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T Kanno

Publications and source records attributed to T Kanno.

At least 163 records · Page 9Linked to original sources
PubMed1998

Intracellular cAMP potentiates voltage-dependent activation of L-type Ca2+ channels in rat islet beta-cells.

Intracellular cAMP-dependent modulation of L-type Ca2+ channel activation in cultured rat islet beta-cells has been investigated using the patch-clamp whole-cell current recording mode. The L-type voltage-dependent Ca2+ current (ICa) showed a fast activation followed by a slow inactivation, and was sensitive to Ca2+ channel blockers, for example nifedipine. Application of a cAMP analogue, dibutyryl cyclic AMP (db-cAMP), increased the magnitude of the peak ICa in a concentration-dependent manner. Values of the half-activation potentials (V1/2), taken from activation curves for ICa, were -16.7 +/- 1.8 and -21.9 +/- 3.4 mV (P < 0.05) before and after application of db-cAMP, respectively, with no change of the slope factor (k) or the reversal potential. Pretreatment with a specific protein kinase A antagonist, Rp-cAMP, prevented the potentiating effect of db-cAMP. These results indicate that in rat islet beta-cells, phosphorylation of cAMP-dependent kinase potentiates the voltage-dependent activation of L-type Ca2+ channels.

Animals↗
PubMed1998

Muscarinic and nicotinic receptor-mediated Ca2+ dynamics in rat adrenal chromaffin cells during development.

To clarify when the cholinergic receptor-mediated secretion mechanism of developing adrenal chromaffin cells is expressed and becomes functional, morphological changes and intracellular calcium dynamics were studied by immunohistochemistry, electron microscopy, and Fura-2 digital image analysis. From embryonic day 14 to 16, adrenal medullary cells were immunoreactive to noradrenaline-synthesizing enzyme (dopamine beta-hydroxylase) but not to adrenaline-synthesizing enzyme (phenylethanolamine N-methyltransferase). These cells contained either no granules or just a few granules of high electron density. Exocytotic figures were rarely observed in cells of the control or in cells after carbamylcholine stimulation. Nerve fibers in the adrenal medulla contained either no clear vesicles or very few. Neither methacholine nor nicotine caused a change of intracellular Ca2+ in most chromaffin cells. From embryonic day 18 to 20, chromaffin cells were immunoreactive to both dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase and they contained relatively numerous secretory granules. Exocytotic figures were often seen in cells after carbamylcholine stimulation. The intra-adrenal nerve fibers contained numerous clear vesicles and a few dense-cored vesicles. Methacholine caused no rise of intracellular Ca2+, but nicotine induced a low to relatively high rise in many cells. From postnatal day 2 or 3 to postnatal week 1, numerous cells were immunoreactive to both dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, whereas some cells were reactive to dopamine beta-hydroxylase alone. Chromaffin cells were divisible into noradrenaline cells and adrenaline cells based on the ultrastructural features of their granules. Methacholine induced a moderate rise of intracellular Ca2+ and nicotine caused a high rise in many chromaffin cells, whereas, in some chromaffin cells, methacholine induced no rise of intracellular Ca2+ and nicotine induced a high rise. These results suggest that morphological changes of the developing cells and the intra-adrenal nerve fibers are related to the expression of a cholinergic receptor-mediated secretion mechanism and that this mechanism via a nicotinic receptor-mediated Ca2+ signaling pathway precedes the muscarinic receptor-mediated one during development.

Adrenal Medulla↗
PubMed1998

Viruses produced from complementary DNA of virulent and avirulent strains of swine vesicular disease viruses retain the in vivo and in vitro characteristics of the parental strain.

