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Y Inomata

Publications and source records attributed to Y Inomata.

At least 91 records · Page 5Linked to original sources
PubMed1997

Generation and characterization of mice lacking gastrin-releasing peptide receptor.

Gastrin-releasing peptide (GRP) is a mammalian bombesin-like peptide which is widely distributed in the central nervous system as well as in the gastrointestinal tract. GRP binds to its high affinity receptor (GRPR) to elicit a wide spectrum of biological effects on behavior, digestion, and metabolism. To define the in vivo function of GRPR, we generated GRPR null mutant mice by gene targeting. The intracerebroventricular administration of GRP caused hypothermia in wild-type mice, but not in mutant mice. The GRPR deficient mice showed significantly increased locomotor activity during the dark period, and social responses scored by sniffing, mounting, and approaching behaviors against an intruder. Aggressive scores such as fighting and biting were not altered in the mutant mice. These phenotypes were observed in mice generated from two independent ES cell clones and backcrossed to a C57BL/6J background. The GRPR deficient mice should be useful for studying the bombesin system in vivo.

Animals↗
PubMed1997

Serotonin as a useful parameter for cold and warm ischemic injury in small bowel transplantation.

We investigated serotonin as a parameter of cold and warm ischemic injury prior to transplantation. Lewis rats were used as both donors and recipients, and the proximal 20 cm of jejunum served as the graft. The grafts were preserved in 4 degrees C lactated Ringer's solution for 0, 6, 12, 18, and 24 hr after harvest for cold ischemia (n=7/group). The superior mesenteric artery was clamped for 0, 15, 30, 60, and 120 min before harvest for warm ischemia (n=7/group). The serotonin concentration was measured in the luminal effluent and the preservation solution before transplantation, and total serotonin was calculated as the sum of these amounts. Finally, transplantation was performed heterotopically. Total serotonin increased significantly with both cold and warm ischemic time (P<0.01 by analysis of variance, Fisher's PLSD); however, between 18 hr and 24 hr of cold ischemic time only, there were no significant changes. Total serotonin levels correlated well with cold and warm ischemic time, as shown by linear regression analysis (cold ischemia: R2=80.2%, P<0.01; warm ischemia: R2=92.8%, P<0.01). We established the cutoff level of total serotonin to predict the graft survival at 2200 ng, and using this critical level, graft survival was predicted by total serotonin with a sensitivity of 71.4% and a specificity of 89.8%. Immunohistochemical staining with the serotonin antibody revealed that the number of serotonin-positive cells decreased with both cold and warm ischemic time. In conclusion, serotonin is a useful parameter of cold and warm ischemic injury before transplantation and can assist in predicting graft survival.

Animals↗
PubMed1997

Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has recently been performed in patients with noncirrhotic metabolic liver diseases. However, long-term outcomes for the preserved native liver and the transplanted liver graft have not been clearly established yet. METHODS: The recipient was a 36-month-old girl with ornithine transcarbamylase deficiency. She underwent APOLT, using her father's left lateral segment. RESULTS: Liver function was normalized soon after APOLT and the patient was able to ingest a normal diet without medication. Coexistence of the well-functioning native liver and graft was demonstrated in a computed tomography scan, Doppler ultrasonography, scintigraphy, and histological examination, during a relatively long-term follow-up period. CONCLUSIONS: APOLT seems to be most useful for the treatment of noncirrhotic metabolic liver diseases.

Biopsy↗
PubMed1997

A hepatic graft tuberculosis transmitted from a living-related donor.

Exclusion of occult diseases in the donor organ and prevention of infectious disease transmission are minimal requirements in organ transplantation. We report here a case of hepatic graft tuberculosis, which was most likely transmitted by the graft from the living-related donor. The course of the recipient included tuberculosis, rejection, and other infections, which led to vanishing bile duct syndrome. Due to various infections and tuberculosis, as well as a strong interaction between rifampicin and tacrolimus, the patient died of pneumonia on day 273 after transplantation. This case emphasizes the importance of care in the selection of a living-related donor for liver transplantation.

Adult↗
PubMed1997

Effects of hypoxemia on early postoperative course of liver transplantation in pediatric patients with intrapulmonary shunting.

