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Biomedical subjects

M Kowada

Publications and source records attributed to M Kowada.

At least 55 records · Page 3Linked to original sources
PubMed1994

Enhancement of ACNU cytotoxicity by pretreatment with O6-methylguanine in ACNU-resistant brain tumors.

O6-Methylguanine is a substrate of the DNA repair enzyme O6-methylguanine-DNA methyltransferase, which is involved in the repair mechanism of DNA damage induced by chloroethylnitrosoureas such as 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). We tested the enhancement effect of O6-methylguanine pretreatment on ACNU cytotoxicity in ACNU-resistant brain tumors. Exposure to O6-methylguanine at various times ranging from 2 to 48 hours increased the cytotoxic effects of ACNU on C6-1 cells, and this effect was highest at higher concentrations 500 and 1,000 microM. Colorimetric cytotoxicity assay revealed at least a two-fold increase in ACNU cytotoxicity relative to controls without O6-methylguanine. Intraarterial ACNU after treatment with O6-methylguanine (two intravenous bolus injections of 80 and 40 mg/kg) significantly (P < 0.05 or P < 0.01) reduced the proliferation activity of transplanted C6-1 tumors for 96 hours after injection, whereas intravenous ACNU together with O6-methylguanine significantly (P < 0.05) reduced C6-1 activity for only 48 hours. Thus, pretreatment with O6-methylguanine prolonged the suppression effect of ACNU. The C6-1 tumors treated only with intravenous or intraarterial ACNU showed transient inhibition and rapid regrowth for 24 hours after treatment. These results indicate that O6-methylguanine increases ACNU cytotoxicity in an in vitro and in vivo brain tumor model.

Animals↗
PubMed1994

Potential of O6-methylguanine or O6-benzylguanine in the enhancement of chloroethylnitrosourea cytotoxicity on brain tumours.

The purine analogues O6-methylguanine and O6-benzylguanine are well-known as a chemical modulator of the DNA repair enzyme O6-methylguanine-DNA methyltransferase. Inactivation of the enzyme by O6-methylguanine or O6-benzylguanine is expected to enhance sensitivity of tumours to chloroethylnitrosoureas. We studied the effect of O6-methylguanine or O6-benzylguanine pretreatment on cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) in brain tumour cells and transplanted brain tumours. Two-hour exposure of O6-methylguanine at higher concentrations (500 microM, 1,000 microM) increased ACNU cytotoxicity by only 2 times in ACNU-resistant C6-1 brain tumour cells. O6-Benzylguanine at concentrations between 10 and 100 microM markedly enhanced the cytotoxic effect. The ACNU sensitivity of the tumour cels pretreated with O6-benzylguanine was 5-40 times that of the cells without O6-benzylguanine. Neither O6-methylguanine nor O6-benzylguanine appreciably enhanced ACNU cytotoxicity of 9 L cells, which were originally sensitive to ACNU. Intracarotid ACNU with O6-methylguanine or O6-benzylguanine decreased proliferating activity of transplanted C6-1 brain tumours significantly during 48 hours. O6-Benzylguanine pretreatment resulted in a greater degree of suppression for a long time. The C6-1 tumours treated only with intracarotid ACNU showed a transient inhibition and a rapid regrowth during 24 hours after the treatment. These results indicate that O6-methylguanine or O6-benzylguanine increases ACNU cytotoxicity and may be feasible for effective combination therapy with chloroethylnitrosourea in the chemotherapy of malignant brain tumours.

Animals↗
PubMed1994

Vascular malformations of the brain in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease).

Six patients with vascular malformation of the brain in hereditary hemorrhagic telangiectasia (HHT) were reviewed to determine clinical and radiographic characteristics of these lesions. There were two patients with arteriovenous fistula (AVF), three with arteriovenous malformation (AVM), and one with multiple AVMs associated with AVF. Seizures were the most common presenting symptom (seen in three patients), and two of them had intracerebral hematomas (ICH). In the remainder, the malformations were incidentally found in the course of evaluation of other diseases. Their locations were variable, but the majority was superficially confined to the cerebral cortex. Arterial supply was from mostly one feeding artery that was a cortical branch of either anterior, middle, or posterior cerebral artery. In six of nine malformations, the venous drainage was through a superficial cerebral vein into either the superior sagittal sinus or transverse sinus. Direct surgery was done on two patients with ICH, artificial embolization on one, and stereotactic radiosurgery on one. The cerebral vascular malformations in HHT are not infrequent, and in particular the importance of computed tomography and cerebral angiography should be recognized in patients with pulmonary AVF associated with HHT.

