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T Tada

Publications and source records attributed to T Tada.

At least 199 records · Page 11Linked to original sources

Rapid translocation of cytosolic Ca2+/calmodulin-dependent protein kinase II into postsynaptic density after decapitation.

The postsynaptic density (PSD) fraction prepared from rat forebrains frozen with liquid nitrogen immediately after dissection (within 30 s after decapitation) contained major postsynaptic density protein (mPSDp), alpha subunit of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at a level of merely 2.7% of the total protein. The content of the protein in the fraction was increased to approximately 10% by placing the forebrains on ice for a few minutes. Accumulation, but to a lesser extent, of the protein after placement was also observed in the particulate, synaptosome, and synaptic plasma membrane fractions with its concomitant decrease in the cytosolic fraction. The distribution change may be translocation of the protein, because the amounts of the losses of the protein in the cytosolic fraction were balanced by the gains in the particulate fractions. By translocation, CaMKII became Triton X-100 insoluble and partially inactivated. The amount of CaMKII transferred from the cytosol to particulate fractions at 0 degrees C was about the same as that contained in the conventional PSD fraction. Furthermore, the thickness of the PSD was increased by the treatment of the forebrains at 37 degrees C, by which the content of CaMKII alpha in the PSD fraction was increased to twofold. These results suggest that most of the CaMKII alpha subunit associated with the PSD fraction (mPSDp) is translocated from cytosol after decapitation. We also showed similar translocation of CaMKII beta/beta'.

Amino Acid Sequence↗

Prevention of TCR-mediated apoptosis by the elevation of cAMP.

The stimulation through TCR-CD3 complexes by immobilized anti-CD3 antibody induced the production of IL-2 and activation-induced cell death (ACD) in the majority of T cell hybridomas. However, some hybridomas produced IL-2 without showing any signs of ACD by the same stimulation, indicating that TCR-CD3-mediated signaling pathways of IL-2 production and of ACD are different. These pathways were discriminated from each other by protein kinase inhibitors and cAMP-elevating reagents such as forskolin. The pathway of IL-2 production but not of ACD was inhibited by protein kinase inhibitors. On the other hand, various cAMP-elevating reagents prevented the T cell hybridomas from TCR-mediated ACD with minimal inhibition of IL-2 production. The elevated cytoplasmic cAMP did not block dexamethasone-induced apoptosis. This indicates that apoptosis is regulated by multiple pathways. Furthermore, the inhibitory effect of cAMP is specific for the TCR-mediated signaling pathway of ACD. Messenger RNA for bcl-2 was detected after treatment with forskolin.

Animals↗

Elevation of transforming growth factor-beta 1 level in cerebrospinal fluid of patients with communicating hydrocephalus after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide that controls the production of extracellular matrix protein. Platelets store a large quantity of TGF-beta 1, which is released at hemorrhage. We recently reported that human recombinant TGF-beta 1 induced communicating hydrocephalus in mice. The aim of this study was to determine whether TGF-beta 1 is related to the development of communicating hydrocephalus after subarachnoid hemorrhage (SAH). METHODS: TGF-beta 1 in the cerebrospinal fluid of 24 patients with SAH was measured with enzyme-linked immunosorbent assay. The levels were compared between hydrocephalic and nonhydrocephalic groups. Western blot analysis was performed to determine active TGF-beta 1 in the cerebrospinal fluid. RESULTS: TGF-beta 1 rapidly decreased from the onset of SAH. The level of TGF-beta 1 of 13 patients showing ventricular dilatation with periventricular low density on computed tomographic scan was 1.07 +/- 0.37 ng/mL on days 12 through 14, which was significantly higher than 0.52 +/- 0.21 ng/mL in patients without ventricular dilatation (P < .02). Furthermore, the TGF-beta 1 level of patients who had undergone ventriculoperitoneal shunt (n = 11) was 1.11 +/- 0.09 ng/mL on days 12 through 14, which was also higher than the level of the nonshunt group (n = 13) (0.56 +/- 0.22 ng/mL; P < .01). A 25-kD band was demonstrated by Western blot analysis in the cerebrospinal fluid of a patient with SAH. CONCLUSIONS: Our results strongly suggest that TGF-beta 1 plays an important role in generating communicating hydrocephalus after SAH.

