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Biomedical subjects

Y Irie

Publications and source records attributed to Y Irie.

At least 19 recordsLinked to original sources
PubMed2000

Early and late chemokine production correlates with cellular recruitment in cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of late mortality in heart transplant recipients. Activated T lymphocytes and macrophages infiltrate the donor heart before vascular intimal thickening develops, but the specific mediators of mononuclear cell recruitment leading to CAV are unknown. Therefore, we sought to define the relationship between chemokine gene expression and production, T lymphocyte and macrophage recruitment, and intimal thickening in a murine model of CAV. METHODS: B10.A or B10.BR strain hearts were transplanted heterotopically into B10.BR mice. Recipients were killed at 1, 4, 7, 14, and 30 days. Donor hearts were assayed for chemokine gene expression with ribonuclease protection and for protein with ELISA. Intragraft cellular infiltration was defined immunohistochemically. Intimal thickening was quantitated morphometrically. RESULTS: Early and late patterns of intragraft chemokine expression associated with distinct cellular infiltration were identified. First, transient MIP-2 and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage infiltration. MCP-1/JE production and macrophage infiltration was greater in allografts than isografts. Second, allografts demonstrated sustained lymphotactin, RANTES, and IP-10 expression, beginning at day 4, correlating with persistent macrophage and T lymphocyte infiltration. Intimal thickening became evident at 14 days. Isografts did not display the late pattern of sustained chemokine gene expression, cellular infiltration, or intimal thickening. CONCLUSIONS: Transient, early MIP-2, and MCP-1/JE production in isografts and allografts correlated with neutrophil and macrophage recruitment, and is likely related to ischemia-reperfusion. In allografts, the delayed induction of chemokines specific for macrophages and T lymphocytes correlated with mononuclear cell infiltration and preceded intimal thickening. This study thus demonstrates a dual pattern of chemokine induction correlating with intragraft mononuclear cell recruitment, associated with ischemia-reperfusion and CAV development. Chemokine-directed interventions may interfere with leukocyte trafficking and inhibit CAV development.

Animals↗
PubMed2000

Central leptin suppresses splenic lymphocyte functions through activation of the corticotropin-releasing hormone-sympathetic nervous system.

Leptin is one of the key afferent signals that regulate food intake and energy expenditure by acting on specific receptors in the hypothalamus. Recently, leptin was reported to activate the peripheral immune system by acting directly on lymphocytes. To elucidate the brain-mediated participation of leptin in the modulation of peripheral immune functions, we examined the effects of intracerebroventricular (icv) injection of murine recombinant leptin on the proliferative response to Concanavalin A (ConA response) of splenic lymphocytes in rats. The ConA response of splenic lymphocytes was markedly reduced 30 min after icv injection of leptin. The suppressive effect of leptin was abolished completely either by surgical severing of the splenic nerves or by icv injection of an antibody against corticotropin-releasing hormone (CRH), but only partially by an anti-urocortin antibody. Icv injection of CRH and urocortin also suppressed the ConA response of splenic lymphocytes, and the effect of urocortin was prevented by the anti-CRH antibody, while that of CRH was not prevented by the anti-urocortin antibody. These results suggest that leptin suppresses peripheral lymphocyte functions, in contrast to the direct activating effects, indirectly through the activation of the CRH (urocortin)-sympathetic nervous system.

Animals↗
PubMed2000

Molecular cloning and characterization of Amida, a novel protein which interacts with a neuron-specific immediate early gene product arc, contains novel nuclear localization signals, and causes cell death in cultured cells.

Amida was isolated by the yeast two-hybrid system as a novel protein which associated with Arc, a non-transcriptional immediate early gene specific to the brain. Amida was confirmed to be associated with Arc in vitro and in vivo. Amida shows no homology to known proteins. Amida is ubiquitously expressed, although it is abundant in the brain. A transfection study revealed that Amida was localized in the nucleus and after 72 h the transfected cells underwent apoptosis. Furthermore, we found two nuclear localization signals and a domain needed for interacting with Arc was encompassed by two nuclear localization signals. Co-transfection experiment with Amida and Arc suggested that Amida transported Arc into the nucleus and negatively regulated Amida-induced cell death. These results indicate that Arc together with Amida may modulate cell death in the brain.

Amino Acid Sequence↗
PubMed2000

Characterization of newly developed SSLP markers for the rat.

