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Biomedical subjects

H Mogami

Publications and source records attributed to H Mogami.

At least 181 records · Page 10Linked to original sources

[Antitumor efficacy of activated macrophages against murine glioma cells].

A crucial manifestation of malignant gliomas is the regrowth of already-invaded neoplastic cells after surgical intervention. One possible approach for inhibiting such tumor growth is to utilize the tumoricidal potential of macrophages. In order to investigate the clinical application of this concept, peritoneal exudate cells (PEC) activated in vitro and in vivo by immunomodulating agents were tested for cytotoxic activity against murine glioma (203-glioma) cells. As immunomodulating agents, heat-killed Propionibacterium acnes (P. acnes), OK-432 and Concanavilin A supernatant (Con A sup) were used in these experiments. P. acnes was provided by Kowa Pharmaceutical Co., Tokyo, and OK-432 by Chugai Pharmaceutical Co., Ltd., Tokyo. Klinische Einheit (KE) units were used to express the strength of the preparation, with 1 KE equal to 0.1 mg of dried streptococci. Con A sup was produced by Con A pulsing of BALB/c splenocytes resuspended in complete medium. PEC harvested from mice to which 5% glycogen in saline had been inoculated intraperitoneally 6 d previously were activated in vitro by P. acnes (P. acnes-PEC), OK-432 (OK-432-PEC) and Con A sup (Con A-PEC). The cytotoxic activities of P. acnes-PEC, OK-432-PEC and Con A-PEC were approximately 25%, 65% and 60%, respectively. PEC were then collected from mice into which either 100 micrograms of P. acnes or 1 KE of OK-432 had been injected intraperitoneally several times. The antitumor effects of P. acnes-PEC and OK-432-PEC were about 35% and 50%, respectively. These activated PEC demonstrated cytotoxic activity against murine glioma in the tumor neutralization assay (Winn assay). Also, the antitumor efficacy of OK-432-PEC belonged mainly to adherent cells. Meningeal gliomatosis (MG) models were prepared for clinical studies. Viable 203-glioma cells (5 X 10(6) were injected percutaneously into the cisterna magna of C57BL/6 mice. The median survival time (MST) of the untreated group was 8.5 days. The MST of the groups treated by intraperitoneal and intracisternal administration of P. acnes were 26 and 33 days. This therapy significantly prolonged the survival time of these models, particularly by the intracisternal treatment. The differential cell count by Giemsa staining and latexphagocytic cell findings revealed that macrophages accounted for more than 90% of the P. acnes-PEC. These results may indicate that activated (PEC) macrophages were induced intracisternally by P. acnes and that activated macrophages induced intraperitoneally exerted antitumor effects in MG models.

Animals↗

[Meningeal gliomatosis model in nude mice].

The nude mouse has been proposed as a model animal for testing the chemosensitivity of human cancer cells, and encouraging results have been obtained. Murine brain tumor models were successfully prepared by direct inoculation of glioma cells into the cerebral hemisphere, an immunologically privileged area. However, the blood-brain barrier was destroyed mechanically by this manipulation. Accordingly, experimental models of MG were established by intracisternal inoculation of human glioma cells (ONS-6, -12, and -16). These cell lines were established by primary explant technique from our biopsy specimens. The outgrown cells were trypsinized and cultured in monolayers. Tumor cells (10(7) in 0.1 ml) were inoculated transcutaneously into the cisterna magna of BALB/c nu/nu mice using a 27-gauge needle. Tumor growth generally occur in no more than 10-20% of nude mice transplanted subcutaneously. Also, nude mice which were transplanted with these 10(7) glioma cells rejected the tumor. MG models which were inoculated with the same tumors intrathecally, however, all died within a month after inoculation. In in vitro studies, the doubling time (DT) of ONS-6, -12, and -16 were 30.5 h, 41.5 h and 60.9 h, respectively. Median survival time (MST) of MG models inoculated with ONS-6, -12, and -16 glioma cells were 8.5 days, 15.5 days and 18.5 days, respectively. These DTs were well correlated with the MST. Clinicopathological features observed in MG models were similar to those seen in diffuse leptomeningeal involvement of glioma in human beings. Tumor cells were disseminated in the diffuse arachnoid space, involving the cerebral hemisphere, spinal cord and throughout the cauda equina. Some tumor cells infiltrated the cerebral parenchyma and Virchow-Robin space. The models will be useful for investigating the pathophysiology of MG and the efficacy of chemotherapeutic agents.

Animals↗

[Surgery of high-flow arteriovenous malformation: with special reference to normal perfusion pressure breakthrough phenomenon].

