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Biomedical subjects

T Ohtsubo

Publications and source records attributed to T Ohtsubo.

87 records · Page 5Linked to original sources

[Biological basis of thermochemotherapy].

Interactive effects of combined treatment with hyperthermia and chemotherapeutic agents or chemical substances were interpreted in the experimental aspects of medical sciences. It was also interpreted how a physiological circumferential conditions in vivo influenced on thermosensitivities of cells, tissues or individuals. Among the physiological conditions, hypoxia and insufficient nutrition apparently enhance thermosensitivity while reduce radiosensitivity. Interactive effects in combined treatments with hyperthermia and alkylating agents varies among the alkylating agent adopted. DNA strand scission by alkylating agent is increased and repair of the DNA damage is suppressed in combination with hyperthermia. Almost all the antimetabolites and botanic alkaloids are reported to show no appreciable interactive effect in combination with hyperthermia. However, a sort of derivatives of mitotic toxins interacts with hyperthermia (unpublished data). Effects of anticancer antibiotics vary due to the variety of the mechanism of action of the antibiotics. Therefore, interactive effects of these antibiotics with hyperthermia also vary among the antibiotics. Most marked interaction with hyperthermia was shown in Mitomycin C, while the cell killing effect of Actinomycin D itself was reduced reportedly by the combined hyperthermia. Further development in thermophysiology may perform an extent of elevation in human whole body temperature. It has been considered internal heating may be more efficient than external heating for the hyperthermia alone. In the other hand, local heating can chemosensitize within the localized heated area where the blood concentration of anticancer drug is even, although variety of intervention could be devised to localize anticancer drug distribution. Variety of heating modalities and the apparatus would be developed which contribute for further interdisciplinary oncotherapy in near future.

Antineoplastic Agents↗

Chemosensitivity of head and neck cancer with the rapid thymidine incorporation assay and its clinical application.

The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%.

Aged↗

[A report of a transsphenoidal operation during pregnancy for a pituitary adenoma].

A 29-year old female, in her second pregnancy, complained of headache, nausea, vomiting and left blurred vision. In spite of improvement of these symptoms in the second postpartum, she complained of recurrent symptoms in her third pregnancy. CT and MRI showed a pituitary adenoma with hematoma. It was totally removed using the transsphenoidal approach during pregnancy at 8 months. The histological examination revealed that the tumor was an acidophilic adenoma with a hemorrhagic change. A healthy baby was born at the full term after the operation. Our transsphenoidal operation during pregnancy was only the second such attempt reported in our collected literature. The management of the pituitary tumor during pregnancy is discussed.

Adenoma↗

[Cellular thermosensitivity].

(1) modes of expression of thermosensitivity and theoretical interpretation of thermal dose, (2) differential thermosensitivities between strains of cells and the possible correlation to heat shock proteins and their syntheses, (3) cell phase responses to hyperthermia, (4) low hyperthermia and the induction of thermotolerance, (5) comparative thermosensitivities at the temperatures between below and above 42.5 degrees C -43 degrees C, (6) Arrhenius plot and mean cellular lethal heating periods, (7) step-up heating and the thermotolerance induction, (8) step-down heating and the thermoenhancement, (9) fractionated high hyperthermia and the thermotolerance induction and (10) modification of thermosensitivity by chemical substance including anticancer drugs; are compactly reviewed mainly on cell level.

Cell Cycle↗

Effect of acidic environment and p53 on apoptosis induction by hyperthermia.

The effect of environmental acidity on the induction of apoptosis by heat was investigated. Human colorectal tumour RKO.C cells, carrying wild-type p53 and isogenic RC10.1 cells deficient in p53, were heated at 42.0 degrees C for 1 h in pH 7.5 or pH 6.6 medium and the apoptosis was assessed based on the flow cytometic determination of DNA content, DNA fragmentation, and PARP cleavage. The degree of apoptosis after heating in pH6.6 medium was greater than that in pH 7.5 medium in both RKO.C cells and RC10.1 cells. When heated in the same pH medium, more apoptosis occurred in the RC10.1 cells than in the RKO.C cells. Heating increased the expression of p53 protein and p21 protein markedly in RKO.C cells and slightly in RC10.1 cells. Expression of these proteins was slightly greater in pH 7.5 medium than in pH 6.6 medium. The expressions of Bax protein and Bcl-2 protein, which are known to control apoptosis, were not altered by heating. It was concluded that an acidic environment enhances heat-induced apoptosis. It was also concluded that heat-induced apoptosis is lessened by p53 and that Bcl-2 and Bax are not involved in the induction of apoptosis by hyperthermia.

