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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 487 records · Page 27Linked to original sources

The lectin concanavalin A stimulates a protein-tyrosine kinase p72syk in peripheral blood lymphocytes.

We report that the activation of porcine peripheral blood lymphocytes (PBL) by lectin concanavalin A (Con A) led to the increase in tyrosine phosphorylation on 84-, 72-, 55-, 40-, and 33-kDa proteins. A non-receptor protein-tyrosine kinase (PTK), p72syk (Taniguchi et al. (1991) J. Biol. Chem. 266, 15790-15796), was detected in PBL around 0.1% of total protein and distributed in both particulate and cytosolic fractions. Furthermore, Con A induced a rapid activation of p72syk within 1 min in a manner similar to the time course of Con A-induced protein-tyrosine phosphorylation. These results suggest that p72syk plays a certain role in the activation of PBL and that p72syk may be one of the major non-receptor PTKs in T cells as well as in B cells.

Animals↗

Participation of poly(ADP-ribose) synthetase in the process of norepinephrine-induced inhibition of major histocompatibility complex class II antigen expression in human astrocytoma cells.

We previously demonstrated that the expression of a transfected poly(ADP-ribose) synthetase cDNA into macrophage tumor cells inhibited interferon-gamma-dependent induction of major histocompatibility complex(MHC) class II antigens. In the present study, we found that addition of norepinephrine to the cultured human astrocytoma STTG1 cells induced mRNA of poly(ADP-ribose) synthetase in 6-14h. Thus, we cultured the cells in the presence of norepinephrine for 24h, and then induced the MHC class II antigen by the addition of interferon-gamma. The expression of MHC class II antigen was inhibited, whereas it was not inhibited when norepinephrine and interferon-gamma were simultaneously added into the culture medium. These results suggest that an increase of poly(ADP-ribose) synthetase by norepinephrine cause the inhibition of interferon-gamma-mediated MHC class II antigen expression.

Astrocytoma↗

Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia.

The effects of hypoxia on protein kinase C (PKC) isozymes (alpha, beta I, beta II, and gamma) were examined in the hippocampus from rats subjected to hypoxic conditions (5% O2 in 95% N2) for 30 min in a chamber. Western blot analysis revealed that the total amounts of PKC-alpha (-26.0% of control) and -gamma (-32.7% of control) were decreased significantly at the end of hypoxia, which was followed by the reduction of that of PKC-beta II (-23.7% of control at 7 days after hypoxia). Whereas, the PKC activities, which were measured by the incorporation of [gamma-32P] into a specific PKC substrate peptide, in both the cytosolic and the particulate fractions did not change. The reductions of PKC-gamma and -alpha at the end of hypoxia may be related to the following neuronal degeneration.

Animals↗

Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction.

The binding of interleukin 2 (IL-2) to the IL-2 receptor (IL-2R) induces a rapid increase in tyrosine phosphorylation of cellular proteins. In a previous study, we have shown that p56lck (lck), a src-family protein tyrosine kinase (src-PTK), physically and functionally associates with the IL-2R beta chain (IL-2R beta). To further investigate a role of src-PTKs in IL-2 signaling, we analyzed a mouse pro-B-cell line, in which lck is not expressed detectably. We observed that in this cell line, IL-2 induces activation of at least two src-PTKs, p59fyn (fyn) and p53/56lyn (lyn). Interestingly, stimulation of this cell line with IL-3 also induces activation of src-PTKs. The activation of fyn or lyn seems to be selective for stimulation with IL-2 or IL-3 since stimulation with IL-6 fails to activate them. Furthermore, we provide evidence for the physical association of fyn with IL-2R beta. Taken together with previous results, our current study suggests that different src-PTKs, each of which is expressed in a cell-type-specific manner, can participate in the IL-2 signal transduction.

Animals↗

Association with B-cell-antigen receptor with protein-tyrosine kinase p72syk and activation by engagement of membrane IgM.