A full-length cDNA copy of the genome of the pathogenic strain, J1'73, of swine vesicular disease virus (SVDV) was constructed and inserted into the plasmid pSVL to generate a recombinant plasmid pSVLSJ1. Infectious virus was produced following transfection of cultured mammalian cells with the plasmid. The recovered virus had the same in vitro properties as the parental strain with regard to antigenicity, plaque size on IBRS-2 cells and single-step growth. Pigs were experimentally infected with the parental virus, J1'73 strain, and viruses recovered from cells transfected with the plasmids pSVLSJ1 and pSVLS00 [Inoue T, Yamaguchi S, Saeki T, Sekiguchi K, J Gen Virol 71: 1,835-1,838 (1990)] corresponding to the pathogenic (J1'73) and non-pathogenic (H/3'76) Japanese strains of the SVDV, respectively. All pigs inoculated with the virus recovered from pSVLSJ1 produced clinical signs of similar severity to those inoculated with the parental J1'73 strain. In contrast, pigs inoculated with the virus recovered from pSVLS00 did not show any clinical signs. Viruses recovered from cells transfected with either pSVLSJ1 or pSVLS00 therefore retained the in vitro characteristics and the in vivo pathogenicity of their respective parental strains.

Animals↗
PubMed1998

Diabetes-induced and age-related changes in fatty acid proportions of plasma lipids in rats.

Diabetes-induced and age-related proportional changes in plasma fatty acids of triglycerides (TG), phospholipids (PL), and cholesteryl esters (CE) were investigated using streptozotocin-induced diabetic and control rats. Among n-6 fatty acids from diabetic rat plasma, increased proportions of 18:2n-6 and 20:3n-6 in all three lipid classes and of 18:3n-6 in PL at 1-3 months old and in TG at 3-5 months old were observed. The proportions of 20:4n-6 decreased in both PL and CE, but were unchanged in diabetic TG. Among the n-3 fatty acids, in the early stage, diabetes caused increases in the proportions of 18:3n-3 in PL and CE and of 20:5n-3 and 22:6n-3 in TG, while 22:5n-3 was decreased later in the disease course. These results suggest reduced delta 5-desaturase activities on 20:3n-6 but not on 20:4n-3, while delta 6-desaturase activity on 18:2n-6 was essentially unaffected. Furthermore, the reduction in delta 9-desaturase activity in diabetic rats may well explain the decreases in the proportions of 16:1n-7 and 18:1n-7. However, the proportion of 18:1n-9, another product of delta 9-desaturase, was significantly increased in CE and PL as compared to the controls. Thus, there was a discrepancy between our results and those of earlier studies with respect to the n-9, n-6, and n-3 fatty acid proportions of plasma lipids in diabetic rats. We also investigated age-related changes in the proportions of plasma fatty acids. Although rather small, age-related changes were evident in both diabetic and control rats.

Age Factors↗
PubMed1998

Interassay calibration as a major contribution to the comparability of results in clinical enzymology.

OBJECTIVE: Factors contributing to the applicability of interassay calibration of methods measuring enzyme catalytic activities are described. Also discussed are the properties essential for such a material. Similarity of specificity for the methods to be calibrated as well as commutability between the material(s) intended to be used as calibrator are the main criteria to be satisfied. RESULT: Several examples demonstrated that interassay calibration is feasible but a multi-enzyme calibrator with a wide commutability for the most popular methods remains to be developed. This is the project of the IFCC Working Group on Calibrators in Clinical Enzymology (WG-CCE). Several experimental data are also presented that indicate that the temperature at which the reaction is carried out is not a limiting factor in the implementation of interassay calibration in clinical enzymology.

Calibration↗
PubMed1998

Validation of an enzyme calibrator--an IFCC guideline. International Federation of Clinical Chemistry.

OBJECTIVES: The objective of this guideline is to improve standardization in clinical enzymology in order to improve intermethod comparability of patients' results. DESIGN AND METHODS: The reference system, combination of the reference method and the reference material, is used to produce a reference value for a given catalytic activity. Sets of methods are formed of methods exhibiting the same analytical specificity. Materials intended to be used as enzyme calibrators are experimentally checked for their commutability. RESULTS: The transfer of accuracy from the reference value to patients' results is dependent on methods (analytical specificity) and on materials (experimentally assessed commutability). The feasibility of this approach was demonstrated with materials of high level for several enzymes and for each of them for several routine methods. CONCLUSION: Expected advantages of this approach in clinical enzymology are presented.

