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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 523 records · Page 29Linked to original sources
PubMed1995

[A study on the rhodopsin gene in Japanese retinitis pigmentosa--screening of mutation by restriction endonucreases and frequencies of DNA polymorphisms].

We analyzed 11 sites of the rhodopsin gene using polymerase chain reaction (PCR) amplification and restriction endonucleases in 30 unrelated Japanese patients with autosomal dominant retinitis pigmentosa (ADRP). No point mutation was found in any patient. The frequencies of the single nucleotide (nt) substitution at nt 269, nt 5145 and nt 5321 were examined in three groups, 38 unrelated patients with ADRP, 23 patients with autosomal recessive retinitis pigmentosa (ARRP), and 67 normal controls. There was no significant difference in the frequencies of substitution among these three groups. The frequencies of A269G, G5145A, and C5321A were 52%, 36%, and 5%, respectively. These values were different from those of the American population. The polymorphisms, A269G and G5145A, are useful as DNA makers for linkage analysis.

Asian People↗
PubMed1995

Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid.

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.

Animals↗
PubMed1995

[Intrathecal infusion of brain-derived neurotrophic factor protects nigral dopaminergic neurons from degenerative changes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced monkey parkinsonian model].

Protective effect of BDNF on nigrostriatal dopaminergic neurons was evaluated with MPTP-induced parkinsonian model in monkey. Twelve adult female Japanese monkeys weighing about 7kg were lesioned with systemic infusion of MPTP according to the following dosing schedules. Group I: normal control (n = 2), group II: continuous infusion of 15mg of MPTP with osmotic minipump (Alzet: 2ML2, mean pumping rate 5 microliters/hour) for 14 days (n = 2), group III: bolus injections of 5mg of MPTP on day 0, 4 and 7 (n = 2), group IV: bolus injections of 5mg of MPTP on day 0 and 4 (n = 6). Half of the animals in each groups except groupI were treated with BDNF, and the other half served as control. In BDNF-treated animals, total 6.5 ml of conditioned culture medium of Chinese hamster ovary containing 1 micrograms protein/ml of BDNF was administered into cisterna magna by osmotic minipump (Alzet: 2ML2) implanted on day 0. Culture medium without BDNF activity was also administered to control animals in the same manner. Neurological findings were evaluated with the Monkey Parkinsonism Rating Scale (MPRS) by Kurlan et al. The animals were sacrificed on day 14 and histological findings of the pars compacta was investigated. All the animals in group I and II showed no symptoms during the experimental periods. Severe parkinsonism was observed in animals regardless of BDNF treatment in group III. In group IV, non-treated animals suffered parkinsonism at the end of the 1st week and deteriorated in the 2nd week. In contrast, BDNF-treated animals stayed asymptomatic during the 1st week and developed parkinsonism in the 2nd week. There were significant differences for MPRS between BDNF-treated and non-treated animals after day 6. Severe neuronal loss was observed in the parkinsonian animals in accordance with clinical symptoms. Neuronal loss was significantly milder in the BDNF-treated animals. These results revealed a protective effect of BDNF on dopaminergic neurons in MPTP-lesioned primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

A novel pyridobenzazepinone derivative with long lasting thromboxane synthase inhibition.

A novel pyridobenzazepinone derivative (Z)-11-(5-carboxypentylidene)-6-methyl-5, 11-dihydropyrido +ad4,3-C] [1] benzazepin-5 (6H)-one (CAS 127654-03-9, KF 13218), inhibited human and bovine platelet thromboxane synthase with IC50 values of 27 +/- 5.8 nmol/l (mean +/- S.E.M.) and 36 +/- 6.9 nmol/l, respectively. The compound did not inhibit cyclooxygenase or 5-lipoxygenase up to a dose of 100 mumol/l and did not antagonize thromboxane A2/prostaglandin H2 receptors. KF13218 inhibited arachidonic acid-induced thromboxane B2 production by human intact platelets with an IC50 value of 5.3 +/- 1.3 nmol/l. The IC50 value of KF13218 for the intact platelets was about 5 times lower than that for the microsomal enzyme. The inhibition of thromboxane synthase in platelets by KF13218 was sustained after removal of the extracellular compound. After oral dosing in rat from 0.03 mg/kg to 3 mg/kg, KF13218 dose-dependently inhibited the thromboxane B2 production in serum, and the inhibition was retained for 72 h. KF13218, at a dose of 0.1 mg/kg p.o. prevented mortality induced by sodium arachidonate in rabbit. It is concluded that KF13218 is a potent, selective and long lasting thromboxane synthase inhibitor.