We have isolated more than 12,000 clones containing microsatellite sequences, mainly consisting of (CA)n dinucleotide repeats, using genomic DNA from the BN strain of laboratory rat. Data trimming yielded 9636 non-redundant microsatellite sequences, and we designed oligonucleotide primer pairs to amplify 8189 of these. PCR amplification of genomic DNA from five different rat strains yielded clean amplification products for 7040 of these simple-sequence-length-polymorphism (SSLP) markers; 3019 markers had been mapped previously by radiation hybrid (RH) mapping methods (Nat Genet 22, 27-36, 1998). Here we report the characterization of these newly developed microsatellite markers as well as the release of previously unpublished microsatellite marker information. In addition, we have constructed a genome-wide linkage map of 515 markers, 204 of which are derived from our new collection, by genotyping 48 F2 progeny of (OLETFxBN)F2 crosses. This map spans 1830.9 cM, with an average spacing of 3.56 cM. Together with our ongoing project of preparing a whole-genome radiation hybrid map for the rat, this dense linkage map should provide a valuable resource for genetic studies in this model species.

Animals↗
PubMed2000

Inhibition by naloxone of promoter activity of the neurofilament gene in SK-N-SH cells.

Chronic administration of morphine is known to decrease the levels of neurofilaments (NFs) in the ventral tegmental area. We ligated a promoter region of the mouse 68-KDa neurofilament (NF-68) gene to the pGL3-enhancer vector containing a luciferase gene, transfected it into SK-N-SH cells and then analyzed transcriptional activity in the cells treated with agonists or antagonists of opiate receptors. The activity of the NF-68 promoter was suppressed by naloxone about 55% at 10(-5) M and 30% at 10(-7) M at 48 h, but suppressed not by morphine. Naltrexone at 10(-5) M suppressed the promoter activity about 20%, but levallorphan, DAMGO, DPDPE and U50488 did not. The inhibition by naloxone was dose-dependent and not reversed by morphine. The inhibitory effect of naloxone was not observed in N18TG-2 cells and PC12 cells. Experiments with various deletion mutants revealed that a region responsible for naloxone suppression spans from -328 to -101 in the gene. These results suggest that naloxone has the ability to suppress transcriptional activity in some neurons.

Animals↗
PubMed2000

[Three-channeled aortic dissection: selection of surgery based on the images].

Three patients with 3-channeled dissection were operated upon. Images of the dissection were enlargement of the false lumens, compression of the true lumen by enlarged false lumens and visceral arteries of false lumen origin. These prevent the use of cardiopulmonary bypass (CPB) and cause malperfusion of the viscera. Three-channeled dissecion is easy to rupture for its peculiar anatomy and total repair of the thoraco-abdominal aorta is mandatory. Fenestration brings functional recovery of malperfused viscera and enables the patients to be placed on CPB for total repair. Two patients underwent infrarenal and descending aorta fenestration followed by the total repair of thoraco-abdominal aorta successfully. A third patient has been placed on the strict CT follow-up following the infrarenal fenestration.

Adult↗
PubMed1999

Up-regulation of uncoupling protein 3 by thyroid hormone, peroxisome proliferator-activated receptor ligands and 9-cis retinoic acid in L6 myotubes.

Uncoupling protein 3 (UCP3), expressed abundantly in the skeletal muscle, is one of the carrier proteins dissipating the transmitochondrial electrochemical gradient as heat, and thereby has been implicated in the regulation of energy metabolism. We have investigated UCP3 mRNA expression in the widely used L6 myocyte cell line by Northern blot analysis. UCP3 mRNA was not detected in L6 myoblasts, but appeared after their differentiation to myotubes. The UCP3 mRNA level was increased when L6 myotubes were treated with increasing concentrations of triiodothyronine (T3), oleic acid, alpha-bromopalmitate and carbacyclin, a non-selective ligand of peroxisome proliferator-activated receptors (PPARs), whereas it was not influenced when treated with selective ligands of PPARalpha (WY 14¿ omitted¿643) and PPARgamma (troglitazone). A ligand of retinoid X receptor (RXR), 9-cis retinoic acid, was also effective by itself and in combination with carbacyclin in stimulating UCP3 mRNA expression. The mRNA analysis of individual PPAR isoforms revealed that L6 cell expressed a significant level of PPARdelta but undetectable levels of PPARalpha and PPARgamma. These results suggest that UCP3 expression in myocytes is differentiation-dependent and regulated by the T3 receptor, RXR and PPARdelta.

Alitretinoin↗
PubMed1999

Induction of uncoupling protein (UCP) 2 in primary cultured hepatocytes.

Uncoupling protein 2 (UCP2) mRNA expression and function was examined in rat primary cultured hepatocytes. UCP2 mRNA was not expressed in freshly isolated hepatocytes, but appeared during a 24-144 h primary culture period. Isolated mitochondria from 144 h cultured hepatocytes showed a lower oxygen consumption rate in the presence of succinate and ADP. However, the ratio of the oxygen consumption rate when media contained succinate alone to that with succinate and ADP was increased by 166% versus control mitochondria. Moreover, the mitochondrial potential in the presence of succinate was decreased by 60%, indicating the potential role of UCP2 in hepatocyte mitochondria as an active uncoupler.

