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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 343 records · Page 19Linked to original sources
PubMed1987

Cell cycle perturbation of cultured C6 glioma cells following short-term contact with a low dose of ACNU.

The purpose of this study was to investigate the cell cycle perturbation of cultured C6 rat glioma cells induced by 1-(4-amino-2-methyl-5-pyrimidyl)methyl-3-(2-chloroethyl)3-nitrosourea hydrochloride (ACNU) using simultaneous flow cytometric measurements of DNA and bromodeoxyuridine (BrdU) content. A new graphic computer program permitted the quantification of cell density in hexagonal subareas and allowed the fraction of BrdU-labeled cells with mid-S phase DNA content (FLS) to be defined in a narrow window. The cell kinetic parameters such as cell cycle time (Tc) and S phase time (Ts) were estimated from a manually plotted FLS curve at 18 and 6 hr, respectively. The major effect of ACNU on the cell cycle was an accumulation of the cells in the G2M phase 12 to 24 hr posttreatment when compared to G2M traverse of untreated cells. For the two-dimensional analysis, cells were labeled with BrdU and then treated with ACNU, or treated with ACNU and then labeled with BrdU. It was concluded that the cells in the S and G2M phases at the time of ACNU administration progressed to mitosis but that the G1 phase cells accumulated in the subsequent G2M phase. Two-dimensional FCM analysis using BrdU provided a useful tool in studying cell cycle perturbation.

Animals↗
PubMed1987

Evolution of criteria for determination of brain death in Japan.

In 1974, the Japanese EEG Society's Ad Hoc Committee on Brain Death published criteria for determining brain death only in cases of acute gross primary brain lesions. In 1983, a new brain death study group was organized to re-evaluate these criteria. During a 6-month period from March 1, 1984, 217 neurosurgical and neurological clinics and emergency services throughout Japan reported 718 brain deaths caused not only by primary lesions but also by secondary brain lesions and diagnosed as such on the basis of the 1974 criteria excluding the condition of "abrupt fall of blood pressure followed by persistent hypotension". The data derived from the 718 cases in this collaborative study were pooled and analyzed, and it became known that the 1974 criteria still are generally reliable. Some changes have been made, however, and new criteria for determination of brain death adopted.

Advisory Committees↗
PubMed1987

Three-dimensional digitizer (neuronavigator): new equipment for computed tomography-guided stereotaxic surgery.

A new device was invented as an adjunct for computed tomography (CT)-guided stereotaxic or open neurosurgery. It is composed of a multijoint three-dimensional digitizer (sensor arm) and a microcomputer, which indicates the place of the sensor arm tip on preoperative CT images. Computed tomography scan is performed preoperatively with three markers placed on the nasion and ears. At surgery, after fixing the patient's head and the sensor arm, sampling of the standard points was done to translate the position of the tip of the sensor arm onto the CT images displayed on a computer screen. In this way positional data from conventional preoperative CT scan can be directly transferred into the surgical field. This system has the unique feature of introducing CT-guided stereotaxis into conventional open neurosurgery.

Brain Neoplasms↗
PubMed1987

rCBF in brain tumours as measured by xenon enhanced CT.

Heretofore, the rCBF of brain tumours has been measured by the 133Xe clearance method, but the resolving power of this method is limited and flow values measured by this method correlate poorly with the anatomical structure. On the other hand, our xenon-enhanced method has several advantages over the conventional isotope method and enables us to evaluate rCBF with a resolving power of 4 mm. With this method, we evaluated rCBF in 15 brain tumour cases and obtained the following results: Mean rCBF value of the tumour is a little lower than that of grey matter and higher than that of white matter with oedematous change. The xenon-enhanced method enables us to distinguish the demarcation between the tumour area and the surrounding oedematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumour which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumours.

Adult↗
PubMed1987

Action spectrum for the induction of single-strand breaks in DNA in buffered aqueous solution in the wavelength range from 150 to 272 nm: dual mechanism.

The induction of single-strand breaks by vacuum-u.v. and far-u.v. radiations (150 nm-272 nm) in plasmid Col E1 DNA in buffered aqueous solution was studied by agarose gel electrophoresis. The results indicated that the mechanisms of DNA strand-break induction are different in the two u.v. regions: above 210 nm the direct excitation of DNA seemed to be the main cause; below 180 nm the photolysis of solvent water seemed to be essential. The demonstration of a systematic protection at 160 nm and not at 209 nm by OH scavengers, such as ethyl alcohol, potassium iodide and D-mannitol, supports the involvement of OH radicals in the vacuum-u.v. region.