Nine pediatric patients (mean age, 10 years) with biliary atresia, who had hypoxemia related to intrapulmonary shunting, underwent living related liver transplantation. The effects of hypoxemia during the early postoperative period after liver transplantation on cardiopulmonary and renal function, as well as on transplanted liver, were analyzed. Based on the degree of shunt ratio calculated by technetium-99m macroaggregated albumin scintigraphy, the nine patients were included in the moderate group (shunt ratio under 40%, n=4) or the severe group (shunt ratio over 40%, n=5). Partial pressure of arterial oxygen was maintained at normal range in the moderate group, while that in the severe group persistently had very low values (<50 mmHg), in spite of a high degree of oxygen supply. However, all patients in the severe group maintained stable cardiopulmonary vital signs, including systemic blood pressure, heart rate, respiratory rate, and cardiac index. They also demonstrated stable renal function. None of the patients died of cardiopulmonary or renal insufficiency after transplantation, but three patients died of portal vein thrombosis, sepsis, and intracranial hemorrhage (one each). The minimal adverse effect of hypoxemia on the transplanted liver was confirmed by a rapid increase of arterial ketone body ratio, low peak values (under 200 IU/L) of aspartate aminotransferase, and a steady decrease of serum total bilirubin. Four patients encountered surgical complications, including two bile leaks from the cut liver surface, two leaks from bilioenteric anastomosis, and one intestinal perforation. Six patients suffered from bacterial infections, including four wound infections, three right subphrenic abscesses, one cholangitis, and two systemic sepses. All patients in the moderate group recovered from hypoxemia, but four of five patients in the severe group have not recovered during the follow-up period between 4 and 9 months. It was concluded that the adverse effects of hypoxemia on cardiopulmonary and renal function and transplanted liver were minimal, so that patients with severe hypoxemia could tolerate the stress of liver transplantation without special management. However, the high incidence of surgical complication and infection suggested the adverse effects of hypoxemia on wound healing and resistance to bacteria infection.

Adolescent↗
PubMed1997

Efficiency of pentoxifylline in donor pretreatment in rat liver transplantation.

Donor pretreatment is a new concept in organ preservation. Pentoxifylline (PTX) has been reported to suppress the activation of Kupffer cells and to decrease injury to the hepatic graft after rat liver transplantation. We evaluated the efficiency of PTX pretreatment on the donor against hepatic injury following cold ischemia (CI) or warm ischemia (WI) using the rat liver transplantation model. Dose dependency: every rat was injected intraperitoneally with PTX (30, 50, or 80 mg/kg) or saline. One hour later, the portal vein (PV) and the hepatic artery (HA) were clamped for 30 min. Transplantation: the donor rat was injected intraperitoneally with 50 mg/kg PTX or saline, 1 hr before laparotomy. Animals were divided into two groups. In the CI group, grafts were preserved for 12 hr in University of Wisconsin solution at 4 degrees C and transplanted. In the WI group, the PV and the HA in the donor were clamped for 30 min before donor surgery, and the grafts were transplanted. Serum levels of tumor necrosis factor-alpha (TNF-alpha), glutathione S-transferase-alpha (GST-alpha), and aspartate transaminase (AST) were measured at 30 min, 3 hr, and 24 hr after reperfusion of the PV. Compared with those of a control group, the serum levels of TNF-alpha, GST-alpha, and AST in the PTX-pretreated groups were significantly lower after both CI and WI at 30 min and further suppressed in the WI group at 24 hr. These results indicate that PTX pretreatment on the donor is effective for suppression of hepatic injury after both CI and WI.

Alanine Transaminase↗
PubMed1997

Impact of the development of a liver transplant program on the treatment of biliary atresia in an institution in Japan.

