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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 847 records · Page 47Linked to original sources

An aspartic proteinase of erythrocyte membranes. Proposed mechanism for activation and further molecular properties.

An aspartic proteinase associated with human erythrocyte membranes was shown to be responsible for autodegradation of the membrane proteins at pH values below 5.0. When the membrane was treated with phospholipase C (Bacillus cereus) or trypsin, and simply heated at 40 degrees C, the membrane-bound latent enzyme was activated, with this being accompanied by dissociation of the enzyme from the membrane. Divalent cations such as Ca2+ and Mg2+ had an inhibitory effect on the dissociation of the membrane-bound enzyme when preincubated with the membrane. The results indicate that the activation of the membrane-bound enzyme is due probably to perturbation of the normal membrane organization. When the purified enzyme was treated with 10mM 2-mercaptoethanol at 37 degrees C, the enzyme (79-82 kDa) was converted to a low molecular mass form with 42-47 kDa without any loss of activity. With the exception of treatments by thiol-reducing reagents, no conversion was observed by a variety of procedures such as exposure to 1 M NaCl and 0.1% sodium dodecyl sulfate, treatment with trypsin and incubation at pH 3.5 for up to 15 h, indicating that the enzyme consists of two polypeptide chains held together by disulfide bonds.

Cathepsin E↗

Intraoperative chemotherapy with carbon particles adsorbing mitomycin C for gastric cancer with peritoneal dissemination in rabbits.

A new dosage form of activated carbon particles adsorbing mitomycin C (MMC-CH) was studied for its therapeutic effects on peritoneal dissemination in both animal experiments and preliminary clinical trials. Rabbits with peritoneal dissemination induced by intraperitoneal transplanted VX2 carcinoma were used as experimental models. Seven days after intraperitoneal transplantation of VX2 carcinoma, mitomycin C at 1 mg/kg in the form of MMC-CH or at 0.185 mg/kg in the form of mitomycin C aqueous solution was given intraperitoneally. The two doses were equal in toxicity. MMC-CH extended survival time statistically significantly longer than did mitomycin C aqueous solution. Preliminary clinical trial with MMC-CH has been made in eight patients with gastric cancer and peritoneal dissemination, with no control group. MMC-CH, 60 to 100 mg/person, was given intraperitoneally before the surgical wound was closed. Patients were observed for more than 1 year. Five of the eight patients survived more than 1 year, and the mean survival time was 13.9 months, whereas in the patients treated previously without MMC-CH the 1-year survival rate was 17% and the mean survival time was 6.5 months. Side effects were temporary and tolerable.

Adsorption↗

[Frequent occurrences of an enlarged submandibular gland following interstitial irradiation therapy in patients with cancer of the tongue].

A submandibular gland enlargement produces complications in the diagnosis of a nodal metastasis during the follow-up period in patients who have been given interstitial irradiation therapy for their oral cancers. Thus, a retrospective study has been made of the records of such affected patients, to accumulate knowledge regarding the frequency, the time of appearance, and the symptoms leading to the gland enlargement. Among 155 cases of squamous cell carcinoma of the tongue, 73 cases were selected for this study by the following criteria: (1) the patients were free of metastatic adenopathy, (2) they had been interstitially irradiated, and, (3) they were followed-up without surgical treatment for more than 6 months after the radiotherapy. Gland enlargement was found to have developed in 70% of the studied patients, that is, in 49 of the 73 cases within 9 months after radiotherapy.

Brachytherapy↗

[Bovine cervical mucus as a substitute of human cervical mucus].

The sperm penetration test (SPT) in cervical mucus (CM) is an important test in screening for sperm-CM incompatibility. For a routine SPT, a sufficient amount of preovulatory CM is necessary, but the amount of human CM is often inadequate. We examined estrous bovine CM as a substitute for human CM in the SPT. Preovulatory human CM and estrous bovine CM were collected and stored frozen at -20 degrees C until use. After being thawed at room temperature, the two CM samples were compared as to their pH, spinnbarkeit and ferning patterns, and it was found that they are quite similar. In Kremer's method of SPT, sperm penetration distance, density and motility were similar in human and bovine CM for 12 hours, but thereafter sperm motility became much lower in bovine CM than in human CM. The results of SPT with spermatozoa from patients with oligozoospermia were quite similar in both CMs. When spermatozoa pretreated with antisperm antibody were used for SPT, sperm penetration was completely blocked in human CM, but no inhibition was seen in bovine CM. From these results, we conclude that bovine CM can be substituted for human CM for some, but not all, purposes.

Animals↗

Influence of cadmium on the metabolism of vitamin D3 in rats.

