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Biomedical subjects

T Takaoka

Publications and source records attributed to T Takaoka.

At least 55 records · Page 3Linked to original sources

High-efficiency transpeptidation catalysed by clostripain and electrostatic effects in substrate specificity.

Clostripain catalyses the transpeptidation between benzoylarginin ethyl ester and amino acid amides, oligopeptides, insulin A- and B-chains and tryptic peptides of myoglobin at millimolar substrate concentrations. The reactions proceed with temporary accumulation of the products, followed by hydrolytic decomposition. The yield was not affected significantly by the type of N-terminal amino acid, but was diminished markedly by the negative charges of the amine components. The yields for natural peptides were linearly related to the charge density of the peptides.

Acyltransferases↗

Postoperative infection prophylaxis for upper gastrointestinal tract surgery--a prospective and comparative randomized study of cefoxitin and ceftizoxime.

A prospective and randomized clinical study was conducted in order to compare cefoxitin (CFX) and ceftizoxime (CZX) as prophylactic antibiotics. Two hundred and three consecutive cases of elective upper gastrointestinal tract surgery, performed at our institute between January, 1983, and March, 1986, were entered in the trial. The patients were assigned randomly, before surgery, to the CFX or to the CZX group. Two grams of the assigned antibiotic was first administered during surgery and then continued at a dose of 1 gram, every 8 hrs for a total of 4 days. One patient was withdrawn from the study due to an allergic reaction. Both groups were comparable in sex, age, underlying disease, diagnosis, operation, and preoperative laboratory data. There were 18 infections related to the operation in the CFX group, while there were only 3 in the CZX group (p less than 0.001). The number of unrelated infections in each group was 6 and 6 respectively (NS). No special differences were found between the two groups regarding the kinds of microorganisms isolated, and no significant differences were seen in the adverse effects of either antibiotic. Our study demonstrated that ceftizoxime was more efficient than cefoxitin in preventing postoperative infection, following upper gastrointestinal tract surgery.

Adult↗

[Multidisciplinary treatment of head and neck cancer].

UNLABELLED: This presentation deals with multidisciplinary treatment of head and neck cancer, especially focusing on maxillary sinus carcinoma (MSC) and nasopharyngeal carcinoma (NPC). Since 1982, a new multidisciplinary treatment incorporating neo-adjuvant chemotherapy has been introduced in the treatment of MSC. The Neo-adjuvant chemotherapy includes cisplatin (CDDP) + peplomycin (PEP), adriamycin (ADR) analogs + CDDP + PEP, and CDDP +5-FU. Two courses of chemotherapy were given intraarterially with the interval of 2 weeks. Routinely, radiotherapy of 40 Gy by Linac was given to the primary tumor site, concomitantly combined with 5-FU intraarterial injections only during the first 10 days, 2 weeks after the end of chemotherapy. Additional treatment was performed according to the extent of the residual tumors. The 5-year survival rate for the 28 patients treated with this therapy was 55%. The 5-year survival rate by T classification was 100% for T2, 76% for T3 and 0% for T4 cases. The preservation rate of maxillo-facial structures and functions was 82%. Concerning NPC, neo-adjuvant chemotherapy included CDDP + PEP, ADR + CDDP + PEP and ADR + cyclophosphamide + PEP. Two courses of chemotherapy were performed, followed by radiotherapy of 60 Gy by Linac. Then intracavitary 60Co therapy was performed, followed by adjuvant chemoimmunotherapy. The 5-year survival rate for 21 patients treated with this therapy was 44%. CONCLUSIONS: (1) The 5-year survival rate was better for patients with MSC who were treated with multidisciplinary treatment incorporating intraarterial neo-adjuvant chemotherapy than that for patients who received other treatment so far. Furthermore, the highest preservation rate of maxillo-facial structures and functions was achieved in the neo-adjuvant chemotherapy group. However, survival rates for T4 cases were very poor, so another approach should be taken. (2) The 5-year survival rate was also better for patients with NPC who were given multidisciplinary treatment than for patients who received other treatment to date. However, there was no decrease of distant metastases, which we aimed initially, despite the introduction of neo-adjuvant chemotherapy.

