Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 199 records · Page 11Linked to original sources

PubMed1999

Activation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells.

Involvement of Akt/Protein kinase B (PKB), a serine/threonine kinase with a pleckstrin-homology domain, in angiotensin II (ANG II)-induced signal transduction was investigated in cultured vascular smooth muscle cells (VSMC). Stimulation of the cells with ANG II led to a marked increase in the kinase activity of Akt/PKB, which coincided with Ser-473 phosphorylation. ANG II-stimulated Akt/PKB activation was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974, but not by pertussis toxin. Akt/PKB activity was stimulated by the Ca2+ ionophore ionomycin, suggesting the possible involvement of Ca2+ in ANG II-stimulated Akt/PKB activation. However, blockade of Ca2+ mobilization by BAPTA-AM only partially inhibited ANG II-stimulated Akt/PKB activation. ANG II-stimulated Akt/PKB activation was inhibited by the tyrosine kinase inhibitors genistein and herbimycin A and by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY-294002. These results indicate that ANG II stimulates Akt/PKB activity via AT1 receptors in VSMC and that the activities of tyrosine kinase and PI3K are required for this activation.

Angiotensin II↗

PubMed1999

Implications of marked fatty infiltration around and in the atrophic atrioventricular node in elderly patients with permanent pacemaker implantation for symptomatic sick sinus syndrome.

The present study undertook an extensive analysis of the histopathological findings of the atrioventricular conduction system in 14 elderly patients treated with permanent pacemakers for sick sinus syndrome (SSS). Special attention was given to the lowest Wenckebach block points of atrioventricular conduction during rapid atrial pacing, and ventricular rate or duration of ventricular pause during chronic atrial fibrillation. An electrophysiological study (EPS) was conducted under sinus rhythm in 13 patients and under junctional escape rhythm in 1 patient. Three of the 14 cases showed a lower Wenckebach block point of 130 beats/min or less. Two of these 3 cases showed excessive fatty infiltration around the atrionodal junction area and into the atrophic atrioventricular node (AVN) itself. Of the 6 patients who had chronic atrial fibrillation after pacemaker implantation, 2 cases showed a slow ventricular response of less than 60 beats/min and/or a long ventricular pause of 3.3 s. One of the 2 cases showed a lower Wenckebach block point of 130 beats/min at the time of EPS. The other, who later progressed to idiopathic atriomegaly, also showed marked fatty infiltration around the AVN. This fatty lesion was closely associated with diffuse disruption of the muscular fibers connecting the atrophic AVN with the atrium. In addition, most of the remaining cases also had an atrophic AVN. In conclusion, a sparse or absent atrionodal connection and an atrophic AVN due to excessive fatty infiltration in the atrionodal transitional area should be investigated in atrioventricular conduction disturbances in the elderly with SSS.

Aged↗

PubMed1999

[Two-phase responses of acid expulsion triggered by alpha-1a adrenoceptor in CHO cell].

Using microphysiometer, we have investigated acid expulsion from CHO cells expressing human alpha-1a adrenoceptor. Time course of extracellular acidification rate after noradrenaline stimulation had two phases; one with a peak within 10 s reached several folds of base rate, and another increased gradually to two folds of base rate and reached plateau around two min. Both phases showed concentration-dependent increase of acidification rates in response to noradrenaline but had distinct pEC50 values; 6.0 for rapid phase and 6.6 for late phase. Amiloride and its analogs inhibited both phases entirely, suggesting that Na/H exchanger mainly mediated these acid expulsion responses. Elimination of Ca by BAPTA/EGTA treatment resulted in extensive reductions of the rapid phase response but small decrease of the late phase response. Several Ca channel blockers, Ni and LOE908 also suppressed the rapid phase while nifedipine, verapamil, SKF96365 and omega-conotoxin GIVA did not. Repeated stimulation with noradrenaline enhanced inhibitory effect of blockers. These results indicate that Ca is one of the elements in the rapid phase but not in the late phase of acid expulsion from CHO cells in response to alpha-1 adrenoceptor stimulation and suggest that Ca from both intracellular storage and some type of Ca channel dominantly participates in the rapid phase.

Acetamides↗

PubMed1999

Apoptotic cell death in neurons and glial cells: implications for Alzheimer's disease.