Buffers↗
PubMed1987

[Application of flow cytometry to the chemosensitivity test by the BrdU labeling method; a preliminary report].

In the present paper we discussed whether a new method of chemosensitivity test could be developed using FCM (flow cytometry) and applied to malignant brain tumor cells labelled with BrdU monoclonal antibody. For this purpose, a basic study was performed with an ACNU-resistant C6 cell line and a sensitive one to see if this method was able to detect the difference of sensitivity between these cell lines. After 8 hours treatment with ACNU (concentration: 10 micrograms/ml), ACNU-sensitive cells revealed on LI (labeling index) of 46%, which was very high in comparison with controls, whereas the figure for ACNU-resistant cells was 34%, which was almost the same LI value as non-treated control cells. This means that change in the BrdU labeling index after chemotherapy in vitro can be used to determine the chemosensitivity of malignant brain tumors when FCM is employed. Furthermore, this method can detect the chemosensitivity of each clone in polyclonal human tumors which is impossible for the HCSA method, since the latter can reveal only the chemosensitivity as a whole in such tumors.

Antibodies, Monoclonal↗
PubMed1987

[Protective effect on the brain of ion-blockers in experimental head injury].

It has been known that various derangements in ionic homeostasis develop following neural trauma. In particular, potassium efflux out of and calcium influx into the cells are thought to play important roles in causing cell damage. Concomitantly we have previously reported that increased extracellular potassium per se provoked by head injury induces convulsive seizure such that the sustained high extracellular potassium leads to animal death. The purpose of the present study was further to examine the beneficial effect of drugs which could inhibit such detrimental ion movements in experimental head injury. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 17.6 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval; time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). Ethacrynic acid, a loop diuretics, blocks carrier-mediated chloride transport into astroglia associated with sodium and water in the presence of high extracellular potassium. Animals were treated with either 0.5-1.0 mg/kg or 2.0-4.0 mg/kg of ethacrynic acid administered via tail vein 10 min before injury. In the other group of animals, a calcium entry blocker, flunarizine was injected intraperitoneally in doses 5, 10 and 20 mg/kg one hour pre-insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Epitope mapping of the carcinoembryonic antigen by monoclonal antibodies and establishment of a new improved radioimmunoassay system.

A comprehensive mapping of epitopes on the carcinoembryonic antigen (CEA) molecule has been achieved by analyses of the specificities of 146 monoclonal antibodies (MAbs) from more than 300 hybridomas established recently. The reactivities of MAbs were analyzed by radioimmunoassays (RIA) with highly purified preparations of CEA and related antigens including normal fecal antigen-1 (NFA-1), NFA-2 in normal adult feces, nonspecific cross-reacting antigen (NCA) in lung and NCA-2 in meconium. The MAbs could be divided into five groups: group I, 23 clones directed to the NCA-common part of the CEA molecule; group II, 31 clones directed to the normal fecal cross-reacting antigen (NFCA)-common part; group III, 46 clones directed to the NFA-1-common part; group IV, 33 clones reactive with the heterogeneous carbohydrate part; and group V, 13 clones directed to the CEA-distinctive part which seemed to be highly specific for CEA. Mutual inhibitions of CEA binding between MAbs of the individual groups revealed that at least 25 different subgroups can be defined i.e., 4, 7, 8, 4, and 2 subgroups in groups I to V, respectively. The epitopes recognized by the group IV MAbs were found to be sensitive to oxidation with periodate, while the epitopes defined by MAbs of the other groups were resistant to this treatment. A solid-phase sandwich-type RIA system for CEA was established by using 2 MAbs from groups II and III as the CEA catcher and an MAb of group V as the tracer. This assay was shown to exhibit improved cancer-specificity and accuracy in the estimation of serum CEA levels.

Antibodies, Monoclonal↗
PubMed1987

[The influences of neurotransmitters on the traumatic unconsciousness, immediate convulsion and mortality in the experimental mice model].

In order to clearing the influence of neurotransmitters in concussive unconsciousness, immediate convulsion and mortality, the following experiments were performed. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 20 cm on to the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in 66% and death in 30% of animals. The severity of consciousness disturbance was evaluated by two parameters; (1) time interval required for the recovery of righting reflex (RR) and (2) time interval for the recovery of spontaneous movement (SM). Agonist or antagonist of various neurotransmitters was given intraperitoneally 0.5 or 2 hours before injury. The following results were obtained although some of them were statistically not significant. Physostigmine shortened both RR (p less than 0.1) and SM (p less than 0.01), whereas scopolamine did not change these intervals. Atropine sulfate shortened both of them. Nevertheless, atropine methylbromide, which dose not pass through blood-brain-barrier, also had same effects. Methamphetamine shortened both RR (p less than 0.1) and SM (p less than 0.05), whereas haloperidol prolonged these intervals. 5-HTP shortened RR (p less than 0.05), but prolonged SM (p less than 0.1). Methysergide shortened both RR (p less than 0.05) and SM (p less than 0.01). Convulsive seizure was suppressed by physostigmine (p less than 0.01) or 5-HTP (p less than 0.20). These results suggested that suppression of dopaminergic and cholinergic systems, and/or activation of serotonergic system contribute to concussive unconsciousness.

