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N Arita

Publications and source records attributed to N Arita.

At least 109 records · Page 6Linked to original sources

[Meningeal gliomatosis--clinical features and results of treatment].

Fifteen (15.6%) patients of 97 with malignant glioma developed meningeal gliomatosis during at least 2 years after the initial treatment. The time between the first surgery and diagnosis of meningeal gliomatosis was less than 1 year in 10 cases, 1 to 2 years in 2 and over 2 years in 2. In the younger age group less than 20 years, the incidence of meningeal gliomatosis was higher (46%) than that (12%) in the older group. Despite intrathecal chemotherapy (cytosine arabinoside, bleomycin and methotrexate), all patients died 2 to 24 weeks after the diagnosis of meningeal gliomatosis. Experimental studies suggest that intrathecal ACNU may be promising for the treatment of meningeal gliomatosis.

Adolescent↗

[In situ nick translation for detection of DNA damages in glioma cells].

DNA damaging agents such as nitrosoureas are widely used for the treatment of malignant gliomas. Therefore, quantitative measurement of DNA damages induced by antineoplastic drugs is useful to judge the efficacy of the drug and understand the pharmacological action of the drug. We have utilized in situ nick translation method to demonstrate "nicks" in DNA of glioma cells treated by various antineoplastic agents. Exponentially growing rat 9 L glioma cells (4 x 10(4] were seeded in the chamber slide. After fourty eight hours, the medium was changed to that containing various concentration of the drug (ACNU, cis-DDP, BLM, ADM and VP-16) and the cell was treated for 1 hour. Then, the cell was fixed for 10 minutes in methanol-acetic acid (v/v 3:1). Following fixation, the cell was incubated in the nick translation mixture containing E. coli DNA polymerase I, 3H-TTP, and 4 dNTP's (ATP, GTP, CTP, CTP and TTP) for 10 minutes at room temperature. The slide was dipped in the autoradiographic emulsion, exposed for 4 days at 4 degrees C, and then developed, the number of the silver grains over nuclei was counted under the microscope. For comparison of the effect of the drug to glioma cells, IC50 (inhibitory concentration of the drug for 50% cell kill) of each drug was determined by treating the cell for 48 hours at the various concentration of the drug. Small number of the silver grains was noted in cells with no treatment. Over IC50 as the concentration of the drug increased, the number of the nick increased in cells treated with bleomycin or adriamycin which are known to produce single strand breaks in DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Capillary permeability factor produced by C 6 glioma cells: role in peritumoral brain edema and possible mechanism of glucocorticoid action].

We studied whether C6 glioma cells produce a diffusible factor that increases capillary permeability of rat brains. Culture supernatant after 4 hours' incubation of C6 glioma cells in serum-free medium was obtained (SUP-N). SUP-N was concentrated 80-fold by dialysis-concentration (MW cut off was 10 kd) (SUP-C). These two supernatant fractions were tested for capillary permeability activity by their infusion into normal rat brains (right caudate-putamen). Control materials (MEM or concentrated MEM) were also infused into the left caudate-putamen as well as supernatants. Capillary permeability was measured by a quantitative autoradiographic method with 14C-aminoisobutyric acid (AIB) and expressed as an unidirectional blood-to-brain transfer constant (K). Effects of infusates were quantitatively estimated by two parameters, i.e., the highest K value (Kmax) (microliter/g/min) and the spatial extent (D1/2) (mm). The protein concentration of SUP-N and SUP-C was 15 and 950 micrograms/ml, respectively. SUP-N showed a slight increase of capillary permeability, particularly, around the needle track (infusion site) in the brain, but it was not significantly different from the control on the value of Kmax. On the other hand, SUP-C markedly increased capillary permeability (Kmax; SUP-C: 10.83 +/- 0.99, control: 2.53 +/- 0.22, p less than .001) and the effect was much more extensive than that of SUP-N (D1/2; SUP-C: 2.23 +/- 0.26, SUP-N: 0.83 +/- 0.07). A factor in SUP-C increased capillary permeability after a lag phase of 1.5 hours reaching the maximum after 6 hours of infusion, and 24 hours later the effect declined to 30% of Kmax at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intrathecal ACNU--a new therapeutic approach against malignant leptomeningeal tumors.