Kasai operation for biliary atresia (BA) and living-related liver transplantation (LRLT) for failed Kasai cases have been performed by the same team in our hospital. Outcome of the treatment for BA in the pretransplantation and posttransplantation era in our institution were compared. As the "pre" group, 35 children first underwent the Kasai operation between 1982 and 1989. The "post" group consisted of 25 patients who underwent Kasai after introduction of the LRLT program in our hospital (1990). As for the reconstruction procedure after portal dissection during Kasai, jejunal interposition hepatic portoduodenostomy for the pre group was intentionally changed to Roux-en-Y procedure for the post group to decrease the risk of duodenal leakage after LRLT. Patients who needed revision of the Kasai decreased from 57% for the pre group to 28% for the post group. There was only one re-revision in the post group compared with seven in the pre group. In the pre group, 10 patients (28.6%) died at age 6 to 16 (mean, 8.5) months before the transplantation program was initiated. In the pre group, three patients could receive a cadaveric liver transplantation in other countries, and seven had LRLT in our hospital. Ten patients (40%) in the post group had LRLT at 7 to 22 (mean, 9.3) months old, and no deaths occurred in this group. When the patients who had liver dysfunction were excluded, the percentage of the patients who could be expected to survive and accomplish growth without undergoing liver transplantation was similar for the two groups, (31.4% v 36%). The change in the reconstruction procedure and the tendency for fewer revisions of Kasai procedure were effects of the start of the liver transplant program. As a general strategy for BA, Kasai operation should be the initial procedure, followed by liver transplantation for failed Kasai. In the late-diagnosed patients, primary LRLT can be considered if the liver has already been cirrhotic. LRLT in the infantile period is a significant component of this strategy for helping all patients to survive.

Biliary Atresia↗
PubMed1997

Hepatic vein reconstruction in 152 living-related donor liver transplantation patients.

BACKGROUND: Hepatic vein (HV) reconstruction is crucial in partial liver transplantation in which the inferior vena cava (IVC) is preserved. METHODS: We reviewed the medical records of 152 living-related donor liver transplantations (LRDLTs) in 150 children (45 left lobe grafts, 106 lateral segment grafts, and 1 right lobe graft) monitored for 12 months or longer. RESULTS: A standard technique was a wide end-to-side anastomosis between the donor HV and cuffs, consisting of the recipient middle and left HV and an incision to the IVC. In 15 of 22 partial grafts with two separated HVs the two vessels were reformed by back table surgery to have a common anastomotic orifice, and two separate anastomoses of the individual vessels were made for the remaining seven grafts. Four patients with an absence of infrahepatic IVCs and two with completely obstructed IVCs had end-to-end anastomoses with recipient IVCs. Four patients with stenotic IVCs had end-to-side anastomoses with new orifices on the IVCs. Two patients had acute HV obstruction caused by twisting of the HV that required laparotomy, and six had late-onset HV obstruction that required radiologic intervention. A tissue expander was placed prophylactically in the right subphrenic space in 10 patients to prevent the dislocation of the graft into the right subphrenic space. CONCLUSIONS: It is important in HV reconstruction in partial liver transplantation to make wide orifices and to adapt each graft to its orthotopic place, taking into consideration graft shape, size of the abdominal cavity of the recipient, and anatomic variations in vessels.

Adolescent↗
PubMed1997

Serum soluble human leucocyte antigen class I in paediatric liver transplantation with live, related donors.

Serum soluble human leucocyte antigen (HLA) class-I is a useful marker for predicting immunological events in organ transplantation. In cadaver liver transplant cases it is especially the case that high amounts of soluble HLA-I are excreted from the grafts. In Japan, almost all liver transplants have been performed from living parent donors to their children. Therefore, it is interesting to know how soluble HLA-I changes in relation to clinical course. As part of this study we first examined serum concentrations of soluble HLA-I in 33 paediatric patients using enzyme-linked immunosorbent assay. Soluble HLA-I is composed of three different sized molecules (45, 39 and 34-36 kDa); then the change of distribution of these three molecules was demonstrated by Western blot analysis. When donor and recipient have different soluble HLA-I band patterns, the origin of the antigen can be assumed by this method. We found that in a comparison between pre- and post-transplants, the six out of eight (75%) patients that suffered episodes of acute rejection showed a significant elevation of soluble HLA-I, and all patients with infectious episodes had an elevated soluble HLA-I. Meanwhile, 10 out of 22 (45%) patients without any clinical complications still showed increased soluble HLA-I. The Western blot analysis showed that the soluble HLA-I molecules were considerably derived from the grafted liver, from one week to 24 months after grafting. In acute rejection, the band signals of donor origin were significantly increased. These signals were attenuated after immunosuppressive therapy. The grafted liver appears to contribute to the increase of soluble HLA-I following liver transplantation, and this increase is greater with the effects of the host immune system.

Adolescent↗
PubMed1997

Hepatic preservation with histidine-tryptophan-ketoglutarate solution in living-related and cadaveric liver transplantation.