Adult↗

Studies on a novel, potent and orally effective cholecystokinin A antagonist, FK-480. Synthesis and structure-activity relationships of FK-480 and related compounds.

We prepared various novel tricyclic 1,4-benzodiazepine derivatives as cholecystokinin (CCK) A antagonists, which were evaluated preliminarily for inhibition of 125I-CCK-8 binding to rat pancreatic membranes in vitro and inhibiting effect on CCK-8-induced inhibition of charcoal meal gastric emptying in mice. On the basis of structure-activity relationship (SAR) studies, as well as the stability and availability of the starting materials of those compounds, (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo- pyrrolo[3,2,1-jk][1,4]benzodiazepin-3-yl]- 1H-indole-2-carboxamide (9f, FK-480) was selected as a candidate compound for further evaluation. The absolute configuration of the precursor of FK-480, (3S)-amino-1,4-benzodiazepine derivative ((S)-8a, R1 = F) was determined by an X-ray crystallographic study of its ureido derivative with (S)-alpha-methylbenzyl isocyanate. FK-480 is now undergoing clinical studies for the treatment of chronic pancreatitis.

Animals↗

[A case of syphilitic keratitis and retinopathy].

This case study focuses on keratopathy and chorioretinopathy resulting congenital syphilis. The patient is a 51-year-old man who had diabetes mellitus for eleven years. Furthermore he had interstitial keratitis due to syphilis. Both fundi showed chorioretinal atrophy. The fundus findings were similar to those of retinitis pigmentosa. We examined the visual field, ERG and dark adaptation. The serological test for syphilis was positive. A diagnosis of congenital syphilis with keratopathy and chorioretinopathy was made.

Choroiditis↗

Experimental study of the mechanism of seizure induction: changes in the concentrations of excitatory amino acids in the epileptic focus of the cat amygdaloid kindling model.

L-glutamate (Glu) and L-aspartate (Asp) are two major excitatory amino acids that may be involved in seizure susceptibility and seizure induction. The concentrations of Glu and Asp were measured by microdialysis in the epileptic focus in a cat amygdaloid kindling model. Sequential changes in Glu and Asp (before, during, and after seizure) were measured in the partial seizure (S4) and generalized seizure (S6) groups. By stimulation at and 50 microA below the partial seizure-triggering threshold in the S4 group and the generalized seizure-triggering threshold in the S6 group, Glu was released from the epileptic focus in the S4 group, and both Glu and Asp were released in the S6 group after seizure and stimulation (below threshold), and the amount of Glu and/or Asp release determined seizure induction. Excitatory amino acids may be the trigger of seizure induction in the cat amygdaloid kindling model.

Amygdala↗

Relationship between physical exercise and health of the elderly people in a rural community.

The significance of life style and regular physical exercise for health of elderly people in a rural community was evaluated by questionnaires. The subjects studied were a group who had been playing gate ball (such as croquet) for more than three years (N = 86) and a group who had not (N = 255). Significantly more males in the group playing gate ball (GB group) than in the group not playing gate ball (n-GB group) reported feeling healthier than three years before. The average overall score for life style which indicates a healthier life style was analyzed. The score for life style of males was significantly lower in the GB group than in the n-GB group. Significantly more males in the GB group did not take snacks or smoke than those in the n-GB group. Regarding regular physical exercise, significantly fewer females in the GB group went for a daily walk than those in the n-GB group. The average score for integrated regular physical exercise was significantly higher in the GB group than in the n-GB group. The scores for regular physical exercise of females in the GB group, even in spite of disability or hypertension, were significantly higher than those in the n-GB group. From this survey it appears that regular physical exercise including gate ball may be beneficial for health of elderly people in a rural community.