Adolescent↗
PubMed1994

Anterior fossa dural arteriovenous malformation supplied by bilateral ethmoidal arteries.

Two cases of dural arteriovenous malformation (AVM) involving the base of the anterior cranial fossa are reported. The nidi in both cases were located in the region of the left cribriform plate and mainly supplied by the anterior ethmoidal arteries of both sides, draining through pial veins into either the cavernous sinus or the superior sagittal sinus. In the first case neurologic symptoms resulted from transient frontal lobe dysfunction presumably due to abnormal venous drainage, and the second case presented with subarachnoid hemorrhage caused by rupture of dural AVM at the base of the anterior fossa. Both cases were surgically managed and the AVMs were successfully obliterated. This unique subgroup of dural AVM in the anterior fossa is thoroughly reviewed in the literature, and the epidemiology, symptomatology, neuroradiology, surgical treatment, and associated vascular lesions are discussed.

Dura Mater↗
PubMed1994

Large pituitary adenoma of the sphenoid sinus and the nasopharynx: report of a case with ultrastructural evaluations.

A unique case of nonfunctioning pituitary adenoma exclusively involving the sphenoid sinus and the nasopharynx is reported. The computed tomography and magnetic resonance imaging (MRI) clearly depicted the presence of a large, soft mass in the sphenoid sinus and its extensive invasion to the sphenoid wing and the clivus. In particular MRI was found useful in delineating precise anatomic relationships between this sphenoid sinus tumor and the pituitary fossa. The sphenoid sinus tumor was partially resected by sublabial transnasal approach, and the intact dura mater of the base of the pituitary fossa was confirmed. Pathologic examinations including immunocytochemical and ultrastructural studies showed that the tumor was classified as a nonfunctioning acidophilic pituitary adenoma. Despite the endocrine-inactive tumor, the presence of small secretory granules in the cytoplasm demonstrated by electron microscopic studies was of significant importance in establishing the diagnosis. This rare tumor is reviewed in the literature in the context of nasopharyngeal extension of pituitary adenomas, and a possibility of ectopic occurrence and growth is also discussed in the presented case.

Adenoma↗
PubMed1994

Case report: saccular aneurysm of the intraorbital ophthalmic artery.

A saccular aneurysm of the intraorbital portion of the ophthalmic artery is extremely rare. We report this entity in a 54-year-old man who also had a dural arteriovenous malformation (AVM) at the base of the anterior cranial fossa. The aneurysmal formation at this unusual site may be explained by a haemodynamic stress that derived from the presence of the dural AVM.

Aneurysm↗
PubMed1994

O6-methylguanine-DNA methyltransferase activity in cerebral gliomas. A guidance for nitrosourea treatment?

The activity of O6-methylguanine-DNA methyltransferase (O6-MT), which removes O6-methyl residues from O6-methylguanine-DNA leading to cell death, has been reported to correlate with sensitivity to nitrosoureas used for chemotherapy of gliomas. We determined O6-MT activity in tumors and matched brain tissue from patients with gliomas. Histological diagnoses were: six malignant astrocytomas, two glioblastomas, two oligodendrogliomas, one ependymoma, and one medulloblastoma. In all cases but one, the activity ranged widely from 39 to 258 fmol/mg protein extract. The wide range of activity of the tumor tissue may indicate varying degree of sensitivity to nitrosoureas. The activity of brain tissue, available from the peritumoral region of five cases, varied between 38 to 415 fmol/mg. Four of the five regions showed a higher value than the respective tumor, and one showed a lower value.

Adolescent↗
PubMed1994

[Preliminary report of radical multiple synovectomy in rheumatoid arthritis].

