Biomedical subjects

M Kowada

Publications and source records attributed to M Kowada.

At least 19 recordsLinked to original sources

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↗

PubMed1991

Mechanism of electrographic seizure generation in the rat brain slice in low magnesium medium: modulatory effect of interictal bursting on seizure generation.

In order to understand the mechanisms underlying seizure generation, the present study investigated the functional and anatomical interaction between seizures and interictal bursts. Bathing rat brain slices of the hippocampus and entorhinal cortex in zero magnesium medium elicited electrographic seizures. In the later period, the electrographic seizures were eventually replaced by the interictal bursts. In this phase, lowering [K+]o and raising [Ca2+]o restored the tonic seizures by suppressing the interictal bursts. A multiple knife cut experiment revealed that the seizures arose in the entorhinal cortex and the interictal bursts originated in CA3. A selective knife cut across the subiculum showed that the interictal bursts, propagating from CA3 to the entorhinal cortex, disrupted and suppressed the electrographic seizures in standard Mg(2+)-free medium.

Animals↗

PubMed1991

Local image filing system in neurosurgery: validity of selective storage of radiographic images.

In an effort to achieve efficient image management in the practice of neurosurgery, a clinical data base system was designed and developed to process, store and retrieve neuroradiologic image information on hospitalized patients with the use of a local image filing system (EFPACS-500, Fuji Electric Co., Ltd). Storage and retrieval of radiographic images were studied to quantify existing procedures and to evaluate the validity of new technology. One of our hospitals (Southern Tohoku Research Institute for Neuroscience) has annually produced approximately 100,000 sheets of film radiographs, resulting in a great deal of serious problems, particularly lack of space for storage. In addition, the overall averaged ratio of selected key films to total files of radiographs was estimated to be 16.3% for hospitalized patients during the past 5 years. It is assumed that, by means of digital storage on this selective basis, radiographic storage problems can be solved with the use of the current data base system which efficiently handles image information involving patient care. In the practical view another substantial improvement in this work is the high functionality of the system, with which radiographic images coupled with a variety of clinical data on patients can be stored in a descriptive fashion.

Database Management Systems↗

PubMed1991

O6-alkylguanine-DNA alkyltransferase activity in human brain tumors.

It is well known that resistance in tumor cells to alkylating agents and, in particular, chloroethylnitrosoureas (CENUs), which are widely used in the chemotherapy of brain tumors, correlate well with activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (O6-AT). We measured O6-AT activity in human brain tumors in order to obtain basic knowledge of whether or not CENU chemotherapy can be applied selectively on brain tumors. The subjects included 17 gliomas (seven malignant astrocytomas, two glioblastomas, two medulloblastomas, two oligodendrogliomas, two ependymomas, one fibrillary astrocytoma, one primitive neuroectodermal tumor) and five non-glial tumors (three meningiomas, two neurinomas). The value of O6-AT activity for the gliomas varied widely and indicated 111 +/- 65 fmol of 3H-methyl adducts transferred/mg protein extract/hr (mean +/- S.D., range 0-258, 18 tumors), while the non-glial tumors showed a relatively high value of 270 +/- 43 fmol/mg/hr (range 225-330, 5 tumors). A significant difference in the O6-AT activity was noted between the gliomas and the nonglial tumors at the p-value of 0.001. Six (38%) out of 17 glioma cases showed a value below 100 fmol/mg/hr and four cases (24%) a value below 60 fmol/mg/hr. These results provide a biological basis for applying CENU chemotherapy on glioma patients with a lower value of O6-AT enzyme.

Brain Neoplasms↗

PubMed1991

[Efficacy of preoperative irradiation in midline oligodendrogliomas. Report of two cases].

Two midline oligodendrogliomas in young males were successfully totally removed after preoperative irradiation. A 33-year-old male with right lower extremity weakness had a large hypervascular mass occupying the left lateral ventricle. Even after 31 Gy whole-brain irradiation, massive bleeding occurred at surgery and resulted in only partial removal. The residual tumor markedly regressed with disappearance of abnormal vascularity after subsequent local boost irradiation. At the second operation, the tumor was totally removed. A 32-year-old male with progressive headache had a hypervascular mass with gross calcification in the right lateral ventricle. The tumor was partially resected due to its abundant vascularity and blood loss. After 60 Gy local irradiation, the tumor was moderately shrunk with a significant reduction in vascularity. At the second operation, the tumor was totally removed. Preoperative irradiation as an adjunct to surgery may increase the resectability of highly vascular tumors such as midline oligodendrogliomas.

Adult↗

PubMed1991

[A case of spinal epidural hematoma associated with idiopathic thrombocytopenic purpura].

Spinal epidural hematoma is a rare clinical entity, and the literature provides reports of 29 cases so far in Japan. A case of spinal epidural hematoma associated with idiopathic thrombocytopenic purpura diagnosed by CT scan and MRI is reported in detail with references to the literature. A 56-year-old female was admitted to our hospital on April 22, 1990, because of sudden onset of nuchal pain and right hemiparesis. Her consciousness was alert, but the deep tendon reflex was depressed, and pathological reflex such as Babinski's reflex was positive on the right side. Nuchal stiffness was observed. CT scan of the head revealed no abnormality, but the scan of cervical area showed an abnormal high density area in the right posterior region of the spinal cord at C2 - 3 level. MRI also revealed a low intensity area in the same region both in T1 and T2 weighted images. On admission, the platelet count was 10,000/microliters, and the bone marrow aspirate showed abundant megakaryocytes. The patient was diagnosed as having spinal epidural hematoma associated with idiopathic thrombocytopenic purpura. The patient was initially treated with a corticosteroid and a hyperosmotic agent. About 15 hours after the onset, her motor function began improving. Conservative therapy was continued, and she could walk 2 weeks after the onset. Spinal epidural hematoma is an uncommon disease commencing with back and radicular pain, paraplegia and rectovesical insufficiency. Early diagnosis and surgical decompression is generally imperative, although an exceptional remission without operation such as was observed in this case may occur.