It is now generally accepted that massive neuronal death due to oxidative stress is a common characteristic of brains in neurodegenerative diseases. Recently, numerous apoptosis-regulating factors and multiple pathways have been identified, and apoptotic cell death has been implicated in neuronal loss in Alzheimer's disease. Although glial cells are more resistant to oxidative stress than neurons, extensive oxidative stress seems to cause apoptotic cell death in glial cells. In fact, signs of apoptosis are observed in both neurons and glial cells in the brains of patients with Alzheimer's disease. This review summarizes current findings regarding apoptotic processes and discusses the possible involvement of apoptosis-regulating factors in the pathology of Alzheimer's disease.

Alzheimer Disease↗

PubMed1999

Time course of changes in mu-opioid receptor mRNA levels in the periaqueductal gray of rat brain by a single or repeated injections of antisense oligodeoxynucleotides.

The effect of phosphorothioated antisense oligodeoxynucleotide (AS ODN) against the mu-opioid receptor (MOR) on MOR mRNA level in the periaqueductal gray (PAG) of rat brain was investigated. The MOR mRNA levels at 3, 6, 12, 24, 48 and 72 h after MOR AS ODN microinjection into the PAG were determined by reverse transcriptase-polymerase chain reaction. The MOR mRNA level was significantly decreased only at 12 h after the injection of 10 microg MOR AS ODN. When 10 microg MOR AS ODN was given three times at the interval of 48 h, MOR mRNA levels were significantly decreased at 6, 12 and 24 h after the last injection of the AS ODN. However, MOR mRNA levels were not significantly changed by three injections at 48-h interval of MOR sense ODN or AS ODNs against delta- and kappa-opioid receptors, although the two latter AS ODNs significantly reduced the respective targeted mRNA levels. In conclusion, the present results show that the selective decrease in MOR mRNA is at least one reason why the reported diminished effects of MOR agonists are produced in animals pretreated with MOR AS ODN, although they could be produced through several mechanisms in which MOR mRNA level does not change.

Animals↗

PubMed1999

Activation of the transcription factor ISGF3 by interferon-gamma.

The interferon-stimulated gene factor 3 (ISGF3) transcription factor has been extensively studied in the context of the type I interferon (IFN-alpha/beta)-mediated antiviral response; it consists of the major DNA-binding component p48, and the signal transducers and activators of transcription (Stat)1 and Stat2. We show here that type II IFN (IFN-gamma) can also invoke the activation of ISGF3 in mouse primary embryonic fibroblasts. In fact, the two Stat proteins were tyrosine phosphorylated in IFN-gamma stimulated cells. Our present findings reveal an additional mechanism by which these two distinct types of cytokines, IFN-alpha/beta and -gamma, can commonly elicit antiviral activities.

Animals↗

PubMed1999

Effective periodontal treatment in a patient with type IIA von Willebrand's disease: report of a case.

von Willebrand's disease (vWD) is one of the most common hereditary hemorrhagic disorders. A mild to moderate deficiency of factor VIII and von Willebrand factor (vWf) often is associated with gingival bleeding. In this case report, the periodontal treatment of a patient with vWD is described. A 45-year-old woman with type IIA vWD was referred for periodontal therapy because of an episode of gingival hemorrhage and percussion pain of teeth #18 and #47. The periodontal findings included probing depths ranging from 2 to 6 mm, horizontal bone loss, and Class II furcation involvement of tooth #46. After consultation with a hematologist, apically positioned flap surgery and hemisection were performed on tooth #46 following completion of oral hygiene instruction, scaling and root planing, and endodontic therapy. The patient was given 500 units of factor VIII including vWf multimer 30 minutes before surgery. After healing of the periodontal tissue, prosthodontic treatment was undertaken on the posterior mandibular sextants. At follow-up, the probing depths ranged from 2 to 3 mm, and gingival bleeding on probing was minimal. The patient's children all had vWD. They had mild to moderate periodontitis with probing depths ranging from 2 to 5 mm and gingival bleeding on probing. With the combined efforts of the periodontist and hematologist, effective periodontal treatment can be provided to patients with von Willebrand's disease.

Adolescent↗

PubMed1999

A novel mutation in the vasopressin V2 receptor gene in a woman with congenital nephrogenic diabetes insipidus.

A 56-year-old Japanese woman with congenital nephrogenic diabetes insipidus (CNDI) is reported. She was diagnosed with CNDI accompanied by advanced gastric cancer. After total gastrectomy, approximately 500 ml fluid per hour was necessary to prevent dehydration. Urinary volume was decreased by administration of hydrochlorothiazide. We detected a novel mutation in the vasopressin V2 receptor gene of her chromosomal DNA. A substitution from G to A was found at the 631 nucleotide position, altering codon 12 from glycine (GGG) to glutamic acid (GAG) in the first extracellular domain. This missense mutation appeared to be the cause of her resistance to arginine vasopressin.