Calibration↗
PubMed1998

Standardizations of clinical laboratory examinations in Japan.

In this paper we introduce Japanese activities concerning laboratory examinations by illustrating three major categories. The first is the contribution of JCCLS to ISO/TC212 clinical laboratory testing and in vitro diagnostic test systems, with NCCLS and CEN TC140. The second is the establishment and promotion of JLAC Classification and Coding for Clinical Laboratory Tests by The Japan Society of Clinical Pathology. The third is a clinical data exchange format between healthcare facilities using MML/MERIT-9 standard, started as a Ministry research project.

Clinical Laboratory Information Systems↗
PubMed1998

Pituitary adenylate cyclase-activating polypeptide causes Ca2+ release from ryanodine/caffeine stores through a novel pathway independent of both inositol trisphosphates and cyclic AMP in bovine adrenal medullary cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) causes both Ca2+ release and Ca2+ influx in bovine adrenal chromaffin cells. To elucidate the mechanisms of PACAP-induced Ca2+ release, we investigated expression of PACAP receptors and measured inositol trisphosphates (IP3), cyclic AMP, and the intracellular Ca2+ concentration in bovine adrenal medullary cells maintained in primary culture. RT-PCR analysis revealed that bovine adrenal medullary cells express the PACAP receptor hop, which is known to couple with both IP3 and cyclic AMP pathways. The two naturally occurring forms of PACAP, PACAP38 and PACAP27, both increased cyclic AMP and IP3, and PACAP38 was more potent than PACAP27 in both effects. Despite the effects of PACAP on IP3 production, the Ca2+ release induced by PA-CAP38 or by PACAP27 was unaffected by cinnarizine, a blocker of IP3 channels. The potencies of the peptides to cause Ca2+ release in the presence of cinnarizine were similar. The Ca2+ release induced by PACAP38 or by PACAP27 was strongly inhibited by ryanodine and caffeine. In the presence of ryanodine and caffeine, PACAP38 was more potent than PACAP27. PACAP-induced Ca2+ release was unaffected by Rp-adenosine 3',5'-cyclic monophosphothioate, an inhibitor of protein kinase A. Ca2+ release induced by bradykinin and angiotensin II was also inhibited by ryanodine and caffeine, but unaffected by cinnarizine. Although IP3 production stimulated by PACAP38 or bradykinin was abolished by the phospholipase C inhibitor, U-73122, Ca2+ release in response to the peptides was unaffected by U-73122. These results suggest that PACAP induces Ca2+ release from ryanodine/caffeine stores through a novel intracellular mechanism independent of both IP3 and cyclic AMP and that the mechanism may be the common pathway through which peptides release Ca2+ in adrenal chromaffin cells.

Adrenal Medulla↗
PubMed1998

Control of hemorrhage during AVM surgery--with special reference to treatment of dilated capillaries and arteries around the nidus.

Control of hemorrhage during AVM surgery is one of the key issues to prevent NPPB. Inadequate procedures for hemostasis of feeders and drainers, so-called dilated capillaries and arteries (moja moja blood vessels) that are located on the side facing the normal brain, and inappropriate surgical strategies for intraoperative hemorrhage from these blood vessels are frequently the main cause of the difficulty in achieving hemostatic control. We conclude that it is important to aggressively reduce the occurrence of intraoperative hemorrhage and prevent or minimize the dilatation of abnormal capillaries and arteries due to inappropriate surgical procedures on the basis of the fundamental surgical strategy, i.e., feeder-->nidus-->drainer. Adequately securing the length and adequate coagulation of hemorrhagic blood vessel, employing a skillful bipolar coagulator technique aimed at controlling intraluminal pressure and blood flow on the central side, are believed to be key factors in hemorrhage treatment.

Blood Loss, Surgical↗
PubMed1998

Mutual link among the approaches to clipping of basilar aneurysms.