Hemodynamic changes are of importance while removing large and high-flow arteriovenous malformations (AVM), because a phenomenon called "normal perfusion pressure breakthrough" may occur. In this report, we evaluated hemodynamic changes in 14 cases of high-flow AVM with cerebral angiogram and intraoperative monitoring of cortical-surface blood flow. The criteria we used for high-flow AVM are; nidus larger than 4 cm, a few large feeders, high-flow shunt in the nidus, and reduced circulation or dilated arteries in the adjacent brain tissue. For last 2 years, we experienced 14 cases of high-flow AVM which fulfilled the criteria, and 9 of these were operated on for total removal of AVM. Of those, 2 cases evolved postoperative local edema and hemorrhage and was thought to be due to "normal perfusion pressure breakthrough." Intraoperative monitoring of cortical-surface blood flow was useful to predict occurrence of "perfusion breakthrough", because blood flow in the adjacent brain tissue increased markedly with feeder clipping. Intraoperative barbiturate protection and postoperative controlled hypotension were thought to be useful for prevention of "normal perfusion pressure breakthrough", though the details of mechanisms are unknown.

Adolescent↗

[Development of experimental meningeal gliomatosis models using nude mice].

Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of human glioma cell lines into nude mice. The tumor growth was steady and fast in MG nude mice if 10(7) cells were implanted. Median survival time (MST) of nude mice inoculated with tumor cells was inversely related to the number of cells inoculated. There was a correlation between in vitro and in vivo (MG models) growth rate, which means that the cell kinetics in vitro are reflected in vivo. The clinicopathological features observed in nude mouse MG models were similar to those seen in diffuse leptomeningeal involvement of gliomas in humans. The models will be useful for investigating the pathophysiology of meningeal gliomatosis and the efficacy of chemotherapeutic agents.

Animals↗

[Cortical somatosensory evoked potential associated with experimental chronic cord compression by epidural neoplasm in rabbits].

An experimental model of spinal cord compression was developed in rabbits by epidural neoplasms which were injected anterior to the T 13 vertebral body and grew into the spinal canal through the intervertebral foramina. With this experimental model, the neurological condition of the animals was monitored using a scale and changes of somatosensory evoked potentials (SEPs) were studied to evaluate the neurophysiological effect of experimental chronic cord compression. The animals were immobilized with pancuronium bromide and artificial respiration was maintained through a tracheostomy. SEPs were recorded by silver ball electrodes which were positioned epidurally over the somatosensory cortex through small burr holes. A subcutaneous needle placed at the nose served as a reference electrode. Right hind paw was stimulated via two percutaneous needles with 0.1 msec rectangular impulses sufficiently strong to produce motor responses, ranging from 10 to 20 volt in control rabbits. Electrical stimuli were delivered at a rate of 1 Hz. The intensity of electrical stimulation was raised up to 300 volt, when no consistent SEP was observed in the rabbit with spinal neoplasm. The SEP was summated by averaging 50 successive cortical transients with the analysis time of 200 and 500 msec. The cortical SEPs in the rabbit normally consisted of a positive-negative sequence, which we labelled P1, N1, P2, N2 and so on. Early peaks, P1 and N1, were observed constantly with average latencies of 30.1 and 53.3 msec respectively in normal rabbits. The variability of amplitudes seen even in control animals made them a less useful measure of function than latencies. Normal SEPs were preserved until the animals demonstrated moderate paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of alveolar soft-part sarcoma with recurrent cerebral metastasis--operative management of the cerebral metastasis].

A female patient noticed a painless swelling at the right thigh at the age of 12. Two years later, she had total removal for the tumor and irradiation. The diagnosis of the tumor was alveolar soft-part sarcoma. At the age of 16 she had left pneumonectomy for its metastasis. The next year the metastatic tumor is detected in the right lung. At 21 she was admitted to our service with a diagnosis of cerebral metastasis. Her chief complaints were headache, nausea and visual disturbance. Neurological examination revealed advanced choked disc and left homonimous hemianopsia. CT scan revealed a large vascular tumor in the right occipital lobe and chest film showed multiple metastatic shadows in right lung. A large bloody tumor was removed totally through right occipital craniotomy. She was discharged with a marked improvement of neurological symptom. Since then she had had 8 times of surgical removal for 10 cerebral metastatic tumors. Several chemotherapy was attempted for three times. At first adriamycin was administered after the first removal of cerebral metastasis. Methyl-CCNU and Picibanil was administered after the second removal. Soon after the chemotherapy, metastatic tumor recurred. Cisplatin was administered for the ninth metastasis. None of these chemotherapy had seemed to be benefit in the management. At 27 she had removal of metastatic tumor on chest wall. She died of respiratory embarrassment in thorax at 30. At autopsy she had metastatic tumors in right frontal lobe, right lung, mediastinum, heart, chest wall, and intestine. During her illness, she graduated from high school and college, and got a good job as a secretary.

