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Biomedical subjects

A Asai

Publications and source records attributed to A Asai.

At least 145 records · Page 8Linked to original sources

Expression of O6-methylguanine-DNA methyltransferase and chloroethylnitrosourea resistance of human brain tumors.

Northern blot analysis with O6-methylguanine-DNA methyltransferase (MGMT) cDNA as a probe was used to analyze the MGMT activity regulating drug resistance of human cells to chloroethylnitrosoureas (CENUs). By this method, the expression levels of MGMT mRNA in six human glioma cell lines and 12 human brain tumor tissues from surgical specimens were determined. These MGMT mRNA levels were compared with the SD10 values of the tumor cells, estimated by cell survival assay, which indicated their resistance to the anticancer drug, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Human brain tumors that were highly resistant to ACNU, such as glioblastoma Gbl1 and metastatic brain tumor Col1 with SD10 values (microM) of above 100, expressed markedly increased amounts of 0.95 kb MGMT mRNA. In contrast, tumor cells such as U-87MG, U-251MG, U-343MG, U-373MG and SF-126 with SD10 values of under 14 indicating low resistance to ACNU scarcely synthesized any MGMT mRNA. These results indicated that the level of expression of MGMT mRNA in human brain tumors determined by Northern blot analysis truly reflects their cellular resistance to ACNU. Thus the Northern method with MGMT cDNA probe reported here is a practical and reliable method for estimation of cellular resistance to CENUs such as ACNU and for screening the chemotherapeutic response to CENUs of human brain tumors.

Blotting, Northern↗

A comparison of CT contrast enhancement and BUDR labeling indices in moderately and highly anaplastic astrocytomas of the cerebral hemispheres.

Contrast enhancement on computerized tomography (CT) scans has been used in directing therapy for presumed intracranial gliomas. However, for moderately anaplastic astrocytomas (MOAAS) and highly anaplastic astrocytomas (HAAS), it provides no information about proliferative potential. The bromodeoxyuridine (BUDR) labeling index (LI), however, indicates proliferative potential, correlating with histologic malignancy and survival. An LI less than 1% is a favorable indicator; LI greater than 5% suggests more aggressiveness. To determine the correlation, if any, between BUDR LI and contrast enhancement, CT scans of 71 patients with cerebral hemisphere tumors labeled with BUDR were retrospectively reviewed. Among 36 MOAAS, the BUDR LI was less than 1% in 77% of enhanced tumors and 61% of unenhanced tumors. Among 35 HAAS, it was less than 5% in 56% of enhanced tumors and 90% of unenhanced tumors. Therefore, contrast enhancement on CT scans does not always correctly predict proliferative potential in these tumors, and biopsy and labeling studies are recommended before therapy.

Adolescent↗

Monoclonal antibody-mediated solid-phase assay for mammalian O6-alkylguanine DNA alkyltransferase activity.

We describe a sensitive, rapid, and simple assay for mammalian O6-alkylguanine DNA alkyltransferase (O6-AGT) utilizing solid-phase DNA as the substrate and a monoclonal antibody (Mab)-based immuno-slotblot (ISB) for quantitation of O6-ethylguanine (O6-EtG). lambda-phage DNA was treated with N-ethyl-N-nitrosourea and immobilized on newly developed hydrophilic latex beads. After incubation with cell extracts to be assayed for O6-AGT activity, the substrate DNA could be isolated easily by a brief centrifugation through 50% glycerol. The amount of O6-EtG retained in the substrate DNA was determined by ISB using the anti-(O6-ethyl-2'-deoxyguanosine) Mab ER-6. As little as 2 fmol of O6-AGT per reaction tube can be reproducibly measured by this procedure, which is suitable for handling large numbers of samples within a short time (e.g., 80 samples within 2 days). In normal and malignant cells, respectively, O6-AGT activity protects against O6-alkylguanine-mediated mutagenesis and oncogenesis following exposure to N-nitroso carcinogens or confers resistance against cytocidal anti-cancer drugs such as chloroethylnitrosoureas and related compounds. The analysis of cellular O6-AGT activity by a highly sensitive, routinely applicable method is, therefore, of particular interest in studies related to carcinogenesis, molecular epidemiology, and clinical oncology.