Animals↗
PubMed1995

Establishment of vasopressin-responsive early proximal tubular cell lines derived from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene.

A little is known about vasopressin receptor in early proximal tubule (S1). The purpose of this study is to establish the vasopressin-responsive S1 cell line derived from transgenic mice harboring temperature-sensitive(ts) simian virus (SV) 40 large T-antigen gene. The cells showed a temperature-sensitive cell growth characteristic of encoding tsSV40. The S1 cells retained a unique morphology specific to proximal tubule. The cells showed the vasopressin-induced increase in intracellular calcium concentration ([Ca2+]i) mediated by both V1a and the putative Vp receptor. Of nineteen clonal cell lines established from the parental cells, three expressed only V1a receptor, and five retained both V1a and Vp receptor. In conclusion, these immortalized S1 cell lines may be useful for studying vasopressin receptor subtypes in S1.

Animals↗
PubMed1995

Distribution of viral RNA in the spinal cord of DBA/2 mice developing biphasic paralysis following infection with the D variant of encephalomyocarditis virus (EMC-D).

DBA/2 mice infected with the D variant of encephalomyocarditis virus (EMC-D) (10(1) PFU/head) developed biphasic hind limb paralysis. As a first step in clarifying its pathogenesis, we examined the distribution of viral RNA in the spinal cord using in situ hybridization. At 3 days post inoculation (DPI), in the spinal cord of mice showing slight paralysis, viral RNA was observed in capillary endothelial cells and a few adjacent glia cells in the funiculus lateralis from thoracic to lumbar enlargement. At 7 DPI, in the spinal cord of mice showing apparent paralysis, viral RNA was observed in a larger number of glia cells in the demyelinated lesion associated with infiltration of macrophages in the funiculus lateralis and in a small number of degenerated neurons in the cornu ventrale. In the funiculus lateralis, viral RNA could not be observed after 28 DPI. On the other hand, viral RNA was observed in degenerated neurons in the cornu ventrale of mice showing the second phase paralysis at 42 DPI. Many CD4+T cells infiltrated around these degenerated neurons. These results suggest that: (1) the viral entry zone was the capillary endothelial cells in the funiculus lateralis; (2) first phase paralysis was due to demyelination caused by EMC-D and associated with macrophage infiltration; (3) second phase paralysis was due to degeneration of motor neurons bearing viral RNA associated with infiltration by CD4+T cells.

Animals↗
PubMed1995

Protective effects of macrophage-derived interferon against encephalomyocarditis virus-induced diabetes mellitus in mice.

The involvement of macrophages in protection against diabetes mellitus in mice of BALB/c (susceptible) and C57BL (resistant) strains infected with the B (non-diabetogenic) or D (highly diabetogenic) variant of encephalomyocarditis (EMC) virus was examined. Pretreatment with the B variant of EMC virus (EMC-B), avirulent interferon (IFN) inducer, or Corynebacterium parvum inhibited diabetes in BALB/c mice infected with the D variant of EMC virus (EMC-D). Treatment of C57BL mice with carrageenan to compromise macrophage function rendered C57BL mice susceptible to EMC-D-induced diabetes. In macrophage culture for BALB/c mice, EMC-B induced IFN at an earlier stage than did EMC-D. The C57BL mouse-derived macrophages produced more IFN than did BALB/c mouse-derived macrophages after stimulation with EMC-D. Moreover, C. parvum increased IFN production in macrophage cultures from BALB/c mice, whereas carrageenan inhibited that in macrophage cultures from C57BL mice. These results suggest that IFN derived from macrophages may have an important role in protecting mice against EMC virus infection.

Animals↗
PubMed1994

Survey of complications of indocyanine green angiography in Japan.

PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.

Aged↗
PubMed1994

Involvement of clathrin light chains in the pathology of Pick's disease; implication for impairment of axonal transport.