Animals↗
PubMed1999

Arcadlin is a neural activity-regulated cadherin involved in long term potentiation.

Neural activity results in long term changes that underlie synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartate-dependent synaptic activity in long term potentiation. The extracellular domain of Arcadlin is most homologous to protocadherin-8; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses and shows a homophilic binding activity in a Ca2+-dependent manner. Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential amplitude and blocks long term potentiation in hippocampal slices. Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying long term memory.

Amino Acid Sequence↗
PubMed1999

Genetic dissection of "OLETF," a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF.

To identify genetic determinants relevant to non-insulin-dependent diabetes mellitus (NIDDM), we performed a genome-wide analysis for quantitative trait loci (QTLs) using 359 backcross progeny of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF strain is a well-studied animal model of obese NIDDM, with features of hyperinsulinemia, hyperglycemia, insulin resistance, and abundant abdominal fat. Our extensive genomic scanning with 218 markers revealed nine significant QTLs, including a strong determinant of obesity on chromosome 1 (Dmo1: LOD = 13.99, for body weight). Two highly significant QTLs for glucose homeostasis were found, one on chromosome 1 (Dmo4 LOD = 7.16, for postprandial glucose level) and the other on chromosome X (Dmo11/Odb1: LOD = 7.81, for postprandial glucose level). These data are comparable to results of our previous studies of the OLETF rat.

Adipose Tissue↗
PubMed1999

Immortal brown adipocytes from p53-knockout mice: differentiation and expression of uncoupling proteins.

Brown adipose tissue (BAT) is the specific site for metabolic heat production in mammals. To establish a novel immortal brown adipocyte cell line, the stromal-vascular fraction containing preadipocytes was obtained from interscapular BAT of mice deficient of a tumor-suppressor gene p53. The p53-deficient cells, tentatively named as HB2 cells, could be cultured in vitro after repeated passages and differentiated into adipocytes in the presence of insulin, T3 and/or troglitazone, expressing some adipocyte-specific genes and accumulating intracellular lipid droplets. The mRNA level of uncoupling protein 1 (UCP1), a mitochondrial protein specifically present in brown adipocytes, was undetectable in HB2 preadipocytes, but increased after adipose differentiation. In HB2 adipocytes, UCP1 mRNA expression was markedly activated after stimulation of the beta-adrenergic receptor pathway. The mRNA of UCP2 and UCP3, recently cloned isoforms of UCP1, were also detected in HB2 adipocytes, but their levels were not influenced by adrenergic stimulation. Thus HB2 cells seem useful for in vitro studies of BAT and UCP functions.

Adipocytes↗
PubMed1999

Localization of mouse type 2 Alu sequence in schistosomes.

Localization of the type 2 Alu sequence (B2), a highly repetitive DNA sequence in the mouse genome, was examined by in situ polymerase chain reaction (in situ PCR) in schistosomes. The signals to the B2 sequence were detected in the cytoplasm of the tegumental membrane and in the nuclei of the mesenchymal, testicular, ovarian and vitelline cells of 8-week Schistosoma japonicum. In contrast, it was difficult to detect any signals of this sequence in 8-week S. mansoni, whereas in 24-week male S. mansoni the signals were observed in the cytoplasm of the tegumental tubercles and in the nuclei of the mesenchymal and testicular cells. On the other hand, in 24-week female S. mansoni the signals were found in the nuclei of the mesenchymal, ovarian and vitelline cells but not found in the tegument. On the contrary, no hybridization band of the B2 sequence was detected in the amplified DNA of 3-week schistosomula of either species. These observations proved that the host DNA sequences existed in restricted schistosome cells and were accumulated in the schistosome body during their development.

Alu Elements↗
PubMed1999

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.

Animals↗
PubMed1999

Superinfection of TT virus and hepatitis C virus among chronic haemodialysis patients.