Pharmacokinetics, toxicity and therapeutic efficacy of intrathecal ACNU, 3-[4-amino-2-methyl-5-pyrimidinyl)methyl)-1-(2-chloroethyl)-1-nitroso urea, were studied in rats to determine if it is a new and effective method for the treatment of malignant leptomeningeal tumors. Pharmacokinetics of intracisternally administered ACNU was studied by macroscopical autoradiography using 14C-labeled ACNU. It was demonstrated that intracisternally administered ACNU distributed in the subarachnoid space and subpial layer of the brain in high concentration and was rapidly eliminated into the systemic circulation. The diffusional transport of ACNU into the deeper part of the brain was limited. More than 3.0 mg/kg of intracisternal ACNU induced progressive loss of the weight of body in normal rats, and 80% of the rat given 6.0 mg/kg died. Increase of capillary permeability, neuronal loss and gliosis were observed in the marginal layer of the brain facing to the subarachnoid space in the rat given more than 3.0 mg/kg of ACNU. Systemic and local toxicity was not observed in the rat given less than 1.5 mg/kg. Therapeutic effect of intrathecal ACNU against leptomeningeal tumors was evaluated in the rat with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells. The median survival time of the rat treated with 1.5 mg/kg of intracisternal ACNU once on day 2 or on day 5 after tumor inoculation was significantly prolonged by 173%, and 214% at maximum, respectively, as compared with that of the untreated animal. These findings suggest that intrathecal ACNU may be of value for clinical trial against leptomeningeal tumors.

Animals↗

Mass screening for hyperprolactinemia and prolactinoma in men.

To determine the incidence of hyperprolactinemia and prolactinoma without symptoms in men, the serum levels of prolactin were measured in 4803 men. Of these, 14 had hyperprolactinemia with prolactin level of over 50 ng/ml, and 3 had prolactin levels of more than 500 ng/ml. Of these 3 subjects, 2 were found to have pituitary prolactinoma by computed tomograph scanning and surgery, the other subject, who was highly suspected to have prolactinoma, refused further examinations. The serum prolactin levels of 51-100 ng/ml in 11 subjects may have been induced by drugs (sulpiride) or unknown factors. The present survey suggests that the incidence of prolactinoma in men in the general population might be estimated to be 1:1600, and that mass screening is useful for early diagnosis of asymptomatic prolactinoma.

Adult↗

Isolated gonadotropin deficiency secondary to glioma in septum pellucidum.

A 21-year-old man, who had had normal sexuality beforehand, noticed a decrease in libido and potency, as well as loss of ejaculation. Endocrine evaluation showed normal serum levels of gonadotropins but a low testosterone level. The response to clomiphene citrate was poor while those to luteinizing hormone-releasing hormone and human chorionic gonadotropin were within normal limits. A tumor found in the septum pellucidum through brain-computerized tomography was resected. Histologically it proved to be a mixed tumor composed of astrocytoma and oligodendroglioma. Three months after the operation the patient had recovered normal sexual functions and endocrine evaluations, including the responsiveness to clomiphene citrate, had been restored. This case suggests the existence of some stimulatory fiber for the secretion of luteinizing hormone in the septum pellucidum.

Adult↗

[Effect of ACNU against experimental brain tumor--immunohistochemical study using anti-BrdU monoclonal antibody].