Clathrin, which constitutes coated vesicles and plays important roles in neuronal functions, has been reported to be involved in the pathology of Alzheimer's disease. In the brains of the patients with Pick's disease, distribution of clathrin was immunohistochemically investigated using monoclonal antibodies binding to different epitopes of clathrin light chain a and b. All the antibodies intensely labeled Pick's body and some perikarya of neurons, indicating impairment of slow axonal transport b (SCb). Antibodies against neurofilament, kinesin and synaptophysin also labeled Pick's body. These observations suggested impairment of axonal transport in the brains with Pick's disease, and might contribute to elucidating the pathology of Pick's body forming. It is implied that common pathological processes might lie in Alzheimer's disease and Pick's disease.

Antibodies, Monoclonal↗
PubMed1994

[Diffuse slow washout pattern (DSWO) on exercise stress thallium-201 myocardial SPECT: correlative study with coronary arteriography and the related clinical factors].

DSWO was shown on bull's eye images of 98 of 1234 patients suspected of having coronary artery disease and examined with thallium-201 myocardial SPECT imaging. Fifty-eight of these 98 patients underwent coronary arteriography, and comparison studies were performed between the bull's eye SPECT images, the results of coronary arteriography and the laboratory data. DSWO was found in 11 of 58 cases (19.0%) of single vessel disease (1VD), 18 of 58 cases (31.0%) of double vessel disease (2VD) and 21 of 58 cases (36.2%) of triple vessel disease (3VD). Three of 58 cases (5.2%) of stenosis of a coronary artery less than 75% of its normal diameter (N group) also showed DSWO. DSWO was closely related with multiple vessel disease, as has been indicated by previous reports, but we also found another patient group that showed minor coronary arterial change (1VD and N group) and manifested DSWO. Based on the study of laboratory data, we clarified that this group of patients tended to show accompanying hypertension and hyperlipidemia as factors influencing the appearance of DSWO. DSWO was accompanied by hypertension and hyperlipidemia in 54.5% and 45.5% in 1VD. These values were higher than those in the 2VD and 3VD cases, which were 33.3% and 38.9% in 2VD, and 19.0% and 28.6% in 3VD, respectively. Hypertension and hyperlipidemia appeared to play an important role in causing DSWO by interfering with coronary circulation.

Adolescent↗
PubMed1994

KF17837 ((E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine), a potent and selective adenosine A2 receptor antagonist.

8-(3,4-Dimethoxystryryl)-1,3-dipropyl-7-methylxanthine exhibited high affinity and selectivity for adenosine A2A receptors in binding assay using rat striatal A2A receptors labeled with [3H]2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosin e (CGS21680). The affinity was stereo selective: the E isomer, KF17837, showed a Ki value of 1.0 +/- 0.057 nM for the A2A receptors, whereas the Z isomer showed much lower affinity. KF17837 had 62-fold selectivity for the A2A receptors versus rat forebrain A1 receptors labeled with [3H]N6-cyclohexyladenosine (CHA). KF17837 was rapidly photoisomerized to form a stable equilibrium mixture (18% E - 82% Z), KF17837S, which showed Ki values of 7.9 +/- 0.055 nM and 390 +/- 68 nM for the A2A and A1 receptors, respectively. The inhibition type was competitive for [3H]CGS21680 binding. In rat pheochromocytoma PC12 cells KF17837S antagonized cAMP accumulation induced by 1 microM CGS21680 via the A2A receptors, with an IC50 value of 53 +/- 10 nM. cAMP accumulation induced by 10 microM 5'-N-ethylcarboxamidoadenosine via the A2B receptors in Jurkat cells (human T-cell line) was inhibited by KF17837S with an IC50 value of 1500 +/- 290 nM. These results indicate that KF17837S (and hence KF17837) is a highly potent and selective adenosine A2A receptor antagonist.

Adenosine↗
PubMed1994

Depolarizing agents and tumor necrosis factor-alpha modulate protein phosphorylation in oligodendrocytes.

