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Biomedical subjects

M Miyagami

Publications and source records attributed to M Miyagami.

At least 19 recordsLinked to original sources

[Ultrastructural findings of arachnoid cysts and epithelial cysts].

There may be several kinds of pathological conditions in the cystic lesion which are clinically diagnosed as benign intracranial cysts on CT scan. Light and electron microscopic studies on cyst walls were important in the differential diagnosis of benign intracranial cysts. We have studied 5 cases of intracranial arachnoid cysts and two epithelial cysts using the light and electron microscopy. Five cases of intracranial arachnoid cysts included two children and three adults (three females and two males). Three cases of them were localized in the middle cranial fossa, one case in the anterior and middle cranial fossa and one case in the lateral ventricle, giving headache and convulsion as the initial complaints. As for the epithelial cysts, one was localized at the para-collicular area complaining enlarged head and swollen anterior fontanelle and the other of four years was located in the fourth ventricle with headache and ataxic gait. On CT all of them demonstrated diffuse low density areas in both the arachnoid and the epithelial cysts without communicating findings between the cystic cavities and subarachnoid space on metrizamide CT cisternography. The arachnoid cyst walls were basically similar in structure to the normal arachnoid membrane and composed of elongated epithelial cells like the arachnoid cell and the connective tissues with lamellar collagen fiber bundles. However, 3 of the 5 cases had only fibrous tissues without epithelial cells. The inner sheath of the arachnoid cyst walls was composed of one or several layers of the arachnoid cells with flattened and relatively electron-dense cytoplasm on electron micrograph. They had a lot of elongated process and were tangled with each other, making large extracellular spaces between them. Below the electron dense arachnoid cells, compact packed cells with interdigitation partly demonstrated intercellular contacts such as numerous desmosomes and tight junctions. In those intercellular spaces collagen fibers and microfibrils were observed. The cells contained abundant cytoplasmic microfibrils and numerous organelles. They were separated from numerous collagen fibers and fibroblasts by non continuous basal lamina under the epithelial cells. Epithelial cyst wall had a layer of cuboidal or columnal epithelium in the inner layer of cyst wall. Those epithelial cells demonstrated granules having positive in PAS and mucicarmine stain in their cytoplasm. On electron microscopical study epithelial cells revealed a lot of microvilli and coating materials on the surface of them without cilia. The basement membranes were well developed under the epithelial cells separated from the connective tissues. In the intercellular clefts of the epithelial cells tight junctions and interdigitations were recognized.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Intra-arterial ACNU chemotherapy employing 20% mannitol osmotic blood-brain barrier disruption for malignant brain tumors.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.

Adolescent

[Chemotherapy with ACNU and radiation therapy in malignant glioma in cerebral hemisphere of adult].

54 cases of malignant gliomas in adults localized in cerebral hemisphere including the location of basal ganglia and corpus callosum in 26% were survived over one month and followed more than 2 years after operation for 10 years recently. Histologically they had 40 cases of glioblastoma multiforme and 14 cases of anaplastic astrocytoma. All malignant gliomas were given an operation and radiation, classifying 4 groups due to chemotherapeutic methods; Group I (20 cases) was treated by intraarterial infusion of ACNU with 20% mannitol. The others were Group II (8 cases) treated by intraarterial infusion of ACNU only, Group III (13 cases) by intravenous infusion of ACNU only and Group IV (13 cases) by no chemotherapy. Post-operative survival rates in the malignant gliomas of Group I were that 1 year survival rate was in 16 out of 20 cases (80%), 2 years in 55%, and 5 years in 25%. In glioblastoma multiforme, 1 year survival rate of Group I was recognized in 70% and 2 years in 36%, a little better than the other treatments. 2 year survival rate of other treatments demonstrated 17% in Group II, 25% in Group III, and 11% in Group IV. CT findings of glioblastoma multiforme in Group I showed no rest tumor in 4 cases and one case of CR, and 3 cases of PR in the follow up study of 10 cases with rest tumor on CT after operation. There were no permanent complications except for temporary mild neurological deficit in 7% of Group I improving within 2 to 3 days after intraarterial infusion of ACNU and 20% mannitol. It is suggested that chemotherapy of Group I by intraarterial infusion of ACNU and 20% mannitol demonstrated a little better therapeutic efficacy than the other Groups, at least within 2 years after operation.

Adult

[MCNU delivery into malignant brain tumor and normal brain tissue by intravenous or intraarterial infusion].

