Biomedical subjects
Publications and source records attributed to N Arita.
A 6-year-old girl developed a glioblastoma in the basal ganglia and brain stem 5 years after surgical excision and local irradiation (5460 cGy) for craniopharyngioma. Clinical and histological details are presented, and the literature on radiation-induced gliomas is reviewed.
A 15-year-old boy developed a glioblastoma in a cerebellar hemisphere 7 years after surgical excision and local irradiation of a pilocytic astrocytoma in the cerebellar vermis. Clinical and histopathological details are presented, and the literature on late malignant recurrence of childhood cerebellar astrocytoma is reviewed.
Distributions of two different subclasses of intermediate filaments, vimentin and glial filaments, were studied immunohistochemically in human brain tumors using specific antiserum to each protein subunit, vimentin and astroprotein (GFAP), Surgical specimens (5 meningiomas, 4 ependymomas, 5 benign astrocytomas, 5 anaplastic astrocytomas and 7 glioblastomas) were fixed in 95% ethanol or ethanol-acidic acid (95:5) and embedded in paraffin Avidin biotin peroxidase-complex (ABC) method (Vectastain) was carried out on 6 microns-thick paraffin sections. All meningioma cells were negative for astroprotein (GFAP) and positive for vimentin. Ependymoma cells showed various patterns of immunoreaction for astroprotein (GFAP) but were invariably positive for vimentin. In benign astrocytomas, many cells (or cell body and processes) were positive for astroprotein (GFAP). Immunoreaction for vimentin was, however, less frequent and intense. In anaplastic astrocytomas, population of astroprotein (GFAP)-positive cells decreased and vimentin-positive cells increased. Astroprotein (GFAP)-positive cells were further decreased in glioblastomas and the population of vimentin-positive cells varied among tissues. The present study suggests that the anaplastic change of astrocytoma cells were associated with decreased expression of glial filaments and increased expression of vimentin filaments. It was also suggests that the expression of both intermediate filaments may be suppressed in highly-malignant glial tumor cells.
Malignant granular cell tumor of the esophagus found in a 70-year-old female was reported. Microscopically, the tumor showed a variety of the histology from compact proliferation of polygonal granular cells in pseudo-epitheliomatous pattern to plexiform proliferation of elongated granular and fibroblastic cells in neurofibromatous pattern, and the tumor cells frequently contained eosinophilic globules in the cytoplasm. Histochemically, argyrophilic neurofibrils in the stroma and argyrophilic cytoplasmic processes or grains were seen. Immunohistochemically, the tumor cells showed positive reaction with S-100 protein (S-100), but all reactions with myoglobin (MG), desmin (DM), fibronectin (FN), creatinine phosphokinase-mm (CPK), factor 8th-related antigen (F8RA), alpha-1-antitrypsin (A1AT), alpha-1-antichymotrypsin (A1ACT), keratin (KN), and carcinoembryonic antigen (CEA) were negative. Electron microscopy revealed that the tumor cells had typical lysosomal granules filled with proteinaceous electron dense materials and fine membrane-bound particles sized 15 to 45 nm resembling virus or neurosecretory granule.