We performed radical multiple synovectomy (RaMS) on rheumatoid arthritis (RA) patients who had multiple swollen joints in the mid or late course of RA. The objectives of this operation are to reduce the quantity of RA synovium as much as possible and to increase the efficacy of anti-rheumatic medication in order to achieve remission.2+ Nineteen RA patients who underwent RaMS were followed up for at least 15 months. In this series, anti-rheumatic medications were not changed after the operation, so that the effectiveness of the RaMS could be evaluated. The patients ranged in age from 44 to 73 years (mean: 55.8 years). The male to female ratio was 2:17. Duration after onset of RA ranged from 2 to 29 years (mean: 15.1 years). The swollen joint score according to Lansbury's evaluation of the RA activity index ranged from 7 to 24% (mean: 14.4%). The synovectomized joint score ranged from 7 to 22% (mean : 13.3%). The weight of the excised RA synovium ranged from 19.0 to 109.9 g (mean : 54.0 g). The number of operations was one in three patients, two in 15 patients and three in one patient. The postoperative results indicated that the modified Lansbury's index (morning stiffness, grip power, ESR, joint score), the values of ESR, CRP, Hb, TNF-alpha and IL-6 in the blood, and the peripheral lymphocyte CD4/CD8 ratio were improved, with a statistically significant difference. At 15 months after the operation, ten of the 19 patients (52.5%) satisfied the proposed criteria for clinical remission of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Longitudinal analysis of glucose metabolism in recurrent meningioma].

We repeatedly measured kinetic rate constants and glucose metabolic rate (kinetic rCMRG1) using dynamic positron emission tomography (PET) and autoradiographic rCMRG1 in a patient with recurrent meningioma. A 50-year-old woman who presented with a left visual disturbance was admitted to our hospital. MR images revealed a mass lesion occupying the left middle fossa. The patient underwent Simpson grade IV surgery. The histological diagnosis was meningothelial meningioma. One year later the tumor had grown back to almost the same size as before treatment and was removed again by Simpson grade IV procedure. Postoperatively, the patient underwent radiation therapy (54 Gy). Two years after the second operation, the tumor was found to have invaded the left orbit and was resected by Simpson grade IV procedure. After additional radiation therapy, the patient was discharged. The rate constants were analyzed preoperatively and whenever the tumor recurred according to the three compartment 18F-fluorodeoxyglucose (FDG) model. Preoperative PET indicated tumor k1 and k2 values higher than in the contralateral gray matter, suggesting high permeability due to absence of the blood-tumor barrier and an abundant blood supply. The tumor k3 value, an indicator of hexokinase activity, was as high as in the contralateral gray matter. When the tumor recurred, the tumor k1, k2 and k3 values remained consistently high, indicating high proliferative activity. In contrast, the contralateral gray matter k1, k2 and k3 values decreased to some extent, suggesting effects of surgery or radiotherapy. Tumor rCMRG1 values, both autoradiographic and kinetic, were enhanced markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed1994

Establishment of the two glioma cell lines: YH and AM.

We have established two human glioma cell lines, which were designated as YH cells and AM cells. The two cell lines have maintained morphological appearance as seen 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.

Adult↗
PubMed1994

[Cerebellar hemangioblastoma associated with fatal intratumoral hemorrhage: report of an autopsied case].

Intracranial hemorrhage associated with brain tumors is rate, but when present, it is often seen in malignant tumors such as glioblastoma and metastasis, and in meningiomas. Hemangioblastomas, benign vascular tumors, rarely develop fatal intracerebral hemorrhage. We thus documented an uncommon case of cerebellar hemangioblastoma associated with massive hemorrhage, the cause of which was thoroughly examined during autopsy. A 69-year-old man was transferred to our Service because of swallowing disturbance and dysarthria. The patient was known to have a cerebellar hemangioblastoma and hydrocephalus, for which VP shunt had been placed. Two weeks after admission he suddenly became comatose and eventually died of progressive herniation. At autopsy it was shown that the brain was edematous and covered with subarachnoid blood clots. The tumor was found involving the cerebellar vermis and the right hemisphere, protruding upward from the superior surface of the cerebellum. Horizontal sections through the cerebellum disclosed a well circumscribed tumor with adjacent hematomas involving the vermis and brain stem. The pathological diagnosis was hemangioblastoma and varix-like abnormal vessels were observed within the tumor. The sites of hematoma and tumor adjacent to the tentorial incisura and the history of VP shunting may suggest that upward herniation played a significant role in rupture of the abnormal vessels, which then led to the devastating hemorrhage in this particular case.