Aged↗

Characterization of protein kinase C activities in postsynaptic density fractions prepared from cerebral cortex, hippocampus, and cerebellum.

Protein kinase C (PKC) activities, especially, substrates and PKC isozymes, associated with postsynaptic density (PSD) fractions isolated from rat cerebral cortex, hippocampus, or cerebellum were investigated. The 17k M(r) major substrate for PKC was associated with PSD fractions prepared from cerebral cortex and hippocampus, and several substrates including 18k M(r) protein were associated with PSD fraction isolated from cerebellum. The content of 17k M(r) substrate was extremely low in the PSD fraction prepared from cerebellum. PKCs-beta and gamma were associated with PSD fractions and PKC-alpha was virtually absent in the fraction prepared from the three different regions of the brain. All of PKCs-alpha, beta, and gamma were associated with synaptosome fractions. The 36k M(r) bands immunoreactive with anti-PKC-beta antibody, probably degradation products of native PKC-beta, were detected in both the PSD and synaptosome fractions from the three regions, and the ratio of the degradation fragments to native PKC molecule was higher in PSD fractions than in synaptosome fractions. The results suggest postsynaptic roles of PKCs-beta and gamma and involvement of proteolytic activation of PKC-beta in the postsynaptic signal processing.

Amino Acid Sequence↗

Distinction of mouse CD8+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms.

Mouse CD8+ T cell clones could be subdivided into two subgroups by the pattern of cytokine production and CD45 isoforms that exactly corresponded with the functionally assigned cytotoxic (CTL) and suppressor (Ts) subsets. All the Ts clones invariably produced IL-10 after stimulation with immobilized anti-CD3, whereas none of CTL clones expressed mRNA of IL-10 by the same stimulation. All the CTL clones were positive for CD45RA Ag, a product of exon 4 of CD45 gene, whereas none of the Ts clones were positive for this Ag. The results are analogous to the situation within CD4+ T cell clones in which Th1 and Th2 subtypes can be distinguished by CD45 isoforms and cytokines they produce. Ts clones could suppress the proliferative responses of both Th1 and Th2 type CD4+ clones by the production of two different cytokines, IL-10 and IFN gamma, respectively, but none of the CTL clones could suppress the proliferation of CD4+ T cells. The participation of an additional nonspecific molecule in the suppression of antibody response is suggested.

Animals↗

Differences of intravenous nitroglycerin responses in left ventricular systolic and end-diastolic pressures and coronary artery diameters during long-term treatment with cutaneous nitroglycerin patches.

The differences of intravenous nitroglycerin responses in left ventricular (LV) systolic and end-diastolic pressures and in coronary artery diameters (cross-tolerance) were investigated in patients receiving nitroglycerin patches. During diagnostic cardiac catheterization, graded doses of 50, 100, and 150 mcg of intravenous nitroglycerin were given. Left ventricular systolic and end-diastolic pressures and left coronary arteriograms were obtained during each dose. Twenty patients with coronary artery disease were studied. Before cardiac catheterization, 10 received nitroglycerin patch (patch group), and 10 did not (control group). In the control group, graded intravenous nitroglycerin doses of 50, 100, and 150 mcg caused decrease in LV systolic pressure of 18 +/- 7%, 20 +/- 5%, and 23 +/- 6%, respectively. In the patch group, the same intravenous nitroglycerin doses decreased LV systolic pressure by 12 +/- 6% (p < 0.05), 19 +/- 7% (NS), and 18 +/- 6% (p < 0.05), respectively, (p value: vs. control group). At the same intravenous nitroglycerin doses, LV end-diastolic pressures were decreased by 48 +/- 14%, 52 +/- 17%, and 56 +/- 9%, respectively, in the control group. However, there were no significant differences in LV end-diastolic pressure between the two groups for any of the three intravenous nitroglycerin doses. The same intravenous nitroglycerin doses caused increase in diameter of the left anterior descending coronary artery and circumflex coronary artery in the control group, which was attenuated significantly in the patch group. Tolerance may develop in LV systolic pressure and coronary artery diameters, whereas it may not develop in LV end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Solvent dependence of optical rotation of (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide.