We have demonstrated that a 72-kDa non-receptor-type protein-tyrosine kinase (p72syk) was co-immunoprecipitated with membrane IgM in digitonin lysates of porcine tonsillar cells and was rapidly activated following the engagement of membrane IgM. This activation was occurred within 5 s, even in the presence of EGTA and 5,5'-dimethyl-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid as extracellular and intracellular Ca(2+)-chelating agents, respectively, as well as in the presence of the protein-kinase-C inhibitor, H-7. Additionally, genistein, a potent protein-tyrosine kinase inhibitor, was capable of reducing both IgM-stimulated Ca2+ mobilization and p72syk activation in a dose-dependent manner. These results indicate that p72syk is physically associated with the B-cell-antigen receptor, participating in antigen-mediated signal transduction in both a Ca(2+)-independent and protein-kinase-C-independent manners.

Animals↗

Interaction of vanadate and iodate oxyanions with adenylyl cyclase of ciliary processes.

Vanadate (VO3-) was found to activate adenylyl cyclase (AC) in ocular ciliary process membrane. This response was additive to that of isoproterenol (ISO) and vasoactive intestinal peptide (VIP), but it was potentiative with forskolin (FSK) and also with Ca2+/calmodulin activation of AC activity. The potentiated response of FSK in the presence of VO3- was due to an increase in Vmax without a change in the apparent affinity of FSK or VO3-, and therefore differs from the potentiated response of activated G-protein (Gs) and FSK, where the affinity of FSK was increased by 1-2 orders of magnitude. Potentiation occurred at low Mg2+ and was not observed at free [Mg2+] > 3 mM. Iodate (IO3-) inhibited the FSK, ISO, and VO3- activations of AC in ciliary process membranes (IC50, 0.3 mM). In vivo topical treatment of the rabbit eye with 50 microL of 5% NaIO3 had no effect alone but completely blocked the intraocular pressure response to a 50-microL topical dose of 1% FSK and partially blocked the response to a 50-microL dose of 0.001% ISO. These findings indicate that some AC enzymes may have a binding site for oxyanions which can directly regulate enzyme activity.

Adenylyl Cyclase Inhibitors↗

Effects of daily administration of methamphetamine on multiple active/passive avoidance performance in rats.

The effects of daily methamphetamine (M-Amp) treatment with (2 mg/kg/day, i.p.) were examined on multiple active/passive avoidance performance (MAP) in rats. After avoidance training, the animals were given M-Amp every day; on the days of learning sessions, which were on alternate days, the drug was administered at 15 min before the session. Daily administration of M-Amp produced enhancement of the number of respondings (running) as an excitatory dimension of behavior, disruption of immobilities as an inhibitory dimension, and impairment of successes as a discriminatory dimension, when compared with saline-treated rats. Following M-Amp withdrawal, recovery from these damages of learned behavior was observed, except the deterioration in the discriminative dimension. In conclusion, the MAP paradigm is good for assessing the behavioral effects of M-Amp treatment, making it easy to distinct the behavioral effects of M-Amp into excitatory-inhibitory and discriminative dimensions. It is important to distinguish the behavioral components induced by M-Amp, since the damage of learned avoidance performance consists of different dimensions in the M-Amp-treated rats. Impairment of discriminative behavior appears to demonstrate an attentional deficit, which may explain the behavioral disorderliness in M-Amp abusers who display no disturbance of apparent consciousness. These results are discussed with association of brain monoamine alterations.

Animals↗

Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.

3T3 Cells↗

Protein-tyrosine kinase p72syk is activated by thrombin and is negatively regulated through Ca2+ mobilization in platelets.

