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Y Shirakata

Publications and source records attributed to Y Shirakata.

At least 37 records · Page 2Linked to original sources
PubMed1998

Direct measurement of graft and recipient liver fossa size by computed tomography for avoiding problems due [correction of clue] to large graft size in living-related liver transplantation.

We investigated the incidence and manifestation of problems associated with large graft size in living-related liver transplantations and assessed the usefulness of determining volume and dimensions of the graft and recipient's liver fossa by computed tomography to indicate the risk. Five of 150 living related liver transplantations had grafts that were too large, resulting in difficulty in primary abdominal closure or in sudden worsening of hemodynamics during primary closure. No significant difference existed in recipient age, sex, body weight, selection of the graft segment, hepatic vein reconstruction, recipient resected liver weight, graft volumetry value, the ratio of body weight of donor relative to recipient, and the percentage of graft weight relative to recipient body weight, between the groups with and without these problems. Mean +/- SEM of maximal dimensional ratio, defined as the maximum of the ratios of 3 dimensions of the graft relative to recipient liver fossa, were 2.36 +/- 0.64 for patients with grafts that were too large and 1.00 +/- 0.02 for the cases without size problems. The mean +/- SEM of liver fossa index, defined as the product of 3 dimensions of recipient liver fossa, were (25.03 +/- 7.18) x 10(4) mm3 and (127.54 +/- 5.07) x 10(4) mm3, respectively. These two indices clearly indicated the risk of problems due to large graft size, and will help to protect recipients and provide a basis for evaluating graft size in reductions.

Child, Preschool↗
PubMed1997

Successful long-term xenoperfusion of the pig liver: continuous administration of prostaglandin E1 and insulin.

For clinical utilization of extracorporeal liver perfusion as an artificial liver assist device, we examined the possibility of long-term xenoperfusion of the pig liver by the continuous administration of prostaglandin E1 (PGE1) and insulin. After a 3-hr perfusion period, pig livers that were xenoperfused with human blood exhibited a drastic decrease in the perfusate volume, a progressive elevation of the hepatic artery pressure, a gradual deterioration of bile production, and a marked increase in the release of creatine kinase-BB component. The continuous administration of PGE1 (25 microg/hr) and insulin (1 U/hr) significantly improved these derangements (P<0.05) and allowed stable perfusion for up to 9 hr. This manipulation also inhibited leukocyte aggregation in the graft, the characteristic perfusate hemolysis, and acceleration of ketogenesis. Histological examination revealed that the interlobular edema and hemorrhage, characteristics of tissue injuries in xenogeneic hyperacute rejection, were markedly alleviated in the PGE1 and insulin-treated group. This study clarifies the finding that the combined administration of PGE1 and insulin is effective for long-term xenogeneic extracorporeal liver perfusion, with the graft viability well maintained.

Alprostadil↗
PubMed1997

Reducing environment protects sinusoidal lymphocytes isolated from normal human liver from apoptosis.

BACKGROUND/AIMS: We previously reported that the populations of lymphocytes and the expression of activated antigens in human sinusoidal mononuclear cells were different from those in peripheral blood mononuclear cells. Attempts to culture these cells for further study failed because they died rapidly under standard culture conditions in vitro after isolation from the liver. In this study, we evaluated the characteristics of cell death and the effects of various culture conditions on the viability of these cells. METHODS: Sinusoidal mononuclear cells were isolated from University of Wisconsin solution that had been perfused through the portal veins of normal healthy human livers harvested for transplantation into living related recipients. RESULTS: 70% of sinusoidal mononuclear cells cultured in vitro were nonviable within 48 h after isolation, while only 10% of peripheral blood mononuclear cells died under the same conditions. Sinusoidal mononuclear cells showed DNA ladder formation of DNA on electrophoresis and characteristic morphological pattern on electron microscopic examination that suggested they had died in an apoptotic manner. The addition of human liver extracts or 2-mercaptoethanol and reduced glutathione to the cultures rescued the sinusoidal mononuclear cells from apoptosis. Furthermore, diamide, a sulfhydryl group specific oxidant, negated the effect of the liver extract. CONCLUSION: In comparison with peripheral blood mononuclear cells, human sinusoidal mononuclear cells were more subject to death by apoptosis ex vivo, which was reversed by exogenous agents producing reducing conditions. These results suggested that hepatic sinusoidal mononuclear cells might express a different sensitivity to redox environment than peripheral blood mononuclear cells.

