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Biomedical subjects

M Shinonaga

Publications and source records attributed to M Shinonaga.

52 records · Page 3Linked to original sources

Effect of recombinant human lipocortin I on brain oedema in a rat glioma model.

Glucocorticoids have been extensively used to treat brain oedema, but little is known on the mechanisms of steroids in the prevention and resolution of tumour-induced brain oedema. Recently, the mechanism of steroid action is thought to involve synthesis of proteins with antiphospholipase activity called lipocortins. In a previous study, we have demonstrated the efficacy of dexamethasone (DEX) in resolving peritumoural oedema in a rat glioma model. Using the same model, we studied the effect of recombinant human lipocortin I on the resolution of peritumoural oedema. Intracerebral tumours were produced in 6-week-old Wistar rats by implantation of rat glioma C6 cells. In comparison with sham-operated controls, the tumour-implanted animals showed significant increase in the cortical water content, which was reduced by DEX administration to the level in the sham-operated controls. The water content within the tumour was also significantly decreased by DEX treatment. On the other hand, there was no difference in water content between lipocortin-treated and non-treated animals. These findings suggest that tumour-induced brain oedema can be reduced by DEX treatment but not by lipocortin. In conclusion, it is doubtful whether glucocorticoids exert their action in resolving brain oedema by inducing PLA2 inhibitory proteins named lipocortins.

Animals↗

Hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis.

A case is presented of 14 year old female with hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis. Evidence of hypothalamic obesity included 1) acute hyperphagia and weight gain, 2) neuroradiology showed hydrocephalus with focal enlargement of the third ventricle, 3) endocrinological studies revealed hyperinsulinaemia and impaired growth hormone (GH) response to arginine, but normal GH response to growth hormone-releasing factor (GRF) and 4) Torkildsen's ventriculo-cisternal shunting resulted in improvement in hyperphagia and obesity.

Adolescent↗

[Management results of primary intracranial malignant lymphoma].

Nineteen cases of primary malignant lymphoma of the central nervous system were reported. The clinical characteristics, diagnostic procedure and therapeutic method, especially concerning chemotherapy, were analysed. The following conclusions were obtained: 1) histological classifications and surgical procedures were not factors involved in prognosis. 2) radiotherapy was regarded as an effective but a palliative treatment. 3) combined chemotherapy for systemic malignant lymphoma, such as VEMP, VEP, COPP, seemed to be of little use for intracranial malignant lymphoma. 4) intra-arterial administration of high-dose methotrexate, ACNU and intravenous administration of high-dose cytosine arabinoside can be expected to be a useful chemotherapeutic approach.

Adolescent↗

[Effect of recombinant human erythropoietin on reduce of homologous blood transfusion in open heart surgery].

We have used recombinant human erythropoietin (rEPO) in order to prevent patients from developing anemia following preoperative autologous blood preservation. Thereby, we have been able to reduce intraoperative homologous blood transfusion during cardiac operations. In June and July, 1989, six middle-aged selective patients received rEPO (200 IU/kg) intravenously every other day starting from fifteen days before the day of their operations. One unit (200 ml) of autologous blood was drawn and preserved every few days. However, no significant differences were observed in red cell counts, hematocrit, hemoglobin and serum protein levels between before and after preservation. Not only preoperative autologous blood preservation with provision of rEPO, but also using the intraoperative autotransfusion system enabled us to perform cardiac operations on 5 out of 6 patients without any homologous blood transfusion. None of the six patients exhibited any undesirable effects due to rEPO administration. Their postoperative courses were excellent.

Blood Preservation↗

Relation between macrophage infiltrates and peritumoral edema.

Peritumoral edema is one of the most serious complications of intracranial neoplasms. However, the exact pathogenesis of peritumoral edema is still unknown. To explore the role of macrophages and LTs in brain tumors, we examined macrophage infiltrates in the brain tumors by immunohistological method using anti-Leu M3 monoclonal antibody and measured tissue LTC4 and LTD4 by HPLC with ODS column and UV spectrophotometer in the wavelength of 280 nm. Nine of 14 gliomas, 10 of 14 meningiomas, and all six metastatic brain tumors had macrophage infiltrates. The correlation was good between macrophage infiltration and peritumoral edema detected on CT. In many cases with peritumoral edema, LTC4 was detected. In most cases without peritumoral edema and many cases with preoperative steroid treatment, LTC4 was not detected. These data suggest that macrophages and LTs may play an important role in the formation of peritumoral edema.

