[Effects of radiation therapy of glioma in children, with special reference to brain atrophy].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Tanaka.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The basic characteristics of cellulose triacetate (CTA) film dosimeter have been investigated with 5, 8, and 15 MeV proton beams. The optical density change per unit absorbed dose for 8 and 15 MeV protons is the same as that given for electron beams, but a little smaller for 5 MeV protons. The CTA dosimeter was found to be useful to obtain dose distributions with high spatial resolution in samples exposed to proton beams.
Explore the source record for details and available documents.
As brain capillaries do various works necessary for maintaining the homeostasis of neurons, their disruptions may play an important role in the establishment of ischemic brain damage. It is also said that brain capillaries response to ischemia more functionally than structurally and their microstructural features remain unchanged for a long time of ischemia. Therefore, a new method is expected to be introduced that can evaluate the ischemic changes of endothelial cells on a histological level more sensitively than conventional histological methods. In the present study we investigated immunohistochemical reactivity of factor VIII related antigen (F VIII RAg), a specific and representative marker of vascular endothelial cells, in normal and ischemic brains. In the experiment, cerebral ischemia was induced by occlusion of the unilateral common carotid artery in adult mongolian gerbils. The periods of occlusion were 1, 2, 3, 6, 12, and 24 hours, in five animals respectively. After occlusion each brain was obtained by decapitation and quickly frozen at -80 degrees C and 5-6 micron sections were cut in a cryostat at -20 degrees C and dried at 37 degrees C. The staining for F VIII RAg was done by the peroxidase-antiperoxidase method using specific antiserum to human F VIII RAg. In normal gerbil's brains, the positive staining for F VIII RAg was observed in endothelial cells of arteries, veins and capillaries. In major vessels the staining was intense, but neurons and glia were not stained.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the properties of the vessels newly formed in cerebral infarcts, we performed enzyme histochemical study for alkaline phosphatase and gamma-glutamyl transpeptidase that are membrane enzyme of capillary endothelial cells in the brain as well as immunohistochemical study for factor VIII related antigen and laminin. Adult mongolian gerbils were used in the experiment to produce cerebral infarcts. The animals showing clear neurological signs of ischemia after occlusion of the left common carotid artery were selected. Following one hour ischemia blood flow was reperfused and the animals were allowed to grow and sacrificed at predetermined intervals ranging from two days to two years. The stainings for alkaline phosphatase and gamma-glutamyl transpeptidase were performed by Brustone method and Rutenburg method respectively, and those for factor VIII related antigen and laminin by PAP method, in frozen sections. Four days after ischemia, vessels of a slightly large size that were running irregularly with reactivity of factor VIII related antigen and circumscribed by laminin were observed in the marginal zone of the infarcts. These newly formed vessels increased in number during the second and the third week also in the center of the infarcts, and one month after ischemia began to decrease. However, a number of vessels were seen in the infarcts, whose features were comparatively similar to those of normal vessels. These vessels remained as long as for two years. The number of the vessels with alkaline phosphatase and gamma-glutamyl transpeptidase activity did not increase during the first week. They increased later during the second and third week.(ABSTRACT TRUNCATED AT 250 WORDS)
In considering immunological approaches to treatment of the patients with malignant brain tumors, it seems very important to enhance the tumor specific immunity. Then, to ascertain whether tumor specific immune response occurs in these patients with malignant brain tumors, lymphocyte blastogenetic responses to tumor cells were examined in 18 patients with malignant brain tumors. Furthermore, to compare the systemic immunological responses with the local responses in the brain tumor tissues, both peripheral blood lymphocyte (PBL) and tumor infiltrating lymphocyte (TIL) were used as blastogenetic stimulators to the tumor cells. The PBL from the patients with malignant gliomas showed any positive blastogenetic response to their own glioma cells in 7 or 12 cases (about 58%). But, TIL from these patients showed a positive response in the only 3 cases (25%). In 6 cases of metastatic brain tumors, otherwise, their PBL showed any positive blastogenetic response to their own tumor cells in 4 of 6 cases (about 67%), and their TIL showed any positive blastogenetic responses in these same 4 cases. So, the tumor specific immunological responses may be stronger in the patient with metastatic brain tumors than in the patient with malignant gliomas. These immunological responses were, furthermore, more weak in the brain tumor tissues than in the systemic immunity. Then, this lymphocyte blastogenetic response to tumor cells were compared with other lymphocyte stimulating examination such as rectine or allogenetic lymphocyte stimulation. Our studies revealed that this lymphocyte blastogenetic response to tumor cells were at lower level compared with rectine such as PHA, PWM, and Con A, or allogenetic lymphocyte stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We studied the effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Microvascular endothelial cells were derived from the endothelial cells of gerbil brain. First, effects of tumor necrosis factor (TNF) or [3H] thymidine up-take by the endothelial cells and human smooth muscle cells were studied. After 4 days exposure to TNF, 50 microCi/ml of [3H] thymidine were added to these cells. [3H] thymidine up-take by the endothelial cells were suppressed by adding TNF dose-dependently. Especially, [3H] thymidine up-take by endothelial cells cultured with 1000 U/ml TNF for 4 days were 25 to 62% of the control values. These cells exposed to 1000 U/ml TNF, furthermore, became spindlelike in appearance and over up each other. But, TNF had no effect on human smooth muscle cells. Second, instead of TNF, interferon-gamma (gamma IFN) were studied in the same way. But, [3H] thymidine up-take by the endothelial cells were not effected by adding gamma IFN. Third, the supernatant of the cultured glioma cells were studied in the same way. The supernatants of 6 glioma cells in 8 cases showed TNF like activity to the endothelial cells of gerbil brain. These supernatants, that is, suppressed [3H] thymidine up-take by the endothelial cells over 50%. These suppression were, furthermore, released by adding 50 microliter anti-TNF antibodies. So, we found the cytotoxic effects of TNF on the endothelial cells of gerbil brain. The supernatants of glioma cells, also, showed TNF like activity to the endothelial cells.