Amino Acid Sequence↗

PubMed1999

Elevated remnant-like lipoprotein particles in impaired glucose tolerance and type 2 diabetic patients.

OBJECTIVE: Impaired glucose tolerance (IGT) in association with insulin resistance is considered to be a risk factor for atherosclerosis. Thus, patients with IGT may have abnormal lipid and lipoprotein profiles. The purpose of this study was to investigate presence of remnant-type hyperlipoproteinemia in patients with IGT. RESEARCH DESIGN AND METHODS: Serum levels of remnant-like lipoprotein particles (RLP) were measured in 541 subjects (362 men and 179 women, age 53 +/- 7.9 years) who visited our health center for routine medical examinations. We measured RLP cholesterol (RLP-C) and RLP triglycerides (RLP-TG) using immunoaffinity gel containing monoclonal anti-human apoproteins A-I (H-12) and B-100 (JI-H) antibodies. After a 75-g oral glucose tolerance test, subjects were divided into three groups: normal, IGT, and type 2 diabetic. RESULTS: After matching for sex, age, and body weight, serum RLP-C in normal, IGT, and diabetic groups were 4.2 +/- 1.7, 6.2 +/- 3.4, and 6.2 +/- 4.2 mg/dl, respectively. The corresponding RLP-TG values were 16.7 +/- 9.2, 28.0 +/- 19.1, and 29.0 +/- 27.2 mg/dl. We found that RLP-C and RLP-TG values were significantly higher in the IGT and diabetic groups compared with the normal group (P < 0.001). In the same order, total serum cholesterol levels were 206 +/- 29, 205 +/- 34, and 206 +/- 34 mg/dl and LDL cholesterol levels were 127 +/- 27, 124 +/- 34, and 123 +/- 34 mg/dl, showing no marked difference in these groups. However, serum levels of triglyceride were higher in the IGT and diabetes groups (155 +/- 76 and 151 +/- 81 mg/dl vs. 106 +/- 41 mg/dl; P < 0.0001). Further, the incidence of remnant hyperlipoproteinemia in normocholesterolemic subjects was up to four times higher in IGT and diabetic groups compared with the normal group. CONCLUSIONS: High serum RLP-C and RLP-TG levels in IGT and diabetic patients may represent an increased risk of atherosclerosis in these patients.

Analysis of Variance↗

PubMed1999

Differential involvement of small G proteins in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive deterioration of cognitive function and memory in association with the wide-spread presence of senile plaques, neurofibrillary tangles and neuronal cell death. However, its pathophysiology remains unknown. GTP-binding proteins with molecular weights of approximately 20,000 are designated small G proteins. In the present study we quantitatively analyzed the small G proteins, Ras, Rap, Ral and Rab in brains removed at autopsy from controls and AD patients to examine whether small G proteins are equally or differentially affected in AD. Western blot analysis indicated that the protein level of Ras and RalB in both the cytosolic and membranous fractions and that of Rap2 in the cytosolic fraction was significantly decreased, while that of Rab8 in the membranous fraction was significantly increased in AD brains compared with controls. The protein level of other small G proteins was not different between control and AD brains. These results suggest a differential involvement of small G proteins in AD.

Aged↗

PubMed1999

New alpha1-adrenoceptor antagonist, JTH-601, shows more than 10 times higher affinity for human prostates than arteries.

PURPOSE: We compared the affinities of a new alpha1-adrenoceptor (AR) antagonist, JTH-601 with those of several alpha1-AR antagonists in human prostates and arteries. RESULTS: In the functional study, noradrenaline produced concentration-dependent contractions in human prostates and mesenteric arteries. The pA2/pKB values for the antagonists in the human prostate were 9.78 for tamsulosin, 8.84 for JTH-601, 8.39 for WB4101, 8.23 for prazosin, 8.12 for JTH-601-G1 (a main metabolite of JTH-601 in human) and 6.57 for BMY7378. Compared these affinities with those in the mesenteric artery, only JTH-601 and JTH-601-G1 exhibited unique uroselectivity, showing 10- to 20-fold higher affinity for the human prostate than for mesenteric artery. The affinity profile of these antagonists suggested that the noradrenaline-induced contractions in the human prostate and the mesenteric artery were mediated by the alpha1L-AR and alpha1B-AR, respectively. In the competition binding study, the pharmacological profiles of the antagonists against [3H]-prazosin were examined in the human prostate and aorta. The resulting pKi values for JTH-601 and JTH-601-G1 were also approximately 10- to 20-fold higher for the human prostate than for the human aorta. CONCLUSION: These results have suggested that JTH-601 and JTH-601-G1 are unique uroselective alpha1-AR antagonists that show higher affinity for the human prostate than for the human arteries.