Animals↗

Correlation between bromodeoxyuridine-labeling indices and patient prognosis in cerebral astrocytic tumors of adults.

Bromodeoxyuridine (BUdR), a nonradioactive thymidine analogue, is taken up by cells in S-phase, and the ratio of BUdR-positive nuclei to the total number of cells counted is defined as the labeling index (LI). In this study, BUdR LI and the clinical course of 50 cerebral astrocytic tumors in adults were analyzed. The obtained LI distributed continuously in a broad range from 0% to 19%. The mean LI of 28 glioblastomas, 12 anaplastic astrocytomas, and ten astrocytomas were 8.5%, 4.2%, and 1.2%, respectively, and these differences were statistically significant (P = 0.05). In the analysis of LI and the recurrence-free period (RFP), regardless of the histologic findings, 23 patients with LI more than 5% had a median RFP of 9.0 months; the median RFP of nine patients with LI of 3% to 5% was 14.7 months. Nine of 13 patients with LI less than 3% have not yet recurred after a median follow-up of 36 months. These differences were also statistically significant by the generalized Wilcoxon test (P = 0.05). The proliferative potential reflected by the BUdR LI is a good clinical indicator for predicting the rate of tumor growth in cerebral astrocytic tumors. In combination with histologic diagnosis, BUdR LI could help in determining a patient's prognosis more precisely.

Adult↗

[Choroid plexus tumors in infancy].

Twelve infants with choroid plexus tumors were reviewed retrospectively. Enlarging head circumference, bulging fontanelle, and vomiting were the major symptoms and signs appearing 2 to 5 weeks (mean = 3.7 weeks) before diagnosis. The average age at diagnosis was 7.7 months. Total removal was performed in 11 patients with choroid plexus papilloma, and partial removal was achieved in 1 patient with a choroid plexus carcinoma. A cerebrospinal fluid (CSF) diversionary shunt was placed temporarily in 6 infants and permanently in 4. Of the two patients not requiring CSF diversionary shunt, 1 needed a subdural-peritoneal shunt postoperatively. Histologically, 11 of 12 tumors were choroid plexus papillomas, and one was a choroid plexus carcinoma. All 12 patients were followed up for 4 months to 11 years (mean = 5.6 years). Eleven of 12 patients were alive at the time of their last check-up. All 11 survivors had normal psychomotor and neurological development. The treatment and outcome of choroid plexus tumors and management of associated hydrocephalus are discussed.

Carcinoma↗

Cell kinetics of rat 9L brain tumors determined by double labeling with iodo- and bromodeoxyuridine.

Rats with 9L brain tumors received intraperitoneal injections of iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) to estimate the duration of the deoxyribonucleic acid (DNA) synthesis phase (Ts) and the potential doubling time (Tp) of individual tumors. Different sequences and intervals (2 or 3 hours) of IUdR and BUdR administration were evaluated. After denaturation, tumor sections were reacted with Br-3, a monoclonal antibody that identifies only BUdR, and then were stained immunohistochemically by the avidinbiotin complex method. An antibody that recognizes both IUdR and BUdR, IU-4, was applied to the sections and identified by the alkaline phosphatase-antialkaline phosphatase method. Nuclei labeled only with IUdR stained blue, while those labeled with BUdR or with BUdR and IUdR stained brown. The fraction of cells that either left or entered the S-phase during the time between administration of IUdR and BUdR was measured to calculate Ts and Tp, assuming that the labeled cohort completed the DNA synthesis at a constant rate. The Ts was 8.8 hours (coefficient of variation (cv) = 0.05) and the Tp was 64.2 hours (cv = 0.08). The sequence and interval of administration of IUdR and BUdR had a minimal effect on Ts and Tp. In studies of 9L cells in monolayer culture, the Ts was 9.6 hours (cv = 0.08) and the TP was 30.6 hours (cv = 0.06). Double labeling with BUdR and IUdR allows the duration of the S-phase and potential doubling time of individual brain tumors to be estimated in situ from a single biopsy specimen.