Chronological changes of glioma tissues treated with local immunotherapy with OK-432 were examined by immunohistochemical method. OK-432 was injected into glioma tissues through Ommaya's reservoir 3 days (3 patients), 7 days (2 patients) and 14 days (2 patients) prior to the operation. Frozen sections surgically obtained from these patients were stained with avidin-biotin-peroxidase complex method using Leu-series monoclonal antibodies for pan T lymphocytes (Leu-1), cytotoxic/suppressor T lymphocytes (Leu-2 a), helper/inducer T lymphocytes (Leu-3 a), B lymphocytes (Leu-12), MHC class I antigen (beta 2m) and MHC class II antigen (HLA-DR). In 2 out of 7 glioma tissues obtained before local injection of OK-432, only few T lymphocytes were found infiltrating around the small blood vessels. In all glioma tissues obtained 3 and 7 days after injection, coagulation necrosis of glioma tissues was observed within 1-2 cm from Ommaya's tube and many T lymphocytes granulocytes and macrophages were infiltrating diffusely in the glioma tissues. Whereas in all glioma tissues obtained 14 days after injection, coagulation necrosis was also observed, however granulocytes and macrophages were scarce. The most of the infiltrating cells were T lymphocytes. Examination of T lymphocytes phenotypes revealed that both cytotoxic/suppressor and helper/inducer phenotypes of T lymphocytes were intermingled with each other in all cases. beta 2m was expressed on the most of glioma cells in all cases before and after injection. Whereas HLA-DR antigen was expressed on the tumor cells in 4 out of 7 cases before injection, however this antigen was expressed in all cases after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Recently lymphocytes from patients with cancer have proved to be activated by interleukin 2 (IL-2), and show a strong cytotoxicity. On the basis of this fact, we have tried to inject lymphokine activated killer (LAK) cells and recombinant IL-2 (rIL-2) directly into the cavity of brain tumor. We describe here preliminary results of the local administration of LAK cells and the rIL-2 to patients with malignant gliomas. Lymphocytes from the patients were separated from venous blood on a Ficoll gradient. By culture with rIL-2 for five days, the lymphocytes were activated to generate LAK activity, which was measured by chromium release assay. These LAK cells were capable of killing various kinds of tumor cells including their own cells. For example, their LAK activity to Daudi cell and self tumor cells was approximately 66 and 49%, respectively. These LAK cells showed a strong killing activity in excess of 40 to 70% against various tumor cells. Furthermore, activated killer cells, such as LAK cells, phytohemagglutinin-activated killer cells, and their precursor cells were serologically studied for the recognition of their biological characteristics. The phenotype of these LAK cells were sensitive to Leu 1, 3a, 7, and extremely so to 11 monoclonal antibodies, whereas LAK precursors were mainly sensitive to Leu 11 monoclonal antibodies. This observation led us to think that LAK cells belonged to the polyclonal cell populations. Following the fundamental studies, we applied this adoptive immunotherapy to 12 patients with malignant gliomas in whom standard therapy turned to be unsuccessful. All patients had histological evidence and progressive disease in spite of standard radiochemotherapy and other treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
Separation of tumor-infiltrating lymphocytes (TIL) from surgical specimen of fourteen gliomas and 6 metastatic brain tumor tissues was achieved by discontinuous density gradients. Comparison of phenotypes between separated lymphocytes and TIL in situ was examined by immunohistochemical method using monoclonal antibodies. The cytotoxic activity of these separated lymphocytes was also examined in short-term 51Cr release assay against fresh autologous tumor cells. Immunohistochemical staining of separated lymphocytes revealed the preservation of cell surface antigens of the lymphocytes. Most of separated lymphocytes were T lymphocytes and both phenotypes cytotoxic/suppressor and helper/inducer T lymphocytes were found. The Leu-3a/2a ratio of separated lymphocytes were compared with TIL in situ in the same patients and these values were almost equal in both lymphocytes. Cell number of separated lymphocytes were 1.2 x 10(5)-2.1 x 10(5)/g in glioma and 1.1 x 10(5)-3.8 x 10(5)/g in metastatic patients. Cytotoxicity against autologous tumor cells was detected in 5 out of 12 glioma and 2 out of 6 metastatic patients. There was no correlation between the cytotoxicity and cell number of separated lymphocytes or HLA-DR antigen expression on tumor cells.
Local hyperthermia using 13.56-MHz radiofrequency (RF) capacitive heating was evaluated in 19 patients with malignant brain tumor. Intraoperative heating was performed in 4 patients. RF applicators were placed on the cerebral convexity and medial surface with the tumor between them. RF power was controlled so as to maintain the brain temperature below 40 degrees C. Under these conditions, the highest temperature of each tumor varied from 44 to 52 degrees C. After heating alone for about 60 min, 3 tumors showed regression on CT scan. Extracranial heating was performed in 15 patients with cerebral glioblastoma. RF applicators were placed on the scalp and applied to diametrically opposite sides of the tumor after bilateral craniectomy not smaller than the size of the applicator. The heating was performed for about 60 min at each session and repeated twice a week for a total of 4 to 10 times in combination with radiation and ACNU-chemotherapy. The brain temperatures were maintained below 42 degrees C. The highest temperatures of the tumor varied from 42 to 46 degrees C. Seven of 13 evaluable tumors on CT scan showed regression after the treatment. Low-density lesions appeared transiently in the brains of 2 patients, located in the RF field. In conclusion, RF capacitive heating can be applied to human malignant cerebral tumors.