Adult↗

A new approach to the modification of cell membrane glycosphingolipids: ganglioside composition of JTC-12 P3 cells altered by feeding with galactose as a sole carbohydrate source in protein- and lipid-free synthetic medium.

A significant difference in the glycosphingolipid composition of JTC-12 P3 cells established from monkey kidney tissue was observed when cells cultured in a protein- and lipid-free synthetic medium containing glucose (DM-160) as a sole carbohydrate source were transferred and cultured in the same medium containing galactose and pyruvic acid (DM-170) in place of glucose. In particular, the amounts of gangliosides GM3, GM2, and GD3 in the cells cultured in DM-170 were 5.3-, 17.8-, and more than 8-fold those in the cells cultured in DM-160, respectively, indicating that anabolism of gangliosides is greatly enhanced in cells cultured in the presence of galactose and pyruvic acid, as compared with cells cultured in the presence of glucose. In fact, after cultivation of cells in the medium with N-acetyl-D-[14C]mannosamine for 96 h, the radioactivity incorporated into the gangliosides of the cells in DM-170 was 10-fold that of the cells in DM-160. Among the gangliosides of the cells in DM-170, highly sialylated molecules such as GD3, GD1a, GD1b, and GT1b were preferentially labeled, indicating that the sialyltransferases responsible for the synthesis of gangliosides are significantly more activated in cells cultured in DM-170 than in DM-160. These observations reveal that the glycosphingolipid composition of the plasma membrane can be modified epigenetically under well-defined conditions and provide important clues for clarifying the roles of glycosphingolipids associated with particular cell functions.

Animals↗

Requirement of serum pretreatment for induction of alkaline phosphatase activity with prednisolone, butyrate, dibutyryl cyclic adenosine monophosphate and NaCl in human liver cells continuously cultured in serum-free medium.

A cell line (HuL-1) derived from normal fetal human liver was adapted to grow continuously in a modified Eagle's minimum essential medium without serum or hormones. The population doubling time of this adapted cell line (HuL-1-317) was about 72 h and the modal number of chromosomes was 54. The morphology of HuL-1-317 cells was round in the absence of serum, but at 37 degrees C with the addition of serum (1-10%), the cells flattened. HuL-1-317 cells had a low level of alkaline phosphatase activity. However the enzyme activity was slightly enhanced by the combination of prednisolone, butyrate, dibutyryl cyclic adenosine monophosphate and a hypertonic concentration of NaCl after 3 days of incubation at 37 degrees C. The increase in alkaline phosphatase activity with the four agents was further amplified dose-dependently by the pretreatment of the cells with serum. The stimulatory effect of the serum was evident at concentrations as low as 1%, and was maximal at 20%. The half life of the effect of serum on alkaline phosphatase induction was 48 h at 37 degrees C. Serum alone could not enhance the enzyme activity without the four agents. The present results indicate that serum contributes to the regulation of alkaline phosphatase induction by the combination of prednisolone, butyrate, dibutyryl cyclic adenosine monophosphate and NaCl in fetal human liver cells (HuL-1-317).

Alkaline Phosphatase↗

Secretion of a novel cell-adhesive protein distinct from fibronectin by mouse L.P3 cells growing in protein- and lipid-free synthetic medium.

