infusion. Slow phase of half-life time of total platinum was very long ranged 86-197 hours. Non-protein bound platinum was rapidly cleared below the measurable level within 2 hours. At the end of 24 hour infusion, about 90% of plasma platinum was bound with plasma proteins. In a case of 2 hour infusion only one-half of platinum was bound. A patient receiving 2 hour infusion exhibited biphasic clearance of total platinum. In the 3 patients receiving divided daily infusion platinum concentration increased day by day. The level at 5th day was about 3 times higher than that of level at first day. In a patient with renal dysfunction slow phase half-life time prolonged markedly; however, his accumulative urinary excretion in first 24 hours did not diminish as compared with the patients with normal renal function.

Adenocarcinoma↗

[A study of combination chemotherapy with cis-diamminedichloroplatinum for advanced genitourinary carcinoma].

The patients with advanced testicular tumors and bladder carcinoma were treated by combination chemotherapies including cis-diamminedichloroplatinum. Four patients with advanced testicular tumors were treated with a combination chemotherapy, consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin or pepleomycin according to Einhorn's regimen. Three patients with advanced bladder carcinoma were treated with a combination chemotherapy consisting of cis-diamminedichloroplatinum, cyclophosphamide, and adriamycin according to Yagoda's regimen. These chemotherapy regimens produced 25% complete and 75% partial responses in testicular tumors and 100% of no change in bladder carcinoma. Although an overall response rate of three patients with bladder carcinoma was 0%, one patient was plateaustable for more than three months. We believe that the combination chemotherapy including cis-diamminedichloroplatinum is promising in the management of patients with advanced testicular tumors or bladder carcinoma.

Adolescent↗

[Inhibitory effect of antineoplastic agents on human cholinesterases].

Human motor endplate acetylcholinesterase was inhibited in vitro by alkylating antineoplastic agents, most strongly by mechlorethamine, followed by DTIC, ACNU, cyclophosphamide and ifosfamide. Eleven other antineoplastic agents did not inhibit the enzyme substantially nor interfered with cholinesterase measurement. Cyclophosphamide and mechlorethamine inhibited human plasma pseudocholinesterase most strongly, followed by thiotepa, ACNU, DTIC, ifosfamide and BCNU. Mechlorethamine, ACNU and ifosfamide inhibited the motor endplate and plasma cholinesterase practically equally, DTIC inhibited motor endplate cholinesterase more strongly, while cyclophosphamide was a more selective inhibitor of plasma cholinesterase. Inhibition of human red blood cell acetylcholinesterase was identical to that of motor endplate acetylcholinesterase; therefore, red cells would be a preferable indicator in monitoring cholinesterase inhibition by antineoplastic agents.

Acetylcholinesterase↗