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T Yagi

Publications and source records attributed to T Yagi.

At least 55 records · Page 3Linked to original sources
PubMed2001

The cadherin-related neuronal receptor family: a novel diversified cadherin family at the synapse.

The cadherin-related neuronal receptor (CNR) family has been identified as a receptor family that cooperates with Fyn, a member of the Src family of tyrosine kinases. The CNR family is composed of 14 members in mice and 15 members in humans. The mRNAs of CNRs are highly expressed in the brain and CNR1 protein is localized at synaptic junctions. Hence CNR family proteins are synaptic cadherins. The unique structure of CNR family cDNAs, which is characterized by complete DNA sequence identity among their 3'-termini including a part of the coding region, prompted us to investigate the genomic organization of this family. The genomic organization of CNRs is divided into 'variable' and 'constant' region exons, analogous to immunoglobulin and T cell receptor gene clusters. This organization raised the possibility that the CNR gene cluster may undergo somatic DNA rearrangement or trans-splicing and produce diversified gene products. Although it is not yet clear that the CNR gene cluster in the neuronal genomic DNA is somatically changed, a recent study suggested the occurrence of trans-transcripts and accumulation of somatic mutations in CNR transcripts (Genes Cells 6 (2001) 151). These results suggested that the proteins from the CNR gene cluster are enormously diversified by unique mechanisms. The localization of CNR1 protein at the synapse and the diversity of CNRs led us to the hypothesis that gene regulation of the CNR family dictates the formation and reorganization of synaptic connections in the nervous system.

Animals↗
PubMed2001

Detection of apoptotic change in the lipopolysaccharide (LPS)-treated cochlea of guinea pigs.

This study was undertaken to examine, electrophysiologically and immunohistochemically, the effect of endotoxin on the guinea pig cochlea. A bacterial endotoxin (lipopolysaccharide, LPS, 5 mg/ml, 0.2 ml) was injected into the middle ear trans-tympanically. The electrocochleograms were continuously recorded from before to 48 h after the injection with an electrode inserted into the facial canal. Then, the animals were sacrificed by intracardiac perfusion of a fixative, temporal bones were removed and immunohistochemically stained for single-stranded DNA (ssDNA) and caspase 3 (CPP32). ssDNA was detected at 48 h in the stria vascularis and spiral ligament. CPP32 was observed in the stria vascularis, the spiral ligament and the organ of Corti. The threshold of the compound action potential increased significantly at 48 h in the LPS group. These results suggest that the activation of CPP32 and fragmentation of DNA are involved in the dysfunction of the cochlea observed under inflammatory conditions.

Action Potentials↗
PubMed2001

The stability of human eye orientation during visual fixation and imagined fixation in three dimensions.

OBJECTIVE: The stabilization of eye movements during voluntary fixation is believed to depend upon the visual feed back, since gaze becomes less stable in the darkness. The temporal variability of human eye orientation in both the horizontal and vertical direction is typically no more than a few minutes of arc. Ocular stability in terms of torsion has, however, been less understood. METHODS: In this study, the stability of gaze in the three dimensions (horizontal, vertical, and torsional) was investigated using a video image analysis system. In ten healthy subjects, eye movements were recorded after fixating the eye on a target in the light and also in the dark (imaginary target). The standard deviations of the eye movements in the three dimensions were calculated during fixation. RESULTS: In the light, the horizontal and vertical eye movements exhibited an alternating sequence of a slow drift and resetting microsaccades, as previously reported. The torsional eye movements, however, showed no such drifts and resetting. In the dark, the horizontal and vertical eye movements exhibited about 2-3 times larger value of the standard deviation than that in the light. In contrast to this, the difference in the standard deviation between the light and dark was not so prominent in case of the torsional eye movement as compared to those of horizontal and vertical. CONCLUSION: These results support the idea that information from the peripheral retina does not significantly influence the feed back system for fixating the target in the light.

Adult↗
PubMed2001

Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage.