Several cell lines growing in protein- and lipid-free synthetic medium secreted cell-adhesive protein(s) into the medium. The conditioned medium (CM) of one of these cell lines, mouse L.P3, showed the highest cell attachment-promoting activity (CPA) among them. Cell-adhesive protein(s) in the CM of L.P3 cells (L.P3-CM) were separated into two types by sequential affinity column chromatography employing gelatin-Sepharose 4B and heparin-Sepharose 4B. One was a gelatin- and heparin-binding cell-adhesive protein (GCP), and was identified as a cellular form of mouse fibronectin. The other was a gelatin-non-binding and heparin-binding cell-adhesive protein (GNCP). The CPA of GNCP preparation was effective for the cell-attachment and spreading of both epithelial and fibroblastic cells. The CPA of GNCP preparation was not blocked by the antiserum and scarcely inhibited in the presence of the synthetic cell attachment-promoting peptide Gly-Arg-Gly-Asp-Ser-Pro, a competitive inhibitor of fibronectin. This suggests that the structure of the cell-attachment site of GNCP is different from that of fibronectin. The GNCP preparation showed little cross-reactivity with anti-mouse laminin antiserum in enzyme-linked immunosorbent assay (ELISA). These results demonstrate the possibility that GNCP in L.P3-CM is a novel cell-adhesive protein distinct from fibronectin or laminin. The secretion of the two types of cell-adhesive proteins by L.P3 cells is discussed.

Animals↗

[Combined radiotherapy and chemotherapy for head and neck cancer].

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neoadjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary.

Animals↗

[Radical excision followed by reconstruction of recurrent cancers of the head and neck].

Various modalities of treatment for recurrent cancers of the head and neck were studied and discussed, focusing especially on radical excision followed by reconstruction. Thirty-two patients with recurrent cancer of the head and neck were given this treatment over a 12-year period. Pectoralis major myocutaneous flap was most commonly used for reconstruction, while free latissimus dorsi myocutaneous flap with microneurovascular anastomosis was used for total cheek defect after surgery for cancer of the maxillary sinus. Five-year survival was 62% in cases of radical excision followed by reconstruction. Simple resection of recurrent lesions was conducted in 36 cases and the 5-year survival was also 62%. Radical neck dissection was performed in 22 cases in which cervical node metastases developed after control of the primary tumor, and the 5-year survival was 52%. On the other hand, the 5-year survival was not obtained in cases treated with radiotherapy alone in this series, while the 5-year survival was only 1% in cases treated with chemotherapy alone. It was concluded that surgery was the most reliable treatment for recurrent cancers of the head and neck, and that radical excision followed by reconstruction played an important role as salvage surgery.

Adult↗

Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells.

Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E2 production by cultured porcine thyroid cells were examined. Both phorbol 12-myristate 13-acetate (PMA) and EGF stimulated prostaglandin E2 production by the cells in dose related fashion. PMA stimulated prostaglandin E2 production over fifty-fold with the dose of 10(-7) M compared with control. EGF (10(-7) M) also stimulated it about ten-fold. The ED50 values of PMA and EGF were respectively around 1 X 10(-9) M and 5 X 10(-10) M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E2 production from 1 to 24-h incubation. The release of radioactivity from [3H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells.

Animals↗

[Multimodality treatment of nasopharyngeal carcinoma].

In the treatment of nasopharyngeal carcinoma (NPC), radiation has been the treatment of choice, because it is effective for locoregional disease. However, the results of radiotherapy for NPC have revealed that local relapse and/or distant metastases occur frequently, and consequently the five-year survival rate is as low as around 30%. Since 1982, we have adopted chemotherapy initially applied prior to radiotherapy (= pre-radiation chemotherapy) for the treatment of NPC in order to achieve better results. The chemotherapy mainly consists of a combination of cisplatin and peplomycin. Twenty-one previously untreated patients with NPC were evaluable. Three complete and fifteen partial remissions were achieved, with an 86% response rate to the chemotherapy. The treatment involving a combination of pre-radiation chemotherapy and radiotherapy resulted in local relapse in one patient and distant metastases in two patients with an 87.5% survival rate according to the Kaplan-Meier method. Immunotherapy is also indispensable in the treatment of NPC. Our present multimodality treatment for NPC consists of a combination of pre-radiation chemotherapy and radiotherapy followed by long-term administration of a biologics such as OK-432.

Adolescent↗

[Multidisciplinary treatment of carcinoma of the oropharynx].