Apoptosis↗

Platysma myocutaneous flap including the external jugular vein with special reference to neck dissection.

Although platysma myocutaneous flap (PTMCF) is suitable for a small intraoral defect, combination with neck dissection (ND) decreases the viability. Therefore, a version of PTMCF was devised to increase the viability. This version consists of three points: preservation of the external jugular vein (EJV), preservation of the facial artery after skeletonization from the submandibular gland, and a new incision around the flap. This procedure was applied to 21 patients with intraoral cancer. All 21 patients underwent some kind of ND. The average viable area of transferred skin was 80%. This rate was significantly better than that for 46 previous cases using Farr's modification with ND, in which the facial artery was divided. Viability of the flaps was analyzed by the vessels preserved, especially by EJV. ND is not a contraindication with this version.

Humans↗

Implications of endoscopic endonasal surgery for the treatment of postoperative maxillary mucoceles.

Recently, endoscopic endonasal surgery has been widely used to treat chronic sinusitis with good results being reported by many investigators. Endoscopic endonasal surgery is a technique available not only for chronic sinusitis but also for other sinus diseases including postoperative maxillary mucoceles. In this report, the indications and limitations of endoscopic endonasal surgery for the treatment of postoperative maxillary mucoceles are discussed based on our experience treating 26 such mucoceles at our clinic. The indications for endoscopic endonasal surgery include mucoceles in close contact with the lateral wall of the inferior nasal meatus and those mucoceles that can be widely opened to the middle nasal meatus. The following cases could not be treated by endoscopic endonasal surgery: mucoceles that were localized in areas distant from the nasal cavity, mucoceles in which the lateral wall of the inferior nasal meatus was bony and intensely thickened, and mucoceles that could not be sufficiently opened to the middle nasal meatus.

Adult↗

Intraoperative identification of regenerated chorda tympani nerve and its relationship to recovered taste function.

This study demonstrated a simple method of repairing the severed chorda tympani nerve and a method of intraoperative identification of regenerated nerves, and evaluated taste function of regenerated nerves. Seven patients who underwent staged tympanoplasty and whose chorda tympani nerve was severed during primary surgery were evaluated. When the chorda tympani nerve was severed during primary surgery, proximal and distal stumps were anastomosed or approximated almost in the original position and fixed with fibrin glue on the temporal muscle fascia used to reconstruct the eardrum by the underlay method. During primary surgery, end-to-end anastomosis was possible in 3 patients but nerve gap defects remained in the other 4 patients. In all 7 patients, regenerated nerves were identified during secondary surgery not in the tympanic cavity but in the submucosal layer of the previously reconstructed eardrum. In all patients, complete or incomplete recovery of taste perception was observed by both the filter paper disk method and electrogustometry, suggesting that the regenerated nerves had actual taste function. From these results, it was concluded that the severed chorda tympani nerve could regenerate in the reconstructed eardrum even if nerve gap defects remained between the proximal and distal cut ends, when repair or approximation of the nerve was properly completed.

Adolescent↗

In vitro effect of hyperthermia on chemoenhancement and uptake of cisplatin in human pharyngeal carcinoma KB cells.

The purpose of this study was to assess the efficacy of hyperthermia (42 or 44 degrees C) as a modifier of cis-diamminedichloroplatinum (II) (CDDP) cytotoxicity and platinum incorporation in human pharyngeal carcinoma KB cells. To maximize the interactive effect, we examined the time sequence of high (above 43 degrees C) or low (below 43 degrees C) hyperthermia and CDDP. Within the dose range of CDDP studied, there was a marked synergism between the effects of heating at 44 degrees C and subsequent CDDP exposure for 5 h. Pretreatment at 44 degrees C for 30 min or at 42 degrees C for 4 h enhanced CDDP cytotoxicity more than posttreatment at 44 degrees C for 30 min or at 42 degrees C for 4 h. However, the chemoenhancement ratio of pretreatment at 44 degrees C for 30 min was higher then that of pretreatment at 42 degrees C for 4 h, although the thermal isotoxic dose decreased the cell count to 60% under both conditions. There was a significant increase in CDDP uptake after hyperthermia at 44 degrees C. These results indicate that high hyperthermia effectively enhances subsequent CDDP cytotoxicity in human pharyngeal carcinoma KB cells.