We have studied the efficacy of intrathecal ACNU against experimental leptomeningeal tumors. In the present report, the effect of ACNU on the growth kinetics of the tumor was evaluated by the immunohistochemical technique using anti-BrdU monoclonal antibody. The experimental leptomeningeal tumor was developed by inoculation of Walker 256 carcinosarcoma cells into the cisterna magna of rats. Seven days after the inoculation of tumor cells, the animals were treated either by intravenous (15 mg/kg) or intrathecal (1.5 mg/kg) ACNU. Four, 12, 24, 48, 96 or 144 hours after treatment, the animals received intravenous BrdU (200 mg/kg). Thirty minutes thereafter, they were sacrificed and the brain was removed. L. I. was calculated by counting the immunoreactive tumor cells. L. I. of the tumor without treatment on the seventh day after inoculation was over 40%. L. I. began to decrease 24 hours after intravenous ACNU, and remained 11% up to 96 hours. On the other hand, L. I. already decreased to 20% 4 hours after intrathecal ACNU and remained to be low (17%) up to 48 hours. However, L. I. increased to 38% at 96 hours. Thus, the effect on the growth kinetics of the tumor differs between intravenous and intrathecal ACNU. These results are considered to be useful informations for determining the optimal dosage of the antineoplastic agent against the brain tumor and developing the effective combination chemotherapy.

Animals↗

[A case of isolated gonadotropin deficiency secondary to glioma in septum pellucidum].

A 21-year-old man, who had had normal sexuality, noticed a decrease in libido and potency as well as loss of ejaculation. Endocrinological evaluation showed normal serum levels of gonadotropins but a low testosterone level. The response to clomiphene citrate was poor while the response to luteinizing hormone-releasing hormone and human chorionic gonadotropin were within normal limits. By the examination of brain computerized tomography a tumor was detected in the septum pellucidum and was resected. Histologically it proved to be a mixed tumor composed of astrocytoma and oligodendroglioma. Two months after the operation the patient had recovered normal sexual functions and the endocrinological functions, including the responsiveness to clomiphene citrate, had been restored. This case suggests the existence of some stimulatory fiber for the secretion of luteinizing hormone in the septum pellucidum.

Adult↗

[Distribution of epidermal growth factor receptor in glioma].

A monoclonal antibody (Amersham) to epidermal growth factor receptor (EGFR) was used for immunohistochemical study to confirm the presence of EGFR in the glioma tissue. Fresh surgical material was stored at -80 degrees C, and frozen sections were stained. Positive staining was demonstrated in 8 of 9 gliomas. In 2 of 8, more than 50% of tumor cells were positively stained. In 4 of 8, positive cells were seen scattered in the tissue. In the remaining 2 gliomas, few tumor cells were positively stained. The most representative staining was seen on the cytoplasmic membrane. But there were also nuclear and cytoplasmic stainings. The distribution of EGFR in the glioma cells suggests possible role of the epidermal growth factor in the proliferation of gliomas.

Adolescent↗

[Effect of MX-2, a morpholino anthracycline derivative, against human and rat glioma cells and experimental leptomeningeal tumors in rats].

MX-2, a new morpholino anthracycline derivative, showed broad anti-neoplastic activity against experimental tumors. Molecular weight of MX-2 is 622.07, and it can cross blood-brain barrier because of its high lipid solubility. In this report, we described its in vitro and in vivo effects on brain tumors. The growth of rat 9L and human KNS-42 glioma cells were markedly inhibited by the medium containing more than 1 ng/ml of MX-2. The inhibitory concentration of MX-2 for 50% cell kill was 1.8 ng/ml for 9L cell and 18 ng/ml for KNS-42, respectively. These values were the almost same as those reported with P388 leukemia. In rats with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, the median survival time was significantly prolonged. The increased life span was 40, 40, 40 (p less than 0.01), and 20% (p less than 0.05) in the animals given intravenous MX-2 of 1.5, 1.0, 0.75, and 0.375 mg/kg on day 1, 5, and 9 after tumor inoculation respectively. These results indicate that MX-2 may be a promising new antineoplastic agent for the treatment of malignant brain tumor.

Animals↗

[Growth activity of meningeal carcinomatosis--immunohistochemical study using anti-BrdU monoclonal antibody].