Today, many gynecologists consider that the first choice of the treatment of prolactinomas is bromocriptine therapy. Because bromocriptine not only decreases the levels of serum prolactin but also reduces the tumor size. On the other hand, the patients with non-functioning adenoma sometimes show hyperprolactinemia, probably because PIF (prolactin inhibiting factor) cannot reach the normal prolactin-producing cells of the adenohypophysis. Therefore non-functioning adenoma with elevated serum prolactin levels should be distinguished from prolactinoma. Eighty five patients with non-functioning adenoma were treated with transsphenoidal operation at Hiroshima University Hospital, and Kansai Rosai Hospital from May, 1978 to March, 1981 and at Osaka University Hospital, The Center for Adult Diseases, and Kansai Rosai Hospital from April, 1981 to May, 1986. Non-functioning adenomas were diagnosed by clinical feature, endocrinologic examination, and immunohistochemical study. There were 42 male and 43 female patients, whose age ranged from 17 to 76 years (mean: 49). The most frequent chief complaint was visual disturbance (86%). Amenorrhea-galactorrhea was complained by 9 female patients. However, 7 of them had visual disturbance at the same time. Hyperprolactinemia was seen in 21 patients (30%). The highest serum level of prolactin was 163.2 ng/ml. All of the patients had macroadenomas. There were 2 invasive adenomas and 83 expensive adenomas in them. After operation, cure or improvement of the visual disturbance was noted in almost all the patients. The serum levels of prolactin were normalized in 16 of 17 hyperprolactinemic patients. In conclusion, transsphenoidal operation is the best treatment of non-functioning adenomas. However, it is difficult to decide before operation whether the macroadenoma with serum prolactin level between 100 and 200 ng/ml is non-functioning adenoma or prolactinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
In the previous reports, we demonstrated that intracisternal ACNU is effective in prolonging the survival time of rats with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, and systemic and local toxicity can be avoided by adjusting the drug dose. In this experiment, we studied distribution of 14C-ACNU in the rat brain after intracisternal administration using a macroscopical autoradiographic method. One muCi of ethylene-14C-ACNU was percutaneously injected into the cisterna magna of normal female Wistar rats weighing approximately 150 g. The animals were sacrificed 5 and 30 minutes, and 3 hours after injection (3 animals in each group). The brain was quickly removed and frozen in Freon. 14C-ACNU autoradiograms were made in coronal sections of the brain, which were cut in 20 mu thick and exposed to the film for 7 days. In 5 minutes after administration, high radioactivity was distributed in the subarachnoid space of the basal and ambient cisterns and hypocampal fissures, and subpial brain tissue up to 1 or 2 mm in depth. High radioactivity was also present in the ventricles and subependymal layer. In 30 minutes after administration, total radioactivity has already reduced in amount, however, local distribution has not changed so much as compared to that of 5 minutes after injection. No radioactivity was observed in the deeper part of the brain. In 3 hours after administration, only a small amount of radioactivity remained in the subarachnoid space and subpial region.(ABSTRACT TRUNCATED AT 250 WORDS)
Bromocriptine (CB) not only lowers serum prolactin (PRL) levels but also reduces tumor size of human prolactinomas. Gen et al and we have suggested that the size reduction of human prolactinomas by bromocriptine treatment results from the reduction in size of individual tumor cell as well as the reduction in number of tumor cells secondary to cell necrosis. This implies that bromocriptine has a cytosuppressive action and possibly a cytocidal action on human prolactinomas which causes reduction in cell size and cell necrosis, respectively. The mechanism of cytosuppressive action of CB has been investigated by using mostly non-neoplastic pituitary tissues of experimental animals. A decrease in exocytosis of secretory granules and a subsequent accumulation of granules within the cells are suggested to cause the reduction in serum levels of PRL in early stage of CB treatment. However we have reported that in spite of a pronounced reduction of serum PRL levels, the number of exocytosis of the granules in human prolactinomas treated with CB for 2 weeks increased to more than 4 times much as that in the untreated prolactinomas. This is a phenomenon which contradictory to the current hypothesis. The present study is intended to clarify whether the phenomenon we observed is specific for human prolactinomas or common also to the prolactinomas in experimental animals. Seventeen female SD rats were used. They were implanted subcutaneously with a pellet of 20 mg of 17 estradiol-benzoate (20% in cholesterol), and left to grow a pituitary tumor for 10 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Ninety-eight patients (16 male, 82 female) with prolactinomas were treated by transsphenoidal operation. The postoperative course was closely related to the tumor size and the preoperative levels of serum prolactin. In 37 (74%) of 50 patients with microadenomas, the levels of serum prolactin returned to normal postoperatively. There were 48 patients with macroadenomas; 27 of these were expansive and 21 were invasive. In 9 (33%) of the 27 patients with expansive macroadenomas, the postoperative levels of prolactin returned to normal; this was not the case in any of the 21 patients with invasive macroadenomas. Of 81 premenopausal women, 35 (43%) resumed normal menstruation postoperatively. All patients with preoperative deficits in the visual field experienced postoperative improvement. There were no postoperative deaths or serious complications in this series. Our data indicate that microprolactinomas are highly curable by transsphenoidal operation alone. In women who plan to have children, prolactinomas should be removed immediately. On the other hand, in patients with macroprolactinomas who manifest high levels of serum prolactin, initial treatment with bromocriptine should be considered because there is little hope for surgical cure and postoperative bromocriptine treatment might be necessary.