The pterional approach for basilar aneurysm clipping, has become the most common approach among surgeons, since it was advocated by Yasargil in 1982. However, other approaches aiming at an adequate but less invasive surgery to meet conditions of peripheral blood vessels (including aneurysmal size, direction and perforating arteries and arteriosclerosis) and the direction of clip insertion have also been developed. The approaches will be recommended to be expanded according to situations of the actual intra-operative findings in the future. The mutual link among the approaches to clipping of basilar aneurysms was investigated.

Adult↗
PubMed1998

Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.

The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.

Administration, Oral↗
PubMed1998

Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum.

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K-ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K-ras. No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K-ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.

Adenoma↗
PubMed1998

Regulation of spontaneous rhythmic contractions in rat pregnant myometrium by corticotrophin-releasing factor.

To elucidate the role of corticotrophin-releasing factor (CRF) in the spontaneous rhythmic contractions of pregnant myometrium, isometric contractions of longitudinal myometrial preparations taken from Sprague-Dawley rats (18-21 days gestation) were measured. CRF (0.03-30 nM) significantly increased the amplitude (117 +/- 4% of control at 30 nM, mean +/- S.E.M.) and significantly decreased the frequency (74 +/- 5%) in a concentration-dependent manner. The area under the tension curve did not increase (89 +/- 8%). Such effects of CRF were not observed in preparations pretreated with the RP diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS, 10 microM), an inhibitor of protein kinase A. In preparations pretreated with indomethacin (1 microM), CRF caused little change in the amplitude but significantly decreased the frequency of the contractions. Intracellular cAMP levels in the preparations, measured by enzyme immunoassay, rose when CRF was applied at 30 nM. These results suggest that the slight positive inotropic action of CRF is due to activation of both cAMP and prostaglandin pathways, whereas the negative chronotropic action is due solely to the cAMP signalling pathway.

Animals↗
PubMed1998

Intrinsic transcriptional activation-inhibition domains of the polyomavirus enhancer binding protein 2/core binding factor alpha subunit revealed in the presence of the beta subunit.

A member of the polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF) is composed of PEBP2 alphaB1/AML1 (as the alpha subunit) and a beta subunit. It plays an essential role in definitive hematopoiesis and is frequently involved in the chromosomal abnormalities associated with leukemia. In the present study, we report functionally separable modular structures in PEBP2 alphaB1 for DNA binding and for transcriptional activation. DNA binding through the Runt domain of PEBP2 alphaB1 was hindered by the adjacent carboxy-terminal region, and this inhibition was relieved by interaction with the beta subunit. Utilizing a reporter assay system in which both the alpha and beta subunits are required to achieve strong transactivation, we uncovered the presence of transcriptional activation and inhibitory domains in PEBP2 alphaB1 that were only apparent in the presence of the beta subunit. The inhibitory domain keeps the full transactivation potential of full-length PEBP2 alphaB1 below its maximum potential. Fusion of the transactivation domain of PEBP2 alphaB1 to the yeast GAL4 DNA-binding domain conferred transactivation potential, but further addition of the inhibitory domain diminished the activity. These results suggest that the activity of the alpha subunit as a transcriptional activator is regulated intramolecularly as well as by the beta subunit. PEBP2 alphaB1 and the beta subunit were targeted to the nuclear matrix via signals distinct from the nuclear localization signal. Moreover, the transactivation domain by itself was capable of associating with the nuclear matrix, which implies the existence of a relationship between transactivation and nuclear matrix attachment.

Amino Acid Sequence↗
PubMed1998

Cytoplasmic sequestration of the polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor alpha (CBFalpha) subunit by the leukemia-related PEBP2/CBFbeta-SMMHC fusion protein inhibits PEBP2/CBF-mediated transactivation.