We have developed an experimental model of leptomeningeal tumor by inoculating Walker 256 carcinosarcoma cells into the cisterna magna of rats. This model was considered to be useful in studying pathophysiology and treatment of malignant brain tumors. In this study, the growth kinetics of this experimental tumor was investigated by using the immunohistochemical technique with an anti-BrdU monoclonal antibody. Walker 256 carcinosarcoma was subcutaneously passaged in female Wistar rats. Seven days after subcutaneous inoculation, the tumor was aseptically removed and minced in Hank's medium by scissors to make single cell suspension of the tumor. The cell suspension was adjusted to 1 x 10(5) cells/ml. And 0.1 ml was inoculated percutaneously into the cisterna magna of female Wistar rats weighing 150 gr. Every day after tumor inoculation, the animal (5 on each day) was sacrificed 30 minutes after intravenous BrdU (200 mg/kg) and perfused by saline. Then, the brain was removed, fixed in ethanol and embedded in paraffin. Coronal sections of the brain 6 mu in thickness were cut and stained by the indirect immunoperoxidase (ABC) method. The anti-BrdU monoclonal antibody (Becton-Dickinson) was diluted in 1:100. The sections were counterstained by hematoxylin. Labelling index (L.I.) of the tumor was obtained by counting immunoreactive cells under the microscope. L.I. of the subcutaneous tumor 7 days after inoculation was 52.4%. In the tumor 1 to 3 days after inoculation, L.I. was still low and between 11.9 and 15.1%. Four or 5 days after inoculation, the tumor cells grew in several layers in the subarachnoid space. L.I. at this stage of the tumor growth was 26.6 to 34.8%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of radiolabeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitros ourea hydrochloride in rat brain tumor: intraarterial versus intravenous administration.

To assess the rationale of intraarterial (i.a.) 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy, distribution of 14C-labeled 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)- 3-nitrosourea in rat glioma was studied after i.a. or i.v. infusion. Immediately after infusion, the tumor located in the hemisphere of intracarotid infusion received 4.6-fold higher radioactivity than the tumor located contralaterally to intracarotid infusion and 2.8-fold higher radioactivity than i.v. infusion. The difference was kept up to 30 min after i.a. infusion. Autoradiographic observation indicated rather uniform distribution of the tracer in the central portion of i.a. infusion. However, in the periphery of i.a. infusion, distribution of the tracer was nonhomogenous. The results indicate that i.a. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea chemotherapy is useful when the tumor has high blood flow and is located in the center of an infused area.

Animals↗

Regional differences in local cerebral blood flow (LCBF) and glucose utilization (LCGU) in the basal ganglia after occlusion of the middle cerebral artery in rats.

Acute effects of occlusion of the middle cerebral artery on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were investigated quantitatively in separate groups of rats using (14C) iodoantipyrine (14C-IAP) or (14C) 2-deoxyglucose (14C-DG) respectively. LCBF was significantly decreased in the ipsilateral cerebral cortices (to less than 45 ml/100 g/min or 30% of the control side) and the lateral part of the striatum (to 22 ml/100 g/min or 10% of the control side) which were supplied by the middle cerebral artery. No significant changes in LCBF were found in any other of the subcortical regions. In contrast to the unanimous decrease of LCBF in the ipsilateral cortices and the lateral striatum, complexed changes in LCGU were found in not only the cortex and striatum but also in many other subcortical regions which were closely related to the distribution of the mesencephalic dopamine neurons, such as globus pallidus, substantia nigra, subthalamic nucleus, nucleus accumbens, olfactory tubercle and lateral habenular nucleus. Relevance of this putative neurotransmitter and GABA on the glucose metabolism in ischemic brain is discussed.

Animals↗

Primary meningioma of paranasal sinuses treated by the transbasal approach.

The authors found the transbasal approach very useful for the treatment of a meningioma originating in the paranasal sinus and massively involving the anterior cranial base. By this approach, both total excision of the tumor and reconstruction of the base of the skull were successfully achieved at the same operation. The usefulness of the transbasal approach as well as the clinicopathologic features of the meningiomas arising in the paranasal sinus are described.

Adolescent↗

Primary myxoma in the pituitary fossa: case report.

A case of primary myxoma in the pituitary fossa is described. The tumor presented as an intrasellar and suprasellar mass and was successfully removed during a transsphenoidal operation. It was verified as a myxoma by histopathological studies, and there was no evidence that it was a metastasis. This is thought to be the first report of this tumor occurring in the pituitary fossa.

Adult↗