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Biomedical subjects

M Kowada

Publications and source records attributed to M Kowada.

At least 73 records · Page 4Linked to original sources
PubMed1993

(14C-methyl)-L-methionine uptake in rat brain tumors before and after treatment with the protein synthesis inhibitor cycloheximide.

Autoradiographic study of (14C-methyl)-L-methionine with brain tumor bearing rats aimed at an elucidation of the mechanism of tracer accumulation in the protein synthesis of tumor. Twice as much tracer accumulated in the tumors compared as in the contralateral gray matter (nontumor region) at 90 min post intravenous injection. The protein-bound fraction of the tumors, expressed as acid-insoluble fraction (AIF), was 1.7 +/- 0.6 (mean +/- standard deviation, n = 6), significantly higher than that (0.8 +/- 0.2) of the nontumor region (p < 0.05 by the Mann-Whitney test). The tumor AIF comprised 82.3 +/- 9.2% of the total amount of the tracers accumulated in the tumors. The protein synthesis inhibitor cycloheximide reduced the tracer uptake and the AIF of the tumors to an almost same level as the nontumor region. These findings indicate that metabolic acceleration of protein synthesis may be a main reason for the high accumulation of (14C-methyl)-L-methionine in tumor.

Animals↗
PubMed1993

Characterization and chemosensitivity of two cell lines derived from human glioblastomas.

We have characterized two human glioblastoma cell lines, which were designated as YH cells and AM cells. The two cell lines maintained morphological appearance observed in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture. Inoculation of AM cells into athymic nude mice formed large tumors at a high incidence. As with chemosensitivity to chloroethylnitrosourea, O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in in vitro cultured cells as well as tumor specimens obtained at surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301 fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the both patients, an MGMT activity of original tumors related with responsiveness to ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the respective tumor specimens comes from selection of ACNU-sensitive cells or alteration in biological characteristics during long term culture. These results suggest that cell lines derived human brain tumors are useful targets for understanding the chemosensitivity of human malignant gliomas and for establishing a pertinent chemosensitivity test.

Animals↗
PubMed1993

Primary central nervous system involvement of the so called 'peripheral T-cell lymphoma'. Report of a case and review of the literature.

Primary central nervous system (CNS) involvement of non-Hodgkin's lymphoma is uncommon and a vast majority of reported cases are of B-cell origin. We present a 52-year-old woman with primary peripheral T-cell lymphoma of the brain. Immunostaining of paraffin-embedded sections proved tumor cells to be positive for T-cell markers MT1 and UCHL1, and negative for B-cell markers MB1, and 4KB5. Radiotherapy combined with steroid therapy rendered neurologic recovery and complete tumor remission confirmed by computed tomography and magnetic resonance imaging. From a review of documented 19 cases of primary CNS T-cell lymphoma including the present case, this disease is characterized by poor prognosis among CNS lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Case report: radiation-induced vasculopathy implicated by depressed blood flow and metabolism in a pineal glioma.

A case of radiation-induced vasculopathy of a pineal glioma was presented with haemodynamic and metabolic changes before and after radiotherapy. After radiation of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week), regional blood flow, oxygen extraction fraction, metabolic rate of oxygen, kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly depressed (20% or greater) compared with the pre-irradiated study. 7 months after radiotherapy, the patient developed transient transient episodes of both right and left upper limb convulsion, terminating in generalized convulsion. When she developed status epilepticus, computed tomography showed extensive low density areas in the territory supplied by the right middle cerebral and the right posterior cerebral arteries. Cerebral angiography revealed diffuse stenosis at both carotid bifurcations and at the origins of the right posterior communicating and posterior cerebral arteries. Haemodynamic and metabolic depression therefore implicated radiation-induced vasculopathy in the present case.

Astrocytoma↗
PubMed1993

Roles of embryonic astrocytes and Schwann cells in regeneration of adult rat dorsal root axons: qualitative observations.