Aged↗
PubMed1994

[Hereditary hemorrhagic telangiectasia associated with cerebral arteriovenous fistula and multiple cerebral arteriovenous malformations: case report].

Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by a triad of mucocutaneous and visceral telangiectasia, recurrent epistaxis and familial history. We reported a rare case of HHT associated with pulmonary and cerebral arteriovenous fistulae (AVF) and multiple cerebral arteriovenous malformations (AVM). The roles of multimodality therapies including artificial embolization, feeder clipping and stereotactic radiosurgery for these multiple cerebrovascular dysplasia in HHT were discussed. In particular the usefulness of radiosurgery to obliterate AVM was emphasized. It is especially useful for multiple AVM's associated with HHT. A 7-year-old boy had presented himself at another hospital 2 years previously with cyanosis of the lips and fingers on exertion. He was diagnosed as having pulmonary AVG and underwent surgery. His mother had suffered from epistaxis in her adolescence, and was then highly suspected as having HHT. She underwent surgical removal of a left fronto-parietal AVM at the age of 16 years. The family history then prompted the patient to have a brain CT done, which eventually demonstrated an abnormal enhancing mass at the left frontal region. He was transferred to our service for further evaluation. Left carotid angiograms demonstrated an AVF supplied by a dilated anterior internal frontal artery of the anterior cerebral artery (ACA), draining directly into the vein of the corpus callosum with a large aneurysmal dilatation, and then draining further into the straight sinus via the vein of Galen. In addition, right carotid angiograms revealed three small AVM's fed by the median artery of the corpus callosum, and the middle internal frontal and paracentral arteries of the right ACA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriovenous Fistula↗
PubMed1993

Influence of O6-methylguanine-DNA methyltransferase activity on chloroethylnitrosourea chemotherapy in brain tumors.

Chloroethylnitrosoureas (CENUs) alkylate DNA at specific sites and inhibit DNA replication in tumor cells. O6-Alkylguanine moieties resulting from alkylation of guanine bases are thought to be one of most lethal adducts in living cells. Effectiveness of CENUs is known to relate well with an enzymic activity of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which recognizes and removes O6-alkylguanine. To improve therapeutic results of CENUs, we have measured MGMT activity of human brain tumors and studied the relationship between MGMT activity and clinical responsiveness to I-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). Thirty-seven patients with brain tumors were entered into the study. The neoplasms included gliomas, non-glial tumors, and brain metastases. The MGMT activity of gliomas was significantly lower than that of non-glial tumors and brain metastases. No significant difference in the enzyme activity was noted between low- and high-grade gliomas. Out of the 22 gliomas 5 tumors indicated a value below 60 fmol/mg, suggestive of a methyl excision repair minus (Mer-) tumor. Two out of 3 evaluable patients with a Mer- tumor responded well to post-operative ACNU adjuvant chemotherapy. Our results suggest that brain tumors include a certain percentage of Mer- phenotype tumors, and that CENUs such as ACNU should be applied selectively on tumors with a low MGMT activity in order to increase the therapeutic effectiveness.

Adolescent↗
PubMed1993

[Usefulness of 201T1C1-SPECT in the evaluation of radiation and chemotherapy for brain tumors].

We investigated the usefulness of Thallium-201 chloride single photon emission computed tomography (T1-SPECT) in the evaluation of radiation and chemotherapy for brain tumors. The subjects were 9 cases (10 tumors) of malignant astrocytomas. T1-SPECT was performed before and immediately after irradiation and/or intraarterial infusion of ACNU. In 5 of 10 tumors, T1-index already changed 1 or 2 months before tumor size changed on the CT. Our results suggested that T1-SPECT was useful for evaluating the viability of tumor.

Aged↗
PubMed1993

Time course of dorsal root axon regeneration into transplants of fetal spinal cord: an electron microscopic study.

