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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 451 records · Page 25Linked to original sources
PubMed1982

[Schmidt Ruppin-D-ASV-induced primary rat brain tumor model for therapeutic screening].

It is important to evaluate the therapeutic and side effects of new therapy for malignant brain tumors in an adequate animal model prior to its initial clinical investigation. For decades, neurooncologists have argued for the use of primary, autochthonous tumors rather than transplanted tumors such as C 6 glioma cells and 9 L gliosarcoma cells. But unfortunately, no spontaneous animal astrocytomas are currently available as usable models. So we tried to establish the model of primary, autochthonous avian sarcoma virus-induced rat gliomas for experimental chemotherapy and immunotherapy. The present study was undertaken to determine the incidence and histologic pattern of tumors and the mean survival time of the animal model used. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of infectious cell free homogeneous subgroup D Schmidt-Ruppin avian sarcoma virus (SR-D-ASV) into 3-day-old inbred Fischer 344 rats induced small sized tumors in all rats 20 days later. The mean survival time of inoculated rats were 58.7 +/- 12 days. As to the classification of SR-D-ASV induced brain tumors in Fischer rats, astrocytoma was 70.6% (protoplasmic astrocytoma 23.5%, fibrillary astrocytoma 47.1%), sarcoma 17.6%, and mixed astrocytoma and sarcoma 11.8%. In conclusion, this SR-D-ASV induced tumor in the rat fulfilled the following criteria for the desirable animal model: (1) Spontaneously arising. (2) Glial origin. (3) Intraparenchymal growth. (4) Uniformly fatal within reasonable time period. Statistic evaluation of the effects of chemotherapy and immunotherapy was considered to be possible.

Animals↗
PubMed1982

Metastatic brain tumor. A clinical and pathologic analysis of 101 cases with biopsy.

A clinical and pathologic analysis was made of 101 patients with surgically treated metastatic brain tumors. The most common primary site was the lung (58.4%), followed by th breast (11.9%), gastrointestinal tract (6.9%), and uterus (5.)%). In 14 patients, the disease began with cerebral symptoms. The overall average survival after craniotomy was 8.0 months, the longest survival being 8l/2 years; patients with one-year survivals composed 18.8% of the cases. The histologic features were almost the same in primary and metastatic tumors. The undifferentiated tumor metastasized most frequently to the brain, and adenocarcinoma of the papillary type also seemed to find the brain fertile ground for metastatic growth.

Adenocarcinoma, Papillary↗
PubMed1982

[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)].

Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.

Adult↗
PubMed1982

[Computed tomographic measurement of regional cerebral blood flow by xenon enhancement (author's transl)].

The present study was conducted to overcome some of disadvantages of cerebral blood flow study by radionuclide, such as poor regionality of flow values and errors involved in pathological brains. Serial CT scanning was carried out during and after inhalation of 50 to 70% non-radioactive xenon in humans. Diffusible gas with high atomic number enhanced gray matter first 19 +/- 4 HU (mean +/- SD) on an average in Hounsfield unit (HU) and later white matter 24 +/- 4 HU. In seven normal subjects, blood flow in gray matter was 82 +/- 11 and that in white matter 24 +/- 5 ml/100 gm/min. Partition coefficient which is not readily obtainable by radionuclide study was 0.9 +/- 0.1 in normal gray matter and 1.4 +/- 0.2 in normal white matter. Two cases were presented to show k-map (clearance rate), lambda-map (partition coefficient) and CBF map, which displayed images of values calculated automatically, in black and white or color on CRT. The first case was a patient with metastatic brain tumor from lung in the left parietal region. The blood flow of the tumor was close to that of gray matter, whereas blood flow of edematous white matter surrounding the tumor was decreased to below 10 ml/100 g/min with partition coefficient ranged from 0 to 0.9. The second case was presented to demonstrate the resolution of the blood flow map obtained by this method. Multiple lacunar infarcts of the basal ganglia and white matter in the size of 1 to 3 mm, which were hardly identified on regular CT picture, were well visualized on CBF map. This method appeared to have several advantages over conventional isotope method and to provide useful clinical and research informations.

Aged↗
PubMed1982

[The influence of pentobarbital and Y-9179 on regional cerebral blood flow and infarction size in the middle cerebral artery occlusion model in cats (author's transl)].

Following permanent occlusion of the middle cerebral artery (MCA) in cats, the effect of delayed administration of pentobarbital (PBT) and a novel imidazole derivative (Nizofenone or Y-9179) on the regional cerebral blood flow (rCBF) was studied. The rCBF was measured for one week by the hydrogen clearance technique without anesthesia. The overall effects of these drugs on histological changes were also assessed. Twenty-four animals, in which platinum electrodes were chronically implanted in the ten predetermined positions, were divided into following three groups. The control, PBT and Y-9179 groups received the vehicle, PBT (25 mg/kg/day) and Y-9179 (6.25 mg/kg/day), respectively. Drug administration was started 30 min after MCA occlusion and continued for three days. In the affected hemisphere of the animals which survived for one week, histological examination revealed ischemic lesions composed of the marginal, reactive and central zones. The infarction ratio calculated as the ratio of the damaged area to the whole hemispheric area was significantly smaller in the drug treated groups than in the control. In the Y-9179 group, the reduction of the area comprizing the central and reactive zones was particularly prominent. There were no apparent differences in the time-course of the rCBFs between the control and Y-9179 groups. Each channel showed reduction of the rCBF following MCA occlusion. Although slight fluctuations of the rCBF were seen during the first three to four hours, the initially dropped rCBF remained stable in both groups. In the PBT group, on the other hand, an increase of the rCBF took place following the administration of the drug in the area where the rCBF was initially reduced less than about 40 ml/100g/min after MCA occlusion. Most of the electrodes showing such an increase in the rCBF topographically corresponded to the reactive or boundary zone. In the control group, vasogenic edema characterized by the perivascular exudation of plasma fluid was prominent in the periphery of the central zone as well as in the inner layer of the reactive zone. Such changes were almost absent in the Y-9179 group, whereas it was more evident and close to the control in the PBT group. So far as the correlation between the course of the rCBF and the final histological outcome was examined, there was no evidence indicating the beneficial effect of the redistribution of the rCBF by PBT. Y-9179 had no significant action on the course of the rCBF but its anti-edema effect might be related to its cerebral protective action. The mechanism of cerebral protection by PBT or Y-9179 needs further clarification.