Adrenergic alpha-Antagonists↗

PubMed1999

Evidence for predominant mediation of alpha1-adrenoceptor in the tonus of entire urethra of women.

PURPOSE: We separated the entire length of the isolated human female urethra into seven parts from external urethral meatus to bladder neck and examined regional differences in contractile responses to noradrenaline, clonidine, acetylcholine and KCl. MATERIALS AND METHODS: The entire urethra was obtained from 9 female patients with a mean age of 72.2 +/- 1.8 years. The entire urethra (35 to 42 mm. in length) was transversely cut into seven parts, and the contractile responses to noradrenaline, clonidine, acetylcholine and KCl of these parts were examined. RESULTS: Noradrenaline but not clonidine produced concentration-dependent contraction in all parts, with a peak amplitude in middle to proximal urethra. In contrast, acetylcholine produced contraction only in proximal urethra and bladder neck. The amplitudes of noradrenaline-induced contraction were normalized against those induced by KCl, revealing similarity in patterns between noradrenaline-induced contractions and urethral pressure profile in human female urethra. These contractions to noradrenaline and acetylcholine were competitively inhibited by prazosin (pK(B): 8.38 +/- 0.10) and atropine (pK(B): 8.52 +/- 0.43), respectively. CONCLUSION: These findings suggest that sympathetic innervation helps maintain resting urethral tonus, mainly through alpha1-adrenoceptors.

Acetylcholine↗

PubMed1998

Functional cooperation of cyclin C and c-Myc in mediating homotypic cell adhesion via very late antigen-4 activation and vascular cell adhesion molecule-1 induction.

Very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1) are a pair of adhesion molecules mediating cell-cell interaction. The binding activity of each depends on its surface expression, yet integrin activity can also be modulated through inside-out signaling. However, the specific intracellular molecules involved in modulating integrin VLA-4 activation via inside-out signaling or in regulating VCAM-1 expression are poorly understood. We show here that constitutive coexpression of cyclin C and c-Myc in hematopoietic BAF-B03 cells induces homotypic cell adhesion, which results from enhanced VLA-4 ligand-binding activity and induced expression of VCAM-1. Furthermore, regulation of cell adhesion appears to be a feature unique to cyclin C, but not other G1 cyclins, E and D3, and its regulatory function is independent of CDK8 kinase activity. Our results provide a novel role for cyclin C and c-Myc in the regulation of cell adhesion through distinct mechanisms.

Animals↗

PubMed1998

Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7.

The interferon regulatory factor (IRF) family of transcription factors regulate the interferon (IFN) system, among which IRF-3 is involved in the virus-induced IFN-beta gene expression. Here we show that another member IRF-7 is critical for the IFN-alpha gene induction. Unlike the IRF-3 gene, the IRF-7 gene is induced by IFNs through activation of the ISGF3 transcription factor, and IRF-7 undergoes virus-induced nuclear translocation. In cells lacking p48, an essential component of IFN stimulated gene factor 3 (ISGF3), ectopic expression of IRF-7 but not IRF-3 can rescue the deficiency to induce IFN-alpha genes. These results indicate that IRF-7 is a key factor in the positive feedback regulation of IFN-alpha/beta production.

Amino Acid Sequence↗

PubMed1998

Functional dissection of the cytoplasmic subregions of the IL-2 receptor betac chain in primary lymphocyte populations.

The interleukin 2 (IL-2) receptor betac chain (IL-2Rbetac) is known to regulate the development and function of distinct lymphocyte populations. Thus far, the functions of the IL-2Rbetac cytoplasmic subregions have been studied extensively by using cultured cell lines; however, this approach has limitations with respect to their functions in distinct primary lymphocyte populations. In the present study, we generated mice each expressing a mutant form of an IL-2Rbetac transgene, lacking the cytoplasmic A- or H-region, on an IL-2Rbetac null background. We show that lack of the H-region, which mediates activation of the Stat5/Stat3 transcription factors, selectively affects the development of natural killer cells and T cells bearing the gamma delta T cell receptor. This region is also required for the IL-2-induced proliferation of T cells in vitro, by upregulating IL-2Ralpha expression. In contrast, the A-region, which mediates activation of the Src family protein tyrosine kinase (PTK) members, contributes to downregulation of the T cell proliferation function. The IL-2Rbetac null mutant mice develop severe autoimmune symptoms; these are all suppressed following the expression of either of the mutants, suggesting that neither the Stats nor the Src PTK members are required. Thus, our present approach offers new insights into the functions of these cytoplasmic subregions of the IL-2Rbetac chain.

