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Biomedical subjects

T Aida

Publications and source records attributed to T Aida.

At least 109 records · Page 6Linked to original sources

Repair of O6-(2-chloroethyl)guanine mediates the biological effects of chloroethylnitrosoureas.

Chloroethylnitrosoureas (CENUs) are alkylating and crosslinking agents used for the treatment of human cancer; they are both mutagenic and carcinogenic. We compared the levels of induction of sister chromatid exchanges (SCEs) and the cytotoxicity of nitrosoureas that alkylate only with CENUs. CENUs are 200-fold more cytotoxic and induce SCEs with 45-fold greater efficiency than agents that do not crosslink; therefore, crosslinking is probably the most important molecular event that leads to cell death and induction of SCEs. The biological and biochemical properties of both human and rat brain tumor cells that are sensitive or resistant to the cytotoxic effects of CENUs have been investigated. CENUs induce SCEs in both sensitive and resistant cells, but to induce similar levels of SCEs, resistant cells must be treated with a 5- to 14-fold higher concentration of CENUs than are used to treat sensitive cells. Resistant cells have a higher cellular level of O6-methylguanine-DNA methyl transferase, increased repair of O6-methylguanine, and 50% fewer DNA interstrand crosslinks formed than do sensitive cells treated with the same concentration of CENU. Based on these findings, we propose that cellular resistance to the cytotoxic effects of CENUs is mediated by O6-methylguanine-DNA methyltransferase and that DNA repair may also modify the mutagenic and carcinogenic properties of CENUs.

Alkylation↗

Investigation of resistance to DNA cross-linking agents in 9L cell lines with different sensitivities to chloroethylnitrosoureas.

The 9L-2, 9L-7, and 9L-8 cell lines, derived from the 9L in vivo rat brain tumor, were treated with nitrosoureas that can alkylate and cross-link DNA and carbamoylate intracellular molecules to various extents. Compared to 9L cells, 9L-2 cells were very resistant to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, and to 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-deoxyglucopyranose. The sensitivity of 9L-7 and 9L-8 cell lines to these drugs was intermediate between 9L and 9L-2. Treatment of 9L, 9L-2, 9L-7, and 9L-8 cell lines with 1,3-bis(trans-4-hydroxycyclohexyl)-1-nitrosourea produced approximately the same level of cell kill. Compared to 9L cells, 9L-2 cells are 10-fold more resistant to the cytotoxic effects, 34-fold more resistant to the induction of sister chromatid exchanges, and have 40% fewer DNA interstrand cross-links caused by treatment with 3-(4-amino-2-methyl-5-pyrimidinyl)methyl-1-(2-chloroethyl)-1-nitrosourea . In contrast, treatment of 9L and 9L-2 cells with 1-ethylnitrosourea produced approximately the same level of cell kill and induction of sister chromatid exchanges. Our results suggest that the resistance of 9L-2, 9L-7, and 9L-8 cells is related to DNA cross-linking and not to alkylation or carbamoylation. We studied the effects of other agents that form DNA cross-links with structures different from those formed by treatment with chloroethylnitrosoureas (CENUs) in 9L and 9L-2 cells. In contrast to results obtained with CENUs, 9L-2 cells were 2-fold more sensitive to the cytotoxic effects, 2-fold more sensitive to the induction of sister chromatid exchanges, and had 3-fold more cross-links formed than 9L cells treated with nitrogen mustard. However, the amount of cell kill, number of sister chromatid exchanges induced, and the DNA cross-linking were the same for 9L and 9L-2 cells treated with cis-diamminedichlorplatinum(II). Our results indicate that cellular resistance to CENUs is highly specific and that the mechanism of resistance does not allow cross-resistance with other DNA cross-linking agents. These and other results suggest that when DNA repair processes mediate cellular resistance to CENUs, other cross-linking agents will not be cross-resistant unless they form alkylation products that are affected by repair processes that mediate resistance to CENUs.

Animals↗

[Surgical results and clinical analysis of 19 cases of acromegaly].

The authors have been analyzed the results from 19 patients who underwent transsphenoidal microsurgery for their pituitary adenomas. All of the patients showed some degree of clinical improvement after surgery. Surgical complications seemed to be negligible except one patient who had suffered from persistent diabetes insipidus postoperatively. The results in terms of postoperative GH levels were almost good in 17 patients in whom preoperative GH levels had been below 100 ng/ml. There was no relationship between postoperative GH values and tumor grades or types (in Hardy's classification) in this group of patients. In 12 of them, postoperative GH values fell and remained below 5 ng/ml, although abnormal GH responses to dynamic testing were still noted. On the other hand, the results were particularly poor in the remaining 2 patients in whom preoperative GH levels had been higher than 100 ng/ml. Postsurgical radiation therapy was applied to 5 cases. Postirradiation GH values decreased in all 5 cases, but did not reach to the normal level (below 5 ng/ml) in 3 of them.

Acromegaly↗

[Case of acoustic neurinoma with intratumoral hemorrhage extending to cerebellar hemisphere].