Animals↗
PubMed1982

[Pathological changes of prolactinomas treated with bromocriptine].

In order to investigate the pathological changes of prolactinomas induced by the treatment with bromocriptine, 12 cases of prolactinoma were studied using immunocytology and electronmicroscopy. Eight cases were treated with bromocriptine, 5 mg/day, for a few days before surgery, while 4 cases were given for several months. 1) Cases of the short-term administration All of the adenomas except one appeared to be eosinophilic by H-E stain. Electronmicroscopically, abundant secretory granules, measuring 100-350 nm, were found throughout the cytoplasm, while exocytosis, frequently seen in the common type of prolactinomas, could not be observed. With immunostains, prolactin was diffusely positive in the cytoplasm of most adenoma cells, though the intensity of immunostaining for prolactin was relatively faint compared with that of normal prolactin cells or usual prolactinomas. Immunoreactive prolactin was demonstrated on accumulated secretory granules, while it was negative in the Golgi apparatus and rough endoplasmic reticulum (ER). 2) Cases of the long-term administration The tumors corresponded to chromophobe adenomas and the immunoperoxidase techniques revealed the absence of prolactin in the cytoplasm. Electronmicroscopically, secretory granules, measuring about 100 nm, were infrequent and lined up along the cell membrane. Marked shrinkage of the Golgi apparatus and ER was noted with various stages of degenerative changes in adenoma cells. In conclusion, bromocriptine not only inhibits the release of prolactin, but also suppresses the synthesis of it at the initial phase. With a long-term administration of bromocriptine, the cell organelles related to the hormone production, such as the Golgi apparatus and ER show gradual shrinkage under the prolonged tonic inhibition for prolactin release and synthesis. This might be the mechanism by which bromocriptine leads prolactinomas to the shrinkage.

Adenoma↗
PubMed1982

[Cerebral vasospasm and lipid peroxidation--lipid peroxides in the cerebrospinal fluid after subarachnoid hemorrhage].

The relationship between lipid peroxides in cerebrospinal fluid (CSF) and the occurrence of cerebral vasospasm following subarachnoid hemorrhage (SAH) was evaluated by analyzing CSF with high-performance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS). Hydroperoxy eicosatetraenoic acids (HPETEs) and hydroxy eicosatetraenoic acids (HETEs) were synthesized by the treatment of arachidonic acid with hydrogen peroxide and cupric chloride. The retention time of these HPETEs and HETEs were determined on HPLC. The position of oxydation occurred was determined after methylation, reduction and trimethyl silylation using GC-MS. Thus the elucidation of positional isomers of HPETEs and HETEs was made possible by the retention time on HPLC. The supernant of CSF after SAH was adjusted to pH 3.0 and then absorbed to octadecyl silyl silica column. The eluted fraction with 15% ethanol-water from octadecyl silyl silica column was analyzed by HPLC detecting at 238 nm. No peak was observed on HPLC at the region of HPETEs and HETEs in the CSF obtained from healthy person. In SAH patients, several peaks were recognized in accordance with the occurrence of cerebral vasospasm. One of the peaks was identified as 5-HETE by HPLC and GC-MS. In 10 SAH patients, semi-quantitative analysis of 5-HETE in the CSF was performed by measuring the height of the peak identified as 5-HETE on HPLC. The close correlation was recognized between the occurrence of cerebral vasospasm and the appearance of 5-HETE in the CSF. The results of the present study suggest that lipid peroxidation is involved in the pathogenesis of chronic vasospasm after SAH.

Arachidonic Acids↗
PubMed1981

Anterior sacral meningocele discovered by whole body computerized tomography: case report.

A case of anterior sacral meningocele which was clearly visualized on whole body computerized tomography is presented. Posterior surgical approach with ligation of the narrow communication between the sacral dural sac and the meningocele alleviated the subjective complaints of a feeling of abdominal distention and of dysuria. For the purpose of postoperative follow-up study, examination by whole body computerized tomography proved to be the best method of evaluating the size of the meningocele and also the state of neighbouring structures.

Adolescent↗
PubMed1981

Characteristics of intracranial meningiomas in childhood.

18 cases of meningiomas in childhood below the age of 15 years at the onset of symptoms and signs were experienced in our clinic. They were studied as for the incidence, age and sex distributions, symptoms and signs at the onset, tumor locations, histological types, presence of cyst, dural attachments, and prognosis, in comparison with cases in adolescence (18 cases) and in adults (498 cases). Distinctive features in childhood meningiomas were: (1) relatively high incidence in the lateral ventricles (11.1%), (2) high incidence of cyst formation in the tumor (16.7%), and (3) of cases without any dural attachment (12.5%). These features were statistically significant as compared to adult cases (p less than 0.05). Features 1 and 2 were also true for adolescence cases. It was also revealed that male patients were predominant in childhood and adolescence (M:F = 10.8) in contrast to female predominance in adults (M:F = 1:1.6). The most frequent histological type was sarcomatous type (6 out of 18). It may be of interest that 3 cases of this malignant type have been alive for more than 10 years.

Adolescent↗