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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 361 records · Page 20Linked to original sources

[Antineoplastic effect of beta-IFN and gamma-IFN on malignant gliomas].

We have compared the anti-tumor effects of beta- and gamma-interferons (IFN) against human glioma cells using in vitro model, flow cytometry and xenograft in nude mouse. Contrary to gamma-IFN which had a negligible effect on the growth of glioma cells, beta-IFN showed a dose dependent growth-inhibitory effect on glioma cells in vitro. Our flow cytometry studies revealed that proportion of DNA contents which represent the S and/or G2M phase of cell cycle was markedly increased in cells treated with beta-IFN. However, in cells treated with gamma-IFN, no perturbations in cell cycle distribution were observed. Regarding the anti-tumor effect examined using xenograft of human glioma cells in nude mouse, the tumor reduction rate which was calculated from the ratio of tumor volume between treated (T) and control (C) groups and expressed as T/C value, was 0.44 in animals treated with beta-IFN. However, T/C value in animals treated with gamma-IFN was 0.80 which was derived from the weaker anti-tumor effect of gamma-IFN as compared with that of beta-IFN. Beta-IFN was found to cause a partial suppression of the growth of glioma strain used in this study which confirms our previous report that beta-IFN is effective in reducing tumor size in 2 of 6 glioma strains tested. On the other hand the anti-tumor effect of gamma-IFN, at least in terms of direct effect, against glioma cells used in this study was minimum. However, the mechanism of gamma-IFN's anti-tumor effect may exert mainly through the potentiation of immuno-defence mechanism and the further studies on its pharmacodynamics will be necessary to evaluate the anti-tumor effect of gamma-IFN.

Animals↗

[Efficacy of interferon-beta and interleukin-2 as cytokines for malignant brain tumor treatment].

The role of Interferon-beta (IFN-beta) as maintenance therapy for malignant gliomas and medulloblastomas was described. The low dose but continuous long-term administration of IFN-beta as a maintenance treatment for malignant gliomas after the induction therapy with surgery and chemoradiotherapy demonstrated the complete remission of the tumor in six cases of malignant gliomas. Such method of IFN-beta administration did not induce any serious side effects and might be useful for treatment of malignant gliomas. In addition, recent advance of adoptive immunotherapy using lymphokine activated killer cells (LAK) was briefly reviewed.

Adolescent↗

[Primary intracranial epidermoid carcinoma accompanied with epidermoid cyst in the cerebellopontine angle--a case report].

A case of epidermoid carcinoma arising in an epidermoid cyst in the cerebellopontine angle is presented. Clinical features and CT appearance are discussed in comparison with those of benign epidermoid cyst. A 43-year-old man was admitted to the Department of Neurosurgery, University of Tokyo Hospital on April 14, 1983, with complaints of right facial numbness and weakness of six months' history. On neurological examination, sensation of the right half of the face was decreased in all modalities. Marked atrophy of the ipsilateral temporal muscle was also noted. Right facial paresis of peripheral type was evident. Gag reflex was decreased on the same side. Except for a slightly increased left deep tendon reflexes, there were no pyramidal tract signs. A CT without contrast material failed to show any abnormalities. A postcontrast CT demonstrated an irregular enhancement in the right cerebellopontine angle. The finding of asymmetry of the ambient cistern indicated minimum mass effect on the metrizamide CT cisternography. Suboccipital exploration of the right cerebellopontine angle was carried out on April 28, 1983. Leaving a part of the capsule indenting the pons between the roots of the fifth and the seventh nerve, we removed a white pearly tumor. Histological diagnosis was typical epidermoid cyst. He left the hospital one month later with signs of the right seventh and the eighth nerve. His postoperative course, however, was beyond our expectation. Over a few months following his discharge, left hemiparesis as well as horizontal and vertical nystagmus gradually developed. He was readmitted on November 10, 1983. A postcontrast CT revealed enlargement of the enhanced lesion filling the right ambient cistern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Surgical indication for extracranial-intracranial arterial bypass determined by cerebral blood flow study and neurological function--a retrospective study].