BACKGROUND: The TT virus (TTV), a new DNA virus found in Japan from a patient with post-transfusion hepatitis non-A-non-G, is frequently positive in the sera of patients with liver disease. It is not established whether this virus causes liver damage. We studied the frequency of superinfection of this virus and hepatitis C virus (HCV) known to be endemic among haemodialysis patients, and the possible deleterious effect of TTV on HCV-induced chronic liver disease. METHODS: We used primers from a conservative region in the TTV genome (Okamoto, 1998) to detect TTV. Sera from 163 dialysis patients positive for anti-HCV and 77 dialysis patients negative for anti-HCV (control) were tested. RESULTS: TT Virus positivity was 35% among HCV antibody (anti-HCV)-positive patients and 45.4% among anti-HCV-negative patients. TT Virus positivity was unrelated to the length of haemodialysis or amounts of blood the patients had received in the past. More anti-HCV-positive patients had a history of transfusion, but TTV positivity was not as closely associated with transfusion as anti-HCV positivity. The severity of chronic liver disease was estimated from peak serum alanine aminotransferase levels in the preceding 6 months. Among anti-HCV positives, TTV-positive patients tended to have less active disease; at least there was no indication that TTV superinfection aggravated chronic hepatitic C in long-term dialysis patients. Four of 35 anti-HCV-negative, TTV-positive patients had chronic active liver disease, while none of the anti-HCV-negative and TTV-negative patients did. CONCLUSIONS: TT Virus infection is prevalent among haemodialysis patients. Its transmission occurs not only by blood transfusion, but also by non-parenteral infection. Superinfection of TTV does not exert deleterious effects on the liver disease induced by HCV. However, it may cause chronic hepatitis in a limited number of patients, but remains dormant most of the time. Triple infection, HCV and TTV plus HBV or HGV (one case each), did not cause severe liver disease.

Antibodies, Viral↗
PubMed1999

[Trial of oral administration of Bifidobacterium breve for the prevention of rotavirus infections].

It was investigated that Bifidobacterium breve YIT4064 (B. breve YIT4064), Which had augmented IgA production and prevented rotavirus-induced diarrhea in mice, prevented rotavirus infection in infants. The effect of B. breve YIT4064 was evaluated in ten infants from an infants home who received 50 mg of the bacterium every day for 28 days (the B. breve group). Nine infants did not receive this (the control group). Though rotavirus shedding in the control group was detected from 2 (a total of 5 stool samples) of 9 infants (a total of 112 stool samples), it was not detected in any infants (a total of 133 stool samples) in the B. breve group during the administration period. From day 8 to day 14 of the test, rotavirus shedding was detected from 4 of 32 stool samples in the control group, but was not detected at all from 38 stool samples in the B. breve group. The frequency of rotavirus shedding in the B. breve group was significantly lower than that in the control group. Further, the frequency in appearances of anti-IgA in stool samples in the B. breve group showed a tendency to increase in comparison with the control group from day 8 to 14 of the test. The oral administration of B. breve YIT4064 significantly decreased rotavirus shedding in stool samples and prevented rotavirus infection.

Administration, Oral↗
PubMed1999

[Aortic valve operations through an upper partial sternotomy].

The median sternotomy has been accepted as the most common approach to the heart, because this approach is easily opened and closed, and easy access to the entire heart is possible. Following the pioneering work by Cosgrove and colleagues of using a parasternal incision for aortic and mitral valve operations, several reports suggested that modified minimal access procedures are likely to be associated with reduced postoperative discomfort and faster recovery. Since July 1997, we have used an upper partial sternotomy and a limited skin incision for isolated aortic valve replacement (AVR) at our hospital. To demonstrate the benefits of this approach, we compared 14 AVR operations using our minimal access incision (group M) with 19 patients undergoing isolated AVR using a conventional sternotomy (group F). In the minimal access group of patients, a small skin incision was made from the second intercostal space to the fourth rib. The pectralis major and intercostal muscle was freed from the sternum, and then a transverse half sternotomy was made in the fourth intercostal space using a striker without injury to the right internal mammary artery. A median partial sternotomy from the supersternal notch to the level of the fourth intercostal space. Cardiopulmonary bypass was connected through the same access site to avoid cannulation of both groins. Conversion to median sternotomy was not necessary in any patient including reexploration for postoperative bleeding. There was no operative mortality, stroke, aortic dissection and perivalvular leaks due to technical factors. In group F, wound infection occurred in 1 patient. One patient in group M required reoperation to control postoperative bleeding. Although mean duration of operation, cardiopulmonary bypass, and cross clamp time in group M was not prolonged, the initiation of cardiopulmonary bypass and aortic crossclamp was delayed by difficulties of cannulations. The distance between the transverse sternotomy (lower edge of divided sternum) and the midpoint of aortic valve annulus was correlated with mean duration of cardiopulmonary bypass and cross clamp time. Our experience demonstrates that isolated AVR through an upper partial sternotomy allows the same quality operations as the full sternotomy, although more clinical experience is required to clarify the benefits of this approach. Excellent exposure of the aortic valve through a partial sternotomy may be attained, if an adequate approach can be selected by the position of aortic valve.

Aortic Valve↗