Animals↗

Purification of DNA-binding transcription factors by their selective adsorption on the affinity latex particles.

A simple method with the use of affinity latex particles has been developed for the fast and efficient purification of sequence-specific DNA-binding proteins on the basis of their ability to selectively bind to their target sequences. Complementary oligodeoxynucleotides that contained a recognition site for a sequence-specific DNA-binding protein were chemically synthesized, annealed and ligated to give oligomers. The oligomers were coupled to latex particles, composed of polyglycidyl methacrylate, using cyanogen bromide to yield affinity latex particles. The concentration of covalently bound DNA on the affinity latex particles was 6 times as much DNA per ml as that in the Sepharose resin conventionally used. By sequential batch-wise procedures with the affinity particles, one of the sequence-specific DNA binding transcription factors, ATF or E4TF3, was quickly and efficiently purified to homogeneity from either a protein fraction in which the factor was enriched or a crude cell extract.

Activating Transcription Factors↗

Subacute brain atrophy after radiation therapy for malignant brain tumor.

Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

Aged↗

Primary intracranial neoplasms in the first year of life.

Forty-one infants with histologically verified primary intracranial neoplasms were studied who had been diagnosed and treated during the first year of life at the Hospital for Sick Children during the years 1975-1986. Forty-one percent of tumors were astrocytomas, 22% were primitive neuroectodermal tumors, and 20% were choroid plexus papillomas. Seventy-one percent were located in the supratentorial compartment and 29% in the infratentorial compartment. Thirty percent were in the cerebral hemisphere, 12% in the optic pathway-hypothalamic region, 5% in the thalamus, 17% in the cerebellum, 5% in the brain stem, 12% in the lateral ventricles, 12% in the III ventricle, and 7% in the IV ventricle. The most common presenting features in this series of patients were vomiting and increasing head size. The symptoms and signs before diagnosis were present for 2 months or less in 87% of cases. Forty-four percent of the tumors were totally resected while only a partial resection or biopsy was carried out in 56%. Sixty-six percent of the patients required a CSF diversionary shunt. Twenty-nine percent of patients received radiotherapy. Slightly more than half of these received radiotherapy immediately after surgery, whereas delayed radiation therapy was performed in the remainder. The surgical mortality was 7.3%. Of the entire group, 39% have died, with most dying within 6 months of surgery. Treatment, survival relative to histologic type, psychomotor development, and neurologic function of the survivors are discussed.

Age Factors↗

Dandy-Walker syndrome: experience at the Hospital for Sick Children, Toronto.

Thirty-five patients with the Dandy-Walker syndrome (DWS) treated over the years 1964-1987 at the Hospital for Sick Children, Toronto, were reviewed. Thirty-three patients (94%) had hydrocephalus at the time of diagnosis. The primary association of aqueduct stenosis was excluded by radiological investigation and clinical course in all patients. Associated central nervous system (CNS) anomalies were present in 10 patients. Seven had occipital encephalocele and in 1 of these there was an associated Klippel-Feil syndrome. Four patients had agenesis of the corpus callosum and 1 patient had polyporencephaly. The treatment of these patients has changed over the years in our institution so that during an earlier period, 3 patients were treated by resection of the cyst membranes. We then went through a period of shunting the lateral ventricle so that 21 patients were treated with either a lateral ventricle to peritoneal or lateral ventricle to atrial shunt. More recently, patients with the DWS have been treated with a cyst-peritoneal shunt and 10 patients were thus treated. Only 1 patient was treated with a simultaneous lateral ventricle and cyst-peritoneal shunt. Nine of the twenty-one patients (43%) with a primary lateral ventricle to peritoneum or lateral ventricle to atrial shunt developed a secondary aqueduct stenosis and an isolated fourth ventricle which required additional cyst-peritoneal shunting. Only 1 of the 10 patients treated with a primary cyst-peritoneal shunt required an additional lateral ventricle peritoneal shunt. Two patients initially treated with a lateral ventricle peritoneal shunt and with a primary cyst-peritoneal shunt subsequently had a percutaneous stereotactic third ventriculostomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal Fluid Shunts↗

Successful combination chemotherapy (cisplatinum, vinblastine, and bleomycin) in the treatment of medulloblastoma disseminated by cerebrospinal fluid: case report.