Transplants of fetal spinal cord support regeneration of severed dorsal root axons and allow synapse formation. To analyze the components of the transplants that provide this favorable environment, we studied whether or not 1) the embryonic spinal cord transplants contain Schwann cells, a major producer of laminin, and 2) whether dorsal roots regenerate into transplants of immature astrocytes. We used calcitonin gene-related peptide (CGRP), laminin and glial fibrillary acidic protein (GFAP) immunocytochemistry to identify regenerated axons, Schwann cells and astrocytes, respectively. CGRP-immunoreactive axons regenerated into embryonic day 14 fetal spinal cord transplants, but the transplant did not contain laminin. Dorsal roots immunoreactive for CGRP also regenerated into suspensions of cultured astrocytes. The transplanted astrocytes also favored the expression of laminin and GFAP. CGRP-labeled axons regenerated and distributed widely into the polycarbonate tubes coated with poly L-lysine and containing medium with or without cultured astrocytes. These results indicate that Schwann cells are not likely to account for dorsal root regeneration into transplants of fetal spinal cord and that astrocytes may in fact induce regeneration. Regeneration may also take place in response to various environments.

Animals↗
PubMed1993

Bilateral vertebral artery occlusion secondary to atlantoaxial dislocation with os odontoideum: implication for prophylactic cervical stabilization by fusion--case report.

A 27-year-old male presented with an unusual atlantoaxial dislocation associated with os odontoideum, after suffering sudden onset of significant neurological deterioration. Angiography demonstrated simultaneous occlusion of the bilateral vertebral arteries assumed responsible for the devastating neurological deficits. He initially underwent cervical immobilization with a Crutchfield tong for 2 months and subsequent posterior fusion using an iliac bone graft and wires. The neurological symptoms gradually subsided, and 5 years later good healing of the bone graft without instability and ample subarachnoid space around the spinal cord were radiologically confirmed. Early prophylactic stabilization of atlantoaxial dislocation due to os odontoideum is recommended to prevent a poor outcome. Careful angiographic evaluation of the vertebrobasilar circulation is important for management of patients with os odontoideum.

Adult↗
PubMed1993

Autoradiographic analysis of (14C-methyl)-L-methionine uptake in transplanted rat brain tumors.

To elucidate metabolic pathways of methionine in brain tumors, we studied autoradiographic images of (14C-methyl)-L-methionine (14C-Met) in transplanted rat brain tumors. 14C-Met accumulated in the tumor almost twice as much as in the gray matter 90 min after injection. The acid-insoluble fraction, which was bound to macromolecules, comprised 84% the total count of the accumulated tracers in the tumor. Analysis of 14C-Met tracer accumulation is informative for understanding amino acid metabolism in brain tumors.

Animals↗
PubMed1993

[An occlusion and stenosis of the venous drainage system in cerebral AVMs--angiographical investigation].

We investigated angiographically occlusion or stenosis of draining veins in cases of arteriovenous malformations (AVMs). The subjects were 51 cases who were diagnosed as cerebral AVMs by angiography in our hospital between April 1973 and January 1991. Those consisted of 8 dural AVMs, 3 mixed pial-dural AVMs, and 40 pial AVMs. Angiography was stereoscopically done in all cases. Angiograms obtained prior to treatment were retrospectively analyzed. Cases of dural AVMs or arteriovenous fistulae in the cavernous sinus were excluded from the subjects. Eight of 51 cases (16%) had occlusion or stenosis of draining veins; i.e., 2 dural AVMs, 1 mixed pial-dural AVM, 5 pial AVMs. One of 2 dural AVMs was located in the sigmoid sinus, and another involved the superior sagittal sinus. One mixed pial-dural AVM was a vein of Galen aneurysm. Occlusion or stenosis was recognized at the junction of the vein of Galen to the straight sinus (3 cases), in the straight sinus (2 cases), at the junction of the vein of Labbe to the transverse sinus (1 case), in the superior sagittal sinus (1 case), and in the sigmoid sinus (1 case). Two of 8 cases with occlusion or stenosis of draining vein presented with hemorrhage at the site of AVMs. In cases of pial AVMs, occlusion or stenosis of draining vein seemed be related to endothelial changes due to turbulent and irregular flow. On the other hand, in cases of dural AVM with dural sinus occlusion, sinus abnormalities may precede the formation of fistulous communications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Time course of dorsal root axon regeneration into transplants of fetal spinal cord: I. A light microscopic study.

Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal cord and establish synaptic connections there. The aims of the present study were to describe the progression of dorsal root growth within the transplants and the maturation of transplant morphology and to determine whether the regenerated dorsal root axons persist within the transplants or eventually withdraw. Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the transplants. The morphology of the transplants was examined from 1 day to over 1 year after surgery, and the regenerated dorsal roots were labeled with immunohistochemical methods to study the subset that contains calcitonin gene-related peptide (CGRP). Embryonic spinal cord transplants survived and grew within the host spinal cord in over 90% of the animals. Transplant volume increased and the morphology of the transplants matured over the first 12 weeks and then did not change for 48-60 weeks. During the first week the transplants were composed of dissociated neurons, glia, and hematogenous cells with considerable extracellular space between them. Subsequently, the grafted neurons became densely aggregated, and non-neuronal elements such as inflammatory cells and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to regenerate into the transplants within 24 hours, formed dense bundles by 4 days, and were still present at 60 weeks, the longest survival period examined. Myelination of axons within transplants began at 2 weeks. Quantitative analysis showed that the area of the transplants occupied by CGRP-labeled axons and the distribution area of the labeled axons within the transplants increased until 12 weeks and persisted unchanged for over 48 weeks. These results indicate that regenerated dorsal root axons are permanently maintained within transplants of embryonic spinal cord and suggest that the transplants can contribute to the permanent restoration of damaged intraspinal neural circuits.

Animals↗
PubMed1992

Modulation of BUdR labeling index in rat brain tumors following intracarotid ACNU administration.

Chloroethylnitrosourea (CENU) chemotherapy has yielded limited benefit on survival of malignant brain tumors. Intracarotid administration of CENU is expected to have the advantage of increasing drug concentration reaching tumors. To understand basic knowledge of intracarotid chemotherapy, we monitor changes of proliferating rate after intracarotid injection of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), using a bromodeoxyuridine (BUdR) labeling index (LI) in transplanted brain tumors of three cell strains. C6-2 tumor cells were in vitro sensitive to ACNU, and C6-2/ACNU and C6-1 cells were resistant. The drug sensitivity to ACNU was as follows: 11.9 microM in the C6-2 cells, 46.0 microM in the C6-2/ACNU cells, and 49.7 microM in the C6-1 cells at SD10, which gives 10% survival of clonogenic cells. The intracarotid ACNU at a dose of 30 mg/kg abruptly decreased the LI to 11% (mean) from 36% in C6-2 transplanted tumors. The LI remained low between 12 and 48 hours after, and then increased to the pretreatment level by 96 hours. In contrast, the LI of C6-1 tumors transiently fell to 15% from 42% at 12 hours after the injection, and subsequently increased to 36% at 24 hours and 37% at 48 hours. These results indicate that intracarotid ACNU administration shortly suppresses proliferating activity of tumors and that combined and alternating chemotherapy are mandatory for enhancing effectiveness of brain tumor chemotherapy.

Animals↗
PubMed1992

Effects of radiotherapy determined by 11C-methyl-L-methionine positron emission tomography in patients with primary cerebral malignant lymphoma.

Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using 11C-methyl-L-methionine (11C Met). Lesions delineated by 11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of 11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma.

Aged↗
PubMed1992

Cross-resistance pattern in brain tumour cells resistant to antitumour chloroethylnitrosoureas.

We tested acquired resistance and cross-resistance of brain tumour cells after repeated treatments of antitumour agents including chloroethylnitrosoureas (CENUs) in clinical use for brain tumour chemotherapy. Within ten repeated 2-day incubation periods with either 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) or methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyr anoside (MCNU), brain tumour cells (9L) developed high degrees of resistance to these drugs, as evidenced by about 3- and 6-fold increases, respectively, at the 10% survival dose (SD10). The resistance has unchanged with time after termination of challenging treatments. Repeated challenges with bleomycin (BLM), cis-diaminedichloroplatinum (II) (CDDP), and methotrexate (MTX) did not develop a significant resistance. ACNU-resistant (9L/ACNU) cells showed complete cross-resistance to MCNU, and MCNU-resistant (9L/MCNU) cells to ACNU. Drug sensitivity to other DNA-damaging agents (BLM, NCS, CDDP, etoposide) than CENUs fluctuated to a lesser extent among 9L parent, 9L/ACNU, and 9L/MCNU cells. These data suggest clinical disadvantage of prolonged adjuvant CENU chemotherapy and advantage of combined CENU chemotherapy with other agents than CENUs in brain tumours.

Animals↗
PubMed1992

The effect of hypoxia on the epileptiform activities induced by magnesium-free medium in rat brain slices.