A case of acoustic neurinoma which developed intratumoral hemorrhage extending to the right cerebellar hemisphere, is reported. A 54-year-old man was diagnosed as cerebello-pontine angle tumor, possibly acoustic neurinoma, from typical clinical course, neurological signs and findings of skull X-P and CT scan at the first visit to our out-patient clinic on July 28, 1981. On August 6, 1981, he was transferred to our in-patient ward in emergency because of sudden onset of headache and impairment of consciousness. At emergency admission, he was found to be comatous and CT scan revealed round-shaped high density in the right cerebellar hemisphere, continuing from the right cerebello-pontine angle tumor with enlarged lateral ventricles, which indicated occurrence of intratumoral hemorrhage. At emergency operation, hematoma in the right cerebellar hemisphere was evacuated and the tumor in the right cerebello-pontine angle was partially resected. Microscopically, the tumor was composed of compact, finely fibrillated cells of Antoni A tissues, and loose patterns of Antoni B tissue, being diagnosed as schwannoma, and also abnormal vascular proliferations were identified just adjacent to foci of hemorrhage noted within tumor tissues. The pattern of abnormal vascular proliferations within this tumor were almost identical with telangiectasia. The authors concluded that intratumoral hemorrhage in this case occurred most likely due to disruption of histologically verified abnormal vascular proliferations.

Cerebellopontine Angle↗

[Transcallosal approach to para-ventricular tumors].

Our experience with the transcallosal approach to para-ventricular tumors is reviewed and our operative technique is described. A group of 7 patients with a variety of tumors affecting the lateral ventricle, 3rd ventricle and basal ganglia have been treated using an anterior transcallosal approach. Using a posterior transcallosal approach, we operated upon 2 patients with thalamic tumors. The anterior part of the body of the corpus callosum is divided in the anterior transcallosal approach and the posterior part of the body of the corpus callosum is divided with preservation of the splenium in the posterior transcallosal approach. The division amounting to approximately 2-3 cm is sufficient exposure. With the exception of tumors affecting the basal ganglia, thalamus and anterior 3rd ventricle, complete excision of each lesion was effected. There were no operative deaths. The complications in this group of patients were primarily related to the nature and location of the primary tumor, but four complications were directly related to the transcallosal approach. Venous infarctions occurred in 2 patients and subdural fluid collections occurred in 2 patients. Therefore, planning of the flap placement and the extent of brain retraction must be based on preoperative angiographic assessment of parasagittal venous tributaries. We performed some detailed studies of the interhemispheric transfer of somesthetic and perceptual motor tasks, as well as psychometric testing post-operatively in 2 patients. No significant clinical deficit subsequent to dividing the anterior part of the body of the corpus callosum could be demonstrated. The results and clinical material indicate that transcallosal approach is a safe, feasible alternative in the management of the tumors in these regions.

Adult↗

[Effect of PS-K on experimental neurogenic tumors in rats induced by ethylnitrosourea].

The effect of PS-K as immunomodulator was studied in Fischer rats bearing neurogenic tumors induced transplacentally by ENU. 114 rats were divided into control and PS-K treated groups. all rats were subjected to an autopsy at death and all of central nervous system were examined macroscopically. Final neurogenic tumor incidence in PS-K treated groups was significantly lower than that in the control group, but distribution of these neurogenic tumors and number of neurogenic tumors in a rat remained unchanged between the control and the each PS-K treated groups. Survival time of PS-K treated groups did not increase than the control group. From these experiments, it might be that induction of neurogenic tumors may be suppressed by administration of PS-K.

Adjuvants, Immunologic↗

[Primary intracranial germ cell tumor with abnormal high value of alpha-fetoprotein after the radiation therapy].

A 7-year-old boy was admitted to Hokkaido University Hospital complaining of headache and vomiting. On admission he was slightly confused and presented Parinaud's sign. CT scan revealed abnormal high density mass with contrast enhancement effect at the pineal region and obstructive hydrocephalus. Laboratory studies showed the normal value of human chorionic gonadotropin and no trace of alpha-fetoprotein. Germinoma was most suspected based on the findings of CT scan and laboratory studies. The radiation therapy was carried out for a month and CT scan taken after the radiation therapy revealed marked reduction of the size of the tumor at the pineal region, and he was discharged. But he was re-admitted 3 months after the discharge complaining of headache and vomitting again. CT scan showed the recurrence of the tumor and laboratory studies showed abnormal high value of A.F.P. After the ventriculo-peritoneal shunt, the sub-occipital craniectomy was performed by the Stein's approach, and the tumor was removed. Pathologically the tumor was a typical yolk sac tumor. This case is a very interesting case because it suggests an alternation of the element of the germ cell tumor by the radiation therapy. At first admission, germinoma was the main element of the tumor judging from the effectiveness of the radiation therapy and laboratory studies. But the main element of the tumor seemed to have changed to yolk sac tumor after the radiation therapy. The relation between the tumor markers and the types of the germ cell tumor and histopathological characters of the intracranial germ cell tumor were discussed.

