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Biomedical subjects

T Yamaguchi

Publications and source records attributed to T Yamaguchi.

At least 703 records · Page 39Linked to original sources
PubMed1997

Vascular endothelial growth factor increases endothelin-converting enzyme expression in vascular endothelial cells.

Endothelin-converting enzyme-1 (ECE-1) is a key enzyme in endothelin processing. Although it has been revealed that ECE-1 expression increases in vascular wall after balloon injury in vivo experimental models, the regulation of ECE-1 expression in vitro remains undefined. In this study, we demonstrated that the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF) increased ECE-1 expression in cultured bovine aortic endothelial cells (BAEC). Northern blot analysis revealed that VEGF increased ECE-1 mRNA expression in 12-24 hours by 2-fold in BAEC, and this effect was dose-dependent. VEGF also increased ECE-1 protein expression detected by immunoblotting in 36 hours in BAEC. Therefore, VEGF increased ECE-1 expression in BAEC, which suggests that ECE-1 induction by VEGF may be involved in endothelin-system upregulation under pathological conditions such as neointimal formation and atherosclerosis.

Animals↗
PubMed1997

A simple method for the propagation and purification of gamma delta T cells from the peripheral blood of glioblastoma patients using solid-phase anti-CD3 antibody and soluble IL-2.

Although gamma delta T cells make up no more than 10% of the peripheral blood mononuclear (PBM) cells, they appear to play an important role in host defense against tumor growth. In order to evaluate their functional activity against tumors and their response to various cytokines, large numbers of cells are required. Here, we describe a newly-devised method for the isolation and expansion of gamma delta T cells from the peripheral blood of cancer patients, in particular those with glioblastoma. Using this approach, a 1000-1500-fold increase in total cell numbers was achieved in two weeks, the proportion of gamma delta T cells in the expanded population being, on average, approximately 30% after 14 days of culture. The method therefore gives a yield of approximately 10-15 x 10(8) gamma delta T cells from only 5 ml of peripheral blood from glioblastoma patients and normal controls. The highly purified gamma delta T cells of glioblastoma patients were shown to bear both a high-affinity interleukin-2 receptor (IL-2R) and a low-affinity IL-12 receptor (IL-12R). They also displayed significant cytotoxicity against autologous tumor cells, but not against autologous fresh or IL-2-treated lymphocytes, and proliferated in response to IL-2, both effects being dependent on the dose of IL-2 used for activation. In addition, overnight incubation with 700 U/ml of IL-2 or 50 ng/ml of IL-12 resulted in significant cytotoxic activity of patients' gamma delta T cells against K562 target cells, the level of activity being almost the same as with similarly-treated gamma delta T cells from normal controls (P > 0.05). These results demonstrate that the patients' gamma delta T cells obtained using this method are intact in terms of cytotoxic function. Thus, this method not only makes it possible to produce large numbers of purified gamma delta T cells but also to produce populations containing both gamma delta T cells and NK cells, both active against tumor targets which might be suitable for clinical trials of adoptive-immunotherapy, especially in cancer patients for whom no effective therapy is available.

Adolescent↗
PubMed1997

Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity.

YM992 ((S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride) is a novel compound that has selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT2A receptor antagonistic activity in vivo. YM992, fluoxetine and citalopram showed 5-HT uptake inhibition activity in l-5-hydroxy-tryptophan (l-5-HTP)-treated mice. YM992 and trazodone attenuated 5-HT2A/2C receptor agonist-induced head-twitches in mice, indicating that these drugs had 5-HT2A receptor antagonistic activity. YM992 and amitriptyline were highly active in the mouse tail suspension test. In contrast, fluoxetine and citalopram showed only a tendency to reduce the immobility time. Single treatment with YM992 as well as trazodone and fluoxetine ameliorated the learning deficit of olfactory-bulbectomized rats, whereas citalopram and amitriptyline showed an ameliorative effect only after chronic treatment. Although YM992 has moderate affinity for alpha1-adrenoceptors, alpha1-adrenoceptor antagonism of YM992 in vivo was 10 times weaker than that of trazodone. These results demonstrate that YM992 has 5-HT uptake inhibition and 5-HT2A receptor antagonistic activity in vivo, and suggest that YM992 may be a novel antidepressant with high efficacy in clinical use.

Animals↗
PubMed1997

Synthesis and evaluation of oligodeoxyribonucleotides containing an aryl(trifluoromethyl)diazirine moiety as the cross-linking probe: photoaffinity labeling of mammalian DNA polymerase beta.