The polyomavirus enhancer binding protein 2 (PEBP2)/core binding factor (CBF) is a transcription factor composed of two subunits, alpha and beta. The gene encoding the beta subunit is disrupted by inv(16), resulting in the formation of a chimeric protein, beta-SMMHC, which is associated with acute myelogenous leukemia. To understand the effect of beta-SMMHC on PEBP2-mediated transactivation, we used a luciferase assay system in which contribution of both the alpha and beta subunits was absolutely required to activate transcription. Using this system, we found that the minimal region of the beta subunit required for transactivation resides between amino acid 1 and 135, which is known to dimerize with the alpha subunit. In contrast, beta-SMMHC, despite having this minimal region for dimerization and transactivation, failed to support transcription with the alpha subunit. Furthermore beta-SMMHC blocked the synergistic transcription achieved by PEBP2 and CCAAT/enhancer binding protein alpha. By using a construct in which the PEBP2 alpha subunit was fused to the glucocorticoid receptor ligand binding domain, we demonstrated that coexpressed beta-SMMHC tightly sequestered the alpha subunit in the cytoplasm and blocked dexamethasone-dependent nuclear translocation of the alpha subunit. Thus, the result suggess that beta-SMMHC inhibits PEBP2-mediated transcription via cytoplasmic sequestration of the alpha subunit. Lastly proliferation of ME-1 cells that harbor inv(16) was blocked by an antisense oligonucleotide complementary to the junction of the chimeric mRNA, suggesting that beta-SMMHC contributes to leukemogenesis by blocking the differentiation of myeloid cells.

Animals↗
PubMed1998

Gut hypertrophy in response to the ratios of casein and whey protein in milk formulas in artificially reared rat pups.

To elucidate the mechanism of gut hypertrophy observed in rats artificially reared (AR) on milk formulas, the effects of four refined formulas with different ratios of casein (C) and whey protein (W), CW 2:8, CW 4:6, CW 6:4 and CW 8:2, on the gut growth of AR rats were examined. Four groups of pups were infused with each formula through an intragastric cannula from age 5 to 15 days. Each of the four milk formulas showed a different character in the stomach, such as no curd, very soft curd, soft curd and hard curd, in response to an increasing ratio of C:W. There were no significant differences in body weight gain among the AR groups and mother-reared (MR) controls. The stomach growth, in weight, of AR rats increased in response to the increasing ratios of C:W. In comparison with MR controls, hypertrophy of the stomach of AR rats appeared within the formulas with higher proportions of casein than whey protein (CW 6:4 and CW 8:2), but not those with lower proportions (CW 2:8 and CW 4:6). The growth of the small intestine was also related to the increasing ratio of C:W in the formulas. A similar pattern of hypertrophy in the hindgut was seen in AR rats. There was no association between hypertrophy of the gut in AR rats and plasma triiodothyronine. The present results clearly demonstrated that the gut growth of AR rat pups was directly influenced by the diet but not by AR per se, and that hard casein-curd in the stomach might be one cause of gut hypertrophy.

Aging↗
PubMed1998

Butyrylcholinesterase genes in individuals with abnormal inhibition numbers and with trace activity: one common mutation and two novel silent genes.

A random population was screened for abnormal dibucaine and fluoride numbers (DN & FN) to find some common mutations in butyrylcholinesterase (BCHE) gene. Of 2375 unrelated individuals, 10 were found to have low DN and FN and were selected for further studies. DNA analysis of these hypocholinesterasemics revealed that seven patients were heterozygous for missense mutation at codon 330 (TTA to ATA; BCHE*330I). The frequency of BCHE*330I mutation was calculated to be at least 0.29% among the Japanese. On the other hand, two novel mutations were found in three families and two individuals including probands whose enzyme activity was very low (silent gene). Polymerase chain reaction and single stranded conformation polymorphism (PCR-SSCP) and restriction fragment length polymorphism (PCR-RFLP) were used for identification of the common and known mutation types such as BCHE*250P (ACT to CCT), BCHE*365R (GGA to CGA), and BCHE*539T (GCA to ACA; K-polymorphism), whereas PCR-SSCP was used in combination with direct DNA sequencing for new mutations like BCHE*446V (TTT to GTT) and BCHE*451X (GAA to TAA).

Butyrylcholinesterase↗