OBJECTIVES: We investigated immunoreactive von Willebrand factor (vWF), a platelet adhesion molecule, in the endocardial endothelium and its relationship to thrombogenesis in the human atrial appendage. BACKGROUND: Intra-atrial thrombogenesis is generally thought to be induced by blood stasis in the atrial appendage involved with atrial fibrillation (AF). Little attention has been paid to alterations of the endocardial endothelium on which the thrombus develops. METHODS: Atrial appendage tissue was obtained at heart surgery or at autopsy from AF and non-AF cardiac patients and from noncardiac patients. Immunohistochemistry for endothelial cell markers including vWF, CD31, CD34 and endothelial nitric oxide synthase (eNOS) and platelet glycoprotein Ib/IX or IIb/IIIa was performed and semiquantitatively graded. RESULTS: In contrast to the apparent immunostaining for CD31, CD34 and eNOS, only focal or little immunoreactive vWF was seen in the endocardium of noncardiac patients. Immunoreactive vWF in the endocardial endothelium was increased in most cardiac patients, particularly in the left, but not in the right, atrial appendage of patients with mitral valvular disease, irrespective of whether AF was present. Platelet adhesion/thrombus formation in the endocardium was found in limited sites in which the overlying endothelium was deficient in eNOS and CD34. When warfarin-treated cases were excluded, there was a significant correlation between the immunohistochemical grade for vWF and the degree of platelet adhesion/thrombus formation in the endocardium. CONCLUSIONS: Immunoreactive vWF in the endocardial endothelium was increased in overloaded human atrial appendage, which may be a local predisposing factor for intraatrial thrombogenesis.

Adult↗
PubMed2001

Detection of the exogenous hGDNF in gerbils under the treatment with AxCAhGDNF adenoviral vector.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors and promotes survival in many populations of cells. We examined the neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia [Brain Res. 885 (2000) 273-282]. Gerbils received AxCAhGDNF or an adenoviral vector encoding bacterial beta-galactosidase gene (AxCALacZ) through administration into the lateral ventricle. Two days later, occlusion of the common carotid arteries for 5 min bilaterally using aneurysm clips produced transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by the adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA-1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. In this paper, we describe in detail the techniques for the detection of the exogenous gene of hGDNF under the treatment with AxCAhGDNF.

Adenoviridae↗
PubMed2001

NADH dehydrogenases: from basic science to biomedicine.

This review article is concerned with two on-going research projects in our laboratory, both of which are related to the study of the NADH dehydrogenase enzyme complexes in the respiratory chain. The goal of the first project is to decipher the structure and mechanism of action of the proton-translocating NADH-quinone oxidoreductase (NDH-1) from two bacteria, Paracoccus denitrificans and Thermus thermophilus HB-8. These microorganisms are of particular interest because of the close resemblance of the former (P. denitrificans) to a mammalian mitochondria, and because of the thermostability of the enzymes of the latter (T. thermophilus). The NDH-1 enzyme complex of these and other bacteria is composed of 13 to 14 unlike subunits and has a relatively simple structure relative to the mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I), which is composed of at least 42 different subunits. Therefore, the bacterial NDH-I is believed to be a useful model for studying the mitochondrial complex I, which is understood to have the most intricate structure of all the membrane-associated enzyme complexes. Recently, the study of the NADH dehydrogenase complex has taken on new urgency as a result of reports that complex I defects are involved in many human mitochondrial diseases. Thus the goal of the second project is to develop possible gene therapies for mitochondrial diseases caused by complex I defects. This project involves attempting to repair complex I defects in the mammalian system using Saccharomyces cerevisiae NDI1 genes, which code for the internal, rotenone-insensitive NADH-quinone oxidoreductase. In this review, we will discuss our progress and the data generated by these two projects to date. In addition, background information and the significance of various approaches employed to pursue these research objectives will be described.

Animals↗
PubMed2001

Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon-specific cell adhesion molecule.

Telencephalin (TLCN) is a cell adhesion molecule selectively expressed in the telencephalon of the mammalian brain. The mutant mice lacking TLCN had no detectable abnormalities in their neural development and synaptic structures. Ablation of TLCN increased the hippocampal long-term potentiation and its saturation level. The TLCN mutation selectively enhanced the performance of the radial maze and water-finding tasks, learning tasks with appetitive reinforcers, but not the contextual fear conditioning and Morris water maze tasks with aversive stimuli for conditioning. Furthermore, the TLCN mutant mice showed an increase of prepulse inhibition of the acoustic startle response. These results suggest that TLCN is a determinant of the dynamic range of synaptic plasticity and plays roles in reward-motivated learning and memory and sensorimotor gating.

Animals↗
PubMed2001

Somatic mutations of synaptic cadherin (CNR family) transcripts in the nervous system.