In order to establish more strict and objective indication for EC-IC bypass, a retrospective study on the surgical effect on cerebral blood flow (CBF) and neurological function was carried out in 37 cases. STA-MCA bypass was carried out on 20 cases with IC occlusion and 17 cases with MCA occlusion. Twenty-two cases with completed stroke, 9 cases with TIA and 6 cases with RIND. All patients were able to ambulate before surgery, and none of them were hemiplegic. CBF study by 133Xe inhalation method was carried out before and 2 to 4 weeks after surgery. Bypass was patent in all cases. Thirty percent of all cases showed more than 16% increase in CBF (++ group) on the side of bypass surgery and another 30% demonstrated 6 to 15% increase (+). On the other hand 30% of cases appeared to be unchanged (+/-), and 10% showed more than 6% decrease (-). The less the pre-operative CBF value was, the more the post-operative CBF was expected to be increased. Patients with pre-operative CBF less than 60% of normal value (ISI = 63 +/- 4) showed remarkable increase (++), and those with 60 to 70% showed moderate increase (+). Contrarily, cases with more than 70% of normal value showed either no change or decrease. Neurological change was evaluated as to disappearance of TIA attack and improvement of hemiparesis or mental dysfunction. Seventy-seven percent of patients in groups with (++) and (+) effect on CBF showed improvement in neurological function, whereas only 27% of patients in groups with (+/-) and (-) effect demonstrated improvement, which was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

[Mechanism of deafferentation pain--experimental research using spinal root resection model].

In rats, autotomy of the digits following dorsal root resection has been observed by many researchers and is considered as an animal model of deafferentation pain. Using C5-Th 1 root resection model of rats, we investigated the role of the ventral roots and pain experience given before deafferentation in the development of autotomy. Male Sprague-Dawley rats of eight weeks old, weighing about 200 g, were used. Animals were divided into two major groups; dorsal root resection group and total (both ventral and dorsal) root resection group. Each group was further divided into several sub-groups, according to the use of formalin injection, before or after surgery, and to the side of formalin injection, the forearm of the affected (root resection) side or unaffected side or of both sides. In pre-injection groups, 0.1 ml of 5% formalin was given subcutaneously on the forearm one hour before surgery. In the postinjection groups, formalin was given within one hour after surgery. Dorsal root resection group without formalin injection was used as control. Under anesthesia with intraperitoneal injection of nembutal, left C 5-Th 1 dorsal root resection was performed by C 4-Th 1 laminectomy and left C5-Th 1 total root resection by opening of the corresponding vertebral foramen. After surgery, we checked neurological findings, systemic condition and local changes of all the extremities everyday during the first week and once a week thereafter for at least three months. In control groups, autotomy was not observed at all during the observation period of three months.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

[Subacute brain atrophy induced by radiation therapy of malignant brain tumors].

In order to analyze brain atrophy after radiation therapy to the brain tumors, we calculated a CSF-cranial volume ratio on CT scan as an index of brain atrophy, and estimated dementia-score by Hasegawa's method in 91 post-irradiated patients with malignant brain tumors. Radiation-induced brain atrophy was observed in 51 out of 91 patients (56%) and dementia in 23 out of 47 patients (49%). These two conditions were closely related, and observed significantly more often in aged and whole-brain-irradiated patients. As radiation-induced brain atrophy accompanied by dementia appeared 2-3 months after the completion of radiation therapy, it should be regarded as a subacute brain injury caused by radiation therapy.

Adolescent↗

[Time course of the cerebroprotective effect of dexamethasone in experimental head injury].

Despite the widespread use of glucocorticoids in patients with severe head injury, the usefulness is still controversial. In the past, the effect was investigated only in terms of dose-response relationship. We have, however, studied the time factor for the administration of dexamethasone to obtain maximal beneficial effect together with investigating the influence of actinomycin-D, an inhibitor of messenger RNA synthesis, before dexamethasone treatment. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 g dropped from a height of 17.8 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval: time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). 4 mg/kg of dexamethasone phosphate was given intraperitoneally 0.5, 4, 6, 12, 18 or 24 hours before injury. Actinomycin-D of 0.5 mg/kg was injected intravenously 1 h before each dexamethasone treatment in separate animals. In the other group of animals, dose was changed with varying time course of dexamethasone pretreatment, e.g., 2, 4, 6 or 8 mg/kg given 0.5, 2 or 4 h before injury. It was found that dexamethasone of 4 mg/kg pretreatment 4-12 hours significantly improved the recovery from consciousness disturbance and death rate. Actinomycin-D given before dexamethasone treatment completely abolished the protective effect of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Identification of HETE in the rat brain and its relevance to ischemic cerebral edema: Part 2].