Adult↗

[Cardiac myxoma metastatic to the brain].

A case of cardiac myxoma presenting as metastatic brain tumor are reported. The patient was a 44-year-old man. One year prior to this admission, he had suffered stroke, which was characterized by right hemiparesis and dysarthria. The computed tomographic (= CT) scan of the head at that time showed a low density on the left basal ganglia and the echocardiogram suggested a left atrial myxoma. At surgery, a polypoid myxoma attached to the atrial septum was totally removed. Right hemiparesis was improved and the patient was discharged. A few months later, the patient was evaluated for multiple cutaneous masses and diagnosed by biopsy as metastatic myxoma. The patient's condition remained unchanged until this admission. In March 1985, the patient had a tonic-clonic convulsion marching from right hand and developed right hemiplegia with drowsy. An echocardiogram failed to reveal recurrence of the cardiac myxoma. A CT scan revealed a 5-cm, relatively circumscribed, low density mass in the left fronto-parietal lobe, ring mottled enhancement after contrast administration and more enhancement in the delayed scanning of 45 min. Craniotomy showed a tender, friable tumor with a yellowish cyst fluid, but apparently not invading the brain parenchyma. After complete excision of the mass, there was rapid lessing in the hemiplegia and improvement in the level of consciousness. A contrast-enhancement CT scan performed 2 weeks after craniotomy revealed no evidence of residual tumor. Pathohistological examination showed spindle-shaped and stellate cells which formed clusters and contained large amounts of acid polysaccharides as demonstrated by the alcian blue method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Local cerebral blood flow and glucose metabolism in experimental meningeal carcinomatosis].

Patients with meningeal carcinomatosis often evolve signs of impairment in higher mental function. Yet, common findings of histological observation are only a sheet of tumor cells on the cortical surface, and no intracerebral mass are noted. To elucidate mechanism of mental disturbances in meningeal carcinomatosis, local cerebral blood flow and glucose metabolism were evaluated in a model of experimental meningeal carcinomatosis. Viable cells (1 X 10(4) of Walker 256 tumor were inoculated into cisterna magna of Wistar rats. Animals were used for autoradiographic study at 1 to 12 days after tumor inoculation. Local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) were measured with quantitative autoradiographic technique using 14C-iodoantipyrine and 14C-deoxyglucose as a tracer, respectively. In the early stage of tumor growth (1 to 3 days after tumor inoculation), reduction of LCGU was averaged to be 31% in the cerebral cortex and 28% in the deep structures, whereas reduction of LCBF was 28% in cerebral cortex and 19% in deep structures on average. In the late stage of tumor growth (4 to 12 days after tumor inoculation), average reduction of LCGU was 57% in the cerebral cortex and 47% in the deep structures. On the other hand, reduction of LCBF was averaged to be 42% in the cerebral cortex and 38% in the deep structures in the late stage of the disease. Reduction of LCGU and LCBF was especially evident in the sensory cortices such as parietal cortex, visual cortex and auditory cortex, and in the auditory centers of the brain stem such as medial geniculate body and inferior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cytosuppressive effect of bromocriptine on human prolactinomas: stereological analysis of ultrastructural alterations with special reference to secretory granules.

To ascertain the mechanisms of bromocriptine in lowering serum prolactin (PRL) levels and reducing the cell size of human prolactinomas, stereological analysis at electron microscope level was performed on six adenomas treated with bromocriptine (10 mg/day for 2 weeks) and four untreated adenomas. The bromocriptine treatment significantly decreased all the major organelles involved in PRL synthesis when expressed in absolute volume per single tumor cell, although it decreased only Golgi apparatus when expressed in relative volume within the cells. Secretory granules, lysosomes, and lipid droplets increased in relative volume but not in absolute volume in bromocriptine-treated adenomas. Consequently, bromocriptine decreased the volume of individual tumor cell to approximately 60% of that of untreated tumor cells. Unexpectedly, exocytosis of secretory granules increased significantly in the bromocriptine-treated adenomas in spite of a remarkable decrease in serum PRL levels. This appears to be contradictory to the current view that a decrease in serum PRL levels with a concurrent increase in the intracellular PRL levels caused by bromocriptine treatment results from the inhibition of exocytosis of secretory granules. The secretory granules of bromocriptine-treated adenomas may contain a small amount of PRL, as suggested by a culture study reporting degradation of PRL by bromocriptine.

Adenoma↗

Effects of bromocriptine on prolactin-secreting pituitary adenomas. Mechanism of reduction in tumor size evaluated by light and electron microscopic, immunohistochemical, and morphometric analysis.