BACKGROUND: Cadherin-related neuronal receptor (CNR) family genes have been identified in the nervous system by screening molecules bound to Fyn-tyrosine kinase. The CNR family is comprised of diverse synaptic cadherins. The genomic organization of the CNR genes, composed of variable and constant regions, is similar to that of the immunoglobulin gene cluster. The nervous system is characterized by the acquisition of diverse function. This feature is similar to the immune system. In the immune system, the generation and selection of immunoglobulin gene mutants is the underlying basis for acquired immunity. We therefore examined somatic regulation of the CNR family genes in the nervous system to determine whether a similar mechanism controls nervous system development. RESULTS: We first demonstrated that approximately 10% of the CNR3 transcripts were trans-transcripts between the variable and constant exons at the adult stage. Furthermore, somatic mutations of CNR3 transcripts accumulated during brain development, with a marked bias for A-to-G and U-to-C transitions. Approximately 70% of the CNR3 transcripts exhibited a mutation characterized by the addition of a CU-repeat; these transcripts contained seven continuous CU-repeats in the 3' untranslated region at the adult stage, whereas the CNR genomic DNA contained six continuous CU-repeats. Interestingly, a high rate of replacement mutations was detected in the first cadherin domain that functions in acquisition of specificity for cell adhesion in cadherins, while in the other regions the occurrence of silent mutations increased during development. CONCLUSION: The present report is the first description of the generation and possible selection of somatic mutations of synaptic cadherin transcripts. The somatic alterations of CNR family transcripts and their synaptic localization have interesting implications for the molecular basis underlying the establishment of somatic rearrangement of neuronal networks.

Amino Acid Sequence↗
PubMed2001

Caspase inhibition reduces apoptotic death of cryopreserved porcine hepatocytes.

Cryopreserved porcine hepatocytes are a ready source of metabolic function for use in a bioartificial liver (BAL). However, cryopreservation is associated with a loss of hepatocyte viability. The mechanism of cell death during cryopreservation is incompletely understood, but may involve apoptosis through caspase activation. This study evaluates the cytoprotective effect of a global caspase inhibitor, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (ZVAD-fmk) during cryopreservation of porcine hepatocytes. Freshly isolated porcine hepatocytes (viability, 97.4% +/- 0.9%) were cryopreserved in 60 micromol/L ZVAD-fmk (+ZVAD group) or without ZVAD-fmk (-ZVAD group) for 24 to 72 hours. Apoptotic and necrotic death were both observed after thawing and after 24 hours of culture. Caspase 3-like activity was significantly reduced by ZVAD-fmk, and was associated with improved viability and reduced apoptotic death of porcine hepatocytes after cryopreservation. Mitochondrial membrane potential (MMP) was increased in cultures of porcine hepatocytes that were cryopreserved in ZVAD-fmk. These results demonstrate the following: 1) Caspase 3-like protease activation and apoptosis occurs in porcine hepatocytes during cryopreservation; and 2) mitochondrial injury in this process is reduced by caspase inhibition.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Effects of prostaglandin E(1) on the efficacy of xenogeneic extracorporeal pig liver perfusion in a canine model of acute liver failure.

Xenogeneic extracorporeal liver perfusion (ECLP) has the potential to become an important tool in the management of patients with severe liver failure. We previously showed that xenogeneic pig liver perfusion may be prolonged for up to 9 hours by the administration of prostaglandin E(1) (PGE(1)). In this study, we used a canine model of acute liver failure to evaluate the effects of PGE(1) on the efficacy of ECLP as a liver-assist device. Liver failure was surgically induced in 12 beagle dogs, with a control group (group 1, n = 4) not connected to the ECLP circuit. Direct cross-circulation between the dogs and the ECLP circuit using a pig liver was performed without (group 2, n = 4) or with (group 3, n = 4) continuous administration of PGE(1) through the portal vein of the pig liver. The duration of cross-circulation in group 3 (9.4 +/- 1.2 hours) was significantly longer than in group 2 (4.3 +/- 1.0 hours). In addition, elevation of blood ammonia, total bile acid, and hyaluronic acid levels was less marked in group 3 compared with the other 2 groups. The ratio of branched-chain amino acids to aromatic amino acids was also improved in group 3. The mean survival time in group 3 (26.6 +/- 0.4 hours) was significantly longer than in group 1 (15.5 +/- 1.3 hours) or group 2 (17.1 +/- 2.9 hours). Continuous administration of PGE(1) to xenogeneic ECLP resulted in a significant improvement in both liver function and survival time of dogs with surgically induced liver failure.

Alprostadil↗
PubMed2001

Secondary sclerosing cholangitis and portal hypertension after O157 enterocolitis: Extremely rare complications of hemolytic uremic syndrome.

The authors experienced an extremely rare case of secondary sclerosing cholangitis and portal hypertension developed as late complications of hemolytic uremic syndrome (HUS) owing to Escherichia coli O157:H7 in a 2-year-old boy. HUS after E coli O157 infection is the most frequent cause of acute renal failure in childhood and occasionally is accompanied by extrarenal complications such as encephalopathy, cardiomyopathy, ischemic colitis, and pancreatitis. Rarely, late colonic stenosis may develop secondary to the ischemic damage. Sclerosing cholangitis and subsequent cirrhosis with portal hypertension are very uncommon as late complications of HUS. To our knowledge, such a case has not been previously reported in the literature. J Pediatr Surg 36:1838-1840.