Brain Neoplasms↗

[Evaluation of radiation immunochemotherapy in the treatment of malignant glioma. Combined use of ACNU, VCR and PS-K].

In a follow up study of 38 patients with supratentrial malignant glioma verified histologically during the 3 years from 1979 to 1982, the same therapeutic method which was the postoperative synchronized radiation-immunochemotherapy was applied. And we investigated the relationships between the survival rate and the histological malignancy, the operative area, and age of admission. Total dose of 5000 to 6000 rad radiation was given after surgery. 0.02 mg/kg of VCR was administered intravenously on the first and the 29th day of radiation, and 2 mg/kg of ACNU was administered intravenously 24 hours after VCR administration. After synchronized radiotherapy, 2 mg/kg of ACNU was given every 6 weeks and 3 g of PS-K was given orally every day. Dose of PS-K was increased especially during the radiation and for 2 weeks after ACNU administration. This radioimmunochemotherapy was applied to 38 patients with malignant glioma, 25 cases of glioblastoma multiforme, 12 cases of malignant astrocytoma, one cases of malignant ependymoma, one case of malignant oligodendroglioma. A complete clinical course of all patients was observed. 18 of 38 cases are surviving. The survival rate of malignant gliomas was 71.2% for one year, 47.6% for 2 years, 34.8% for 3 years. The survival rate of glioblastoma was 56.3% for one year, 36.9% for 2 years, 12.3% for 3 years. The survival rate of the patients receiving macroscopically total removal was higher than that of the patients receiving subtotal removal. The survival rate of the younger patients (under 49 years old) was higher than that of the older patients (over 50 years old). Side effect of this therapy was myelosupression in 75.8%.

Adjuvants, Immunologic↗

[Surgical management of trigeminal neuralgia, hemifacial spasm, paroxysmal tinnitus and nystagmus by neurovascular decompression].

Trigeminal neuralgia, facial spasm, tinnitus, vertigo, and glossopharyngeal neuralgia are believed to be the symptoms complex of hyperactive dysfunction of the cranial nerve caused by vascular cross compression at the root entry (exit) zone of the appropriate nerve. Posterior cranial fossa approach for the neurovascular decompression was enhanced by Jannetta et al (1975). From their experiences of surgery, they emphasized that these symptoms were relieved by surgery. In this report, we will discuss the etiology of the disease, the neurotological examination, the angiographic findings, the operative findings and results in a series of 10 patients who have undergone neurovascular decompression. The series consisted of 4 cases with trigeminal neuralgia, 5 cases with facial spasm, and 1 case with paroxysmal tinnitus accompanied by facial spasm. The postoperative progress in these all patients was excellent and relieved of the symptoms. There was neither mortality nor any significant complication. We stress that the neurovascular decompression surgery is now well justified as the definite treatment for the trigeminal neuralgia and facial spasm, because the surgery can be performed easily and safely by the neurosurgeons. The indication of the neurovascular decompression for the acoustic nerve and glossopharyngeal nerve is still controversial. In our own case, tinnitus was paroxysmal and complicated with facial spasm, not synchronous with facial spasm, but with nystagmus. This selective synchronism between tinnitus and nystagmus is a particular feature of our clinical instance. This particular clinical experience may provide some highly significant suggestions in considering the applicability of neurovascular decompression to the acoustic nerve.

Aged↗

[A histopathological study on a glioma with radiation necrosis and brain stem spongiform degeneration (author's transl)].

A histopathological study on an autopsy case of 38-year-old female who had suffered from huge glioma and received radiation therapy as well as operation and chemotherapy was reported. The tumor mainly involved the right frontal lobe and partially invaded to the left cerebral hemisphere. Subarachnoidal dissemination of tumor cells was noticed in cerebellum, brain stem and spinal cord. Under the microscope the tumor was mainly consisted of astrocytic tumor cells, while oligodendrocytic ones and those with anaplastic or bizarre nuclei were observed among them. Though ependymomatous appearance was partially seen, no true rosette was found. From these findings the tumor was histologically diagnosed as anaplastic glioma. Simultaneously, there was massive coagulative necrosis which was limited to the irradiated area in the tumor tissue and surely attributable to irradiation. In addition, proliferation of gemistocytic astrocytes which was independent of glioma itself was widely observed in the field of irradiation. Another remarkable finding was spongiform degeneration which was located in the subpial area of brain stem including degenerative products of myelin sheaths and axons with neither inflammatory changes not gliosis. In some papers it is suggested that such a lesion has something to do with irradiation or chemotherapy. But in our case this lesion was found in non-irradiated area and no intramedullary injection of chemical agents was performed. Further, the distribution of this lesion was for the most part restricted to the domain of the pontine cistern which had been huge owing to stagnant hemorrhagic fluid. Therefore, it is highly probable that this lesion was caused by the abnormal pia-glial barrier.

Adult↗