In 13 Fischer 344 rats transplanted intracerebrally with 9 L gliosarcoma, 13 normal Fischer 344 rats and 4 clinical cases of malignant glioma, a new water-soluble nitrosourea (MCNU) was given and the concentration was measured in blood, tumor tissues, normal brains around the tumors and normal hemispheres by intravenous or intraarterial infusion of MCNU. At 5 min. after administration of MCNU 20 mg/kg (4-5 mg/body) in 9 L gliosarcoma bearing Fischer rats, mean MCNU concentration in the blood was not different between 20 micrograms/ml intravenous and 23 micrograms/ml intraarterial administrations whereas that in the tumor tissues by intracarotid infusion of MCNU was 40 +/- 14.4 micrograms/g which was about two times as much as 22.9 +/- 8.13 micrograms/g by intravenous infusion of MCNU. Mean MCNU concentration of normal brains around tumor tissues was 2.49 micrograms/g in intravenous and 8.95 micrograms/g in intracarotid infusion. MCNU concentration of tumor tissues in 4 cases of malignant gliomas was higher by intracarotid administration than by intravenous administration compared to that in the blood. Maximum tumor/blood ratio of MCNU was 1.94 in intracarotid administration for the malignant glioma. It is suggested that intraarterial administration was more useful than intravenous infusion as an administration route for malignant brain tumors.

Animals

[Therapeutic efficacy of intracarotid infusion of 20% mannitol with ACNU in Fischer rats with intracerebrally implanted 9L gliosarcoma].

The purpose of this study was to investigate the therapeutic effect of intracarotid infusion of 20% mannitol with ACNU chemotherapy in Fischer 344 rats with intracerebrally implanted 9L gliosarcoma, compared with giving them only ACNU intraperitoneally. Thirty 9L gliosarcoma bearing Fischer 344 rats were evaluated in the following 3 groups. Group I: control (no treatment); group II: treated by ACNU 20 mg/kg intraperitoneally on the 7th day after implantation of 9L gliosarcoma cells; group III: treated by intracarotid infusion of 20% mannitol 3.1 ml/min. and with the same dose of ACNU as in group II. Mean survival time after the inoculation of tumor cells into the brain was 15.1 days (group I), 21.8 days (group II) and 27.9 days (group III). In group II all tumor-bearing Fischer rats died within 24 days after inoculation of tumor cells, whereas in group III 5 out of 6 rats survived more than 25 days after them. Group III evidenced necrosis and degenerative findings with vacuole and microcyst without vascular proliferation in tumor tissues more than group II on the 7th day after ACNU treatment for the experimental brain tumor. On the 7th day after ACNU treatment of each group, BrdU labeling index was calculated in order to evaluate tumor proliferation. The Mean BrdU labeling index in tumor cells of group III demonstrated 7.5%, against 14.5% (about one half) in group II. From our experimental study of survival time and BrdU labeling index, it is suggested that osmotic blood brain barrier disruption chemotherapy by intracarotid infusion of 20% mannitol and ACNU was more effective than simple treatment by intraperitoneal injection of ACNU in the Fischer rats with intracerebrally implanted 9L gliosarcoma.

Animals

[Diagnostic value of neuron specific enolase (NSE) in the cerebrospinal fluid of malignant brain tumor with intrathecal metastasis].

Neuron specific enolase (NSE) in the cerebrospinal fluid (CSF) and serum of 54 cases of brain tumors, in the tumor tissues of 10 brain tumors and in the cyst fluids of 7 brain tumors was measured by radioimmunoassay with NSE measurement kit (Eiken Chemistry co.) NSE values in the cerebrospinal fluid of 35 malignant brain tumors showed abnormal increase higher than 10 ng/ml in 17 cases (about 50%) of them, whereas all of benign cases were lower than 10 ng/ml. The means and standard deviations of NSE in the cerebrospinal fluid of malignant tumors were 20.63 +/- 20.78 ng/ml in the astrocytoma grade 3 and 4, 19.73 +/- 15.5 ng/ml in the medulloblastoma and 12.4 +/- 8.9 ng/ml in the germ cell tumor. NSE values in the CSF of 12 brain tumors with intrathecal metastasis were 28.0 +/- 18.9 ng/ml (mean +/- SD) showing about three times as much as those without intrathecal metastasis. There was significant difference between these groups (p less than 0.01). All cyst fluids including in 7 cases of brain tumors demonstrated high values of NSE even if they were benign tumor and their NSE values in CSF were normal. NSE values of brain tumor tissues had no correlation with malignancy, but were higher in the periphery of the tumors than in the center. NSE values of CSF in brain tumors might be changed in relation with the improvement or deterioration on clinical state and CT. It might be suggested that the measurement of NSE in the CSF had significance as a monitor of therapeutic efficacy and prognosis for the brain tumors.

Animals

[Delayed radiation necrosis of the temporal lobe following radiation therapy of maxillary carcinoma].