Child, Preschool↗
PubMed2001

Three-dimensional analysis of eye movements during off vertical axis rotation in patients with unilateral labyrinthine loss.

3D analysis of eye movements during off vertical axis rotation (OVAR) was carried out in seven subjects with unilateral labyrinthine loss (ULL). The modulation component (MOC) of these patients was not different from that of normal subjects. However, the horizontal MOC was significantly smaller when the rotation was directed towards the diseased side as opposed to the healthy side. With rotation to the diseased side, most subjects exhibited a horizontal bias component (BIC) to the opposite side as compared with the diseased side in normal subjects. The vertical and torsional BICs were also influenced to some extent by lack of input from the unilateral labyrinth. These results indicate that a unilateral otolith organ plays a major role in the production of the horizontal BIC contralateral to the direction of rotation, which is strongly related to the velocity storage mechanism in the central nervous system. In addition, the unilateral otolith organ exerts some influence on the generation of the horizontal MOC and also the BIC of vertical and torsional eye movements.

Acceleration↗
PubMed2001

Effects of theophylline withdrawal in well-controlled asthmatics treated with inhaled corticosteroid.

We examined effects of theophylline withdrawal in 17 adult asthmatics whose symptoms were well controlled under a treatment of a combination of theophylline and inhaled beclomethasone dipropionate (iBDP). We measured daily symptoms, daily peak flow values, spirometry, peripheral blood eosinophil count (EOS), and serum eosinophil cationic protein (sECP) at intervals of 1-3 weeks for 3 months after theophylline withdrawal. Twelve patients experienced exacerbation of asthma (exacerbation group), whereas the remaining 5 patients exhibited no symptoms (stationary group). In the exacerbation group, forced expiratory volume in 1 sec (FEV1) and percent vital capacity (% VC) gradually decreased until exacerbation of asthma, and the extent of these decreases within the first week after the withdrawal was greater compared with that at later than the third week. V25/HT decreased in both the exacerbation and stationary groups. In particular, the extent of the velocity of expiratory flow at 25% of the vital capacity/height (V25/HT) decrease in the exacerbation group was much greater than that of FEV1 or % VC in this group. Neither EOS nor sECP changed significantly during the clinical course in any patient. The rapid decrease in FEV1 and % VC after the withdrawal suggests that under treatment with iBDP, theophylline causes direct bronchodilating effects on smooth muscle, rather than anti-inflammatory effects. These results also suggest the importance of theophylline on peripheral as well as central airways.

Adult↗
PubMed2001

Transgenic and gene "knockout" models in alcohol research.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Paula L. Hoffman and Takeshi Yagi. The presentations were (1) cAMP signaling in ethanol sensitivity and tolerance, by Boris Tabakoff; (2) Synaptic signaling pathways of Fyn-tyrosine kinase, by Takeshi Yagi; (3) Ethanol drinking and sensitization in dopaminergic and serotonergic receptor knockouts, by Tamara J. Phillips; (4) ICAM-1 is involved in early alcohol-induced liver injury in the mouse given enteral alcohol, by Hiroshi Kono; and (5) Strategies for targeted and regulated knockouts, by Robert O. Messing and Doo-Sup Choi.

Adenylyl Cyclases↗
PubMed2001

Successfully resected hepatoblastoma in a young adult with chronic hepatitis B: report of a case.

Hepatoblastoma usually occurs in children, but a few cases have also been reported in adults. We report the unusual case of hepatoblastoma in an 18-year-old adult with chronic hepatitis B. He visited a local hospital with right upper abdominal pain. Abdominal ultrasound showed a large mass in the right lobe of his liver. He was referred to our hospital and admitted for further examination. At admission, liver function tests gave slightly elevated results (aspartate aminotransferase (AST) 103 IU/l, alanine aminotransferase (ALT) 63 IU/l). A test for hepatitis virus revealed that he was a hepatitis B surface antigen (HBsAg) carrier and had experienced seroconversion. His alpha-fetoprotein (AFP) was elevated to 1 548 000 IU/ml. Abdominal ultrasound showed a 109 x 96 x 80-mm mass with mosaic pattern in the right lobe of the liver and right portal vein thrombus. Abdominal computed tomography (CT) demonstrated a large low-density mass occupying the right lobe, with some high-density parts that showed calcification. From these results, we diagnosed hepatoblastoma in a young adult. A right lobectomy was performed. Pathological examination showed a highly differentiated hepatoblastoma. Adjuvant chemotherapy was performed with cisplatin and pirarubicin. The patient has been well and free of recurrence for 12 months, and his AFP level remains almost normal.

Adolescent↗