We reported the detection of 11-hydroxy-eicosatetraenoic acid(HETE) in rat brain and its relevancy to ischemic brain edema. But the further study disclosed that the peak of 11-HETE on high performance liquid chromatography (HPLC) had been contaminated by dibutyl phthalate. The results and our speculation about the roles of 11-HETE in ischemic brain turned out to be incorrect. Re-examination of lipoxygenase products in rat brain was performed using gas chromatography-mass spectrometry (GC-MS) and HPLC. The rat middle cerebral artery (MCA) occlusion model was used. The rat was sacrificed by in situ freezing 24 and 72 hours after MCA occlusion. The identification and quantitative study of HETEs in normal and ischemic rat brain was performed by HPLC and GC-MS. In the present study, several kinds of HPLC were used to prevent misinterpretation by the contamination. Sham operated control rat brain contained only 15-HETE and its content was 2.1 +/- 2.1 (mean +/- SE) ng/g wet weight. In 24 hours ischemic brain, 11-HETE newly appeared and the 15-HETE content was increased. But these increases were not statistically significant. The hemisphere rendered ischemic for 72 hours contained all HETEs, namely, 5,9-, 8- and 12-, 11-, and 15-HETEs. Their amounts were 18.3 +/- 2.8, 16.6 +/- 3.0, 23.7 +/- 14.9, 14.0 +/- 3.4, 19.8 +/- 5.5 ng/g wet weight, respectively. All HETE contents except 8- and 12-HETEs were significantly increased 72 hours after MCA occlusion when ischemic cerebral edema reached its maximum (p less than 0.01, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Interactions of human fibroblast interferon with chemotherapeutic agents and radiation against human gliomas in nude mice.

The growth inhibitory effects of the combination of beta-interferon (beta-IFN) and conventional anticancer drugs such as adriamycin (ADM) and ACNU were evaluated in nude mice receiving subcutaneous transplants of human glioblastoma. Next, the anticancer and radiation sensitizing effects of beta-IFN on human glioblastoma was also evaluated in nude mice model. After three weeks of combined treatment, tumour reduction rates (treated/control values) were evaluated by the Battelle's method. In conclusion, the growth inhibitory effect of IFN was most enhanced when IFN was administered following radiotherapy. Furthermore, the combined effect was enhanced in proportion to the dose of radiation.

Animals↗

Enhancement of ATPase activity by a lipid peroxide of arachidonic acid in rat brain microvessels.

The effects of 15-hydroperoxyarachidonic acid (15-HPAA) on Na+, K+- and Mg+-ATPase activities in the blood-brain barrier (BBB) were examined using rat brain microvessels (MV). 15-HPAA markedly stimulated these ATPase activities in MV at low concentrations whereas the synaptosomal Na+, K+-ATPase activity was inhibited in a dose-dependent manner. Further neurochemical analysis revealed that this stimulatory effect of 15-HPAA in MV was not due to a simple detergent-like action of the compound on the membranes but rather to stimulation of the phospholipase A2 and lipoxygenase activity within MV. In addition, it was shown that free radical reactions were involved in the mechanism. Since such anti-edema drugs as 1,2-bis(nicotinamido)propane were proved to be potent suppressors of the enhanced ATPase activity, further speculations on the role of this effect for ischemic brain edema are offered.

Adenosine Triphosphatases↗

Aneurysms of the posterior cerebral artery: report of ten cases.

Ten cases of posterior cerebral artery (PCA) aneurysm are presented. There were 13 aneurysms in the 10 patients: 6 saccular, 5 fusiform, 1 broad-based, and 1 giant fusiform serpentine aneurysm. Eight patients underwent operation: clipping for 2 saccular aneurysms, trapping for 1 saccular and 3 fusiform aneurysms, and coating for 2 fusiform or broad-based aneurysms. Microsurgical cerebral revascularization techniques were attempted in 2 cases: after a fusiform aneurysm had been excised, end-to-end anastomosis of the residual two ends of the PCA was performed and, after a giant serpentine aneurysm had been trapped, the superficial temporal artery was anastomosed transcortically to the distal PCA. Two patients died before operation because of rebleeding and vasospasm. Postoperative neurological deficits include contralateral hemiparesis, homonymous hemianopsia, hemihypesthesia, and ipsilateral 3rd nerve palsy. Our results suggest that, despite the good collateral circulation of the PCA, some ischemic events may occur after trapping procedures and that cerebral revascularization techniques may have some benefit in the treatment of unclippable aneurysms in this region.

Adolescent↗

Effects of ACNU and radiotherapy on malignant glioma.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Adolescent↗