Female↗

PubMed1991

[A case of central pontine myelinolysis with neurological recovery after administration of glucocorticoid].

A survival case of central pontine myelinolysis (CPM) is reported herein with a review of 22 MRI-analyzed CPM survivors in the literature. A 65-year-old male was struck on the forehead while in a traffic accident. He was almost fully conscious and neurologically free on admission. Laboratory data were normal except hyponatremia [122 mEq/l] and hypoproteinemia [5.8 g/dl]. 2 hours later he became drowsy and left hemiparesis. The CT scan showed right frontal cerebral hematoma leading to a remarkable midline shift. Immediately, aspiration of the hematoma was performed. On the next day, he returned to the initial neurological level. On the third day, however, he again became comatose followed by tetraparesis and ataxic respiration. While the CT scan at that time did not display any abnormality in the pons, the severe dysfunction of the brain stem occurred after the correction of hyponatremia strongly suggesting CPM. The serum Na levels were kept between 110 and 125 [mEq/l]. In addition, 375 mg of methylprednisolone had been daily administrated during and after a gradual correction of the hyponatremia, because glucocorticoid proved to be effective in the models of CPM. The neurological condition began to improve on the 14th day after admission. Eventually, he became conscious and independent in his daily activities, the time span being 8 months after the trauma. The trident MRI lesion in the basis pontis was 5 mm in diameter and much smaller than clinically expected. The 23 MRI-analyzed CPM survivors were reviewed in the literature including the present case. There were 7 males and 16 females, with a mean age of 48.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography.

A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR.

Adult↗

PubMed1990

A correlation between serum immunosuppressive acidic protein and altered immunocompetence in patients with brain tumours.

The present investigation was conducted to document a correlation between the serum levels of immunosuppressive acidic protein (IAP) and depressed lymphocyte responsiveness to mitogens in vitro in patients with intracranial tumours, and to delineate the possible roles of IAP upon immunocompetence in these patients. It was thought that high concentrations of IAP present in the serum of brain-tumour patients may play a significant role in the immunosuppression seen in this patient population. The effect of IAP upon mitogen-stimulated lymphocyte function was evaluated by tritiated (3H)-thymidine incorporation. Lymphocytes from both 30 patients with intracranial tumours and 30 normal individuals were incubated for 90 hours in culture medium in the presence of three mitogens: phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). Lymphocytes obtained from patients with brain tumours and cultured in autologous serum displayed a significant depression of 3H-thymidine incorporation, as was observed in previous studies. In addition, a significant suppression of mitogen-induced activation of the normal lymphocytes was demonstrated in the presence of allogeneic patients' serum and the percentage of inhibition was found significantly proportional to the IAP concentrations. Furthermore it was also demonstrated that increased levels of serum IAP could significantly correlate with two in vivo aspects of impaired cellular immunity: the decreased lymphocyte counts in the peripheral blood and diminished cutaneous delayed hypersensitivity reactions measured by purified protein derivative (PPD) skin test reactivity. On the other hand, an attempt was also made to investigate changes in humoral immunity and immunoglobulin concentrations were observed not to correspond to the serum IAP levels. These studies suggest a possible connection between serum IAP levels and altered cellular immune competence in brain-tumour patients.

Adolescent↗

PubMed1990

Linkage between O6-methylguanine-DNA methyltransferase (O6-MT) activity and cellular resistance to antitumour nitrosoureas in cultured rat brain tumour cell strains.

We have examined O6-methylguanine-DNA methyltransferase (O6-MT) activity of rat brain tumour cell strains with reference to cellular resistance to antitumour nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (nimustine, ACNU) and methyl-6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyrano side (ramustine, MCNU). The values of O6-MT activity were 52 and 160 fmol/mg protein extract in 9L and C6 rat brain tumour cells, respectively; while HeLa S3 cells, as a methyl excision repair positive (Mer+) cell strain, revealed a rather high value of 488 fmol/mg. 9L cells indicative of a low O6-MT activity showed 13 microM for ACNU and 18 microM for MCNU at a 10% survival dose (SD10), determined by a clonogenic cell assay as an index of cellular resistance. In contrast to this, C6 cells revealed a SD10 value of 67 microM and 36 microM for ACNU and MCNU, respectively, indicating higher resistance than 9L cells. HeLa S3 cells showed the highest SD10 value as follows: 84 microM for ACNU and 73 microM for MCNU. The relationship between the O6-MT activity and the cellular resistance was almost linear, with relatively resistant cell lines exhibiting the higher levels of the O6-MT activity. This correlation between the O6-MT activity and the cellular resistance to nitrosoureas as ACNU and MCNU was not observed among other antitumour drugs, which included bleomycin (BLM), neocarzinostatin (NCS), cis-diamminedichloroplatinum (II) (CDDP), and etoposide (VP-16) in clinical use for brain tumour chemotherapy. This indicates that O6-MT activity can be an indicator of cellular resistance to antitumour nitrosoureas in the chemotherapy of brain tumours.

Animals↗