Photolabile 2'-deoxy- E -5-[4-(3-trifluoromethyl-3 H-diazirin-3-yl)styryl]uridine and its protected phosphoramidite derivatives have been synthesized and introduced into DNA oligomers through solid-phase DNA synthesis. The (trifluoromethyldiazirinyl)stylyl moiety of this nucleoside was found to be sufficiently stable for automated DNA synthesis. In addition, this moiety was found to be stable at 60 degrees C in aqueous solution under the annealing conditions for duplex formation with complementary strands, since >95% of the photolabile nucleoside remained after heating for 1 h. The oligo(dT) 15mer analog bearing the photolabile residue was activated/decomposed by near-UV irradiation. In photoaffinity cross-linking experiments with recombinant rat DNA polymerasebeta, constituted from a 40 kDa polypeptide, using oligo(dT) 15mer analogs bearing the photolabile residue near the 3'-terminus, a covalently bound complex of 45 kDa was obtained in the presence of complementary templates. Thus it was demonstrated that our method for synthesis of photolabile oligodeoxyribonucleotides may be useful for studies of DNA-related enzymes and DNA binding proteins.

Animals↗
PubMed1997

Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK.

Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6. Janus kinases (JAKs) are known to associate with certain cytokine receptors, e.g. gp130, the signal transducing subunit of IL-6 receptor, and the common beta chain of IL-3 receptor, which can be activated upon receptor dimerization in response to cytokines. Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using a yeast two-hybrid system we have identified the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs.

Antigens, CD↗
PubMed1997

Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid.

We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection: concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.

Animals↗
PubMed1997

N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines: synthesis and wide range of antagonism at the human 5-HT1A receptor.

A series of N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines was prepared and examined for their 5-HT1A receptor antagonist activity. The parent compound 3a and seven analogs bearing five kinds of substituents on the chroman ring were prepared from the corresponding 8-hydroxychroman intermediates. Radioligand binding assays proved the compounds 3a-h to have high affinity for the rat hippocampal 5-HT1A receptor with varied selectivity for adrenaline alpha1 and dopamine D2 receptors. Their antagonism was evaluated in a forskolin-stimulated adenylate cyclase assay performed with CHO cells expressing the human 5-HT1A receptor. Among the series, the C6-fluoro analog 3c showed both extremely potent affinity (Ki = 0.22 nM) and antagonism (EC50 = 13 nM) for the 5-HT1A receptor. Correlation analysis using substituent descriptors revealed a linear and negative correlation between molar refractivity of the C6-substituent and the binding affinity expressed in pKi.

Animals↗
PubMed1997

Cutaneous reflex activity of the cat forelimb during fictive locomotion.

To investigate mechanisms of rhythmic modulation of cutaneous reflex by the central pattern generator for locomotion, we made intracellular recordings from elbow flexor motoneurons, biceps brachii (Bi) and brachialis (Br), and quantitatively analyzed excitatory postsynaptic potentials (EPSPs) evoked by stimulation of superficial radial (SR) nerves during forelimb fictive locomotion, which was evoked in immobilized, decerebrate cats with the low thoracic spinal cord transected. We found that (1) in both Br and Bi, SR stimulation evoked trisynaptic EPSPs (segmental latencies were 2.10 +/- 0.39 ms for Br and 2.07 +/- 0.93 ms for Bi), (2) the SR-EPSPs of Br and Bi were rhythmically modulated with a similar pattern; the maximal and minimal EPSPs appeared in the flexor and extensor phase, respectively, (3) however, there were differences as follows. In the control state where fictive locomotion was absent, the mean amplitude of SR-EPSPs of Br (4.65 +/- 2.76 mV, n = 14) was much larger than that of Bi (1.25 +/- 1.22 mV, n = 10). During fictive locomotion, the maximum amplitude of SR-EPSPs of Br was 5.63 +/- 1.79 mV (n = 18), and the minimum was 3.82 +/- 1.69 mV (n = 18); that is, the maximum during fictive locomotion was larger or smaller than that of the control, while the minimal were always smaller. In contrast, SR-EPSPs of Bi were modulated over the control level; the maximum was 3.97 +/- 1.71 mV (n = 16) and the minimum was 2.24 +/- 1.11 mV (n = 16), both the maximum and the minimum during locomotion being larger than that of the control. These results may suggest that two mechanisms are involved in the rhythmic modulation, first, cyclic facilitation in the flexor phase, and secondly, cyclic inhibition in the extensor phase. The former was involved in both cases of Bi and Br motoneurons, while the latter would be involved only in the case of Br motoneurons.