Activation of platelets by thrombin results in a dramatic increase in tyrosine phosphorylation on multiple cellular proteins (Ferrell, J. E., and Martin, G. S. (1988) Mol. Cell. Biol. 8, 3603-3610; Golden, A., and Brugge, J. S. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 901-905; Nakamura, S., and Yamamura, H. (1989) J. Biol. Chem. 264, 7089-7091). However, none of the responsible protein-tyrosine kinase has been reported so far. We report here that p72syk, one of the non-receptor-type protein-tyrosine kinases, is activated following thrombin stimulation in blood platelets. Washed porcine platelets were stimulated by thrombin, and the activation of p72syk was assessed in an immunoprecipitation kinase assay. The activity of p72syk increased within 5 s, reached a maximum at 10 s, and decreased to a basal level within 60 s after 0.5 unit/ml thrombin stimulation. The amount of immunoprecipitated p72syk was not altered throughout the time course. This activation was greatly enhanced in a dose-dependent manner and was completely canceled by the pretreatment of platelet suspension with hirudin, a specific antagonist of thrombin. In the Ca(2+)-depleted condition both extra- and intracellularly, the activation of p72syk was still persistent; in contrast, the deactivation process was completely abrogated even at 120 s after thrombin stimulation. In addition, the replenishment of Ca2+ resulted in a similar deactivation pattern as seen in the Ca(2+)-rich condition. Furthermore, this deactivation was also canceled by the pretreatment of platelets with W7, a calmodulin antagonist, as well as ML9, a myosin-light-chain kinase inhibitor. These results indicate that p72syk can be a responsible enzyme to the protein-tyrosine phosphorylation events following the platelet activation by thrombin and may be negatively regulated by Ca2+ in a calmodulin-dependent manner, inter alia myosin light-chain kinase, in thrombin-stimulated platelets.

Animals↗

Effect of oxymetazoline on aqueous humor dynamics and ocular blood flow in monkeys and rabbits.

OBJECTIVE: To evaluate the ocular effects of oxymetazoline hydrochloride, an alpha 2 agonist, in cynomolgus monkeys and albino rabbits. METHODS: Intraocular pressure was measured before and for 6 hours after application to glaucomatous monkey eyes. Outflow facility and aqueous flow rates were measured in normal monkey eyes. Uveoscleral outflow was measured in rabbit eyes. Ocular peak pulse volume was determined with the ocular blood flow system in normal and glaucomatous monkey eyes. RESULTS: Single applications of ozymetazoline reduced (P < .001) intraocular pressure up to 6.0 +/- 1.0 mm Hg (mean +/- SEM). Enhancement of the ocular hypotensive effect was observed with 5-day twice-daily administration. Outflow facility was unaltered; aqueous flow rate was decreased (P < .001) by 39% in the treated eyes compared with baseline values; and uveoscleral outflow was increased (P < .005) by 56% in the treated eye. Peak pulse volume was unchanged. CONCLUSION: Oxymetazoline reduces intraocular pressure by decreasing aqueous humor flow rates and increasing uveoscleral outflow. Oxymetazoline may have clinical potential as an ocular hypotensive drug.

Animals↗

Reduction of low-molecular-weight acid phosphatase activity in Alzheimer brains.

Recent studies in Alzheimer brains have shown aberrant protein phosphorylation, suggesting an alteration in protein kinases and/or phosphoprotein phosphatases. In the present study, the activity of acid phosphatase was investigated in samples prepared from postmortem normal human and Alzheimer brains. p-Nitrophenyl phosphate, a nonprotein phosphoester, was used as a substrate for acid phosphatase. The separation profile on Sephadex G-100 gel filtration chromatography revealed that two major forms of high-molecular-weight and low-molecular-weight acid phosphatase were present in the crude extracts of both rat and human brains. Another class of zinc ion (Zn2+)-dependent acid p-nitrophenyl phosphatase was also detected in rat and human brains. In Alzheimer brains, the low-molecular-weight acid phosphatase activity was significantly decreased compared to that in control brains; however, the high-molecular-weight and Zn(2+)-dependent acid phosphatase activity in control and Alzheimer brains was not different. These results suggest that reduced activity of the low-molecular-weight acid phosphatase, which possesses phosphotyrosine protein phosphatase activity, might be linked to aberrant protein tyrosine phosphorylation found in Alzheimer brains.