Prolactin-secreting pituitary adenomas were studied to clarify the mechanism by which bromocriptine reduces tumor size. Patients examined consisted of three groups: Group I (four cases) received no medication, Group II (six cases) continued bromocriptine treatment (10 mg/day for 2 weeks) until the operation, and Group III (five cases) discontinued the treatment 1 week before the operation. Adenomas in Group II showed a variety of degenerative and necrotic changes of tumor cells in addition to marked decrease in volume of individual cell. Adenomas in Group III showed divergent structural changes. Irreversible changes seen in Group II became more pronounced with a marked increase in stromal tissue. Proliferative areas consisting of intermediate-sized cells were found in the scarce stromal tissue. The findings seem to indicate that the reduction in size of prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as from cell loss secondary to necrosis.

Adenoma↗

Accumulation of amyloid in pituitary adenomas.

The accumulation of amyloid in pituitary adenomas was examined in relation to the types of adenoma and the effect of bromocriptine treatment. Amyloid had accumulated in 34 of 48 adenomas (71%). The occurrence in prolactin-secreting adenomas and growth hormone-secreting adenomas was 79%, respectively, while that in non-functioning adenomas was 50%. Treatment with bromocriptine enhanced the occurrence and extent of the amyloid accumulation in prolactin- or growth hormone-secreting adenomas. Electron microscopy revealed the initial appearance of the amyloid fibrils in the smooth endoplasmic reticulum and a possible sequential process of their release from the cells. The presence of secretory granules in vesicles containing amyloid fibrils and their simultaneous release with amyloid fibrils suggested that degradation of secretory granules was involved in the formation of amyloid.

Adenoma↗

Purification of astroprotein (astrocyte-specific cerebroprotein) by reversed-phase C-1 HPLC.

A method for purification of astroprotein (an astrocyte-specific cerebroprotein) with HPLC is described. A linear gradient from 30 to 70% acetonitrile in 0.1% trifluoroacetic acid (pH 2.2) was applied to the reversed-phase C-1 (particle size 10 micron) column. Cerebroproteins from the crude extract from human glioma were clearly separated by this procedure. Highly purified astroprotein was homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and has immunoreactivity to antiserum against astroprotein. Reversed-phase C-1 HPLC offers advantages over previously available preparative techniques in the higher purity and better separation time of the products.

Chromatography, High Pressure Liquid↗

Usefulness of intraoperative cortical blood flow measurement by heat clearance method for monitoring cerebral ischaemia during therapeutic carotid ligation.

Changes of regional cortical blood flow (rCBF) was monitored by the heat clearance method during the operation of cervical carotid ligation combined with superficial temporal artery and middle cerebral artery anastomosis for the treatment of inaccessible aneurysms of the internal carotid artery in eight patients. There were three types of rCBF responses upon closure of the internal carotid artery, with or without bypass blood flow. Based on the responses, the internal carotid artery was ligated abruptly or occluded gradually. The usefulness of the method for monitoring cerebral ischaemia for therapeutic carotid ligation is discussed.

Body Temperature↗

Prolactin secretion in acromegalic patients before and after selective adenomectomy.

PRL secretion before and after transsphenoidal adenomectomy was studied in 13 patients with acromegaly. Six patient had elevated basal serum PRL levels before surgery, while 7 patients had normal levels. In every patient, the basal serum GH level decreased to less than 5.0 ng/ml after surgery. In the group (group A) with high basal serum PRL levels (mean +/- SD, 41.3 +/- 5.8 ng/ml) before surgery, the PRL levels decreased significantly (P less than 0.0002) to less than 10.0 ng/ml (4.8 +/- 3.6 ng/ml) after the operation. However, in the group (group B) with normal levels (10.8 +/- 4.4 ng/ml) before surgery, PRL levels changed little (7.8 +/- 3.1 ng/ml) after the operation. In group A, the increment of PRL after TRH injection decreased or disappeared (P less than 0.02; 4.1 +/- 2.4 ng/ml) after surgery compared with that before surgery (39.2 +/- 25.9 ng/ml). On the other hand, in group B, the increment of PRL after TRH injection was nearly unchanged (17.1 +/- 7.0 ng/ml) after surgery compared with that before surgery (19.3 +/- 8.0 ng/ml). The results indicate that PRL is secreted from the pituitary adenoma in acromegalic patients with hyperprolactinemia, while PRL secretion from the normal part of the pituitary gland is decreased.

Acromegaly↗

Hypothalamic hamartoma: report of two cases.

Two histologically confirmed hypothalamic hamartomas, one in a 7-year-old boy and another in a 10-year-old boy, are reported. One patient had precocious puberty, epileptic laughter, and abnormal behavior; the other had cerebral seizures. Partial removal of the tumors had no effect on precocious puberty; however, behavior improved in the first patient, and seizure control improved in the second patient.

Child↗