Animals↗
PubMed1997

Effects of aminoguanidine on systemic inflammatory response syndrome induced by platelet activating factor and by lipopolysaccharide in rats.

We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.

Animals↗
PubMed1997

An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT.

JAK is believed to be an essential tyrosine kinase that mediates signals from the cytokine receptor to its downstream events. JAK associates with the cytoplasmic domain of the type I cytokine receptor superfamily and upon the ligand stimulation it can be activated, resulting in the receptor phosphorylation. In signaling from gp130, a common signal transducer for the IL-6 family cytokines, STAT3, a transcription factor that contains an SH2 domain, is recruited by phosphotyrosines on gp130 and is subsequently phosphorylated by gp130-associated JAKs. In this study, we attempted to find a new target for JAK that is directly activated by JAK, independent of gp130 tyrosine phosphorylation, by using a yeast two-hybrid system. In the process we found that the JH2 domain of JAK1, JAK2 or JAK3 could specifically associate with the carboxy-terminal portion of STAT5, but not with STAT3 or STAT1. The interaction was confirmed using both a transient expression system in a cell line and a GST-fusion protein binding assay. Furthermore, we showed that the activation of STAT5 via gp130 did not need any phosphotyrosines on gp130 while that of STAT3 strictly depended on phosphotyrosines on gp130. Mutations of STAT5 that eliminated the interaction with JAK1 reduced the activation of STAT5 upon the gp130 stimulation, although such mutants could be still activated through erythropoietin receptor. These results indicate that STATs are activated through cytokine receptors by two distinct mechanisms, one dependent on receptor tyrosine phosphorylation and the other mediated by the JAK-STAT direct interaction.

Animals↗
PubMed1997

Post-ischaemic treatment with orotic acid prevents neuronal injury in gerbil brain ischaemia.

We studied the effects of orotic acid, a precursor of pyrimidine nucleotide, on delayed neuronal death of hippocampal CA1 neurones induced by global cerebral ischaemia in Mongolian gerbils. Neuronal damage was significantly reduced in animals treated with orotic acid 2 h before ischaemia at doses of 100, 200 or 300 mg kg-1, i.p. A dose of 300 mg kg-1 given 24 h after ischaemia also suppressed CA1 neuronal damage, but had no effect when given at 48 or 72 h. These results demonstrate a protective effect of orotic acid on ischaemic neuronal damage with a wide therapeutic time window.

Animals↗
PubMed1997

Effects of green tea catechins on the progression or late promotion stage of mammary gland carcinogenesis in female Sprague-Dawley rats pretreated with 7,12-dimethylbenz(a)anthracene.

Effects of the green tea catechins (GTCs) on the late promotion or progression stage of mammary gland carcinogenesis were examined in female Sprague-Dawley (SD) rats pretreated with 7,12-dimethylbenz(a)anthracene (DMBA). A total of 84 7-week-old rats received a 50 mg/kg body weight intra-gastric dose of DMBA, and starting 13 weeks thereafter, when the tumor incidence had reached 50%, three groups of 28 animals each were placed on diet containing 0.5% Polyphenon E (58.4% content (-)-epigallocatechin gallate (EGCG)) (groups 1a and 1b), 0.5% EGCG-80 (81% content of EGCG) (groups 2a and 2b) or basal diet alone (groups 3a and 3b) for 23 weeks. The experiment was terminated at week 36. The growth (i.e. change in mean diameter) of mammary tumors present at week 13 (groups 1a, 2a and 3a) was not influenced by the treatment with EGCGs, with no significant intergroup differences in the lesion incidences, multiplicity or size being observed. Values for these parameters did show a tendency for decrease in group 2b (Polyphenon E) as compared to group 3b (control) during the study, but they were not significantly reduced at the sacrifice time point. These results indicate that GTCs are not effective at inhibiting progression of rat mammary carcinogenesis, but Polyphenon E may exert a weak inhibitory effect on the early promotion stage.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Gazelle herpesvirus 1: a new neurotropic herpesvirus immunologically related to equine herpesvirus 1.