In order to understand the mechanisms underlying the seizure generation, the present study has investigated the effect of hypoxia on the transition between seizure and interictal bursting. Bathing rat brain slices of the hippocampus and entorhinal cortex in magnesium-free medium elicits electrographic seizures. However, they are eventually replaced by the interictal bursts. It has previously been shown that the interictal bursts, arising in the hippocampal area CA3, are propagated to and disrupt the seizure generation in the entorhinal cortex. In this report we demonstrate that hypoxia promotes the seizure reappearance in the entorhinal cortex by suppressing the interictal bursts in CA3.

Animals↗
PubMed1992

Radiation-induced bilateral cystic frontal lobe necroses demonstrating a fluid-blood level--case report.

A 41-year-old male developed radiation-induced bilateral cystic frontal lobe necroses after irradiation for an olfactory neuroblastoma. Computed tomography (CT) and magnetic resonance (MR) imaging revealed the lesions, one containing a fluid-blood level on CT scans and niveau formation on MR images. It was proved to be a coagulated hematoma within the cyst at surgery. Such a fluid-blood level in a radiation-induced cyst has never been reported, although hemorrhage frequently accompanies delayed radiation necrosis. Positron emission tomography with multiple tracers may be useful in differentiating cerebral radiation necrosis from tumor recurrence, because of absence of abnormal tracer accumulation.

Adult↗
PubMed1992

Recurrent brain abscess associated with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)--case report.

A 53-year-old mentally handicapped female with hereditary hemorrhagic telangiectasia complicated by pulmonary arteriovenous fistula developed a recurrent brain abscess in the left frontal region. She responded well to surgical drainage and antibiotic therapy. Previously, she had two brain abscesses of the left parieto-occipital and right parietal regions removed on separate occasions at 38 and 40 years of age. Although pulmonary arteriovenous fistula was eventually confirmed by angiography at age 41 years, surgical removal of the pulmonary lesion was not indicated due to multiplicity and large vascular shunting. Early recognition of pulmonary arteriovenous fistula in patients with hereditary hemorrhagic telangiectasia is emphasized for diagnosis of brain abscess and prevention of recurrence.

Arteriovenous Fistula↗
PubMed1992

Development of resistance to antitumor chloroethylnitrosoureas in vitro in brain tumor cells.

Rat brain tumor cell lines (9L, C6-1, C6-2), human brain tumor cells (T98G), and HeLa S3 cells were studied to assess their acquired resistance to the chloroethylnitrosoureas (CENUs), 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyr anosid e (MCNU), after 10 repeated exposures of a panel of different drug concentrations. Assay end-point was colony-forming ability after 24-h drug exposure. Intrinsic resistance was tested at the 10% survival dose (SD10) and C6-1, T98G, and HeLa S3 cell lines were 3 to 16 times more resistant to ACNU than 9L and C6-2 cell lines. After repeated exposures to ACNU, 9L and C6-2 cells acquired 2- and 5-fold resistance to ACNU respectively, whereas C6-1 and T98G cells retained a resistance almost equivalent to the respective parent cells. HeLa S3 cells also acquired resistance to ACNU, as evidenced by a 3.5-fold increase. The SD10 of the cells to MCNU ranged from 4.3 microM (C6-2 cells) to 151.7 microM (T98G cells). After long-term exposure to MCNU, all five cell lines became significantly resistant compared to their respective parent cells. The easily obtained acquired resistance to CENUs suggests a clinical disadvantage of continual and repeated adjuvant monochemotherapy with these agents.

Animals↗
PubMed1992

Distribution of DNA cleavages induced by bleomycin and neocarzinostatin in a defined sequence of rat glioma cells.

We have demonstrated the usefulness of a highly reiterated sequence of rat DNA as a probe sequence for evaluating the effect of bleomycin (BLM) and neocarzinostatin (NCS) at the level of individual nucleotides. The 370 base pairs (bp) DNA fragment, purified from rat glioma C6 cells after Hind III digestion, was labeled with 32P at either the 3'- or the 5'-ends and then divided into 167 bp and 203 bp by Hae III. These end-labeled DNA fragments were reacted in vitro with BLM or NCS, and electrophoresed on the denaturating 8% polyacrylamide gels according to Maxam and Gilbert's sequencing protocol. BLM created DNA strand breaks at the guanine-cytosine and guanine-thymine (5'----3') sequences, and NCS cleaved DNA at the position of thymines and adenines. The highly reiterated sequence of rat brain tumor DNA therefore provides adequate knowledge of DNA damages induced by BLM and NCS.

Animals↗