Apoptosis↗
PubMed1996

Purification of a novel MHC class I element binding activity from thymus nuclear extracts reveals that thymic RBP-Jkappa/CBF1 binds to NF-kappaB-like elements.

We purified a DNA binding protein that recognizes a portion of the MHC class I regulatory element region 1/NF-kappaB binding site whose expression correlates with the expression of a MHC class I transgene in the thymus. The N-terminal amino acid sequence and the molecular size matched the RBP-Jkappa protein, also known as the EBV C-promoter binding factor, CBF1. Anti-peptide sera reactive with RBP-Jkappa/CBF1 also reacted with this protein in gel mobility shift assays. Although RBP-Jkappa/CBF1 is ubiquitously expressed, binding to the MHC class Ia NF-kappaB site was limited to the thymus. Comparison of the DNA binding specificities of RBP-Jkappa/CBF1 in thymic and splenic nuclear extracts revealed strong binding from both extracts to an IFN-beta kappaB site containing the RBP-Jkappa/CBF1 consensus sequence (CGTGGGAA). In contrast, only the thymic nuclear extract showed strong DNA binding activity with probes containing the NF-kappaB recognition sequences present in the MHC class Ia, IL-2Ralpha, and granulocyte-macrophage CSF promoters. Thus, RBP-Jkappa/CBF1 in thymic extracts demonstrates a clearly distinguishable DNA binding specificity that correlates with tissue-specific expression of a class I transgene. This, coupled with the fact that our previous study showed enhanced expression of the transgene in CD4+CD8+ thymocytes, suggests that RBP-Jkappa/CBF1 may play a role in the development of the immune system.

Amino Acid Sequence↗
PubMed1996

Long-duration xenogeneic extracorporeal pig liver perfusion with human blood.

Hepatic xenografts can tolerate hyperacute rejection owing to their lower susceptibility to humorally mediated injury. We investigated the possibility of long-duration xenoperfusion without immunologically controlling natural antibodies or complements. Pig livers were perfused for 9 h with human blood (Group 1) or pig blood (Group 2). Physiological conditioning and administration of prostaglandin E1 and insulin was characteristic of our system. The portal vein and hepatic artery pressure and bile production did not significantly differ between the two groups. Despite a gradual decrease throughout the perfusion, overall oxygen consumption was significantly higher in Group 1. Liver enzymes were released at higher levels in Group 1. Histological examination revealed intact hepatic architecture in Group 2, while in Group 1 interlobular morphology was severely damaged by endothelial disruption, although hepatic sinusoidal architecture was preserved. It is concluded that, despite biochemically and histologically confirmed tissue injury, graft viability was well-maintained in xenoperfusion even without immunological manipulations.

Alprostadil↗
PubMed1996

Experiences of 120 microsurgical reconstructions of hepatic artery in living related liver transplantation.

BACKGROUND: We reviewed 120 microsurgical reconstructions of a hepatic artery in living related liver transplantation and discussed the problems encountered. METHODS: From January 1991 to July 1994 we performed a series of 105 living related liver transplantations on children with end-stage liver disease. Arterial reconstruction was performed under the optical field of a continuous zoom magnification of approximately 10 times with an operating microscope. RESULTS: Twenty-six percent of the graft arteries were less than 2 mm in diameter. The time required for an arterial reconstruction was 49.5 +/- 1.8 minutes. In 15 of the 31 cases in which there were two graft arteries, two arterial reconstructions were required. The caliber differences between the graft artery and the recipient artery in 30 instances was dealt with by cutting an undersized artery obliquely (17 instances), by fish-mouth method (10 instances), by end-to-side anastomosis (1 instance), or by funnelization method (2 instances). In one case we performed an intimal dissection of a recipient hepatic artery and substituted a splenic artery. Consequently, hepatic arterial thrombosis occurred in only two cases (1.7%). CONCLUSIONS: Microsurgical technique has overcome the high risk of hepatic arterial thrombosis in cases of fine graft arteries, enabled the reconstruction of arteries with caliber difference, and decreased arterial complications with its delicate manipulation.

Adolescent↗
PubMed1995

Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506.