Animals↗

PubMed1998

Allelic loss on chromosome 9 in bladder cancer tissues and urine samples detected by blunt-end single-strand DNA conformation polymorphism.

Allelic loss on chromosome 9 is the most frequent and earliest genetic event in bladder carcinogenesis, and its detection in urine samples would be useful for detecting bladder cancer. A highly sensitive method to detect loss of heterozygosity (LOH) at 5 polymorphic loci on chromosome 9p and 9q was developed by the use of blunt-end single-strand DNA conformation polymorphism (blunt-end SSCP) analysis. Tumor tissues, urine samples and peripheral blood lymphocytes from 34 patients with transitional cell carcinoma of the bladder were analyzed. LOHs on 9p and/or 9q were found in 24 (71%) of 34 tumor samples and 23 (70%) of 33 urine samples, while no allelic loss was detected in 20 urine samples from benign urothelial diseases. The frequency of allelic loss in tumor tissues was 67%, 71% and 80% in the pTa, pT1 and > or = pT2 stages and 50%, 80% and 79% in G1, G2 and G3 tumors, respectively. In comparison with a urine cytological examination, LOH on chromosome 9 was detected in 70% of urine samples diagnosed as transitional cell carcinoma, 67% of those as atypia and 70% of those as no malignant cells. Thus, detection of LOH on chromosome 9 from urine samples by blunt-end SSCP is a more sensitive diagnostic modality than cytologic examination for detecting bladder cancer. It would be useful for postoperative management of bladder cancer, particularly when the allelic loss is revealed in the tumor tissues obtained at first surgery.

Carcinoma, Transitional Cell↗

PubMed1998

PKC and tyrosine kinase involvement in amyloid beta (25-35)-induced chemotaxis of microglia.

Microglia are activated by amyloid beta (Abeta) in vivo and in vitro, and Abeta-activated microglia may be involved in the pathogenesis of Alzheimer's disease (AD). We investigated the mechanism of microglial chemotaxis induced by Abeta (25-35), an active fragment of Abeta. Abeta (25-35) 0.1 and 1 nM stimulated microglial chemotaxis. The protein kinase C (PKC) inhibitors chelerythrine (0.5 and 2 microM), calphostin C (1 microM) and staurospine (10 nM) significantly inhibited the microglial chemotaxis induced by Abeta (25-35) (1 nM). The chemotactic effect of Abeta (25-35) on microglia was desensitized by pretreatment of microglia with 1 ng/ml 12-O-tetradecanoylphorbol 13-acetate (TPA). Pretreatment of cells with Abeta (25-35) (1 nM) also desensitized the chemotactic effect by Abeta (25-35) (1 nM). The desensitization by TPA or Abeta (25-35) was inhibited when staurosporine was present in the pretreatment media. The tyrosine kinase inhibitor herbimycin A (0.1 and 1 microM) significantly inhibited the microglial chemotaxis induced by Abeta (25-35) (1 nM). Based on these observations, it seems likely that PKC and tyrosine kinase are involved in the Abeta-induced chemotaxis of microglia.

Alkaloids↗

PubMed1998

Differential expression of rat brain synaptic proteins in development and aging.

We have previously reported the differential involvement of synaptic proteins in Alzheimer's disease (AD). As AD is an aging-associated disease, in the present study we examined the developmental and aging-related changes in synaptic proteins such as synaptophysin, synaptobrevin, synaptotagmin, synaptosomal-associated protein 25 (SNAP-25), syntaxin 1/HPC-1 and drebrin in the rat brain. Immunoblot analyses of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that the protein level of synaptophysin and synaptobrevin increased after birth, being highest at 24 weeks, and then decreased with aging. Synaptotagmin was detected at E19, with levels increasing after birth to 96 weeks. SNAP-25 levels were highest at 4 weeks, and then decreased with aging. Syntaxin 1/HPC-1 levels were high at E19 and 1 week, decreasing rapidly from 2 weeks onwards, and drebrin levels were highest at E19 and 1 week, and decreased during aging. The present results suggest that the expression of each synaptic protein is differentially regulated in development and aging.

Aging↗