Membrane depolarization and changes in ionic fluxes have been implicated in the signaling mechanisms between neurons and glial cells. We report here that K(+)-induced depolarization of cultured ovine oligodendrocytes (OLGs) decreases the phosphorylation of myelin basic protein (MBP) and 2'3'-cyclic nucleotide phosphohydrolase (CNPase). Membrane depolarization and decrease in phosphorylation of MBP and CNPase can also be elicited by inhibition of the inward rectifier with Ba2+ but not by inhibition of outward K+ channels with 4-aminopyridine or tetraethylammonium. These findings demonstrate that modulation of K+ currents can influence phosphorylation states of OLG proteins. Tumor necrosis factor-alpha (TNF-alpha), an immune peptide implicated in autoimmune demyelinating diseases, also inhibits the phosphorylation of these proteins. In contrast to elevated [K+]o, TNF-alpha does not decrease the stimulatory effect of protein kinase C activators or phosphatase inhibitors on MBP and CNPase phosphorylation, suggesting that depolarizing agents and TNF-alpha act via distinct mechanisms. We postulate that the presence of elevated extracellular K+ and/or cytokines under certain pathological conditions can perturb OLG function by altering the phosphorylation states of their proteins and perhaps affect myelin maintenance, contributing to demyelination.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1994

Accumulation of amyloid beta-protein precursor (APP) in Purkinje cells and increase of amino-terminal fragments of APP in cerebrum and cerebellum of aged rat brain.

In aged rat brain, amyloid beta-protein precursor (APP) is accumulated in dendrites and cell bodies of Purkinje cells as full-length or truncated APP, because dendrites and cell bodies are positively stained by antibodies against both the amino- and carboxy-termini of APP. Western blot analysis of homogenates of brains of aged and young rats showed no apparent differences except for an increase in amino-terminal fragments in cerebrum and cerebellum of aged rat. These results indicate that the expression, transport or metabolism of APP in specific regions of brains may be affected by the aging process.

Aging↗
PubMed1994

[Z-100 as radiation mucositis protector in head and neck tumor management].

To study the radioprotective effect of Z-100 against mucositis, twenty-five patients with head and neck malignancies were received external irradiation of 30-61.2 Gy (mean 44.4 Gy) concurrent with Z-100 injection twice a week. Of these cases, an incidence of dysphagia was less than 20% and white coating mucositis below 50%. Frequency of radiation mucositis in these regions was reduced compared to our previous experiences; efficacy of 88%. This combined therapy seems to be a promising method.

Adult↗
PubMed1994

Lymphotoxin lacks effects on 75-kDa receptors in cytotoxicity on U-937 cells.

We examined differences in cytotoxic activity between human lymphotoxin (LT) and tumor necrosis factor (TNF) as functions of their interaction with two types of TNF receptors, 55-kDa (p55R) and 75-kDa (p75R). Cytotoxic activity of LT was much lower than that of TNF on a human monocytic cell line, U-937, on which p75R was predominant. Monoclonal antibodies specific for p55R (htr-5 and htr-9) and p75R (utr-1) significantly diminished TNF cytotoxicity, whereas, utr-1 was only slightly inhibitory to LT cytotoxicity, and htr-5 reduced it significantly. TNF individual binding to p75R increased cytotoxic activity when p55R was occupied by htr-9 and a mutein of TNF which significantly lost affinity to p75R. However, LT binding to p75R did not increase. Scatchard analysis with [125I]LT and [125I]TNF showed that LT still had approximately half of the affinity to p75R and slightly less affinity to p55R than TNF. These results indicate slight cytotoxicity of LT compared to TNF, due to inability of LT to signal through p75R on U-937 cells without significant loss of affinity to p75R.

Humans↗
PubMed1994

Chromaffin cells express Alzheimer amyloid precursor protein in the same manner as brain cells.

Amyloid precursor protein (APP) 695 is remarkably expressed in the brain as compared with APP751 and APP770 which are dominant in other tissues. This study showed that human and bovine adrenal medullae dominantly expressed mRNA of APP695 as do brain nerve cells, while the adrenal cortexes expressed mRNAs of APP751 and APP770 as in other non-neural tissues. In immunohistochemistry, chromaffin cells of young rat adrenal medullae and primary cultured bovine chromaffin cells were significantly stained with a monoclonal antibody (mAb) against the common domain of the amino-terminal side of human APPs. At higher magnification, the immunostained cells revealed that APP was granularly distributed not only in the perikaryon but also in the cell processes. These results suggest that primary cultured chromaffin cells representing the state of adrenal medulla in vivo are a useful model for studying the pathophysiological functions of APPs and the mechanism of processing of APPs as a model of neuronal systems.

Adrenal Cortex↗