To evaluate the roles of extracellular FKBP12, we examined the effect of extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and clinically. The ability of FK506 to suppress phytohemagglutinin-induced proliferative response of human peripheral blood mononuclear cells was inhibited in the presence of recombinant FKBP12 dose-dependently. We measured plasma levels of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34 patients receiving FK506 after liver transplantation. In 7 patients with acute cellular rejection, plasma FKBP12 increased significantly at the onset of rejection compared with 1 week before onset (P < 0.05) and further increased to or remained at more than 250 ng/ml 1 week after onset. In 22 of 27 patients without acute cellular rejection, plasma FKBP12 was less than 70 ng/ml during the 4 weeks after transplantation. In the other 5 of 27 patients without acute cellular rejection, plasma FKBP12 exceeded 250 ng/ml. Rapid increase of plasma FKBP12 was observed in only one of these 5 patients, at the onset of high fever due to a liver abscess. There was no significant difference in whole blood trough levels of FK506 between the patients with or without acute cellular rejection. These results suggest that the rapid increase in plasma levels of FKBP12 may contribute to the occurrence and progress of acute cellular rejection probably by inhibiting the immunosuppressive activity of FK506.

Adolescent↗
PubMed1995

A mini Cl- channel sensitive to external pH in the basolateral membrane of guinea-pig parietal cells.

1. Voltage-independent whole-cell Cl- currents were recorded from both single, isolated parietal cells and parietal cells within gastric glands obtained from the fundus of guinea-pig stomach. 2. The Cl- currents were rapidly suppressed by a Cl- channel blocker, NPPB (5-nitro-2-(3-phenylpropylamino)-benzoate), added to the (basolateral) bathing solution in a concentration-dependent manner with a half-maximal inhibition concentration of 12 microM. 3. The selectivity sequence among anions was I- > Br- > Cl- > F-, corresponding to Eisenman's sequence I. 4. The Cl- currents were independent of cytosolic Ca2+, cyclic AMP, cyclic GMP, GTP-gamma-S and cell volume, and were not affected by application of acid secretagogues, omeprazol, arachidonic acid or prostaglandin E2. 5. Reduction of pH in the (basolateral) bathing solution immediately inhibited the Cl- current with a pK (-log of KD) of 6.3, whereas changes in intracellular pH had no effect. 6. The single-channel conductance was estimated to be 0.46-0.6 pS by variance noise analysis during inhibition of whole-cell Cl- currents by NPPB or acidic pH. 7. It is concluded that pH-sensitive 'mini' Cl- channels, with a sub-picosiemens unitary conductance, exist in the basolateral membrane of guinea-pig parietal cells.

Animals↗
PubMed1995

A maxi Cl- channel coupled to endothelin B receptors in the basolateral membrane of guinea-pig parietal cells.

1. To study endothelin (ET) receptors in guinea-pig stomach, ET-binding assays and in vitro autoradiography were performed on fundic cell suspensions and on sections of the fundus, respectively. ETA and ETB receptor subtypes were found to coexist in the parietal cells. 2. Endothelin 1 (ET-1) added to the (basolateral) bathing solution was found to activate noisy whole-cell Cl- currents within about 1 min in both single, isolated parietal cells and those within gastric glands obtained from the fundus. 3. ET-1-induced Cl- currents were rapidly blocked by a Cl- channel blocker (NPPB) added to the (basolateral) bathing solution in a concentration-dependent manner with a half-maximum inhibition concentration of 33 microM. 4. The anion selectivity sequence of the ET-1-induced conductance was I- > Br- > Cl- > F-, corresponding to Eisenman's sequence I. 5. Changes in extracellular pH between 5 and 8 did not affect the ET-1-induced activation of Cl- currents. 6. Similar activating effects were also observed with ET-3 and a specific ETB receptor agonist (IRL1620). An ETB receptor antagonist (IRL1720) prevented the ET-1 effect, whereas an ETA-selective antagonist (FR139317 or BQ123) failed to antagonize the ET-1 effect. 7. In the whole-cell mode, unitary Cl- channel events could be observed in association with ET-1-activated macroscopic currents. The single-channel conductances were around 200 and 350 pS at negative and positive membrane potentials, respectively. 8. It is concluded that gastric parietal cells of guinea-pig possess pH-insensitive 'maxi' Cl- channels coupled to ETB receptors in the basolateral membrane.