In order to obtain further information on the effects of cadmium (Cd) on the mechanism of activation of vitamin D3 in the kidney, the serum concentrations of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were determined by radioimmunoassay techniques. The serum concentration of 1,25(OH)2D3 in Cd-exposed rats was always higher than that in control rats. The concentrations of serum 1,25(OH)2D3 in parathyroidectomized rats (PTX), both in the control and in the Cd-exposed groups, were markedly lower than those in non-PTX rats. On the other hand, the concentration of serum 24,25(OH)2D3 in Cd-exposed rats was less than that in control rats. In other words, the pathway from secretion of parathyroid hormone (PTH) to synthesis of 1,25(OH)2D3 or 24,25(OH)2D3 was normal, but the pathway from stimulation of PTH to secretion of PTH was abnormal. These results suggest that rats exposed to Cd for 90 days were in a state of either deficiency of 1,25(OH)2D3 or excess secretion of parathyroid hormone. Although hypophosphatemia occurred in the Cd-exposed rats, the 1,25(OH)2D3 serum level in rats was not increased by PTX. On the basis of these results, it is suggested that hypophosphatemia occurring after the exposure of rats to Cd is a secondary hypophosphatemia.

24,25-Dihydroxyvitamin D 3↗

Chemotherapy for carcinomatous peritonitis and pleuritis with MMC-CH, mitomycin C adsorbed on activated carbon particles. Clinical trials.

A new drug dosage form comprising activated carbon particles adsorbing mitomycin C (MMC-CH) is designed to slowly release its components, and has affinity for the tumor surface and lymph nodes and a tendency to stay long in the local portion. The therapeutic index of MMC-CH in experimental carcinomatous peritonitis is 3.1 times as high as that of MMC-solution. In clinical experiments 81 patients with carcinomatous effusions were administered with MMC-CH (2.0-2.4 mg/kg in terms of MMC) in bolus intracavitarily. Fifty-one patients responded well to the MMC-CH therapy. Nineteen patients were alive for more than 6 months. The responders showed marked improvement in subjective symptoms, and 26 patients became dischargeable from hospital. Bone marrow suppression and peritoneal irritation were main adverse effects, but the symptoms were temporary and not so serious in spite of a high dose of MMC.

Charcoal↗

A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis).

We describe a new low density lipoprotein (LDL) apheresis system using dextran sulfate cellulose column in an automated column regenerating unit (LDL continuous apheresis). Two columns containing 150 ml of dextran sulfate cellulose were used, and the whole extracorporeal circulation was about 400 ml in volume. After 600 ml of plasma was adsorbed into the first column, the second column was used as an adsorbent and meanwhile the first column was regenerated. Thus, the 2 columns were used alternately without losing the potency of the columns. As the apparatus was automatically controlled by a computerized unit, no extra manipulation is necessary compared with the conventional single-column method. By treating 4-5 liters of plasma, non-high density lipoprotein (HDL)-cholesterol levels decreased by 63-71%, and HDL-cholesterol levels remained unchanged. Thus, this new method of LDL apheresis can safely reduce LDL-cholesterol to any desired level and will be applicable for the treatment of child and adult family hypercholesterolemic patients with severe coronary heart disease.

Adult↗

Effects of CS-514 on serum lipoprotein lipid and apolipoprotein levels in patients with familial hypercholesterolemia.

Effects of CS-514, a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on serum lipoprotein lipid and apolipoprotein levels were studied in 13 heterozygous patients with familial hypercholesterolemia. Treatment with 10 mg of CS-514 twice daily reduced total serum cholesterol, low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) cholesterol levels by 25%, 33%, and 33%, respectively, and increased high-density lipoprotein (HDL) cholesterol levels by 15%. Apolipoprotein B, E, and C-II levels decreased by 24%, 20%, and 19%, and apolipoproteins A-I and A-II levels increased by 10% and 7%, respectively. One patient showed abnormally high levels of SGOT, SGPT, and serum alkaline phosphatase, which returned to normal levels immediately after the cessation of CS-514. No other adverse effects were observed. Thus, CS-514 reduces atherogenic lipoproteins and apolipoprotein B, and increases HDL and apolipoprotein A-I and A-II, and appears to be a useful drug for heterozygous familial hypercholesterolemia.

Adult↗

The role of radiotherapy in the management of adenoid cystic carcinoma of the head and neck.

Sixty-eight patients with adenoid cystic carcinoma (ACC) of the head and neck treated by radiation with or without surgery were reviewed. The tumors were located in the major salivary glands in 15 patients and in the minor glands of various sites, mostly in the palate and/or upper gum, in 53. The local control rate was naturally better in the patients with elective postoperative radiation and those with recurrent disease who underwent radiation after repeated surgery for the purpose of tumor reduction than in patients with residual and/or inoperable tumors. For localized tumors in the oral cavity or maxillary sinus, local control was excellent using brachytherapy or "trimodal" combined therapy (radiation, drugs, and minor surgery). The effectiveness of radiation seemed to be more significantly related to the size of the tumor than the dose of radiation. The prognosis of the patients with a predominantly "solid" histologic pattern was apparently worse and presented fulminating progression of the disease. Among patients with a histologically typical cribriform pattern and/or undetermined pattern, although distant metastasis developed frequently, the majority survived a relatively long period without functional or cosmetic disturbance to their normal activities associated with slow progression of the disease. In minor gland tumors, as long as the lesion was localized and a solid histologic pattern was unlikely, radical radiation could be considered an effective choice with the advantage of enhancing the quality of life for the patients.

Adolescent↗