Animals↗
PubMed1987

[Treatment of autochthonous rat brain tumors with chemotherapy and radiotherapy].

The authors tried to establish a model of primary, autochthonous avian sarcoma virus-induced rat glioma for experimental chemotherapy and radiotherapy. It was found that the intracerebral inoculation of 2 X 10(6) FFU/5 microliter of an infectious cells-free homogeneous sub-group D Schmidt-Ruppin avian sarcoma virus into 3-day-old inbred Fischer rats induced brain tumors in all rats. The mean survival time of the inoculated rats was 58.7 +/- 12 days. With regard to the classification of the induced brain tumors in Fischer rats, astrocytoma accounted for 70%. This ASV-induced tumor in rats fulfills the following criteria for a desirable animal model. Spontaneously arising. Glial origin. Intraparenchymal growth. Uniformly fatal within a reasonable time period. In the present study, the therapeutic effects of anticancer drugs, such as ACNU and vincristine were evaluated and additionally, the effect of ACNU used in conjunction with radiation was also evaluated in this model. The mean survival time of rats was prolonged significantly with ACNU (20 mg/kg) or radiation therapy (1,000 rads), respectively, and in cases where ACNU was used together with radiation, the mean survival time was prolonged further still, but not very significantly, in comparison with radiation therapy alone. In conclusion, the ASV-induced rat glioma model was considered to be closely akin to a spontaneous brain tumor in terms of morphology, blood supply and kinetics of the primary tumor. Moreover, the therapeutic sensitivity of this model to anticancer drugs was fairly similar to that of human anaplastic astrocytoma. Considering these observations, this model seems to be an excellent experimental brain tumor model which is useful for evaluating the effect of new therapies against malignant brain tumors.

Animals↗
PubMed1987

[Lipid composition of human malignant brain tumors].

Malignant transformation is characterized by the uncontrolled proliferation of cells. And changes in the composition of glycolipids, cell surface component which may be involved in regulation of cell growth, were often observed in the malignant transformation. In this study, cholesterol, lipid-bound phosphorus, cerebroside, sulfatide and ganglioside were quantitated in the tissue of 20 human malignant brain tumors (malignant glioma, 8; low grade glioma, 4; metastatic tumor, 7; malignant meningioma, 1). As compared with normal brain, all tumor tissue contained lower cholesterol, sialic acid, cerebroside and sulfatide. Metastatic brain tumor or glioma showed characteristic patterns in the content of ganglioside, cerebroside and sulfatide respectively. The ganglioside patterns of metastatic tumor or glioma contained a greater proportion of structurally simpler gangliosides than normal brain. And in metastatic tumor, GM3 was a major ganglioside. On the contrary, glioma had increased proportion of GM3 and GD3 gangliosides. High grade glioma such as Grade 3-4 contained higher proportion of GM3 and GD3, whereas low grade glioma (Grade 1-2) contained less proportion of GM3 and GD3.

Brain Neoplasms↗
PubMed1987

[Phase I study of a recombinant gamma interferon (S-6810)].

A phase I study of a recombinant gamma interferon (S-6810) was conducted in a cooperative study involving 11 institutions. S-6810 was administered at doses of 2, 4, 8, 12, 32 and 64 X 10(6) U/m2 by one-hour infusion for 5 consecutive days. A total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills occurred in about 80% of patients. The incidences of other toxicities were fatigue in 50%, gastrointestinal toxicities in 30-40%, and changes in hepatic enzymes and hematologic toxicities in 20-30%. Dose-limiting factors were judged to be hypotension, leukopenia and central nervous toxicity. Maximum tolerated dose was 64 X 10(6) U/m2 and an optimal dose for phase II study was considered to be 6 X 10(6) U/m2 by daily chronic schedule. Blood concentration was highest at the end of infusion, and then decreased rapidly with a biphasic curve. The peak concentrations were elevated by escalation of doses. A partial response was observed in a patient with mycosis fungoides.

Adult↗