A case of delayed radiation necrosis following radiation therapy for maxillary carcinoma was reported. The diagnosis of this case for the radiation necrosis was clinically suggestive and established by the pathological findings of autopsy. This 66 year-old man had been treated by the partial resection for the right maxillary carcinoma with chemotherapy (pepleomycin 110 mg, adriamycin 20 mg). Pre- and postoperatively total dose of 5040 rads were irradiated with cobalt therapy during 42 days at a dose of 180 rads and 5 times in a week through two ports at 8 x 8 cm field including right orbital region. Three years 7 months after radiation therapy he complained of disorientation, recent memory disturbance and slight left hemiparesis. On enhanced CT irregular ring enhanced mass lesion was seen in left temporal lobe inside the radiation field with extensive low density over temporal lobe on plain CT. MR imaging demonstrated that T 1-weighted spin echo images with a 50-msec repetition time (TR) and 22-msec echo time (TE) had irregular low signal intensity and extensive high signal intensity combined with partially low intensity in the central area on T2 weighted spin echo images with 2300 msec TR and 100 msec TR. There were not appeared vascular obstruction and stenosis on right carotid angiogram. He improved remarkably on clinical symptoms and CT by treating of dexamethasone and osmotic diuretics, but died of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Neuroradiological image analysis and prognostic factors of malignant gliomas in the cerebral hemisphere of adults].

54% cases of malignant gliomas followed more than 2 years were studied about prognostic factors focusing on neuroradiologic image analysis in the two groups classified survival cases over 2 years and dead cases within 2 years after surgical treatment. 21% cases of malignant gliomas having tumor infiltration or edema to contralateral hemisphere on CT and MRI before treatment were dead within 2 years. 80% of recurrent malignant gliomas had abnormal shadow on CT due to tumor recurrence in primary tumor site or ventricular wall and/or contralateral hemisphere continuing with there. Remote metastasis discontinuing with primary site was demonstrated in only 20% of them. Over 90% of glioblastoma multiforme showing irregular tumor stain with arteriovenous fistula on angiogram were dead within 2 years, whereas in the cases without tumor stain the alive cases more than 2 years increased comparing with those having tumor stain.

Adult

[The effect on the tumor vessel permeability by hyperosmotic blood brain barrier disruption].

The limited effect of chemotherapy on malignant brain tumors has been related to tumor cell insensitivity to the drugs and to their ineffectual delivery to the tumor. The studies by Groothuis and Neuwelt et al have shown that the studies of tumor vessel permeability show considerable variability in different areas of tumors and between different tumor models. The present studies used the 9L gliosarcoma model in Fischer 344 rats to evaluate the increase of tumor vessel permeability by osmotic BBB opening on drug delivery to the tumor, brain adjacent to tumor (BAT), and brain distant to tumor using cis-diamminedichloroplatinum (CDDP) as a chemotherapeutic agent which was water soluble and rarely permeable to BBB. In addition the difference of delivery to normal brain and tumor tissue were studied on intravenous or intracarotid administration of cisplatin with or without intracarotid infusion of graded (20%, 25%) hyperosmolar mannitol. Evans blue, which binds to plasma albumin, was used to provide a visual marker of BBB opening. 20% or 25% hyperosmolar mannitol infusion to right internal carotid artery for BBB disruption was done at 0.12 ml/sec for 30 sec with controlled respiration after temporally clipping of right common carotid artery. Then cis-diamminedichloroplatinum (CDDP) was infused at 0.5 mg/ml/100 gr (body weight). In control studies isotonic saline instead of mannitol was infused to intracarotid artery at identical rate and volume. In 14 9L gliosarcoma bearing rats and 3 normal rats cis-diamminedichloroplatinum (CDDP) delivery to tumor and normal brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Immunocytochemical localization of factor VIII-related antigen in tumors of the human central nervous system.

Using both immunohisto- and immunocytochemical techniques with periodate-lysine-paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII-related antigen (FVIIIR:Ag) in 12 cases of tumors of the human central nervous system (CNS) and one sample of non-tumor brain tissue. FVIIIR:Ag was found both extracellularly and intracellularly. It was localized in the vascular lumen, between endothelial cells, and in the endothelial cell basement membrane. In the endothelial cell cytoplasm, FVIIIR:Ag was found in the endoplasmic reticulum, perinuclear space, and in intracytoplasmic vacuoles and vesicles. Characteristic of malignant tumors (six out of seven) was a strongly-positive dilated endoplasmic reticulum. This may reflect increased FVIIIR:Ag synthesis in the endothelial cells of malignant tumors. Only one of five benign tumors showed such staining. Six of 12 tumors and the non-tumor brain showed perinuclear FVIIIR:Ag. Both ad- and abluminal vesicles in the tumor endothelial cells contained FVIIIR:Ag suggesting that endocytosis, transcellular transport, and/or endocytosis, as well as FVIIIR:Ag synthesis occurs. The non-tumor brain showed normal capillary structure and very little FVIIIR:Ag immunoreactivity. The relationship of these FVIIIR:Ag abnormalities to the hypercoagulable state seen in some malignant brain tumor patients remains to be clarified.