From 1963 through 1986, we examined 91 patients with carcinoma of the oropharynx. Of these 91 patients, the primary treatment modality was chosen for 75 patients. The patients were divided into 2 groups according to the periods of treatment. In group I (1963-1973), 33% of the patients were applied combined radiotherapy and chemotherapy, and 28% chemotherapy followed by surgery as their initial treatment. In group II (1974-1986), 65% of the patients were applied combined radiotherapy and chemotherapy, and 21% a multimodal treatment consisting of radiotherapy combined with chemotherapy followed by composite resection. Five-year survival rate was 36% in group I and 51% in group II, which indicated a progress in the treatment of carcinoma of the oropharynx. The role of surgical treatment for carcinoma of the oropharynx was discussed. It appears that composite resection and reconstructive surgery produced a great benefit in the treatment of residual diseases after radiotherapy or recurrent diseases. Then our new treatment modality incorporating neo-adjuvant chemotherapy was presented. The literatures in terms of neo-adjuvant chemotherapy were reviewed.

Adult↗

Unsaturated fatty acids in mammalian cell strains cultured for more than 10 years in serum-free synthetic media.

In cultured cells, essential lipids are usually supplied by the serum added to the culture medium. However, in a serum-free medium, essential lipids would need to be synthesized by the cells. Cell strains derived from kidney, spleen, uterine carcinoma and fibroblasts were cultured in serum-free synthetic media for more than 10 years and their fatty acids were analyzed capillary column gas-liquid-chromatography. The following conclusions were drawn: 1. Polyunsaturated fatty acids were not detected. Thus, prostaglandins are not appear to be essential for initiation of DNA synthesis in these cells. 2. A compensatory increase of the content of monounsaturated fatty acids was detected. 3. A large difference in vaccenic/oleic acid ratio was found among several strains of cells, but the ratio does not reflect that of the original tissues.

Animals↗

Cinemicrography of human erythroblasts--direct measurement of generation time and delineation of their pedigrees.

To clarify the mode of erythropoiesis, the in vitro proliferation of single human erythroblasts was recorded continuously for 80 hours by time-lapse, phase-contrast cinemicrography. Progenies from single erythroblasts were followed, their pedigrees were delineated, and their generation times were measured by counting the frames of the film. In one erythroblast pedigree, a daughter cell continued to divide three times to yield eight smaller erythroblasts; another daughter cell yielded four progenies, three of which abruptly lost most of their cytoplasm and became immobile. The generation time ranged from 15.8-30.0 hours (mean +/- SD: 23.3 +/- 4.8 hours), which corresponded to generation times calculated from in vivo data, such as the mitotic index, isotope labeling, or red cell turnover. Paired daughter cells showed very similar generation times. During succeeding mitoses, erythroblast size and nucleus/cytoplasma ratio decreased, cytoplasm darkened, and cell movement became more prominent. These studies on clonal cell proliferation using cinemicrography provide considerable information on the mechanism of hemopoiesis.

Cells, Cultured↗

Combination chemotherapy with cisplatin and peplomycin in squamous cell carcinoma of the head and neck.

Ninety-three patients with head and neck cancer were treated with combined cisplatin-peplomycin chemotherapy (CP therapy). Cisplatin (CDDP) 50 mg/m2 i.v. (intravenous) or i.a. (intraarterial) over 2 hr was given with hydration and mannitol diuresis on day 1. From day 2 through day 6, peplomycin (PEP) 5 mg/day was administered by 5-hr i.v. or i.a. infusion, or 24-hr continuous hypodermic injection. Of 85 who were evaluable, there were 22 complete responses or CR (26%) and 36 partial responses or PR (42%), with an overall response rate of 68%. Concerning of the route of administration, i.a. infusion obtained the higher CR and overall response rates than i.v. infusion. Effectiveness was clearly greater in previously untreated cases than in cases that had received some previous therapeutic modality. Looking at response in relation to the number of the courses, at least 2 courses of CP therapy are required. Side effects were recognized in 68 out of 87 evaluable cases (78%). Nausea and vomiting were the most common (62%). Renal toxicity was observed in 24% and was mostly transient. From the above results, it is considered that the CP therapy is effective, not only for the palliative treatment of advanced and recurrent cancer of the head and neck, but also as neo-adjuvant chemotherapy of stage III and IV cases.

Adult↗