A new cholecystokinin-A antagonist, (S)-N-[1-(2-fluorophenyl)- 3,4,6,7-tetrahydro-4-oxo-pyrrolo[3,2,1-jk][1,4]benzodiazepine-3-yl]- 1H-indole-2-carboxamide (FR120480; 1), is a chiral compound that shows considerable solvent dependence of its optical rotation. Not only the absolute values, but also the signs (+ or -) for this compound change in various solvents. The optical rotation of 1 inherently correlated to the electron donating property characterized by donor number of the solvent. The 1H NMR study implied that hydrogen bonds were formed between electron donor groups of the solvents and the NH groups of indole and amide of 1. In accordance with the NMR results, X-ray crystallography of the tetrahydrofuran solvate of 1 showed that hydrogen bond formation occurred between the oxygen atom of tetrahydrofuran and the amide group of 1.

Benzodiazepinones↗

Negative selection of thymus-dependent CD4+8+ intestinal intraepithelial lymphocytes by internal superantigens.

CD4 and CD8 double-positive (DP) T cells were transiently found in the Peyer's patch of mice 2 to 3 weeks after birth and preceded the appearance of DP intestinal intraepithelial lymphocytes (iIEL). DP iIEL were detected in euthymic-specific pathogen-free mice, but not in athymic and germ-free mice. The pattern of V beta genes expressed on these DP iIEL was similar to that of CD4 single-positive peripheral T cells, which reflected the negative selection by internal superantigens, M1s, and I-E. CD8 SP T cells did not receive such a strict negative selection with these antigens. DP iIEL expressed a high density of T cell receptor alpha beta and CD3 and responded to immobilized anti-CD3 to undergo blastogenesis and de novo IL2 receptor expression. These results indicate that DP iIEL are mature thymus-dependent T cells immigrated to intraepithelial space via the Peyer's patch in response to intestinal antigenic stimulation.

Animals↗

Thymic epithelial tumours: evaluation of malignant grade by quantification of proliferating cell nuclear antigen and nucleolar organizer regions.

Cellular proliferation was studied by quantification of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions (AgNORs) of cells in 29 thymic epithelial tumours: 8 noninvasive (7 cortical and 1 mixed) thymomas, 11 invasive/metastatic (all cortical) thymomas, and 10 thymic carcinomas. Thymic carcinoma showed the highest percentage of cells positive for PCNA (14.73 +/- 5.419%) and the largest mean number of AgNORs per nucleus (4.89 +/- 0.756). The mean percentage of PCNA-positive cells and number of AgNORs in thymoma groups were as follows: in noninvasive thymoma 2.96 +/- 1.256% and 2.73 +/- 0.647, respectively, and in invasive/metastatic thymoma 4.41 +/- 1.823% and 3.68 +/- 1.148, respectively. The differences in PCNA and AgNORs were statistically significant between thymic carcinoma and each of thymoma groups. The overlap of the values between these tumours was minimal in the PCNA stains, although it was considerable in AgNOR counts as previously noted. However, there was no statistically significant difference in these markers between noninvasive and invasive/metastatic thymomas. These results indicate that thymoma in general is a slow-growing tumour compared with thymic carcinoma and that noninvasive thymoma is similar to invasive/metastatic thymoma with regard to proliferative activity; these latter two tumours may represent an essentially identical type in different stages of progression.

Antigens, Neoplasm↗

Parental imprinting on the mouse X chromosome: effects on the early development of X0, XXY and XXX embryos.