Adrenal Cortex Hormones↗

Effect of dexamethasone on neurotransmitter amines in a rat glioma model.

Vasogenic brain edema was produced by transplantation of rat glioma C6 cells into rat brain. Using this model, we measured neurotransmitter concentrations and water content of regional brain tissue. In the tumor-implanted controls, monoamine neurotransmitters in the hypothalamus, cortex, and striatum significantly decreased. When treated with DEX, these monoamines tended to return to the levels of the sham-operated controls. Additionally, DEX markedly lowered tumoral monoamines. In the nonsurgical animals, DEX significantly increased norepinephrine but not DA. Regardless of treating with DEX or not, water content showed no changes in the hypothalamus and striatum in the tumor-implanted animals. However, the increase in water content in the cortex was significant, and this increase could be reduced by DEX to the levels of controls. Water content of tumor tissue could also be markedly reduced by DEX. In the nonsurgical animals, there were no changes in water content between DEX-treated and nontreated animals. In conclusion, brain edema produced by the brain tumor may reduce noradrenergic and dopaminergic activities. This is more likely due to compression anoxia caused by the tumor mass, glial hydrops, and edema fluid. It is presumed that the effect of DEX is due to reduction of water content of the tumor and peritumoral white matter as well as by increasing noradrenergic activity.

Animals↗

Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing alpha- and beta-type transforming growth factors.

A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of alpha- and beta-type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues.

Cell Line↗

[Growth factors produced by rat glioma cells: activities of transforming growth factors].

Growth factors contained in cultured medium of rat glioma C6 cells (C6 cells) were examined mainly for the activity of transforming growth factors (TGFs). Cultured medium of C6 cells was dialyzed against acetic acid, lyophilized and chromatographed by gel-permeation method, the fractions were assayed by soft agar colony formation, iodine 125 (125I)-epidermal growth factor (EGF)-binding competition and incorporation of tritium-thymidine. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A 31-1-1 (3T3) cells, were used as indicator cells for the soft agar colony assay. 3T3 cells were also used for the incorporation of tritium-thymidine. EGF receptor-rich A 431 cells were used for 125I-EGF-binding competition assay. The activity of alpha-type TGFs was examined by soft agar colony formation of NRK49F cells and inhibition of EGF-binding to A 431 cells since TGF alpha has sequence homology with EGF and binds to EGF receptors on the cell membrane, while the activity of beta-type TGFs was examined by soft agar colony formation of 3T3 cells and NRK 49 F cells with the addition of EGF. High level of activities of both TGF alpha and TGF beta were detected in 14,000 to 45,000 daltons, and also high level of the activity of DNA synthesis was detected at the same molecular weight. These results suggest that C6 cells produce TGF alpha and TGF beta as well as platelet-derived growth factors (PDGFs)-analogue. Since amplification of EGF receptor gene has been demonstrated in glioma, TGF alpha released by glioma may provide autocrine stimulation through the binding to the amplified EGF receptors. TGF beta is known to increase EGF receptors on the cell membrane. TGF beta has been demonstrated not only to stimulate but also inhibit cell proliferation under certain circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistological evaluation of macrophage infiltrates in brain tumors. Correlation with peritumoral edema.