A herpesvirus was isolated from Thomson's gazelle (Gazella thomsoni) kept at a zoological garden in Japan during an outbreak of epizootic acute encephalitis. The virus, gazelle herpesvirus 1 (GHV-1), was serologically related to equine herpesvirus 1 (EHV-1). However, DNA fingerprints of GHV-1 were different from those of EHV-1 and other equine herpesviruses. Southern hybridization with probes of cloned BamHI fragments derived from UL and US segments of EHV-1 revealed differences in the DNA restriction profiles throughout the entire genome. Nucleotide sequences were determined for a conserved region of an essential envelope glycoprotein B (gB) gene and a type-specific glycoprotein G (gG) homologue gene. The predicted amino acid sequence of GHV-1 gB showed 97, 92, 61, and 57% identity to EHV-1, EHV-4, feline herpesvirus, and pseudorabies virus, respectively, indicating that GHV-1 was closer to EHV-1 than any other herpesvirus. The GHV-1 gG gene showed 93.2, 92.3, and 53% identity to EHV-1, EHV-8, and EHV-4 gGs, respectively. GHV-1 was virulent to suckling mice of the ICR strain by intracerebral inoculation and was virulent to 4-week-old BALB/c mice by intranasal inoculation, causing neurological symptoms and death. We conclude that GHV-1 is a new type of equine herpesvirus with strong neurotropism.

Amino Acid Sequence↗
PubMed1997

Analysis of lymph node metastasis in early gastric cancer: rationale of limited surgery.

BACKGROUND: Since the majority of patients with early gastric cancer show long-term survival after surgery, a special attention must be directed to preserving gastric function in these patients. Little is known about the protocol of surgical treatment appropriate for early gastric cancer patients. This study was designed to determine the appropriate surgical procedure for early gastric cancer. METHODS: The clinicopathologic features of 52 patients with node-positive early gastric cancer were reviewed retrospectively from hospital records between 1969 and 1994 and were compared with those of 582 patients with node-negative early gastric cancer. Nodal status of positive nodes in the 52 cases was investigated. RESULTS: Depth of invasion, lymph vessel invasion, and tumor size were associated with lymph mode metastasis. Node-positive patients with early gastric cancer had a poorer survival rate than node-negative patients (P < 0.05). Patients with five or more positive nodes and positive nodes distant from the common hepatic artery showed an extremely poor prognosis. CONCLUSIONS: The surgical procedures most appropriate for the treatment of early gastric cancer are as follows: (1) local gastric resection without lymphadenectomy for mucosal cancers of < 2 cm in diameter and for elevated submucosal cancers of < 1 cm in diameter, (2) gastrectomy with dissection of the perigastric nodes, the nodes along the left gastric artery and the common hepatic artery, for the treatment of other early gastric cancers.

Aged↗
PubMed1997

Overexpression of bax enhances the radiation sensitivity in human breast cancer cells.

Bax-alpha, a splice variant of bax which promotes apoptosis, is expressed in many kinds of untransformed cell lines and breast tissue, whereas only weak or no expression could be detected in breast cancer cell lines and malignant breast tissue. Human breast cancer MCF-7 cells, which have a weak bax gene expression, were stably transfected with pCX2neo bax, encoding human bax and neomycin-resistant genes, and two unique clones (MCF-7/bax-1 and MCF-7/bax-2) were thus generated which expressed different levels of bax-alpha. Sensitivity to ionizing radiation (IR) was examined and each was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax, and IR was found to induce intranucleosomal DNA fragmentation in stable transfectant but not in parent cells, thus suggesting that this sensitization is due to apoptosis. We suggest that exogenous bax-alpha expression might therefore be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may potentially have a therapeutic application by enhancing radiation sensitivity in breast cancer cells.

Apoptosis↗
PubMed1997

An adult case of duodenal anomaly.

A distal gastrectomy reconstruction using the Billroth II procedure was performed for epigastralgia and liver dysfunction caused by a duodenal anomaly in an adult. Hypotonic duodenography revealed the duodenum to be obliterated at the junction of the second and third portion, while the third portion was joined to the first portion. Endoscopic retrograde cholangiopancreaticography (ERCP) and ultrasonography showed a normal construction of the common bile and pancreatic ducts, as well as gallstones. To prevent ingested food from the stomach from entering the obliterated second portion, a distal gastrectomy (Billroth II) was thus performed. The patient has remained asymptomatic for 4 years since surgery. A distal gastrectomy reconstructed by a gastrojejunostomy is thus considered to be an effective method for improving the symptoms caused by food stasis in the obliterated second portion of the duodenum.

Cholangitis↗