Antigens

[Tubular bodies (Weibel-Palade) in the endothelial cell of glioblastoma].

Authors have studied the ultrastructure of endothelial cells in the microvessels of malignant and benign gliomas and in particular, the numbers of tubular bodies (Weibel-Palade) in endothelial cells of glioma microvessels in related with blood vessel proliferation. Glioblastoma 6, astrocytoma grade II 1, oligodendroglioma 1 and 2 samples of non-tumor brain tissue were analyzed quantitatively using light and electron microscope with Karnovski fixative. All tissues were obtained from the center, the intermediate and the margin in each tumor tissue and just outside of the tumor at operation. 389 microvessels were examined in the total gliomas electronmicroscopically. Tubular body was first described by Weibel and Palade in the vascular endothelial cells of various organs in both man and animals. This is now considered to be an organelle specific to the endothelial cell, but its function is still unknown. Tubular body observed in the endothelial cells of the gliomas vessels consisted of a membrane-limited round, oval or elongated shaped intra cytoplasmic body (about 0.1-0.2 micron) which contained tubules of 150-200 A outer diameter. Tubular bodies were classified in the two types. One of them (mature type) was relatively electron dense to be more compact, the other (immature type) had relatively pale matrix. In the immature type they are located in close proximity to the Golgi complex or endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma

[ACNU delivery to malignant glioma tissue by osmotic blood brain barrier modification with intracarotid infusion of hyperosmoral mannitol].

Drug delivery to the tumor has been one of the major subjects in the field of brain tumor chemotherapy because of blood brain barrier. Recent studies including quantitative autoradiographic studies revealed that blood brain barrier is present and intact in the brain adjacent to tumor where viable tumor cells are infiltrating, and also in the tumors which are early in the development. In 1972 Rapoport et al demonstrated that it is possible to transiently and reversibly open the blood brain barrier by an intracarotid infusion of a hyperosmoral solution. This technique is found to increase cerebrovascular permeability to chemotherapeutic agents. Six cases of glioma, including 4 astrocytoma grade 4, 1 astrocytoma grade 3, 1 astrocytoma grade 2, were treated during operation with intracarotid infusion of ACNU 100 mg/body/5 min. (1.3-2.2 mg/kg) following intracarotid infusion of 20% mannitol 200 ml (1.3-1.6 ml/sec) through the catheter in the internal carotid artery set preoperatively, and ACNU concentration in tumor tissues and blood were measured at 5, 10, 15, 20, 25, 30, 40, 60 minutes after that. On every case mannitol contrast enhancement CT was studied by the intracarotid infusion of 60% conray 100 ml/5 min. following the intracarotid infusion of 20% mannitol 200 ml comparing with contrast enhancement CT and plain CT. Maximum ACNU concentrations in blood were 2.12-4.12 micrograms/ml (mean 3.1 +/- 0.74) at 5 min. after the intraarterial administration of mannitol and ACNU on every case. At 20 min. following the administration ACNU levels were decreased to half level (mean 1.49 +/- 0.42 microgram/ml) and 0.58 +/- 0.18 microgram/ml at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Ventricular enlargement in experimental occlusion of superior sagittal sinus--in reference to histopathological findings (author's transl)].

An experimental occlusion of superior sagittal sinus was made in dogs according to ligation with thread at the posterior third portion of the sinus. Ventricular enlargement and histological changes in the cerebrum were studied in various stage after occulusion of the sinus. In the acute stage, no ventricular enlargement occured. However, in the chronic stage, nine dogs out of 12 dogs showed enlargement of the ventricle. Hitological examination revealed peeled ependymal layer from subependymal tissue, edematous findings in the periventricular tissue, perivascular gliofibrosis, perivascular hemorrhage, exanguination of plasm, and venous stasis in the ventricular wall and cerebral cortex in convexity. Extracellular space in the subependymal tissue, and the space between pial and glial membrane were widened remarkably. Two factors were raised by authors as the pathogenesis for ventricular enlargement. One factor was the hydrodynamic disturbance of CSF according to the CSF malabsorption into the superior sagittal sinus through arachnoid villi. The other one was the disturbance of venous circulation due to occlusion of the sinus.

Animals