Antineoplastic Agents↗

Effects of cis-diamminedichloroplatinum (CDDP) and cis-diammine (1,1-cyclobutanedicarboxylate) platinum (CBDCA) on thermotolerance development and thermosensitivity of the thermotolerant cells.

The interactive effects of combined treatment with heat and CDDP (0.5 micrograms/ml) or CBDCA (10 micrograms/ml) were examined on the surviving fractions of V-79 cells. Both CDDP and CBDCA treatment induced a slight enhancement in thermosensitivity of thermotolerant cells. The development of thermotolerance during step-up heating was partially inhibited by simultaneous treatment with CDDP or CBDCA throughout the heating process. Simultaneous heat treatment at 42 degrees C with either drug showed marked interactive effect and inhibited the thermotolerance developed during 42 degrees C heating.

Animals↗

In vitro effects of hyperthermia combined with cisplatin or peplomycin on the human maxillary carcinoma cell line IMC-2.

We examined the interactive effects of hyperthermia combined with cisplatin (CDDP) (0.5 micrograms/ml) or peplomycin (PEP) (1.0 microgram/ml) on surviving fractions of human maxillary carcinoma IMC-2 cells. Either CDDP or PEP enhanced the 44 degree C thermosensitivity of thermotolerant cells after heating at 42 degrees C for 2 hours. The development of thermotolerance at 42 degrees C with either of the two drugs for 2 hours was not inhibited by CDDP, but it was partially inhibited by PEP. Moreover, for PEP throughout the entire period of 42-44 degrees C step-up heating, the 44 degree C thermosensitivity of thermotolerant cells after heating at 42 degrees C with PEP for 2 hours was enhanced similarly to that at 44 degrees C with PEP. Heating at 42 degrees C combined with either of the two drugs showed a marked interactive effect.

Antineoplastic Agents↗

Effect of heat-drug sequences on thermoenhancement and uptake of cis-DDP in human pharyngeal carcinoma.

To discover the point of maximum interactive effect, we examined the time sequence of high (above (42.5 degrees C) or low (below 42.5 degrees C) -hyperthermia and cis-diammine dichloroplatinum (II) (CDDP). Simultaneous or post-hyperthermic CDDP (0.5 micrograms/ml) treatment at 43 degrees C resulted in a slight synergistic effect, with thermoenhancement ratios (TER) of 1.42 or 1.38, respectively, and there was a significant increase CDDP uptake after both combinations compared with pre-hyperthermic CDDP treatment. However, at 42 degrees C, the maximal interaction (TER = 8.57) was obtained when KB cells were simultaneously heated with CDDP, there was also a significant increase of CDDP uptake by simultaneous procedures compared with pre or post-hyperthermic CDDP treatment. These results indicate that simultaneous or post-hyperthermic CDDP treatment for high-hyperthermia and simultaneous CDDP treatment for low-hyperthermia are the most effective means of CDDP thermochemotherapy with hyperthermia.

Antineoplastic Agents↗

Right side hepatic resection under right thoracoabdominal incision with special reference to a highly anatomical systematized method.

The results of 31 right side hepatic resections approached through thoracoabdominal incision are described, with emphasis on the benefit of the approach and systematized liver resection. Regarding postoperative mortality rate (0%) and morbidity rate (32.3%), the thoracoabdominal approach for right side hepatic resection seemed as safe and effective as the conventional abdominal approach. Even though there were no significant differences in the complications, the fluctuation of alanine aminotransferase and the hospital stay, the average operation time for the right segmentectomy through the thoracoabdominal approach was 1.3 hours less (p = 0.0078) than that of the abdominal approach. Technically, this approach was accomplished in almost the same fashion as in the abdominal approach by the utilization of systematized hepatic resection. Thoracotomy itself was not more harmful than the abdominal approach, even in patients with impaired liver function. This combination could take the advantage of a shorter operation time.

Adult↗