1. Living-related liver transplantation has some advantages in the evaluation of novel clinical protocols, since many complicated factors affecting initial graft function are almost uniform in grafts obtained from healthy donors. 2. To compare histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solution in terms of tissue oxygenation in living-related liver transplantation, oxygen saturation of haemoglobin (SO2) in hepatic tissue and its heterogeneity (CV, coefficient of variation) were measured by near-infrared spectroscopy. The HTK and UW groups consisted of 15 and 49 successful transplants respectively, in which no statistical differences in background were observed. 3. In the HTK group, hepatic SO2 after portal vein reflow was higher (P < 0.01) than that in the UW group, as was that after hepatic artery reflow (P < 0.05). In the UW group, hepatic SO2 remained at the lower level at the end of the operation. 4. Furthermore, the increase in CV after portal vein reflow was normalized after hepatic artery reflow in the HTK group. However, the CV remained at a high level at the end of the operation in the UW group. 5. Postoperative peak aspartate aminotransferase level in the HTK group was lower than that in the UW group (P < 0.05). 6. In cadaveric liver transplantation, higher hepatic SO2 and lower CV of hepatic SO2 in the early phase after reperfusion compared with the UW group (n = 18) were also observed in the HTK group (n = 30) (P < 0.05). 7. In conclusion, recovery of tissue oxygenation and its heterogeneity after reperfusion in HTK-preserved livers were more rapid and homogeneous than in UW-preserved livers in living-related liver transplantation. Accordingly, HTK solution may be a potential alternative to UW solution.

Adenosine↗
PubMed1997

Application of a tissue expander for stabilizing graft position in living-related liver transplantation.

In living-related liver transplantation, a portion of the whole liver, usually the left lateral segment or the left lobe, is harvested for use as the graft liver. A relatively small graft may twist around the hepatic venous anastomosis, causing outflow blockage. After an initial experience of such a complication in the early post-transplantation period in one case, we began to apply a tissue expander to obliterate the dead space left after emplacement of a relatively small graft. Commercially available tissue expanders, ordinary employed in plastic surgery, were used for five pediatric recipients (6-14 yr old) whose ratio of graft weight to recipient body weight ranged from 0.74 to 1.72. The expander, filled with 240-350 ml saline, was put into the space to the right of the graft. Aspiration of the expander content was started after the 5th-7th postoperative day (POD), at a rate of 50 ml of fluid a day. The expanders were taken out on the 11th-14th POD after complete removal of the content. Complications observed in the five cases were right shoulder pain (5/5), fluid collection after removal of the expander(2/5), chylous ascites (1/5), and one instance of bile leakage. All the complications were successfully managed and controlled conservatively. There was no outflow obstruction detected by Doppler ultrasonography before or after removal of the expander. This is a simple and safe method for preventing the early onset of outflow block after partial liver transplantation.

Adolescent↗
PubMed1997

[A case of recurrent gastric cancer with liver metastasis responding to combination chemotherapy with cisplatin and carmofur].

The patient was a 65-year-old male with recurrent gastric cancer accompanied by metastasis to the liver and distant lymph nodes. He was treated by combination chemotherapy consisting of cisplatin 20 mg/body (day 8-14) and Carmofur 400 mg/body (on consecutive days), in three four-week courses of therapy. After 1 course of administration, the target lesion was reduced in size and the performance status was improved. Generally, a partial response was confirmed by computed tomography (CT). The patient has survived for 8 months in a state of PR. Adverse effects were mild and transient. Though treatment of recurrent gastric cancer with liver metastasis is often ineffective, this case suggests that a combination therapy of cisplatin and carmofur might be effective.

Aged↗
PubMed1997

Pharmacological profile of the novel antidepressant 4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno-[2,3-d]pyrimidine monohydrate hydrochloride.