Animals↗
PubMed1995

NF1 gene mutations in Japanese with neurofibromatosis 1 (NF1).

Neurofibromatosis 1 (NF1) is an autosomal dominant disease characterized by abnormalities in multiple tissues derived from the neural crest. We analysed 50 unrelated Japanese patients for NF1 mutations by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis for exons 28 to 36. Here, we demonstrate a single base pair (bp) insertional mutations in exon 31 in one patient (5843insA/5844insA/5845insA/5846insA) and a single adenine to guanine transitional mutation 4 bp upstream from the 3' end of intron 31 in two unrelated cases. The insertional mutation in exon 31 was novel and resulted in premature termination of the transcript. The other intron 31 mutations resulted in 4 bp insertions of cDNA between exon 31 and exon 32 with premature termination of the transcript, indicating that those transitions of intron 31 caused aberrant splice acceptor sites upstream from the 5' end of exon 32. However, as the same mutation of intron 31 has been reported previously in two cases of unrelated Caucasians, the splice junction mutation of intron 31 is thought to be common among different ethnic groups.

Adenine↗
PubMed1995

Twenty-four hour monitoring of pH in the gastric tube replacing the resected esophagus.

BACKGROUND: Peptic ulcers in the gastric tube replacing the resected esophagus develop silently and cause serious problems. In this study, the acidity of the gastric tube was examined by 24-hour pH monitoring to determine if the acidity of the gastric tube was sufficient to cause peptic ulcers. STUDY DESIGN: The acidity of a gastric tube was evaluated by 24-hour pH monitoring of both the fundus and the antrum in 55 patients treated for carcinoma of the esophagus. The correlation between the fasting serum gastrin concentration and the intraluminal acidity of the completely vagotomized gastric tube was examined. RESULTS: In the patients with high postoperative acidity in the fundus or the antrum (46 percent of the 41 patients examined), the intraluminal pH remained consistently low, even long after operative treatment. Significant correlations existed between the percentage of time that the pH remained below 3 preoperatively and postoperatively in both the fundus and the antrum (r = 0.4777, p = 0.0386, and r = 0.7597, p = 0.0002, respectively). The percentage did not decrease significantly postoperatively. A significantly negative correlation (r = -0.783401, p < 0.0001) was found between the fasting serum gastrin level and the proportion of time that the nocturnal pH in the antrum remained below 3. CONCLUSIONS: Even long after esophagectomy, the pH of the gastric tube is low enough to cause peptic ulcers, especially in patients with high preoperative acidity. In these patients, the intraluminal pH in the antrum of the gastric tube correlates inversely with the fasting serum gastrin level.

Aged↗
PubMed1993

Role of the Q10 class I regulatory element region 1 in controlling tissue-specific expression in vivo.

The MHC class I regulatory element (CRE) region 1 has been previously described as a positive cis-acting regulatory element essential for class I gene expression. We have generated transgenic mice (CBA x C57BL/6) with the MHC class I gene H-2Dd driven by two different 400-bp promoter regions of Q10, a nonpolymorphic MHC class I gene expressed in the liver, kidney, and fetal yolk sac. One transgene contained the wild-type Q10 promoter (Q10WT/Dd). The second construct (Q10M3/Dd) had 2 bp substitutions introduced in region 1 of the CRE that reconstituted the CRE inverted repeat present in classical class I genes. Mice containing the wild-type Q10/Dd gene expressed membrane-bound H-2Dd molecules in a tissue-restricted expression pattern similar to that observed for endogenous Q10. In mice containing the mutant construct (Q10M3/Dd), H-2Dd was also expressed in the thymus, a tissue not normally associated with Q10 expression but, surprisingly, the Dd was not expressed in other lymphoid tissues. Furthermore, thymic expression was greatest on double positive (CD4+ CD8+) thymocytes. Thymic Dd expression was correlated with the presence of what appears to be a previously unidentified transcription factor in thymocytes that is capable of interacting with the CRE-inverted repeat. These results show that the mutations in region 1 altered the tissue-specific regulation of the Q10 promoter in vivo, although an intact inverted repeat did not restore the ubiquitous pattern of expression characteristic of classical class I genes. Thus, these results indicate that elements in addition to CRE region 1 in the Q10 promoter region serve to limit ubiquitous tissue expression.

Animals↗