A case of successful combination chemotherapy using cisplatinum, vinblastine, and bleomycin (PVB therapy) to treat medulloblastoma disseminated by cerebrospinal fluid is presented. In this case, a locally recurrent tumor and several disseminated tumors were seen to decrease in size on CT examinations. Pain in the lower extremities and urinary incontinence improved during three courses of PVB therapy administered during a period of 9 weeks. These results suggest that combination PVB therapy may offer one of the treatments of choice for recurrent or disseminated medulloblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Multiple saccular cerebral aneurysms associated with systemic lupus erythematosus--case report.

A rare case of multiple saccular cerebral aneurysms in a patient with systemic lupus erythematosus (SLE) is presented. The aneurysms were located at the junction of the left internal carotid artery (ICA) and the posterior communicating artery (PComA), at the anterior communicating artery, at the middle cerebral artery, at the junction of the right ICA and the PComA, and at the top of the basilar artery. All the aneurysms, except for the one on the basilar artery, which was unruptured, were successfully clipped. Histopathological examination of one resected aneurysmal dome confirmed the diagnosis of transmural arteritis secondary to SLE. Postoperatively, she died of a massive hemorrhage from a rectal ulcer. The etiology and prognosis of cerebral aneurysms in SLE are discussed.

Arteritis↗

[Radiation-induced brain atrophy].

Clinico-pathologic characteristics of radiation-induced brain atrophy were reviewed. Radiation-induced brain atrophy becomes obvious 2 to 3 months after radiation therapy in more than half of the patients who have been irradiated to the brain. Mental and neurologic deterioration were well correlated with the severeness of brain atrophy. Pathologically, demyelinating process secondary to direct neurotoxicity of irradiation seemed to be responsible for the entity. A large target field or whole brain irradiation and the senility of patients were major risk factors. The most important differential diagnosis is normal pressure hydrocephalus which is basically curable. The prognosis of radiation-induced brain atrophy is poor. The only possible method to protect the brain from this pathologic entity is to minimize target field as much as possible.

Age Factors↗

Malignant growth hormone-secreting pituitary adenoma with hematogenous dural metastasis: case report.

A rare case of growth hormone-secreting pituitary adenoma with hematogenous metastasis to the dura mater of the cerebral convexity is presented. Immunohistological staining was essential to the diagnosis. The histological findings demonstrated that the metastasis was blood-borne. Extensive removal of the tumor and postoperative chemotherapy resulted in partial remission. The mechanism of metastasis, the histological findings, the treatment, and the prognosis are discussed.

Adenoma↗

Primary leiomyosarcoma of the dura mater. Case report.

A rare case of leiomyosarcoma arising from the dura mater is presented. A definite histological diagnosis was based on the electron microscopic features. Extensive removal of the tumor and postoperative radiation therapy resulted in complete remission. The etiology and the origin of this tumor are discussed.

Aged↗

Leptomeningeal and orbital benign lymphophagocytic histiocytosis. Case report.

An extremely rare case of isolated histioproliferative lesions arising from the subarachnoid space of the left occipital convexity and the orbit is presented. The presence of histiocytes showing lymphophagocytosis and positivity for S-100 protein staining confirmed that the lesions represented extranodal forms of sinus histiocytosis with massive lymphadenopathy.

Adult↗

[Decreased tumor viability of gliomas after radiation therapy, evaluated by dynamic CT scan].

The tumor viability of 28 gliomas after radiation therapy has been investigated by dynamic CT scan that estimated 4 parameters (Area, Peak, Time of Peak, and, Height of Plateau) from a time-density curve. Glioblastoma showed higher values of Area and Peak, whereas astrocytomas showed lower values when compared to those found in normal gray matter. After radiation therapy, the Area and Peak decreased and the Time to Peak was prolonged, suggesting a decrease in blood volume and blood flow in the tumor tissue. The increased Height of Plateau showed an increased permeability of the tumor-vessels. These results suggest that a dynamic CT scan provides a useful indicator of the change in tumor-viability after radiation therapy.

Adult↗