This is a first report on the investigation of the antidepressant activity of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride, CAS 99487-26-0) in comparison with maprotiline (CAS 10347-81-6), desipramine (CAS 58-28-6), imipramine (CAS 113-52-0) and trazodone (CAS 25332-39-2). MCI-225 inhibited the synaptosomal uptake of noradrenaline (NA, Ki = 35.0 nmol/l), serotonin (5-HT, Ki = 491 nmol/l), and dopamine (Ki = 14,800 nmol/l), although it did not inhibit MAO-A and MAO-B activities. MCI-225 showed high affinity only for the 5-HT3 receptor (Ki = 81.0 nmol/l) among all receptors tested including M1, M2, alpha 1, and H1 receptors. The inhibition of the von Bezold-Jarisch reflex by MCI-225 (ID50 = 22.2 mg/kg, p.o.) suggests its antagonistic action on the 5-HT3 receptor. MCI-225 dose-dependently reduced reserpine-induced hypothermia (0.3-10 mg/kg, p.o.) and potentiated yohimbine-induced lethality (3-100 mg/kg, p.o.) in mice. These effects of MCI-225 were as potent as desipramine and more potent than maprotiline, imipramine and trazodone. MCI-225 and desipramine did not change either 5-HTP-induced head movements or p-CA-induced hyperactivity in rats. In forced swimming tests in rats, the minimum effective doses of MCI-225, maprotiline, desipramine, and imipramine were 1, 30, 10 and 30 mg/kg, p.o., respectively, for 5-days administration. Only MCI-225 had shown its full activity with this short term treatment. MCI-225 (10 mg/kg, p.o.) decreased the REM sleep period without affecting slow-wave sleep or wakefulness in rats. Even at 100 mg/kg, p.o. MCI-225 and trazodone did not inhibit oxotremorine-induced tremor, lacrimation or salivation in mice in contrast with imipramine. These results suggest that MCI-225, which selectively inhibits NA uptake and antagonizes the 5-HT3 receptor, has potential as a new type of potent antidepressant.

Animals↗
PubMed1997

Living-donor liver transplantation in Kyoto, 1997.

Although a new law allowing for organ retrieval from brain-dead donors was recently put into force, living donors remain the major source for liver transplantation in Japan. The number of LDLT cases in Kyoto University has increased yearly, reaching 336 transplantations in 329 patients in November 1997. Because the program has expanded without support from cadaveric organ sources, we have been confronted with difficulties with graft size mismatches, major ABO blood group incompatibilities and highly deteriorated emergency cases. Despite innovations in surgical techniques which have reduced vascular complications, and several immunomodulations to mitigate complications of mismatched blood groups, graft survival in these cases remains approximately 20% lower than that for less complicated transplants. This report summarizes our recent struggles with these problems and some of our solutions.

Adolescent↗
PubMed1996

Postoperative monitoring of the oxygenation state of the graft liver in cases with hepatopulmonary syndrome.

Postoperative changes in the oxygen saturation of hemoglobin in the graft liver (graft SO2) were monitored by near-infrared spectroscopy in four cases complicated by hepatopulmonary syndrome. A plastic cylinder was placed in the abdominal wall, and optical measurements of the graft liver were obtained through this window. Our findings were as follows; (1) graft SO2 decreased after abdominal wall closure, and decreased further 1 day after surgery. (2) Graft SO2 was maintained despite severe hypoxemia, with partial pressure of oxygen in arterial blood as low as 50 mmHg. High hematocrit was beneficial for oxygenating the graft. (3) Graft livers could tolerate hypoxia with a graft SO2 as low as 20%. (4) It may be useful to monitor graft SO2 during the critical period after transplantation for the assessment of graft function.

Adolescent↗
PubMed1996

Factors associated with postoperative respiratory complications in pediatric liver transplantation from living-related donors.

Factors associated with respiratory complications (RCs) after pediatric living-related liver transplantation were statistically analyzed in the first 100 cases where surgery was performed at Kyoto University. The overall incidence of postoperative RCs was 45%, including atelectasis (23%), pleural effusion (23%), and pneumonia (12%). Univariate and multivariate analyses were performed with regard to the association between postoperative RCs and 13 pre- and intraoperative variables that were considered to represent the preoperative medical status of the patients and the severity of operative insult. The following four independent variables were found to have prognostic significance with regard to the postoperative RCs: (1) history of preoperative RCs, (2) height < or = -2 SD from the mean for the age, (3) United Network for Organ Sharing score = 1, and (4) intraoperative blood loss > or = 20% of body weight. Postoperative death was highly affected by postoperative RCs: 8 of 11 deaths during the study period were directly or closely related to postoperative RCs. We conclude that postoperative RCs are major contributing factors to operative morbidity and mortality in pediatric living-related liver transplantation, which may possibly be reduced by intensive respiratory management of patients with the above risk factors for postoperative RCs.

Adolescent↗