Intraspinal transplants of fetal CNS tissue permit or enhance the regeneration of cut central axons of adult dorsal root ganglion (DRG) neurons. Some of these regenerated axons establish synapses with transplant neurons. The aims of the present study were to determine when regenerated DRG axons begin to form synapses with transplanted embryonic spinal cord neurons and whether these synapses are permanent. We also examined the development of transplant neuropil in areas innervated by the regenerated axons. Whole pieces of Embryonic Day 14 spinal cord were introduced into hemisection cavities made at the level of the lumbar enlargement, and the cut L4 or L5 dorsal root was juxtaposed to the transplant. Regenerated DRG axons immunoreactive for calcitonin gene-related peptide (CGRP) were labeled by immunohistochemical methods and examined by electron microscopy from 1 week to 1 year after surgery. CGRP-immunoreactive axon terminals made synaptic contacts with dendrites and perikarya of transplant neurons by 1 week after axotomy. The morphology of the synapses was immature. Large growth cone-like structures were also present at 1 week but not at 2 weeks or later. At 2 weeks, regenerated unmyelinated axons formed terminals similar to those found in animals surviving for 48 weeks. Axoaxonic synapses in which the pre- and postsynaptic elements were immunolabeled for CGRP and regenerated CGRP-labeled myelinated axons were observed at 4 weeks and later. The area of distribution of CGRP staining increased until 12 weeks and the synaptic density of regenerated CGRP-labeled terminals increased for 24 weeks. The results indicate that the synaptic terminals of regenerated primary afferent axons are permanently retained within fetal spinal cord transplants. Transplants may therefore contribute to the permanent restoration of interrupted neural circuits.

Animals↗
PubMed1993

Regeneration of adult dorsal root axons into transplants of dorsal or ventral half of foetal spinal cord.

Several dorsal root axons regenerate into the transplants of foetal spinal cord (FSC) and form synapses there. It is unknown whether the growth is specific to transplants of dorsal half FSC, a normal target of most dorsal root axons, or whether it is due to properties shared by transplants of ventral half FSC. We used calcitonin gene-related peptide immunohistochemistry to label subsets of regenerated host dorsal root axons, and morphometric analysis to compared neuronal populations within both transplants. Adult Sprague-Dawley rats received intraspinal grafts of dorsal or ventral half FSC (E14), and the L4 or L5 dorsal root was cut and juxtaposed to the grafts. Three months later sagittal sections were prepared for immunohistochemistry and Nissl-Myelin stain. Histograms of the perikaryal area showed that the transplants of dorsal half FSC consisted of small neurons predominantly, whereas transplants of ventral half FSC consisted of neurons of variable sizes. Dorsal root axons regenerated into both transplants, but growth into dorsal half FSC was more robust. These results indicate that both transplants provide an environment that supports dorsal root regeneration, but that the environment provided by dorsal half FSC is more favorable. Transplants of dorsal half FSC may offer advantages for the long-term goal of repairing of damaged spinal cord circuits.

Animals↗
PubMed1993

Electrophysiological responses in foetal spinal cord transplants evoked by regenerated dorsal root axons.

Cut dorsal root axons regenerate into intraspinal transplants of foetal spinal cord (FSC) and establish synaptic connections there. The aim of the present study was to determine whether transplant neurons are driven synaptically in response to electrical stimulation of regenerated dorsal root axons. Adult Sprague-Dawley rats received FSC transplants (E14) into dorsal quadrant cavities at the lumbar enlargement. The cut L4 or L5 dorsal root stump was placed at the bottom of the lesion cavity and secured between the transplant and host spinal cord. Four to ten weeks later the animals were prepared for electrical stimulation and recording. We stimulated regenerated dorsal roots and recorded extracellular single unit post-synaptic activities which were evoked close to the dorsal root-transplant interface. We used intracellular recording to observe several examples of monosynaptic EPSPs in transplant neurons evoked by dorsal root stimulation. These results indicate that the regenerated dorsal root axons establish functional connections with neurons within the transplants and suggest that FSC transplants can be used to reconstruct functional connections between neurons that have been interrupted by spinal cord injury.

Animals↗