Acid Phosphatase↗

Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck.

Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL-2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts.

Animals↗

The interleukin-2 receptor complex and signal transduction: role of the beta-chain.

Proliferation of lymphocytes is regulated by a variety of cytokines, among which interleukin-2 (IL-2) is well characterized for its potent ability to promote cell growth. The IL-2 signal(s) is transmitted to the cell interior via its homologous receptor (IL-2R). The functional high affinity IL-2R is a multichain complex consisting of at least three distinct components, IL-2R alpha, beta and gamma. None of these components possess an intrinsic protein tyrosine kinase (PTK) domain. cDNA expression studies, have revealed the critical role of IL-2R beta, but not IL-2R alpha, in the IL-2R-mediated intracellular signaling process. Studies utilizing mutants of IL-2R beta identified an essential cytoplasmic region, defined as the 'serine-rich' region, for IL-2-induced cell growth. With respect to the involvement of PTK(s) in IL-2R mediated signal transduction, it has been demonstrated that p56lck, a member of the src-family PTKs interacts with the IL-2R beta. In fact, IL-2 stimulation increases the PTK activity of p56lck. Another cytoplasmic region of the receptor, defined as the 'acidic' region has been found to be critical for the association of p56lck with the IL-2R beta. Interestingly the 'serine-rich' and 'acidic' regions of IL-2R beta are both required for the PTK activation of p56lck. Expression studies with mutant IL-2R beta cDNAs have revealed a bifurcation in the IL-2 signaling pathway. One pathway involves the src-family PTK activation which is linked to the activation of p21ras and the subsequent induction of c-fos/c-jun protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung.

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (Kd) values of 53 +/- 2 and 4687 +/- 124 nM and maximum binding capacity (Bmax) values of 7 +/- 1 and 133 +/- 27 pmol/mg protein (n = 5) respectively. The IC50 values of various amines were as follows: IMP, 9 x 10(-5) M; propranolol, 5 x 10(-4) M; haloperidol, 6 x 10(-4) M; ketamine, 9 x 10(-3) M; dopamine, 1 x 10(-2) M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with Kd values of 54 +/- 2 and 5277 +/- 652 nM and Bmax values of 7 +/- 1 and 103 +/- 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.

Adult↗

A case of spontaneous intramural hematoma of the esophagus.

The authors experienced a case of spontaneous intramural hematoma of the esophagus (SIHE). This 44-year-old Japanese woman was admitted to our hospital because of chest pain accompanied by minimal hematemesis. Endoscopy revealed an elevated intraluminal bleeding bulge. Barium esophagograms showed a smooth and giant elevated intraluminal lesion. CT and MRI also revealed thickening of the esophageal wall. Fasting and intravenous hyperalimentation were prescribed on admission. The conditions improved and she became asymptomatic on the fifth day of hospitalization. Subsequent examinations by esophagography and endoscopy showed that the elevated lesion had disappeared and that the inflamed mucosal lesion had improved. The prognosis of cases of SIHE is excellent under conservative therapy, but close follow-up care is necessary.

Adult↗

Liver scintigraphy in a patient with Gaucher disease.

Liver scintigraphy including SPECT was performed in a patient with Gaucher disease and compared with other methods. Multiple photon-deficient areas in the liver and spleen were recognized, and in evaluating the reticuloendothelial system of the liver, liver SPECT image was superior to US, CT and MR images.

Adult↗

99mTc-HMDP accumulation in a phyllodes tumor of the breast, a case report.

In a patient with breast tumor, 99mTc-HMDP accumulation in the tumor was recognized in evaluating bone metastasis. Surgery and histopathology revealed that the tumor was a phyllodes tumor. This scintigraphic finding was thought to be rare and phyllodes tumor should be included in differential diagnosis when 99mTc-HMDP accumulation in the breast was recognized.

Breast Neoplasms↗