Solitary late recurrence is an unpredictable behavior pattern of renal cell carcinoma. We describe a patient with recurrence at the cranial bone 10 years after surgical management and another with recurrence at the sacral bone 13 years after treatment with radiotherapy and alpha-interferon. Both patients have been followed satisfactorily for 9 months. Unpredictable behavior of renal cell carcinoma makes lifelong followup of patients necessary. If a solitary recurrence is detected operative management definitely should be considered depending on the site of recurrence.
A 56-year-old man died of widespread metastases of malignant fibrous histiocytoma (MFH) primarily developed in the left lower gingiva after a rapid clinical course is reported. Primary and metastatic tumors showed light and electron microscopic, histochemical and immunohistochemical characteristics of MFH together with cytoplasmic hyaline globules and stromal osteoids. Hyaline globules revealed periodic acid-Schiff positive and diastase resistant reactions but not positive with any histochemical and immunohistochemical reactions. Osteoids were partially calcified and rimmed by osteoblastic tumor cells. The present case of MFH may provide difficulties in the differential diagnosis from some osteoid-forming sarcomas in soft tissues with relation to the histogenesis.
We found combination chemotherapy with cisplatinum, vinblastine, and bleomycin (PVB therapy) effective in the treatment of a patient with a pineal germ cell tumor with peritoneal dissemination. The metastatic complication may have been attributable to the ventriculoperitoneal shunt tube. After the first course of PVB therapy, the disseminated tumors were decreased in size; no residual tumors were detected after the third course by laparoscopic examination, computed tomographic scanning, or echogram. Our results suggest that combined PVB therapy is effective in the treatment of extraneural metastasis from intracranial germ cell tumors.
Experimental models of meningeal gliomatosis (MG) have been produced by intracisternal inoculation of rat C6 and 9L glioma cells into Wistar and Fischer 344 rats, respectively. Tumor growth was steady and rapid in both MG models when more than 10(6) tumor cells were implanted. The median survival time of the rats inoculated with tumor cells was inversely related to the number of the cells inoculated. The clinicopathological features observed in both MG models were similar to those seen in diffuse leptomeningeal involvement of gliomas in humans. The models may be useful for investigating the pathophysiology of MG and for the determination of the efficacy of chemotherapeutic agents in brain-tumor chemotherapy.
Leptomeningeal dissemination is one of the major causes which increase the morbidity and mortality of the patients with malignant brain tumors. The incidence of this complication is increasing, however, no sufficient treatment is available at present. Therefore, in an attempt to establish a new treatment, we studied toxicity and therapeutic effect of intrathecal ACNU (nimustine hydrochloride) using experimental animals. Systemic and local toxicity was tested in normal rats that received ACNU intracisternally. The animals given ACNU more than 3.0 mg/kg progressively lost their body weight, and ACNU 6.0 mg/kg was fatal in 80% of animals. Animals given ACNU less than 1.5 mg/kg gained weight in the same rate as in control animals. Increased capillary permeability to intravenous Evans blue was observed in the subpial region of the brain in the rats given ACNU 6.0 mg/kg intracisternally. The increase of capillary permeability was dominant along the ambient cistern, hypocampal fissure, and at the base of the brain. Demyelinization and loss of neurons were seen in the same areas as well. These changes were not observed in the animal given ACNU less than 1.5 mg/kg. Therapeutic effect of intrathecal ACNU against the leptomeningeal tumor was studied in rats with meningeal carcinomatosis which was induced by intracisternal inoculation of 1 X 10(4) cells of Walker 256 carcinosarcoma. The median survival times of the animal given ACNU 1.5 mg/kg intrathecally on day 2 or 5 after tumor inoculation were prolonged by 55 to 64%, and 64 to 145%, respectively, as compared to those of untreated control animals (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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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)
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.
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.
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.