Peritumoral edema is one of the most serious complications of intracranial neoplasms; however, the exact pathogenesis of this condition is still unknown. To explore the effect of macrophages in brain tumors on the pathogenesis of peritumoral edema, 42 specimens of primary or metastatic brain tumors were studied. Frozen sections were examined by an immunoperoxidase staining technique with anti-Leu-M3 monoclonal antibody. Eight of 14 gliomas demonstrated Leu-M3-positive cell (macrophage) infiltration. The two glioblastomas showed a moderate or marked degree of macrophage infiltration. Twelve of 16 meningiomas demonstrated varying degrees of macrophage infiltration. All six metastatic brain tumors exhibited prominent macrophages in intra- and peritumoral tissues. Four acoustic neurinomas and two hemangioblastomas showed a slight to moderate degree of macrophage infiltration. Excellent correlation was found between the degree of macrophage infiltration seen on immunoperoxidase staining and the peritumoral edema detected on computerized tomography brain scans of patients with supratentorial tumors, especially meningiomas. Macrophages are known to secrete various substances (including arachidonate metabolites) that may interfere with vascular permeability. These data suggest that macrophages infiltrating brain tumors may play an important role in the pathogenesis of peritumoral edema.

Antibodies, Monoclonal↗

[Chemotherapy for experimental subarachnoid dissemination model of brain tumor].

Chemotherapy was applied for experimental subarachnoid dissemination model of brain tumor which was established in male Wister-SPF (SLC) rats inoculated intracisternally with 2 X 10(5) C6 rat glioma cells. Nontreated animals died about 24 days after inoculation. Autopsy findings of the animals showed localized or multifocal invasion of the tumor on leptomeninges in cisterna magna, and partially infiltration into the parenchyma of the cerebellum and medulla oblongata. Three days after inoculation, the tumor deposition and proliferation already occurred. Several tumor cell layers were found in the subarachnoid space over the cerebellomedullary surface. Tumor bearing animals were at first treated by single agent. These are ACNU administered intraperitoneally, methotrexate administered intracisternally, and OK-432 administered intraperitoneally. In the next stage, combination of these drugs was applied. ACNU, 3 mg/kg i. p., on Day 3, was effective in elongation of median survival time by 23.6%, statistically significant (P less than 0.02). Methotrexate, 0.25 mg/kg i.th., on Day 3, was also effective in elongation of median survival time by 8.4%, statistically significant (P less than 0.05). OK-432, 0.1 KE/kg i. p., daily, 14 times, from Day 3 to Day 16, was ineffective in elongation of median survival time. Combination of ACNU, methotrexate and OK-432, in the same schedule as described above, produced the longest median survival time of 42.4%, statistically significant (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Unilateral exophthalmos caused by organized hematoma of the orbit--report of a case (author's transl)].

The authors reported a case with unilateral proptosis of over ten years' duration due to organized hematoma of the orbit. It has generally been accepted that any given hemorrhage within the orbit can be resolved in a relatively short period of time. Persistent intraorbital hematoma, therefore, in the form of organized hematoma is very unusual in incidence and has been reported very few in the literature. Our patient presented himself with a ten-and-several-year history of unilateral exophthalmos, limited ocular movement and decreased visual acuity on the involved side. There was no specific symptom when compared with the other intraorbital tumors. Total resection of the tumor was performed through transcranial frontozygomatic approach. Histopathologic examination revealed evidence of organized hematoma without definite sources of bleeding such as microangioma, microaneurysm or arteriovenous malformation. Retrospective review of history failed to uncover episodes of hemorrhagic tendency or direct trauma to the head or the orbit. Subsequently a diagnosis of spontaneous organized hematoma was made. Great emphasis was laid on the fact that CT-scan was one of the most useful diagnostic tools. Our surgical approach was introduced and discussed.

Adult↗

Development of an endocardioscope for repair of an atrial septal defect in the beating heart.

The purpose of this study was to evaluate the possibility of surgical treatment of an atrial septal defect in the beating heart without cardiopulmonary bypass. The first step was to develop an endocardioscope that permitted observation of the inside of the beating heart. To visualize the inside of the beating heart, the tip of the endoscope was covered with a glass adapter. The endocardioscope was inserted through the right atrial appendage in eight beagles. The atrial septum, foramen ovale, coronary sinus, tricuspid valve, and chordae tendineae were identified without hemodynamic derangement. The second step was to attempt to close the foramen ovale with clips or staplers. We were able to close the foramen ovale with these devices, but a safer, easier device is needed. The endocardioscope we developed should prove to be a useful tool for minimally invasive surgical treatment of heart diseases, such as atrial septal defect.

Animals↗