To examine the effects of X-chromosome imprinting during early mouse embryogenesis, we attempted to produce XM0, XP0, XMXMY, XMXPY and XMXMXP (where XM and XP stand for the maternally and the paternally derived X chromosome, respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses suffered from severe growth retardation or abnormal development characterized by deficient extra-embryonic structures at 6.5-7.5 days post coitum (dpc). A cytogenetic study suggested that two XM chromosomes remaining active in certain nonepiblast cells were responsible for the serious developmental abnormality found in these embryos disomic for XM. Although matings involving females heterozygous for Rb(X.2)Ad hinted at the paucity of XP0 embryos relative to those having the complementary karyotype of XMXMXP, further study of embryos from matings between females heterozygous for In(X)1H and Rb2Ad males did not substantiate this observation. Thus, the extensive peri-implantation loss of XP0 embryos shown by Hunt (1991) may be confined to X0 mothers. Taken together, this study failed to reveal a parentally imprinted X-linked gene essential for early mouse embryogenesis other than the one most probably corresponding to the X-chromosome inactivation centre.

Animals↗

CD69 cell surface expression identifies developing thymocytes which audition for T cell antigen receptor-mediated positive selection.

CD69, an 'activation marker' that is rapidly induced on mature T cells after stimulation through the T cell antigen receptor (TCR) was found to be expressed on approximately 10% of normal thymocytes. All of these CD69+ thymocytes express alpha beta TCR, and they include both TCRlowCD4+CD8+ and TCRhighCD4+CD8- or CD4-CD8+ thymocytes. The CD69+ cells can be further segregated into heat-stable antigen (HSA)+TCRlow, HSA+TCRhigh and HSA-TCRhigh thymocyte populations. None of CD69+ cells express the mature T cell marker Qa-2. Thus CD69+ cells present in vivo appear phenotypically to represent transitional cell populations between immature TCRlowHSA+Qa-2-double-positive cells and mature TCRhighHSA-QA-2+ single-positive cells. In addition, TCR engagement by MHC molecules is required for CD69 expression in the thymus. Taken together, the CD69+ thymocytes appear to represent the cells auditioning in positive selection process or they are the cells that have been positively selected recently. Analysis of a TCR transgenic mouse model revealed an increased number of CD69+ thymocytes in a positively selecting thymus, whereas no CD69+ transgenic TCR+ thymocytes were observed in the non-selecting thymus. Based on the results of this study, we suggest that the surface expression of CD69 serves as a useful marker to identify and trace those thymocytes that are engaged in the TCR-mediated positive selection process in the thymus.

Animals↗

Detection of active form of transforming growth factor-beta in cerebrospinal fluid of patients with glioma.

We examined transforming growth factor-beta (TGF-beta) activity in cerebrospinal fluid of 39 patients with various brain tumors, and found it in 10 glioma cases that had lesions related to subarachnoid space or ventricle. In one glioma case, TGF-beta detected on admission disappeared after radiation and chemotherapy. We confirmed that five glioma cell lines produced TGF-beta, and that four of them produced active form of TGF-beta directly. The active form of TGF-beta was also identified from cerebrospinal fluid before the acidification treatment in two cases. The calculated contents were 110 ng/ml and 18 ng/ml. These results indicate that active form of TGF-beta is directly produced by tumor cells in patients with glioma, and may contribute to immunodeficiency of the host.

Brain Neoplasms↗

Expression of 20 KD homologous restriction factor of complement on myocardial cells: an immunohistochemical study using acetone-fixed and paraffin-embedded tissues.

Expression of 20 KD homologous restriction factor of complement (HRF20) (CD59) in normal human heart was immunohistochemically examined with monoclonal antibody (MAb) 1F5. HRF20 was clearly demonstrated on the cell surface membrane and intercalated discs of myocardial cells throughout the ventricular walls. Therefore, this factor may protect normal cardiomyocytes from complement deposition, which has been demonstrated on infarcted cardiomyocytes. Expression of HRF20 was also observed on endothelial cells of the endocardium and on blood vessels, including arteries, capillaries, and veins, and on the Schwann-cell sheath of peripheral nerve fibers. In the present study, we found that the epitopes of HRF20 were well preserved for immunohistochemistry even in acetone-fixed and paraffin-embedded tissues, as well as in frozen tissues that have been conventionally used for HRF20. This method using paraffin sections allows for easier staining and greater accuracy in histological examination.

Acetone↗